ERCP

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Preface ERCP PAST, PRESENT AND FUTURE ERCP past

1 Since its initial description over 3–2 decades ago, ERCP has evolved from a diagnostic to a therapeutic procedure. Such an evolution, however, has required developments in technology to include marketing of a side-viewing duodenoscope with an elevator to facilitate cannulation, use of therapeutic instruments with larger accessory channels, and creation and marketing of a wide variety of endoscopic accessories. In addition to technology evolution, there have been evolutions in techniques and training to bring us to ERCP present. From the latter standpoint, ERCP is currently recognized as an advanced therapeutic procedure usually requiring an additional year of training beyond a standard 3-year gastroenterology training program.

ERCP present With the exception of performing concomitant sphincter of Oddi manometry (SOM), diagnostic ERCP has largely been supplanted by non-invasive imaging to include abdominal CT, MRI-MRCP and EUS. Therapeutic ERCP was initially described over 30 years ago when Classen and Kawai independently described endoscopic sphincterotomy in Germany and Japan, respectively. From a diagnostic standpoint, ERCP is still used to define the etiology of acute relapsing pancreatitis (divisum, anomalous PB union, annular pancreas, SOD . . .), to differentiate chronic pancreatitis from intraductal papillary mucus secreting neoplasm (IPMN), to define the presence or absence of common bile duct stones in jaundice, cholangitis, or acute pancreatitis and to distinguish benign from malignant biliary strictures. From the latter standpoint, however, ERCP remains an imperfect technology, and meta-analyses of series reviewing brush cytology or endoscopic biopsy to distinguish benign from malignant biliary stenoses suggest only a 30–50% positivity, even in the setting of malignancy. ERCP is also used diagnostically to define the etiology of smoldering pancreatitis to include diagnosis of ductal disruption and sphincter edema. Currently, ERCP has evolved into a primary therapeutic modality. For the past three decades, therapeutic maneuvers have been centered on, and facilitated by, endoscopic sphincterotomy. Despite changes in sphincterotome design (pull, push, needle-knife, long-nose, 20–30 mm wire, monofilament vs braided cutting wire, standard vs rapid-exchange system, single/double/triple lumen technology), technique of use (pure cut, blended current, pulsed current/Erbe generator) and length and direction of incision, enlarging the pancreaticobiliary orifice to facilitate access to strictures, stones, and ductal disruptions remains the most common therapy undertaken with ERCP. While balloon dilation of the biliary sphincter may theoretically offer comparable access to biliary sphincterotomy without the potential risk of bleeding and perforation complications, the rates of procedural pancreatitis, often severe, are prohibitive without the use of adjunctive measures such as pancreatic duct stent placement. As such, the use of balloon dilation of the papilla has been relegated to bit parts in our therapeutic armamentarium, most commonly in the setting of coagulopathy and Billroth-II anatomy. Changes that have occurred over the past decade in the endoscopic treatment of biliary stones have included improved mechanical lithotriptors and electrohydraulic and laser lithotripsy under direct cholangioscopic visualization. Changes in malignant stricture therapy include evolution from plastic prostheses to self-expandable metal stents (SEMS). For benign strictures, dilating balloons have become stronger and have been marketed with larger diameters. Treatment has evolved from placement of a single polyethylene prosthesis to 2, 3, 4, and even 5 stents in parallel. Studies are currently underway looking at the use of completely covered 8–10 mm SEMS in an attempt to treat a subgroup of these patients with a single endoscopic manipulation. The treatments of postoperative biliary leaks have become routine and endoscopic papillectomy has replaced surgical resection for most ampullary adenomas. On the pancreatic side, obstructing calculi have become a major indication for pancreatic endotherapy although approximately 50% of such patients require pretreatment with extracorporeal shock wave lithotripsy (ESWL) prior to removal. Obstructing strictures are also routinely being treated, although results remain more nebulous than those reported for benign biliary stenosis and there appears to be discordance between resolution of the stricture (20–30%) and symptomatic improvement (67–80%). Treatment of ductal disruption has now become standard therapy in high-volume ERCP centers. The latter include amenable pancreaticocutaneous fistulas (external fistula) and internal fistulas (pseudocyst, high amylase pleural effusion, pancreatic ascites, pancreaticoenteric or pancreaticobiliary fistula). Data are clear that fistulas are much more likely to close if a transpapillary stent bridges the area of duct disruption. In contrast, a glandular disconnection (disconnected gland syndrome) in which the major ix

PREFACE

component of ongoing glandular secretions is from the disconnected upstream duct is unlikely to close unless there is concomitant transgastric or transenteric drainage of an associated fluid collection.

ERCP future There are multiple possible scenarios for ERCP in the future. These include widespread application of techniques or technology that are currently used only in high volume centers. Examples include semi-routine use of cholangioscopy to rule out retained CBD stones or to better define the etiology of biliary strictures. The latter will likely require disposable cholangioscopes. On the other hand, widespread application of durable video cholangioscopes or pancreaticoscopes is potentially feasible. Other procedures that are utilized infrequently may become commonplace if technologic and reimbursement issues can be solved. These include endoscopic delivery of brachytherapy or photodynamic therapy (PDT) to patients with unresectable, hilar cholangiocarcinoma. They include a more widespread approach to the endotherapy of pancreatic necrosis, treating not only the ductal disruption that is invariable in severe necrosis but also its consequences, to include drainage of associated fluid collections and debridement of necrotic debris. It is possible that ERCP in the future will become aggressively more therapeutic. An example might be injection of a litholytic agent into the pancreatic duct in patients with chronic calcific pancreatitis. Prostaglandin inhibitors as well as long-acting neuromodulators may also be injected intraductally in painful chronic pancreatitis. Stent placement may evolve to solve the problems of occlusion by bacterial biofilm or mucosal hyperstasia with plastic and metal prostheses, respectively. It is possible that intraductal injection of chemotherapeutic or immunomodulating drugs may play a bit part or a major role in the future management of pancreaticobiliary malignancies. Certainly work will continue on ways to minimize procedurally-related pancreatitis, the major complication of ERCP. The latter will include modifications of technique, prophylactic PD stents and pre- or intra-procedure injection of drugs, intravenously or directly into the pancreatic duct. On the other hand, protenomics promises what conventional tumor markers (CA19-9, CEA, alterations in p53, K-Ras . . .) have not delivered: early diagnosis of PB malignancy or definition of an extremely high risk patient group who perhaps require more, as opposed to fewer, diagnostic procedures. The future of ERCP is like, “The check is in the mail.” It may or may not arrive. Even if it does, the check may be so delayed as to prove almost worthless. The evolution of ERCP, of course, will not occur in a vacuum and its future will be contingent upon parallel advancements in imaging and lab testing and breakthrough technology or techniques in other disciplines such as laparoscopic or transgastric surgery, more effective and less toxic chemoirradiation, or even alternative endoscopic therapies delivered by EUS. Nevertheless, we predict a bright decade for ERCP and suggest that even at its 50th anniversary, it will remain a vibrant technology and technique in the care of patients with PB disease. It is with this timeline and cumulative perspective that the editors have assembled this ERCP text. Many of the world’s experts have contributed chapters and video material in an attempt to make this book not only relevant, but comprehensive, for any endoscopist who utilizes ERCP in their practice. Omissions, if any, are ours. Technology changes rapidly and reusable cholangioscopes (e.g. Spy ScopeTM) will have been introduced by the time this text is published and it is likely that other technology may be rendered obsolete. Clinical trials may fuel or dampen our enthusiasm for one procedure or another. Despite this, the editors have done their best to produce a text that will put both evolving technology and current techniques into clinical perspective. After all, ERCP remains a clinical tool to facilitate patient care and improve clinical outcomes. It is our hope and intention that this book facilitates and improves that care. Todd H. Baron, MD Richard A. Kozarek, MD David L. Carr-Locke, MD

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List of Contributors Dr Douglas G. Adler Assistant Professor of Medicine, Director of Therapeutic Endoscopy Huntsman Cancer Center University of Utah School of Medicine Salt Lake City UT USA Dr Sushil K. Ahlawat Assistant Professor of Medicine Department of Medicine, Gastroenterology Division Georgetown University School of Medicine Georgetown University Hospital Washington DC USA Dr Jawad Ahmad Assistant Professor of Medicine and Co-Medical Director of Liver Transplantation University of Pittsburgh Pittsburgh PA USA Dr Firas H. Al-Kawas Professor of Medicine and Chief of Endoscopy Gastroenterology Division Georgetown University Hospital Washington DC USA Dr Raed M. Alsulaiman Assistant Professor of Medicine and Consultant Internist, Gastroenterologist King Faisal University King Fahd Hospital of The University Alkhobar Kingdom of Saudia Arabia Dr Tiing Leong Ang Consultant Gastroenterologist Department of Medicine Changi General Hospital Singapore Dr John Baillie Professor of Medicine Division of Gastroenterology Wake Forest University Health Sciences Winston-Salem NC USA Dr Alan Barkun Professor of Medicine and Chairholder the Douglas G. Kinnear Chair in Gastroenterology Director, Division of Gastroenterology McGill University and the McGill University Health Centre Montréal, Québec Canada

Dr Todd H. Baron Professor of Medicine Mayo Clinic College of Medicine Rochester MN USA Dr Suryaprakash Bhandari Associate Consultant Institute of Advanced Endoscopy Jaslok Hospital Mumbai India Dr Kenneth F. Binmoeller Director, Interventional Endoscopy Services California Pacific Medical Center San Francisco CA USA Dr William R. Brugge Associate Professor of Medicine, Harvard Medical School Director of Endoscopy, GI Unit Massachusetts General Hospital Boston MA USA Dr Jonathan M. Buscaglia Therapeutic Endoscopy Fellow Division of Gastroenterology and Hepatology The Johns Hopkins University School of Medicine Baltimore MD USA Dr David L. Carr-Locke Director The Endoscopy Institute Brigham & Women’s Hospital Boston MA USA Dr Annie On-On Chan Associate Professor of Medicine Department of Medicine University of Hong Kong Queen Mary Hospital Hong Kong Dr Suyi Chang Gastroenterologist Kaiser Permanente Walnut Creek CA USA Dr Ann M. Chen Clinical Instructor University of California, Irvine Comprehensive Digestive Disease Center Orange CA USA xi

LIST OF CONTRIBUTORS

Professor Guido Costamagna Professor of Surgery and Gastroenterology Digestive Endoscopy Unit Universita Cattolica “A Gemelli” Roma Italy Dr Giovanni D. De Palma Chief, Section of Diagnostic and Therapeutic Endoscopy Department of Surgery and Advanced Technologies University of Naples Federico II Naples Italy Dr Jacques Deviere Professor of Medicine Chairman, Department of Gastroenterology and Hepatopancreatology ULB—Hôpital Erasme Brussels Belgium Dr James J. Farrell Director of Pancreaticobiliary Endoscopy and Endoscopic Ultrasound Division of Digestive Disease UCLA School of Medicine Los Angeles CA USA

Dr Gregory G. Ginsberg Professor of Medicine Director of Endoscopic Services Gastroenterology Division Hospital of the University of Pennsylvania Philadelphia PA USA Dr Jaquelina M. Gobelet Fellow of The Latin American Advanced Gastrointestinal Endoscopy Training Center Santiago Chile Dr Khean-Lee Goh Professor of Medicine Head of Gastroenterology and Hepatology Chief of GI Endoscopy Faculty of Medicine University of Malaya Kuala Lumpur Malaysia

Dr Paul Fockens Professor of Gastrointestinal Endoscopy Director of Endoscopy Academic Medical Center University of Amsterdam Amsterdam Netherlands

Dr Nalini M Guda Clinical Assistant Professor of Medicine University of Wisconsin School of Medicine and Public Health Pancreatic Biliary Center St Luke’s Medical Center Milwaukee WI USA

Dr Victor L. Fox Director GI Procedure Unit and Endoscopy Program Children’s Hospital Boston Harvard Medical School Boston MA USA

Dr Robert H. Hawes Professor of Medicine Division of Gastroenterology/Hepatology Digestive Disease Center Medical University of South Carolina Charleston SC USA

Dr James T. Frakes Clinical Professor of Medicine University of Illinois College of Medicine at Rockford and Rockford Gastroenterology Associates Ltd Rockford IL USA

Dr Jürgen Hochberger Chefarzt Med Klink III—Gastroenterologie— Intervent. Endoskopie St Bernward Krankenhaus Hildesheim Germany

Dr Martin L. Freeman Professor of Medicine, University of Minnesota Director, Pancreaticobiliary Endoscopy Fellowship University of Minnesota and Hennepin County Medical Center Minneapolis MN USA

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Dr Joseph E. Geenen Clinical Professor of Medicine Medical College of Wisconsin Director, Pancreatic Biliary Center St Luke’s Medical Center Milwaukee WI USA

Dr Kunal Jajoo Advanced Endoscopy Fellow The Endoscopy Institute Brigham and Women’s Hospital Boston MA USA Dr Ann Marie Joyce Gastroenterologist Gastroenterology Department Lahey Clinic Burlington MA USA

LIST OF CONTRIBUTORS

Dr Anthony N. Kalloo Professor of Medicine Director, Division of Gastroenterology and Hepatology The Johns Hopkins University School of Medicine Baltimore MD USA Dr Peter B. Kelsey Assistant Professor of Medicine Harvard Medical School Gastrointestinal Unit Massachusetts General Hospital Boston MA USA Dr Michael B. Kimmey Professor of Medicine Division of Gastroenterology University of Washington Medical Center Seattle WA USA Dr Michael L. Kochman Professor of Medicine and Professor of Medicine in Surgery Gastroenterology Division Hospital of the University of Pennsylvania Philadelphia PA USA Dr Tadashi Kodama Chief of Gastroenterology Kyoto Shimogamo Hospital Kyoto Japan Dr Tatsuya Koshitani Chief of Endoscopy Unit Department of Gastroenterology Kyoto City Hospital Kyoto Japan Richard A. Kozarek Executive Director, Digestive Disease Institute Virginia Mason Medical Center Clinical Professor of Medicine University of Washington Seattle WA USA Dr Yuk Tong Lee Honorary Clinical Associate Professor The Chinese University of Hong Kong Prince of Wales Hospital Shatin, NT Hong Kong Dr Glen A. Lehman Indiana University Medical Center Indianapolis IN USA Dr Joseph W. Leung Mr & Mrs C.W. Law Professor of Medicine Division of Gastroenterology and Hepatology UC Davis Medical Center Sacramento CA USA

Dr Chi Leung Liu Honorary Professor of Surgery Department of Surgery University of Hong Kong Queen Mary Hospital Hong Kong Dr Simon K. Lo Director of Endoscopy, Cedars-Sinai Medical Center Clinical Professor of Medicine David Geffen School of Medicine at UCLA Division of Digestive Diseases Cedars-Sinai Medical Center Los Angeles CA USA Dr Jürgen Maiss Department of Medicine I University Erlangen-Nürnberg Erlangen Germany Dr Amit Maydeo Director, Institute of Advanced Endoscopy Chief, Department of Endoscopy and EUS Jaslok Hospital Mumbai India Dr Detlev Menke Leading Consultant Department of Medicine III St. Bernward Hospital Hildesheim Germany Dr Desiree E. Morgan Associate Professor, Diagnostic Radiology Department of Radiology University of Alabama at Birmingham Birmingham AB USA Dr Claudio Navarrete Director of Minimally Invasive Surgery Clinica Alemana-Universidad del Desarrollo Chair of The Latin American Advanced Gastrointestinal Endoscopy Training Center Santiago Chile Dr Horst Neuhaus Professor of Medicine Department of Gastroenterology Evangelisches Krankenhaus Düsseldorf Düsseldorf Germany Dr Wai Choung Ong Asian Institute of Gastrenterology Jubilee Hills Hyderabad India Dr Wai Choung Ong Asian Institute of Gastrenterology Jubilee Hills Hyderabad India xiii

LIST OF CONTRIBUTORS

Dr William M. Outlaw Fellow Division of Gastroenterology Wake Forest University Health Sciences Winston-Salem NC USA

Dr Chan-Sup Shim Professor of Medicine Digestive Disease Center Soon Chun Hyang University Seoul Korea

Dr Bret T. Petersen Professor of Medicine Division of Gastroenterology and Hepatology Mayo Clinic College of Medicine Rochester MN USA

Dr Lalit Shimpi Professor of Medicine Department of Gastroenterology & GI Endoscopy Jehangir Hospital in association with Apollo Hospitals Pune India

Dr Jeffrey L. Ponsky Department of Surgery University Hospital of Cleveland Cleveland OH USA Dr G. Venkat Rao Asian Institute of Gastroenterology Jubilee Hills Hyderabad India Dr Nageshwar Reddy Asian Institute of Gastroenterology Jubilee Hills Hyderabad India Dr Banerjee Rupa Asian Institute of Gastroenterology Jubilee Hills Hyderabad India Dr Stefan Seewald Professor of Gastroenterology Department of Interdisciplinary Endoscopy University Medical Center Hamburg-Eppendorf Germany Dr Dong Wan Seo Associate Professor of Medicine and Director of Endoscopy Unit Division of Gastroenterology, Department of Internal Medicine Asan Medical Center, University of Ulsan College of Medicine Seoul South Korea

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Dr Hardeep M. Singh Fellow, Department of Gastroenterology Kaiser Permanente Los Angeles Medical Center Los Angeles CA USA Dr Adam Slivka Professor of Medicine University of Pittsburgh Pittsburgh PA USA Dr Nib Soehendra Professor of Surgery, Director, Department of Interdisciplinary Endoscopy University Medical Center Hamburg-Eppendorf Germany Dr Ellert J. van Soest Department of Gastroenterology and Hepatology University of Amsterdam Amsterdam The Netherlands Dr Geoffrey Spencer Instructor of Medicine Division of Gastroenterology Hospital of the University of Pennsylvania Philadelphia PA USA Dr Joseph Sung Professor of Medicine Director, Institute of Digestive Disease The Chinese University of Hong Kong Prince of Wales Hospital Shatin, NT Hong Kong

Dr Syed G.Shah Consultant Gastroenterologist Department of Gastroenterology Pinderfields General Hospital Wakefield UK

Dr Paul R. Tarnasky Clinical Associate Professor of Medicine University of Texas Southwestern Methodist Dallas Medical Center Dallas TX USA

Dr Stuart Sherman Professor of Medicine and Radiology Clinical Director of Gastroenterology and Hepatology Director of ERCP Indiana University Medical Center Indianapolis IN USA

Dr Yoshihide Tatsumi Chief, Department of Gastrointestinal Diseases Matsushita Health Care Center Moriguchi Osaka Japan

LIST OF CONTRIBUTORS

Dr Mark Topazian Associate Professor of Medicine Mayo College of Medicine Rochester MN USA Dr Eduardo Valdivieso Professor of Surgery Pontificia Universidad Javeriana, Colombia Fellow of The Latin American Advanced Gastrointestinal Endoscopy Training Center Santiago Chile

Dr Benjamin Chun-Yu Wong Professor of Medicine Department of Medicine University of Hong Kong Queen Mary Hospital Hong Kong Dr Gregory Zuccaro Jr Director, Center for Endoscopy and Diseases of the Pancreas and Bile Ducts Department of Gastroenterology and Hepatology Cleveland Clinic Cleveland OH USA

Dr James L Watkins Division of Gastroenterology and Hepatology Indiana University Medical Center Indianapolis IN USA

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Dedication To our families, friends and colleagues who tolerate us To our teachers and students who taught us everything we know To our patients who amaze us and To our contributors who helped us, We dedicate this to you.

Acknowledgements Virginia Mason Medical Center:

Mayo Clinic Brigham & Women’s Hospital:

Hannah Scott, Word-Processing Terrance King, AV Support Donna Smith, Practice Support Mindy K. Parker, Secretarial Support Sandra Healey, Secretarial Support

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SECTION 1

Chapter

1

GENERAL TOPICS

Medicolegal Issues James T. Frakes

INTRODUCTION TO MEDICOLEGAL ISSUES The medicolegal environment Medicine is an imprecise science, influenced by the vagaries and unpredictable nature of biologic systems and the art of interpersonal relationships. Human illnesses are, from the outset, adverse outcomes of life, and it is often difficult for physicians to correct or mitigate these illnesses. Furthermore, the techniques, tools, and technology available to aid in this task often have associated inadequacies or risks. Therefore, restoring biologic function to its former healthy state is oftentimes incomplete, sometimes unsuccessful, and occasionally complicated by iatrogenic injury. Negative or adverse outcomes may include cognitive or technical failures, ineffective therapies, complications of therapy, high costs and extended hospitalizations, and missed work and life activities. Any or all of these may lead to patient dissatisfaction and a desire to assign blame and seek compensation. It is in this environment of personal illness and fear, limited medical art and science, patient dissatisfaction, and legal avenues for redress that medicolegal issues arise. Especially in the United States, there has been a steady increase in both lawsuits filed for medical malpractice and the size of awards granted for damages.1 Physicians and insurance companies generally blame unrealistic patient expectations, avaricious trial lawyers and inappropriately high jury awards for the increased number of lawsuits, which in turn lead to high malpractice insurance rates, diminished access to certain types of medical care and the costly practice of defensive medicine. Alternatively, attorneys and some patients blame true medical negligence, high medical costs, inadequate policing of incompetent physicians, and poor financial management by insurance companies for the worsening medicolegal climate. It is therefore appropriate for physicians to study medicolegal issues, especially in their specialty areas of practice, to optimize patient outcomes, limit patient harm and dissatisfaction, and minimize the risk of malpractice litigation.

Medicolegal issues in gastroenterology and gastrointestinal endoscopy Gastroenterologists, like all physicians, have reason to be concerned about malpractice litigation. But, data specific to gastroenterology and endoscopy are scarce. Many commercial insurance carriers are unwilling to share data on claims and awards, regarding this as proprietary information and fearing possible adverse publicity or stimulation of even greater malpractice litigation activity. One association of insurers, the Physician Insurers Association of America (PIAA), pools information from approximately 30 physician-owned

or managed insurance companies in the United States and periodically publishes data. These data probably provide the best picture of medical malpractice claims currently available. It is interesting to note that despite the increasingly complex nature of gastroenterology and gastrointestinal endoscopy, gastroenterologists are sued less often than most other specialty groups, ranking 21st of 28 specialty groups in the number of claims reported in the PIAA data.2 Gastroenterologists accounted for about 2% of claims and 1.4% of PIAA indemnity payments. About one of five gastroenterology claims resulted in indemnity payment. The highest indemnity payment has been $2.9 million, almost triple the largest gastroenterology payment reported in 1999.3 According to PIAA data, despite the fact that most gastroenterologists spend most of their time performing procedures, the basis for claims in gastroenterology from 1985 to 2004 involved cognitive issues 60% of the time, including consultations, diagnostic interviews, evaluations, medication prescriptions, injections and vaccinations. Procedural misadventures accounted for about 40% of the claims during that time period, including procedures on the hollow gut or biliary tract, including endoscopic retrograde cholangiopancreatography (ERCP). The vast majority of these endoscopy cases involved perforation of the gut, while a much smaller percentage included pancreatitis, hemorrhage, dental injury or falling from the bed while sedated. Issues involving informed consent as a secondary allegation occurred about 17% of the time.

Medicolegal issues in ERCP Because ERCP is one of the most technically difficult procedures performed by gastrointestinal endoscopists and because complications, sometimes severe, are more common than with other endoscopic procedures, ERCP might be expected to account for a disproportionate number of claims against gastroenterologists. However, the relative risk of litigation arising from ERCP, despite the significantly higher rate of complications, appears to be less than twice that of significantly less complex procedures such as flexible sigmoidoscopy or gastroscopy.4 In one Canadian database, ERCPrelated events accounted for only about 6% of gastrointestinal-related legal actions from 1990 to 1997.5 One possible explanation for this seeming paradox is the more intensive informed consent processes for ERCP when compared with simpler endoscopic procedures. This hints at the importance of adequate informed consent as a risk management strategy. After a discussion of legal principles of importance in medical practice, specific risk management strategies for ERCP will be outlined below, including sound medical practice, avoidance of complications, and truly informed consent. 3

SECTION 1 GENERAL TOPICS

IMPORTANT LEGAL PRINCIPLES IN MEDICAL PRACTICE Elements of a malpractice case: the principles of tort law

The general concept

The most common form of a medical malpractice action falls under the principles of tort law, a “civil wrong” rather than a criminal action. Such civil wrongs are generally compensated by monetary redress. To succeed in a medical malpractice action, the plaintiff must prove four basic legal elements by a preponderance of evidence (the fact at issue is more probable than not) rather than proving beyond a reasonable doubt as in criminal actions.4,6,7 These four basic elements that must be proven are: 1. The physician owed a duty of care to the patient. 2. The physician breached that duty by violating the applicable standard of care. 3. The breach of duty caused an injury. 4. The patient’s injury is compensable (damages).

The standard of care is a legal concept describing the duty that physicians must fulfill in their care of patients.4,7,8 A failure to practice within the standard of care is a breach of that duty, one of the four central elements of a malpractice case. The standard of care is usually established through expert testimony, published data and accepted practice guidelines. Of these, the most important in court is expert testimony. Expert testimony seeks to establish a standard of care reflecting the practice that is customary among competent gastroenterologists in good professional standing who are practicing with reasonable diligence, and should reflect the current practice at the time of the injury. Simply stated, the standard of care is “good patient care.” It is not defined as optimal or best medical practice exhibited by only a few noted experts in the field but rather what would be expected from a reasonable peer under the same circumstances.

Duty

Majority and minority standards

The physician’s duty to the patient arises from the physician–patient relationship. If there is no physician–patient relationship there is no malpractice risk. The relationship is usually created through an office visit, hospital visit or performance of a procedure, but may be created without actual face-to-face meeting between the physician and patient. For example, an appointment for an office visit or endoscopic procedure or the prescribing of a colon cleansing agent prior to colonoscopy might create such a physician–patient relationship. Clearly defining a physician’s duty or role in the management of a patient, thereby limiting the scope of the duty, might help to reduce subsequent liability. Once established, the physician-patient relationship continues until officially and appropriately terminated by the patient or physician.

Because there are often many ways to manage a clinical problem, more than one standard of care may be applicable for evaluating or treating a condition. Practicing the “majority” standard, or most commonly taken approach by most peers, is usually the most defensible method of practice. A less common approach, the “minority” standard, may be acceptable, but should be explained in terms of why a strategy differing from the usual was employed. As stated in one recent publication, “physicians who practice in ignorance of the majority standard do so at their peril.”7

Breach of duty The duty of the physician once the physician–patient relationship has been established is to practice within a reasonable standard of care. Failure to meet the standard of care constitutes negligence and is the central issue in most medical malpractice litigation. While often difficult to define, a reasonable standard of care is usually established with the aid of expert witnesses acting as medicolegal consultants.

Causation To be successful in a medical malpractice suit, the plaintiff must prove that substandard care was the proximate (substantial rather than minor) cause of injury.

Injury Further, to succeed, the plaintiff patient must establish that some type of physical or psychological injury occurred. Having shown that a breach of duty caused an injury, one or more of three types of damages might be awarded in the form of monetary payments. These include general damages for pain and suffering; special damages for past, present and future medical expenses, loss of income, wages and profits; and punitive damages for gross negligence such as intentional harm, conscious indifference, or fraud. Punitive damages are generally not covered by malpractice insurance. 4

STANDARDS OF CARE

Guidelines Guidelines, or so-called practice parameters, developed by specialty societies, federal agencies, or panels of experts may be useful in establishing standards of care. These professional guidelines are often widely available and provide consensus statements codifying professional custom which may then form the actual basis for a legal standard of care. The validity of such guidelines stems from the sponsoring organization’s expertise and prestige, the nature and purpose of the guideline, conflicting views held by other authorities, and the direct applicability of the guideline to the case under consideration. While it might be tempting to assume that clinical guidelines would reduce malpractice risk by helping physicians understand a consensus of “good care,” in reality such guidelines are more likely to be used in malpractice litigation by the plaintiff as evidence that the physician failed to meet the standard of care.

Expert testimony The most common method of establishing a standard of care and subsequently a breach of duty is to rely on expert testimony from a medical witness. Such an expert witness should be appropriately licensed and board certified and should have been practicing in the medical specialty area in question for at least 3 of the previous 5 years.9,10 For such testimony the expert should receive reasonable compensation not based on a contingency fee. The opinion of the medical expert should be unbiased and non-emotive, and as such it should not matter whether the expert is retained by the plaintiff or the defendant. Expert testimony requires a review of the medical record and an opinion regarding the patient’s care. Such an opinion

Chapter 1 Medicolegal Issues

may be given in a variety of formats including affidavit, deposition or even testimony in court. The expert medical witness provides an important service to patients, physician colleagues, and the courts provided that such opinions are thoughtful, accurate and unbiased.

Vicarious liability While most medical malpractice actions are taken against an individual directly involved with an alleged wrongdoing, there is also a legal concept which allows liability to be extended beyond someone who directly caused an injury to persons on whose behalf that person may have acted. This may mean that physicians may be held liable not only for their own actions but also for the actions of others in some type of subordinate role. Such liability is referred as vicarious liability.11,12

Respondeat superior Respondeat superior is a legal principle that holds a master responsible for the wrongdoings of his servants. These “master–servant” definitions have evolved to include employer–employee relationships, corporate agent relationships, and teacher–student relationships.12–15 These relationships may apply to preceptors, proctors, administrators or employers. Such a concept allows blame to be shared among doctors, trainees, nurses, institutions, etc. and may provide additional financially responsible defendants, some with potentially greater resources than the original defendant, to share the liability for an injury.

Preceptor The concept of a preceptor as a teacher or instructor in the area of gastrointestinal endoscopy is central to the training of young physicians new to the specialty and to practicing physicians acquiring new skills. Such a preceptor endoscopist might be found vicariously liable for current or future acts of his trainee. More to the point of ERCP, a supervising endoscopist might be held liable for part of the damages arising from a trainee learning the procedure, an experienced colleague acquiring new skills, or either in future misadventures. The degree of liability attributable to each of the principals would depend on many factors, including knowledge on the part of the patient that the procedure would be performed by a trainee, the experience of the trainee and whether the trainee was performing the procedure within an appropriate standard of care such that the procedure was done for reasonable indications and with appropriate skill. With regard to future injuries after completion of training, liability would hinge on the appropriateness of training and the veracity of credentials.

Proctor A physician who observes and monitors another physician, particularly one seeking privileges, is known as a proctor. Proctors have no duty to the patient and therefore no liability since their role is simply to assess the capabilities of the physician being monitored. If the proctor becomes involved in the care of the patient, however, this could change. To avoid such entanglement, the proctor should not interfere with the proctored physician, should have a thorough understanding of proctoring and hospital endoscopy privileges, should not offer advice or interact with the patient, should only report to the hospital or regulatory committee, and in the event he/she witnesses substandard medical care which is harmful to the patient, should consider contacting an appropriate superior,

asking the proctored physician to discontinue the questionable actions, or, as a last resort, intervening with careful appropriate documentation.

Employer liability A physician may be held responsible for an adverse outcome attributable to substandard service by office staff such as violations in patient confidentiality, violations in sterile technique, or failure to provide appropriate training and supervision to ensure the proper functioning of office staff.

Administrator If a physician acts in an administrative capacity in an endoscopy unit or gastroenterology division, he/she has a duty to patients receiving care in that unit. Failure to develop policies and procedures that ensure a safe environment and comply with state and federal regulations may constitute vicarious liability. Such responsibilities may include the acquisition and maintenance of endoscopic equipment, privileging, infection control and workplace safety. Further, if the responsible director knew or should have known that an unskilled physician was practicing in the unit and did not take appropriate corrective actions, vicarious liability could exist.

Hospital liability Hospitals may be held responsible for the mistakes of a hospitalbased physician employed by that institution or for inadequate oversight provided by endoscopy unit or gastroenterology division directors. They may also incur vicarious liability for improperly privileging physicians who are inadequately trained to perform a certain service.13,15

Summary In summary, the gastroenterologist or gastrointestinal endoscopist may incur liability for mistakes of individuals whom they supervise even if they themselves were unaware of the improper actions and even after their immediate supervisory role had ended. All of the aforementioned roles of preceptor, proctor, employer and administrator should be approached with care and forethought. An understanding of potential vicarious liability may allow better risk management strategies to minimize exposure to liability.

INFORMED CONSENT Introduction Medical malpractice actions most commonly involve the “tort of negligence” wherein a physician is felt to have practiced below the standard of care (“breach of duty”). There is, however, a common and independent cause of malpractice action involving the failure to obtain informed consent.16–19 This is often a secondary allegation filed along with an allegation of practicing below the standard of care.

Theory of informed consent The ethical and legal requirement to obtain informed consent prior to a procedure comes from the concept of personal patient autonomy and is rooted in the theory of patient self-determination. Against such a backdrop, the courts have found that a person’s right to selfdetermination warrants that a physician obtain informed consent. The competent patient, after receiving appropriate disclosure of 5

SECTION 1 GENERAL TOPICS

material risks of the procedure in question, and understanding the risks, benefits and alternative approaches, then makes a voluntary and uncoerced informed decision of whether to proceed. Early on, the consent process operated under a provider-based standard (professional standard of disclosure) whereby the physician was expected to disclose information about the treatment that reasonable physicians believed relevant and that reasonable physicians generally disclosed to their patients in similar circumstances. More recently, however, courts have been moving toward a patient-based standard which mandates that a treating physician disclose as much information as a reasonable patient would wish to know. The essential elements of informed consent include: 1. The nature and character of the proposed procedure, preferably in non-technical terms. 2. The reason or indication for the procedure. 3. The likely benefits of the procedure. 4. The material risks and complications of the procedure, including their relative incidences and severities. 5. The alternatives to the procedure, including those which may be more or less hazardous than the one proposed, and the alternative of no treatment. The consent process should also include an assessment of the individual’s competence to understand the information presented and the opportunity for patients to ask questions. Obtaining informed consent is a process that includes more than placing a signature on a standardized consent form. It involves mutual communication and decision making and can advance the physician–patient relationship. It can also be a risk management tool, transferring responsibility for risk to the patient who has understood and accepted that even competently performed procedures can have adverse outcomes.

Material risks One essential element of disclosure is discussion of the risks and potential complications of the procedure. These risks should include procedure-specific material risks, those that a reasonable patient would want to know in order to make an appropriate decision. The four elements of risk that the physician needs to consider include: 1. The nature of the risk. 2. The magnitude of the risk. 3. The probability that the risk may occur. 4. The timing of the risk, whether contemporaneous with the procedure, post-procedure or delayed. Deciding what material should be disclosed is often not easy. One authoritative text on informed consent states: “The physician must walk a fine line between providing pertinent risk information and overwhelming the patient with frightening statistics. Providing too much extraneous information may be as likely to impair informed decision making as providing too little.”20

Controversial areas The trend toward a patient-oriented standard of disclosure has allowed for a broader interpretation of the “material risks.” What a “reasonable patient would wish to know” in making an appropriate decision might now argue for pertinent disclosure of the experience level and personal complication history of the specific physician, rather than national averages, as well as any pertinent economic interests of the physician. This question of the endoscopist’s personal experience might be especially applicable to complicated

6

endoscopic procedures such as ERCP. In a legal case involving difficult and risky brain surgery, a physician was found liable for not informing the patient regarding his lack of experience.18

Exceptions to informed consent There are several exceptions to the informed consent process. These include: 1. emergencies where the patient is incapacitated to a degree that consent cannot be obtained and delay would put the patient at risk; 2. waiver of the right of self-determination, where the patient assigns that right to the physician; 3. therapeutic privilege, where the physician believes that informed consent would be detrimental to the patient, usually in an emotional sense; 4. legal mandate, whereby the court orders the patient to undergo medical therapy without the patient’s consent; 5. incompetency, where the patient is unable to make a decision and that responsibility is given to the patient’s legal guardian.

Informed refusal This doctrine holds that a patient who refuses a procedure or treatment must do so in a well informed way and that it is the physician’s duty to ensure that such refusal is informed.

Legal consequences of failing to obtain informed consent Failure to obtain informed consent is most often a secondary allegation attached to a charge of practicing below the standard of care. However, it can be an independent cause of malpractice action alleging that even though the injury was not due to substandard care, the patient would have refused the treatment or procedure if material risks had been known. The plaintiff would have to show, however, that a reasonable person in the same position would not have undergone the procedure knowing that a small risk of injury existed. If there was absolutely no consent obtained for medical treatment, or if the treatment went well beyond the scope of consent, a charge of battery could be lodged. Although rare, a charge of battery is a criminal charge and is not covered by most malpractice insurance.

RISK MANAGEMENT STRATEGIES FOR ERCP Introduction Risk management is a process designed to identify reasons for poor patient outcomes and to suggest corrective actions to prevent both patient injury and malpractice risk. The formal process includes defining situations that place the patient and physician at risk, determining the likelihood and significance of these circumstances, applying risk management strategies to individual cases and developing preventive measures. The following risk management strategies are generalizable to all medical practice and all gastrointestinal endoscopic procedures, but have been adapted to apply specifically to ERCP. They include sound medical practice, including proper training; rigorous privileging; understanding and avoiding complications and lawsuits; and dealing with lawsuits once filed.

Chapter 1 Medicolegal Issues

Sound medical practice The best defense against adverse outcomes and malpractice suits is good medical practice. The first step in developing sound medical practice is attaining competence through proper training.

Competence Competence is defined as the “minimal level of skill, knowledge, and/or expertise derived through training and experience that is required to safely and proficiently perform a task or procedure.”21 Simply stated, this means having been trained adequately to develop endoscopic skills and acquire the knowledge required not only to recommend and perform endoscopic procedures, but to interpret and correctly manage the findings of these procedures. Thus competence assures a safe, accurate, technically safe procedure. Conversely, incompetently performed endoscopy, particularly ERCP, can result in patient injury, incorrect or missed diagnoses, and incomplete procedures, which in turn lead to missed or delayed diagnoses, additional procedures and other testing for the same condition. There are two components to ensuring competence: training and subsequent demonstration of competence.

Training The American Society for Gastrointestinal Endoscopy (ASGE) has promulgated guidelines to ensure adequate training in gastrointestinal endoscopy, patient monitoring and sedation and analgesia.22 Training in ERCP should take place within the context of a global clinical training program in the fields of adult or pediatric gastroenterology or general surgery. Training obtained outside of a formal training program must conform to the same guidelines as for formal fellowship or residency training, and short courses on endoscopy, or ERCP in particular, are not adequate to attain competence. Once training is complete, competence should be assessed and evaluated by the training program director who can provide documentation of the individual’s competence. Alternatively, direct observation by an impartial credentialed endoscopist might also suffice for an endoscopist who received training outside of a formal training program. Complex diagnostic and therapeutic procedures are employed less frequently than standard procedures and are more prone to have complications and adverse outcomes. These advanced endoscopic procedures, including ERCP, require greater skill and are concentrated in the hands of fewer individuals. The ASGE recommends that trainees wishing to acquire advanced endoscopic skills should have first completed a standard endoscopy training program during an approved GI fellowship (or equivalent training) and then receive further training in specific advanced procedures. Training in ERCP is covered elsewhere in this book (Chapter 7), and the information will not be recounted in detail here, but available data suggest that at least 180–200 ERCPs are required for the usual trainee to achieve competence.23,24 In addition, expert endoscopists are generally expected to perform at a 95–100% technical success level, and current research supports establishing a standard of 80–90% technical success before trainees are deemed competent in a specific skill.21 This type of training in ERCP is necessary to assure good patient outcomes and minimize complications and failed procedures which could subsequently result in malpractice litigation.

Continued competence Ensuring continued competence is an additional safeguard against adverse patient outcomes and malpractice litigation. Maintaining

clinical and endoscopic skills in ERCP requires an ongoing effort. This effort includes staying current with GI literature concerning ERCP, engaging in continuing medical education activities and achieving familiarity with new endoscopic technologies. In addition, the endoscopist performing ERCP must also maintain an adequate case volume to maintain expert procedural skills. In general, studies have shown a correlation between higher case volumes and greater technical success.24–26 Furthermore, higher ERCP volume has been associated with lower complication rates, especially with respect to severe complications. Also, there is probably an important effect of lifetime experience. Some experienced individuals may, based on that lifetime experience, be able to maintain high success rates and low complication rates despite performing only a modest volume of ERCPs.26

New technology ERCP has been a robust field for the development of new endoscopic techniques and procedures. New techniques require new skills both major and minor. A major skill is a new technique or procedure that involves a high level of complexity. Such techniques require formal training within a training program or through the guidance of a preceptor before competence can be assessed. Within the realm of ERCP, these major skills require interventions beyond standard biliary stone removal and simple stent placement. Minor skills include new non-experimental developments that are merely minor extensions of an accepted and widely available technique or procedure. These techniques for ERCP require limited education and practical exposure such as that which can be obtained from short courses, training videos, CD-ROMs, DVDs and interactive computer programs. A few caveats regarding malpractice exposure are needed with regard to new endoscopic technology. Endoscopists wishing to acquire new technologies should not overestimate the need for these nor overestimate their own skill level in seeking to acquire such techniques. Who is “experienced” enough to appropriately incorporate new or more advanced skills into one’s practice and how is the training acquired? No rigid standards apply, but my personal guideline for experience and skill would be three years of experience beyond training, 95% technical success in gaining access to the desired duct, and a low personal complication rate compared to national averages. Further, there should be a compelling clinical need in one’s practice and a persuasive lack of an alternative expert to refer to. Skills should be acquired in a formal training program or through a hands-on preceptorship with an experienced expert. It would not be wise to undertake a newly described but inadequately assessed technique or to engage in cases which are risky or difficult early in the endoscopist’s experience. Ignoring these caveats will expose patients to adverse outcomes and endoscopists to malpractice litigation. A further caveat relates to vicarious liability. The expert endoscopist should not train the unprepared novice endoscopist to take on complex difficult tasks before that trainee has the necessary training and experience to safely acquire these skills. Furthermore, training less-than-expert ERCP endoscopists for a technically difficult and seldom needed procedure exposes patients, endoscopists, and trainers to lawsuits, including lawsuits involving vicarious liability. These procedures should probably be conducted at advanced centers for complex or high risk cases, and ERCP, particularly with advanced techniques, should be concentrated among fewer

7

SECTION 1 GENERAL TOPICS

endoscopists who would thereby perform these procedures more frequently.

Ensuring competence through privileging Privileging is the process by which an institution authorizes an individual to perform a specific procedure.21 These privileges should be determined separately for each type of procedure, particularly for advanced procedures such as ERCP. The privileging process includes a review of credentials provided by the training program or trainer, and a review of the training experience and case load for each procedure for which privileges are requested. Finally, an actual observed level of competency should be assured through proctoring, particularly for advanced procedures. Additionally, institutions should have guidelines on recredentialing and reprivileging which ensure continued competence in all procedures, but particularly the more complex advanced procedures such as ERCP. Hospitals have a duty to exercise due care in granting privileges to physicians and they expose themselves to liability for granting specialized privileges to the poorly trained or inexperienced.12,13,15 This vicarious liability extends not only to the hospital, but also to individuals in administrative roles such as the director of the endoscopy unit.

Peer review Peer review is intended to identify problems related to adverse outcomes, prevent their recurrence and help in the reprivileging process. Ideally, this should be done in a non-threatening manner, but should be a formal process with a written record. Each physician should have a personal compilation of his/her own adverse events for comparison with peers.7,21,27 Patients have a right to know, in general terms, the physician’s outcome profile.

Interpersonal skills Another component of sound medical practice, in addition to cognitive and procedural competence and careful privileging, is the interpersonal skill of the practitioner. This must be developed during training and polished once in practice. Effective communication with the patient and family and with other physicians and healthcare providers is a critical element in good healthcare and risk management. Conversely, patient dissatisfaction with physician interpersonal and communication skills can be a major factor in the decision to file a lawsuit.28,29 Displaying a positive caring attitude and communicating honestly, beginning with the initial interview and extending to informed consent and beyond, are critical in forming a healthy physician–patient relationship. This good patient rapport decreases the likelihood of lawsuits. It also helps define the role of the physician, limiting the physician duty, and transferring some of the responsibility for an adverse event to the informed patient.

UNDERSTANDING WHY COMPLICATIONS AND LAWSUITS OCCUR ERCP has evolved from a diagnostic tool to a predominately therapeutic procedure for a variety of pancreaticobiliary problems. It is a complicated and sometimes dangerous procedure which can result in a wide range of short-term complications including pancreatitis, hemorrhage, perforation and infection. These complications and other adverse outcomes can lead to patient injury, dissatisfaction and lawsuits. 8

COMPLICATIONS OF ERCP Complications of ERCP and sphincterotomy have been covered in excellent detail by Freeman elsewhere in this book (Chapter 6). Discussions of risk management strategies, however, require reviewing some of the information presented elsewhere. The complications of ERCP and sphincterotomy can vary widely in different clinical circumstances. These complications appear to be related primarily to patient-related factors, including the indication for the procedure, and to the technical skill of the endoscopist.26 The risk factors for overall complications include suspected sphincter of Oddi dysfunction and technique-related factors such as difficult cannulation, the use of precut sphincterotomy in inexperienced hands, failure to achieve biliary drainage, and use of percutaneous transhepatic biliary access. All of these risk factors result in higher rates of complications for endoscopists who have low case volumes. Patient related risk factors for post-ERCP pancreatitis include younger age, female sex, suspected sphincter of Oddi dysfunction, prior post-ERCP pancreatitis, absence of jaundice and absence of chronic pancreatitis. Furthermore, many of the patient-related risk factors are cumulative. Technique-related risk factors include difficult cannulation, multiple contrast injections of the pancreatic duct, performance of pancreatic sphincterotomy, balloon dilation of the biliary sphincter and precut sphincterotomy in inexperienced hands. Risk factors for hemorrhage include coagulopathy, acute cholangitis, bleeding during the procedure, resumption of anticoagulation immediately after the procedure, and endoscopist inexperience. Although rare, perforation during ERCP is probably more common with Billroth II anatomy, with needle-knife access sphincterotomy, and in patients suspected of having sphincter of Oddi dysfunction. Furthermore, the sequelae of perforations are sometimes magnified by delays in recognition and management. Cholangitis complicating ERCP results mainly from failed or incomplete biliary drainage, or from failure to give preprocedure antibiotics in the patient with biliary obstruction.

Why are lawsuits filed? Data regarding lawsuits involving endoscopy are scarce and usually relate to the more common endoscopic procedures. Information on the total volume and causes of ERCP-related lawsuits is even more scarce. However, an analysis of a personal series of reviews of 59 cases of alleged ERCP malpractice is particularly instructive as to the reasons for ERCP lawsuits.30 Half of the cases involved pancreatitis; 16 sustained perforation after sphincterotomy (8 of which involved precutting), and 10 had severe biliary tract infection; 15 of the patients died. In this series, the most common allegation, in 32 cases, was that the procedure or associated therapeutic maneuver was not indicated. This was also a secondary allegation in another 16 patients. These allegations were based on inadequate or weak evidence for biliary or pancreatic pathology. The second commonest allegation, in 19 cases, was that procedures were performed negligently. This was a secondary allegation in 4 additional cases. Poor post-ERCP care was alleged in a total of 15 cases and inadequate informed consent was cited as a secondary allegation in 15. The author and accompanying editorials30–32 concluded that ERCP carries a risk of life-threatening complications, that it should be performed only for good indications and after non-invasive techniques have been exhausted, and only with truly informed consent. Also,

Chapter 1 Medicolegal Issues

precutting for marginal indications is particularly hazardous. Finally, it was stated that “Speculative ERCP, sphincterotomy, and precuts, are high risk for patients and for practitioners.”

STRATEGIES TO AVOID COMPLICATIONS AND LAWSUITS A risk-factor assessment may help the endoscopist decide whether or not to perform ERCP and, if ERCP is undertaken, aids in making decisions regarding the techniques to be utilized.

Indications Patients with marginal indications for ERCP are most likely to develop complications,26 or as stated by Peter Cotton in a 2001 editorial, “ERCP is most dangerous for people who need it least.”33 Based on his more recent analysis of lawsuit reviews,30 he would likely add “and they are most likely to sue.” As a risk management strategy, marginal cases should be avoided and alternative imaging techniques such as endoscopic ultrasonography (EUS), magnetic resonance cholangiopancreatography (MRCP), or intraoperative cholangiography should be utilized instead. Although “marginal cases” are admittedly difficult to define, some clinical settings that fit this description include patients with vague abdominal pain without objective evidence of biliary or pancreatic pathology, mildly abnormal serum liver chemistries without jaundice, precholecystectomy, or suspected sphincter of Oddi dysfunction.

Technique Useful technique-related risk management strategies exist in addition to patient- or indication-related risk factors for complications, particularly for post-ERCP pancreatitis. These include avoiding multiple injections of the pancreatic duct and avoiding either pancreatic sphincterotomy or precut sphincterotomy in inexperienced hands. Regarding post-sphincterotomy hemorrhage, attention to preexisting coagulopathy is important, as is delaying restarting anticoagulants for at least three days after sphincterotomy. Avoiding sudden precipitous “zipper cuts” is also important, as is injecting the edges of the sphincterotomy if any bleeding is detected or coagulopathy is present. With cholangitis, care should be taken not to inject an obstructed segment if the endoscopist is unprepared to establish drainage. Some feel that it is helpful to aspirate the obstructed or infected segment before injecting contrast. Careful stent selection to maximize successful drainage is also important, as are pre- and post-procedure antibiotics. The risk of perforation can be lowered by avoiding repeated “hook and pull” maneuvers with the duodenoscope, difficult anatomies (Billroth II or Roux-en-Y gastroenterostomies, minor papilla cannulations, short intramural segments), and riskier pathologies (sphincter of Oddi dysfunction, multiple large stones or snare removal of ampullary neoplasms). Of course, good technique is important for the sphincterotomy including appropriate length, good control and orienting the cut in the 11:00 to 1:00 o’clock position. One of the big problems with perforation is delayed diagnosis, so a high index of suspicion and early evaluation with CT scanning with oral contrast is important. Surgery should be considered for large leaks or fluid collections, in patients with severe pain, guarding or crepitus, with signs or symptoms of major sepsis, or in the clinical situation of deterioration or no improvement within the first 24 hours. Risk of cardiovascular complications is decreased by remembering that these are the

leading cause of death from ERCP.34 One should not be hesitant to use an anesthesiologist for assistance in appropriate clinical situations. As a further risk management strategy, if ERCP is performed in high-risk patients such as younger patients, women with normal bilirubin or possible sphincter of Oddi dysfunction, prolonged attempts at cannulation and other high-risk maneuvers should be avoided and the placement of a pancreatic stent should be considered in appropriately experienced hands.26 Pancreatic stents appear to be particularly helpful in preventing post-ERCP pancreatitis in patients with sphincter of Oddi dysfunction and in those who have undergone pancreatic sphincterotomy or precut access sphincterotomy. However, such stenting has not been proven to be safe or effective in less experienced hands. Furthermore, needle-knife access sphincterotomy is probably best avoided entirely by the less experienced. A final word on technique concerns contrast allergies. The appropriate risk management strategy is simply to have and adhere to a specific policy regarding contrast allergies. Short-cutting the policy regarding contrast allergies simply for patient convenience may well result in an adverse outcome and would be extremely hard to defend in court. Either not having a policy (ignorance of the problem or having not dealt with it) or ignoring a well-thought-out policy would be indefensible.

Informed consent As described earlier, obtaining informed consent is a process which extends beyond the actual signing of a signature on a standardized form. It includes assessing the competence of the individual, disclosure of appropriate information to allow an informed decision, and ensuring that the decision made by the patient is voluntary. It is a communication and decision-making process which can cement the physician–patient relationship and serve as a risk management tool. Within the realm of gastrointestinal endoscopy, this management of risk is especially important with ERCP. Transferring some responsibility for the appreciable risks to the patient, who has understood and accepted that even competently performed ERCP can result in severe adverse outcomes, is a significant risk management tool. The possibility of severe adverse outcomes with ERCP is so real that they cannot be glossed over or minimized if the patient is to be truly informed and the decision making is to be truly shared. Some even advocate disclosing personal experience level and outcomes in the consent process.27

Documentation Good documentation is an essential risk management tool and also a component of good medical care. The old adage “If it isn’t written down, it didn’t happen” is often true in litigation. If a discussion is well documented in the notes, a court will generally accept that something was discussed or did occur. Conversely, lack of documentation may persuade a court or jury that a conversation did not occur if the patient denies it. Written documentation has generally been viewed as adequate, although some have advocated videotaping the consent process as an extreme method of documenting exactly what occurred.7 Documentation of informed consent is extremely important with ERCP. A simple note affirming that discussions occurred regarding the nature of the procedure, alternatives, risks (enumerating the major risks), sedation, and an opportunity for questions goes far in assuring that the physician has fulfilled this part of the duty to the patient and that the patient has participated in the decision9

SECTION 1 GENERAL TOPICS

making process, thereby accepting some of the risk of the procedure.

Managing complications ERCP is difficult and complex. Complications will occur even with good patient selection and good technique. The risk is real and unavoidable. Complications happen with all endoscopies and it is important that they be handled well. The fact that a complication has occurred is not malpractice in and of itself. The failure to make a timely diagnosis of the complication could be, however. It is important that the endoscopist recognize the possibility of post-ERCP complications and be attentive to their signs and symptoms. Early diagnosis and treatment are often vitally important. As important as early diagnosis and treatment is communication with the patient and family. A full explanation of the situation and the plan of treatment is necessary. Empathy, compassion, and honesty are essential. But this does not require self-denigration or an unnecessary admission of wrongdoing. Complications are a known risk of ERCP and informed consent has allowed the patient to accept and share in that risk. During the treatment of complications, it is important to maintain contact with the patient and family so as not to engender feelings of abandonment and further to ensure that all necessary consultations are obtained expeditiously. Although often personally uncomfortable for the physician, such continued contact with the patient and family promotes good medical care, demonstrates compassion and helps manage legal risk. Finally, it is important to inform the insurance carrier following any major complication or significantly litigious situation.

LIMITING FINANCIAL AND PSYCHOLOGICAL COSTS OF LAWSUITS

A SUMMARY OF RECOMMENDATIONS

Insurance

Freeman’s analysis has suggested that avoidance of marginal indications for ERCP may be the single best way to avoid complications.26 Cotton’s article on ERCP-related lawsuits suggests that avoidance of marginal indications also may be the single best way to avoid medical litigation.30 These insights plus recent opinions on medicolegal issues31,32 suggest the following risk management strategies to avoid ERCP-related complications and lawsuits: 1. Practice within a reasonable standard of care and avoid risky cases. See Box 1.1. 2. Use good ERCP technique, avoiding advanced ERCP techniques if inexperienced and utilizing pancreatic duct stents for high risk patients if appropriately experienced. 3. Utilize informed consent as a communication and decisionmaking process to transfer some responsibility for risk to the patient, who has understood and accepted that even competently performed procedures can have adverse outcomes. 4. Employ good documentation of clinical events, decision making and informed consent. 5. Be vigilant to assure early recognition and management of complications, communicating honestly and with empathy and compassion with the patient and family, and maintaining contact with them throughout the post-complication period. Drs. Freeman and Cotton have persuasively demonstrated that to minimize the risk of ERCP-related complications and lawsuits one should avoid ERCP that is marginally indicated, too difficult for one’s experience level or if ERCP is performed infrequently. 10

BOX 1.1 RISKY CLINICAL SITUATIONS FOR ERCP-RELATED COMPLICATIONS AND LAWSUITS Marginal cases Vague abdominal pain without objective evidence of biliary or pancreatic pathology Mildly abnormal serum liver chemistries without jaundice in the pre-cholecystectomy patient Suspected sphincter of Oddi dysfunction Technically difficult cases Past history of difficult cannulation or post-ERCP pancreatitis Precut (access) sphincterotomy Minor papilla cannulation Percutaneous biliary access Billroth II or roux-en-y gastroenterostomy Obstruction at the biliary bifurcation Infrequent cases Sphincter of Oddi manometry Pancreatic therapeutics Large or intrahepatic stones Snare ampullectomy

Every physician should have adequate indemnity coverage for lawsuits that occur now or in the future. Keeping adequate malpractice insurance is important to ensure that injured patients have access to compensation if they are inappropriately injured and to safeguard the financial well-being of the individual physician and institution.

If a lawsuit is filed The possibility of being sued is unavoidable. Nothing, not even superb medical practices, will absolutely protect one from a lawsuit. The severity of adverse patient outcomes is a more important predictor of plaintiff success in winning a malpractice claim than whether the physician was indeed negligent.35 Sympathetic juries and judges often wish to reward an injured plaintiff irrespective of actual negligence. It is important that physicians, particularly those involved in high-risk procedures such as ERCP, accept realistic goals and realize that lawsuits may occur. It is also important to remember that medical litigation is a long and stressful process for physicians and their families. Psychologic support is important, but casual discussion of lawsuits is inadvisable since discussions with friends and colleagues can be elicited through subpoena. It is also heartening to note that physicians win the majority of malpractice suits. In Cotton’s recent analysis of 59 ERCP lawsuit cases, where the final outcome was available in 40, 16 were withdrawn, 14 were settled, and of the 10 going to trial, half were decided for the plaintiff and half for the defense.30 Obviously if a lawsuit is filed, the physician’s insurance carrier must be notified and it is the responsibility of the physician to aid the insurance company in the defense of the case.

Chapter 1 Medicolegal Issues

Physicians should become educated in the litigation process. Depositions generally benefit plaintiffs and are used as tools to gain information to help press cases against defendants. During deposition, physicians should be truthful but volunteer as little information as possible. Excessive elaboration can only harm the defendant. In deposition and at trial demeanor is important. Arrogance, anger, or dismissive behavior will only reflect poorly upon the physician and engender sympathy for the plaintiff. It is also important to be well prepared for any type of testimony. Malpractice attorneys are usually intelligent and well versed. Physicians should be similarly knowledgeable and well prepared and should be deliberate in their testimony, pausing before every answer to ensure a proper and accurate response.

standards of care and informed consent. The pancreaticobiliary endoscopist must realize that the deviations from a reasonable standard of care most likely to lead to ERCP related medical litigation include procedural indications, procedural technique, post-ERCP care and issues of informed consent. With this understanding, the endoscopist performing ERCP can formulate and adopt risk management strategies to improve patient safety, satisfaction and outcomes while minimizing the risk of litigation. These strategies include practicing within a reasonable standard of care, focusing attention on the informed consent process and documentation, and understanding specific patient-related and technique-related risk factors for complications and lawsuits (Box 1.1).

SUMMARY ERCP is a complex and difficult procedure with significant risks for adverse patient outcomes and for medical litigation. It is important for endoscopists performing ERCP to understand liability issues related to ERCP, including vicarious liability, and to understand the legal principles important in medical practice, including the elements of a malpractice case,

Acknowledgements The author is pleased to acknowledge Martin L. Greene, MD for help with access to data from the Physicians Insurers Association of America, Arnold M. Rosen, MD for constructive suggestions in editing the manuscript, and Brenda Paulson for preparation of the manuscript.

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Feld AD, Walta D. Malpractice, tort reform, and you: an introduction to risk management. Am J Gastroenterol 2004; 99(2):977–980. Physician Insurers Association of America: PIAA risk management review: Gastroenterology. Rockville, MD, Research Department, Physician Insurers Association of America, 2005. Physician Insurers Association of America: A risk management review of malpractice claims: gastroenterology summary report. Rockville, MD, Research Department, Physician Insurers Association of America, 2000. Gerstenberger PD. Malpractice in gastrointestinal endoscopy. Gastrointest Endosc Clin N Am 1995; 5(2):395–389. Springer J. ERCP: new standards, new challenges. Can J Gastroenterol 2002; 16(3):175–176. American Society for Gastrointestinal Endoscopy. Medical Malpractice. In: Petrini JL, Feld AD, Gerstenberger PD, et al. (eds.) Risk management for the GI endoscopist. Oak Brook, IL: American Society for Gastrointestinal Endoscopy; 2001:10–13. Norton I, Schroeder KW. Reporting, documentation, and risk management. In: Ginsberg GG, Kochman M, Norton I. Gostout CJ, eds. Clinical Gastrointestinal Endoscopy. London: Elsevier Science; 2005:107–112. American Society for Gastrointestinal Endoscopy. Standards of care. In: Petrini JL, Feld AD, Gerstenberger PD, et al. (eds.) Risk management for the GI endoscopist. Oak Brook, IL: American Society for Gastrointestinal Endoscopy; 2001:2–3. American College of Physicians. Guidelines for the physician expert witness. Ann Intern Med 1990; 113:789. Greene ML. Medical-legal consultation in gastroenterology. Gastrointest Endosc Clin N Am 1995; 5(2):403–419. Gerstenberger PD. Risk management for the endoscopy center. Gastrointest Endosc Clin N Am 2002; 12(2):367–384. American Society for Gastrointestinal Endoscopy. Vicarious liability. In: Petrini JL, Feld AD, Gerstenberger PD, et al. (eds.) Oak

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23. Jowell PS, Baille J, Branch S, et al. Qualitative assessment of procedural competence: a prospective study of training in endoscopic retrograde cholangiopancreatography. Ann Intern Med 1996; 125:983–989. 24. Freeman ML. Training and competence in gastrointestinal endoscopy. Reviews in Gastroenterological Disorders 2001; 1(2):73–85. 25. Petersen BT. ERCP outcomes: defining the operators, experience and environments. Gastrointest Endosc 2002; 55(7):953–958. 26. Freeman ML. Adverse outcomes of endoscopic retrograde cholangiopancreatography. Reviews in Gastroenterological Disorders 2002; 2(4):147–168. 27. Cotton PB. How many times have you done this procedure, doctor? Am J Gastroenterol 2002; 97(3):522–523. 28. Hickson GB, Federspiel CF, Pichert JW, et al. Patient complaints and malpractice risk. JAMA 2002; 287:2951–2957.

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29. Levinson W, Roter DL, Mullooly JP, et al. Physician-patient communication: the relationship with malpractice claims among primary care physicians and surgeons. JAMA 1997; 277:553–559. 30. Cotton PB. Analysis of 59 ERCP lawsuits; mainly about indications. Gastrointest Endosc 2006;63:378–382. 31. Peterini JL. Fools rush in . . . Gastrointestinal Endosc 2006;63: 383–384. 32. Frakes JT. The ERCP-related lawsuit: “Best avoid it!” Gastrointest Endosc 2006;63:385–388. 33. Cotton P. ERCP is most dangerous for people who need it least. Gastrointest Endosc 2001; 54:535–536. 34. Freeman ML. Sedation and monitoring for gastrointestinal endoscopy. In: Yamada T, ed. Textbook of Gastroenterology. Philadelphia, PA: Lippincott, Williams & Wilkins; 1999:2655–2667. 35. Brennan TA, Sox CM, Burstin HR. Relation between negligent adverse events and the outcomes of medical-malpractice litigation. N Engl J Med 1996; 335(26):1963–1967.

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GENERAL TOPICS

The ERCP Room Michael B. Kimmey

INTRODUCTION Physicians, staff and patients all appreciate the benefits of an ERCP procedure performed in a pleasant and efficient working environment. A well-planned procedure room can contribute to a successful and comfortable procedure for the patient and the medical staff. In this chapter, the components of the ideal ERCP room will be reviewed. Most ERCPs are performed in the hospital, usually in the outpatient department. This facilitates doing the procedure on hospitalized patients and allows ready access to inpatient hospital facilities for patients who need observation following the procedure. Although ERCPs can be performed in ambulatory surgery centers, current reimbursement policies in the United States do not include ERCP as an approved procedure for this setting. In addition, the higher capital costs for radiographic equipment and the ongoing costs of single-use ERCP accessories discourage the performance of ERCPs in this environment. The ERCP room can be a part of a gastrointestinal endoscopy unit where other endoscopic procedures are performed, or may be part of the hospital’s radiology department. The choice of location is often dependent on the number of ERCP cases done at the facility.1 The efficiencies of having the ERCP room in the endoscopy unit should not be overlooked. These include time savings for the physicians, nurses and technical personnel as well as reduction in time spent transporting patients and equipment. The financial benefit of these time savings is likely to justify the capital cost of the fluoroscopy equipment for endoscopy units doing over 300–400 procedures per year. In addition, fluoroscopy can be used for other endoscopic procedures such as dilation of complex strictures, placing esophageal and enteral stents, and facilitating overtube placement for enteroscopy.

DESCRIPTION OF THE ROOM The ERCP room should be large enough to accommodate all of the necessary equipment to do ERCP as well as a comfortable space for the patient, physician and two endoscopy assistants. When ERCP needs to be performed under deep sedation or general anesthesia due to patient intolerance of conscious sedation, there should also be sufficient space for anesthesia equipment and personnel. If fluoroscopy is performed using a C-arm, there needs to be sufficient room around the patient table to allow the image intensifier arm to move without being encumbered by other equipment in the room. All of these factors add up to a need for the ERCP room to be 50–100% larger than procedure rooms where routine endoscopy is performed. A room size of approximately 300 square feet has been recommended by some authorities.2,3

The ERCP room is best configured around the location of the fluoroscopy equipment and patient table. This is usually placed centrally in the room to allow access to both sides of the table and to allow adequate room for movement of the fluoroscopy unit’s C-arm. A more complete description of the options for fluoroscopy equipment, including the use of spatially fixed or mobile units can be found below. Figure 2.1 shows a generic diagram of a typical ERCP room layout and an actual ERCP room in use is shown in Figure 2.2. The patient table should be at least 30 inches wide to accommodate large patients and also allow safe patient repositioning during the procedure. It should also be sturdy enough to accommodate heavy patients, preferably to at least 400 pounds. There should be room under the head of the table for the assistant’s knees while sitting at the patient’s head and attending the patient’s airway. There should be adequate shielding below the table to reduce exposure of personnel to scattered radiation. Tables that are fixed to the fluoroscope should have a movable top for positioning the patient under the fluoroscope. Some physicians also prefer to have the table tilt to facilitate gravitational movement of contrast and air bubbles, although modern ERCP techniques and accessories have made this requirement less important than previously. Controls for table movement should be readily accessible to the endoscopist who should be able to move the table top while simultaneously holding the endoscope, if an assistant or x-ray technologist is not available. Appropriate placement of fluoroscopic and endoscopic monitors is very important. Monitors can be mounted on movable carts or booms that are fixed to the ceiling of the room. Poor monitor placement has been identified as a major contributor to endoscopist musculoskeletal injuries.4 Monitors should be set so that the endoscopist’s eye level is three-quarters toward the top of the monitor screen. Since not all endoscopists are the same height, provision for adjusting monitor position is necessary. Monitors should be placed on the opposite side of the patient, generally at a level above the head of the table directly in front of the endoscopist so that neck rotation and strain are avoided. Monitors should not restrict movement of the C-arm of the fluoroscopic unit and should not be obstructed by the airway nurse or anesthesiologist. Ideally, endoscopic and fluoroscopic image monitors should be mounted side by side. A second fluoroscopic monitor that displays the last captured radiographic image is optional. An additional monitor that can be used interchangeably for intraductal ultrasound, cholangioscopy and sphincter of Oddi manometry is also appropriate for units that perform these specialized procedures (Fig. 2.3). Older monitors built with cathode ray tube technology are being increasingly replaced with flat screen monitors as the quality of these smaller flat screen monitors is rapidly improving. Vital sign monitors are usually placed at a lower level for primary viewing by the seated endoscopy assistant or nurse, although most 13

SECTION 1 GENERAL TOPICS

A

Accessory cart

B

C

B Monitors A

Endoscope processor

Patient

C

D C-arm

D Sink

Fig. 2.3 This photograph shows A a ceiling-mounted boom holding monitors for fluoroscopy, B the endoscopic image, C accessories such as endoscopic ultrasound, and D patient vital signs.

Lead aprons

Storage cabinets

Fig. 2.1 A schematic diagram of a typical ERCP room is shown, indicating the positions of personnel including A the endoscopist, B airway nurse, C accessory assistant, and endoscopic trainee, D radiology technician.

Fig. 2.4 Endoscopic processors and the endoscope are shown on this boom.

D

B A

C

Fig. 2.2 An ERCP is being performed by A the endoscopist, assisted by B the airway nurse, C accessory assistant, and D GI trainee. 14

endoscopists also prefer to be able to observe vital signs intermittently when there are any concerns raised by the assistant. The endoscope processor, light source and electrosurgery generator are generally kept together on a cart or boom that is behind the endoscopist (Fig. 2.4). The top shelf of the cart is best left open to use as a working surface. The endoscope can either be laid on top of the cart when not in use, or hung on the side of the cart. A water pump for irrigation is another useful tool that can be kept on this cart or stand. There are a number of types of electrosurgery generators that can be used during ERCP. Monopolar current is commonly used for sphincterotomy; however, bipolar current should also be available for the control of bleeding. Generators that contain both monopolar

Chapter 2 The ERCP Room

Digital vs conventional imaging

and bipolar cautery are preferred to reduce the number of generators on the cart and conserve space. Recently, an electrosurgical generator that uses a microprocessor to automatically adjust current has become popular in ERCP rooms, and may reduce the frequency of “zipper” cuts and endoscopically visible but not necessarily clinically significant post-sphincterotomy bleeding.5

Most modern x-ray imaging units use digital techniques for image manipulation and capture, although older conventional radiographic units are still used by some hospitals. Digital imaging has several advantages over conventional analog imaging including better image quality, the capability of image manipulation after acquisition, and easier and less expensive image storage and transfer. In addition, radiation exposure is reduced because less radiation is needed to produce an image. Image quality in pancreatography has been shown to be better for digital over conventional imaging, especially for evaluating side branch abnormalities.7

RADIOLOGIC IMAGING EQUIPMENT Radiologic imaging will also be addressed in Chapter 3. ERCP involves the use of fluoroscopy to monitor contrast injections and to guide the use of accessory devices that are inside the pancreatic or biliary ducts. Image capture and storage capability is also necessary to document radiographic findings for patient care and follow-up. The key components of the radiographic equipment include the xray tube, image intensifier, monitor, table, and hardware for image capture and storage. These components will be described and their critical specifications discussed. A comparison of commercially available radiographic equipment can be found in Table 2.1.

Imaging components and specifications The tube that generates the x-rays is usually placed under the fixed table or at the bottom of the mobile C-arm. X-rays then go up through the patient and are either scattered or penetrate through to be captured by the image intensifier which is placed over the patient. The size of the image is determined by the diameter of the image intensifier. For ERCP, a 12 or 14 inch image intensifier is ideal so that the entire biliary tree or pancreatic duct can be visualized on one screen without patient or fluoroscope movement. The image intensifier is also the most important component for achieving optimal image resolution, an important feature for seeing small diameter guidewires.8 Staff exposure to radiation is mostly due to scatter of the x-ray beam as it passes through the patient.9–11 This exposure can be greatly reduced with adequate shielding around the image intensifier and also below the table top (Fig. 2.5). Thin lead shields can be custom fitted to most parts of the image intensifier and table to block the scattered radiation. Images can be captured on radiographic “spot films” or increasingly as digital images. The former requires manual placement of x-ray cassettes and subsequent film development or conversion to digital images. Newer units capture digital images directly, reducing the need for x-ray technologists and making the images available for viewing immediately.

Fixed versus portable equipment The first decision to be made about the radiographic equipment is whether the fluoroscope and image intensifier are fixed to the patient table or whether a portable or mobile radiographic unit is used in conjunction with a freely movable table or stretcher for the patient. The main advantage of a portable radiographic unit is that it is generally of lower cost than a fixed unit. This allows mobility to other parts of the GI suite and hospital so that the capital costs can be shared and its use maximized. Hence, it is an option to be considered for low volume ERCP units. In addition, patients can be moved in and out of the ERCP room on the same stretcher that they lie on during the procedure. The main disadvantage of a mobile radiographic unit is it requires a separate operator or technician to be present during the ERCP procedure. The portable unit or patient stretcher must be moved during a procedure, and imaging parameters changed using controls that are not easily accessible to the endoscopist. In addition, radiation exposure to staff and patients is substantially higher with the mobile units due to difficulties providing adequate shielding and generally higher power outputs.6 These portable units formerly had inferior image quality compared to fixed units, however equipment is currently available that provides image quality that is comparable to fixed units.

Controls Ideally, all controls for fluoroscopy and image capture should be within close reach of the endoscopist. This allows the endoscopist to perform all aspects of the ERCP procedure without assistance from a radiologist or technician. Newer equipment makes this quite

Manufacturer

Model

Minimum room size

Mobile (Y/N)

C-arm (Y/N)

Digital (Y/N)

PACSb Compatible (Y/N)

General Electric/OEC Omega Philips Philips Philips Siemens Siemens Siemens

9900 elite CS-50 Pulsera Easy Diagnost Eleva MultiDiagnost Eleva Iso-C Sireskop SD Artis MP

Variable 16′ × 20′ Variable 15′ × 21′ 19′ × 22′ 10′ × 10′ 16′ × 20′ 16′ × 20′

Y N Y N N Y N N

Y Y Y N Y Y N Y

Y Y Y Y Y Y Y Y

Y Y Y Y Y Y Y Y

Image intensifier diameter (inches)

Resolution

List pricea

12 14 12 15 15 12 16 16

1000 × 1000 1024 × 1024 1000 × 1000 1024 × 1024 1024 × 1024 1024 × 1024 1024 × 1024 1024 × 1024

$179 600 $650 000 $175 000 $511 600 $933 000 $150 000 $435 000 $735 000

Table 2.1 Comparison of radiographic equipment used for ERCP a

Manufacturer’s list price in October 2005; actual cost will vary with local purchasing contracts. Picture Archiving and Computerized Storage system.

b

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SECTION 1 GENERAL TOPICS

A

B

Fig. 2.5 Lead shields mounted on A the image intensifier and B patient table reduce radiation exposure to staff from scattered radiation.

feasible and many busy units no longer involve radiology personnel during the procedure. Older units and mobile units usually require the presence of a technologist to set up the examination, make changes to x-ray parameters during the procedure and in some cases move the mobile C-arm unit.

Image capture and storage Most current hospitals store radiographic images using a Picture Archiving and Computerized Storage (PACS) system. Images obtained during ERCP are ideally transferred to the PACS system for access by referring physicians, and in some settings, review and interpretation by a radiologist. Using the central hospital PACS system is preferred over local storage within the endoscopy unit for ease of access and to avoid the need for endoscopy unit quality controls for storage and retrieval of images. A local computer hard drive to store images temporarily and a writable CD drive can be useful for downloading images for educational conferences, however.

Radiographic hardware Fixed fluoroscopy units usually have housing units for the x-ray tube and associated hardware. These units can take up considerable space in the procedure room which needs to be included in planning room dimensions. In addition, a console for entering individual patient data and setting imaging parameters is usually placed outside the ERCP room or behind a leaded glass shield to reduce radiation exposure to technical personnel. If placed in a separate room, the presence of a window for the technologist or assistant to see into the room is desirable (Fig. 2.6).

Equipment and device storage Accessories are integral to the practice of ERCP. A range of accessories are needed for ERCP (Table 2.2; see also Chapter 4) and should be readily available during each procedure. There are a number of options for storage of these accessories. Mobile carts are available for this purpose or customized cabinets or shelves within the room can be used (Fig. 2.7). Accessories should be clearly labeled for quick access during a procedure. A regularly updated inventory 16

Fig. 2.6 A console for entering patient data is outside the ERCP room. The procedure can be viewed by technical personnel through a leaded glass window, thereby reducing their radiation exposure.

system is also essential to avoid the problem of not having a needed accessory for a specific procedure.Endoscopes are generally stored with the other endoscopes for the endoscopy unit, outside of the procedure room. The endoscopes should hang free and not be coiled within an instrument case. Air and suction valves should be removed from the endoscopes during storage. Lead aprons and thyroid collars should be stored near a door, either inside or outside of the room. This minimizes disruption of fluoroscopy when someone enters the room and needs to put on lead shielding.

MISCELLANEOUS ISSUES Each staff member involved with an ERCP procedure should have a radiation dosimeter. Provision should be made for storage of these dosimeters outside of the procedure room to avoid recording of scattered radiation that is not associated with the individual to whom the dosimeter is assigned. The dosimeter should be in a convenient location to serve as a reminder to staff to wear the dosimeter during each procedure.Drugs used during the procedure should be readily available. Sedative medications are usually checked out for each individual patient from a central medication storage area. Emergency drugs, such as atropine, naloxone, and flumazenil need to be readily available for each case and not be locked up in an area that delays access to them in an emergent situation.

Chapter 2 The ERCP Room

Essential accessories for all ERCP rooms

Additional accessories for specialty centers

Electrosurgery generator Ground pads Guidewires (0.018–0.035 inch) Cannulas Sphincterotomes Stents Plastic—range of diameters (3–10 French) and lengths (3–15 cm) Self-expanding metal Stone retrieval balloons (8.5–15 mm balloon diameters) Stone retrieval baskets Mechanical lithotriptor and catheters Dilating balloons—range of diameters (4–10 mm) and lengths (2–6 cm) Dilating catheters Brush cytology catheters Intraductal biopsy forceps Snares and foreign body forceps for stent retrieval Injection needles Multipolar electrocautery probes

Manometry catheters Intraductal ultrasound catheters Intraductal “baby” scopes Electrohydraulic or laser lithotriptor fibers Argon plasma coagulation probes

Table 2.2 Accessories for the ERCP room Fig. 2.7 A cart holding the accessories commonly used during ERCP should be stored nearby the procedure table.

REFERENCES 1. Lennard-Jones JE, Williams CB, Axon A, et al. The Working Party of the Clinical Services Committee of the British Society of Gastroenterology Provision of gastrointestinal endoscopy and related services for a district general hospital. Gut 1991; 32:95–105.

2. Sivak MV Jr, Manoy R, Rich ME. The endoscopy unit. Chapter in: Gastroenterologic Endoscopy, 2nd edn. Edited by MV Sivak; Philadlelphia: WB Saunders, 1999. 3. Gostout CJ, Ott BJ, Burton D, et al. Design of the endoscopy procedure room. Gastrointest Endosc Clin N Am; 1993:509–524. 17

SECTION 1 GENERAL TOPICS

4. O’Sullivan S, Bridge G, Ponich T. Musculoskeletal injuries among ERCP endoscopists in Canada. Can J Gastroenterol 2002; 16:369–374. 5. Perini RF, Sadurski R, Cotton, PB, et al. Post-sphincterotomy bleeding after the introduction of microprocessor-controlled electrosurgery: does the new technology make the difference? Gastrointest Endosc 2005; 61:53–57. 6. Johlin FC, Pelsang RE, Greenleaf M. Phantom study to determine radiation exposure to medical personnel involved in ERCP fluoroscopy and its reduction through equipment and behavior modifications. Am J Gastroenterol 2002; 97:893–897. 7. Uomo G, deRitis R, Rabitti PG, et al. Does endoscopic digital pancreatography constitute an advance in pancreatic imaging? Gastrointest Endosc 1998; 48:67–71.

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8. Bushong SC. Radiologic science for technologists: physics, biology, and protection. 8th edn. St Louis: Mosby, 2004. 9. Chen MYM, Van Swearingen FL, Mitchell R, et al. Radiation exposure during ERCP: effect of a protective shield. Gastrointest Endosc 1996; 43:1–5. 10. Campbell N, Sparrow K, Fortier M, et al. Practical radiation safety and protection for the endoscopist during ERCP. Gastrointest Endosc 2002; 55:552–557. 11. Buls N, Pages J, Mana F, et al. Patient and staff exposure during endoscopic retrograde cholangiopancreatography. Br J Radiol 2002; 75:435–443.

SECTION 1

Chapter

3

GENERAL TOPICS

Radiologic Issues in ERCP Desiree E. Morgan

The scope and practice of ERCP has changed dramatically over the past 10 years. With the advent of MRCP, in academic and in private settings alike, the proportion of therapeutic to diagnostic ERCP cases has greatly increased,1,2 This shift in practice patterns heightens the importance of communication between the endoscopist and radiologist in order to provide the patient with the best possible interpretation of images acquired during ERCP. It cannot be stressed enough that the interaction between physicians leads to the most accurate and consistent reporting,3 whether the patient is undergoing a diagnostic or a therapeutic ERCP examination. This chapter will focus primarily on techniques of image acquisition during ERCP, using examples of pathology (discussed in depth elsewhere in the book) to demonstrate imaging principles. Prior to the ERCP procedure, review of other imaging studies (CT, MRI, or ultrasound) is often helpful to plan and expedite the case. If therapeutic endoscopic interventions are intended, availability of the pancreatobiliary surgeon or vascular/interventional radiologist for treatment of potential complications or participation in combined procedures is desirable. The patient’s history of medical allergies, including contrast material, should be ascertained during the consent process. ERCPs may be performed in dedicated rooms with fixed fluoroscopy (conventional or digital system) units, or with C-arm fluoro units in endoscopy suites or outpatient centers. While the benefits of lower expense, convenience and versatility for C-arm units make them desirable to some users, the cost of dramatically increased xray dose to patients and ERCP personnel must be considered.4 Our ERCPs take place in dedicated digital fluoroscopy rooms within an endoscopy suite located in our hospital. The images acquired in the endoscopy fluoro rooms are transmitted to and archived within the Department of Radiology PACS (picture archiving and communication system), and the digital images are available throughout the hospital and clinics of our medical center once they are transmitted to the PACS. Fluoroscopy rooms designed for ERCP should be large enough to accommodate the video endoscope machinery, supply cart, patient monitoring devices, and the conventional or digital x-ray device. Digital systems allow “on the fly” change in magnification factors and rapid image acquisition generally ranging from two to seven films per second, features often helpful during ductal evaluation. Exchange of x-ray film cassettes in conventional fluoroscopy units adds time both for acquisition and development of images, and generally requires the assistance of a radiology technologist. Most fixed fluoroscopy units, whether digital or conventional, have the x-ray beam source in the table and an image intensifier in the tower. Consideration of the x-ray source is important when shielding the patient is necessary, such as during ERCP in pregnant patients. During most ERCPs, the patient is generally positioned in either a prone or left lateral decubitus (LLD) position. Changes in the patient position are key to visualization of both normal ducts and

duct pathology. In this chapter, the patient position will be described relative to the tabletop rather than the image intensifier. For example, left anterior oblique (LAO) refers to prone patient with left side angled down against the table top and right side angled up. Radiation dose is important to patients and ERCP personnel, and should be monitored with quality assurance testing of the equipment and monthly quantification of exposure measured by radiation badges worn by the endoscopist, his or her technical assistants, and the nurses involved in the procedure. The amount of exposure to personnel varies according to their position relative to the patient. In a controlled, phantom study of radiation doses to personnel during ERCP, Johlin et al.4 described that the largest doses are received by the person at the head of the table, generally the nurse who monitors the patient and administers drugs. The next highest dose is received by the endoscopist, who stands at the right hand corner of the fluoro table, and the lowest dose is received by the assistant who stands alongside the endoscopist at the level of the patient’s abdomen. The low dose received by the assistant at the patient’s abdomen is explained by the use of vertically oriented lead drapes that attach to the fluoro tower and diminish the amount of scatter radiation. Some fluoro units are equipped with right angled vertical lead drapes which can be maneuvered to shield both the head and side of the tower. Alternatively, some centers utilize a lead bead curtain at the head of the table to diminish dose to personnel in this position. Other means that should be employed to decrease dose to patients and personnel alike during ERCP include lowering the tower as close to the patient as possible during the procedure (anytime the fluoro is on as well as when making exposures), collimating the x-ray beam manually (using buttons generally located on the tower), and standing back from the table. The scatter radiation is inversely proportional to the distance squared from the x-ray beam, so even stepping back a small amount is helpful. Conversely, leaning over the head of the patient while fluoro is on greatly increases the dose to the nurse.4 Finally, measures to conserve exposure in the first place by using minimal fluoro time or pulsed fluoro will decrease the dose to all persons in the ERCP room. For pregnant patients, limiting fluoro time is critical. Also, to reduce dose to the fetus, shielding of the mother’s abdomen (from the direction of the x-ray source) with lead aprons is warranted. While the above discussion pertains to ERCPs performed with either fixed fluoroscopy or C-arm equipment, it should be stressed that the amount of scatter radiation produced by most C-arm units is of the order of 100-fold that of fixed equipment. This is due to lack of shielding at the x-ray source and lack of shielding of the x-ray beam that enters the patient, as well as issues of fixed distance from the x-ray source to the patient and “enhanced fluoro” features which double the energy of the x-ray beam for “higher resolution.” Readers are referred to several articles in the radiology literature5,6 and an excellent therapeutic ERCP specific article on this subject,7 19

SECTION 1 GENERAL TOPICS

and are strongly urged to pay particular attention to these issues when purchasing equipment for their endoscopy centers. During the ERCP procedure, the orientation of the fluoroscopic image on the image intensifier tower may be viewed in a number of ways. Some endoscopists prefer to view the fluoroscopic image just as it is obtained, that is, with the prone patient’s left side on the right side of the image intensifier screen and the cephalad portion projecting at the bottom of the screen (Fig. 3.1). The “head” of the ERCP table equals the “foot” of the x-ray fluoro table; in this scenario, what you see is what you get. Most prefer to flip the image so that the anatomy appears upright and in anatomic position on the image intensifier (Fig. 3.2). But when the fluoro tower is moved, one must remember this inverse relation to achieve the desired location of the x-ray beam in the patient’s body. The orientation of the image on the tower may easily be changed during the exam. Contrast preferences also vary among endoscopists. Some prefer to dilute contrast to half strength when looking for stones. Others use full strength contrast injected slowly while looking stringently for filling defects, or employ the technique of chasing the initial contrast injection with saline to achieve a lesser opacity through which stones may become more evident. Still others use full strength

contrast with the argument that the bile in a potentially obstructed or dilated system (Fig. 3.3) will dilute the contrast enough to preclude having to do so proactively. In addition, the use of fullstrength contrast allows earlier detection of pancreatic duct injection, minimizing the volume and potentially reducing the risk of pancreatitis. Also, with conventional radiographic film screen combinations, the exposure creates a “white duct on black background” image. With digital images, the “black on white” images that appear similar to the fluoroscopic image can be filmed or viewed as such, or converted to a standard “white on black” appearance on PACS or film, if preferred. In my opinion, retroperitoneal and free air (Fig. 3.4) are easier to detect with “white on black” images, as are small stones (Fig. 3.5), but to my knowledge, there has been no formal, controlled perception study to support this theory. The sequence of images obtained during ERCP should tell the story of the examination, whether diagnostic or therapeutic. Initially, a scout radiograph obtained with the patient prone reveals any residual contrast, calcifications, tubes, drains, or stents already in place, and any other material that may obscure the region of interest during contrast injection (Fig. 3.6). Most gallstones are nonradiopaque and will not be seen on the scout radiograph, however pancreatic stones frequently may (Fig. 3.7). Once contrast is administered, radiopaque stones in either ductal system may be obscured (see Fig. 3.7). The

Fig. 3.1 Direct projection of ERCP image on fluoroscopic tower. Early injection into the CBD in this patient with Mirizzi Syndrome and cholelithiasis demonstrates orientation without adjustment. The patient’s head is at the foot of the table, and he is prone, so that the right side projects to the left of the screen. Fig. 3.3 Spot radiograph demonstrating adequate visualization of multiple small faceted gallstones (arrows) in a dilated Type 1 choledochal cyst.

A

Fig. 3.2 Vertically and horizontally flipped projection of ERCP image on fluoroscopic tower. Later injection into the CBD in the same patient (Fig. 3.1) with Mirizzi Syndrome and cholelithiasis demonstrates orientation with adjustment so that it is viewed in anatomic position with the patient’s head at the top and his left side on the left of the screen. Note stone (arrow) impacted in cystic duct approximately 1 cm above its insertion into the common hepatic duct. 20

B

Fig. 3.4 Subhepatic free intraperitoneal air (arrow) after biliary sphincterotomy comparing A “black on white” to B “white on black” image presentation. Note large amount of air in the extrahepatic duct after sphincterotomy.

Chapter 3 Radiologic Issues in ERCP

A

B

A

Fig. 3.5 Small distal common bile duct stone (arrow) in dilated system comparing A “black on white” to B “white on black” image presentation.

B

Fig. 3.6 Scout radiograph in a patient about to undergo ERCP. The radiopaque oral contrast from abdominal CT performed 12 hours earlier is located in the hepatic flexure of the colon, potentially interfering with visualization of the extrahepatic bile duct. Because this patient was being evaluated for suspected post traumatic (gun shot wound) bile leak from the intrahepatic ducts more superiorly, the exam was performed (see Fig. 3.20). diagnostic images should include early filling as well as full duct opacification and generally are acquired with a nine inch or six inch image intensifier field of view mode. These overview images of the bile and or pancreatic ducts should be supplemented with spot radiographs of abnormal or suspicious findings. The spot images may be obtained at different degrees of magnification (six or 4.5 inch mode) for emphasis. Delayed films often are critical for assessing biliary drainage (Fig. 3.8) or lack thereof, or for demonstrating small calculi. A final film obtained with a large image intensifier field of view (12 or 15 inch) is helpful to evaluate potential retroperitoneal (Fig. 3.9) or intraperitoneal air. For calculation of actual duct size with digital or standard radiographic images, knowledge of the scope caliber enables a simple proportion to be created to determine the exact magnification for each image (Fig. 3.10). In a hypothetical example, if an older 13.5 mm caliber therapeutic endoscope is used during an ERCP where there is biliary dilation above a strictured region, the exact degree of duct dilation may be calculated by measuring the dilated portion of the duct as well as the scope on the image. The following simple proportion is then set up: 17 (measured caliber of scope 25 (measured caliber of on film) = dilated duct) 13.5 mm (actual scope caliber) X mm

C

Fig. 3.7 Severe chronic pancreatitis. A Innumerable pancreatic calcifications are present on the ERCP scout radiograph. B Following injection of contrast into the main pancreatic duct, the radiopaque intraductal calcifications are obscured by contrast. Parenchymal calcifications should project apart from the opacified duct lumen; however in markedly dilated ductal systems the sheer caliber of the opacified duct may obscure even parenchymal calcification. C Corresponding abdominal CT image through the body of the pancreas shows parenchymal and ductal calcifications in this patient.

21

SECTION 1 GENERAL TOPICS

Fig. 3.8 ERCP drainage film. Spot radiograph after stent insertion above the level of obstruction by the impacted cystic duct stone in this patient with Mirizzi syndrome (same patient as Figs 3.1 and 3.2) reveals emptying of the right and extrahepatic bile ducts. If the patient is turned to a supine position and the head of the table tilted up, drainage of the left intrahepatic ducts may also be verified.

Fig. 3.10 Calculation of individualized magnification factor during ERCP. The caliber of the upstream CBD (arrow) may be set up in a proportion to the measured scope caliber (arrowhead) on the film to correct for magnification produced by short object-to-image distance of the x-ray beam.

The hypothetical duct measures 19.9 mm. If the scope was a newer 11.5 mm model, the caliber of the duct would be 16.9 mm. Solving for X alleviates the need to calculate pixel correction measurements (for digitally acquired spot images) or to estimate magnification on standard radiographic spot images. This is also important when calculating the length from the papilla to a stricture in order to select the appropriate length stent, although the use of a ruled catheter or wire withdrawal may be more accurate for selecting stents than use of x-ray film measurements8 (see Chapter 16 for further details). If a new or different size scope is utilized for a particular procedure, this information should be communicated to the radiologist to insure accuracy of measurements.

BILE DUCT OPACIFICATION

Fig. 3.9 Retroperitoneal air after sphincterotomy. Final film obtained after scope removal reveals air outlining the right upper renal pole (arrow) and right adrenal gland (arrowhead), indicating duodenal perforation. 22

The distal portion of the common bile duct is readily opacified by injection of the major papilla or ampulla of Vater. The normal caliber of the injected extrahepatic bile duct ranges from 3 mm up to 9 mm, with the larger normal caliber more typically seen in older individuals9–12 and in patients who have undergone cholecystectomy,12–16 although the wider caliber does not significantly increase in the postoperative period.9 This is opposed to the relatively smaller upper limits of normal for duct caliber as measured by cross sectional imaging such as ultrasound or CT, where there is not active injection occurring to distend the duct,13–16 yet the same trends in larger normal calibers in older and post-cholecystectomy patients are seen.12,15,16 Variability of insertion of the cystic duct leads to different degrees of obliquity required for adequate visualization. In the case of a long common channel between the CBD and cystic duct

Chapter 3 Radiologic Issues in ERCP

(Fig. 3.11), the best position to identify entrance of the cystic duct or to visualize potential cystic duct stones is typically left anterior oblique (Fig. 3.12). The best position to identify the confluence of right and left hepatic ducts, particularly important in the evaluation of hilar tumors (Fig. 3.13), is right anterior oblique. With the patient prone or in left lateral decubitus position, there is preferential opacification of the left intrahepatic ducts (Fig. 3.14A) due to gravity. Placing the patient

A B

C

in a right decubitus position or supine position helps to opacify the right-sided ducts. The posterior segmental branches may be best seen with the patient supine. In some patients, it is necessary to tilt the head of the table down to opacify the right intrahepatic ducts, and other endoscopic measures such as proximal CHD injection or balloon occlusion injected may help to opacify all of the IHD concurrently (Fig. 3.14B). If there is complete opacification of the intrahepatic duct system and the cystic duct and gallbladder do not fill despite changing the patient’s position, cystic duct obstruction should be suspected.17 Changing the patient’s position (Fig. 3.15) in attempts to visualize all intrahepatic ducts is especially critical in patients with strictures near the confluence, as is injecting near the stricture (Fig. 3.16). Inadequate filling may result in overestimation of strictures, and the “shouldered” feature of malignant strictures may not be ideally demonstrated without adequate duct filling (Fig. 3.17). Likewise the characteristics of benign strictures are better delineated with adequate duct filling (Fig. 3.18). Changing the patient’s position may also help to correctly identify the source of bile leak if aberrant or overlapping ductal structures are present (Fig. 3.19). As in the case of injecting near a stricture to better characterize its extent and character, injecting near the site of a bile leak

D

Fig. 3.11 Long common cystic duct/ common bile duct channel, ERCP/CT correlation. A ERCP spot radiograph revealing a large amount of amorphous stone debris in the long cystic duct and common duct which overly one another in a straight anterior to posterior (AP) direction. B–D Corresponding successively caudal axial CT images obtained after ERCP reveal the relationship of the cystic duct and common hepatic duct in this patient, with the wall between the lumens well depicted on B (arrow) and C by the presence of residual biliary contrast. The wall ends approximately 1 cm above the ampulla on D.

Fig. 3.13 Hilar stricture. The very tight stricture (arrow) of the right main bile duct is well seen in the right anterior oblique projection in this patient with a Klatskin tumor. The patient underwent right hepatectomy and L hepaticojejunostomy with biliary margin free of tumor.

A

Fig. 3.12 ERCP depiction of long common cystic duct/common hepatic duct channel with left anterior oblique projection. When the prone patient is angled with the left side down on the fluoro table, the wall between the cystic duct and common bile duct lumens is better seen. The distal, smooth common bile duct stricture is due to a nonhyperfunctioning neuroendocrine tumor of the pancreatic head in this patient.

B

Fig. 3.14 Preferential flow of contrast due to gravity. A Early filling of the common bile duct with the patient in prone position reveals stone (arrow) impacted at cystic duct remnant. B after stone retrieval, the entire intrahepatic duct system is opacified during injection using balloon occlusion technique. 23

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A

B

Fig. 3.15 Hilar strictures due to lymphoma. A The long, relatively smooth stricture (arrowheads) of the main left and right bile ducts in the hilum is well seen on the prone image. There is also dilation of the posterior segmental branch duct (arrow) which drains aberrantly into the left duct. B With the patient obliqued, the strictured region (white arrow) of the aberrant duct is now evident.

A

Fig. 3.18 Chronic pancreatitis stricture. Opacification of the bile and pancreatic ducts reveals a smooth conical stricture of the distal common bile duct and upstream dilation in a pattern typical of inflammatory stricture. There is dilation of the main and side branch pancreatic ducts, and a stricture is present in the mid body region of the main pancreatic duct in this patient with severe chronic pancreatitis.

B A

Fig. 3.16 Primary sclerosing cholangitis. A Injection of contrast in the mid common bile duct reveals partial visualization of the tight strictures of the right and left ducts in the porta, with some reflux of contrast into the cystic duct and gallbladder. B Injection within the right bile duct just above the confluence demonstrates improved visualization of the diffusely strictured ductal system in this patient with primary sclerosing cholangitis. The left ducts were not opacified further during ERCP, making it difficult to exclude cholangiocarcinoma.

A

Fig. 3.19 Post cholecystectomy bile leak. A Prone image during filling of the common and intrahepatic ducts reveals contrast within the drain in the right upper quadrant. Both the stapled end of the cystic duct and an aberrant right branch overlie the drain. No early film was obtained to determine the site of leak; however, with the patient obliqued slightly in B, contrast appeared to extravasate from the aberrant duct rather than the cystic duct stump. Note air bubbles in distal CBD after stent placement in B.

B

Fig. 3.17 Shouldered stricture. A Early injection of the distal common bile duct demonstrates narrowing in the superior pancreatic head. B With further filling the persistent shouldering (arrow) of the malignant stricture is better depicted. Note the layering of contrast in the underfilled duct above the stricture on A, underestimating the extent of upstream dilation, better seen on B. Gallstones are present within the gallbladder. 24

B

(Fig. 3.20) or obstructing stone (see Figure 3.2) is important to fully understand the pathology. In the case of the endoscope obscuring portions of the bile duct (generally this occurs in the suprapancreatic portion of the extrahepatic duct) (Fig. 3.21), attempts to change scope position to allow direct visualization of the duct may be necessary. For long bile duct strictures, obtaining orthogonal view spot images may help characterize the stricture and demonstrate extrinsic effect. The same is true for intrahepatic bile duct abnormalities produced by hepatic parenchymal disease such as polycystic liver disease (Fig. 3.22) or cirrhosis. Drainage films may be facilitated by tilting the head of the table up for several minutes prior to image exposure (see Fig. 3.8).

PANCREATIC DUCT OPACIFICATION The pancreas is oriented with the head and tail located relatively more posteriorly within the patient compared to the neck and body

Chapter 3 Radiologic Issues in ERCP

A

B C

D

E

Fig. 3.20 Post traumatic bile leak. A Initial ERCP injection into the bile duct shows extravasation from two right-sided intrahepatic ducts. B After stent placement the ducts have emptied, with residual intrahepatic extravasated contrast remaining near the drain. C Axial CT image reveals the disrupted hepatic parenchyma due to gun shot wound. D Two weeks later, repeat ERCP with injection into the extrahepatic CBD reveals no extravasation. E Injection directly into the affected right duct structures (arrow) further characterizes the ducts as sealed.

Fig. 3.21 Endoscope obscuring majority of the malignant stricture of the common bile duct in a patient with pancreatic adenocarcinoma involving the superior head region. Note adjacent stricture of the main pancreatic duct. See Fig. 3.31 for biopsy image of same patient. region. Thus, with injection at the level of the papilla, contrast must travel against gravity, or posteriorly in the patient, to reach the tail region when the patient is prone on the fluoroscopic table. Changing the patient to the supine position will often allow more prompt visualization of the duct in the pancreatic tail (Fig. 3.23). The main pancreatic duct is approximately 20 cm long and variable in caliber.17 In general, the caliber of the duct is greatest in the downstream or head region next to the papilla, tapering continually towards the upstream or tail region. Normal caliber of the injected pancreatic duct in general is 4 mm in the head, 3 mm in the body, and 2 mm in the tail,17,18 though larger diameters are considered normal in advanced age.19 If the patient has a pronounced anterior to posterior

Fig. 3.22 Deviation of intrahepatic bile ducts due to polycystic liver disease. Injection into the right biliary duct system demonstrates a long, smooth stricture of the extrahepatic and central right-sided ducts, with superior displacement and draped appearance of peripheral ducts in a patient with large intrahepatic parenchymal cysts.

curve of the pancreas within the abdomen (readily noted with CT or MR axial images), combined RAO and LAO images may best lay out the duct for complete visualization. Because the normal pancreatic duct drains rapidly, image acquisition during active contrast injection at a rate of two to three images per second may avoid repeated injections and allow complete visualization of all portions including pathologic regions of the duct. This may be critical in that repeated pancreatic injections have been shown to increase risk for post ERCP pancreatitis.20–22 In general, it is the focal change in caliber of either the bile or pancreatic duct that indicates pathology and warrants further image acquisition. If the catheter is placed farther into the duct up to the 25

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Fig. 3.23 Complete visualization of the main pancreatic duct. Injection into the distal main pancreatic duct reveals normal smooth transition from largest caliber in the head to smallest caliber in the tail.

A

B

Fig. 3.24 Chronic pancreatitis. A Early filling of the main pancreatic duct shows dilation in the tail region, upstream from a smooth stricture (arrow) in the proximal body region. B With further injection and repositioning of the scope, there is better demonstration of the stricture in the body (white arrow), as well as side branch dilation and a second focal inflammatory stricture of the main pancreatic duct in the neck region (black arrow).

A

B

Fig. 3.25 Acinarization during pancreatic duct injection. A Early filling of the main pancreatic duct reveals a loop variation in the head region and obscuration of the pancreatic duct by the scope. B With further injection under pressure there is acinarization of contrast and filling of the tight malignant stricture (arrowheads) in the pancreatic neck region, accompanied by upstream dilation in a patient with pancreatic adenocarcinoma.

location of a suspected stricture or filling defect, the interpreting physician can be relatively certain that the affected area is visualized adequately (Fig. 3.24). Although most often not intentionally produced, when acinarization occurs distal or downstream to a stricture (Fig. 3.25), one may be sure that the diminished caliber or obstruction of the duct is not due to technical factors. 26

It is also important to remember that when contrast passes through a strictured region to fill a more dilated proximal duct segment, there will be dilution of the contrast and sometimes layering (see Fig. 3.17) of the contrast,3 making estimation of the length of stricture or the degree of upstream dilation potentially inaccurate. In addition, extravasation from the duct upstream to the strictured region, as is often seen in patients with chronic pancreatitis who have a dominant stricture and chronic pseudocyst formation, may only be seen with deep cannulation and injection immediately adjacent to the affected portion of the main pancreatic duct. Likewise to show that a leak has sealed, injection of contrast near the site of prior extravasation (see Fig. 3.20) during follow-up studies is helpful to exclude technical factors such as underfilling of the affected duct that may produce false negative results. If extravasation occurs from either the pancreatic or bile duct, the size of the cavity (if contained rather than freely extravasated contrast is present) may be underestimated on ERCP due to the relative limited volume of contrast injected, and is better assessed with crosssectional imaging (Fig. 3.26). The evaluation of the filling defects within either duct may be difficult without good communication between the endoscopist and radiologist. Distinguishing between air bubbles that tend to be round or oval (Fig. 3.27) and small gallstones or pancreatic concretions that tend to be angular or faceted (see Fig. 3.3) but which may also be round, can generally be accomplished by changing patient position.23,24 With the head of the table tilted up, gallstones will proceed downward within the duct system, and air bubbles will rise upward (Fig. 3.28). Air bubbles are to be expected after sphincterotomy. Sometimes, such a large amount of air enters the duct that identification of stones is no longer possible (see Fig. 3.4). In the case of precut sphincterotomy to access the duct, there will be no initial injection to clearly document the presence of stones prior to the introduction of air into the duct system. Paying particular attention to the shape and movement of intraductal filling defects may help distinguish between the two, even in this circumstance. When filling defects are removed without documentation of their presence on the images, there is no way for an accurate interpretation to occur after the fact. Since the most common indication for endoscopic retrograde cholangiography remains “suspected biliary obstruction”17 and for endoscopic sphincterotomy continues to be “choledocholithiasis,” documentation of stones on images obtained prior to stone removal and/or communication of real-time endoscopic findings help to ensure consistent reporting. In addition, the performance of sphincterotomy must be communicated Since there is a slightly higher risk of perforation during ERCP when sphincterotomy is performed,25–27 the presence of retroperitoneal and free air should be sought more stringently in those patients. On the other hand, the radiologist cannot assume that a sphincterotomy has occurred because the instrument is documented on an image; the sphincterotome may simply be used to cannulate the major papilla in patients with a difficult entry angle.28 Similarly, pancreatic guidewire or stent placement may be performed solely to facilitate biliary cannulation29,30 and images documenting this event do not imply pancreatic disease. Communication of the endoscopist’s thoughts during a procedure is helpful to avoid errors related to misinterpretation of these phenomena and to provide the most accurate report. In the case of minor papilla injection or therapeutic maneuver (minor papillotomy and/or stent placement), the long scope position (Fig. 3.29) typically employed to access the more proximal papilla

Chapter 3 Radiologic Issues in ERCP

A

B

D

E

C

Fig. 3.26 Extravasation from pancreatic duct. A Early film obtained during ERP demonstrates smooth distal main pancreatic duct and sidebranches in the head region. B and C With deeper cannulation and further injection, extravasation into an amorphous cavity is present in the mid body region. D After pancreatic duct stent is placed and the patient is placed supine, the contrast spreads out further within the cavity. E Accompanying axial CT image demonstrates cystic collection in the mid body region in this patient with duct disruption due to evolving subacute pancreatitis.

A

Fig. 3.27 Gas bubbles in main pancreatic duct. With wire exchange and deep cannulation there is introduction of air and formation of smooth, round bubbles in the main pancreatic duct.

may be a hint to the interpreting radiologist that the duct of Santorini has been injected, even if the major papilla and typical features of pancreas divisum (Fig. 3.30) are not documented elsewhere in the procedure. But again, for the most effective reporting, this information should be rapidly communicated by the endoscopist. Some therapeutic maneuvers and their respective images speak for themselves such as biopsy (Fig. 3.31), stone extraction (Fig. 3.32) or stent placement (Fig. 3.33) so long as an image is obtained to document the event. However, in other circumstances such as in patients with sphincter of Oddi dyskinesia, both the bile and pancreatic ducts may be morphologically normal, and the diagnosis cannot be made on the basis of images alone. Communication of manometric measurements, if acquired, and clinical factors in these patients is critical to insure an accurate interpretation of the radiographs. In summary, the modern-day practice of ERCP involves a large percentage of therapeutic procedures and frequently does not permit

B

C

Fig. 3.28 Gallstones versus air bubbles. A Initial injection into a type 4 choledochal cyst demonstrates multiple filling defects (arrow) in the distal aspect of the dilated duct. B After sphincterotomy, several rounded filling defects suggestive of air bubbles are more clearly seen within the more superior aspect of the duct. C With the head of the table tilted up, there is downward migration of the stones/debris (arrow); the rounded air bubbles have risen and are no longer evident. 27

SECTION 1 GENERAL TOPICS

Fig. 3.29 Long scope position. Spot radiograph obtained during injection of the minor papilla demonstrates long scope position often, but not always, utilized to cannulate the minor papilla in patients with pancreas divisum. Note changes of mild chronic pancreatitis.

the radiologist to be in the endofluoroscopy suite concurrently with the endoscopist; therefore communication is critical to the rendering of adequate radiologic reporting and concurrence with endoscopic findings. Some centers are equipped with inter-departmental intercoms and videomonitors to allow real-time discussion between the endoscopist and radiologist while they are physically located in different rooms. In the case of more remote (both spatial and temporal) endoscopy/radiology cooperation, voice recognition dictation systems that allow immediate reporting, digital medical record archiving, and hospital system-wide accessibility to documents enable rapid reporting of ERCP but cannot replace real-time communication. If real-time exchange is not feasible, then careful documentation of normal or abnormal structures and image documentation of endotherapeutic maneuvers during ERCP are of paramount importance!

Fig. 3.30 Pancreas divisum. Injection of the major papilla in short scope position reveals concurrent visualization of bile duct and typical arborizing ventral pancreatic ducts in a patient with pancreas divisum.

Fig. 3.31 Endoscopic biopsy. Spot radiograph reveals open forceps deployed to region of malignant biliary stricture for tissue sampling of suspected tumor.

A

B

C

Fig. 3.32 Stone extraction. A Spot image reveals mild common duct dilation with rounded 7 mm stone and balloon inflated above the stone prior to sweeping the duct. B After unsuccessful balloon sweeping, a wire basket was placed around the stone and in C retrieved successfully. 28

Chapter 3 Radiologic Issues in ERCP

A

B

C

Fig. 3.33 Restenting through tumor overgrowth. A Injection into the lumen of the distal common bile duct in a pancreatic carcinoma patient who underwent wire mesh stent placement three months earlier for palliative biliary drainage reveals near occlusion of the lumen due to tumor ingrowth. B After deep wire cannulation and injection of dilated upstream bile ducts, C, a longer stent was successfully placed through the occluded stent, re-establishing biliary drainage.

REFERENCES 1. Cotton PB. Evaluating ERCP is important but difficult. Gut 2002; 51:287–289. 2. NIH state-of-the-science statement on endoscopic retrograde cholangiopancreatography (ERCP) for diagnosis and therapy. NIH Consensus Sci Statements. 2002; 19(1):1–26. 3. Technical Considerations in Imaging. In: Taylor AJ, Bohorfoush AG III (eds) Interpretation of ERCP with Associated Digital Imaging Correlation. Philadelphia, Lippincott-Raven, 1977: pp 1–24. 4. Johnlin FC, Pelsang RE, Greenleaf MG. Phantom study to determine radiation exposure to medical personnel involved in ERCP fluoroscopy and its reduction through equipment and behavior modifications. Am J Gastroenterol 2002; 97:893–897. 5. Cousin AJ, Lawdahl RB, Chakraborty DP, et al. The case for radioprotective eyewear/facewear: practical implications and suggestions. Invest Radiol 1987; 22:747–750. 6. Boone JM, Levin DC. Radiation exposure to angiographers under different fluoroscopic imaging conditions. Radiology 1991; 180:861–861. 7. Heyd RL, Kopecky KK, Sherman S, et al. Radiation exposure to patients and personnel during interventional ERCP at a teaching institution. Gastrointest Endosc 1996; 44:287–292. 8. Seibert DG. Biliary stricture measurement and stent selection. Am J Gastroenterol. 1997; 92:1510–1514. 9. Mageed AW, Ross B, Johnson AG. The preoperatively normal bile duct does not dilate after cholecystectomy: results of a five year study. Gut 1999; 45:741–743. 10. Mahour G, Wakim K, Ferris D. The common bile duct in man: its diameter and circumference. Ann Surg 1967; 165:415–419. 11. Edholm P, Jonsson G. Bile duct stones related to age and duct width. Acta Churg Scand 1962; 124:75–79. 12. Kaim A, Steinke K, Frank M, et al. Diameter of the common bile duct in the elderly patient: measurement by ultrasound. Eur Radiol. 1998; 8:1413–1415. 13. Morgan B, Rathod A, Crozier A, et al. Biliary distensibility during per-operative cholangiography as compared with preoperative ultrasound: a four year follow up study. Clinical Radiology 1996; 51:338–340.

14. Sauerbrei EE, Cooperberg PL, Gordon P, et al. The discrepancy between radiographic and sonographic bile-duct measurements. Radiology 1980; 137:751–755. 15. Bowie JD. What is the upper limit of normal for the common bile duct on ultrasound: how much do you want it to be? Am J Gastroenterol. 2000; 95(4):897–900. 16. Daradeh S, Tarawneh E, Al-Hadidy A. Factors affecting common bile duct diameter. Hepatogastroenterology 2005; 52:1659–1661. 17. Schoeman MN, Huibregtse K, Reeders JWAJ. Endoscopic Cholangiography and Pancreatography (ERCP), In: Van Leeuwen DJ, Reeders JWAJ, Ariyana J (eds), Imaging in Hepatobiliary and Pancreatic Disease: A Practical Clinical Approach. London, W. B. Saunders, 2000: pp 309–332. 18. Ohnuma N, Takashi H, Tanabe M, et al. The role of ERCP in biliary atresia. Gastrointest Endosc 1997; 45:365–370. 19. Hastier P, Buckley MJ, Dumas R, et al. A study of the effect of age on pancreatic duct morphology. Gastrointest Endosc. 1998; 48:53–57. 20. Cheng CL, Sherman S, Watkins JL, et al. Risk factors for post-ERCP pancreatitis: a prospective multicenter study. Am J Gastroenterol. 2006; 101:139–147. 21. Testoni PA. Why the incidence of post-ERCP pancreatitis varies considerably? Factors affecting the diagnosis and the incidence of their complication. J Pancreas 2002; 3:195–201. 22. Freeman ML. Post-ERCP pancreatitis: patient and technique related risk factors. J Pancreas 2002; 3:169–176. 23. Thompson WM, Halvorsen RA, Foster WL, et al. Optimal cholangiographic technique for detecting bile duct stones. AJR 1986; 146:537. 24. Train JS, Novick A, Dan SJ, et al. Radiolucency in the common bile duct simulating a gallstone. AJR 1987; 148:136. 25. Siegel J, Ben-Zvi J, Pullano W, Cooperman A. Effectiveness of endoscopic drainage for pancreas divisum: endoscopic and surgical results in 31 patients. Endoscopy 1990; 22:129–133. 29

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26. Suissa A, Yassin K, Lavy A, et al. Outcome and early complications of ERCP: a prospective single center study. Hepatogastroenterology 2005; 62:352–355. 27. Masci E, Toto G, Mariani A, et al. Complications of diagnostic and therapeutic ERCP: a prospective multicenter study. Am J Gastroenterol 2001; 96:417–423. 28. Gulliver D, Cotton P, Baillie J. Anatomic variants and artifacts in ERCP interpretation. AJR 1991; 156:975–980.

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29. Maeda S, Hayashi H, Hosokawa O, et al. Prospective randomized pilot trial of selective biliary cannulation using pancreatic guidewire placement. Endoscopy 2003; 35:721–724. 30. Goldberg E, Titus M, Haluszka O et al. Pancreatic-duct stent placement facilitates difficult common bile duct cannulation. Gastrointest Endosc 2005; 62:592–596.

SECTION 1

Chapter

4

GENERAL TOPICS

Endoscopes, Guidewires and Accessories Sushil K. Ahlawat and Firas H. Al-Kawas

INTRODUCTION ERCP (endoscopic retrograde cholangiopancreatography) has become the preferred technique for the management of patients with a variety of benign and malignant pancreaticobiliary disorders. Success and safety of the procedure depends to a large extent on the indication of the procedure, skills of the examiner and an organized and functional ERCP unit. In addition to a dedicated ERCP room and a fluoroscopy unit, essential equipment for ERCP includes a duodenoscope and a variety of ancillary devices or accessories. A growing range of ERCP accessories have been developed to support the increasing demands and complexity of therapeutic ERCP. This chapter describes current and emerging accessories that are currently available to use during diagnostic and therapeutic ERCP.

ment channel, accessory elevator, and a working length of 120 cm. These features provide an adequate angle of approach and allow intubation of difficult bowel loops and performance of complex therapeutic maneuvers. Initial experience with this oblique-viewing therapeutic endoscope allowed duct access and therapy in two patients with surgically altered anatomy.1 In both patients, prior multiple attempts at ERCP with standard duodenoscope and colonoscope had failed.

ACCESSORIES

ENDOSCOPES

Accessories are devices or pharmacologic agents that help the endoscopist accomplish his diagnostic or therapeutic intent. Cannulation of the desired duct is a prerequisite to successful diagnostic and therapeutic ERCP. A variety of devices are currently available to gain duct access. In particular, the use of sphincterotomes/guidewires and precut sphincterotomes has increased our ability to achieve biliary cannulation.

Duodenoscopes

Cannulas

Side viewing video endoscopes are equipped with an elevator and are used routinely for diagnostic and therapeutic ERCP procedures. The elevator facilitates cannulation and placement of some accessories (Fig. 4.1), while large diameter working channel of therapeutic duodenoscopes (4.2 and 4.8 mm) allow the use of large accessories. Many current ERCP endoscopes combine a large, “therapeutic” channel with a standard size insertion tube. Smaller, 7.4 mm pediatric duodenoscopes with a 2.2 mm channel are available for examination in neonates. Unfortunately, the small channel limits the use of the endoscope to mostly diagnostic purposes since the use of smaller accessories restricts the therapeutic potential of this endoscope. In general, the standard adult duodenoscope can be used in most children above the age of two. A jumbo-size duodenoscope (5.5 mm channel) was previously available as a “mother/baby” scope system. However, this system was difficult to manipulate and is now rarely used.

Standard ERCP cannulas are 5 Fr (French) to 7 Fr catheters, with a straight, tapered or a rounded tip that can accept up to a 0.035-inch guidewire (Fig. 4.2A). Use of a triple-lumen device or the attachment of a side-arm adaptor will allow contrast injection without removing the guidewire. The use of tapered (4.5 Fr-4 Fr-3.5 Fr) or ultra-tapered (5 Fr-4 Fr-3 Fr) tip catheters may allow better duct access in some patients. However, some tapered tip cannulas will only accommodate a smaller-caliber guidewire (= 0.025-inch). No published studies have directly compared cannulation success rates between standard and tapered catheters. Tapered tip catheters may be associated with a higher risk of submucosal injection. Standard cannulas with or without guidewires are limited in their ability to vary the angle of approach to the papilla. The Swing-tip catheter (Olympus America Inc., Lehigh Valley, PA) (Fig. 4.2B) overcomes the limitations of conventional catheters and offers the endoscopist the ability to bend the cannula tip in either direction, thereby facilitating biliary cannulation2,3 or selective entry into the right or left hepatic ducts. The Cremer needle tip catheter (Cook Endoscopy, Winston-Salem, NC) is 1.8 mm in diameter and has a metal needle tip design that facilitates minor papilla cannulation (Figs 4.3a and 4.3b). The standard pancreaticobiliary manometry catheter is a water-perfused 5 Fr catheter with a tip diameter of 3.5 Fr and is used during sphincter of Oddi motility studies (Fig. 4.4A). A variety of catheter types can also be used. Some manometry catheters have a longer “nose” to help maintain catheter position. The standard catheter has three side ports spaced 2 mm apart for simultaneous pressure measurement. The Lehman (Cook Endoscopy) catheter sacrifices

Forward-viewing endoscopes Upper endoscopes, colonoscopes, and enteroscopes are occasionally used in patients with altered anatomy such as previous choledochoduodenostomy, Billroth II gastrectomy, or in patients with hepaticojejunostomy. Since conventional forward viewing endoscopes do not have an elevator, they are limited with respect to control of accessories during cannulation or therapy. In addition, visualization of the ampulla may be limited. A prototype oblique-viewing endoscope is currently available (Pentax Medical Montvale, NJ) with a viewing angle of 45° and a field of view of 130°, a 3.8-mm-diameter instru-

31

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eter became available. Early data suggest that this catheter is associated with a lower risk of post procedure pancreatitis.5

Sphincterotomes

Fig. 4.1 4.2 mm channel duodenoscope (courtesy of Pentax Medical, Montvale, NJ).

A

B

Fig. 4.2 A ERCP cannulas (courtesy of Cook Endoscopy, Winston-Salem, NC). B Swing-tip ERCP cannula (courtesy of Olympus America Inc., Lehigh Valley, PA).

B A

32

Pull type (Erlangen) sphincterotomes were originally designed for the performance of sphincterotomy. They consist of a Teflon catheter containing a continuous wire loop with 2–3 cm of exposed wire exiting at a variable distance from the tip (Fig. 4.5A). In precut sphincterotomes, the cutting wire extends to the tip (Fig. 4.5A). The other end of the wire is insulated and connected to an electrosurgical unit. Over the last decade or so, endoscopists have recognized the need to angle the catheter upward to selectively enter the bile duct.6 Subsequently, prospective randomized trials comparing standard catheters with sphincterotomes have shown a cannulation rate of 84–97% with sphincterotomes compared with 62–67% with standard catheter.7,8 Therefore, in many institutions, sphincterotomes have become the primary cannulation device in ERCP. Currently, sphincterotomes are available with single, double and triple lumens. Double lumen sphincterotomes allow for the introduction of a wire to facilitate cannulation or to accomplish a therapeutic task. Contrast can be injected after removing the wire or by adding a side arm. Triple lumen sphincterotomes allow injection of contrast without removing the wire. Unfortunately, because of the small size of the injection lumen, contrast flow is slow and difficult for the assistant because of the force required during infusion. The use of a small syringe facilitates injection. A sphincterotome is available that incorporates a combination of cutting and balloon stone extraction (Boston Scientific, Natick, MA); however, adding the lumen increases the catheter diameter and tip size which may make cannulation more difficult. When sphincterotomy is performed, a variety of generator currents can be used: cutting, auto-cut, coagulation or blended. Limited data suggest that the use of a pure cutting current is associated with a lower risk of pancreatitis after sphincterotomy9 while the use of an “auto-cut” is associated with a lower risk of bleeding during sphincterotomy. This autocut feature has essentially eliminated the Zipper cut phenomenon after sphincterotomy. When performing pancreatic sphincterotomy, pure “cutting” current is often used to reduce the risk of pancreatic duct injury and subsequent stricture formation. Rotatable sphincterotomes have recently been introduced to offer the endoscopist the ability to change the orientation of the sphincterotomes. Preliminary data suggest that this may be useful in improving cannulation, especially in patients with unusually oriented or distorted papillae,10 or in patients with Billroth II anatomy. Rotatable sphincterotomes may also help orient the cutting wire during sphincterotomy. However, no published data is available to support this theory.

Fig. 4.3 A Cremer cannula (courtesy of Cook Endoscopy, Winston-Salem, NC). B Endoscopic view showing Cremer cannula and minor papilla.

Access sphincterotomes

one port for aspiration of water out of the pancreatic duct during infusion to prevent overfilling of the pancreatic duct and thereby reduce the risk of post procedure pancreatitis.4 Standard water perfused motility recording systems are used for sphincter of Oddi manometry (Figs 4.4B and 4.4C). Recently a micro transducer cath-

Precut or “access” sphincterotomy refers to a variety of endoscopic techniques used to gain access to the bile or pancreatic duct after conventional methods of cannulation have failed (see Chapter 9). Needle-knife and precut sphincterotomes are the two most commonly used devices to gain access into the bile duct. The needleknife was first described by Kees Huibregtse in 1981 and is essentially a bare wire that protrudes 4–5 mm from the end of a Teflon catheter (Fig. 4.5B). Several papers have discussed the use of this device.

Chapter 4 Endoscopes, Guidewires and Accessories

A

B

Duodenal baseline

C

Fig. 4.4 A Endoscopic view showing motility catheter. B Manometry tracing (normal sphincter of Oddi pressure). C Sphincter of Oddi motility recording system.

A

B introduced.12 It has the advantage of having separate lumens for contrast and guidewire. Biliary sphincterotomy can be immediately completed by using the same instrument and is facilitated by having a preloaded slippery wire. Data comparing different precut techniques are limited.13

Guidewires Fig. 4.5 A Standard and precut sphincterotome (courtesy of Cook Endoscopy, Winston-Salem, NC). B Needle-knife sphincterotome (courtesy of Cook Endoscopy, Winston-Salem, NC).

Newer versions include additional lumen for wire (double lumen) and both wire and contrast (triple lumen) introduction. The precut sphincterotome was first reported by Nib Soehendra and the Hamburg group in 1996 (Fig. 4.5A). This sphincterotome allows “papillary roof incision.”11 A double lumen version has been recently

Guidewires are the cornerstone of diagnostic and therapeutic ERCP. During ERCP, guidewires are used for achieving and maintaining access and placing and exchanging devices. Examples include difficult cannulation, sphincterotomy, navigating strictures, stricture dilation, tissue sampling, stent placement, mini-scope placement, and manometery. Ideal guidewire characteristics for gaining access to lumen differ from those for advancement of accessories. Guidewires with slippery and flexible leading tips are generally used to gain access through tight biliary strictures. On the other hand, stiff and taut guidewires are best used for advancement of devices such as biliary 33

SECTION 1 GENERAL TOPICS

stents or dilators. Stiff and taut wires also minimize lateral deviation and facilitate forward axial transmission of forces. Friction can aid in maintaining wire tensions but it hinders both wire and device movement. A variety of guidewires are currently available (Table 4.1) and these vary in materials, length, diameter, and design to optimize performance.14 In general, three guidewire designs are available for ERCP applications: (1) Monofilament wires are designed for rigidity and are made of stainless steel. (2) Coiled wires are stiff and flexible and have an inner monofilament core and outer spiral coil made of stainless steel. Inner core and outer spiral coil provide stiffness and flexibility respectively. Most coiled wires are Teflon painted in order to minimize resistance and are optimal for traversing tortuous biliary strictures because of their improved trackability resulting from combination of stiffness and flexibility. (3) Coated or sheathed wires have a monofilament core made of stainless steel or nitinol and an outer sheath made of Teflon, polyurethane, or another lubricious polymer. The outer sheath material can be designed to improve radiopacity, slipperiness, and electrical insulation properties. Coated wire tip flexibility depends on the taper of the inner core. Many wires have platinum tipped core to improve fluoroscopic visualization. The configuration of the guidewire can be straight or angled (J-shaped) (Fig. 4.6A). Some wires have graduated or continuous markings for visual endoscopic measurement or movement detection. Most wires are only minimally steerable in the radial direction.

Guidewires are advanced under fluoroscopic monitoring through ERCP catheter or sphincterotome that imparts stiffness and direction. Guidewire passage is easier after flushing water through dry or contrast-filled devices because of minimal friction. Moistening of exposed portions of hydrophilic wires prevents drying and sticking. Maintenance of wire position is critical for safe and effective use of over the wire accessories such as dilators and stents. The risk of

B

A

Fig. 4.6 A Straight and angled tip guidewires (courtesy of Boston Scientific, Natick, MA). B Endoscopic view showing the markings on the guidewires.

Wire type/name (manufacturer)

Diameter (inch)

Length (cm)

Core material

Sheath material

Tip material

MONOFILAMENT Axcess 21 (CE) Cope (CE)

0.021 0.018

480 480

Nitinol SS

None None

Platinum Platinum

COILED Standard Wires (CE)

0.018, 0.025, 0.035, 0.038

400–480

SS

Stainless coil, Teflon painted

Stainless tapered core + coil

COATED Tracer (CE) Protector Plus (CE) Roadrunner (CE) Zebra (BS) Jagwirea (BS) Hydra (BS) Glidewire (BS)

0.035 0.035 0.018 0.025, 0.035, 0.038 0.035, 0.025 0.035 0.018, 0.025, 0.035

260–480 480 480 260, 450 450 260, 450 450, 260

Nitinol Nitinol Nitinol Nitinol Nitinol Nitinol Nitinol

Platinum, hydrophilic Platinum Platinum Platinum, endoglide Platinum, hydrophilic Tungsten, hydrophilic Platinum

Geenen Endotorque (CE) Pathfinder (BS) LinearGuideV (O) X wirea (CM)

0.035 0.018 0.035 0.035, 0.025

450 450 270, 450 260, 450

SS Nitinol Nitinol Nitinol

Teflon Teflon Teflon Teflon Teflon Endoglide coating Polyurethane hydrophilic coat on entire length Teflon Endoglide Polytetrafluoroethylene Hydrophilic

Table 4.1 Currently available Guidewires for ERCP applications (adapted with permission from reference no. 14)

a Available in a stiff version. SS = Stainless Steel. CE = Cook Endoscopy, Winston-Salem, NC. BS = Boston Scientific, Natick, MA. CM = ConMed, Utica, NY. O = Olympus America Inc., Lehigh Valley, PA.

34

Platinum Platinum, hydrophilic Hydrophilic Nitinol

Chapter 4 Endoscopes, Guidewires and Accessories

wire displacement can be minimized by using guidewires that have graduated or continuous markings or movement detection printed distance markers and movement guides (Fig. 4.6b). In addition, fixation of the proximal end (outside of the patient) on an immobile accessory device can also lower the risk of wire dislodgement. Currently available guidewire types include conventional, hydrophilic, and “hybrid,” ranging from 0.018 to 0.035 inch in diameter and 260 to 480 cm in length.15 These are summarized in Table 4.1. Wire lengths above 400 cm are used for exchange of devices. Only coated wires should be used during electro-cautery applications. Data is limited regarding the relative efficacy of specific wires for ERCP applications. Clinical experience suggests that coated and hydrophilic wires improve the ultimate success of those ERCP procedures requiring access through difficult papillae or strictures. Completely hydrophilic wires are subject to inadvertent displacement from ducts or strictures and can make the catheter exchange difficult. However, newer combination wires such as Jagwire, Hydra jagwire (Boston Scientific, Natick, MA), FX, X (ConMed, Utica, NY), and Metro (Cook Endoscopy, Winston-Salem, NC) may provide the best combination of a slippery tip with a stiffer shaft (Fig. 4.6a) Limited data suggest that biliary cannulation using a guidewire through a sphincterotome lowers the risk of post-ERCP pancreatitis, presumably because of less pancreatic injection.16 Teflon coated wires are least expensive. Hybrid wires are more user friendly but more expensive. A useful and detailed review of guidewires can be found in a recent Americal Society for Gastrointestinal Endoscopy (ASGE) technology assessment report.14

Wire safety Perforation and failed device placement are the two main wirerelated risks in the pancreas or biliary tree during ERCP. Applying excessive force below a stricture or at an acute angle can result in wire-related perforation. Loss of wire tension or access from a stricture while using rigid devices such as biliary dilators can also result in perforation. Wire-guided sphincterotomy can transmit significant electric current from the cutting wire through standard Teflonpainted guidewires into the bile duct. Intact, coated wires are effectively insulated against transmission of short circuits or induced

currents. All damaged wires are potential sources of dangerous currents.

Exchange assistance devices Multiple devices are frequently required for a successful therapeutic ERCP. Frequently, an exchange or series of exchanges over a previously placed guidewire is required to introduce subsequent device(s). Several exchange assistance devices have been developed by different manufacturers to facilitate exchange of over-the-wire accessories in order to reduce reliance on an expert assistant and to allow the use of a short (260 cm) wire. These devices may reduce fluoroscopy time and increase efficiency.17 Potential problems with exchange assistance devices include a restriction in the choice of accessories, difficulty in re-using the same accessory during the procedure, and cost.

Rapid Exchange Biliary System The Rapid Exchange (RX) Biliary System (Boston Scientific, Natick, MA) is based on a monorail design that provides the endoscopist with control over the guidewire and subsequent exchanges. The system is composed of three integral units: a guidewire locking device (Fig. 4.7A), a specially designed RX catheter, and a 260-cm guidewire. A locking device secures the position of the guidewire during exchange of over-the-wire accessories, advancement of accessories, and manipulation. The locking device can accommodate multiple guidewires that can be secured at any time and thus allow for multiple therapeutic interventions. Cannulation devices (i.e. cannula, sphincterotome) have a proximal open-channel (beginning at 5 to 30 cm from the tip) that allows the guidewire to exit at this point rather than at the hub of the endoscope. Once cannulation is achieved, the wire is separated from the catheter (Fig. 4.7B) and is secured in the guidewire locking device at the suction cap. A variety of RX accessories are available to use with this system. Potential benefits of RX Biliary System include shorter total procedural and post cannulation times and a reduction of fluoroscopy exposure.18 However, the cost may be higher than the standard equipment and the endoscopist may be limited to using RX accessories. Cost-benefit studies using the RX Biliary System are not available.

Fig. 4.7 Rapid exchange system. A Locking device. B Guidewire stripping from the catheter. (A and B Courtesy of Boston Scientific, Natick, MA).

A

B

35

SECTION 1 GENERAL TOPICS

B

A

Fig. 4.8 Fusion system A Fusion catheter. B Biopsy valve with locking mechanism. (A and B Courtesy of Cook Endoscopy, WinstonSalem, NC).

Fusion system This system is made by Cook Endoscopy (Winston-Salem, NC). It consists of either a double lumen catheter or a triple lumen sphincterotome. The design of this system facilitates the exchange of accessories without removing the guidewire or exchanging the initially placed catheter/sphincterotome over the full length of the guidewire. The main difference between this new system and the conventional design is that a side hole is placed at 6 cm from the tip of the catheter (or any accessories from this line of products except the stent introducer system in which the side hole is placed at 2.5 cm) (Fig. 4.8A). The total length of the guidewire is 185 cm and the length of most accessories is 220 cm. To provide proper control of these much shorter accessories and guidewire, the system utilizes a special disposable biopsy valve with a locking mechanism to anchor the guidewire while performing exchanges (Fig. 4.8B). A major advantage of the Fusion system is in the ability to place multiple stents without removing the guidewire. With this system, the guidewire is left within the bile duct across the stricture or papilla, and this facilitates deployment of subsequent stents without concerns about losing access across the stricture. In situations where intervention requires the use of standard length or conventional accessories, a standard length guidewire can be inserted through the end of the catheter or sphincterotome after removing the inner nylon stylet, and exchange can be performed in the usual manner. Controlled data regarding the efficiency with Fusion system is not available.

V-system The Olympus V-system (Olympus America Inc., Lehigh Valley, PA) integrates Olympus endoscopes and endotherapy devices. This design offers the option of guidewire manipulation by the physician or by the assistant and may allow easier exchange of catheters using a short guidewire. The V-endoscope has an increased elevator angle and V-groove that allows the endoscopist to “lock” the wire when the elevator is closed. This endoscope design may also enhance selective biliary cannulation capability. The V-system features a C-Hook, Vmarkings, and V-sheath for device control in addition to the Vgroove on the elevator of the duodenoscope (Fig. 4.9A). The C-Hook attaches the device to the endoscope just below the biopsy port (Fig. 4.9B) and allows a choice of control of the device 36

A

B

Fig. 4.9 V-system A V-scope tip. B Hook. (A and B Courtesy of Olympus America Inc., Lehigh Valley, PA).

by the physician or the assistant. V-markings are present on the proximal portion of all V-system devices. When the V-marking on the accessory device reaches the biopsy port of the endoscope, the tip of the catheter has reached the endoscope elevator V-groove indicating that raising the elevator at that point would lock the guidewire in the V-groove. The V-sheath design allows the guidewire sheath and the injection/handle sheath to be separated offering the choice of control by the endoscopist or the assistant. The V-scope and V-system accessories can also be used with long 0.035″ and smaller guidewires and with ERCP accessories from other device manufacturers. Initial evaluation using this system (V-scope) has shown improved reliability of guidewire fixation;19 however, limited data exist on efficiency of catheter/guidewire exchanges.20

Drainage devices Drainage devices include stents and nasobiliary drains. Stents are used for a variety of purposes and are available in various materials and configurations. Nasobiliary and nasopancreatic drains are infrequently used in the US.

Plastic stents Plastic stents are made of polyethylene or Teflon and are available in varying size, shapes and length for biliary and pancreatic pathologies. A pusher tube is used to place plastic stents over a guidewire with or without a guiding catheter. Delivery systems are available for plastic stents that combine the pushing and guiding catheters. The standard stent delivery system for 10 Fr comprise a 0.035 inch guidewire (480 cm) and a 6 Fr radio-opaque Teflon (260 cm in length)

Chapter 4 Endoscopes, Guidewires and Accessories

guiding catheter with a tapered tip to facilitate cannulation and a pusher tube. Some guiding catheters have two metal rings (placed 7 cm apart) at the distal end that helps in identification and measurement of the stricture length. The pusher tube is made of Teflon (8, 10, and 11.5 Fr) and used for positioning the stent during deployment. Most plastic stents are made of radiopaque polyethylene and are available in sizes varying from 3 to 11.5 Fr. They also vary in length and configuration. There is no inner catheter for the 3–7 Fr stent delivery systems. Straight “Amsterdam” type stents are predominantly used for biliary drainage (Fig. 4.10a). Based on Poiseuille’s law there is a clear relationship between stent diameter and duration of stent patency (Fig. 4.11).21 A straight configuration also appears to improve stent patency. Attempts to improve stent patency by eliminating side holes, changing stent material or coating the inner surface with a hydrophilic substance have generally not been successful.22,23 Double pigtail configurations (Fig. 4.10A) help anchor

A B

the stent to prevent upward or downward migration. These stents are frequently used to maintain drainage in patients with difficult bile duct stones and in some patients with hilar strictures. Single pigtail stents (Fig. 4.10B) are frequently used in the pancreatic duct to prevent inward migration. Limited data suggest that smaller stents (i.e. 3 and 4 Fr) will lead to less damage when used in a normal pancreatic duct and that elimination of side holes and flaps may prolong patency and promote spontaneous migration of pancreatic stents.24 New pancreatic stents have become available recently that are constructed to have running channels and no side holes (GI Supply, Camp Hill, PA). Limited data are available in reference to their superiority over currently used stents.25 Stents are usually removed using snares, baskets and foreign body forceps. Large bore (10 Fr) stents can be removed through the channel of a therapeutic endoscope with the aid of a snare. Smaller stents, i.e. 3 Fr and 5 Fr pancreatic stents can also be removed via the working channel of the endpscope using a foreign body forceps (e.g. rat tooth forceps). The Soehendra stent retriever (Cook Endoscopy, Winston-Salem, NC) consists of a screw-tipped wire-guided device that allows stent removal while maintaining guidewire position. It is also available with an extended tip design to facilitate cannulation. In patients with difficult strictures, maintaining wire access can also be accomplished by using a wire and a snare.26

Self-expandable metal stents

Fig. 4.10 A Straight and double pigtail stents (courtesy of Olympus America Inc., Lehigh Valley, PA). B Single pigtail stent (courtesy of Cook Endoscopy, Winston-Salem, NC).

Patency rate of prostheses

Prostheses diameter*

12F

10F

Multiple 7F

Self-expandable metal stents (SEMS) were introduced to prolong stent patency over plastic stents. SEMS expand to 8–10 mm in diameter and do not occlude from bacterial biofilm. In the US, commonly available SEMS have an open mesh design and include the Wallstent (Boston Scientific, Natick, MA), the Spiral Z-Stent and Zilver stent (Cook Endoscopy, Winston-Salem, NC), and Flexxus (ConMed, Utica, NY) (Table 4.2, Figs 4.12A and 4.12B). SEMS are made of stainless steel or nitinol, a nickel–titanium alloy that provides a high degree of flexibility and is kink resistant. However nitinol is less radiopaque than stainless steel and additional radiopaque (gold or platinum) markers are added to the stents to improve radiopacity in order to facilitate proper positioning during deployment. Covered SEMS are also available. One example is the Wallstent (Boston Scientific, Natick, MA) which has a polymer (Permalune) coating on the inside of the stent except for the proximal and distal 1 cm. This membrane is designed to prevent tumor in growth and prolong stent patency.27 The delivery system for preloaded self-expanding metal stents (SEMS) varies in design (Table 4.2). The wire mesh metal stents are collapsed and constrained on a 6/6.5 Fr introducer catheter by an

7F

1

2

3 4 Patency rate (months)

5

6

7

* 3 French = 1mm

Fig. 4.11 Bar graph showing relationship between stent diameter and the duration of functional patency (adapted from reference #21 with permission © 2004 American Society for Gastrointestinal Endoscopy).

Material Length (cm) Diameter (mm) Stent foreshortening Introducer Diameter (Fr)

Wallstent a (BS)

Luminexx a (CM)

Zilver a (CE)

Elgiloy 4/6/8/10 8/10 Y 7.5/8

Nitinol 4/6/8/10 8/10 N 6/7.5

Nitinol 4/6/8 6, 8, 10 N 7

Table 4.2 Self-expandable biliary metal stents

a According to the manufacturer Magnetic Resonance Imaging compatible. CE = Cook Endoscopy, Winston-Salem, NC. BS = Boston Scientific, Natick, MA. CM = ConMed, Utica, NY.

37

SECTION 1 GENERAL TOPICS

A

A

B

B

Fig. 4.14 A Fluoroscopy image of dilator balloon. B Soehendra dilator (courtesy of Cook Endoscopy, Winston-Salem, NC). Fig. 4.12 Self-expandable metal stent. A Endoscopic view of the stent. B Fluoroscopy image of the stent. B A

A B

Fig. 4.13 A Cytobrush (courtesy of Cook Endoscopy, WinstonSalem, NC). B Fluoroscopy image showing biliary biopsy forceps (arrow).

8/8.5 Fr overlying plastic sheath. Smaller 7/7.5 Fr introducer systems are also available. The entire system is advanced over the guidewire through the endoscope channel and passed under fluoroscopic guidance across the stricture using radiopaque markers. The Wallstent delivery system allows recapture and repositioning of the stent before reaching the 80% marker. Major limitations of currently available SEMS are cost and the difficulty in removing uncovered stents after placement.

Nasobiliary and pancreatic drainage catheters Nasobiliary drainage catheters are used for temporary drainage of the biliary tree and are available as 250 cm long 5 Fr to 7 Fr diameter catheters with 5 or 9 sideports that facilitate drainage flow. Multiple tip configurations are available. Nasopancreatic drainage catheters are 5 Fr in diameter and may be used to drain the main pancreatic duct after sphincterotomy or to irrigate and drain pancreatic pseudocysts. Biliary and pancreatic indwelling drainage catheters are placed over the wire using a 0.035 inch guidewire. A nasal transfer tube is needed for rerouting the tube from the mouth to the nose. A connecting tube is needed for irrigation and drainage.

Tissue sampling devices Brush cytology devices are available as single or multiple lumen systems. Using the single-lumen cytology system, cell loss is inevitable because the brush is pulled back through the whole length of the catheter. It is useful to aspirate bile from the catheter to collect any dislodged cells within the catheter to improve the diagnostic yield. Double-lumen cytology brush systems are preferable (Fig. 4.13a) and allow the guidewire and brush to pass through two 38

Fig. 4.15 A Stent retriever (courtesy of Cook Endoscopy, WinstonSalem, NC). B Endoscopic view showing stent retrieval (arrow).

separate lumens so that access is not lost. In addition, this design minimizes cell loss by eliminating the need to pull back the brush through the entire length of the catheter. Biliary biopsy forceps (Olympus America Inc., Lehigh Valley, PA and ConMed, Utica, NY) are useful for selectively obtaining biopsy specimens from the bile duct under fluoroscopy (Fig. 4.13b).28

Stricture dilation devices In general, pancreaticobiliary dilation can be accomplished using balloons (Fig. 4.14A) or bougies (Fig. 4.14B). Balloon dilators are made of non-compliant polyethylene and are available in different sizes and lengths: 4, 6, 8, or 10 mm in diameter and 2–4 cm long. Balloons are passed over a guidewire through the accessory channel of the endoscope. A radiopaque band proximal to the taper indicates the point of maximal dilation. Soehendra dilators (Cook Endoscopy, Winston-Salem, NC) are standard-shaped bougies that are available in 6–11.5 Fr diameters. These are passed over a guidewire, the 10 Fr and 11.5 Fr size dilator require the use of a large accessory channel. Threaded-Tip “Soehendra” Stent Retrievers have also been used to dilate very tight pancreaticobiliary strictures that otherwise allow only passage of a guidewire. The wire-guided screw-tipped device is used to negotiate high-grade strictures (Figs 4.15A and 4.15B). A modified device is now commercially available as a dilator (Cook Endoscopy, Winston-Salem, NC).

Stone extraction accessories Accessories useful for stone extraction include double-lumen balloon catheters, wire baskets and mechanical lithotriptors. The stone

Chapter 4 Endoscopes, Guidewires and Accessories

extraction balloon (Fig. 4.16A) consists of a 5–6.8 Fr double-lumen catheter with a balloon at the tip (8–18 mm size). Multi-size stone extraction balloons are currently available (8.5, 12, and 15). Prior to insertion into the endoscope it is useful to ensure that the balloon inflates correctly. The balloon catheter can be inserted over a guidewire or directly into the desired duct without guidewire. Stones can also be removed using a wire basket (Fig. 4.16B). The basket is shaped such that the wires open like a trap to engage the stones. Basket function varies depending on the number of wires. Newer design baskets can be advanced over a preplaced wire allowing the basket to reach difficult areas (Trapezoid Basket, Boston Scientific, Natick, MA and Flower basket, Olympus America Inc., Lehigh Valley, PA). The Trapezoid basket has a handle that is designed to provide the endoscopist with the ability to perform mechanical lithotripsy. Unfortunately, the small basket size limits its efficacy in capturing and crushing large (>1.5 cm) stones.

Mechanical lithotriptors Lithotripsy wire baskets facilitate removal of large (>1.5 cm) common duct stones by crushing the stones before extraction. The original

B

A

Soehendra lithotriptor (Cook Endoscopy, Winston Salem, NC) requires cutting the handle of the basket and removing the endoscope prior to stone fragmentation. This device consists of a 14 Fr metal sheath and a self-locking crank handle (Fig. 4.17A). The lithotriptor can be used with most standard stone extraction baskets. Another mechanical lithotriptor is a pre-assembled through-thescope lithotripsy basket which can be inserted through a therapeutic duodenoscope (Fig. 4.17B and 4.17C) (BML lithotripsy baskets by Olympus Medical Inc., Lehigh Valley, PA). This device is available in disposable and reusable versions. A single-piece disposable mechanical lithotriptor with the basket, metal sheath and crank handle is also available (Monolith, Boston Scientific, Natick, MA). In one report, the disposal lithotripter was easy to use and its performance was comparable to a standard reusable lithotriptor.29

Cholangioscopes Duodenoscope-assisted cholangiopancreatoscopy (Figs 4.18A and 4.18B) allows for the direct visualization of the biliary and pancreatic ducts. In the past, a dedicated mother–daughter system was required. Currently, a variety of electronic and fiberoptic miniscopes are available that can be passed through a 4.2 mm channel therapeutic duodenoscope for direct visualization of the biliary and pancreatic duct.30–31 These instruments are now available in 8 Fr and 9 Fr sizes.32 They have a small working channel (1.2 mm) that allows passage of small diameter forceps and fibers for tissue acquisition and for the application of laser and electrohydraulic lithotripsy. Limitations include the fragility of these devices, the small working channel and the need for two endoscopists (one for each endoscope). Recently, a “homemade” support system was reported, allowing one endoscopist to use the system.33 These devices are discussed in more detail in Chapters 20 and 21.

Ultrasound probes

Fig. 4.16 A Endoscopic view of stone extractor balloon. B Stone extractor basket (courtesy of Olympus America Inc., Lehigh Valley, PA).

Increased availability of high frequency ultrasound probes have made it possible for experts to use these devices for evaluating biliary strictures. Endoscopic ultrasound probes are introduced free hand or over the wire (Fig. 4.19) through the working channel of the duodenoscope allowing for “real time” evaluation of biliary strictures and surrounding vascular structures. Limited data suggest that these

C

A B

Fig. 4.17 A Soehendra mechanical lithotriptor Handle (courtesy of Cook Endoscopy, Winston-Salem, NC). B Through the scope mechanical lithotriptor (courtesy of Olympus America Inc., Lehigh Valley, PA). C Fluoroscopy image of mechanical lithotriptor. 39

SECTION 1 GENERAL TOPICS

B

A

Fig. 4.20 Endoscopic view showing identification of pancreatic duct orifice using methylene blue spray (arrow). Fig. 4.18 A Cholangioscope (courtesy of Pentax Medical, Montvale, NJ). B Fluoroscopy image of cholangioscope. “reverse” sphincterotomes are available for use in patients with Billroth II type anatomy. In most patients, however, sphincterotomy can be performed using standard accessories such as needle-knife. The endoscopist should make sure that appropriate accessories are available before initiating ERCP.

Single vs reusable accessories

Fig. 4.19 Intraductal ultrasound probe (courtesy of Olympus America Inc., Lehigh Valley, PA).

probes can enhance our ability to distinguish between benign and malignant biliary strictures.34 Patient selection, operator experience and cost continue to be limiting factors before wider use of this technology is advocated.35

OTHER “ACCESSORIES” Pharmacologic and chemical agents are not considered accessories in the classic definition. However, secretin injection, with or without the use of methylene blue has been reported to facilitate cannulation of the pancreatic duct, especially in patients with pancreas divisum (Fig. 4.20).36,37 These agents are also helpful in identifying the pancreatic duct opening after biliary sphincterotomy or endoscopic ampullectomy. Glucagon and hyoscyamine often are used to relax motility and have been found to be of similar efficacy but were never compared with placebo in a randomized controlled trial.38

Accessories for use in patients with altered anatomy Standard accessories are designed for use with a duodenoscope and are usually 200 to 260 cm in length. However, in patients with surgically altered anatomy such as Roux-en-Y gastroenteric anastomosis, the standard ERCP scope may not be able to reach the ampulla, and the use of a longer scope such as pediatric colonoscope or enteroscope may be needed. Some accessories such as balloons, sphincterotomes and push catheters are available in longer versions for this purpose (Cook Endoscopy, Winston-Salem, NC). In addition, 40

The choice between single use, disposable and reusable accessories for ERCP depends on various medical and economic factors.39 Additionally, there are liability issues that may result from reusing single use devices. Several studies have evaluated reuse of ERCP accessories. Lee et al. found that a reusable sphincterotome could be safely and efficiently used.40 A disposable sphincterotome was costeffective after 2.2 uses and a reusable sphincterotome after 7.9 uses. A recent study also found reusable sphincterotomes and stone extraction baskets to be safe and cost-effective when compared with single-use devices.41 According to a recent ASGE guideline on disposable endoscopic accessories, the selection of reusable or disposable devices must be based upon local purchase costs, reprocessing costs and abilities, storage and disposable facilities, and personal preferences.39

Storage of accessories A special room with a fluoroscopy unit offers the advantage of a better floor plan, organization and ready access to stored accessories that are required for the procedure (see Chapter 2). The room is organized to facilitate the use of needed equipment such as endoscope/processor, monitors, and the fluoroscopy unit. The fluoroscopy and endoscopy monitors should be placed side by side at the endoscopist eye level to avoid the need for repeated turning, which can displace scope position and additionally puts body strain on the endoscopist. The dedicated ERCP room should be large enough to house and store accessories in cabinets that are properly labeled and easily accessible to the assistant at the time of procedure. Easily retrievable accessories at the time of procedure will increase procedure efficiency by reducing time lost in looking for accessories when needed.

RADIATION EXPOSURE ERCP relies on the use of fluoroscopy but the risks associated with radiation exposure to patients and to personnel during the procedure are not well documented (see Chapter 3). A recent prospective study suggested that personnel as well as patients may be exposed to radiation doses that equate to an estimated additional lifetime fatal cancer

Chapter 4 Endoscopes, Guidewires and Accessories

risk of 1 in 3500–7000.42 Radiation exposure to the personnel is proportionally related to the distance and duration of fluoroscopy. Higher voltage and lower current for fluoroscopy is used to minimize radiation exposure to the personnel. Various other strategies that are used to minimize radiation exposure include protective lead shielding, the use of digital imaging, and an “under-couch” X ray emitter tube. Doubling the distance from the source reduces the radiation dose received by a factor of 4. Therefore, the operator should be vigilant in avoiding prolonged use of fluoroscopy and should stand as far back as possible from the patient during exposure. Exposure to patients particularly those at high risk such as young patients and pregnant women (discussed further in Chapter 23) can be minimized by shielding the pelvic area with a lead-lined apron. In addition, obtaining “hard copy” fluoroscopic images in lieu of spot radiographs can further reduce exposure.43 Ongoing quality assurance programs should be instituted with hospital radiation safety officers.

Stability

Incremental innovation • Simpler • Cheaper

Rapid adoption

Learning curve: safety and efficacy issues Time

CONCLUSIONS

Fig. 4.21 Graph illustrating the natural history of an endoscopic device (adapted from reference # 44 with permission © 2004 American Gastroenterological Association).

The natural history of an endoscopic device involves an initial learning curve followed by rapid adoption and then a relatively slow phase of stability followed by an incremental innovation (Fig. 4.21).44 ERCP accessories have also followed this natural history. Major advances have been made over the last decade. In general, many new accessories are in fact evolutions of old ones as a result of innovations by endoscopists in collaboration with product engineers and specialists. In addition, several products developed for other intra-luminal interventions such as vascular, cardiac and urologic diseases have similar applications in ERCP. Guidewires and expandable metal stents are examples. Therefore, many “new” accessories are in fact

new applications or modifications of available products. This means that many products are approved using 510K pre-market notification to the Food and Drug Administration. Therefore, many products may not have rigorous pre-marketing evaluation and their use may be based on word of mouth, personal experience or at best, case series. Major limitations continue to be cost compared to reimbursement and the lack of cost-effectiveness and pre-marketing studies.45,46

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Law N and Freeman ML. ERCP by using a prototype obliqueviewing endoscope in patients with surgically altered anatomy. Gastrointest Endosc 2004; 59:724–728. Igarashi Y, Tada T, Shimura J, et al. A new cannula with a flexible tip (swing tip) may improve the success rate of endoscopic retrograde cholangiopancreatography. Endoscopy 2002; 34:628–631. Laasch HU, Tringali A, Wilbraham L, et al. Comparison of standard and steerable catheter for bile duct cannulation in ERCP. Endoscopy 2003; 35:669–674. Sherman S, Troiano FP, Hawes RH, Lehman GA. Sphincter of Oddi manometery: decreased risk of clinical pancreatitis with the use of modified aspirating catheter. Gastrointest Endosc 1990; 36:462–466. Wehrmann T, Stergiou N, Schmitt T, et al. Reduced risk for pancreatitis after endoscopic micro transducer manometery of the sphincter of Oddi: A randomized comparison with the perfusion manometery technique. Endoscopy 2003; 35: 472–477. Rossos PG, Kortan P, Haber G. Selective common bile duct cannulation can be simplified by the use of a standard papillotome. Gastrointest Endosc 1993; 39:67–69. Schwacha H, Allgaier HP, Deibert P, et al. A sphincterotomebased technique for selective transpapillary common bile duct cannulation. Gastrointest Endosc 2000; 52: pp 387–391. Cortas GA, Mehta SN, Abraham NS, et al. Selective cannulation of the common bile duct: a prospective randomized trial comparing

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14.

15. 16. 17.

standard catheters with sphincterotomes. Gastrointest Endosc 1999; 50:775–779. Elta GH, Barnett JL, Wille RT, et al. Pure cut electrocautery current for sphincterotomy causes less post-procedure pancreatitis than blended current.Gastrointest Endosc. 1998 Feb; 47(2):149–153. Shah RJ, Antillon MR, Springer EW, et al. A new rotatable papillotome (RP) in complex therapeutic ERCP: indications for use and results. [abstract] Gastrointest Endosc (2003) 57: AB206. Binmoeller KF, Seifert H, Gerke H, et al. Papillary roof incision using the Erlangen-type pre-cut papillotome to achieve selective bile duct cannulation. Gastrointest Endosc (1996) 44:689–695. Uchida N, Tsutsui K, Kamata H, et al. Precutting using a noseless papillotome with independent lumens for contrast material and guidewire. J Gastroenterol Hepatol 2005; 20:947–950. Al-Kawas FH. Biliary access during endoscopic retrograde cholangiopancreatography: How to precut and a word of caution! J Gastroenterol Hepatol 2005; 20:805–806. American Society of Gastrointestinal Endoscopy (ASGE). Guidewires in gastrointestinal endoscopy. Gastrointest Endosc 1998; 47:579–583. Jacob L, Geenen JE. ERCP guide wires. Gastrointest Endosc 1996; 43:57–60. Lella F, Bagnolo F, Colombo E, et al. A simple way of avoiding post-ERCP pancreatitis. Gastrointest Endosc 2004; 59:830–834. Farrell RJ, Howell DA, Pleskow DA. New technology for endoscopic retrograde cholangiopancreatography: improving 41

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18.

19.

20.

21.

22.

23.

24.

25.

26.

27.

28.

29.

30. 31. 32.

42

safety, success, and efficiency. Gastrointest Endoscopy Clin N Am 2003; 13:539–559. Aliperti G, Branch S, Geisman R, et al. Comparison of new rapid exchange technique with standard device during ERCP. A multicenter trial. Digestive Disease Week, May 16–19, Orlando, FL. Beilstein MC, Ahmad NA, Kochman ML, et al. Initial evaluation of a duodenoscope modified to allow guidewire fixation during ERCP. Gastrointest Endosc 2004; 60:284–287. Joyce AM, Ahmad NA, Kochman ML, et al. Multicenter comparative trial of the V-System for therapeutic ERCP. Gastrointest Endosc 2005; 61:AB208. Siegel JH, Pullano W, Kodsi B, et al. Optimal palliation of malignant bile duct obstruction: Experience with endoscopic 12 French prostheses. Endoscopy 1988; 20:137–141. Catalano M, Geenen J, Lehman G, et al. Tannenbaum: Teflon stents versus traditional polyethelene stents for treatment of malignant biliary stricture. Gastointest Endosc 2002; 55: 354–358. Costamagna G, Mutignani M, Rotondano G, et al. Hydrophilic hydromer-coated polyurethane stents versus uncoated stents in malignant biliary obstruction: a randomized trial. Gastrointest Endosc. 2000; 51(1):8–11. Rashdan A, Fogel EL, McHenry L Jr, et al. Improved stent characteristics for prophylaxis of post-ERCP pancreatitis. Clin Gastroenterol Hepatol. 2004; 2(4):322–329. Raju GS, Gomez G, Xiao SY, et al. Determinants of pancreatic injury induced by short-term indwelling stents and modulation of the same by a novel stent design. Gastrointestinal Endoscopy 2004; 59(5):106. Tarnasky PR, Morris J, Hawes RH, et al. Snare beside-a-wire biliary stent exchange: a method that maintains access across biliary strictures. Gastrointest Endosc 1996; 44:185–187. Isayama H, Komatsu Y, Tsujino T, et al. A prospective randomized study of “covered” versus “uncovered” diamond stents for the management of distal malignant biliary obstruction. Gut. 2004; 53(5):729–734. Tamada K, Higashizawa T, Tomiyama T, et al. Ropeway-type bile duct biopsy forceps with a slit for a guidewire. Gastrointest Endosc 2001; 53:89–92. Sorbi D, Van Os EC, Aberger FJ, et al. Clinical application of a new disposable lithotripter: a prospective multicenter study. Gastrointest Endosc 1999; 49:210–213. Shim CS, Neuhaus H, Tamada K. Direct cholangioscopy. Endoscopy 2003; 35:752–758. Kodama T, Tatsumi Y, Kozarek RA, et al. Direct pancreatoscopy. Endoscopy 2002; 34:653–660. Kodama T, Tatsumi Y, Sato H, et al. Initial experience with a new peroral electronic pancreatoscope with an accessory channel. Gastrointest Endosc. 2004; 59:895–900.

33. Farrell JJ, Bounds BC, Al-Shalabi S, et al. Single-operator duodenoscope-assisted cholangioscopy is an effective alternative in the management of choledocholithiasis not removed by conventional methods, including mechanical lithotripsy. Endoscopy. 2005; 37(6):542–547. 34. Levey MJ, Vasquez-Sequerios E, Wiersema MJ. Evaluation of pancreatobiliary ductal system by intraductal US. Gastrointest Endosc 2002; 55:397–408. 35. Jha R, Al-Kawas FH. Nothing quite new is perfect. How good is IDUS in patients with isolated biliary strictures? Am J Gastroenterol 2004; 99:1690–1691. 36. Devereaux BM, Fein S, Purich E et al. A new synthetic porcine secretin for facilitation of cannulation of the dorsal pancreatic duct at ERCP in patients with pancreas divisum: a multicenter, randomized, double-blind comparative study. Gastrointest Endosc 2003; 57:643–647. 37. Park SH, de Bellis M, McHenry L et al. Use of methylene blue to identify the minor papilla or its orifice in patients with pancreas divisum. Gastrointest Endosc 2003; 57:358–363. 38. Lahoti S, Catalano MF, Geenen JE, et al. A prospective, doubleblind trial of L-hyoscyamine versus glucagon for the inhibition of small intestinal motility during ERCP. Gastrointest Endosc 1997; 46:139–142. 39. ASGE Technology Status Evaluation Report: disposable endoscopic accessories. Gastrointest Endosc 2005; 62: 477–479. 40. Lee RM, Vida F, Koarek RA, et al. In vitro and in vivo evaluation of a reusable double-channel sphincterotome. Gastrointest Endosc 1999; 49:477–482. 41. Prat F, Spieler JF, Paci S, et al. Reliability, cost-effectiveness, and safety of reuse of ancillary devices for ERCP. Gastrointest Endosc 2004; 60:246–252. 42. Naidu LS, Singhal S, Preece DE, et al. Radiation exposure to personnel performing endoscopic retrograde cholangiopancreatography. Postgrad Med J 2005; 81: 660–662. 43. Axelrad AM, Fleischer DE, Strack LL, et al. Performance of ERCP for symptomatic choledocholithiasis during pregnancy: techniques to increase safety and improve patient management. Am J Gastroenterol 1994; 89(1): 109–112. 44. Pasricha PJ. The future of therapeutic endoscopy. Clin Gastroenterol Hepatol. 2004; 2(4):286–289. 45. Narain MA, Cockel R. How should endoscopic accessories be selected: trial and error? Gut 2000; 46:305–306. 46. Ganz RA. The development and implementation of new endoscopic technology: what are the challenges? Gastrointest Endosc 2004; 60:592–598.

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5

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Sedation and Analgesia for ERCP Gregory Zuccaro Jr

INTRODUCTION From the technical perspective, endoscopic retrograde cholangiopancreatography (ERCP) is unlike routine upper endoscopy and colonoscopy. The instrument itself is side viewing rather than forward viewing. The procedure goal is not to simply reach the cecum or duodenum, but rather to cannulate small openings with even smaller devices. The time to completion is often significantly longer. We now require trainees to spend extra time acquiring these advanced skills before we consider them competent to perform this demanding procedure. However, in most units, sedation and analgesia is provided in a fashion similar to routine procedures. This chapter will address issues of sedation and analgesia for ERCP, with emphasis on those aspects that might distinguish it from routine endoscopy. An increasing number of endoscopists have chosen to have another provider (i.e. a nurse anesthetist or anesthesiologist) provide sedation for their patients, including ERCP. In some units, deep sedation (defined below) is administered, and in others general anesthesia is routine. The comments in this chapter are directed toward those units and endoscopists that provide sedation and analgesia themselves.

PHYSIOLOGY OF SEDATION AND ANALGESIA FOR ERCP As endoscopists we describe the sedation and analgesia we provide as “conscious sedation.” Not only is that term oxymoronic, but it further incorrectly implies that all sedation and analgesia for endoscopy is the same. To explore this fully, it is essential to review the American Society of Anesthesiologists’ statement on the Continuum of Sedation.1 In this statement, four discrete levels of sedation are described (Table 5.1). For most routine endoscopy, it is assumed that what we incorrectly and imprecisely refer to as conscious sedation actually corresponds to the ASA’s category of moderate sedation. However, note the differences between moderate sedation, and the next category, referred to as deep sedation. In moderate sedation, the patient is able to make a “purposeful” response to verbal or verbal plus gentle tactile stimulation; for example, the patient might be sleeping, but arouses with calling of his/her name or gentle tap on the shoulder, and can give a “thumbs up” or other positive response when asked. Due to the length and difficulty of some ERCP procedures, the level of sedation is often further along the continuum. In the definition for deep sedation, repeated or even painful stimulation may be necessary to obtain a response. Many endoscopists will admit that for at least part of the time, their ERCP patients’ responsiveness better

fits the deep rather than moderate category. We have found that, during serial assessments of level of sedation during ERCP, 85% of patients are deeply sedated for a portion of the procedure.2 Obviously, responsiveness alone during an ERCP procedure is not of high importance, in that the patient’s cooperation or movement is not necessary to complete the procedure. Rather, it is the cardiopulmonary correlates of this level of responsiveness that are essential to consider. It must be recognized that sedation is a continuum, and that it is impossible for the endoscopist to target a specific level of sedation with accuracy. More frequently, patients undergoing sedation for gastrointestinal endoscopy may go from minimal to moderate to deep sedation during the same procedure. A tenet of the ASA guidelines is that skills must be present to rescue patients from a level of sedation deeper than the intended target; i.e. if moderate sedation is the goal, skills must be present to effectively manage any situation that might arise in deep sedation, thereby bringing the patient back to a state of moderate sedation. Similarly, if the goal is provision of deep sedation, skills must be present to effectively manage any situation that might arise in general anesthesia.

SAFETY OF SEDATION AND ANALGESIA Before we discuss the specific actions appropriate for deep sedation during ERCP, we should consider what is known about the safety of our sedation practice. It may be argued that the safety of existing endoscopic practice is not entirely known. Our colleagues in anesthesiology have devoted considerable time defining the safety of general anesthesia, and it is helpful to consider their literature as a prelude to analyzing ours. Death does occur as a result of anesthesia. Prior to the 1980s, there were approximately 2 deaths per 10 000 anesthesias administered. The Institute of Medicine has asserted that this rate has fallen to approximately 1 death per 200 000 to 300 000 anesthesias administered.3 This dramatic change is attributed to improved monitoring, development and implementation of practice guidelines, and other systematic approaches to reducing errors.4–7 To corroborate this, Legasse reviewed mortality rates from anesthesia published by 21 different investigators, and further examined anesthesia experience in a suburban vs urban hospital system between 1992 and 1994. Preventable deaths persist despite an ongoing quality improvement process. Peer review determined that human error contributed to 2.6% of deaths in the suburban system, and 4.7% of deaths in the urban hospital system.8 Not all deaths related were to error; among other factors patients’ preoperative ASA physical status (Box 5.1) correlated with anesthesia mortality.9 A few conclusions may be drawn from reviewing the anesthesia literature: • Morbidity and mortality rates, and factors that contribute to them, can be identified in the literature. 43

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Minimal sedation (anxiolysis)

Moderate sedation/analgesia (“conscious sedation”)

Responsiveness

Normal response to verbal stimulation

Purposeful response to verbal or tactile stimulation

Airway

Unaffected

No intervention required

Spontaneous Ventilation Cardiovascular Function

Unaffected Unaffected

Adequate Usually maintained

Deep sedation/analgesia

General anesthesia

Purposeful response following repeated or painful stimulation Intervention may be required May be inadequate Usually maintained

Unarousable even with painful stimulus Intervention often required Frequently inadequate May be impaired

Table 5.1 ASA levels of sedation (reproduced with permission from the American Society of Anesthesiologists)

Conventional sedation

BOX 5.1 ASA PHYSICAL CLASSIFICATION SYSTEM

10

Silvis Quine11 Arrowsmith12 Sieg13

(reproduced with permission from the American Society of Anesthesiologists)

Death

NR 0.07% 0.5% 0.008%

0.001% 0.03% 0.03% 0%

0.3% 0.2% 0.3% 0.38%

0 0 0 0

Propofol Walker37 Rex38 Huss39 Clark40

Class 1: Patient has no organic, physiologic, biochemical or psychiatric disturbance. The pathologic process for which operation is to be performed is localized and does not entail systemic disturbance. Class 2: Mild to moderate systemic disturbance caused either by the condition to be treated surgically or by other pathophysiologic processes.

Adverse effects

Table 5.2 Large case series reflecting mortality and severe cardiopulmonary adverse eventsa related to sedation and analgesia for endoscopy a

including aspiration, laryngospasm, respiratory arrest.

Class 3: Severe, systemic disturbance or disease from whatever cause, even though it may not be possible to define the degree of disability with finality. Class 4: Severe systemic disorders that are already life threatening, not always correctable by operation. Class 5: The moribund patient who has little chance of survival but is submitted to operation in desperation.

• As expected, sicker patients are at increased risk of adverse outcomes from anesthesia. • Morbidity and mortality rates can be improved with better monitoring, training, and implementation of practice guidelines and systems to reduce error. • Despite all efforts to improve anesthesia’s safety record, human error continues to cause death. How do endoscopists fare with respect to sedation and analgesia? Considering the millions of endoscopic procedures performed every year, safety data for sedation and analgesia are relatively scant (Table 5.2). Most clinical series and controlled trials focus on objective endpoints such as oxygen desaturation, use of reversal agents, or subjective endpoints like patient satisfaction. Many of these studies are not large enough to allow relevant observations on morbidity and mortality. In the 1974 ASGE endoscopy survey, three deaths were attributed to sedation (0.001%).10 In the early 1990s Quine surveyed 36 hospitals where upper GI endoscopic procedures were performed and reported death likely attributable to sedation in 0.03%, and 44

cardiopulmonary arrest in 0.07%. Midazolam and diazepam were equally likely to have been the benzodiazepine utilized. There was a strong correlation between higher doses of benzodiazepines and lack of patient monitoring with adverse outcomes.11 Arrowsmith analyzed data from over 21 000 procedures, and determined a death rate of 0.03% related to sedation and analgesia and 0.5% due to cardiorespiratory arrest.12 Complications were similar with midazolam and diazepam. In distinction, Sieg et al. found no deaths and 16 significant cardiopulmonary adverse events related to sedation (0.008%) among 190 000 EGD and colonoscopy procedures performed in several facilities.13

PRACTICE GUIDELINES FOR SEDATION AND ANALGESIA BY NON-ANESTHESIOLOGISTS The American Society of Anesthesiologists have developed practice guidelines for the provision of sedation and analgesia by nonanesthesiologists, which may apply to all settings outside the operating room, including the emergency department, pulmonary and cardiology suites, and the gastroenterology lab.14 These guidelines were developed by a rigorous analytic process, in an attempt to create evidence-based guidelines. A series of statements regarding all aspects of care for sedated patients was generated, focusing on a clinical intervention and the desired outcome (example: availability of an individual solely dedicated to patient monitoring and safety improves clinical efficacy and/or reduces adverse outcomes). Then, the available evidence from the literature for each statement was

Chapter 5 Sedation and Analgesia for ERCP

judged as supportive (sufficient information from adequately designed studies to describe a statistically significant relationship between an intervention and a clinical outcome), suggestive (evidence from case reports and descriptive studies provides a directional assessment of the relationship between an intervention and clinical outcome, but the type of information does not permit a statistical assessment of significance), equivocal (while studies exist, no clear direction can be determined for clinical outcomes related to an intervention), inconclusive (while studies exist they are not useful to judge a relationship between an intervention and a clinical outcome), insufficient (too few studies to assess a relationship) and silent (no studies were identified). In addition to an assessment of the literature, a group of consultants from all specialties administering sedation was assembled, and their opinion sought on the validity of each of the statements, rated on a scale of 1 (strongly disagree) to 5 (strongly agree). Summarized below is a portion of the literature assessment, consultant opinion, and recommendations for moderate and deep sedation for each aspect of patient care discussed in the ASA guidelines, followed by selected comments, focusing specifically on those aspects most relevant to ERCP:

airway which respond to mechanical and chemical stimuli by affecting tone of the upper airway muscles; this mechanism may help to prevent aspiration. The second influence on upper airway muscles is related to the level of wakefulness of the patient (e.g. snoring reflects an increased airway resistance). Agents used in moderate or deep sedation affect the upper airway muscles more than the diaphragm and produce more depressant effects on airway function than on diaphragmatic function.21–23 Topical anesthetics may contribute to airway obstruction by removing airway mediated reflex brainstem stimulation.24 Given the potential for ventilatory problems surrounding the upper airway, the ASA as well as individual practitioners have focused considerable attention on recognition of patients who are at greater risk of airway failure before any sedative or analgesic agent is administered.14 This evaluation is intended to identify patients in whom positive pressure ventilation, with or without tracheal intubation, may be difficult or impossible. The patient history should identify prior problems with anesthesia or sedation, including difficult airway. Patients with sleep apnea or habitual stridorous snoring are also at high risk for airway problems related to sedation. Other risk factors include advanced rheumatologic or osteoarthritic cervical spine disease, and chromosomal abnormalities such as trisomy 21. Head and neck findings potentially associated with difficulty in positive pressure ventilation include a short neck with limited neck extension, decreased hyoid-mental distance (<3 cm in an adult), presence of a neck mass, evidence of cervical spine disease or trauma, tracheal deviation, or dysmorphic facial features (as in Pierre-Robin syndrome). Additional physical findings that raise the possibility of difficult positive pressure ventilation include a small mouth opening (<3 cm in adult), a high, arched palate, macroglossia, tonsillar hypertrophy, a non-visible uvula, micrognathia, retrognathia, trismus or significant malocclusion of the jaw. Langeron has noted the following factors predicting difficult mask ventilation: presence of a beard, BMI >26, lack of teeth, age >55 years and a history of snoring.25 The presence of any of these findings on history or physical examination does not necessarily imply that only an anesthesiologist may safely provide sedation or analgesia for endoscopy; rather, they are signals that the use and amount of sedation, type of procedure contemplated, or other factors might be modified to minimize risk to the patient. In extreme examples, or when there is significant doubt regarding safety, involvement of an anesthesiologist is reasonable.

Patient evaluation Statement:

Pre procedure patient evaluation improves clinical efficacy and/or reduces adverse outcomes. Literature: Insufficient Consultants: Strongly agree Summary of recommendations: Elements of the pre-sedation history should be established prior to the procedure, including abnormalities of any major organ system, previous experiences with sedation/anesthesia/surgery, current medications, history of allergic reactions, fasting interval prior to the procedure or test, and history of tobacco, alcohol, or substance abuse. Elements of the physical exam include vital signs, auscultation of heart and lungs, evaluation of the airway, head and neck. Laboratory testing should be guided by the patient’s underlying conditions, the procedure to be performed, and the likelihood that results of any test might influence the management of sedation. Comments: The airway consists of those structures through which air passes during ventilation, from the nose to the alveoli. A detailed discussion of the anatomy, physiology and response to sedation of the entire airway is beyond the scope of this review. There are, however, salient facts with which individuals administering sedation and analgesia must be familiar. Adverse outcomes in patients receiving sedation and analgesia are frequently due to airway difficulties.15–17 In particular, the upper airway is the “weak link” where airway obstruction is most likely to occur. With sedation, obstruction of the airway may occur due to the tongue falling posteriorly, causing obstruction at the level of the oropharynx.18,19 Analysis of sedated patients identified decreased diameter of the pharynx at the level of the soft palate and epiglottis as a potential cause of airway obstruction.20 Airway patency is controlled by a complex neuromuscular system. There are two main influences on the control of upper airway muscles. The first involves receptors throughout the upper and lower

Pre procedure preparation Statement:

Pre procedure patient preparation (e.g. counseling, fasting) improves clinical efficacy and/or reduces adverse outcomes. Literature: Insufficient Consultants: Agree for moderate sedation, strongly agree for deep sedation 45

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Summary of recommendations: Informed consent should be obtained in all cases. Patients should fast for the appropriate time preprocedure so as to ensure complete gastric emptying. Patients receiving sedation should be aware of the proscription against driving while the effects of sedation persist. Post-procedure instructions should be discussed prior to sedation and written instructions provided.

Nevertheless, this is a cumbersome technique not typically utilized in gastrointestinal endoscopy. Capnography is based on the principle that carbon dioxide absorbs light in the infrared region of the electromagnetic spectrum. Quantification of the absorption leads to the generation of a curve, which represents a real-time display of the patient’s respiratory activity (Fig. 5.1A–5.1C). Capnography has been utilized to allow the safe titration of propofol by a qualified gastroenterologist during ERCP and EUS.27 Bispectral index (BIS) monitoring represents a complex mathematical evaluation of electroencephalographic parameters of frontal cortex activity, corresponding to varying levels of sedation. The BIS scale varies from 0 to 100 (0, no cortical activity or coma; 40–60, unconscious; 70–90, varying levels of conscious sedation, 100, fully awake). Theoretically this index should reflect the same level of sedation regardless of the medications used, except for ketamine. In a preliminary observational study, involving 50 patients undergoing ERCP, colonoscopy, and upper endoscopy, BIS levels were found to correlate with a commonly used score for the degree of sedation.28 A BIS range of 75–85 demonstrated a probability of >96% that the patient would exhibit an acceptable sedation score. However, there was increasing variability of the BIS score with deeper levels of sedation. Additionally, there was no correlation between the BIS score and standard physiologic parameters such as pulse oximetry, blood pressure or heart rate. The BIS algorithm employed for this study was validated only for deeper levels of sedation, and therefore, may not be a sensitive indicator of moderate levels of sedation and analgesia that are utilized during endoscopy. Although only pulse oximetry is currently routinely utilized, these other advanced monitoring techniques merit further study, particularly given the increased frequency of undertaking deep sedation for endoscopic procedures.

Monitoring Statement:

Patient monitoring (i.e. level of consciousness, respiratory function, hemodynamics) at regular intervals improves clinical efficacy and/or reduces adverse outcomes. Literature: Insufficient Consultants: Strongly agree Summary of recommendations: Monitoring of patient response to verbal commands (for moderate sedation) or for stronger stimuli (for deep sedation) should be routine. All patients should be monitored by pulse oximetry. Ventilatory function should be monitored by observation and/or auscultation. Blood pressure and pulse should be monitored at 5-minute intervals during the procedure. EKG monitoring should be performed in all patients undergoing deep sedation. Comments: Just as has occurred in the field of anesthesiology, automated advance monitoring techniques have been increasingly utilized in gastrointestinal endoscopy. Pulse oximetry has become a de facto standard of care during sedation and analgesia for endoscopy, owing to the evidence that clinical observation alone is inaccurate in the detection of hypoxemia and that supplemental oxygen can minimize the degree of desaturation and hopefully its deleterious effects. To date, neither pulse oximetry nor supplemental oxygen administration has yet been shown to decrease the severity or incidence of cardiopulmonary complications. It is important to point out that pulse oximetry does not measure alveolar hypoventilation, which is measured by hypercapnea or a rise in arterial carbon dioxide pressure. Furthermore, it must be remembered that a pulse oximeter is not an apnea monitor; the early stages of significant hypoventilation may be concurrent with a normal pulse oximetry, particularly if the patient is receiving supplemental oxygen. Although oxygen administration may prevent hypoxemia and its deleterious effects, it will not detect the development of hypercapnea. Deleterious consequences of alveolar hypoventilation include myocardial depression, acidosis, intracranial hypertension, narcosis, and arterial hypertension or hypotension. Transcutaneous CO2 monitoring (PtcCO2) is a non-invasive method for measuring arterial CO2. An electrode is placed on the skin, which is heated to “arterialize” the microcirculation. CO2 then diffuses through the skin and into an electrolyte solution between the skin/electrode interface, which produces carbonic acid. A pH reading is then rendered and the CO2 value is obtained via the Henderson-Hasselbach equation. Nelson et al. utilized this technique in 395 patients undergoing ERCP and concluded that it did prevent severe CO2 retention better than standard monitoring.26 46

Availability of an individual responsible for patient monitoring Statement:

Availability of an individual who is dedicated solely to patient monitoring and safety improves clinical efficacy and/or reduces adverse outcomes. Literature: Silent Consultants: Agree for moderate sedation, strongly agree for deep sedation Summary of recommendations: An individual (not the endoscopist) should be present to monitor the sedated patient. During deep sedation, this person should have no other responsibilities. For moderate sedation, this individual may perform minor, interruptible tasks provided that adequate mechanical and personal monitoring is maintained. Comments: Fundamental to this discussion is the choice each unit makes as to the level of sedation they provide. If a unit contends that they provide moderate sedation, then their patients should meet those criteria, particularly with respect to level of responsiveness. If a unit

Chapter 5 Sedation and Analgesia for ERCP

A mmHg

60 30 0

CO2

B mmHg

60 30 0 CO2

C

V mmHg

60 30 0

CO2

SPO2

Fig. 5.1 A Capnography tracing reflecting normal respiration. B Capnography tracing showing an interruption in regular respiration, followed by resumption of normal breathing. C Simultaneous EKG, capnography and pulse oximetry tracings.

acknowledges deep sedation, then the appropriate level of monitoring must take place, both personal and automated.

Anesthetic induction agents used for sedation and analgesia (e.g. propofol) Statement:

Intravenous sedation/analgesic medications specifically designed to be used for general anesthesia (e.g. propofol) improve clinical efficacy and/or reduce adverse outcomes. Literature: Suggestive for moderate sedation, insufficient for deep sedation Consultants: Equivocal Summary of recommendations: Patients receiving propofol should be monitored as for deep sedation, even if moderate seda-

tion is the target level. Practitioners should be qualified to rescue patients from any level of sedation, including general anesthesia. Comments: Propofol is a highly lipophilic compound formulated in a glycerol, egg phosphatide and soybean emulsion. It is a substituted phenolic compound not related structurally to barbiturates, narcotics, or benzodiazepines. Due to its lipophilic nature, immediately upon administration it distributes first to peripheral tissues and the central nervous system. It is metabolized in the liver, and a conjugated metabolite is excreted in the urine. It is rapidly cleared from the blood, both due to its distribution to the central nervous system and peripheral tissues, and due to effective hepatic metabolism. The presence of liver disease or renal disease does not 47

SECTION 1 GENERAL TOPICS

appear to significantly alter the effective dosing of this agent.29,30 Propofol possesses sedative and amnesic, but very limited analgesic properties. It may be utilized for moderate and deep sedation for minor procedures such as endoscopy, deep sedation in intensive care settings, and for induction and maintenance of general anesthesia. Similar to benzodiazepines, the sedative effects of propofol are mediated primarily through gamma-aminobutyric acid (GABA) receptors in the brain. The binding of GABA to its receptors, located in the cerebrum and cerebral cortex, leads to decreased ability of neurons to generate an action potential. Propofol binds to receptors which increase GABA affinity for its receptor, thereby producing decreased cognition, sensory, memory and motor function.31 Propofol does not work on the exact same GABA receptors as the benzodiazepines, and therefore pharmacologic antagonists for benzodiazepines do not reverse the effects of propofol.32 Sedation and amnesia are dose-dependent; however, propofol produces less amnesia than midazolam at equivalent sedative doses.33,34 There may be considerable adverse hemodynamic effects from propofol, particularly at doses required for deep sedation or general anesthesia. Cerebral blood flow may decrease by 50%, and systemic blood pressure by a third. Cardiac output may fall without a compensatory rise in pulse rate.35 These effects may be accentuated with concomitant use of a parenteral narcotic. Effects on blood pressure and ventilatory effort are accentuated in the elderly. It has been suggested that maintaining a constant blood level by continuous infusion of propofol will result in less hemodynamic compromise compared to periodic bolus infusion with resultant peak levels.36 There are in fact multiple clinical series and randomized controlled trials that support the use of propofol by gastroenterologist-nursing teams. An attribute of a large case series is that some comment can be made regarding safety and efficacy, and while smaller in patient number, controlled trials offer a comparison between two or more sedation and analgesia regimens. In the majority of these case series and controlled trials, propofol was administered in the periodic bolus technique. The largest case series where propofol was administered by an endoscopist-nurse team was published by Walker et al.37 Deep sedation was achieved in the majority of the 9152 cases. Due in large part to the rigorous training the care givers received, propofol sedation was quite safe, with no reported deaths, and only seven

instances of respiratory compromise which responded to temporary support with bag and mask ventilation. Rex, et al., reported a similar series of 2000 patients receiving propofol sedation with periodic bolus by an endoscopist-nursing team.38 Again, propofol delivery was quite safe in the hands of this highly trained and focused team, with no deaths and only four patients required temporary bag and mask ventilatory support. Heuss, et al., provided propofol for 2574 patients undergoing a variety of endoscopic procedures and found a similar safety profile.39 Clarke et al. also report a similar safety profile in over 28 000 patients.40 In these, the largest case series of endoscopist-nurse administered propofol, most patients requiring ventilatory support were undergoing upper endoscopy. Rex has speculated that increased bolus dosing to facilitate esophageal intubation contributes to the increased likelihood of transient ventilatory insufficiency.41 Several prospective, randomized controlled trials have compared endoscopist-nurse administered propofol with conventional parenteral sedation with narcotic and benzodiazepine combinations.42–45 In our experience with gastroenterologist-nurse administered propofol for ERCP and EUS, we found that while patient satisfaction was similar, recovery time was significantly shortened with propofol compared to conventional sedation, and patients had a higher recovery of baseline activity level and dietary intake 24 hours after the procedure.42 While the study was powered only to detect a difference in recovery times, physiologic monitoring parameters showed a trend of actually being better in the propofol group as compared to the conventional sedation group. That said, it is clear from our experience that propofol sedation requires a highly motivated and trained team of gastroenterologists and nurses. Moreover, in most units, if propofol is given as a sole sedation agent, it is more likely to be administered by an anesthesiologist or similarly skilled individual.

SUMMARY Our data indicate that a significant number of patients undergoing ERCP will at some point of the procedure be deeply sedated. Both personal and automated monitoring of these patients should be appropriate for this level of sedation. The ability to rescue a patient from any level of sedation should be available, if necessary, as spelled out by the ASA guideline.

REFERENCES 1.

American Society of Anesthesiologists Website; www.asahq. org.2004. 2. Patel S, Vargo JJ, Khandwala F, et al. Deep sedation occurs frequently during elective endoscopy with Meperidine and Midazolam: Am J Gastroenterol 2005; 100(12):2689–2695. 48

3. Committee on Quality of Health Care in America IOM: To Err is Human: Building a Safer Health System. Edited by Kohn L, Corrigan J, Donaldson M. Washington, National Academy Press, 1999; 241. 4. Sentinel events: approaches to error reduction and prevention. J Comm J Qual Improv 1998; 24(4):175–186.

Chapter 5 Sedation and Analgesia for ERCP

5. Gaba DM. Anesthesiology as a model for safety in health care. BJM 2000; 320:785–788. 6. Stoelting R. APSF response to IOM medical error report. Anesthesia Patient Safety Foundation Newsletter 2000; 15(1):1. 7. Cooper JB, Gaba DM, Liang B, et al. The National Patient Safety Foundation agenda for research and development in patient safety. Med Gen Med 2000; E38. 8. Lagasse R, Anesthesia safety; model or myth? Anesthesiology 2002; 09:1609–1617. 9. American Society of Anesthesiologists Website; www.asahq.org 2004. 10. Silvis SE, Nebel O, Rogers G, et al. Endoscopic complications: Results of the 1974 American Society for Gastrointestinal Endoscopy survey. JAMA 1976; 235:928–930. 11. Quine MA, Bell GD, McCloy RF, et al. Prospective audit of upper gastrointestinal endoscopy in two regions of England: safety, staffing, and sedation methods. Gut 1995; 36:462–467. 12. Arrowsmith JB, Gerstman BB, Fleischer DE, et al. Results from the American Society for Gastrointestinal Endoscopy/U.S. Food and Drug Administration collaborative study on complication rates and drug use during gastrointestinal endoscopy. Gastrointestinal Endoscopy 1991; 37:421–427. 13. Sieg A, Hachmoeller-Eisenbach U, Eisenbach T. Prospective evaluation of complications in outpatient GI endoscopy: a survey among German gastroenterologists. Gastrointestinal Endoscopy 2001; 53:620–627. 14. Gross JB, Bailey PL, Caplan RA, et al. Practice guidelines for sedation and analgesia by non-anesthesiologists. Anesthesiology 2002; 96:1004–1017. 15. Keenan RL, Boyan CP. Cardiac arrest due to anesthesia, JAMA 1985; 252(16):2373. 16. Caplan RA, Posner KL, Ward RJ, et al. Adverse respiratory events in anesthesia: a closed claims analysis, Anesthesiology 1990; 72:828. 17. Cheney FW, Posner KL, Caplan RA. Adverse respiratory events infrequently leading to malpractice suits: a closed claims analysis, Anesthesiology 1991; 75:932. 18. Morikawa S, Safar P, DeCarlo J. Influence of the head-jaw position upon upper airway patency, Anesthesiology 1961; 22:265. 19. Safar P, Escarraga LA, Chang F. Upper airway obstuction in the unconscious patient, J Appl Physiol 1959; 14:760. 20. Shorten GD, Opie NJ, Graziotti P, et al. Assessment of upper airway anatomy in awake, sedated and anaesthetised patients using magnetic resonance imaging, Anaesth Intensive Care 1994; 22:165. 21. Hwang J-C, St. John WM, Bartlett D Jr. Respiratory-related hypoglossal nerve activity: influence of anesthetics, J Appl Physiol 1983; 55:785. 22. Nishino T et al. Comparison of changes in the hypoglossal and the phrenic nerve activity in response to increasing depth of anesthesia in cats. Anesthesiology 1984; 60:19. 23. Hillman DR, Platt PR, Eastwood PR. The upper airway during anesthesia. BR J Anaesth 2003; 91(1):31–39. 24. Deegan PC, Mulloy E, McNicholas WT. Topical oropharyngeal anesthesia in patients with obstructive sleep apnea. Am J Respir Crit Care med 1995; 151(4):1108–1112. 25. Langeron O, Masso E, Huraux C, et al. Prediction of difficult mask ventilation. Anesthesiology,2000 May; 92(5):1217–1218. 26. Nelson DB, Freeman ML, Silvis SE, Cass OW, Yashke PN, et al. A randomized, controlled trial of transcutaneous carbon dioxide monitoring during ERCP. Gastrointest Endosc 2000; 51:288–295. 27. Vargo JJ, Zuccaro G, Dumot JA, et al. Gastroenterologistadministered propofol for therapeutic upper endoscopy with

28.

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44.

45.

graphic assessment of respiratory activity: a case series. Gastrointest Endosc 2000; 52:250–255. Bower AL, Ripepi A, Dilger J, Boparai N, Brody FJ, Ponsky JL. Bispectral index monitoring of sedation during endoscopy. Gastrointest Endosc 2000; 52:192–196. Servin F, Desmonts JM, Haberer JP, et al. Pharmacokinetics and protein binding of propofol in patients with cirrhosis. Anesthesiology 1988; 69(6):887–891. Ickx B, Cockshott ID, Barvais L, et al. Propofol infusion for induction and maintenance of anaesthesia in patients with endstage renal disease. Br J Anaesth 1998; 81(6):854–860. Trapani G, Altomare C, Sanna E, et al. Propofol in anesthesia. Mechanism of action, structure-activity relationships, and drug delivery. Curr Med Chem 2000; 7:249–271. Hales TG, Lambert JJ. The actions of propofol on inhibitory amino acid receptors of bovine adrenomedullary chromaffin cells and rodent central neurons. Br J Pharmacol 1991; 104:619–628. Peduto VA, Concas A, Santoro G, et al. Biochemical and electrophysiologic evidence that propofol enhances GABAergic transmission in the rat brain. Anesthesiology 1991; 75:1000–1009. Whitehead C, Sanders LD, Oldroyd G, et al. The subjective effects of low dose propofol; a double blind study to evaluate dimensions of sedation and consciousness with low-dose propofol. Anaesthes 1994; 490–496. Smith I, Monk TG, White PF, et al. Propofol infusion during regional anesthesia: sedative, amnestic, and anxiolytic properties. Anesth Analg 1994; 79:313–319. Karski JM, Tearsdale SJ, Boylan J, et al. Propofol for continuous intravenous sedation after aortocoronary bypass graft surgery. Dose finding study [abstract]. Can J Anaesth 1994; 41(pt 2):A17. Walker JA, McIntyre RD, Scleinitz PF, et al. Nurse-administered propofol sedation without anesthesia specialists in 9152 endoscopic cases in an ambulatory surgery center. Am J Gastroenterol 2003; 98:1744–1750. Rex DK, Sipe BW, Kinser KM, et al. Safety of propofol administered by registered nurses with gastroenterologist supervision in 2000 endoscopic cases. Am J Gastroenterol 2002; 97:1159–1163. Heuss LT, Schieper P, Drewe J, et al. Risk stratification and safe administration of propofol by registered nurses supervised by the gastroenterologist: a prospective observational study of more than 2000 cases. Gastrointest Endosc 2003; 57:664–671. Clarke AC, Chiragakis L, Hillman LC, et al. Sedation for endoscopy: the safe use of propofol by general practitioner sedationists. Med J Aust 2002; 176:158–161. Rex DK, Overley CA, Walker J. Registered nurse-administered propofol sedation for upper endoscopy and colonoscopy: why? when? how? Reviews in Gastroenterological Disorders 2003; 3:70–80. Vargo JJ, Zuccaro G, Dumot J, et al. Gastroenterologistadministered propofol versus meperidine and midazolam for ERCP and EUS: a randomized controlled trial with cost effectiveness analysis. Gastroenterology 2002; 123:8–16. Sipe BW, Rex DK, Latinovich D, et al. Propofol versus midazolam/ meperidine for outpatient colonoscopy: administration by nurses supervised by endoscopists. Gastrointest Endosc 2002; 55:815–825. Wehrmann T, Grotkamp J, Stergiou N, et al. Electroencephalogram monitoring facilitates sedation with propofol for routine ERCP: a randomized, controlled trial. Gastrointest Endosc 2002; 56:817–824. Ulmer BJ, Hansen JJ, Overly CA, et al. Propofol versus midazolam/ fentanyl for outpatient colonoscopy: administration by nurses supervised by endoscopists. Clin Gastroenterol Hepatol 2003; 1:425–423.

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6

GENERAL TOPICS

Complications of ERCP: Prediction, Prevention and Management Martin L. Freeman

INTRODUCTION ERCP has evolved from a diagnostic modality to a primarily therapeutic procedure for pancreatic as well as biliary disorders. ERCP alone or with associated biliary and pancreatic instrumentation and therapy can cause a variety of short-term complications including pancreatitis, hemorrhage, perforation, cardiopulmonary events, and others (Box 6.1). These complications can range from minor—with one or two additional hospital days followed by full recovery, to severe and devastating with permanent disability or death. Complications may cause the endoscopist significant anxiety and exposure to medical malpractice claims. Major advances in complications of ERCP have occurred in several areas: standardized consensus-based definitions of complications;1 large scale multicenter multivariate analyses that have allowed clearer identification of patient and technique-related risk factors for complications;2–7 and introduction of new devices and techniques to minimize risks of ERCP.

DEFINITIONS OF COMPLICATIONS, ADVERSE EVENTS, UNPLANNED EVENTS AND OTHER NEGATIVE OUTCOMES In 1991, standardized consensus definitions for complications of sphincterotomy were introduced1 (Table 6.1). Severity is graded primarily on number of hospital days and type of intervention required to treat the complication. This classification allows uniform assessment of outcomes of ERCP and sphincterotomy in various settings. Beyond immediate complications, there is an increasing awareness of the entire spectrum of negative (as well as positive) outcomes including technical failures, ineffectiveness of the procedure in resolving the presenting complaint, long-term sequelae, costs, extended hospitalization, and patient (dis)satisfaction. Accordingly, the terminology has evolved from “complications” to “adverse events” to “unplanned events.” Adverse events must be viewed in context of the entire clinical outcome: a successful procedure with a minor or even a moderate complication may sometimes be a preferable outcome to a failed procedure attempt without any obvious complication: failure at ERCP usually leads to a repeated ERCP, or to an alternative percutaneous or surgical procedure which may result in significant additional morbidity, hospitalization and cost.

ANALYSES OF COMPLICATION RATES Reported complication rates vary widely, even between prospective studies. In two large prospective studies, pancreatitis rates ranged

between 0.74% for diagnostic and 1.4% for therapeutic ERCP respectively in one study5 compared with 5.1% (about 7 times higher) for diagnostic ERCP and 6.9% (5 times higher) for therapeutic ERCP in another prospective study.3 Reasons for such variation include: (1) definitions used; (2) thoroughness of detection; (3) patient-related factors; (4) procedural variables, such as use of pancreatic stents, or extent of therapy. For all these reasons, it should not be assumed that a lower complication rate at one center necessarily reflects better quality of practice. Most recent studies have utilized multivariate analysis as a tool to identify and quantify the effect of multiple potentially confounding risk factors, but these are not infallible as many potentially key risk factors were not examined in most studies, and some are overfitted (too many predictor variables for too few outcomes). Only a limited number of studies have included more than 1000 patients. Tables 6.2, 6.3 and 6.4 show a summary of risk factors for complications of ERCP and sphincterotomy based on published multivariate analyses.

OVERALL COMPLICATIONS OF ERCP AND SPHINCTEROTOMY Most prospective series report an overall short-term complication rate for ERCP and/or sphincterotomy of about 5 to 10%.2–7 There is a particularly high rate of complications for sphincter of Oddi dysfunction (up to 20% or more, primarily pancreatitis, with up to 4% severe complications), and a very low complication rate for routine bile duct stone extraction, especially in tandem with laparoscopic cholecystectomy (under 5% in most).2 Sphincterotomy bleeding occurs primarily in patients with bile duct stones, and cholangitis mostly in patients with malignant biliary obstruction. Summaries of multivariate analyses of risk factors for overall complications of ERCP and sphincterotomy are shown in Table 6.2. Although relevant studies are heterogeneous and sometimes omit potentially key risk factors, several patterns emerge (Table 6.2): (1) Indication of suspected sphincter of Oddi dysfunction was a significant risk factor whenever examined. (2) technical factors, likely linked to the skill or experience of the endoscopist, were found to be significant risk factors for overall complications. These technical factors include difficult cannulation, use of precut or “access” papillotomy to gain bile duct entry, failure to achieve biliary drainage, and use of simultaneous or subsequent percutaneous biliary drainage for otherwise failed endoscopic cannulation. In turn, the ERCP case volume of the endoscopists or medical centers, when examined, has always been a significant factor in complications by both univariate or multivariate analysis.2–7 (3) Death from ERCP is rare (less than 0.5%), but most often related to cardiopulmonary complications, 51

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highlighting the need for the endoscopist to pay attention to issues of safety during sedation and monitoring. Notably, risk factors found not to be significant are the following: (1) older age or increased number of coexisting medical conditions—on the contrary, younger age generally increases the risk

both by univariate and multivariate analysis; (2) smaller bile duct diameter, in contrast to previous observations; and (3) anatomic obstacles such as periampullary diverticulum or Billroth II gastrectomy, although they do increase technical difficulty for the endoscopist.2–7

PANCREATITIS BOX 6.1 COMPLICATIONS OF ERCP

Pancreatitis is the most common complication of ERCP, with reported rates varying from 1% to 40%, with a rate of about 5% being most typical. In the consensus classification, pancreatitis is defined as clinical syndrome consistent with pancreatitis (i.e. new or worsened abdominal pain) with an amylase at least three times normal at more than 24 hours after the procedure, and requiring more than one night of hospitalization1 (Table 6.1). Some events are difficult to classify in the consensus definitions, such as patients with postprocedural abdominal pain and elevation of amylase to just under three times normal, or those with dramatic amylase elevations but minimal symptoms that are not clearly suggestive of clinical pancreatitis. There are many potential mechanisms of injury to the pancreas during ERCP and endoscopic sphincterotomy: mechanical, chemical, hydrostatic, enzymatic, microbiologic, and thermal. Although the relative contribution of these mechanisms to postERCP is not known, recent multivariate analyses have helped to identify the clinical patient and procedure-related factors that are independently associated with pancreatitis.

• Pancreatitis • Hemorrhage • Perforation • Cholangitis • Cholecystitis • Stent-related • Cardiopulmonary • Miscellaneous

Pancreatitis

Bleeding

Perforation

Infection (cholangitis)

Mild

Moderate

Severe

Clinical pancreatitis, amylase at least three times normal at more that 24 h after the procedure, requiring admission or prolongation of planned admission to 2–3 days Clinical (i.e. not just endoscopic) evidence of bleeding, hemoglobin drop <3 g, no transfusion Possible, or only very slight leak of fluid or contrast, treatable by fluids and suction for ≤3 days >38°C for 24–48 hr

Pancreatitis requiring hospitalization of 4–10 days

Hospitalization for more than 10 days, pseudocyst, or intervention (percutaneous drainage or surgery)

Transfusion (4 units or less), no angiographic intervention or surgery Any definite perforation treated medically 4–10 days

Transfusion 5 units or more, or intervention (angiographic or surgical) Medical treatment for more than 10 days, or intervention (percutaneous or surgical) Septic shock or surgery

Febrile or septic illness requiring more than 3 days of hospital treatment or percutaneous intervention

Table 6.1 Consensus definitions for the major complications of ERCP Any intensive care unit admission after a procedure grades the complication as severe. Other rarer complications can be graded by length of needed hospitalization.

Definitea

Maybeb

Noc

Suspected sphincter of Oddi dysfunction Cirrhosis Difficult cannulation Precut sphincterotomy Percutaneous biliary access Lower ERCP case volume

Young age Pancreatic contrast injection Failed biliary drainage Trainee involvement

Comorbid illness burden Small CBD diameter Female sex Billroth II Periampullary diverticulum

Table 6.2 Risk factors for overall complications of ERCP in multivariate analyses a

significant by multivariate analysis in most studies. significant by univariate analysis only in most studies. c not significant by multivariate analysis in any study. b

52

Chapter 6 Complications of ERCP: Prediction, Prevention and Management

Definitea

Maybeb

Noc

Suspected sphincter of Oddi dysfunction Young age Normal bilirubin History of post-ERCP pancreatitis Difficult or failed cannulation Pancreatic duct injection Pancreatic sphincterotomy (especially minor papilla) Balloon dilation of intact biliary sphincter Precut sphincterotomy

Female sex Acinarization Absence of CBD stone Lower ERCP case volume Trainee involvement

Small CBD diameter Sphincter of Oddi manometry Biliary sphincterotomy

Table 6.3 Risk factors for post-ERCP pancreatitis in multivariate analyses a

significant by multivariate analysis in most studies. significant by univariate analysis only in most studies. c not significant by multivariate analysis in any study. b

Definitea

Maybeb

Noc

Coagulopathy Anticoagulation <3 days after ES Cholangitis prior to ERCP Bleeding during ES Lower ERCP case volume

Cirrhosis Dilated CBD CBD stone Periampullary diverticulum Precut sphincterotomy

ASA or NSAID Ampullary tumor Longer length sphincterotomy Extension of prior ES

Table 6.4 Risk factors for hemorrhage after endoscopic sphincterotomy in multivariate analyses a

significant by multivariate analysis in most studies. significant by univariate analysis only in most studies. c not significant by multivariate analysis in any study. b

Patient-related risk factors for post-ERCP pancreatitis The risk of post-ERCP pancreatitis is determined at least as much by the characteristics of the patient as by endoscopic techniques or maneuvers (Table 6.3). Patient-related predictors found to be significant in one or more major studies include younger age, indication of suspected sphincter of Oddi dysfunction, history of previous postERCP pancreatitis, and absence of elevated serum bilirubin.2–8 Women may have increased risk, but it is difficult to sort out the contribution of sphincter of Oddi dysfunction, a condition that occurs almost exclusively in women. In one meta-analysis, female gender was clearly a risk,8 and women account for a majority of cases of severe or fatal post-ERCP pancreatitis.9 Patients with multiple risk factors have a dramatically enhanced risk.3 Sphincter of Oddi dysfunction, most often suspected in women with post-cholecystectomy abdominal pain, poses a formidable risk for pancreatitis after any kind of ERCP whether diagnostic, manometric or therapeutic. Suspicion of sphincter of Oddi dysfunction independently triples the risk of post-ERCP pancreatitis to about 10–30%. The reason for heightened susceptibility in these patients remains unknown. Contrary to widely held opinion that sphincter of Oddi manometry is the culprit, recent multivariate analyses show that empirical biliary sphincterotomy or even diagnostic ERCP has similarly high risk.3 With the widespread use of aspiration instead of conventional perfusion manometry catheters, the risk of manometry has probably been reduced to that of cannulation with any other ERCP accessory. Most previous studies linking manometry with risk have been from tertiary centers in which manometry is always performed in patients with suspected sphincter of Oddi dysfunction,

thus losing the ability to separate the contribution of risk from the procedure from that of the patient. Two studies specifically compared risk of post-ERCP pancreatitis in patients having ERCP for suspected sphincter of Oddi dysfunction with and without sphincter of Oddi manometry and found no detectable independent effect of manometry on risk.2,10 Absence of a stone in patients with suspected choledocholithiasis has been found to be a potent single risk factor for post-ERCP pancreatitis in patients suspected of having stones, thus fitting into the category of possible sphincter of Oddi dysfunction. These observations point out the danger of performing diagnostic ERCP to look for bile duct stones in women with recurrent post-cholecystectomy pain, as there is generally a low probability of finding stones in such patients, and a high risk of causing pancreatitis. It is an erroneous and potentially dangerous assumption that merely avoiding sphincter of Oddi manometry will significantly reduce risk. History of previous post-ERCP pancreatitis has been found to be a potent risk factor (odds ratio = 2.0 to 5.4),3,7 and warrants special caution. Advanced chronic pancreatitis, on the other hand, confers some immunity against ERCP-pancreatitis, perhaps because of atrophy and decreased enzymatic activity.3 Pancreas divisum is only a risk factor if minor papilla cannulation is attempted. Despite many early studies suggesting small bile duct diameter to be a risk factor for pancreatitis, most recent studies have shown no independent influence of duct size on risk; small duct diameter may have been a surrogate marker for sphincter of Oddi dysfunction in the earlier studies utilizing only univariate analysis. ERCP for removal of bile duct stones has been found to be relatively safe with respect to pancreatitis rates (<4%) in multicenter studies regardless of bile duct diameter.2 Neither the presence of periampullary 53

SECTION 1 GENERAL TOPICS

diverticula nor Billroth II gastrectomy have been found to influence risk of pancreatitis.2

Technique-related risk factors for post-ERCP pancreatitis Technical factors have long been recognized to be important in causing post-ERCP pancreatitis. Papillary trauma induced by difficult cannulation has a negative effect that is independent of the number of pancreatic duct contrast injections, which is also a risk factor.2,3,6 Pancreatitis occurred in one study after 2.5% of ERCP in which there was no pancreatic duct contrast injection at all.3 Acinarization of the pancreas, although undesirable, is probably less important than generally thought and has not been found to be significant in two recent studies.3,7 Overall, risk of pancreatitis is generally similar for diagnostic and therapeutic ERCP.2–7 Performance of biliary sphincterotomy does not appear to add significant independent risk of pancreatitis to ERCP,3,7 a finding that is contrary to widely held opinion. This is probably not due to the safety of sphincterotomy, but rather to the risk of diagnostic ERCP. Pancreatic sphincterotomy of any kind,3 including minor papilla sphincterotomy7 was found to be a significant risk factor for pancreatitis, although the risk of severe pancreatitis has been very low (less than 1%), perhaps because nearly all of these patients had pancreatic drainage via a pancreatic stent. Precut or access papillotomy to gain access to the common bile duct is controversial with respect to risk of pancreatitis and other complications. Use among endoscopists varies from under 5% to as many as 30% of cases.11 There are many variations on precut technique: standard needle-knife inserted at the papillary orifice and cutting upwards; needle-knife “fistulotomy” starting the incision above the papillary orifice and then cutting either up or down; use of a pull-type sphincterotome wedged in the papillary orifice, or into the pancreatic duct. Any of the above techniques has the potential to lacerate and injure the pancreatic sphincter, and precut techniques have been uniformly associated with a higher risk of pancreatitis in multicenter studies involving endoscopists with varied experience, with precut sphincterotomy found significant as a univariate or multivariate risk factor for post-ERCP pancreatitis and/or overall complications.2,5 In contrast, many series from tertiary referral centers have found complication rates no different than for standard sphincterotomy, suggesting that risk of precut sphincterotomy is highly operator-dependent.11 In one study, endoscopists performing more than one sphincterotomy a week averaged 90% immediate bile duct access after precutting, versus only 50% for lower volume endoscopists, a success rate which hardly justifies the risk of complications.2 Comparative studies of precut with standard sphincterotomy are hard to interpret because indications and settings may be very different, with precut preferentially performed in lower risk situations such as obstructive jaundice, and prominent papillae. In addition, increasing use of pancreatic stents in series from tertiary centers may have neutralized the otherwise higher risk of precut sphincterotomy.7 Complications of precut sphincterotomy vary with the indication for the procedure, occurring in as many as 30% of patients with sphincter of Oddi dysfunction in older studies without use of pancreatic stents.2 Paradoxically, in patients with sphincter of Oddi dysfunction, needle-knife sphincterotomy over a pancreatic stent placed early in the procedure has been shown to be substantially 54

safer than conventional pull-type sphincterotomy without a pancreatic stent.12 There has been controversy as to whether increased risk of precut sphincterotomy is due to the technique itself or due to prolonged cannulation attempts that often precede its use. A randomized trial at one tertiary center found no significant difference in pancreatitis or overall complication rates between prolonged cannulation and early use of precut without a pancreatic duct stent.13 Risk of post-ERCP pancreatitis escalates in patients with multiple risk factors.3 The interactive effect of multiple risk factors is reflected in the profile of patients developing severe post-ERCP pancreatitis. In one study, females with a normal serum bilirubin had a 5% risk of pancreatitis; with addition of difficult cannulation risk rose to 16%; with further addition of suspected sphincter of Oddi dysfunction (i.e. no stone found), the risk rose to 42%.3 In two different studies, nearly all of the patients who developed severe pancreatitis were young to middle-aged women with recurrent abdominal pain, a normal serum bilirubin, and with no biliary obstructive pathology.3,9 These observations emphasize the importance of tailoring the approach of ERCP to the individual patient. One recent study has clearly shown that trainee participation adds independent risk of pancreatitis.7 In contrast, most multicenter studies have failed to show a significant correlation between endoscopists’ ERCP case volumes and pancreatitis rates.2,3,5 It is possible that none of the participating endoscopists in those studies reached the threshold volume of ERCP above which pancreatitis rates would diminish (perhaps greater than 250–500 cases per year). However, most American endoscopists average less than two ERCP’s per week,3 and the reported rates of pancreatitis from the highest volume tertiary referral centers in the US are often relatively higher than those in private practices. All of these observations suggest that case mix is at least as important as expertise in determining risk of postERCP pancreatitis.

Specific techniques to reduce risk of post-ERCP pancreatitis It stands to reason that the most expeditious method of cannulation will likely be the safest. Use of a papillotome or steerable catheter for biliary cannulation has been prospectively compared to a standard catheter in a number of randomized trials.11 Although all showed significantly higher success with the sphincterotome, there was no difference in rates of pancreatitis or other complications. Another randomized trial did show significant reduction of pancreatitis risk when a guidewire was used in conjunction with a papillotome, as opposed to a papillotome alone.14 Pancreatic stent placement can reduce risk of post-ERCP pancreatitis in a number of settings (Table 6.5), and is widely performed at many advanced centers for this purpose (Fig. 6.1). Specific situations where placement of a pancreatic stent has been shown to reduce risk include biliary sphincterotomy for sphincter of Oddi dysfunction, pancreatic sphincterotomy, precut sphincterotomy, balloon-dilation of the biliary sphincter, and endoscopic ampullectomy, and probably after difficult cannulation.15–20 A meta-analysis suggests that use of pancreatic stents in high-risk patients reduced rates of pancreatitis by about two thirds, with virtual elimination of severe post-ERCP pancreatitis.18 While effective in high-risk cases, placement of pancreatic stents is usually unnecessary regardless of cannulation difficulty in older, jaundiced patients especially if they have a pancreatic duct obstructed by cancer.

Chapter 6 Complications of ERCP: Prediction, Prevention and Management

Setting

Benefit

Biliary sphincterotomy for SOD yes Pancreatic sphincterotomy for SOD trend Biliary balloon dilation for stone trend Precut (access) biliary sphincterotomy “High risk” including difficult cannulation Endoscopic ampullectomy

yes

Evidence RCT RCT (abstract) retrospective case-control RCT (abstract)

yes/trend RCT × 2 yes/trend RCT, Retrospective case-control

Table 6.5 Pancreatic stents to reduce risk of post-ERCP pancreatitis RCT = randomized controlled trial.

A

B

C

D

Fig. 6.1 Placement of pancreatic stent to reduce risk of post-ERCP pancreatitis. A A guidewire passed to body of pancreatic duct around genu. B 4 Fr single pigtail 9 cm long unflanged pancreatic stent placed. C Endoscopic view of guidewire in pancreatic duct after biliary sphincterotomy. D 4 Fr single pigtail pancreatic stent placed with drainage of pancreatic juice.

Pancreatic stenting has limitations as a strategy to reduce risk as many endoscopists and their assistants are unfamiliar with their placement and may have a substantial failure rate, leaving the patient worse off than if no attempt was made.20 Small caliber wires (0.018″ or 0.025″) are often required, and techniques for deep insertion of such guidewires may be unfamiliar to many endoscopists. Small tortuous ducts and ansa pancreaticus (360° alpha loop) may post a challenge even for the most experienced endoscopist. A technique has been described which avoids deep wire passage and allows universal success at placing stents in difficult anatomy;20 a small caliber nitinol tipped wire can be knuckled inside the main pancreatic duct just beyond the sphincter and allow delivery of a small caliber short stent without need for passing the wire around tight turns in a tortuous duct.

Unfortunately, pancreatic stents may cause problems. They may migrate inside the pancreatic duct, especially stents of straight configuration without a pigtail on the duodenal end, and those with dual inner flanges. This complication can largely be avoided by use of a single pigtail on the duodenal end. The major concern about pancreatic stents is the potential to cause ductal or parenchymal injury or even perforation; duct and parenchymal injury has been reported in up to 80% of patients with normal ducts, using conventional 5 French or greater polyethylene stents, and sometimes leads to severe ductal stenosis and relapsing pancreatitis.21,22 Strategies to avoid this complication included use of smaller caliber stents (3 or 4 French), which have been shown to be associated with dramatically lower rates of duct injury,23 and use of stents made of softer materials. Pancreatic stents placed for prevention of post-ERCP pancreatitis in normal ducts should be documented to pass by x-ray or removed within a few weeks. If they have not passed by then, they need to be removed. Balloon-dilation of the biliary sphincter has been introduced as an alternative to sphincterotomy for the extraction of bile duct stones. Although trials from overseas have shown complications to be equivalent to or less than for sphincterotomy, balloon dilation has been associated with a markedly increased risk of pancreatitis in the US, resulting in two deaths in one study,24 and with a higher risk of pancreatitis by meta-analysis of pooled studies.25 In general, balloon dilation of the intact biliary sphincter for extraction of bile duct stones is not recommended unless there is a relative contraindication to sphincterotomy such as coagulopathy or need for early anticoagulation. In contrast, balloon dilation performed after biliary sphincterotomy to facilitate large stone extraction may be relatively safe and may reduce need for excessively large sphincterotomy and its associated risk of perforation or bleeding. Thermal injury is thought to play some role in causing pancreatitis after biliary and pancreatic sphincterotomy. A number of randomized trials have compared the impact of pure cutting versus blended current, with mixed results but generally lower rates of pancreatitis using the pure cut current.15,26 Automated current delivery systems programmed to deliver a specific tissue effect are now widely used. None of the available studies suggest a significant difference in rates of pancreatitis between these units compared with blended current, so that it is not yet clear whether automated current delivery systems provide the same benefit for prevention of pancreatitis as do those using pure cutting current.

Pharmacological agents Many pharmacological agents have been investigated as potential agents to reduce post-ERCP pancreatitis, but results have generally been mixed or negative. In meta-analyses of randomized controlled trials, gabexate (a protease inhibitor) or somatostatin has been found to be marginally effective but only if given over an extended infusion (up to 12 hours after ERCP), while shorter infusions (less than 4 hours) are generally ineffective.15 Neither of these agents is available in the United States, and the cost-effectiveness of prolonged infusions severely limits the cost-effectiveness and practicality of these agents. More promising agents in single pilot studies have included NSAID, secretin, and Ulistatin, a long-acting protease inhibitor.15 However each of these agents has been found to be effective in only a single trial, and it seems likely that these agents may join the ranks of other promising agents whose efficacy did not hold up under further multicenter trials. Agents shown not to be effective include interleukin 10, octreotide, corticosteroids, 55

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allopurinol, platelet-activating factor inhibitors, heparin, and use of non-ionic contrast.15 Thus it appears that at this time, meaningful pharmacologic prophylaxis against post-ERCP pancreatitis is currently not feasible.

Prevention and treatment of post-ERCP pancreatitis The single most important way to avoid post-ERCP pancreatitis is to avoid performing ERCP for marginal indications, especially in patients at higher risk of complications. Paradoxically, the risk is often higher and potential benefit of therapy lower in marginally indicated ERCP than for patients with obstructive jaundice. ERCP should generally be avoided when the probability of finding stones or other obstructive pathology is low and other methods are available, or situations in which the risk/benefit ratio of conventional diagnostic or biliary therapeutic ERCP is excessive (such as suspected sphincter of Oddi dysfunction). Alternative imaging techniques such as intraoperative laparoscopic cholangiography, MRCP and endoscopic ultrasound are safer alternatives for excluding obstructive biliary pathology. Patients who have negative evaluation by these alternative techniques, but who are still suspected to have a pancreatic or biliary cause for recurrent symptoms, are probably best served by referral to a tertiary ERCP center capable of advanced techniques for diagnosis including endoscopic ultrasound, advanced therapeutics including pancreatic endotherapy, for near-certain ability to place pancreatic stents. Once the decision has been reached to proceed with ERCP, cannulation and sphincterotomy techniques should be tailored to the risk profile of that individual. In low risk cases such as elderly patients with obstructive jaundice, manipulation is generally well tolerated, and whatever techniques are effective at gaining bile duct access and drainage are reasonable. In high-risk cases, manipulation should be minimized, and placement of a pancreatic stent considered. Placement of pancreatic stents is recommended in most patients with suspected sphincter dysfunction, history of post-ERCP pancreatitis, difficult cannulation, or prior to precut sphincterotomy with unclear papillary anatomy or other risk factors. For pancreatic stent insertion, size of stent should be tailored to the caliber and course of the pancreatic duct, with small caliber (3 to 5 French) pancreatic stents that are generally either short (2–3cm), or long (7–10cm) and unflanged. Use of precut sphincterotomy in high-risk patients is probably best performed primarily by experts, probably best done early rather than late in the procedure, and after placement of a pancreatic stent in high-risk circumstances or unclear papillary anatomy. Treatment of post-ERCP pancreatitis is like that for any other cause of acute pancreatitis. Early recognition of impending postERCP pancreatitis can be facilitated by checking serum amylase or other enzymes within a few hours after the procedure in patients who are at high risk or who have abdominal pain. If serum amylase or lipase is normal, probability of developing pancreatitis is very low and the patient can be considered for same-day discharge if otherwise reasonable. On the other hand, if the pancreatic enzymes are significantly elevated, premature same-day discharge may be avoided, and pre-emptive hospitalization for observation, fasting and vigorous intravenous hydration initiated. Severely ill patients should be hospitalized in the intensive care unit with help obtained from other specialists in managing the patient.

56

HEMORRHAGE Bleeding seen endoscopically during sphincterotomy is often reported as a complication, but of itself does not represent an adverse outcome to the patient. Some degree of bleeding, ranging from oozing to severe bleeding, is seen at the time of sphincterotomy in about 10–30% of cases. Clinically significant hemorrhage is defined in the consensus criteria (Table 6.1) as clinical evidence of bleeding such as melena or hematemesis, with or without an associated fall in hemoglobin, or requirement for secondary intervention such as endoscopy or blood transfusion, and occurs in 0.5–2% of sphincterotomies.2 Clinical presentation is generally delayed from 1 to as many as 10 days after sphincterotomy.2

Risk factors for hemorrhage after sphincterotomy For clinically significant hemorrhage (Table 6.4), risk factors include any degree of bleeding during the procedure, presence of any coagulopathy or thrombocytopenia (including hemodialysis-associated coagulation disorders), initiation of anticoagulant therapy within three days after ES, and relatively low case-volume on the part of the endoscopist (performance of not more than one sphincterotomy per week), which may reflect less precise control of the incision or less effective endoscopic control of bleeding once it has occurred.2 Factors that do not appear to raise risk include use of aspirin or nonsteroidal anti-inflammatory drugs, making a longer incision, or enlarging a previous sphincterotomy.2 The effect of newer antiplatelet agents such as Plavix is unknown. Some studies have shown additional risk factors for significant hemorrhage to include use of precut sphincterotomy.

Methods to prevent and treat hemorrhage Bleeding after sphincterotomy can mostly be avoided by avoiding sphincterotomy in patients with risk factors such as coagulopathy. Once sphincterotomy is undertaken, risk can be minimized by correction of any coagulopathies, withholding anticoagulant medications for as many as three days afterwards, and by use of meticulous endoscopic technique. Prophylactic injection of the sphincterotomy site with epinephrine or even a sclerosing agent in patients with coagulopathy may reduce risk of hemorrhage. Newer computerized tissue-effect electrocautery units have been shown to reduce risk of immediate bleeding but have not as yet been shown to decrease the incidence of clinically significant hemorrhage. Once hemorrhage occurs, either immediately during sphincterotomy, or delayed, it can generally be controlled with endoscopic therapy via injection of dilute epinephrine. Balloon-tamponade using standard occlusion balloons may allow temporary control of bleeding and improve visualization of the bleeding site. Thermal therapy such as bipolar coagulation or clipping can follow (Fig. 6.2). Caution should be taken to avoid thermal injury or clip placement over the pancreatic sphincter, especially if the bleeding site is on the right-hand wall of the sphincterotomy incision. Rarely, angiography or surgery is required for refractory bleeding.

PERFORATION Perforation may occur within the bowel wall by the endoscope, extension of a sphincterotomy incision beyond the intramural portion of the bile or pancreatic duct with retroperitoneal leakage,

Chapter 6 Complications of ERCP: Prediction, Prevention and Management

A

B

C

D

A

B

Fig. 6.4 A Distal migration of a biliary stent with perforation of the opposite wall of the duodenum. The stent was placed five days prior for hilar tumor obstruction. The patient presenting with an acute abdomen. B CT scan showing tip of stent and air in retroperitoneum anterior to the right kidney.

Fig. 6.2 Endoscopic injection and clipping of sphincterotomy bleed. A Bleeding from left edge of sphincterotomy. B Injection of epinephrine. C Positioning of endoscopic clip. D Final placement of two clips on left edge of sphincterotomy with hemostasis.

Fig. 6.5 CT scan obtained immediately after biliary sphincterotomy perforation shows air in subcutaneous tissues, free intraperitoneal and retroperitoneal air. This patient developed crepitus during ERCP with sphincterotomy and lithotripsy for large stone. A nasobiliary drain was placed. No contrast extravasation was demonstrated either through nasobiliary drain or by CT, suggesting a favorable course for nonoperative management. This patient was treated with nasobiliary and nasogastric drainage, antibiotics, and recovered fully without further intervention. (Courtesy Dr Oliver Cass.) Fig. 6.3 Fluoroscopic image after biliary sphincterotomy with large retroperitoneal perforation. A nasobiliary drain has been placed, and large amounts of retroperitoneal air outlining the right kidney are apparent, with contrast tracking into retroperitoneum around the nasobiliary drain. As the leak was recognized immediately and was large and ongoing, this patient was managed with urgent operative intervention with oversew of the perforation but without duodenotomy, and was discharged home 5 days later.

or occur at any location due to extramural passage or migration of guidewires or stents (Figs 6.3, 6.4A, 6.4B, and 6.5). Perforation is now reported in less than 1% of ERCP and sphincterotomies.2–7 Risk factors for sphincterotomy perforation have been difficult to quantify due to the rarity of perforation. It is probable that bowel perforation is more common in patients with Billroth II anatomy, and sphincterotomy perforation after needle-knife precut techniques, and in patients with suspected sphincter of Oddi dysfunction, all situations where control and extent of the required incision is uncertain.27,28

Treatment of post-ERCP perforation varies with the type and severity of the leak and clinical manifestations. Bowel wall perforations must generally be treated surgically, while guidewire or stent-related perforations can usually be treated endoscopically by providing adequate ductal drainage.28 Keys to avoiding perforation during sphincterotomy are to limit the length of cutting wire in contact with the tissue and to use stepwise incisions. If perforation is suspected during a sphincterotomy, injection of a small amount of contrast while pulling the papillotome through the incision over a guidewire will confirm or exclude extravasation and allow proactive treatment. Endoscopic clipping may be attempted in order to close a definite leak.29 In most cases, a nasobiliary and/or nasopancreatic drain should be placed (depending on the sphincter cut), and the patient treated with nasogastric suction, intravenous antibiotics, strict fasting, and in-hospital observation. The importance of early recognition and endoscopic drainage of suspected perforations is

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supported by the observation that nearly all patients with immediate recognition and endoscopic drainage did well with conservative management, in comparison with poor outcomes including need for surgery and some mortality in patients with delayed recognition.29 Once a perforation of any kind is suspected, a CT scan of the abdomen should be obtained to assess for contrast leakage and any retroperitoneal or intraperitoneal air (Fig. 6.5). If the leak is sizeable and ongoing as suggested by contrast extravasation, or the patient’s clinical condition deteriorates, prompt drainage via surgery or the percutaneous route is advisable (Fig. 6.3).

CHOLANGITIS AND CHOLECYSTITIS Cholangitis (ascending bile duct infection) and cholecystitis (gallbladder infection) are potential complications or sequelae of ERCP and/or sphincterotomy. Risk factors for cholangitis after ERCP and sphincterotomy consist primarily of failed or incomplete biliary drainage2–7 and use of combined percutaneous-endoscopic procedures.2 Other risk factors may include jaundice especially if due to malignancy, and operator inexperience.2 Several studies have shown that prophylactic antibotics can reduce the rate of bacteremia, but few studies have shown a reduction in clinical sepsis following ERCP, and a meta-analysis concluded that there was no clinical benefit to routine administration of antibiotics.30 Thus the principal recommendation regarding prevention and treatment of cholangitis is obtaining successful and complete biliary drainage.

LONG-TERM COMPLICATIONS/SEQUELAE Recent studies have shown that if the gallbladder is left intact after sphincterotomy, both early and late cholecystitis occur more frequently than previously thought. Not surprisingly, both cholecystitis and recurrent bile duct stones are more common if the gallbladder left in situ contains stones. There is increasing concern about potential long-term sequelae of various components of endoscopic therapy, including endoscopic biliary and pancreatic sphincterotomy. These include recurrent stone formation, possibly resulting from sphincterotomy stenosis, or bacterobilia due to duodenal-biliary reflux, or “sine-materia” cholangitis. Recurrent stones and other biliary problems may occur in from 6% to 24% of patients undergoing longterm follow-up. Recurrent pancreatitis, presumably due to thermal injury to the pancreatic sphincter, may occur after biliary sphincterotomy. The long-term effects of pancreatic sphincterotomy, which is increasingly performed in patients with and without chronic pancreatitis, are largely unknown.

OPERATOR EXPERIENCE AND COMPLICATIONS The effect of endoscopic expertise on outcome of ERCP is difficult to evaluate but is likely profound. Simple comparisons of complication rates of ERCP between centers can be misleading, since the case mix, intent of the procedure, and success rates at achieving biliary and pancreatic duct access vary widely. A number of studies have evaluated operator factors in complications of ERCP. Lower ERCP case volume, defined variably, was significantly associated with higher overall complications by univariate and multivariate analysis in all studies which have evaluated that risk factor. In one study, endoscopists who performed more than one sphincterotomy per 58

week had somewhat lower rates of overall complications (8% vs 11%), but substantially lower rates of severe complications (0.9% vs 2.3%);2 in a multivariate model utilizing only information available prior to ERCP, lower procedure volume was one of only three variables which predicted complications of sphincterotomy.2 Lower case volume was significantly associated with higher rates of hemorrhage after sphincterotomy in two studies.2,5 In contrast, lower ERCP case volume has not consistently been found to correlate with rates of post-ERCP pancreatitis, suggesting the importance of case-mix in determining this complication. The available data probably underestimate the influence of operator experience on outcomes of ERCP, since high-volume endoscopists attempt higher-risk cases, and also have higher success rates at duct access. In one study endoscopists averaging more than 100 ERCP cases per year had 96.5% success at bile duct access compared with 91.5% for lower volume endoscopists.3 In two other studies, rates for failure and complications of ERCP by higher volume endoscopists were significantly lower than those of lesser-volume endoscopists.2,5 Failure to complete ERCP may have as much negative impact on patients as complications in terms of cost, need for further interventions, and extension of hospital stay. It is not known what minimum volume of cases is required in order to maintain proficiency, but probably in excess of 100 cases per year to sustain good outcomes for routine biliary therapy, and 200–250 cases per year for advanced pancreatic techniques. A minority of endoscopists in the US achieve such volumes of ERCP. The data suggest that outcomes will be optimal if fewer endoscopists perform more ERCP. It is not feasible or palatable to suggest that all ERCP be performed at advanced centers. Rather, adequate training and ongoing case volume should be a prerequisite for performing ERCP in practice. Larger groups should concentrate all their ERCP to a few dedicated individuals rather than dilute the experience, and smaller groups who are unable to sustain adequate volumes should consider contracting their ERCP work out to more experienced individuals. Endoscopists who perform limited amounts of complex ERCP should be amenable to prompt referral to a specialized center of potentially complex cases including difficult biliary problems, all pancreatic therapeutics, and most cases of suspected sphincter of Oddi dysfunction. The key is for each endoscopist to find the optimal balance between risk and benefit for the individual patient and their own individual expertise and experience (Box 6.2).

BOX 6.2 STRATEGIES TO REDUCE COMPLICATIONS OF ERCP • Improved training • Education of endoscopists regarding risk factors • Avoidance of marginally indicated ERCP • Referral to advanced centers for complex or high-risk cases • Fewer endoscopists performing more ERCP

Chapter 6 Complications of ERCP: Prediction, Prevention and Management

REFERENCES 1.

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14. 15. 16.

Cotton PB, Lehman G, Vennes JA, et al. Endoscopic sphincterotomy complications and their management: an attempt at consensus. Gastrointest Endosc 1991; 37:383–391. Freeman ML, Nelson DB, Sherman S, et al. Complications of endoscopic biliary sphincterotomy. N Engl J Med 1996; 335:909–918. Freeman ML, DiSario JA, Nelson DB, et al. Risk factors for postERCP pancreatitis: a prospective, multicenter study. Gastrointest Endosc 2001; 54:425–434. Masci E, Toti G, Mariani A, et al. Complications of diagnostic and therapeutic ERCP: a prospective multicenter study. Am J Gastroenterol. 2001; 96:417–423. Loperfido S, Angelini G, Benedetti G, et al. Major early complications from diagnostic and therapeutic ERCP: a prospective multicenter study. Gastrointest Endosc 1998; 48:1–10. Vandervoort J, Soetikno RM, Tham TC, et al. Risk factors for complications after performance of ERCP. Gastrointest Endosc. 2002; 56:652–656. Cheng C, Sherman S, Watkins JL, et al. Risk factors for post-ERCP pancreatitis: a prospective multicenter study. American Journal of Gastroenterology 2005 (in press). Masci E, Mariani A, Curioni S, et al. Risk factors for pancreatitis following endoscopic retrograde cholangiopancreatography: a meta-analysis. Endoscopy 2003; 35:830–834. Trap R, Adamsen S, Hart-Hansen O, et al. Severe and fatal complications after diagnostic and therapeutic ERCP: a prospective series of claims to insurance covering public hospitals. Endoscopy 1999; 31:125–130. Singh P, Gurudu SR, Davidoff S, et al. Sphincter of Oddi manometry does not predispose to post-ERCP acute pancreatitis. Gastrointest Endosc. 2004; 59:499–505. Freeman ML, Guda NL. Cannulation techniques for ERCP: a review of reported techniques. Gastrointest Endosc 2005; 61:112–125. Fogel EL, Eversman D, Jamidar P, et al. Sphincter of Oddi dysfunction: pancreaticobiliary sphincterotomy with pancreatic stent placement has a lower rate of pancreatitis than biliary sphincterotomy alone. Endoscopy. 2002; 34:280–285. Tang SJ, Haber GB, Kortan P, et al. Precut papillotomy versus persistence in difficult biliary cannulation: a prospective randomized trial. Endoscopy. 2005; 37:58–65. Lella F, Bagnolo F, Colombo E, et al. A simple way of avoiding post-ERCP pancreatitis. Gastrointest Endosc. 2004; 59:830–834. Freeman ML, Guda NM. Prevention of post-ERCP pancreatitis: a comprehensive review. Gastrointest Endosc 2004; 59:845–684. Tarnasky, P, Palesch, Y, Cunningham J, et al. Pancreatic stenting prevents pancreatitis after biliary sphincterotomy in patients with

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29.

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sphincter of Oddi dysfunction. Gastroenterology 1998; 115:1518–1524. Fazel A, Quadri A, Catalano MF, et al. Does a pancreatic duct stent prevent post-ERCP pancreatitis? A prospective randomized study. Gastrointest Endosc 2003; 57:291–294. Singh P, Das A, Isenberg G, et al. Does prophylactic pancreatic stent placement reduce the risk of post-ERCP acute pancreatitis? A meta-analysis of controlled trials. Gastrointest Endosc. 2004; 60:544–550. Harewood GC, Pochron NL, Gostout CJ. Prospective, randomized, controlled trial of prophylactic pancreatic stent placement for endoscopic snare excision of the duodenal ampulla. Gastrointest Endosc. 2005; 62:367–370. Freeman ML, Overby CS, Qi DF. Pancreatic stent insertion: consequences of failure, and results of a modified technique to maximize success. Gastrointest Endosc. 2004; 59:8–14. Smith MT, Sherman S, Ikenberry SO, et al. Alternations in pancreatic ductal morphology following polyethylene pancreatic stent therapy. Gastrointest Endosc. 1996; 44:268–275. Kozarek RA. Pancreatic stents can induce ductal changes consistent with chronic pancreatitis. Gastrointest Endosc. 1990; 36:93–95. Rashdan A, Fogel EL, McHenry L Jr, et al. Improved stent characteristics for prophylaxis of post-ERCP pancreatitis. Clin Gastroenterol Hepatol. 2004; 2:322–329. Disario JA, Freeman ML, Bjorkman DJ, et al. Endoscopic balloon dilation compared with sphincterotomy for extraction of bile duct stones. Gastroenterology 2004; 127:1291–1299. Baron TH, Harewood GC. Endoscopic balloon dilation of the biliary sphincter compared to endoscopic biliary sphincterotomy for removal of common bile duct stones during ERCP: a metaanalysis of randomized, controlled trials. Am J Gastroenterol. 2004; 99:1455–1460. Elta GH, Barnett JL, Wille RT, et al. Pure cut electrocautery current for sphincterotomy causes less post-procedure pancreatitis than blended current. Gastrointest Endosc 1998; 47:149–153. Enns R, Eloubeidi MA, Mergener K. ERCP-related perforations: risk factors and management. Endoscopy. 2002; 34:293–298. Howard TJ, Tan T, Lehman GA, et al. Classification and management of perforations complicating endoscopic sphincterotomy. Surgery. 1999; 126(4):658–663. Baron TH, Gostout CJ, Herman L. Hemoclip repair of a sphincterotomy-induced duodenal perforation. Gastrointest Endosc. 2000; 52:566–568. Harris A, Chan AC, Torres-Viera C, et al. Meta-analysis of antibiotic prophylaxis in endoscopic retrograde cholangiopancreatography (ERCP). Endoscopy. 1999; 9:718–724.

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7

GENERAL TOPICS

ERCP Training Jürgen Hochberger, Detlev Menke, and Jürgen Maiss

INTRODUCTION

CLINICAL TRAINING IN ERCP

Diagnostic and interventional endoscopy is in a state of continuous technological advancement and in the past few decades the latter has replaced surgery for many gastrointestinal disorders. One example is the development of endoscopic retrograde cholangiopancreatography (ERCP) for the nonsurgical treatment of common bile duct stones.1–3 Endoscopic therapy for common bile duct stones can be as simple as sphincterotomy and as complex as the use of lithotripsy devices.4–6 Proficiency in all aspects of ERCP requires several years of practical training and continuous refinement of knowledge.7–11 A standardized mandatory teaching program for gastrointestinal (GI) endoscopy has not been established so far. Historically, endoscopic training has consisted primarily of “learning by doing” under the supervision of an experienced endoscopist.12,13 With the advent of non-invasive tests such as magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS), ERCP has moved from a diagnostic to an almost purely therapeutic procedure.14,15 This creates a new challenge to the education of young endoscopists, since ERCP procedures are becoming more concentrated in large or mid volume endoscopy centers while the number of ERCPs performed in smaller hospitals is decreasing. These smaller hospitals are often located in rural areas and provide limited ERCP services such as sphincterotomy, stone extraction and stent implantation. Threshold numbers of ERCP procedures that must be performed by trainees for credentialing were published in the Gastroenterology Core Curriculum in 1996.12 This document indicated that fellows had to complete 100 ERCPs, including 25 therapeutic cases (20 sphincterotomies and 5 stent placement cases). Jowell et al. found a minimum number of 180–200 ERCPs needed to be performed before a trainee can be considered competent for non-supervised ERCP (Fig. 7.1).16 Approximately 80–100 ERCPs per endoscopist per year seems necessary to maintain sufficient competence for biliary procedures. More than 250 ERCPs per endoscopist per year seems mandatory for developing and maintaining expertise level in complex therapeutic procedures in the pancreas.17 ERCP volume plays a role in complication rates. In some studies a minimum of 40–50 sphincterotomies (EST) per endoscopist per year is associated with a lower complication rate than when performed by endoscopists who perform less.18,19 Rabenstein showed that both the number of ERCPs and ESTs performed in the past as well as the number of ERCPs currently performed by the endoscopist seem to influence success and complication rates.20 Finally, objective outcomes and medicolegal concerns play an increasing role in daily GI practice.7,21,22 In light of all of these issues, this chapter will cover the training options for the beginner as well as for the practicing gastroenterologist to acquire or maintain ERCP skills.

Prior to acquiring the skills necessary for the performance of ERCP in a safe, effective, and comfortable manner, the endoscopist must first understand the indications, risks, and limitations of the procedure. In addition to this knowledge, training and proficiency in manual and technical skills are other aspects of a competent endoscopist. To this end, the American Society for Gastrointestinal Endoscopy (ASGE) published a new core curriculum for training in ERCP in March 2006.23 In most fellowship training programs traditional ERCP training follows education in diagnostic gastroscopy and colonoscopy and is often begun when the trainee has been introduced to polypectomy, hemostasis or EUS training as part of a “learning pyramid.”24 Fellows begin their ERCP training by observing the procedure and/or assisting the primary endoscopist. In Europe this initial experience may involve maneuvering x-ray equipment during the procedure or in some institutions the trainee may perform the duties of the assisting endoscopy nurse in order to learn how to properly handle catheters, guidewires and other accessories. Accompanying learning aids include the review of video material, ERCP atlases, or interactive computer programs. In most cases the first practical steps to learning ERCP involve understanding how to maneuver a sideviewing endoscope by passing the endoscope during the early stages of the procedure. This involves incrementally learning how to intubate the esophagus, maneuver along the lesser curvature of the stomach, appreciate the “setting sun phenomenon” at the passage of the pylorus, maneuver around the superior duodenal angle, and finally to bring the endoscope in an appropriate “short” position in front of the papilla. It is often easier for the trainee to begin this process by placing the patient in the left lateral decubitus position with the patient’s left arm behind their back instead of starting primarily in a prone position. Now that most ERCPs are performed for therapeutic purposes, it is controversial if cannulation is the most appropriate step for the trainee to learn after he or she is able to competently maneuver the duodenoscope to the papilla. For example, it is well known that routine stent exchange in the setting of a prior sphincterotomy requires a lower number of procedures (60) to obtain competence than cannulation of a native papilla (180–200), and is associated with a lower risk profile.16,25 Patients with benign biliary strictures, chronic obstructive pancreatitis, and recurrent bile duct stones in the setting of prior sphincterotomy may be good cases for the trainee to perform in the early stages of his/her ERCP experience. Schutz and Abbot developed an ERCP grading scale based upon procedural difficulty. In a single-center study they used benchmarks such as cannulation rates to gauge competency in attempted procedures. A modification of this score was adopted by the ASGE as part 61

SECTION 1 GENERAL TOPICS

1

Cholangiography

.90

.80

.80 Probability of achieving acceptable score

Probability of achieving acceptable score

1 .90 .70 .60 .50 .40 .30 .20

n=155 167 135 120 158 184 133 112 73

0

.70 .60 .50 .40 .30 .20

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.10

Pancreatography

n=120 106 108 93 119 151 103 96

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40

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Deep common bile duct cannulation

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.90

.90

.80

.80 Probability of achieving acceptable score

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6

80 100 120 140 160 180 200

ERCPs, n

1

59

.10

.70 .60 .50 .40 .30 .20 .10 n= 89 119 89 0 20 40 60

Deep pancreatic duct cannulation

.70 .60 .50 .40 .30 .20

80 119 113 92

81

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80 100 120 140 160 180 200

.10 n= 20 22 0 20 40

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80 100 120 140 160 180 200

ERCPs, n

26

36

34

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21

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ERCPs, n

from Jowell, PS et al Ann Intern Med 1996; 125:983–989

Fig. 7.1 Probability (95% Cls) of achieving an acceptable score for cholangiography, pancreatography, deep pancreatic cannulation and deep biliary cannulation during fellows’ training in ERCP determined by Jowell et al. for 17 GI fellows during 1450 ERCP procedures.16

of their quality-assessment document.26,23 Absolute numbers of procedures partially performed by a fellow may not realistically reflect competency. Where possible, trainee logbook records should specify particular skills completed by the fellow (cannulation, sphincterotomy, stent placement, tissue sampling), as well as indicate cases that the trainee completed without assistance. ASGE guidelines for advanced endoscopic training state that most fellows require at least 180 cases to achieve competency, with at least half of these cases being therapeutic. It must be emphasized that performance of these numbers of procedures does not automatically bestow competency, rather that competency can be assessed after this number of procedures has been performed. Though nearly all GI training programs offer some exposure to ERCP, not all of the trainees may ultimately perform ERCP after the completion of their training. All fellows should at least develop an understanding of the diagnostic and therapeutic role of the procedure, including indications, contraindications, and possible complications. This exposure is generally accomplished within the context of a 3-year gastroenter62

ology fellowship training program.23 The decision by a program director as to whether to train one or more fellows each year to achieve sufficient competency will depend in some measure on the volume of ERCPs performed at the institution and the availability of experts in ERCP to supervise the training of fellows. With data from Jowell et al. to suggest that well over 200 cases are required for most trainees to consistently cannulate the desired duct, programs with a limited case volume will have to weigh their training objectives with what is feasible. For example, with an annual volume of 400 cases and three fellows, it would be reasonable to have one fellow perform 300 or more cases and provide the other two with an exposure to ERCP, rather than have all three individuals equally share cases, with a low likelihood that any of the three would reach competency by the end of the fellowship. Trainees who elect to pursue additional training in ERCP in order to attain procedural competence should have completed at least 18 months of a standard gastroenterology training program as per the Gastroenterology Core Curriculum. The minimum duration of

Chapter 7 ERCP Training

training required to achieve advanced technical and cognitive skills is usually 12 months. This period of advanced training may be incorporated into the standard three-year fellowship program or may be completed during an additional year dedicated to advanced endoscopic procedures.23

TRAINING MODELS AND SIMULATORS There have been a number of initiatives aiming to improve endoscopic training.23,27–30 Courses using plastic dummies for gastroscopy and colonoscopy are to be mentioned in this context. However, these models have the disadvantage of allowing minimal interventions to be performed and they could not be established for ERCP training.13

Computer simulators Apart from mechanical simulators, different computer simulation systems have been developed.31,13,24 In 1990 Christopher Williams introduced a computer simulator for colonoscopy and ERCP.29 Williams stated that in 1982 his group had already adapted a simple electronic video game for training left–right hand coordination. The next generation simulator was connected to an MS-DOS computer with friction brakes to provide mechanical limitations. The provocation of audible signals, such as patient groans and “patient protest,” when undue force or insufflation was used, was already integrated at that time.29 In the mid-1980s an interesting, realistic computerassisted simulator, the Robotics Interactive Endoscopy Simulation (RIES) System was introduced for esophagogastroduodenoscopy (EGD) and ERCP.32–34 His aim was to integrate a functioning endoscope into an interactive environment, thus creating a realistic visual appearance. The system reached a high level of technical sophistication with functioning sphincters of the papilla of Vater and tactile feedback. In addition to catheter movements a virtual sphincterotomy could be performed.33 However, at that time computer simulators required expensive platforms and therefore were not widely accepted. Nowadays, because of the enormous evolution in electronics and computers, the capabilities of any standard personal computer system are far higher than that of the high-end computers of 10 years ago. This may be the main reason for the development of different endoscopy computer simulation models seen in the late 1990s and early 2000s.The first of these models had been the Simbionix GI-MentorTM in the form of a dummy (“Mr. Silverman”).35 The current model GI-Mentor IITM (Simbionix Corporation, Cleveland, Ohio), as well as the AccuTouchTM computer simulator (Immersion Medical Inc., Gaithersburg, MD) not only allows simulation of different diagnostic and interventional procedures at different levels of difficulty but also includes didactic teaching modules with anatomy and pathology atlases.13,31 Both systems create a relatively realistic virtual endoscopic environment. ERCP modules with parallel x-ray and endoscopic simulations, virtual sphincterotomy, stone extraction, etc. have been implemented. Aabakken et al. described their experience using the Simbionix simulator in a one-day training program involving 33 participants. Of the participants who completed a questionnaire, 85% rated the simulator training as somewhat or very useful in their education; 61% of the trainees indicated that it would have a potential role in the training and re-certification of physicians. Bar-Meir reported similar results in which the GI-Mentor was used during a workshop. This workshop involved 71 gastroenterologists with more than one year of endoscopic experience.

Modern medical simulator technology has been shown to distinguish the upper endoscopy skill level between novices and experts.36,37 Similar results have been shown for sigmoidoscopy and colonoscopy.38–40 However, a prospective randomized trail including 9 simulator-trained and 7 bedside-trained residents in internal medicine failed to show a significant benefit for the computer simulator group in sigmoidoscopy training.41 However, Sedlack and Kolars from Mayo Clinic, Rochester, MN, could prove the value of prior computer simulator training in the education of fellows in colonoscopy and subsequently developed a special course program for fellowship training.42,43 In a prospective study that applied computer-based colonoscopy simulation, 4 novice fellows received 6 hours of simulatorbased training, compared to 4 novice fellows without training. Simulator-trained fellows outperformed traditionally trained fellows during their initial 15 colonoscopies in all performance aspects except for time of insertion (p < 0.05). Three parameters (depth of insertion, independent completion, and ability to identify landmarks) demonstrated a continued advantage up to 30 colonoscopies. Beyond 30 procedures, there was no difference in the performance of the two groups.43 Unfortunately, validation of the use of additional computer simulator training compared to clinical training alone does not exist for ERCP training. However, there is data concerning the use of three different ERCP training models by participants and tutors who attended an ASGE ERCP workshop, as discussed below.44

ERCP TRAINING IN LIVE ANIMALS Since the beginning of the 1990s anesthetized pigs and dogs have been used in systematic endoscopy training courses, especially for ERCP techniques (Fig. 7.2).34,45–47 The major advantages of using live animals for training are the natural tissue sensation, elasticity, and realistic tactile feedback which occurs with the use of organs similar to those found in humans. Substantial restrictions to the use of animals include: ethical considerations, animal welfare, concern for cleanliness, need for additional endoscopes designated for animal

Fig. 7.2 ERCP hands-on training in the pig. Animal training courses have been established since the beginning of the 1990s for ERCP training in specialized training institutions. However, they require a considerable logistic and financial effort. 63

SECTION 1 GENERAL TOPICS

use, and cost. Furthermore, the procedures must be performed in special animal facilities which may mandate separate permission for animal experiments, and the procedures often require veterinary and anesthesiology support. If one does not allow an adequate amount of fasting time, the pig stomach remains filled with food, impairing endoscopic visualization. The anatomy of the pig’s upper gastrointestinal tract is relatively similar to that of the human, though there are some differences that impact ERCP training. There are separate papillae for the bile duct and pancreatic duct. The biliary papilla is located about 1.5–2 cm distal to the pylorus at the roof of the duodenal bulb. The pancreatic papilla is located more distally and is often difficult to find due to its small size and deep location in the duodenum. A polyp-like structure at the pylorus, called the “torus pylorus”, resembles a papilla with an impacted stone and can be used for practicing needle-knife techniques. Problems encountered during examination of the upper gastrointestinal tract of pigs include the often dilated stomach and the excessive distance to the pylorus because of the long snout. During ERCP training courses, perforation of the bile duct not infrequently occurs, necessitating sacrifice of the animal earlier than anticipated. An evaluation of participants and tutors of three different training models for ERCP during an ASGE ERCP hands-on workshop including the animal model are outlined below.44

easy handling. CompactEASIE® is a modified lightweight version (weight 15 kg) developed in 1998 and focuses exclusively on interventional endoscopic applications.13,58 This model uses a specially prepared porcine upper gastrointestinal organ package (esophagus, stomach and duodenum) and includes the common bile duct, gallbladder and liver (Fig. 7.2) for use as an ERCP training device.13,59,60 An advantage of the lightweight model is the nearly radiotranslucent ground plate which can be easily positioned under x-ray equipment (Figs 7.3 and 7.4). For ERCP interventions such as sphincterotomy and stent placement the hepatobiliary system with liver, extrahepatic bile ducts and

“EX VIVO” PORCINE TISSUE MODELS (COMPACTEASIETM, ERLANGER ENDOTRAINERTM ETC.) The use of a pig stomach for diagnostic gastroscopy the training has been widely available for many years.48 In 1997 Hochberger and Neumann presented the first generation of training models that used specially prepared pig specimens for training interventional flexible GI endoscopy.49–51 Training in endoscopic ulcer hemostasis could be demonstrated by reliably reproducing spurting arterial bleeding. Since then the model has been used in training more than 30 interventional techniques.24,50–52 Additionally a colon model for stricture management, proctoscopic interventions, and EMR in the lower GI tract has been developed.53,54 The Erlangen Active Training Simulator for Interventional Endoscopy (EASIE) was developed by integrating an endoscopic environment into the surgical “Biosimulation Model” of Neumann.55,56 The original model of Neumann was a relatively heavy model which was not suitable for therapeutic flexible endoscopic interventions. It had been primarily designed for teaching laparoscopic and open surgical procedures. The 30 kg simulator consists of a rotatable plastic thorax-abdomen dummy. Upper gastrointestinal organ packages, obtained from ordinary slaughtering processes as used in the meat industry, are thoroughly cleaned and placed into a special simulator mold. Similar to the POP simulator of Szinicz et al.,57 a roller pump can be used to drive an artificial blood circulation with citrated and diluted blood through the arteries of previously heparinized organs of parenchymal resections. According to the idea of Hochberger, this perfusion system was used for the first time to simulate arterial spurting bleeding in hollow gastrointestinal organs.51 This was achieved by sewing segments of porcine splenic arteries into the anterior wall of the stomach and connecting them to an artificial blood circuit. The CompactEASIE® is a simplified version of the original “Biosimulation Model” (EndoTrainer) and is specially designed for 64

Fig. 7.3 Training set up using the compactEASIE “ex vivo” animal part simulator for ERCP training under fluoroscopic control.

Fig. 7.4 Organ package including upper GI tract with esophagus, stomach, duo-denum, biliary system and liver mounted on the CompactEASIE “ex vivo” animal part simulator.

Chapter 7 ERCP Training

A

B

C

D

Fig. 7.5A–D Cannulation and sphincterotomy in the “ex vivo” porcine model. The biliary papilla is located at the transition of parts I and II of major side of the porcine duodenum. It has a relatively long intraduodenal precourse. Once in place, training for cannulation, sphincterotomy and plastic and metal stent placement as well as many other different procedures in the bile duct can be undertaken (from left to right above and below). The separately drained pancreatic papilla is usually to small, deep in the duodenum and mostly not suited for training purposes.

the gallbladder are dissected and added to the upper GI tract. However, in the pig, as mentioned above, the pancreatic duct and biliary system are drained via separate duodenal papillae. The larger, biliary papilla is usually located at the roof of the duodenal bulb and is quite flat. The pancreatic papilla, located deep in the descending duodenum or even the fourth (horizontal) portion, is small, difficult to cannulate, and it is generally not used for training. Additional artificial papillae can be implanted in the duodenum or stomach. Endoscopists, especially beginners in ERCP, have to first adapt to the pig anatomy, as is the case in live pig training courses. It is possible to perform conventional endoscopic sphincterotomy (EST) as well as needle-knife techniques (Fig. 7.5). Techniques that can be performed include basic accessory exchange and advanced techniques such as selective cannulation of the left and right hepatic ducts and intrahepatic segments. Furthermore, the cystic duct can be used to demonstrate guidewire steering and catheter manipulation. Unilateral and bilateral hilar stent placement can be performed using plastic and metal stents. Bilateral hilar metal stent placement as well as retrieval of proximally migrated plastic biliary stents is part of expert training programs. Bile duct stone can be simulated by inserting 3–5 mm long pieces of 8.5 Fr plastic stents into the bile duct. Extraction techniques can then be demonstrated using balloons and baskets after performing EPT. Recently Matthes and Cohen reported on an interesting creation of a so-called “neo-papilla.”61 Analogous to the Grund “Interphant”

Fig. 7.6 Neo-papilla as developed by Matthes and Cohen in 2006 trying to overcome the natural differences of human and porcine anatomy. They created an artificial papilla made from the muscular structure of a chicken heart with common drainage of an artificial biliary and pancreatic duct made from porcine vessels. The neo-papilla is located contrary to the pig’s papilla at the minor curvature and serves especially for cannulation and sphincterotomy training.61

or “Susi” simulator, a chicken heart is used to simulate the muscles of the sphincter apparatus.13,62 As opposed to the natural duodenal papilla of the pig they were able to simulate the human anatomical situation by integrating a bile duct and a pancreatic duct (Fig. 7.6). Furthermore, the papilla could be situated more distally into the duodenum as in the human.61 All organs used for these simulations are subject to veterinary inspection and comply with the pertinent food hygiene regulations. The organ packages must be specifically prepared and adapted to the topics and objectives of the course in which they are utilized. The organs from the recently slaughtered animals can be stored for several months in sealed plastic bags at a temperature of about −18°C. The organs are thawed the night prior to the training session. Since 2002, simple versions of the original CompactEASIE® and EndoTrainer simulators have become available. A company, Hammerhead Design (Mt. Pleasant, SC), developed a simple two-part plastic mold similar to the CompactEASIE® simulator. However instead of screw pins, this simulator uses a flexible net suspended over the specimen to keep the stomach in position on the mold. The ASGE also developed a simulator mold similar to the CompactEASIE® model called “EndoTrainer X” which also uses a plastic net that is fixed over the specimen. Neumann et al. published a pilot study using the “Erlanger EndoTrainer.” An experienced endoscopist and nurse used the simulator to demonstrate positioning of the duodenoscope, cannulation, guidewire insertion, sphincterotomy, stone extraction and plastic stent placement.63 In 2001, Maiss et al. presented their experience with interventional ERCP training using the CompactEASIE biologi65

SECTION 1 GENERAL TOPICS

cal simulator.64 They analyzed nine structured training courses from March 1999 to July 2001 using the CompactEASIE “ex vivo” simulator. The courses were designed for team-training groups of three doctors and three nurses per simulator. All courses were performed at the endoscopy unit of the Department of Medicine I, University Hospital in Erlangen, Germany. In total, 188 participants were trained. The workshop structure included three 30-minute theoretical lectures and video demonstrations concerning an introduction to ERCP, sphincterotomy techniques, treatment of stones and biliary strictures as well as pathological findings at ERCP (pitfalls, tips and tricks). Three blocks of 1.5 h, 1.5 h and 1 h of hands-on training were integrated in the course. After demonstration by the tutor, the trainees were supervised in performing papillary cannulation, sphincterotomy techniques, guidewire exchange techniques, stone extraction and stenting. Only advanced trainees received simulator experience in needle-knife techniques and metal stent placement. Each group was instructed by an experienced endoscopist and GI assistant. At the end of the course a standardized questionnaire served for evaluation of the course. 132 trainees (78 doctors, 53 nurses, 1 unspecified) of the 188 trainees (70%) completed the questionnaire. Nearly all trainees (97%) rated the training as excellent or good. The evaluations of the participants concerning the single techniques trained are listed in Table 7.1. Evaluations of the realism of the anatomical environment, the optical impression and the tactile feedback are listed in Table 7.2.

Technique

Excellent

Good

Insufficient

No statement

Cannulation Sphincterotomy Stent implantation (plastic) Stent implantation (metal) Needle-knife

66% 60% 57%

27% 30% 26%

2% 2% 1%

5% 8% 16%

16%a

8%a

4%a

72%a

36%a

20%a

3%a

41%a

Table 7.1 Realism of ERCP techniques trained in the harvested pig specimen CompactEASIETM simulator. Results of the evaluation of nine hands-on training workshops on interventional ERCP obtained from 132 participants (of 188 total) between March 1999 and July 2001 a hands-on training for experts only, therefore 72% and 41% of questionnaires with “no statement”.

Criteria

Excellent

Good

Insufficient

No statement

Anatomical environment Visual feel Tactile feedback

37%

53%

3%

7%

48% 35%

45% 49%

2% 3%

5% 13%

Table 7.2 Realism of the anatomical environment, visual impression and tactile feedback using the harvested pig specimen CompactEASIETM simulator in an ERCP setting (see Figure 7.2). Results of the evaluation of nine hands-on training workshops on interventional ERCP training obtained from 132 participants (of 188 total) in workshops between March 1999 and July 2001

66

Since then, different levels of training for beginners, advanced endoscopists and experts have been developed using the CompactEASIE simulator in “hands on” workshops in Hildesheim and Erlangen, Germany (Table 7.3).

ARTIFICIAL TISSUE MODELS As previously mentioned Grund and colleagues at the University of Tübingen, Germany developed an innovative static model using animal parts.13,62 These simulators have also been utilized for specific ERCP techniques. The models employ a plastic bile duct and a papilla made from a chicken heart to allow training of sphincterotomy techniques. The model is not commercially available and there are no published data validating its use in ERCP training.

COMPARISON OF DIFFERENT ERCP TRAINING MODELS Sedlack et al. compared three different ERCP training models used at an ASGE advanced ERCP training course.44 A live, anesthetized pig model was compared to the CompactEASIE “ex-vivo” simulator and to the Simbionix GI Mentor ERCP computer module. Ten course participants and 10 experienced faculty practiced biliary cannulation and other interventional maneuvers for 20–30 minutes per model and then evaluated model parameters. A 7-point Likert scale (1 = very unrealistic, 7 = very realistic was used to assess (1) tissue pliability, (2) papillary anatomy, (3) visual realism, (4) cannulation realism, and (5) overall ERCP experience. A similar scale was used to assess the utility of each model for teaching basic or advanced ERCP techniques (1 = not useful at all, 7 = very useful). The CompactEASIE harvested porcine model scored the highest for “realism” and usefulness in teaching basic and advanced ERCP skills. The scores for the computer model were significantly lower (p < 0.05) than those of the live and CompactEASIE porcine models in nearly all areas except for “papillary anatomy.” Course faculty favored the CompactEASIE harvested pig model, whereas the course participants favored the live pig model. Analyzing the results of the combined group (tutors plus trainees) the harvested pig organ model was rated most promising. The “ex vivo” model seems best suited to translate didactic contents and experience from the experienced tutor to the learner, while offering a relatively realistic endoscopic environment. This type of training model offers a compromise between live animal courses located in special training facilities and computer simulator training. Prospective trails comparing the use of simulators and/or live animals to clinical ERCP training are needed before they can be recommended as standard training curricula.

DATA SUPPORTING THE ROLE OF ERCP TRAINING ON SIMULATORS Since 1997, regular training workshops on interventional endoscopic techniques using the CompactEASIE®-simulator have been established at the Department of Medicine at the University of ErlangenNuremberg in Germany and recently in Hildesheim, Germany, as well as in numerous international teaching centers and national society endoscopy courses throughout the world. The EASIE group

Chapter 7 ERCP Training

ERCP—Beginners • Cannulation, standard • Guide wire exchange techniques (standard or ‘rapid exchange’, etc.) • Spincterotomy (guide wire) • Stone extraction – basket – basket along guide wire – balloon • Plastic stents ERCP—Advanced • Stricture management – dilatation – bougienage • Selective intrahepatic cannulation left / right • Cannulation of the “difficult papilla” with – sphincterotome – steerable catheters (“swing tip” etc.) – guidewire • Needle-knife sphincterotomy • Complication management – post-sphincterotomy bleeding, injection – post-sphincterotomy bleeding, clips • Metal stents – distal common bile duct – hilar, unilateral • Difficult bile duct stones – mechanical lithotripsy, emergency device (e.g. Soehendra) – mechanical lithotripsy, through the channel device (e.g. Olympus) – avoidance and management of complications • ERCP in Billroth II anatomy with side viewing scope – endoscopic techniques for negotiating entero-enteric anastomoses

– cannulation – sphincterotomy – stenting – stone extraction • ERCP in Billroth II anatomy with pediatric colonoscope or gastroscope without elevator – endoscopic techniques for negotiating entero-enteric anastomoses – cannulation – sphincterotomy – stenting – stone extraction ERCP—Experts • Cholangioscopy • Laser lithotripsy – “smart laser lithotripsy” via balloon – “smart laser lithotripsy” via steerable catheter etc. • ERCP with Double Balloon Enteroscope in Billroth II anatomy or after entero-enteric anastomoses – Roux-en-Y intubation, gaining access to the papilla – india ink and Lipiodol marking of afferent loop – cannulation with a 200 cm instrument – sphincterotomy, instruments, strategy – stenting – stone extraction – laser lithotripsy – complication management (injection hemostasis, clipping) • Metal stents – bilateral hilar stenting, “Y” side-to side – bilateral hilar stenting, “Y” through mesh – combined biliary and enteral metal stenting

Table 7.3 ERCP techniques trained according to level of education in current workshops in Hildesheim and Erlangen, Germany using the CompactEASIETM harvested specimen simulator

has propagated the “EASIE Team Training Concept” for the simultaneous training of doctors and nurses in different interventional endoscopic techniques.13,59,60,65 Simulator training in interventional endoscopy provides an effective opportunity for endoscopy trainees to gain considerable experience in ERCP techniques without time limitation and patient risk. In a prospective, randomized trial using the EASIE simulator for hemostasis training, trainees in New York City achieved significant improvement in their performance of multiple skills on the simulator after only three workshops.66 It appears that a structured educational program with access to simulator training in addition to supervised patient care would also enhance ERCP education. Such efforts should benefit patients by improving the skill level of trainees before they perform actual procedures and could result in a lower complication rate when trainees are involved with actual cases, leading to better patient outcomes. The results of the actual hemostasis cases performed in the New York study highlight this potential.66 After the pilot project in New York, a second program which involved the training of 35 gastroenterology fellows from 25 French universities confirmed these results.67

ACQUIRING TEACHING SKILLS AS TUTOR FOR HANDS-ON WORKSHOPS The benefit of the trainee from hands-on workshops is likely a combination of the amount of unsupervised time using the model, expert instruction, high faculty-to-student ratios, and formal skill evaluations with opportunity for feedback.52 To make simulator training accessible to more physicians, an expanded number of experts need to receive training on how to use these models to teach others. Potential instructors need to know how to set up the equipment, how to conduct the workshops, and how to evaluate the trainees using the model. The training of tutors who are available to a wide geographic distribution should enable greater local simulator availability. Only by doing so can simulator-based workshops be integrated into standard endoscopy education. An additional benefit of focusing efforts to develop the educational skills of endoscopy instructors is to promote uniformity in endoscopy education.68,69 For hemostasis training we conducted a pilot study that examined the feasibility of short train-the-trainer sessions to achieve these goals. Seven senior endoscopists without prior EASIE simulator

67

SECTION 1 GENERAL TOPICS

experience were enrolled in this study to serve as the “New Tutors Group.” Five expert endoscopists with EASIE team training experience instructed the New Tutors Group in a one-day train-the-trainer session. The next day, eight additional gastroenterology fellows attended a one-day hemostasis workshop conducted by the New Tutor Group and underwent pre-/post-training evaluations on the simulator by their instructors. In nearly all parameters assessed, fellows under the direction of newly trained trainers made significant progress in just one day. Tutors trained in this manner were able to provide an educational experience similar to that provided by experts who have conducted many hands-on workshops. The same has not yet been proven for ERCP training.

MAINTAINING SKILLS IN ERCP There is little doubt that the knowledge gained from hands-on courses decreases over time. Little is known about the volume of ERCP cases needed to maintain skills acquired during these sessions in order to continue to achieve good outcomes. While simulator training has the potential to facilitate the maintenance of ERCP skills as well as to teach individuals in practice how to use new devices, there is no data that confirms this benefit. In addition, there is no data of how often such refresher courses would be needed. Train-the-trainer sessions for “ex vivo” ERCP simulator training as successfully put

into practice for EASIE hands-on hemostasis courses would are needed.52,70

OPEN QUESTIONS AND PERSPECTIVES FOR ERCP TRAINING IN THE FUTURE In 2003 Kowalski et al. performed a survey concerning ERCP training among US gastroenterology fellows. In a short questionnaire, they assessed training program, personal ERCP experience, perceptions regarding training adequacy, and post-training practice plans. Graduating fellows performed a median of 140 ERCPs and 35 sphincterotomies during training, with an associated median comfort level for independently performing sphincterotomy of 7.5 on a scale of 1 to 10. The median estimated success rate for independent free cannulation was 75%. Based on non-parametric correlation and regression analysis, 180 ERCPs would be necessary to achieve a free cannulation rate of 80% and 69 sphincterotomies to achieve a comfort level of 8 on a scale of 1 to 10. Only 36% of fellows achieved the number of procedures and cannulation success. Sixtyfour percent of fellows did not achieve procedural competence and 33% reported inadequate ERCP training. Nevertheless, 91% of fellows said they expected to perform unsupervised ERCP after training. The authors concluded that the majority of graduating fellows did not achieve an acceptable success rate during training, yet still intended to perform ERCP after training.

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47. Noar MD. An established porcine model for animate training in diagnostic and therapeutic ERCP. Endoscopy 1995; 27:77–80. 48. Freys SM, Heimbucher J, Fuchs KH. Teaching upper gastrointestinal endoscopy: the pig stomach. Endoscopy 1995; 27:73–76. 49. Hochberger J, Neumann M, Hohenberger W, et al. Neuer Endoskopie-Trainer für die therapeutische flexible Endoskopie. Z Gastroenterol 1997; 35:722–723 (AB). 50. Hochberger J, Neumann M, Hohenberger W, Hahn EG. [EASIEErlangen Education Simulation Model for Interventional Endoscopy—a new bio-training model for surgical endoscopy]. Biomed Tech (Berl) 1997; 42 Suppl:334. 51. Hochberger J, Neumann M, Maiss J, et al. EASIE—Erlangen Active Simulator for Interventional Endoscopy—a new bio-simulationmodel—first experiences gained in training workshops. Gastrointest Endosc 1998; 47 (Suppl.):AB116. 52. Matthes K. Simulator training in endoscopic hemostasis. Gastrointest Endosc Clin N Am 2006; 16:511–527. 53. Maiss J, Matthes K, Naegel A, et al. Der coloEASIE-Simulator—Ein neues Trainingsmodell für die interventionelle Kolo- und Rektoskopie (The coloEASIE-Simulator—a new training model for interventional colonoscopy and rectoscopy). Endo heute 2005; 18:190–193. 54. Hochberger J, Maiss J. Currently available simulators: ex vivo models. Gastrointest Endosc Clin N Am 2006; 16:435–449. 55. Neumann M, Hochberger J, Felzmann T, et al. Part 1. The Erlanger endo-trainer. Endoscopy 2001; 33:887–890. 56. Neumann M, Stangl T, Auenhammer G, et al. Laparoscopic cholecystectomy. Training on a bio-simulation model with learning success documented using score-cards. Chirurg 2003; 74:208–213. 57. Szinicz G, Beller S, Bodner W, et al. Simulated operations by pulsatile organ-perfusion in minimally invasive surgery. Surg Laparosc Endosc 1993; 3:315–317. 58. Maiss J, Hildebrand V, Bayer J, et al. miniEASIE—Ein neues, auf die Belange der interventionellen Endoskopie reduziertes Trainingsmodell. Endoskopie heute 1999; 12:53. 59. Maiss J, Nägel A, Tex S, et al. EASIE-team-training ERCP— Experiences with a new training concept for interventional ERCP. Endoscopy 2000; 32:E65. 60. Hochberger J, Maiss J, Nägel A, et al. Polypectomy, endoscopic staining techniques, mucosectomy—A new structured team training course in a close to reality endoscopy simulator (EASIE). Endoscopy 2000; 32:E23. 61. Matthes K, Cohen J. The Neo-Papilla: a new modification of porcine ex vivo simulators for ERCP training (with video). Gastrointest Endosc 2006; 65:in press. 62. Lange V, Grund KE. Education in intraluminal endoscopy— experiences up to now. Chirurg 2001; 72: suppl 164–165. 63. Neumann M, Mayer G, Ell C, et al. The Erlangen Endo-Trainer: lifelike simulation for diagnostic and interventional endoscopic retrograde cholangiography. Endoscopy 2000; 32:906–910. 64. Maiss J, Tex S, Naegel A, et al. EASIE Team Training ERCP— Experiences with a new training concept for interventional ERCP. Endoscopy 2001; 33, Suppl. 1:AB 2119 (Abstr.). 65. Hochberger J, Maiss J, Neumann M, et al. EASIE-Team-Training in Endoscopic Hemostasis—Acceptance of a systematic training in interventional endoscopy by 134 trainees. Gastrointest Endosc 1999; 49:AB143. 66. Hochberger J, Matthes K, Maiss J, et al. Training with the compactEASIE biologic endoscopy simulator significantly improves hemostatic technical skill of gastroenterology fellows: a randomized controlled comparison with clinical endoscopy training alone. Gastrointest Endosc 2005; 61:204–215.

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67. Maiss J, Wiesnet J, Proeschel A, et al. Objective benefit of a 1-day training course in endoscopic hemostasis using the “compactEASIE” endoscopy simulator. Endoscopy 2005; 37:552–558. 68. Waye JD, Leicester RJ. Teaching endoscopy in the new millennium. Gastrointest Endosc 2001; 54:671–673. 69. Ladas SD, Malfertheiner P, Axon A. An introductory course for training in endoscopy. Dig Dis 2002; 20:242–245. 70. Matthes K, Cohen J, Kochman ML, et al. Efficacy and costs of a one-day hands-on EASIE endoscopy simulator train-the-trainer workshop. Gastrointest Endosc 2005; 62:921–927. 71. Kalloo AN, Singh VK, Jagannath SB, et al. Flexible transgastric peritoneoscopy: a novel approach to diagnostic and therapeutic interventions in the peritoneal cavity. Gastrointest Endosc 2004; 60:114–117.

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72. Rattner D, Kalloo A. ASGE/SAGES Working Group on Natural Orifice Translumenal Endoscopic Surgery. October 2005. Surg Endosc 2006; 20:329–333. 73. Kantsevoy SV, Jagannath SB, Niiyama H, et al. Endoscopic gastrojejunostomy with survival in a porcine model. Gastrointest Endosc 2005; 62:287–292. 74. Hochberger J, Lamade W. Transgastric surgery in the abdomen: the dawn of a new era? Gastrointest Endosc 2005; 62: 293–296. 75. Jagannath SB, Kantsevoy SV, Vaughn CA, et al. Peroral transgastric endoscopic ligation of fallopian tubes with long-term survival in a porcine model. Gastrointest Endosc 2005; 61:449–453. 76. Pai R, Fong D, Fishman D, et al. Natural Orifice Transluminal Endoscopic Surgery (NOTES) Cholecystectomy: A Transcolonic Survival Study in a Porcine Model. Gastrointest Endosc 2006; 63: AB229, 623 (Abstr.) Abstract #623.

SECTION 2

Chapter

8

TECHNIQUES

Cannulation of the Major and Minor Papilla Douglas G. Adler, Bret T. Petersen, and Todd H. Baron

CANNULATION OF THE MAJOR PAPILLA Introduction As the vast majority of ERCP procedures involve selective cannulation of the biliary tree and/or main pancreatic duct, command of techniques to access these ducts via the major duodenal papilla are fundamental to clinical success. Because most ERCPs are performed with therapeutic intent, failure to cannulate produces global procedural failure, emphasizing the importance of cannulation. In the course of training in therapeutic ERCP, learning to cannulate the desired duct consumes the most time, effort, and energy on the part of both the trainee and the instructor. In clinical practice, more time will likely be spent on cannulation than on any other maneuver. Efforts during and after training should focus not only on successful cannulation, but also on efficient, safe, and minimally traumatic cannulation.

Intubation Esophageal intubation with a duodenoscope is most easily done with the instrument held horizontally and parallel to the examination table with the patient’s neck slightly flexed. Often only upward tip deflection (backward tension on the large wheel) combined with gentle advancement is required to pass through the hypopharynx to the level of the upper esophageal sphincter, although some right or left tip deflection (via backward rotation of the lateral wheel) can often be helpful. Despite the assumption that intubation is done blindly, evaluation of the oral cavity, epiglottis, vocal cords and the pharynx can all be accomplished with side viewing instruments. Once the scope has been advanced to the upper esophageal sphincter (UES), gentle pressure combined with subtle tip deflection will often be adequate for esophageal intubation to proceed. Rotation and slight downward tip deflection (forward on the large wheel) will allow esophagoscopy to be performed, if required. This is easier and has less potential for complication when the endoscope is at the gastroesophageal junction. If detailed evaluation of the esophagus is not indicated, the duodenoscope can be advanced in a neutral position while examining the esophageal wall for landmarks such as the Z-line and the transition to gastric mucosa. Passage through the stomach is usually straightforward. Immediately upon entering the stomach, leftward endoscope torque and brief tip extension (large wheel forward) combined with endoscope advancement and air insufflation will allow visualization of the fundus and a portion of the gastric body. A lowering of the left hand to the level of the table and simultaneous partial extension of the left

elbow (“dropping the left hand”) will also facilitate this initial maneuver. Once the gastric body has been identified the endoscope is advanced, following the direction of the gastric folds, allowing it to pass along the surface of the greater curvature of the stomach towards the antrum. During this advancement, the endoscopist should slowly raise the left hand back to the vertical position so that the endoscopic image rotates in a clockwise manner and the incisura, when seen, appears to be horizontal. The posterior gastric wall will be rightward in the endoscopic field. Identification of the pylorus often occurs at this time. Advancement at this point with the endoscope tip in a neutral position will bring the pylorus (and a limited view of the post-bulbar duodenum) into full view. This image will be replaced with further advancement with the classic “setting sun” as the endoscope approaches and ultimately traverses the pylorus, resulting in a close view of the duodenal bulb with its characteristic mucosa. During attempts at traversal through the pylorus, some upward tip deflection combined with lateral tip deflection can be helpful if the tip of the endoscope repeatedly “rolls” off of the pylorus. Passage through the stomach can sometimes be difficult when the patient is in the prone position. Flexure of the patient’s right knee, combined with rotation of the patient’s shoulders to approximate a left-lateral decubitus position, is often helpful if difficulty is encountered. Inexperienced endoscopists will often over-flex the tip of the endoscope upon arrival into the stomach, which can result in retroflexion in the fundus. Gastric transit can also be difficult in patients with a J-shaped stomach or in obese patients. It should be emphasized that the duodenoscope is designed to easily pass through the stomach and that if repeated attempts at passages through the stomach fail it is rarely the fault of the instrument. Often, a return to first principles via withdrawal of the endoscope to the distal esophagus, removal of excessive air, and careful re-intubation of the stomach will allow successful passage. Once past the pylorus, tip extension (large wheel forward) will provide a global view of the duodenal bulb and will show the proper route for further advancement to the second portion of the duodenum. Gentle advancement combined with tip flexion will allow the instrument to follow the curve of the duodenum to the long endoscope position, with the shaft of the endoscope still against the greater curvature of the stomach (Fig. 8.1). The maneuver will leave the tip of the endoscope at the end of the second or beginning of the third portion of the duodenum. The standard shortening maneuver consists of full rightward deflection of the lateral wheel and full upward of the large wheel (often locking both) followed by withdrawal and simultaneous clockwise torque applied to the endoscope 73

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CBD

PD S

Fig. 8.1 Illustration when duodenoscope is in the long position. Note endoscope is against greater curvature of the stomach.

CC

Fig. 8.2 Illustration of typical anatomy of the ampulla of Vater. A short common channel (CC) is present. The septum (S) separates the common bile duct (CBD) and pancreatic duct (PD). A B

shaft by the right hand. The tip flexion helps to help bow the duodenal wall and position the duodenoscope “under” the papilla. In some patients, only a “long” endoscope position (with the endoscope shaft following the greater curvature of the stomach) will allow adequate alignment and orientation to the major papilla to be obtained. For patients under conscious sedation, the long endoscope position may be difficult to tolerate for long periods, due to gastric distension.

Evaluation of the papilla and initial positioning

Upon arrival in the 2nd duodenum and following the standard shortening maneuver (with the shaft of the endoscope now flush against the lesser curvature of the stomach), the endoscopist will usually be in a position to readily identify the major papilla. Rarely, the papilla can be difficult to identify at all as it may be obscured behind a fold, distorted or ablated in patients with malignancy, or indistinct in patients with bowel wall edema (as can be encountered in patients with acute pancreatitis or severe hypoalbuminemia). In some patients with aberrant anatomy, the papilla can be located proximally, just beyond the apex of the duodenal bulb, or distally, near the junction of the second and third duodenum. Once identified, a brief evaluation of the papilla allows assessment of the type and size of the papilla and any unusual features that may affect cannulation 74

Fig. 8.3 A Illustration of separate openings for the CBD and PD. B Actual papilla with separate openings. Bile can be seen around the biliary opening.

specifically or the procedure as a whole (periampullary diverticula, visibly impacted stones, etc.). Most patients with native papillary anatomy will have a single ampullary orifice that provides access to a common channel that further bifurcates via a septum into the distal common bile duct (CBD) and the main pancreatic duct (PD), also known as the duct of Wirsung (Fig. 8.2). A minority of patients will have two separate orifices (Figs 8.3A and 8.3B), but this may not always be apparent on initial evaluation as these two separate openings may be in close proximity. While the overall size and shape of the papilla can sometimes provide information about the possible length of the intraduodenal segment of the distal CBD or the angles at which the CBD and PD diverge from the common channel, in general, the intra-papillary anatomy can be difficult to define via inspection alone. As a general rule of thumb, time spent on proper positioning prior to attempts at cannulation is time well spent. A thorough examination of the papilla from several angles with the wheel locks off and with variations in torque applied at the endoscope head, the positions of the main and lateral wheels, and subtle alterations in the depth of endoscopic intubation will often provide the endoscopist with several possible positions from which to attempt cannulation. At the same time, these maneuvers will usually lead to the selection of a presumed optimal position from which to first attempt cannulation.

Chapter 8 Cannulation of the Major and Minor Papilla

Standard catheters Catheters and sphincterotomes preloaded with guidewires Placement of pancreatic guidewire or stent followed by biliary cannulation Precut “access” sphincterotomy Needle-knife (with or without pancreatic duct stent placement) Freehand starting at orifice Freehand starting above orifice “fistulotomy” Transpancreatic Rendezvous techniques

Table 8.1 Biliary cannulation methods

Opinions differ regarding the optimal distance from the tip of the endoscope to the papilla, but 2–3 cms of distance is commonly used. This “middle-length” distance allows for changes in knob and elevator position and depth of endoscopic intubation to have a clearly visible effect on the view of the major papilla. In addition, when using sphincterotomes, this distance allows adequate room for proper bowing to occur. Attempting to cannulate from an extremely close position, while affording an excellent view of the ampullary orifice, may not allow endoscopic maneuvers to significantly change the view of the papilla and will not allow for significant bowing of a sphincterotome, as these devices need at least partial extension out of the accessory channel to function properly. Cannulating from a long distance from the papilla, although valuable in certain situations, may require excessive cannula or sphincterotome extension, decrease the mechanical advantage of extended accessories, and therefore limit the usefulness of these devices.

Cannulation of the common bile duct There are a variety of methods used to cannulate the common bile duct (Table 8.1). Personal preferences vary regarding whether cannulation should be attempted with a cannula or a sphincterotome. This decision is usually based on the indication for the procedure as a whole, and whether the procedure will require a sphincterotomy. Regardless of which device is first selected to cannulate the biliary tree, several principles universally apply. When facing the major papilla en face, the biliary orifice will nearly always be located in the left upper quadrant, corresponding to the 9 o’clock to the 12 o’clock position (Fig. 8.4). The angle of the distal CBD can often be extrapolated, at least partially, by evaluating the angle and direction of the intraduodenal portion of the distal CBD. This angle, combined with the presumed location of the biliary orifice in the major papilla, will help to guide attempts at cannulation. Using these two pieces of information, one can project an imaginary line into the lumen showing the direction the CBD would take if it extended beyond the papilla. The endoscopist should manipulate the endoscope and cannulating device to move along this imaginary line into the CBD. Typically, approaches to the biliary orifice directed perpendicularly to the duodenal wall will not produce access to the biliary tree, although this is frequently attempted by the novice endoscopist as it may not be appreciated that the axis is incorrect. Examination of the catheter position under fluoroscopy will show the inappropriate axis. An upward sweeping motion of the catheter is required to allow the device tip to mirror the true direction of the distal CBD (Fig. 8.5). Once the tip of the selected device has partially engaged the orifice

Bile duct location

Fig. 8.4 Illustration of the location of the CBD opening on the papilla when viewed en face.

at its most superior point, and hopefully above the septum of the common channel separating the CBD and the PD, direct access may be obtained by applying gentle pressure to the cannulating device. Other maneuvers, such as gentle relaxation of the elevator, a subtle withdrawal of the device and/or the endoscope, and reduced bowing (if a sphincterotome is being used) will often allow deep entry into the CBD in this situation. Simultaneous un-bowing of the sphincterotome in conjunction with pulling the scope shaft more tightly along the lesser curve of the stomach is often a very effective technique to achieve selective CBD cannulation once the tip of the sphincterotome has been inserted into the papillary orifice. Although simple in conception, cannulation of the CBD can often be quite difficult, even for experienced endoscopists. Patients can have aberrant papillary or duodenal anatomy (see below) that complicates attempts at cannulation. They may have seemingly normal anatomy, yet access to the CBD may not be obtained via standard maneuvers. Over time, a set of more advanced techniques have been developed that can assist in a variety of situations.

Standard techniques for biliary cannulation Cannulation with a sphincterotome

With the rise of noninvasive techniques to evaluate the pancreaticobiliary tree, ERCP has evolved into an almost purely therapeutic technique. As such, initial attempts at cannulation are frequently performed with a sphincterotome rather than a standard biliary catheter. Sphincterotomes can be bowed at their tips by placing the cutting wire under tension. Use of a sphincterotome can often facilitate rapid access to the CBD as the angle of the distal duct can be more closely approximated from within the duodenal lumen (Figs 8.5A and 8.5B). Sphincterotomes are available in many different specifications. Different sphincterotomes from various manufacturers often have very different mechanical properties (catheter shaft thickness, degree of bowing, length of cutting wire, catheter tip diameter, length, and degree of tapering, etc) and can be designed to accept wires of different diameters (most commonly 0.025 inches or 0.035 inches) which can also affect how the devices operate (see Chapter 4). For example, a sphincterotome with a 30 mm length of cutting wire will often flex to a greater extent than a sphincterotome with a 20 mm length of cutting wire, but will need to be more fully advanced into the lumen to allow complete bowing. Likewise, a 75

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A

sphincterotome designed to accommodate a 0.035″ wire is likely to be stiffer than a device for a 0.025″ wire. Although some sphincterotomes are specifically designed to be rotated clockwise or counterclockwise in a controlled manner to assist in obtaining an adequate orienta-tion to the papilla, most sphincterotomes can be rotated to some degree. It should be stressed that for a sphincterotome to properly and fully bow, the cutting wire must be advanced out of the endoscope and into the lumen. Attempts at bowing with the cutting wire partially within the endoscope channel will limit the ability of the device to flex. Bowing with the cutting wire in the endoscope channel can sometimes be valuable as it allows the sphincterotome to flex in a dynamic manner when advanced out of the channel while simultaneously applying tension to the cutting wire. There have been few studies comparing sphincterotomes to standard catheters for initial biliary cannulation.1–6 In these studies sphincterotomes provided faster and easier access to the biliary tree, although no large scale studies have been done on this topic to date.

Guidewire assisted cannulation If attempts at cannulation with a standard catheter or a sphincterotome are unsuccessful, a guidewire can be inserted through either device to assist in cannulation (Fig. 8.6). Guidewire cannulation can be performed via several different techniques. The guidewire can be advanced into the papilla by itself with the accessory in contact with the papilla. Conversely, the cannula or sphincterotome can be advanced into the ampullary orifice for several millimeters prior to attempts at guidewire advancement. Both of techniques are performed under endoscopic and fluoroscopic guidance to allow assessment of extraluminal guidewire position. Most currently available guidewires have a soft, hydrophilic segment as their leading segment, facilitating passage of the guidewire through a tortuous common channel. Guidewire cannulation has several advantages: it is relatively atraumatic, the guidewire itself does not generate significant hydrostatic pressure (thus minimizing the risk of post-ERCP pancreatitis if the wire accesses the pancreatic duct) and the position of the guidewire (and thus the duct cannulated) can be easily detected via fluoroscopy. Guidewire cannulation carries a small risk pancreatitis if the guidewire is forcefully advanced into a side branch of the pancreatic duct causing trauma. Guidewire-induced perforation typically occurs within the papillary structures themselves. If the 76

Fig. 8.5 A Cannulation of the bile duct using a standard catheter. Note steep trajectory that the biliary axis takes. B Bowed sphincterotome facilitates biliary cannulation by achieving the steep axis.

B

Fig. 8.6

Biliary cannulation using a guidewire.

sphincterotome (with or without a guidewire) exits the intraduodenal segment of the bile duct, either purposefully or accidentally, a unique form of precut sphincterotomy may be performed by cutting the tissue between the papillary orifice and where the guidewire exits.7 The biliary orifice is then exposed (Figs 8.7A and 8.7B). Guidewire cannulation has been evaluated formally in only a limited manner. In the only study of its kind, Lella et al. compared guidewire cannulation to traditional methods of cannulation in 400 patients when performed by one endoscopist.8 In this study, both techniques had a very high success rate (approximately 98% for either method) but there were no cases of post-ERCP pancreatitis in the guidewire cannulation group compared to eight cases in the control group. This was likely due to the lack of hydrostatic pressure incurred by the pancreatic duct during guidewire cannulation.

Pancreatic duct stent placement to facilitate biliary cannulation If attempts at biliary cannulation consistently result in entry to the pancreatic duct, placement of a pancreatic duct stent can often facilitate access to the CBD (Figs 8.8A and 8.8B). Pancreatic duct stent placement has several potential advantages. First, pancreatic duct stents appear to reduce the risk of post-ERCP pancreatitis, likely by ensuring pancreatic ductal decompression and drainage. This is especially true in patients who have experienced repeated pancreatic duct injections.9–11 Secondly, pancreatic duct stents may also help to block the pancreatic duct orifice from further attempts at cannula-

Chapter 8 Cannulation of the Major and Minor Papilla

A

B

Fig. 8.7 A The tip of a sphincterotome has passed from the papillary orifice through the intraduodenal portion of the bile duct during attempted biliary cannulation. B After severing the intraduodenal portion.

B

A

Guidewire placement in the pancreatic duct to facilitate biliary access If attempts at biliary cannulation result in repeated pancreatic duct cannulation, another option to facilitate biliary cannulation is a technique that involves the use of two separate guidewires. A guidewire is advanced to the mid- to distal pancreatic duct, and the cannula or sphincterotome is removed leaving the guidewire in place. The device is preloaded with a second guidewire and biliary cannulation is re-attempted (Fig. 8.9A–C) (b). The angle of the first wire emanating from the pancreatic orifice can give clues that can assist in biliary cannulation. In addition, attempts at biliary cannulation, when observed under fluoroscopy, will readily reveal whether or not the second guidewire is simply being advanced into the pancreas. Leaving a guidewire in the pancreatic duct, even for protracted amounts of time, does not generate intraductal hydrostatic pressure and does not appear to be associated with an increased risk of postERCP pancreatitis. Although this technique has been known and practiced for several years, only one randomized study and one small case series have been performed to evaluate this technique formally, both with very encouraging results.14–16

Precut biliary sphincterotomy and associated techniques The term “precut” refers to the action of performing a sphincterotomy (the “cut”) prior to obtaining biliary access (the “pre-”). The term is often used, both in print and in speech, interchangeably with the term “needle-knife sphincterotomy.” In fact, the term “precut” refers rather to a group of high-risk techniques to obtain biliary access if standard maneuvers are unsuccessful. These techniques are collectively termed access sphincterotomy techniques, and carry a greater risk of complications. These techniques will be summarized briefly here and are discussed in detail in Chapter 9.

Fig. 8.8 A Endoscopic view of biliary cannulation above the previously placed pancreatic duct stent. B Fluoroscopic view of the same patient. Pancreatic duct stent is seen (arrow).

tion, both minimizing further pancreatic manipulation and facilitating cannulation of the biliary orifice. Lastly, the direction at which the pancreatic duct stent exits the papilla may give clues, via extrapolation, about the optimal angle to further approach the papilla to obtain biliary access. This latter benefit is most useful when the anatomy is distorted by severe duodenal edema or by tumor. Pancreatic stent placement to facilitate biliary cannulation has not been well studied, but the limited available data supports the efficacy and safety of this approach.12 The optimal type, size, and configuration of a pancreatic stent that would both facilitate biliary access and minimize the risk of post-ERCP pancreatitis are unknown. One study has suggested that 3Fr pancreatic stents without internal flaps are superior to short length 5Fr pancreatic stents for preventing post-ERCP pancreatitis,13 but many physicians use 5Fr stents routinely. Stents used in this setting without internal flaps will typically fall out spontaneously after several days, but can pass prematurely immediately following placement. Internal flaps prevent premature stent dislodgement, but may not pass spontaneously and require another endoscopic procedure for removal. Smaller stents and those without internal flaps, however, may become dislodged when placed prior to attempted biliary cannulation.

Needle-knife sphincterotomy Needle-knife sphincterotomy refers to the use of a catheter capable of delivering electrosurgical current through a wire to directly dissect the major papilla in vivo to obtain ductal access. The standard needleknife design incorporates a bare wire that can be extended through a modified biliary cannula. These devices do not routinely have the capability to bow as do most sphincterotomes. The most common way this device is used involves beginning the sphincterotomy at the level of the biliary orifice and moving in a cephalad direction (Fig. 8.10A and 8.10B). Another variation on this technique involves beginning the incision above the level of the ampullary orifice and attempting to cut directly into the CBD via the creation of a biliary fistula; this approach is referred to as precut fistulotomy (Fig. 8.11). Once the CBD is accessed, a standard sphincterotome can be used to extend the sphincterotomy, if needed.17–23 Because the endoscopist is cutting into the papilla and the duodenal wall without the benefit of a guidewire in the CBD, complications such as bleeding, perforation, and pancreatitis can easily develop. Complications can occur in as many as one-third of all needle-knife sphincterotomies, emphasizing the risk involved with this approach, although most reports using this technique suggest complication rates approximating 15–18% (significantly higher than seen when sphincterotomy is performed with standard sphincterotomes). Complication rates may not decrease despite both increased experience and success in obtaining biliary access with needle-knife sphincterotomy.24 Placement of a pancreatic duct stent prior to 77

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A

B

C

Fig. 8.9 A Illustration of double wire technique. B Endoscopic view of sphincterotome alongside pancreatic guidewire. C Fluoroscopic view of double wire technique.

78

A

B

A

B

Fig. 8.10 Illustration of precut sphincterotomy technique using a needle-knife beginning at the papillary orifice. A Without pancreatic duct stent. B With pancreatic duct stent.

Fig. 8.11 A Illustration of precut fistulotomy technique. B Successful precut fistulotomy. The cut was performed with a needle-knife and is well above the papillary orifice (arrow).

Chapter 8 Cannulation of the Major and Minor Papilla

A

Fig. 8.12

Illustration of transpancreatic septotomy technique.

performing needle-knife sphincterotomy may decrease the risk of post-ERCP pancreatitis by preventing trauma or obstruction of the pancreatic orifice due to swelling. Needle-knife sphincterotomy is a high-risk technique used to obtain ductal access, and is not intended for indiscriminate use. In general, prior to attempting needle-knife sphincterotomy, legitimate attempts at cannulation with standard techniques should have been attempted. Failed biliary cannulation in the setting of clinical situations such as cholangitis, a visibly impacted stone at the level of the ampulla, and obstructive jaundice due to malignancy are all appropriate for cannulation attempts using this technique. However, not all patients are ideal candidates for needle-knife sphincterotomy. In clinically stable patients undergoing ERCP for chronic abdominal pain or for abnormal liver function tests of unclear etiology, needleknife sphincterotomy may not be warranted due to the associated risks.

Endoscopic transpancreatic papillary septotomy Endoscopic transpancreatic papillary septotomy is a technique whereby biliary access is attempted via the use of a traction-type sphincterotome with its tip located in the pancreatic duct, but with the endoscope and the sphincterotome oriented for a biliary sphincterotomy. This allows the cut to begin in the pancreatic duct but to traverse the septum between this structure and the CBD, ultimately resulting in biliary access (Fig. 8.12). Results with this technique have been mixed, with some practitioners having a very high success rate with low rates of complications, while others have incurred complications at a level comparable to that of standard needle-knife sphincterotomy.25–28 Endoscopic transpancreatic papillary septotomy is not widely performed at the present time as it is unclear if it offers any significant benefit over standard needle-knife sphincterotomy.

Cannulation in patients with periampullary duodenal diverticula Duodenal diverticula are common in the general population. Those occurring in proximity to or the papilla are sometimes known as periampullary diverticula, while diverticula directly involving the major papilla are sometimes referred to as ampullary diverticula. This terminology is not standardized and many authors simply use the term periampullary diverticula in a catch-all manner. Data

B

Fig. 8.13 A Endoscopic view of papilla within diverticulum. Note papillary orifice (arrow) is facing the wrong direction. The intraduodenal portion of the bile duct is seen (arrowhead). B After cannulation, the papilla orients properly.

suggest that, although asymptomatic in many patients, ampullary diverticula can actually predispose patients to pancreatobiliary disease, most commonly stone disease.29–31 Common bile duct cannulation may sometimes be easier in the presence periampullary diverticula if accessible. The challenge is gaining the appropriate axis for access. In some cases, the ampulla abuts the diverticula, while in others the papilla is partially or completely located within the diverticula. The resultant distortion in the anatomy may render standard approaches and landmarks useless. The relative locations of the biliary and pancreatic orifices within the ampulla can even be reversed due to rotation of the ductal system within the ampulla. In addition, the ampullary orifice may be located eccentrically within the diverticula, and may be oriented away from an endoscopically approachable position (Fig. 8.13A and 8.13B) and, in rare cases, may not even be identifiable endoscopically. Cannulation in patients with duodenal diverticula can range from straightforward to extremely challenging, and in general the presence of ampullary diverticula will add a layer of complexity to cannulation of either duct. In one retrospective analysis of ERCP in 72 patients with periampullary diverticula, difficulty in cannulation was encountered in 79% of cases as compared with 10% of cases in patients without diverticula (p < 0.001).32 If the ampulla is located within the diverticula and oriented away from the endoscope, an endoscopic clip can be applied to the edge of the diverticula to provide a more open view of its interior while at the same time often everting the major papilla.33 Sometimes two devices can be advanced side-by-side through a large caliber accessory channel and used together to manipulate the diverticula. Ultrathin forceps advanced alongside a catheter or sphincterotome can apply traction or tension to diverticula, whereas conventional forceps can be used in conjunction with a cannulating guidewire. Similarly, the use of two separate endoscopes simultaneously to gain access in patient with an intradiverticular ampulla has been reported.34 Pancreatic duct stenting of patients with diverticula may facilitate access at cannulation with routine devices or needle-knife sphincterotomes.35 Given the tortuous nature of the CBD and PD in these patients, guidewire cannulation can be extremely helpful in these patients. Narrow (0.025″ or less), hydrophilic guidewires may be able to follow the course of an irregular duct and allow deep biliary or pancreatic access. Although standard biliary sphincterotomy in the 79

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setting of a diverticulum does not carry a higher complication rate, a needle-knife precut sphincterotomy may be particularly dangerous if the intraduodenal portion of the bile duct cannot be clearly delineated. On the other hand, in the presence of a pantaloon diverticulum, the intraduodenal anatomy may be more apparent than in the usual situation, making needle-knife precut sphincterotomy easier.

Repeat ERCP If cannulation fails, an alternative is consideration for referral of the patient to a more experienced endoscopist. In one study of 113 patients referred to a tertiary institution for repeat ERCP after a failed prior attempt at another hospital, successful cannulation of the desired duct was achieved in 96% of attempts.36 Thus, second attempt ERCP is generally worthwhile if clinically indicated and ERCP expertise is geographically available. A more recent study from the same institution confirmed these results.37 Yet another option is to repeat the ERCP on another day. Only one study published from a teaching institution addressed the success rate of repeat ERCP by the same endoscopist after a failed initial attempt.38 At repeat endoscopy access to the desired duct was achieved in 87.5% of the patients. A needle-knife was used in 21% and no complications occurred with repeat ERCP.

Rendezvous techniques In some situations, endoscopic attempts at cannulation will be unsuccessful despite all of the above approaches. In patients in whom internal biliary drainage is still desired, one can achieve this goal via a so-called “rendezvous” procedure. The procedure can be performed several ways, but essentially entails having an interventional radiologist obtain percutaneous biliary access. This access can be obtained either via a peripheral duct or via a transcystic approach (through a percutaneous cholecystostomy). A catheter or a guidewire is passed in an antegrade manner into the bile duct and through the ampulla and into the duodenum.39–43 In some situations, the transampullary guidewire or catheter can be placed during a surgical procedure, most commonly during cholecystectomy.44 Once the guidewire is passed into the duodenum, endoscopic access can be achieved by grasping the guidewire with a polypectomy snare or a biopsy forceps and withdrawing it through the accessory channel. Standard cannulas and/or sphincterotomes are then advanced over the wire to allow endoscopic access. If a small diameter percutaneous drainage tube (5Fr or less) has been placed in the duodenum instead of a guidewire, it is often a simple manner to cannulate next to the tube to access the biliary tree. After accessing the bile duct, any and all required therapeutic maneuvers can be performed (sphincterotomy, stone extraction, transpapillary stenting, etc). The percutaneous catheter or guidewire can be removed after endoscopic biliary access and drainage are secured. If larger catheters were placed percutaneously, they may need to be left in place until a mature tract has formed. The decision and timing of catheter removal should be coordinated with the interventional radiology team. Rather than to pass a wire antegrade as described above, one alternative is to endoscopically cannulate alongside the drain. After successful cannulation, the drain is progressively withdrawn during the procedure to allow retrograde therapeutic intervention. This has been referred to as “parallel cannulation.”45 There is no consensus on whether it is superior for patients to have a percutaneous placement of a guidewire alone or a formal drainage catheter. In general, if ERCP is to be performed immedi80

ately following a percutaneous biliary access procedure, a guidewire alone or a low-profile (3Fr) catheter can be placed. Unprotected guidewires have been associated with laceration of the liver capsule and parenchyma during manipulation, and placement without a small diameter protective sheath should be discouraged. If ERCP and internalization of biliary drainage is to be delayed, placement of a larger caliber drainage tube (10Fr or greater) seems warranted. Endoscopic rendezvous without the need for percutaneous access has been described through side-to-side choledochoduodenal anastomoses to facilitate cannulation of the bile duct for the treatment of sump syndrome.46 A modern variation on this theme is to perform an EUS-guided rendezvous procedure.47–49 In this situation, a linear echoendoscope is used to identify a bile duct (which, unlike a blood vessel, has no Doppler flow signature). The bile duct selected for access can be an intrahepatic or extrahepatic duct. Using an FNA needle, biliary access is obtained and cholangiography can be performed. Under fluoroscopy, a guidewire is advanced through the FNA needle into the bile duct in an antegrade manner and, ultimately, through the ampulla to allow endoscopic cannulation to proceed as described above. In some cases, ERCP may be obviated if drainage, via a stent, can be achieved via EUS alone.

Cannulation of the pancreatic duct

When facing the major papilla en face, the pancreatic orifice will nearly always be located in the mid to right lower quadrant, corresponding to the 1 o’clock to the 5 o’clock position (Fig. 8.14). In contrast to cannulation of the common bile duct, cannulation of the ventral pancreatic duct (Duct of Wirsung) is usually performed with the catheter oriented in a more straight-on direction (Fig. 8.15). Cannulation of the pancreatic duct is usually achieved in a short endoscope position, with a more anterior facing endoscope lens view (leftward rotation of the lateral wheel). The endoscope should be at or slightly “above” the level of the major papilla (as opposed to the bile duct where a “below” the papilla position is favorable). The middle distance between the tip of the endoscope and the papilla is (2–3 cm) described for biliary cannulation is often useful in pancreatic cannulation, although a closer approach is sometimes required.

Pancreatic duct location

Fig. 8.14 Illustration of the location of the PD opening on the papilla when viewed en face.

Chapter 8 Cannulation of the Major and Minor Papilla

Establish diagnosis of pancreas divisum Endoscopic therapy for patients with pancreas divisum Minor papilla sphincterotomy Stone extraction Stent placement Endoscopic therapy for non-divisum patients in whom major papilla cannulation fails

Table 8.2 Indications for minor papilla cannulation

Fig. 8.15 Cannulation of the pancreatic duct using a standard catheter. Note flat trajectory that the pancreatic axis takes.

Fig. 8.17

Minor papilla almost adjacent to major papilla.

CANNULATION OF THE MINOR PAPILLA Standard techniques Fig. 8.16 Prior small biliary sphincterotomy (arrow). The pancreatic duct is cannulated separately.

Guidewire cannulation of the pancreatic duct is recommended as it is much less likely to produce hydrostatic overpressure in the pancreatic duct, thus minimizing the risk of post-ERCP pancreatitis. Smaller diameter guidewires (0.025″ or less) are recommended by some endoscopists for pancreatic guidewire cannulation, as are hydrophilic guidewires, although many modern guidewires have a hydrophilic tip that is quite helpful for pancreatic cannulation. More aggressive techniques, such as needle-knife sphincterotomy, are rarely required for pancreatic duct access. In patients who have undergone prior biliary sphincterotomy, the pancreatic orifice is usually easier to identify as a separate opening located below and to the right (as the endoscopist faces the papilla) of the biliary sphincterotomy (Fig. 8.16). However, in some instances it may be more difficult to identify. The orifice may be located anteriorly or within the prior biliary sphincterotomy in a patient with a long combined sphincter (>10 mm). It is often helpful to look for residual ampullary structures such as mucosal fronds, as the pancreatic orifice is usually within the confines of this ampullary remnant. Although most commonly used to facilitate cannulation of the minor papilla in patients with pancreas divisum, intravenous secretin can assist in cannulation of the main pancreatic duct as well.50

Indications for cannulation of the minor papilla are listed in Table 8.2. Although cannulation of the minor papilla can be performed to confirm the diagnosis of pancreas divisum, non-invasive imaging studies such as thin-slice coronal CT,51 secretin-MRCP52 and EUS53 can provide the diagnosis of pancreas divisum with a high degree of accuracy (see Chapter 42). If cannulation of the minor papilla is performed only for diagnosis of pancreas divisum, deep cannulation is often not required. However, as in most other aspects of ERCP, cannulation of the minor papilla is undertaken in order to perform therapeutic interventions, and deep cannulation is mandatory. Additionally, in non-divisum patients, cannulation of the minor papilla can allow therapeutic interventions when cannulation of the main pancreatic duct cannot be achieved.54 Minor papilla sphincterotomy is discussed in detail in Chapter 15. This chapter will discuss cannulation of the minor papilla. A standard duodenoscope is used. Because a long endoscope position may be required to achieve an en face position of the minor papilla, a more flexible, smaller caliber “diagnostic” scope may provide an advantage over a more rigid therapeutic channel endoscope, though this has not been formally studied. The first step for minor papilla cannulation is to locate the minor papilla. It is located proximally to the major papilla on the medial wall. The distance from the major papilla is variable, being immediately adjacent or several centimeters cephalad (Fig. 8.17). In addition, the minor papilla may be very small or quite prominent (Fig. 8.18). Rarely, the minor papilla is within a diverticulum. Careful 81

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Fig. 8.18 Prominent minor papilla in patient with pancreas divisum and acute recurrent pancreatitis.

Fig. 8.19

Probing of mucosal folds to expose the minor papilla.

inspection is needed, and in some cases probing of the folds can allow identification (Fig. 8.19), although care must be taken not to traumatize the duodenum as edematous and friable tissue may make identification of the minor papilla particularly difficult. The minor papilla may be recognized by carefully withdrawing the endoscope from the position of the major papilla. However, the long endoscope position is frequently useful to allow identification and initial cannulation because of an improved endoscopic view, as well as an improved fluoroscopic view, because the endoscope is not over the distal (head) pancreatic duct (Fig. 8.20). If the endoscope is already in a shortened position, it may need to be brought back into the stomach and re-advanced so in the long position. It must be stressed that once cannulation of the minor papilla is achieved, or at least a guidewire has been positioned well into the main pancreatic duct, it is almost always advantageous to shorten the endoscope because of improved mechanical advantage and patient comfort. Secretin stimulates secretion of water and bicarbonate from pancreatic ductal cells and has been used for many years as an adjunct 82

Fig. 8.20 Long endoscope position with diagnostic cannulation of the minor papilla using a metal tipped catheter. The endoscope is not overlying the main pancreatic duct. Note prior biliary stent.

to minor papilla cannulation, since the output of juices can be identified endoscopically. Secretin is available from several sources. SecreFloTM (RepliGen Corp., Waltham, MA, USA) is a synthetic porcine secretin administered at a dose of 1 clinical unit/kg (200 nanograms/ kg) and is FDA approved for aiding in minor papilla cannulation. It has been shown in a randomized, placebo-controlled, double-blind, comparative trial in patients with pancreas divisum and was found to significantly improve minor papilla cannulation rates and to shorten cannulation time.55 ChiRhoStimTM (ChiRhoClin, Inc., ChiRhoClin, Inc, Burtonsville, MD, USA) is a purified synthetic peptide with an amino acid sequence identical to the naturally occurring hormone and has also been shown to improve cannulation of the minor papilla as compared to placebo.56 It is administered at a dose of 0.2 mcg/kg over one minute. It is now reimbursable with CPT code 43271. An advantage of this agent is its prolonged stability with 24 months in freezer, one year in refrigerator, and six months at room temperature. In the absence of severe chronic pancreatitis and/or complete ductal obstruction, pancreatic output should occur within several minutes. In patients in whom cannulation is unsuccessful, minor papilla cannulation may be facilitated by spraying dilute dyes such as methylene blue57 and indigo carmine58over the duodenal mucosa in the region suspected to contain the minor papilla. The output of pancreatic juice from the minor papilla minor papilla orifice creates an enlarging spot as pancreatic juice washes away the dye (Fig. 8.21). In patients with incomplete pancreas divisum, the dye can be mixed with contrast and injected into the major papilla. The minor papilla is then identified by dye decompressing through the accessing papilla. Minor papilla cannulation to obtain a dorsal ductogram is facilitated by the use of a needle tip catheter specifically designed for this indication (ERCP-1-CRAMER, Cook Endoscopy, Winston-Salem, NC).59 This catheter does not accept a guidewire, but the nose of the catheter dilates the opening and further facilitates catheter and guidewire based cannulation. Some endoscopists prefer to use ultratapered 3Fr catheters and 0.018 inch wires (Roadrunner, Cook Endoscopy; Glidewire, Boston Scientific).60,61 We prefer to identify the minor papilla with a needle-tip catheter as mentioned above.

Chapter 8 Cannulation of the Major and Minor Papilla

A

B

C

D

Fig. 8.21 Minor papilla identification (arrow) after spraying with dilute methylene blue.

Fig. 8.23 Rendezvous in a patient with incomplete divisum. A A prominent minor papilla is seen. B A guidewire catheter is passed through the major papilla out through the minor papilla. C A catheter is passed over the guidewire to dilate the minor papilla. D The minor papilla is easily cannulated using a sphincterotome.

into the correct axis may be useful. This may also be preferable if it is anticipated that minor papilla sphincterotomy using a pull sphincterotome is to be performed (see Chapter 15).

Advanced techniques Fig. 8.22 Minor papilla cannulation using a 5Fr catheter preloaded with a 0.035″ hydrophilic wire.

Once it is accurately identified and a pancreatogram is obtained, the catheter is left in place to dilate the orifice until the team is completely prepared with the catheter used for deep cannulation. When ready, the metal tip catheter is removed and a 0.035 inch Terumo wire (Glidewire, Boston Scientific) preloaded into a 5Fr catheter is quickly passed into the channel and used to probe the papillary opening (Fig. 8.22). Our success rate approximates 100% without the need for precut sphincterotomy. The 0.018″ wire is frequently too floppy for manipulation. On rare instances, however, the wire will pass into the duct, although the catheter will not. In this case, the guidewire is left in place and a needle-knife is passed alongside the guidewire. A “precut” is preformed by following the path of the wire in order to enlarge the opening to the minor papilla.62 An alternative to this is the use a biliary dilation catheter (PassageTM, Boston Scientific), which accepts an 0.035-inch guidewire. In some cases, an en face orientation to the minor papilla cannot be achieved for initial cannulation. In this setting, use of a sphincterotome to bow

In patients with incomplete divisum who require endoscopic therapy of the minor papilla and/or dorsal duct, a rendezvous technique can be employed. After cannulation of the major papilla, a guidewire is passed from the ventral duct into the dorsal duct and out though the minor papilla. On occasion, a catheter will follow the wire and act as a dilator to allow subsequent retrograde cannulation of the minor papilla (Fig. 8.23A–8.23D). One novel method of minor papilla cannulation is the use of EUS. EUS can be used two ways, both of which involve needle puncture of the main pancreatic duct using a linear array echoendoscope. The first method is to pass a guidewire antegrade into and through the minor papilla (e.g. rendezvous).63 The endoscope is withdrawn and a standard duodenoscope is inserted. The wire exiting the minor papilla is used to facilitate cannulation. The other technique involves injecting contrast mixed with dilute methylene blue into the main pancreatic duct. Again, the echoendoscope is withdrawn and exchanged for a side-viewing duodenoscope. Methylene blue is seen exiting and defining the orifice of the minor papilla, facilitating cannulation.64 When all the above methods have been exhausted and attempted cannulation has failed, true minor papilla precut techniques can allow successful cannulation. However, these techniques are best reserved for experts in therapeutic endoscopy, since severe complica83

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tions can occur. The technique for precutting the minor papilla is discussed in Chapter 15. Using the techniques described in this chapter, expert endoscopists can achieve successful minor papilla ductography in 90–100%

of patients with pancreas divisum without the use of minor papilla precut and/or EUS. Moreover, deep cannulation of the minor papilla is achievable in most of these patients as well as individuals without divisum.

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Chapter 8 Cannulation of the Major and Minor Papilla

35. Fogel E, Sherman S, Lehman GA. Increased selective biliary cannulation rates in the setting of periampullary diverticula: main pancreatic duct stent placement followed by pre-cut biliary sphincterotomy. Gastrointest Endosc. 1998; 47:396–400. 36. Kumar S, Sherman S, Hawes RH, et al. Success and yield of second attempt ERCP. Gastrointest Endosc. 1995 May; 41(5):445–447. 37. Choudari CP, Sherman S, Fogel EL, et al. Success of ERCP at a referral center after a previously unsuccessful attempt. Gastrointest Endosc. 2000 Oct; 52(4):478–483. 38. Ramirez FC, Dennert B, Sanowski RA. Success of repeat ERCP by the same endoscopist. Gastrointest Endosc. 1999 Jan; 49(1):58–61. 39. Calvo MM, Bujanda L, Heras I, et al. The rendezvous technique for the treatment of choledocholithiasis. Gastrointest Endosc. 2001 Oct; 54(4):511–513. 40. Petzold V, Rosch T, Born P. Combined endoscopic and percutaneous transhepatic approach in postsurgical common bile duct occlusion. Dtsch Med Wochenschr. 2001 Oct 26; 126(43):1197–2000. German. 41. Monkemuller KE, Linder JD, Fry LC. Modified rendezvous technique for biliary cannulation. Endoscopy. 2002 Nov; 34(11):936. 42. Dickey W. Parallel cannulation technique at ERCP rendezvous. Gastrointest Endosc. 2006 Apr; 63(4):686–687. 43. Shlansky-Goldberg RD, Ginsberg GG, Cope C. Percutaneous puncture of the common bile duct as a rendezvous procedure to cross a difficult biliary obstruction. J Vasc Interv Radiol. 1995 Nov– Dec; 6(6):943–946. 44. Lella F, Bagnolo F, Rebuffat C, et al. Use of the laparoscopicendoscopic approach, the so-called “rendezvous” technique, in cholecystocholedocholithiasis: a valid method in cases with patient-related risk factors for post-ERCP pancreatitis. Surg Endosc. 2006 Mar; 20(3):419–423. 45. Dickey W. Parallel cannulation technique at ERCP rendezvous. Gastrointest Endosc. 2006 Apr; 63(4):686–687. 46. Peterson BT. Biliary rendezvous or solo combined procedure for therapy of sump syndrome. Gastrointest Endosc. 1996 Feb; 43(2 Pt 1):176–177. 47. Kahaleh M, Wang P, Shami VM, et al. EUS-guided transhepatic cholangiography: report of 6 cases. Gastrointest Endosc. 2005 Feb; 61(2):307–313. 48. Kahaleh M, Hernandez AJ, Tokar J, et al. Interventional EUS-guided cholangiography: evaluation of a technique in evolution. Gastrointest Endosc. 2006 Jul; 64(1):52–59. 49. Lai R, Freeman ML. Endoscopic ultrasound-guided bile duct access for rendezvous ERCP drainage in the setting of intradiverticular papilla. Endoscopy. 2005 May; 37(5):487–489.

50. Devereaux BM, Lehman GA, Fein S, et al. Facilitation of pancreatic duct cannulation using a new synthetic porcine secretin. Am J Gastroenterol. 2002 Sep; 97(9):2279–2281. 51. Itoh S, Takada A, Satake H, et al. Diagnostic value of multislice computed tomography for pancreas divisum: assessment with oblique coronal reconstruction images. J Comput Assist Tomogr. 2005 Jul–Aug; 29(4):452–460. 52. Hellerhoff KJ, Helmberger H 3rd, Rosch T, et al. Dynamic MR pancreatography after secretin administration: image quality and diagnostic accuracy. AJR Am J Roentgenol. 2002 Jul; 179(1):121–129. 53. Lai R, Freeman ML, Cass OW, et al. Accurate diagnosis of pancreas divisum by linear-array endoscopic ultrasonography. Endoscopy. 2004 Aug; 36(8):705–709. 54. Song MH, Kim MH, Lee SK, et al. Endoscopic minor papilla interventions in patients without pancreas divisum. Gastrointest Endosc. 2004 June; 59(7):901–905. 55. Devereaux BM, Lehman GA, Fein S, et al. Facilitation of pancreatic duct cannulation using a new synthetic porcine secretin. Am J Gastroenterol. 2002 Sep; 97(9):2279–2281. 56. Devereaux BM, Fein S, Purich E, et al. A new synthetic porcine secretin for facilitation of cannulation of the dorsal pancreatic duct at ERCP in patients with pancreas divisum: a multicenter, randomized, double-blind comparative study. Gastrointest Endosc. 2003 May; 57(6):643–647. 57. Park SH, de Bellis M, McHenry L, et al. Use of methylene blue to identify the minor papilla or its orifice in patients with pancreas divisum. Gastrointest Endosc. 2003 Mar; 57(3):358–363. 58. Ohshima Y, Tsukamoto Y, Naitoh Y, et al. Function of the minor duodenal papilla in pancreas divisum as determined by duodenoscopy using indigo carmine dye and a pH sensor. Am J Gastroenterol. 1994 Dec; 89(12):2188–2191. 59. Dunham F, Deltenre M, Jeanmart J, et al. Special catheters for E.R.C.P. Endoscopy. 1981 Mar; 13(2):81–85. 60. Schleinitz PF, Katon RM. Blunt tipped needle catheter for cannulation of the minor papilla. Gastrointest Endosc. 1984 Aug; 30(4):263–266. 61. Khalid A, Slivka A. Pancreas Divisum. Curr Treat Options Gastroenterol. 2001 Oct; 4(5):389–399. 62. Wilcox CM, Monkemuller KF. Wire-assisted minor papilla precut papillotomy. Gastrointest Endosc. 2001 Jul; 54(1):83–86. 63. Will U, Meyer F, Manger T, et al. Endoscopic ultrasound-assisted rendezvous maneuver to achieve pancreatic duct drainage in obstructive chronic pancreatitis. Endoscopy. 2005 Feb; 37(2):171–173. 64. Dewitt J, McHenry L, Fogel E, et al. EUS-guided methylene blue pancreatography for minor papilla localization after unsuccessful ERCP. Gastrointest Endosc. 2004 Jan; 59(1):133–136.

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Access (Precut) Sphincterotomy: Conceptual Philosophy and Technical Details Amit Maydeo, Suryaprakash Bhandari, and Hardeep Singh

INTRODUCTION With the advent of imaging modalities like MRCP and EUS, there are very few indications left for diagnostic endoscopic retrograde cholangiopancreatography (ERCP). However, with the development of better endoscopic technologies including specialized cannulae, hydrophilic wires and endoprostheses, the indications and possibilities of therapeutic ERCP have dramatically expanded. The ability to selectively cannulate the bile duct and/or the pancreatic duct is a prerequisite before being able to perform further endoscopic therapy in the biliary and pancreatic system. The anatomy and the appearance of the ampulla of Vater is however not uniform and varies in every patient. Ampullae can be flat or bulging; exposed or covered by duodenal folds; distorted or inflamed and untouched or previously tampered with. In fact, the ampulla of Vater is usually the biggest hurdle in performing a therapeutic ERCP for the beginner endoscopist. The fact remains that in spite of all the advances in technology and technique, there continue to be some instances when even the most experienced endoscopist will be unable to cannulate the desired duct. It is when the standard techniques of cannulation fail that one needs to resort to specialized techniques of ductal cannulation. Precut, or access sphincterotomy as it is popularly called, is primarily designed for gaining access into the biliary or pancreatic duct when the conventional methods of selective cannulation fail. In this chapter we will focus predominantly on the conceptual philosophy behind the techniques of precut “accessotomy” and describe in detail the different techniques and tools which are commonly used. We will also review the existing published literature regarding the usefulness and complications of these techniques when used in different clinical situations.

INDICATION FOR PRECUT As a general rule, precut accessotomy should be performed when standard techniques of selective cannulation fail. However, the definition of cannulation failure is itself unclear and the decision to resort to a precut usually depends on a number of factors including the indication of the procedure, anatomy of the ampulla/ duodenum and most importantly the training, comfort and threshold of the endoscopist. Though some of these factors are subjective, most endoscopists agree that precut should not be done for purely diagnostic purposes and until a sincere attempt to cannulate has been made by an experienced and skilled endoscopist.

The use of precut accessotomy varies from center to center (Table 9.1). Binmoeller et al. described employing a precut in 38% of 327 patients,1 while Foutch reports using precut in only 11% of 456 patients.2 One perspective is that trauma to the ampulla and pancreatic duct should be minimized in order to avoid complications, and therefore precut should be considered early in the procedure. Others prefer to leave precut as a “last resort” or “rescue” method, to be employed only when multiple exhaustive attempts at standard cannulation have failed. There seems to be a general agreement however that multiple unsuccessful attempts at cannulation tend to increase complications such as pancreatitis and, therefore, it is better to perform a precut accessotomy early before damaging the ampulla/ ductal epithelium further. Many experienced endoscopists therefore resort to a precut if a few attempts (3–5) of selective cannulation fail. There are some clinical situations when precut is the preferred method of initial cannulation. In patients with an impacted gallstone at the ampulla of Vater, it may be easier to precut over the stone, rather than attempting to cannulate around the stone through the papillary orifice. In patients with a previous Billroth II operation it may be better to cannulate the bile duct and place a stent over which a precut of the ampulla is done. Similarly stenting followed by precut may be the preferred method of cannulating and cutting the minor papilla in symptomatic patients with pancreas divisum. We favor utilizing precut accessotomy early in the course of the procedure. Typically, we allow 3–5 targeted attempts at wire-guided cannulation using a smooth-tipped, short-nosed, short-wire sphincterotome (Clever cut, Olympus Optical Co. Japan) and a 0.032-inch, J-shaped glide wire (Terumo Corp., Japan). We avoid unnecessary probing and traumatization of the ampulla and the ductal epithelium. If this fails to provide access in 3–5 attempts and the ampullary anatomy is suitable for a precut, we proceed with the accessotomy technique.

TECHNIQUE OF PRECUT ACCESSOTOMY Conceptual philosophy of the technique Siegel first reported the technique of “precut papillotomy” in 1980, using a standard sphincterotome inserted into the papillary orifice to expose the bile duct.3 Since then many expert endoscopists of the world have utilized the precut using either the modified Erlangen sphincterotome or the needle-knife. Different techniques have been 87

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described using these instruments with the cut being made from below upwards or from above downwards. Regardless of the type of instrument used for the precut, the basic principle is to unroof the ampulla of Vater by cutting open its superficial layers and thereby exposing the biliary epithelium. It is mandatory that the duodenal peristalsis is suppressed with an antiperistaltic drug and the patient is well sedated for a clear, quiet and accurate visualization of the ampulla of Vater. This period of proper and careful inspection of the ampulla is of prime importance to plan the precut accessotomy rather than immediately starting the cut. If the ampulla is covered with duodenal folds, one needs to lift the overhanging folds and inspect the ampulla properly before beginning the cut. During this inspection, it is necessary to appreciate the orientation and direction of the bulging portion of the ampulla which usually indicates the bile duct direction below the surface. The ampulla of Vater is covered by the duodenal mucosa on its outermost part with the submucosa below it and then the muscular layer covering the bile duct and pancreatic ducts (Fig. 9.1). Therefore, though the biliary and pancreatic ducts open finally at the ampullary orifice, the bile duct actually courses upwards and towards the left just below the ampullary roof, whereas the pancreatic duct courses towards the right and in a more straight direction. Therefore, for entering the biliary or pancreatic ducts, unroofing of the superficial ampullary layers needs to be done in the directions of the required ducts. It is mandatory therefore to imagine the ampullary and ductal anatomy precisely before beginning the precut.

Author

Year

Technique

Pre-cut (n)

% of Pre-cut

Akashi

2004

Transpancreatic

172

10

Goff

1999

Transpancreatic

51

26

Rabenstein

1997

Needle-knife

694

33

Binmoeller

1996

Short nosed Erlangen type sphincterotome

123

38

Foutch

1995

Needle-knife

52

11

Huibregtse

1986

Needle-knife

190

19

Table 9.1 Percentage of precut accessotomy utilizing different techniques

A

88

B

Once the ampullary anatomy is clearly imagined, the cut should be made in a layer by layer manner starting from the ampullary orifice. For bile duct entry, the cut is made slowly from the orifice upwards and somewhat towards the left. Whichever instrument is used for the cut, each stroke of the cut has to be superficial and should be a clean incision using a pure cut or blended current. It is imperative that all the strokes of the cut are made in one direction only without changing the direction with each stroke. Similarly it is mandatory that the depth of each stroke has to be superficial and not deep. Once the superficial layer of the mucosa is cut, the bulge of the bile duct is usually evident with a whitish covering. This needs to be further cut superficially in the same direction until the “Salmon” pink epithelium of the bile duct is exposed. The bile duct can be carefully probed using a delicate instrument like an ERCP cannula or a soft-tipped sphincterotome along with a glide wire (Fig. 9.2). During the precut, some oozing may take place. This is likely to obscure vision and thereby prevent further progress of the cut. In this case, it is a good idea to spray diluted epinephrine solution (1 : 20000) on the cut surface of the ampulla until the oozing stops. If this is not enough to control the bleeding, direct coagulation of the bleeding spot can be done after careful inspection of the bleeding area. If, in spite of an adequately made cut in the proper direction, the bile duct bulge is not seen, one should carefully inspect to see if the cut has been made on either side of the bulge rather than on the bulge itself. In this case it may be a good idea to identify the pancreatic orifice first and then look for the biliary bulge above and on the left of the pancreatic orifice. In rare instances, the biliary orifice is located on the right of the pancreatic orifice instead of the left.

THE TECHNIQUE OF NEEDLE-KNIFE PRECUT ACCESSOTOMY The needle-knife consists of a catheter with a straight retractable diathermy wire at the end. When current is applied, the needle can be used to make a cut through the papillary mucosa to gain access to the bile duct. There are a variety of different approaches to precut accessotomy when using a needle-knife. The most common method is the free-hand needle-knife technique. With this technique, the needle-knife is gently inserted into the papillary orifice and the incision is made superiorly toward the 11 o’clock position. This upward motion is directed through manipulation of the elevator, large wheel,

Fig. 9.1 The ampulla of Vater, conceptual anatomy of this complex organ. The papillary folds A are like the peels of an onion B. The CBD and PD orifices lie hidden in the core of the onion. The CBD direction is left and upward, the PD is right and straight. Cannula getting stuck in the folds is the commonest problem.

Chapter 9 Access (Precut) Sphincterotomy: Conceptual Philosophy and Technical Details

A

B

C

D

E

F

Fig. 9.2 Serial images showing layer by layer deroofing of the papilla using a needle-knife. A The first mucosal layer being cut with needle-knife. Note the direction of the cut is towards 11 o’clock position. B The second submucosal layer being cut with the needle-knife. C The third muscle layer being cut with the needle-knife. D–F Exposed “Salmon” pink epithelium of the bile duct with free flowing bile.

or by applying upward torque on the shaft of the endoscope. Usually the incision should be approximately 5 mm in length, but the exact size of the cut would depend on the size and anatomy of the papilla. Huibregtse advises taking a few “practice swings” in order to map out the path of the cut, prior to performing the precut.4 Current is applied only while the wire is moving within the tissue, so as to avoid coagulation and edema of the papilla. Blended current was used most often in large case series on needle-knife papillotomy.2,4,5 One small trial by Baron et al. showed no difference in complication rates in patients undergoing needle-knife papillotomy with blended versus pure cutting current.6 After the initial cut is made, further cuts are made in the same direction, in an effort to slowly dissect down toward the bile duct. Once the bile duct orifice is exposed, the needle is withdrawn and the needle-knife catheter can be used to carefully enter the duct. Alternatively, a tapered tip catheter or a flexible guidewire can be used to enter the duct. When the duct has been successfully cannulated, therapeutic maneuvers can be performed in the same manner as with normal cannulation. There is much data to support the use of needle-knife papillotomy as a safe and effective method for selective cannulation of the bile duct. Rabenstein et al. published a large retrospective review of the benefits and risks of needle-knife papillotomy in 694 patients.5 In this study, the author achieved a successful initial cannulation in 70% of patients, and with a second attempt, was able to cannulate the duct in 85% of patients. The most common complications were bleeding and pancreatitis. The overall complication rate was the same in the group that underwent needle-knife papillotomy compared to those that underwent conventional sphincterotomy (7%). Other studies have yielded similar results.2,6,7 However, whether needle-knife papillotomy confers an increased risk of pancreatitis

remains controversial. A meta-analysis performed by Masci et al. found precut papillotomy to be associated with an increased risk of post-ERCP pancreatitis (Odds Ratio 2.71).8 It is likely that the discrepancy in these results indicates that the risks of needle-knife papillotomy depend on proper patient selection and on the experience of the endoscopist. Another way of gaining access using a needle-knife is by performing a suprapapillary fistulotomy. Typically this is done by inserting the needle a few millimeters above the papillary orifice in the 11 o’clock orientation, and cutting in a downward motion toward the orifice. The motion is again repeated slowly in an effort to extend the depth of the cut and eventually expose the bile duct. A variation of this technique involves puncturing the papilla above the orifice and cutting in an upward direction. Once the duct is exposed, the duct is gently entered in the same manner. The study by Baron et al. and a large study by O’Connor et al. of over 500 patients demonstrated suprapapillary fistulotomy to be a safe and effective maneuver for gaining access to the CBD.6,9 However, one limitation of this method is that the created incision cannot be as large as a conventional precut, which may make therapeutic maneuvers more difficult. Mavrogiannis et al. found that although success rates of selective cannulation were comparable between patients undergoing suprapapillary fistulotomy versus needle-knife papillotomy, stone extraction was more difficult in the fistulotomy group.10 A final method employs inserting a stent into the pancreatic duct and then using the needle-knife to cut over the stent to perform a papillotomy or fistulotomy. In this technique, the stent has two roles. First, if the pancreatic duct has been repeatedly injected and manipulated while attempting cannulation, placement of a temporary stent may help prevent post-ERCP pancreatitis.11 Secondly, a stent placed 89

SECTION 2 TECHNIQUES

in the pancreatic duct may serve as a guide for performing the precut. Although we do not routinely place pancreatic stents prior to performing a precut, there is some rationale for this technique.

TRACTION PAPILLOTOME TECHNIQUES Another approach to performing a precut employs the use of a traction papillotome. This technique was pioneered by Binmoeller and Soehendra, who describe performing a “papillary roof incision” using an Erlangen-type precut papillotome in order to achieve selective cannulation of the bile duct.1 Proponents of this technique claim that traction papillotomes allow for a more controlled incision compared to a needle-knife. This type of papillotome has a one cm monofilament diathermy wire and a short tip that extends beyond the cutting wire. The leading tip of this specialized papillotome is inserted into the papillary orifice. The instrument is then swung in the 11 o’clock direction as current is delivered, and the incision is typically 5 to 10 mm in length. Although the authors originally described using pure cutting current at 40–50 W, blended current can also be used. As with a needle-knife papillotome, the incision is repeated in the same direction to gradually and carefully fillet open the roof of the papilla and expose the biliary orifice. Once the duct is identified, the orifice is probed with the tip of the papillotome until cannulation is achieved. Although we are not aware of any studies comparing traction papillotomy to needle-knife, success and complication rates appear comparable to those seen in large studies of needle-knife papillotomy.1,2,5,6 A variation of this method is trans-pancreatic precut sphincterotomy, originally described by Goff in 1995.12 This technique involves inserting the traction papillotome into the pancreatic duct. Next the papillotome is used to make an incision toward the common bile duct, cutting the inter-ductal septum and unroofing the papilla in the process. A retrospective study by Goff including 51 patients found the rate of success and complications to be comparable to conventional methods.13 Unfortunately, a larger study by Akashi et al. published in 2004 found a higher incidence of complications and lower success rate with the trans-pancreatic technique.14 It is our opinion, that if this maneuver is used, it should only be done in

Author

Year

Technique

Akashi Goff Rabenstein Binmoeller

2004 1999 1997 1996

Foutch Huibregtse

1995 1986

Transpancreatic Transpancreatic Needle-knife Papillary roof incision Needle-knife Needle-knife

Eventual success (%)

% of Precut complications

95 98 85 100

10 2 7 5

90 84

6 3

Table 9.2 Percentage of cannulation success and complication rates with different methods of precut

special circumstances and by an experienced endoscopist. Moreover, a pancreatic duct stent should be inserted post-sphincterotomy to minimize procedural pancreatitis.

CONCLUSION There is extensive data indicating that precut techniques can contribute to successful selective cannulation of the bile duct, but there are some associated risks (Table 9.2). Typical risks ascribed to precut accessotomy include pancreatitis, perforation and bleeding. The data regarding the frequency of these complications is variable, and there remains some controversy whether these complications are the result of the precut, or whether they are the result of multiple failed attempts at standard cannulation. Also, rates of complications may vary with the technique of precut used. Nevertheless, there is agreement that precut accessotomy is a technique that should only be utilized in the proper clinical situation. It is only after sincere and careful attempts at standard cannulation have failed, that precut accessotomy should be considered. Furthermore, it should be emphasized that precut should not be a substitute for sound endoscopic technique. Endoscopists performing this procedure should not only have extensive experience in performing the various techniques of precut, but should also be well-versed in how to manage possible endoscopic complications.

REFERENCES 1.

2.

3. 4.

5. 6.

7.

90

Binmoeller KF et al. Papillary roof incision using the Erlangentype pre-cut papillotome to achieve selective bile duct cannulation. Gastrointestinal Endoscopy, 1996; 44:689–695. Foutch PG. A prospective assessment of results of needle-knife papillotomy and standard endoscopic sphincterotomy. gastrointestinal endoscopy, 1995; 41:25–32. Siegel JH. Precut papillotomy: a method to improve success of ERCP and papillotomy. Endoscopy, 1980; 12:130–133. Larkin CJ, Huibregtse K. Precut sphincterotomy: indications, pitfalls, and complications. Current Gastroenterology Reports, 2001; 3:147–153. Rabenstein T et al. Benefits and risks of needle-knife papillotomy. Gastrointestinal Endoscopy, 1997; 46:207–211. Abu-Hamda EM, Baron TH, et al. A retrospective comparison of outcomes using three different precut needle-knife techniques for biliary cannulation. J of Clinical Gastroenterology, 2005; 39:717–721. Huibregtse K et al. Precut papillotomy via fine-needle-knife papillotome: a safe and effective technique. Gastrointestinal Endoscopy. 1986; 32:403–405.

8. Masci E et al. Risk factors for pancreatitis following endoscopic retrograde cholangio-pancreatography: a meta-analysis. Endoscopy, 2003; 35:830–834. 9. O’Connor HJ et al. Suprapapillary fistulosphincterotomy at ERCP: a prospective study. Endoscopy, 1997; 29:266–270. 10. Mavrogiannis C et al. Needle-knife fistulotomy versus needleknife precut sphincterotomy for the treatment of commmon bile duct stones. Gastrointestinal Endoscopy. 1999; 50:334–339. 11. Freeman ML, Guda NM. Prevention of post-ERCP pancreatitis: a comprehensive review. Gastrointestinal Endoscopy, 2004; 59:845–864. 12. Goff JS. Common bile duct pre-cut sphincterotomy: transpancreatic sphincter approach. Gastrointestinal Endoscopy 1995; 41:502–505. 13. Goff JS. Long-term experience with the trans-pancreatic sphincter pre-cut approach to biliary sphincterotomy. Gastrointestinal Endoscopy 1999; 50:642–645. 14. Akashi R et al. Pancreatic sphincter precutting to gain selective access to the common bile duct: a series of 172 patients. Endoscopy, 2004; 36:405–410.

SECTION 2

Chapter

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Sphincter of Oddi Manometry Nalini M Guda and Joseph E Geenen

INTRODUCTION AND SCIENTIFIC BASIS Sphincter of Oddi was first described in 1887 by Ruggero Oddi as a distinct anatomical and physiological entity. The sphincter is composed of smooth muscles encircling the distal end of the common bile duct and the main (ventral) pancreatic duct. The muscles are arranged in both a circular and a figure of eight configuration and are about 4–10 mm in length. The main function of the sphincter is to regulate bile and exocrine pancreatic secretions and to prevent reflux of duodenal contents into the ducts. In addition to a basal pressure the sphincter of Oddi has a phasic contractile activity. The basal pressure is the predominant mechanism which regulates the release of biliary and pancreatic secretions into the duodenum. Phasic contractions are thought to be important in preventing the duodenal reflux into the ducts. Phasic contractions are related to the migratory motor complex of the duodenum. Neural regulation does not appear to play an important role since even in post-transplant patients the sphincter of Oddi function appears preserved. Chemical regulation is important. Cholecystokinin and secretin cause sphincter relaxation. Patients with abnormalities in the contraction of the sphincter of Oddi are labeled as having sphincter of Oddi dysfunction. It is also known as papillitis, papillary stenosis, post cholecystectomy syndrome, papillary spasm, biliary dyskinesia, tachyoddia etc. Detailed clinical presentation of those with sphincter of Oddi dysfunction is described elsewhere in this book (Chapter 34). Sphincter of Oddi manometry provides data regarding the basal pressure of the sphincter, the frequency of contractions and the amplitude of contractions occurring at the sphincter. Manometry of the sphincter of Oddi is performed at the time of ERCP for those with a clinical suspicion of biliary or pancreatic type of pain thought to be related to either dyskinesia or stenosis of the biliary and/or pancreatic sphincters. Sustained basal pressures (>40 mm of Hg) on manometry are thought to be due to sphincter of Oddi stenosis and sphincterotomy in these situations has been shown to result in relief of symptoms.1,2 Sphincter of Oddi Manometry (SOM), though invasive, is considered the gold standard for measurement of biliary motility.3 Though there is some concern whether a few minutes of pressure observations would reflect the pressure dynamics over 24 hours, currently this is the accepted method of measurement. There are other non-invasive means of detecting the sphincter of Oddi dysfunction: Morphine-Prostigmin Provocative Test (Nardi Test), Ultrasonographic Assessment of Extrahepatic Bile Duct and Main Pancreatic Duct Diameter After Secretory Stimulation and Quantitative Hepatobiliary Scintigraphy. There are also limited data regarding the use of secretin stimulated MRCP and EUS in the evaluation of SO dysfunction. In a pilot study of 18 patients with idiopathic acute recurrent pancreatitis there appeared to be a high concordance

rate between ERCP and secretin MRCP in diagnosis of SO dysfunction.4 In a similar study secretin was injected and pancreatic duct diameter was subsequently measured by ultrasound in patients with idiopathic acute recurrent pancreatitis. Those with dilated duct diameter beyond 20 minutes were suspected to have sphincter of oddi dysfunction. All patients underwent SO manometry in 3–7 days. Using SO manometry as the gold standard the sensitivity and specificity of secretin stimulated ultrasound in diagnosis of SO dysfunction was 88% and 82%.5 These techniques have not been evaluated in larger series of patients and in those without pancreatitis. At the current time none of the non-invasive methods have superior operating characteristics compared to the conventional SOM (Table 10.1).6

TECHNIQUE Patient preparation As with all endoscopic procedures patients should be fasting for at least 6 hours. Drugs that either stimulate or relax the sphincter of Oddi should be avoided at least 12 hours prior to the scheduled manometry. Drugs that are thought to stimulate the sphincter include narcotic analgesics and other cholinergic agents. Drugs that relax the sphincter include nitrates, glucagon, calcium channel blockers and other anti-cholinergic agents. Midazolam in doses >2 mg has been shown to reduce the basal sphincter pressure.7 Benzodiazepines and Meperidine (Demerol) when given at a dose of <1 mg/kg body weight do not appear to alter the sphincter pressures and are considered acceptable for sedation.8 Propofol sedation has been shown to have no effect on the sphincter of Oddi basal pressures.9 Similarly use of general anesthesia for sedation has not been shown to have any effect on the sphincter of Oddi.10 Patients could be sedated either by conscious sedation or by anesthesia depending on the patient’s tolerance. There has been an increasing trend to perform these procedures either with propofol or general anesthesia. The patient is placed usually in a prone position as with any standard ERCP procedures.

Preparation of equipment The hydraulic capillary infusion pump should be filled with 500 cc of sterile water and sealed tightly. The valve on the nitrogen tank attached to the perfusion system should be opened to a pressure of 100 PSI. The low pressure valve on the machine should be opened to 7 PSI. Gently tap the transducer dome to remove any air. Initially the transducers are attached to the connecting catheters and the connecting catheters are in turn connected to the triple lumen catheters. Turn on the perfusion valve. Prime the triple lumen and the duodenal catheters (if used). It is recommended that the perfusion system should be switched on for at least 15 minutes before 91

SECTION 2 TECHNIQUES

the procedure. Care should be taken to avoid any air bubbles (Fig. 10.1). The duodenoscope is introduced into the duodenum as with any standard ERCP procedure. The duct of interest is initially cannulated with a catheter and guidewire. Catheters with 5 Fr diameter are generally used. A triple lumen sphincterotome would be useful since ease of initial cannulation with a sphincterotome has been demonstrated and moreover if sphincterotomy needs to be done it would result in cost savings and reduce need for additional equipment. After selective cannulation one can check for the location of the catheter by gently aspirating. Presence of bilious material confirms presence in the bile duct (Fig. 10.2) and a clear aspirate is suggestive of pancreatic duct cannulation (Fig. 10.3). If needed, contrast could be injected into the duct for better visualization of the anatomy and to rule out any other structural problem. Injection of contrast into the bile duct prior to sphincter of Oddi manometry has been shown to increase the mean pressure but not the basal sphincter pressure.11 Such evaluation has not been performed in the pancreatic duct. It is suggested that, prior to manometry, if a cholangiogram or pancreatogram were to be routinely obtained, it might obviate manometry if another etiology or anatomic abnormality was seen which could explain a patient’s symptoms. We routinely inject contrast material into the bile or pancreatic ducts to evaluate the biliary and pancreatic duct anatomy and to rule out any other struc-

Diagnostic modality Provocative—Nardi test Pain with contrast injection CBD dilation/delayed drainage LFT abnormalities DISIDA scan US fatty meal SO manometry

Yes

Maybe

No x x

x x x x x

Table 10.1 Tests used in evaluating SOD DISIDA: diisopropyl iminodiacetic acid (nuclear medicine scan).

tural causes including strictures, stones etc., which could explain the symptoms and obviate manometry. Moreover injection of contrast also helps in passing the guidewire deep into the duct without passing the wire into side branches and potentially causing duct perforation in case of pancreatic duct cannulation. Duct configurations including ansa pancreaticus will be seen easily if initial contrast injection is made prior to advancing the wire (Figs 10.4 and 10.5). After injection of contrast into the duct a 0.018 inch guidewire is passed deep into the duct of interest and the cannula is exchanged if one is to perform wire-guided manometry. Over the guidewire a manometry catheter (monorail) is introduced deep into the biliary or pancreatic ducts. We recommend introducing the catheter deep into the duct and trying not to touch any of the walls of the duct since this could result in false results. Pressure recordings are usually obtained within the duct as prior studies have shown that those with SO dysfunction have higher intraductal pressures. Prior to introducing the manometry catheter care should be taken to obtain a duodenal pressure recording which is usually set as zero pressure. The recording should be equal in all channels and establishes a baseline value. Historically an extra catheter was attached to the duodenoscope shaft and served to provide continuous intraluminal duodenal pressure. The motility catheter itself should be withdrawn carefully 1–2 mm increments while pressures are measured. It is recommended to obtain a reading at every black mark while withdrawing the catheter and to record pressures at each station for at least two minutes. Phasic waves should be recorded separately from the basal pressures. It is very important to have a continuous communication between the endoscopist and the technician/nurse assisting with manometry. Information regarding the position of the catheter, number of black marks visible, duodenal contractions and patient activity should be communicated by the endoscopist to the technician/nurse performing the recordings. Similarly the technician/nurse should communicate the average baseline pressure, phasic waves and any interference in the recording to the endoscopist. It is a team effort and communication is the key to accurate manometry (Figs 10.6, 10.7 and 10.8 demonstrate normal

Fig. 10.1 Photograph of Arndorfer Perfusion Pump.

92

Chapter 10 Sphincter of Oddi Manometry

Fig. 10.4 Cholangiogram prior to performing SO manometry. Fig. 10.2

Photograph of catheter aspirating bile.

Fig. 10.3 Photograph showing clear aspirate from the duct suggesting pancreatic duct.

duodenal pressure, elevated biliary sphincter pressure and phasic contractions). It is recommended to study pressures in both biliary and pancreatic ducts. Data from several studies have shown that often times the pressures are abnormal only in one segment (sphincter choledochus or pancreaticus) of the sphincter of Oddi in 35–65% of the patients.6 Data also suggest that those with pancreatitis often have abnormal pancreatic sphincter basal pressures while those with biliary type of pain and abnormal liver functions have higher basal pressures of the bile duct sphincter.12 It is recommended that the manometric abnormality be seen for at least 30 seconds and should be seen at least in two or more pull throughs. If, however, the basal pressures are clearly normal or abnormal, one can limit to a single pull through. The interobserver variability in manometric readings is good. There is controversy if the measurement of the average of the basal measurements from the three ports in the standard catheter and the two ports in the modified catheter should be used to make a determination of pressure. We perform a station pull through at least two times. We average the recordings and prefer to see elevated pressures at more than one station and in both the pull through maneuvers.

Fig. 10.5

Fig. 10.6 pressure.

Pancreatogram prior to performing SO manometry.

Manometry tracing showing the basal duodenal

93

SECTION 2 TECHNIQUES

Fig. 10.7

Manometry tracing showing elevated biliary pressure.

2 mm

Manometry tracing showing phasic contractions.

Fig. 10.9 Schematic representation of the Arndorfer triple lumen manometry catheter.

2mm

1 mm

Fig. 10.8

20mm 0.018* guide wire

Parameter

Abnormal values

Basal pressure Phasic wave amplitude Phasic wave frequency Phasic wave retrograde propogation

>40 mm of Hg >350 mm of Hg >8/min >50% total

Table 10.2 Abnormalities in SO Manometry Interpretation of the Manometry recordings: Before interpretation of readings is done, care should be taken to establish a basic duodenal pressure recording. Typically this is the average of the three recordings when the triple lumen catheter is placed freely in the duodenum through the duodenoscope prior to cannulation. The elevator should be in the down position and the catheter should not touch any duodenal wall to avoid any errors. (Table 10.2) We currently use a triple lumen Arndorfer pneumohydraulic capillary perfusion system (Arndorfer Medical Specialties, Greendale, Wisconsin, USA) (Fig. 10.9). The Arndorfer catheter is perfused at 0.25 ml/minute with distilled water. Efficacy of perfusion with physiological solutions has not been established. The perfusion catheter has three side holes and pressure should be recorded at all the three side holes.13 Sacrificing one of the ports to provide for aspiration has been shown to reduce the incidence of pancreatitis when performing manometry of the pancreatic duct but not the bile duct.14,15 Aspiration cannot be done with wire-guided mano. Perfusion at a lower rate could accurately measure the basal sphincter but the accuracy of phasic waves is unreliable. Once pressure measurements have been made, one has to decide whether to do a sphincterotomy. Techniques of sphincterotomy are 94

described elsewhere in this book (see Chapters 12 and 14). For sphincterotomy one must have deep cannulation of the desired duct. Sphincterotomy is performed by a traction sphincterotome over a guidewire. The cutting wire should track up to the middle of the papilla and in biliary sphincterotomy should be oriented between the 10 o’clock and 12 o’clock position. Automated electrical generators delivering pulse current reduce excessive rapid cutting “zipper effect.” There is debate over the superiority of the type of current in prevention of bleeding and post-ERCP pancreatitis. In a meta-analysis it was shown that pure cut current was associated with a slightly increased risk of immediate post-sphincterotomy bleeding; however, there were no significant differences in the rates of delayed bleeding or pancreatitis.16 We recommend using pure cutting current for pancreatic sphincterotomy and blended current for biliary sphincterotomy using standard electrical generators. Irrespective of whether the pressure is elevated or not or whether biliary and/or pancreatic sphincterotomy is performed, it is a standard practice now to place a stent in the pancreatic duct to reduce the risk of post-ERCP pancreatitis post-manometry (Fig. 10.10). This has been documented well in various studies.17,18 It is not clear at this time whether a small caliber 3 Fr stent is better than a larger bore stent. Preliminary data indicate that a modified 5 Fr straight stent with the inner flange removed is associated with lower rates of pancreatitis compared to the 3 Fr pigtail stents.19 Insertion of 3 Fr pigtail stents is a little more difficult and one can use only a wire of 0.018 inch diameter. Catheters with microtransducers at the tips of the catheters are available and these can record real-time data when cannulation is achieved. Since there is no perfusion involved with these systems they may reduce the risk of post-ERCP pancreatitis. These catheters

Chapter 10 Sphincter of Oddi Manometry

ware to available esophageal manometry equipment. We currently use PolygramNet (Medtronic, Minneapolis, MN) to record and assess sphincter pressures. A manometry catheter with one port sacrificed to aid suction of the perfused saline is also available (Lehman SO Manometry catheter, Cook Endoscopy, Winston-Salem, NC). The catheter is 5 Fr in diameter and has a 5 mm or 1.5 cm tip. Both catheters are relatively easy to use for cannulation. While an Arndorfer catheter is an over-the-wire catheter, one could use the Lehman catheter without the wire or alternatively, it could be introduced over the wire. We use the Arndorfer infusion pump (Arndorfer Medical Specialties, Greendale, Wisconsin, USA).

COMPLICATIONS Fig. 10.10 Radiograph of the 3 Fr pancreatic stent to prevent postERCP pancreatitis.

Fig. 10.11 sleeve.

Picture of the new manometry catheter with Dent

are stiffer than the regular manometry catheters and are difficult to cannulate. Its usage is not widespread and data are limited.20 Sleeve catheters were recently developed. They have the advantage of perfusion of 0.04 ml/min and the fluid is collected back in the sleeve. The sleeve also helps stabilize the catheter in the sphincter zone without touching the side walls of the duct and providing erroneous values. This is not yet commercially available and clinical studies are in progress evaluating the efficacy of these catheters21 (Fig. 10.11).

Indications for sphincter of Oddi manometry • Pain if suspected to be pancreatobiliary in nature with or without liver function abnormality (Geenen—Hogan classification) • Idiopathic recurrent pancreatitis

EQUIPMENT The following is the standard equipment which is required for manometry. 1. Standard diagnostic or therapeutic duodenoscope 2. Hydraulic capillary Infusion system 3. Manometry catheter 4. Recording system: Dynagraph/computerized/solid state system

Catheters We prefer the Arndorfer catheter since it is a validated manometry catheter (Arndorfer Medical Specialties, Greendale, Wisconsin, USA). The pressure recordings can be done with addition of soft-

As with any ERCP, pancreatitis remains the foremost complication of pancreaticobiliary manometry (see also Chapter 6). It is the patient characteristics that predispose these individuals to increased frequency of post-ERCP pancreatitis. Manometry by itself does not pose any greater risk.22 Techniques that possibly reduce the risk of pancreatitis include initial injection of contrast into the pancreatic duct so that when the wire is introduced into the main duct repeated manipulations into side branches and duct disruption is avoided. One needs to perform a quick station pull through. There is concern of over-perfusing with saline for manometry and hence an aspiration catheter is thought to be beneficial for pancreatic manometry because of the ability to continuously aspirate saline.14 If wire-guided manometry is done first in the pancreatic duct, it is probably beneficial to leave the wire in the pancreatic duct and cannulate the bile duct alongside of the wire, to do biliary manometry. This will make sphincterotomy/stent placement in the pancreatic duct easier after biliary manometry. The wire might facilitate drainage of the pancreatic duct as well by keeping the PD opening patent. Care should be taken with pancreatic duct sphincterotomy. Unlike biliary sphincterotomy the length of sphincterotomy is relatively small, approximating to 5–6 mm. It is now recommended to place a small caliber pancreatic stent in most if not all patients with suspected sphincter of Oddi dysfunction who undergo pancreatic instrumentation of any kind, including those with normal pancreatic manometry.18,23 Three, 4, or 5 French stents have been used for this purpose. If a 3 Fr pigtail stent is placed one has to use 0.018 “wire in the pancreatic duct. Larger diameter wires will not allow for deployment of 3 Fr stents. Currently the pigtail end of the catheter is not marked. We recommend using a permanent marker to make a circumferential mark at the pigtail end of the stent so that when the stent is out of the scope one will know the end of the length of the stent to be placed in the pancreatic duct rather than deploying the entire stent in the pancreatic duct. Once the marking is visible, the stent is pushed out into the duodenum by lowering the elevator and moving the up/down wheel to the down position. Once the entire stent is out of the elevator of the scope, the inner wire is pulled out while keeping the pusher catheter in place. Care should be taken not to raise the elevator during this operation (tapered tip ERCP catheter) as there is a risk of pushing the pigtail portion of the stent into the pancreatic duct. If one is not comfortable and familiar with 3 Fr pigtail stents we recommend using a straight stent with inner flange removed so that the stent would migrate distally into the duodenum spontaneously similar to the unflanged 3 Fr stent. Bleeding both immediate and delayed is another major complication of sphincterotomy and is addressed in the chapter of sphincter95

SECTION 2 TECHNIQUES

otomy. If bleeding is seen, one could inject dilute epinephrine or sometimes even contrast material. A submucosal injection is required for tamponade effect. This could be done with the cannulating catheter itself and an injection with an injection needle catheter might not be necessary. In difficult situations hemoclips have been used. Bleeding is usually seen towards the apex of the sphincterotomy. In rare instances of continued major bleeding, octreotide infusion to reduce the splanchnic circulation might be beneficial. The risk of bleeding is especially high if one extends an existing sphincterotomy or in the presence of a periampullary diverticulum, and caution should be exercised. Papillary stenosis following sphincterotomy is a delayed complication more commonly seen with pancreatic sphincterotomy.

Post-sphincter of Oddi manometry patients should be monitored in the recovery area for at least 4–6 hours. In case of any complaints of significant pain or nausea, one should check serum amylase and lipase to help rule out procedural pancreatitis. Four-hour serum amylase and lipase levels have been shown to be predictive of postERCP pancreatitis.24 Patients could have pain only without pancreatitis after SO manometry and it might be reasonable to watch them overnight or to provide adequate analgesia.25 In case of suspected pancreatitis, we recommend adequate hydration and we routinely administer 1–2 liters of intravenous fluids over 6–8 hours. Analgesia is important. Patient-controlled analgesia might be beneficial. For detailed description of post-ERCP complications and management of the same, please refer to Chapter 5.

REFERENCES 1.

2.

3.

4.

5.

6. 7.

8.

9. 10.

11.

12.

13.

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Geenen JE, Hogan WJ, Dodds WJ, et al. The efficacy of endoscopic sphincterotomy after cholecystectomy in patients with sphincterof-Oddi dysfunction. N Engl J Med 1989; 320(2):82–87. Toouli J, Roberts-Thomson IC, Kellow J, et al. Manometry based randomised trial of endoscopic sphincterotomy for sphincter of Oddi dysfunction. Gut 2000; 46(1):98–102. Lans JL, Parikh NP, Geenen JE. Application of sphincter of Oddi manometry in routine clinical investigations. Endoscopy 1991; 23(3):139–143. Mariani A, Curioni S, Zanello A, et al. Secretin MRCP and endoscopic pancreatic manometry in the evaluation of sphincter of Oddi function: a comparative pilot study in patients with idiopathic recurrent pancreatitis. Gastrointest Endosc 2003; 58(6):847–852. Di F, V, Brunori MP, Rigo L, et al. Comparison of ultrasoundsecretin test and sphincter of Oddi manometry in patients with recurrent acute pancreatitis. Dig Dis Sci 1999; 44(2):336–340. Sherman S, Lehman GA. Sphincter of Oddi dysfunction: diagnosis and treatment. JOP 2001; 2(6):382–400. Fazel A, Burton FR. The effect of midazolam on the normal sphincter of Oddi: a controlled study. Endoscopy 2002; 34(1):78–81. Sherman S, Gottlieb K, Uzer MF, et al. Effects of meperidine on the pancreatic and biliary sphincter. Gastrointest Endosc 1996; 44(3):239–242. Goff JS. Effect of propofol on human sphincter of Oddi. Dig Dis Sci 1995; 40(11):2364–2367. Sherman S, Hawes RH, Madura JA, et al. Comparison of intraoperative and endoscopic manometry of the sphincter of Oddi. Surg Gynecol Obstet 1992; 175(5):410–418. Blaut U, Sherman S, Fogel E, et al. Influence of cholangiography on biliary sphincter of Oddi manometric parameters. Gastrointest Endosc 2000; 52(5):624–629. Raddawi HM, Geenen JE, Hogan WJ, et al. Pressure measurements from biliary and pancreatic segments of sphincter of Oddi. Comparison between patients with functional abdominal pain, biliary, or pancreatic disease. Dig Dis Sci 1991; 36(1):71–74. Toouli J, Roberts-Thomson IC, Dent J, et al. Manometric disorders in patients with suspected sphincter of Oddi dysfunction. Gastroenterology 1985; 88(5 Pt 1):1243–1250.

14. Sherman S, Troiano FP, Hawes RH, et al. Sphincter of Oddi manometry: decreased risk of clinical pancreatitis with use of a modified aspirating catheter. Gastrointest Endosc 1990; 36(5):462–466. 15. Sherman S, Hawes RH, Troiano FP, et al. Pancreatitis following bile duct sphincter of Oddi manometry: utility of the aspirating catheter. Gastrointest Endosc 1992; 38(3):347–350. 16. Guda N, Partington S, Freeman M. Does the type of current (pure vs blended) matter for post ERCP complications: a meta analysis. Gastrointest.Endosc. 61(5). 2005. Ref Type: Abstract. 17. Fazel A, Quadri A, Catalano MF, et al. Does a pancreatic duct stent prevent post-ERCP pancreatitis? A prospective randomized study. Gastrointest Endosc 2003; 57(3):291–294. 18. Freeman ML, Guda NM. Prevention of post-ERCP pancreatitis: a comprehensive review. Gastrointest Endosc 2004; 59(7): 845–864. 19. Thomas M, Catalano MF, Geenen JE. A prospective comparative stent study for prophylaxis of post ERCP pancreatitis: comparison of 5 Fr straight stent vs 3 FR pigtail stent. Gastrointest.Endosc 61(5), 196. 4–1-2005. Ref Type: Abstract. 20. Wehrmann T, Stergiou N, Schmitt T, et al. Reduced risk for pancreatitis after endoscopic microtransducer manometry of the sphincter of Oddi: a randomized comparison with the perfusion manometry technique. Endoscopy 2003; 35(6):472–477. 21. Craig AG, Omari T, Lingenfelser T, et al. Development of a sleeve sensor for measurement of sphincter of Oddi motility. Endoscopy 2001; 33(8):651–657. 22. Singh P, Gurudu SR, Davidoff S, et al. Sphincter of Oddi manometry does not predispose to post-ERCP acute pancreatitis. Gastrointest Endosc 2004; 59(4):499–505. 23. Tarnasky P, Cunningham J, Cotton P et al. Pancreatic sphincter hypertension increases the risk of post-ERCP pancreatitis. Endoscopy 1997; 29(4):252–257. 24. Testoni PA, Bagnolo F, Caporuscio S, et al. Serum amylase measured four hours after endoscopic sphincterotomy is a reliable predictor of postprocedure pancreatitis. Am J Gastroenterol 1999; 94(5):1235–1241. 25. Wong GS, Teoh N, Dowsett JD, et al. Complications of sphincter of Oddi manometry: biliary-like pain versus acute pancreatitis. Scand J Gastroenterol 2005; 40(2):147–153.

SECTION 2

Chapter

11

TECHNIQUES

Balloon Dilation of the Papilla Chan-Sup Shim

INTRODUCTION

TECHNIQUE

Endoscopic biliary sphincterotomy (EST) has become a cornerstone of therapeutic endoscopic retrograde cholangiopancreatography (ERCP) of the biliary tree. The most common indication for EST is to enlarge the access of the bile duct for stone extraction. The possible adverse consequences of EST include bacterial colonization and chronic inflammation of the biliary tree, the clinical relevance of which is poorly understood.1 While increased incidence of primary choledocholithiasis is an acceptable and relatively harmless longterm result of EST, some experts express concern about the risk of biliary malignancy. Longitudinal studies of patients who have had biliodigestive anastomoses and surgical sphincteroplasty suggest an incidence of late bile duct cancer between 5.6 and 7.4%.2,3 Endoscopic papillary balloon dilation (EPBD) is an alternative to EST for removing bile duct stones.4–7 In an effort to avoid permanent destruction of the biliary sphincter, EPBD seemed to be an attractive alternative to early investigators, such as Staritz and Meyer zum Buschenfelde, who first reported it in 1983.8 In this procedure, a balloon is inflated to enlarge the opening of the bile duct at the level of the biliary sphincter. The main theoretical advantage of this technique is that it does not involve cutting the biliary sphincter. Therefore, acute complications such as bleeding and perforation should be less likely, and the function of the biliary sphincter is also preserved.5 The enthusiasm for the potential advantages of EPBD over EST for the avoidance of short-term complications of bleeding and perforation, while preserving the biliary sphincter and possibly reducing the long-term sequelae of EST was soon dampened by reports of serious post-procedure pancreatitis.9 Therefore, EPBD was nearly abandoned as a treatment for bile duct stones, but its use was revived with the development of laparoscopic cholecystectomy. With several groups reporting favorable results using EPBD for stone extraction, conservation of the biliary sphincter regained popularity in the 1990s. In 1995, Mac Mathuna et al. reported good results with EPBD for treating bile duct stones in 100 consecutively treated patients.4,5 The results of subsequent randomized, controlled trials comparing EST to EPBD are conflicting. Some authors have reported an increased incidence of post-procedure pancreatitis, while others have not, and an argument has been presented against EPBD and its failure to provide adequate access for extracting difficult (large or multiple) bile duct stones.6,7,10 The final success rates for EST and EPBD are comparable; the reported success rates of stone removal are 81–99% for EPBD 4,6,7,10 and 85–98% for EST.6,7 Randomized trials comparing EPBD with EST suggest that EPBD is at least as effective as EST in patients with small to moderate-sized bile duct stones.5,6,10–18

During the informed consent process, the risks and benefits of EPBD compared to EST should be discussed with patients and consent obtained if EPBD is being considered. Preprocedural antibiotics are administered as appropriate. The procedure is performed using a standard duodenoscope. During the procedure, identification of candidates for whom the EPBD is indicated can be simplified by comparing the bile duct stone size to the diameter of the duodenoscope on the same radiographic image; patients with stones that have a diameter equal to or less than that of the duodenoscope are considered eligible. After diagnostic ERCP and selective bile duct cannulation a standard 0.025 or 0.035 inch guidewire is inserted into the bile duct. After removing the cannula, an 8-mm balloon-tipped catheter (Fig. 11.1) (Hurricane RX dilation balloon or Wire-guided CRETM balloon; Boston Scientific, Natick, MA, USA; balloon length 3 cm, maximum inflated outer diameter 8 mm) is passed over the guidewire, positioned across the papilla, and inflated with diluted contrast medium at a pressure of 8 atm (Fig. 11.2). The balloon is expanded slowly with a mixture of contrast medium and saline (50/50) paying close attention to the waist of the balloon. When the waist disappears, the inflation is stopped. Care must be taken to avoid rapid application of excessive pressure (Fig. 11.2). The dilation is maintained for 15–30 seconds. When the bile duct is less than 8 mm in diameter a 6-mm × 2-cm balloon can be used. Other dilator balloons can also be used (e.g. Hurricane Rx dilation balloon; Boston Scientific, Natick, MA, USA, PET balloon; ConMed Endoscopic Technologies, Billerica, MA, USA, Quantum balloon; Cook Endoscopy Winston-Salem, NC, USA). The smaller balloons pass readily through a diagnostic duodenoscope, such as an Olympus JF-240, whereas the 24 Fr balloon requires a biopsy channel of at least 3.2 mm. After papillary dilation, the stones are removed using Dormia baskets and/or retrieval balloon catheters (Fig. 11.2). Mechanical lithotripsy (BML-3Q-1, -4Q-1; Olympus Medical System Corporation, Tokyo, Japan) can be used to fragment stones if they are over 10 mm in diameter as determined from the cholangiogram. If the stones are too large to engage within a mechanical lithotripsy basket, an electrohydraulic lithotripter can be in the next session used to crush the stones after introducing a baby cholangioscope (CHFBP30; Olympus Medical Systems, Tokyo, Japan) through the dilated papilla. The initial ERCP session is performed within 60 min, and if complete clearance of the stones fails, a biliary stent or nasobiliary catheter can be inserted to prevent stone impaction. Data from outside the US suggest that pancreatic duct stent placement is not required after EPBD is performed. The optimal size of the balloon in EPBD has not yet been established. Most studies have reported results with 8-mm diameter 97

SECTION 2 TECHNIQUES

A

B

Fig. 11.1 Dilating kit consisting of 8-, 10-, 12-, 15-, 18-, and 20-mm balloons, syringe/gauge assembly and inflation handle. dilation balloons, although some studies have used balloons up to 15 mm in diameter.8 Theoretically, the larger the balloon, the easier it is to extract large stones, although more complications after dilation may be likely, and pancreatitis or damage to the sphincter may be expected. However, there is insufficient information to support these concerns. In contrast, Staritz et al. reported no complications, even after using 15-mm balloons.8 Other points of EPBD to be clarified are the optimal pressure for dilation, the optimal duration of dilation, and the optimal number of dilations. Other operators have reported the use of different protocols, such as a maximal pressure of less than 1.5 atmospheres,5 a duration of 45–60 seconds after the disappearance of the balloon waist,7 or repeated dilation protocols.4 It is still unknown which protocol is best for the complete removal of stones and the preservation of sphincter function. To answer these questions, more studies that focus on the various EPBD techniques are needed.

D

C

INDICATIONS FOR AND LIMITATIONS OF ENDOSCOPIC BALLOON DILATION In the recent meta-analysis by Baron et al., the incidence of bleeding was significantly less after EPBD compared to EST.16 Clinically significant post-EST bleeding occurs in 2–5% of EST patients.17,18 In addition, patients with coagulopathy and those requiring anticoagulation within 3 days of the procedure are at increased risk for bleeding.17 Thus, transient discontinuation of anticoagulation, correction of coagulopathy with fresh frozen plasma, or platelet transfusion are frequently used to avoid bleeding after EST, though these measures might be inadequate to prevent it. EPBD provides a useful alternative to EST in such cases. No articles have described bleeding after EPBD.4,6,7,10 In light of this, EPBD should be considered a viable alternative to EST in patients with an underlying coagulopathy or the need for anticoagulation following EST, as such patients have a higher incidence of post-EST bleeding.17 EPBD may significantly reduce the risk of bleeding compared to EST in patients with advanced cirrhosis and coagulopathy. In these patients, EPBD is recommended over EST for treating choledocholithiasis.19 Another population in which EPBD may be an attractive option is those patients who refuse blood transfusion for religious reasons, and patients with difficult anatomy that prevents safe orientation of the papillotome for EST (e.g. prior Billroth II gastrectomy, Fig. 11.3; or intradiverticular location of the papilla, Fig. 11.4).14 Bergman et al. reported a randomized trial of EPBD and EST for removing bile duct stones in patients with a prior Billroth II gastrectomy.14 Compared to patients with a normal anatomy, patients with prior Billroth II gastrectomy had a significantly increased risk of 98

E

Fig. 11.2 Endoscopic balloon dilation in a patient with multiple small CBD stones. A The endoscopic cholangiogram demonstrated multiple stones in the common bile duct. After diagnostic ERCP, a 0.035-inch guidewire was passed through the ERCP catheter into the common bile duct, and the catheter was removed. B–D A balloon-tipped catheter is inserted into the common bile duct over the guidewire. The balloon is inflated once it is located across the papilla. The biliary sphincter can be seen as a “waist” in the balloon. C The biliary sphincter is considered adequately dilated if the waist has disappeared completely. E After removing the balloon and guidewire, stones are extracted using a Dormia basket.

Chapter 11 Balloon Dilation of the Papilla

A

B

C

D

E

F

G

H

I

J

K

L

Fig. 11.3 Serial endoscopic images A–H and retrograde cholangiograms I–L show endoscopic papillary balloon dilation of the biliary sphincter in a patient with two bile duct stones and prior Billroth II gastrectomy. A Endoscopy shows an image of the papilla, upside-down. B Two filling defects are seen on the cholangiogram. C–F The balloon is advanced over a guidewire and is inflated with diluted contrast. G Transient oozing of blood is observed at the papilla after deflating the balloon, but it does not develop into serious hemorrhage. H–L A stone is removed with a basket catheter.

bleeding after EST. Early complications occurred in 19% of the patients who underwent EPBD as compared to 39% of the patients who underwent EST. Endoscopic stone removal in patients with a prior Billroth II gastrectomy and Billroth II anastomosis poses one of the great challenges to the biliary endoscopist. Several methods

and instruments have been developed to enable EST in Billroth II patients.10 Currently, the most widely accepted technique consists of a needle-knife sphincterotomy over a previously inserted endoprosthesis.20 Compared to standard EST in the normal anatomic situation, all of these techniques are more demanding and probably 99

SECTION 2 TECHNIQUES

A

B

C

D

E

F

Fig. 11.4 Endoscopic images of EPBD in a patient with a CBD stone and a papilla with an intradiverticular location. A The major papilla is located in the diverticulum. B Small EST is performed. C,D After cannulation of a guidewire, the balloon catheter is inflated over the guidewire up to 15 mm. E,F After removing the balloon, the stone is evacuated with a basket catheter through the widely opened papilla.

associated with a smaller sphincterotomy incision, less successful stone removal, and a higher rate of acute complications.14 When EST is used for such patients, careful consideration must be given to the direction and length of the incision, and a high level of skill is required to avoid severe complications. With EPBD, however, once a catheter is inserted into the common bile duct, the balloon catheter is simply inserted and the balloon is inflated. Therefore, patients with Billroth II anatomy apppear to be especially suited for stone removal using EPBD.

LIMITATIONS OF EPBD The success of stone removal and procedure time varies between EPBD and EST. Vlavianos et al. performed a univariate logistic regression analysis assessing the success of bile duct stone removal after EPBD. The following parameters were analyzed: sex, age, randomization, presentation with jaundice, acute cholangitis or acute pancreatitis, diameter of the common bile duct (CBD) on the initial cholangiogram, number of stones, and size of the largest stone. Of these, age, diameter of the CBD, and size and number of stones were significantly associated with success (Table 11.1). Multivariate logistic regression analysis showed that only the size of the largest stone was an independent predictor of success for duct clearance. On average, these patients had a 12-mm diameter CBD and up to two 10-mm stones. These were taken as cut-off points in the statistical analysis.11 Larger stones are more difficult to remove using EPBD because the biliary opening is enlarged to a greater degree with EST. In fact, in many patients in the studies examined in the analysis by Baron et al. comparing EPBD to EST, patients were excluded based on 100

Variable a

Odds ratio

95% CI

Likelihood ratio c2

P Value

0.98

0.95–1.00

3.88

0.049

CBD diameter (mm) <12 ≥12

3.24 1

1.20–8.72

8.14

0.017

Number of stones ≤2 >2

2.08 1

0.90–4.80

7.5

0.024

Size of stone (mm) <10 ≥10

10.0 1

1.14–44.64

17.72

<0.001

Age

Table 11.1 Parameters predicting success of EPBD from the univariate analysis a The success decreases with increasing age. CI, confidence interval; CBD, common bile duct.

stone size or number. Patients were excluded if CBD stones had a diameter = 12,21 = 14,22 = 15,10 or = 20 mm,23 or if there were more than five23 or ten10 stones. The limitation of EPBD for extracting large bile duct stones is highlighted by the more frequent need for mechanical lithotripsy as an adjunctive procedure. This likely lengthens the procedure time. Indeed, in three studies used in this analysis, the protocol called for the use of mechanical lithotripsy in the EPBD group if the diameter of any CBD stone was = 8,5 = 11,12 or = 12 mm.24 Therefore, EPBD may be more technically difficult to perform and more time-consuming than EST.21

Chapter 11 Balloon Dilation of the Papilla

In an analysis classifying the patients according to stone size, both treatment approaches ultimately achieved similar success rates and needed similar numbers of treatment sessions for patients with stones less than 10 mm in diameter. For patients with stones over 10 mm in diameter, EPBD required a significantly greater mean number of treatment sessions than EST due to the technical difficulty in retrieving large stones after EPBD. EPBD is a possible alternative to EST, especially in patients with impaired hemostasis. However, large stones may be difficult to remove with EPBD alone. Therefore, ideal patients for selecting EPBD over EST are those with a limited number of CBD stones (≤ 3), CBD stones with a maximum diameter = 10 mm, and minimally dilated bile ducts.10,11,23,24 It is also important to use extreme caution when EPBD is applied in the following clinical settings: the presence of severe acute cholangitis, a history of previous or ongoing acute pancreatitis, age = 50 years, and difficult biliary cannulation,25 especially because of reports describing fatal pancreatitis in younger patients.26 In patients with severe cholangitis, one should consider placing a biliary stent to ensure adequate drainage if EPBD is performed. In the other clinical settings mentioned, placement of a pancreatic duct stent could be considered to prevent post-ERCP pancreatitis.

COMPLICATIONS Early complications, defined as those occurring within 24 h of the procedure, are pancreatitis, bleeding, infection (cholangitis or cholecystitis), and perforation. The meta-analysis of randomized, controlled trials by Baron et al. showed the early complication rate of EPBD was comparable to EST for removing common bile duct stones during ERCP.16 Overall, the early complication rates were similar in EPBD and EST, 10.5 vs 10.3%, p = 0.9 (Table 11.1). Of

note, the bleeding rate was higher in the EST group (2.0 vs 0%, p = 0.001), while the rates of infection (2.7% for EPBD vs 3.6% for EST, p = 0.3) and perforation (0.4 vs 0.4%, p = 1.0) were similar (Table 11.2). The rate of pancreatitis was higher in the EPBD group (7.4 vs 4.3%, p = 0.05) (Table 11.2). One patient death occurred in each group, yielding a mortality rate of 0.2%. In those patients suspected of having developed immediate EPBD-related complications, complete blood counts, liver enzymes, and serum amylase are measured within 24 h after the procedure. Abdominal roentgenograms, US, and CT are obtained if needed. Hemorrhage is one of the most common and serious complications of EST, and the presence of coagulopathy is one of the risk factors for hemorrhage. In the meta-analysis by Baron et al.,16 bleeding was clearly reduced when EPBD was performed as compared to EST for the removal of CBD stones, but nearly all comparative studies of EPBD and EST excluded patients with coagulopathy and liver disorders. When bleeding occurs in cirrhotic patients, they may also develop further complications, such as hepatic failure. Komatsu et al. treated 24 cirrhotic patients with CBD stones using EPBD.7 Although hemostasis was impaired due to liver dysfunction, no bleeding occurred and all patients responded well to treatment. In particular, no complications were seen in four patients with ChildPugh class C, or in six patients with severe coagulopathy. The rate of EST-related hemorrhage was 30% (6/20), whereas the rate for EPBD-related hemorrhage was 0% (p = 0.009). Regarding the rates of hemorrhage in relation to Child-Pugh class, most (n = 5) of the bleeding complications occurred in patients with Child-Pugh class C cirrhosis, while bleeding occurred in only one patient with ChildPugh B cirrhosis.19 Based upon these results, EPBD appears to be the preferred strategy in patients with CBD stones and an underlying coagulopathy and those who require full anticoagulation within 72 h

Vlavianos11

Fujita 22

Arnold 23

Minami 5

Bergman 6

Ochi 10

Natsui 24

Yasuda 12

Total

Pancreatitis (EPBD)

5/103 (1 severe)

15/138

6/30 (2 severe)

2/20

7/101 (2 severe)

0/55

4/70

2/35

41/552 7.4%a

Pancreatitis (ES)

1/99 (severe)

4/144

3/30

2/20

7/101 (1 severe)

2/55

3/70

2/35

24/554 4.3%a

Bleed (EPBD)

0

0

0

0

0

0

0

0

0/552 0%b

Bleed (ES)

0/99

2/144

2/30

0/20

4/101

0/55

2/70 (1 severe)

1/35

11/554 2.0%b

Infection (EPBD)

2/103

4/138

3/30

0/20

4/101

0/55

2/70

0/35

15/552 2.7%c

Infection (ES) 20/554

1/99

11/144

0/30

0/20

5/101

0/55

3/70

0/35 3.6%c

Perforation (EPBD)

0/103

0/138

0/30

0/20

2/101

0/55

0/70

0/35

2/552 0.4%

Perforation (ES)

0/99

0/144

0/30

0/20

1/101

1/55

0/70

0/35

2/554 0.4%

Death (EPBD)

0

0

0

0

1

0

0

0

1/552

Death (ES)

1

0

0

0

0

0

0

0

1/554

Table 11.2 Procedure-related complications based on prospective trials comparing Endoscopic Balloon Dilation (EPBD) and Endoscopic Sphincterotomy (EST) for treating choledocholithiasis a

p = 0.05 (pancreatitis in EPBD vs. EST. bp = 0.001 (bleeding in EPBD vs. EST. cp = 0.3 (infection in EPBD vs. EST.

101

SECTION 2 TECHNIQUES

of stone removal27 since these patients are at higher risk for postsphincterotomy bleeding following EST.17 Procedure-related pancreatitis needs to be addressed. In recent years, five prospective randomized controlled trials of EPBD versus EST have been performed.6,11,22,23 The frequency and severity of postEPBD pancreatitis are summarized in Table 11.3.28 Of these, the Dutch6 and United Kingdom11 studies showed similar efficacy and safety between the two methods. Their incidence of pancreatitis was similar in patients undergoing EPBD and EST, in the range of 5 to 7%. In the Japanese study,22 the rate of pancreatitis was slightly higher with EPBD than with EST; however, there were no reports of severe pancreatitis and all patients recovered with conservative treatment. In addition, Mac Mathuna et al.4 and Komatsu et al.7 conducted large-scale studies, but they were not randomized controlled trials; the incidence rates of pancreatitis were 5 and 7%, respectively. No severe pancreatitis or fatalities occurred (Table 11.3). The mechanism of post-EPBD hyperamylasemia and pancreatitis is not clear, although it seems to be multifactorial. Balloon compression of the papilla or the pancreatic duct orifice may provoke peripapillary edema or sphincter of Oddi spasm.15,23 Bile duct cannulation per se or transpapillary manipulation (stone extraction, nasobiliary drainage) may also induce edema or spasm. The peri-papillary edema or spasm may in turn obstruct the flow of pancreatic juice and eventually induce pancreatic edema or pancreatitis associated with hyperamylasemia.15,23 Contrast medium injection or cannula-

tion of the pancreatic duct is also likely to have some effect on the pancreas and pancreatic secretions.29 Several studies have examined the risk factors for post-ERCP pancreatitis. The most important risk factors were related to either patient characteristics or the ease of cannulation. In the study by Bergman et al.15, none of these factors was associated with EPBDinduced pancreatitis. However, a univariate analysis revealed that stone size, distal bile duct stricture, mechanical lithotripsy, multiple endoscopic sessions, additional EST, and endoscopic nasobiliary drainage after EPBD were significant risk factors for the development of acute pancreatitis after EPBD (Table 11.4), although in the multivariate analysis, mechanical lithotripsy was the only risk factor for pancreatitis after EPBD (Table 11.5).30.31 Yasuda et al. reported an increased rate of hyperamylasemia after EPBD in patients who underwent mechanical lithotripsy as compared to patients in whom stones were fragmented with extracorporeal shock-wave lithotripsy (ESWL), a fact that might be explained by the reduced manipulation of the papillary complex in the latter group.12 Sugiyama et al. reported an incidence rate of more than 30% in patients with a history of pancreatitis,25 which may limit the use of EPBD for treating CBD stones in the setting of acute pancreatitis. Younger patients have a higher risk of post-ERCP pancreatitis,32 though many of the EPBD studies have not included patients younger than 50 years old, the very group for whom concern exists on the long-term complications of EST. In addition, some studies

PANCREATITIS SEVERITY Investigator (Ref. No.)

Year

No. of patients

Patients with pancreatitis (%)

Mild

Moderate

Severe

Death

Bergman (6) DiSario (26) Arnold (23) Vlavianos (11) Fujita (22) Tsujino (28)

1997 2004 2001 2003 2003 2004

101 117 30 103 144 304

7 (7.0) 18 (15.4) 6 (20.0) 5 (4.9) 15 (10.4) 15 (5.0)

5 7 4 2 12 8

0 5 0 2 3 7

2 6 2 1 0 0

0 2 0 0 0 0

Table 11.3 Frequency and severity of post-EPBD pancreatitis in randomized studies

Risk factor

Patients with pancreatitis (11/156)

Patients without pancreatitis (145/156)

p

Pre-endoscopic papillary balloon dilation related Stone size (≥10 mm) Distal bile duct stricture Age <60 years Female sex Previous cholecystectomy Periampullary diverticulum Bile duct diameter (mean ± SD [mm]) Multiple stones (≥2) Pancreatic contrast injection (≥1)

9 (81.8) 3 (27.3) 4 (36.4) 7 (63.6) 4 (36.4) 4 (36.4) 17.1 ± 3.9 7 (63.7) 7 (63.7)

54 (48.6) 6 (5.4) 50 (45) 50 (45) 29 (26.1) 32 (28.8) 14.8 ± 4.5 62 (55.8) 62 (55.9)

0.036 0.008 0.83 0.24 0.46 0.51 0.31 0.73 0.71

Post-endoscopic papillary balloon dilation related Mechanical lithotripsy Multiple endoscopic session (≥2) Additional EST ENBD after EPBD

7 (63.6) 6 (54.5) 3 (27.3) 4 (36.4)

25 (22.5) 25 (22.5) 2 (1.8) 16 (13.5)

0.003 0.02 0.00 0.046

Table 11.4 Risk factors for pancreatitis after endoscopic papillary balloon dilation in a univariate analysis 102

Chapter 11 Balloon Dilation of the Papilla

Risk factor

Adjusted odds ratio

95% CI

P

Mechanical lithotripsy Multiple ERCP session (≥2) Stone size (≥10 mm) Multiple stone (≥2) Female sex Age ≥60 years

5.25 2.81 1.24 1.44 1.92 0.58

1.29–21.31 0.67–11.86 0.27–5.84 0.16–12.65 0.48–7.63 0.43–7.82

0.02 0.16 0.35 0.74 0.36 0.68

Table 11.5 Risk factors for pancreatitis after endoscopic papillary balloon dilation in a multivariate analysis

have used gabexate mesylate, a protease inhibitor, to prevent postERCP pancreatitis.22 Although gabexate mesylate was given to both the EST and EPBD groups, it might have reduced the severity of pancreatitis in the EPBD group.33 Several studies have suggested that pancreatic duct stent placement reduces the risk of post-ERCP pancreatitis in high-risk patients.29,30,32 Recently, pancreatic duct stent placement has been used in a non-randomized comparative trial of patients undergoing EPBD to remove CBD stones.33 Although no significant difference was seen in the rate of pancreatitis when pancreatic duct stents were placed, pancreatic duct stent placement might be useful for preventing post-ERCP pancreatitis in young patients undergoing EPBD. Acute pancreatitis is usually mild and occurs in approximately 6% of patients after EPBD for bile duct stone extraction. EPBD often results in hyperamylasemia (25%), although this is usually clinically inconsequential. Hyperamylasemia, however, may represent pancreatic irritation or latent pancreatic injury. Particular care is necessary when EPBD is performed on younger patients, those with a history of pancreatitis, and patients with a non-dilated bile duct, or when cannulation is difficult, given the high frequency of hyperamylasemia. While performing EPBD, careful attention should also be paid to gentle handling of the papilla, avoiding unnecessary pancreatic opacification, and the injection of contrast medium into the pancreatic duct. In addition to pancreatic duct stent placement after EPBD, potential safeguards for prevention of pancreatitis after EPBD include gradual inflation of the balloon at a low pressure, intravenous infusion of isosorbide dinitrate34 and temporary placement of a nasobiliary drainage catheter, which may act by preventing pancreatic duct obstruction from residual stones or papillary edema.35 Infection is another potential problem that can be challenging to the endoscopist. The incidence of cholangitis and cholecystitis appears to be higher following EST than in EPBD, although in the analysis by Baron et al. the difference did not reach statistical significance. In patients with severe cholangitis, one should consider placing a biliary stent to ensure adequate drainage if EPBD is performed. Currently, cholecystectomy is recommended in patients with gallstones after EST, as there is a high rate of acute cholecystitis. Several authors have reported that the incidence of cholecystitis is significantly lower after EPBD than after EST.6,10 Natsui et al. diagnosed acute cholecystitis in 25.0% of EST patients and in 0% of EPBD patients who had gallbladder stones after endoscopic treatment.24 It is hasty to conclude that cholecystectomy is unnecessary for all patients with gallbladder stones after EPBD, as most gallbladder stones migrating to the bile duct are probably less likely to pass spontaneously into the duodenum and more likely to cause cholangitis. Perforation is a very rare, but potentially fatal, complication following EPBD. In the meta-analysis by Baron et al., there was no

difference between EST and EPBD in rates of perforation (0.4% each).16 Recurrent bile duct stones are a late complication of EPBD and EST. Several studies have shown that 3–20% of patients who underwent EST developed recurrent bile duct stones during a median period of 9–15 years.36 The permanent destruction of the sphincter mechanism by EST results in ascending bacterial infection of the biliary tract, which might be involved in the formation of brown pigment stones. In contrast, manometric studies have shown that EPBD does not completely restore the sphincter function to its intact state, but could preserve it better than EST.5,10,12 Therefore, we would expect EPBD to reduce the recurrence of bile duct stones as compared to EST in patients without an intact gallbladder.37

LARGE BALLOON DILATION AFTER MINIMAL BILIARY SPHINCTEROTOMY (EST) EPBD was first initiated for the purpose of extracting common bile duct stones while minimizing damage to the sphincter of Oddi. According to the stone size, both EPBD and EST approaches ultimately achieve similar success rates and need similar numbers of treatment sessions for patients with stones less than 10 mm in diameter. However, for patients with stones over 10 mm in diameter, EPBD requires a significantly greater mean number of treatment sessions than EST. This is due to the technical difficulty in retrieving large stones after EPBD, as the papillary orifice cannot be enlarged to the same extent as after EST. The limitation of EPBD for extracting large bile duct stones is highlighted by the more frequent need for mechanical lithotripsy as an adjunctive procedure, which likely lengthens procedure time. To overcome the limitations of conventional EPBD, “large balloon dilation after minimal biliary sphincterotomy” has been devised. Balloon dilation after minimal EST is effective for retrieving large biliary stones without the use of mechanical lithotripsy (Figs 11.5 and 11.6). Although EST with a large incision may be effective in reducing the need for mechanical lithotripsy, a large incision has a higher risk of perforation and possibly a higher risk of bleeding than standard EST. This innovative, novel method incorporating slow dilation of the papilla to a large diameter, can provide a larger opening than a large EST (Fig. 11.5) and prevents perforation and bleeding. This method of stone retrieval is easy to perform and can effectively treat large or multiple bile duct stones (Fig. 11.6). The balloons employed in this technique are larger than those currently used for standard endoscopic balloon dilation of the bile duct (Fig. 11.1), but similar to those used in preliminary studies of balloon dilation of the papillary sphincter.7,9 Although the technical aspects of EST are well described, the criteria for creating a sphincterotomy that is adequate for removing large stones have not been established. It is usually impossible to evaluate the adequacy of a sphincterotomy based on anatomic parameters alone. Data from an earlier era when sphincterotomy was performed at laparotomy indicate that sphincteroplasty was generally superior to sphincterotomy in terms of adequacy.38 Moreover, complete elimination of sphincter function by EST is not always possible. Biliary manometric studies after EST confirm that sphincterotomy is incomplete in most cases.39 EST has been performed after endoscopic balloon (8–10 mm) dilation in cases when dilation was inadequate.5 Therefore, this 103

SECTION 2 TECHNIQUES

A

B

D

E

C

Fig. 11.5 A case of large balloon dilation after minimal EST in a patient with multiple large extrahepatic bile duct stones. A Retrograde cholangiogram shows multiple large stones that completely fill the extrahepatic bile duct. B,C After minimal EST, a large balloon is inflated up to 18 mm over the guidewire and through the sphincterotomized papilla. D The papillary orifice is dilated fully and the bile duct mucosa is readily seen. E The cholangiogram shows a completely evacuated extrahepatic bile duct after sweeping out the multiple stones with the balloon catheter.

A

B

C

D

E

F

Fig. 11.6 A huge stone is impacted at the bile duct bifurcation. A,B After sphincterotomy, large balloon dilation was performed up to 18 mm. C,D Removal with a large basket catheter and mechanical lithotriptor failed, and retrieval of the large stone was attempted with a retrieval balloon catheter C. The stone was pulled out with a retrieval balloon catheter C and extracted from the papilla D. E,F The huge stone (4.5 × 2.0 cm) was finally evacuated without crushing.

104

Chapter 11 Balloon Dilation of the Papilla

technique is unique, as balloon dilation is performed after EST, using large-diameter balloons, to extract bile duct stones that resisted removal with conventional techniques. Mechanical lithotripsy is another alternative for removing such stones, with an overall success rate of over 80%,40 although this procedure can be lengthy and requires a second session in 30% of cases.41 Using a therapeutic duodenoscope (TJF 240; Olympus Medical System, Tokyo, Japan), the endoscope is advanced to the duodenum. It is important to use a duodenoscope with a large working channel (4.2 mm in diameter), for easier passage of large balloons. The difference from conventional EPBD is that EST is performed before the balloon catheter is inserted. In most cases, a major EST is not required and a minimal is sufficient. This is because the purpose of EST is not to dilate the sphincter of Oddi (SO), but to direct the direction of SO dilation. When using a large balloon catheter to dilate the SO without EST, it is difficult to predict the direction in which the SO will dilate. Therefore, by performing a minimal EST, the direction of papilla dilation can be predicted. Another reason for minimal EST is to prevent post-procedure pancreatitis by minimizing the peri-papillary edema after dilating the papilla. After EST, a guidewire is inserted into the bile duct and a balloon catheter is guided over the wire. The diameter of the balloon catheter should be 15–20 mm. A balloon catheter that was initially developed for dilation in pyloric stenosis (Wire-guided CRETM balloon; Boston Scientific, Natick, MA, USA) can be useful (Fig. 11.1). The diameter of the balloon catheter is determined by the size of the bile duct stone and the size of the bile duct proximal to the tapered segment. EST with a small incision up to the pancreatic orifice is performed over a guidewire. Endoscopic papillary dilation is performed slowly with a large balloon (maximum of 20 mm in diameter) to match the size of the bile duct. Approximately 1 min of balloon dilation time is sufficient. Dilation with large-diameter balloons is performed at the same session after EST. Over-the-guidewire type balloons for esophageal/ pyloric dilation are used. The balloon catheters are passed over a guidewire and positioned at the biliary orifice; the middle portion of the balloon is gradually filled with diluted contrast medium under endoscopic and fluoroscopic guidance to maintain the correct position and to observe the gradual disappearance of the waist in the balloon, which is taken to indicate progressive dilation of the orifice. Once the waist has disappeared, the balloon is kept in position for 20–45 seconds, after which it is deflated and removed. A standard stone basket or retrieval balloon catheter is then used to remove the stones. In a few cases, the waist in the balloon decreases, but does not disappear completely, in this case keeping the balloon in place for over 45 seconds may be useful. Stones are then retrieved from the bile duct with a retrieval balloon catheter or a stone basket. After stone retrieval, washing the bile duct with normal saline may help to detect any remaining stones. A dilation time lasting less than 1 minute may actually induce bleeding, which may be attributable to insufficient compression time by the balloon. After dilating the papilla for 1 min, the balloon catheter is removed and a basket is inserted to remove the stone. If the stone is too large to pass through the papilla, mechanical lithotripsy can be used. In those patients in whom stone clearance is still impossible, a nasobiliary drain or biliary stent can be placed and another session can be performed at a later time using large diameter balloons.

Ersoz et al. reported that dilation with a large-diameter balloon after EST was useful for clearing bile duct stones in patients with a tapered distal bile duct. By using a larger balloon, the distal duct can be shaped into a near square, facilitating stone removal. Patients with distal CBD stenosis or a narrow common bile duct are at risk of bleeding, perforation, or bile duct injury after complete balloon dilation. Therefore, it seems prudent to avoid excessive dilation in patients with risk of balloon dilation beyond the width of the common bile duct. In one study this technique was successful in 89% of patients. In the remaining 11%, stone removal was achieved easily after mechanical lithotripsy. EST followed by dilation with a large-diameter balloon was also effective for clearing 95% of large-diameter (15–28 mm) bile duct stones (Fig. 11.6), with mechanical lithotripsy required in only two patients.42 In 19 of 24 patients, extrahepatic bile duct stones were removed without endoscopic mechanical lithotripsy (EML) after dilating the ampulla.43 Stone retrieval was successful in all cases without the need to crush large stones up to 14 ± 3 mm.44 Standard EST is the classical treatment modality for extrahepatic bile duct stones. However, for large bile duct stones (usually >15 mm in diameter), EML is used to break the large stones into small fragments. If multiple large bile duct stones are present, repeated EML is needed to remove the extrahepatic bile duct stones. However, if the ampulla can be dilated widely (Fig. 11.5), such large stones can be removed without the use of EML (Figs 11.5 and 11.6). Patients in whom bile duct stones cannot be cleared because of a tapered distal bile duct and patients with large, square, or barrel-shaped stones would benefit from this procedure. The most common complications of this procedure are mild cholangitis, pancreatitis, bleeding, and perforation. Complications occurred in 15.5% of patients in one study,40 with most (10.3%) being mild and self-limiting. Moderately severe bleeding developed in three patients (5.2%), which was attributed to EST, and all recovered without the need for surgery. Perforation did not occur in any patient who underwent dilation with a large diameter balloon.45 Mild pancreatitis developed in two patients (3.4%). Theoretically, the risk of pancreatitis by large balloon dilation after minimal sphincterotomy is less than balloon dilation alone. It is probable that after EST, the force exerted by balloon dilation is directed more toward the common bile duct than the pancreatic orifice. Minimal EST before a large balloon dilation might decrease the risk of pancreatitis as compared to dilation alone. Bleeding occurs in 2–5% of patients undergoing EST to remove bile duct stones.46,47 In contrast, no significant bleeding has been observed after endoscopic balloon dilation.6,7 The bleeding rate (9%) reported by Ersoz et al. was higher than the rate reported for standard EST and EPBD.40 Therefore, bleeding is a potentially important complication, particularly in patients with a tapered distal bile duct. Studies of larger series of patients are warranted to determine the frequency of this complication. In conclusion, large balloon dilation after minor EST may be helpful in the case of bile duct stones that are difficult to extract using EST and conventional techniques. This procedure could reduce the sessions of EML and shorten the procedure time, and thus serve as an effective treatment modality for multiple large extrahepatic bile duct stones.

105

SECTION 2 TECHNIQUES

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106

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Chapter 11 Balloon Dilation of the Papilla

38. 39.

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41.

42.

papillary balloon dilatation for bile duct stones: late complications after stone removal. Gastrointest Endosc 2005; 61(5):AB209. Kozloff L, Joseph WL. Transduodenal sphincteroplasty for biliary tract disease, Am J Surg 1975; 41:125–130. Wehrman T, Wiewer K, Lembrecke B, et al. Effect of endoscopic sphincterotomy on Oddi manometry results in patients with or without papillary stenosis. Gastroenterol 1995; 33:662–668. Cipoletta L, Costamagna G, Bianco MA, et al. Endoscopic mechanical lithotripsy of difficult common bile duct stones. Br J Surg 1997; 84:1407–1409. Sorbi D, Van Os EC, Aberger FJ, et al. Clinical application of a new disposable lithotripter: a prospective multicenter study. Gastrointest Endosc 1999; 49:210–213. Ersoz G, Tekesin O, Ozutemiz AO, et al. Biliary sphincterotomy plus dilation with a large balloon for bile duct stones that are difficult to extract. Gastrointest Endosc. 2003 Feb; 57(2):156–159.

43. Yoo BM. Large balloon-lithotripsy (LB-L) in patients with large extrahepatic bile duct tones. Gastrointest Endosc 2005; 61: AB244. 44. Minami A, Okuyama T, Hitose S. Small sphincterotomy combined papillary dilatation with large balloon permits retrieval of large stones without lithotripsy second report. Gastrointest Endosc 2005; 61:AB213. 45. Hwang JH, Kim YG, Lee KC, et al. Endoscopic sphincterotomy plus endoscopic papillary large balloon dilatation for large bile duct stones. Korean J Gastrointest Endosc 2006; 32:184–189. 46. Leung JW, Chan FK, Sung JJ. Endoscopic sphincterotomy induced hemorrhage: a study of risk factors and the role of epinephrine injection. Gastrointest Endosc 1995; 42:550–554. 47. Freeman ML. Complications of endoscopic biliary sphincterotomy: a review. Endoscopy 1997; 29:288–297.

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Chapter

12

TECHNIQUES

Biliary Sphincterotomy Horst Neuhaus

INTRODUCTION Diagnostic ERCP has been increasingly replaced by MRCP and endoscopic ultrasound which are comparable in accuracy but are non-invasive or less invasive, respectively. ERCP is now mainly performed for therapeutic pancreaticobiliary interventions. Endoscopic sphincterotomy (EST) of the biliary sphincter is used for the treatment of disorders of the papilla of Vater or to facilitate adjunctive procedures in the bile duct. Since the introduction of EST in 1973, a variety of complementary methods have been developed for the management of ductal obstruction. They have become invaluable tools for minimally invasive therapy of biliary diseases and have gained widespread acceptance throughout the world. The need for EST depends on the indication. Data from several prospective, multicenter trials have allowed the determination of the clinical, anatomical and technical parameters and their relation to the efficacy and safety of EST. Outcomes following EST can be affected by ductal cannulation prior to EST, by subsequent therapeutic interventions, and by the expertise of the endoscopist.

DESCRIPTION OF THE TECHNIQUE Premedication, duodenoscopy and the approach to the papilla are the same as for diagnostic ERC, as discussed in Chapters 5 and 8. The use of a therapeutic endoscope is recommended since the large diameter instrumentation channel allows for insertion of large diameter stents and accessories required for therapeutic interventions. The initial use of a standard sphincterotome for deep bile duct cannulation is recommended for several reasons. First, when it is anticipated that a sphincterotomy will be needed, exchange to a sphincterotome from another catheter is avoided. Secondly, it allows variable upward tip deflection in order to introduce the tip of the catheter into the biliary orifice; the tip deflection is then relaxed to achieve deep cannulation. Steerable catheters are comparably effective and safe for this technique but their additional use does not seem to be cost-effective for routine use.1 Two randomized controlled trials showed success rates of 84% and 97%, respectively, for primary cannulation with sphincterotomes which were superior to the use of standard catheters with no significant differences in safety.2,3

Instruments (see also Chapter 4) The type of the sphincterotome should be selected according to the individual anatomic situation and the preference of the endoscopist. According to a prospective US multicenter trial standard reusable devices are satisfactory for most cases of EST and yield cost savings as compared to disposable triple lumen sphincterotomes.4 However these results are not directly transferable to other health

care systems and an individual cost analysis is recommended for each center. Tapered devices, which require smaller wires (0.025″ or less) can be easier to insert into the papilla but are also more prone to cause tissue trauma and contrast infiltration than those with a more blunted tip. A recently developed ultra-smooth tapered rounded polished tip may overcome this potential problem (Fig. 12.1). Modern sphincterotomes provide a lumen for insertion of a guidewire and an integrated hub for contrast injection. These devices allow repeated injection of contrast media without need for guidewire removal. This approach can be very helpful in difficult cannulation or in targeting ductal strictures with the wire under fluoroscopic guidance. Sphincterotomes with a preloaded guidewire are convenient for the assistant and may accelerate the procedure. Recently developed technologies which utilize short-length guidewires seem to be additionally helpful since they reduce the over-the-wire exchange to a short part of the total device length while locking the wire. They offer the option of guidewire manipulation by the endoscopist which can be advantageous depending on the expertise of the operator and the assistant. Sphincterotomes also differ in cutting wire length, wire characteristics and shaft stiffness. A short, 20 mm cutting wire can be precisely controlled but it tends to draw the cutting direction toward the 2 o’clock position. Contact with the sphincter may be inadequate, thus making the cutting difficult in some situations. However, the advantage of shorter cutting wires (e.g. exposed length of 25 mm) over a 30 mm wire device is the reduction of risk of an uncontrolled large cut when inserted too deep into the bile duct. In addition, the proximal part of a long cutting wire may come into contact with the elevator of the duodenoscope or duodenal wall; the former causes wire breakage when electocautery current is applied. This problem can be overcome by use of a sphincterotome that is coated on the proximal part of the cutting wire (Fig. 12.2). A thin monofilament wire provides a clean, sharp cut but may break more easily than a braided wire during application of electrocautery. There are no formal trials that compare the efficacy and safety of these different devices. As experience grows, each endoscopist will develop preferences for a limited array of standard accessories depending on expertise, skill of assistants and patient selection. The use of special sphincterotomes can be limited to particular cases. A thin device with a 4.0 Fr ultra taper tip is useful after failed cannulation using standard techniques in the setting of a small papilla, suspicion of a narrow ductal orifice or difficulty in achieving proper cutting orientation. The latter problem can be overcome by the use of a rotatable sphincterotome. This instrument utilizes a specially designed handle that allows for controlled tip rotation. Sphincterotomes with a tip length of more than 5 mm can occasionally be helpful when there is difficult access to the papillary orifice as seen. in patients with a juxtapapillary duodenal diverticulum or altered surgical anatomy. Push-type or sigmoid shaped 109

SECTION 2 TECHNIQUES

A

Fig. 12.1 Smooth, tapered, rounded, polished tip of a sphincterotome with colored markers that allow for determination of the depth of insertion.

Fig. 12.2 Sphincterotome with a coated proximal portion of the cutting wire avoids direct contact with the elevator of the duodenoscope and to the duodenal wall. A

B

Fig. 12.3 A Approach to the papillary orifice with the tip of a sphincterotome. B Bowing the sphincterotome to allow its insertion towards 11 o’clock into the opening of the common bile duct. sphincterotomes have been developed for EST in patients with Billroth II anatomy.

Procedure The papilla is usually approached with the sphincterotome from a distance so that its precurved distal part is evident upon exiting the endoscope. Alternatively the tip of the sphincterotome is gently introduced into the papillary orifice. A short, straight position of the duodenoscope facilitates a precise control of the device. Subsequent bowing of the tip usually allows its insertion towards 11 o’clock into the opening of the common bile duct (Figs 12.3A, 12.3B). Straightening the tip and gently withdrawing the endoscope results in further anchoring the tip of the device within the common bile duct. It can be then further advanced to achieve deep cannulation. Such a smooth, direct approach may fail and the procedure can become difficult and frustrating. Careful injection of contrast may allow visualization of the biliary anatomy for targeted guidance of the tip 110

B

Fig. 12.4 A Passage of a guidewire with a radiopaque hydrophilic tip in the direction of the bile duct under fluoroscopic guidance prior to contrast injection. B Careful injection of dilute contrast medium allows confirmation of common bile duct cannulation; a filling defect in the distal bile duct is seen. of the sphincterotome or insertion of a guidewire. However repeated injections may induce edema of the papilla and increase the likelihood of post-ERCP pancreatitis. Alternatively, a guidewire can be gently passed in the direction of the bile duct under endoscopic and fluoroscopic guidance without contrast injection. For this approach guidewires with a soft tip, preferably hydrophilic, should be used to reduce the risk of ductal injury (Figs 12.4A, 12.4B). A recent large randomized trial compared biliary cannulation with a guidewire through a sphincterotome with a sphincterotome alone. The success rates were comparably high for both methods but the rate of pancreatitis was significantly lower in the guidewire group.5 However all procedures were performed by a single endoscopist and these results require confirmation in a multicenter trial. Cannulation of the bile duct with a sphincterotome with or without use of a guidewire should succeed in approximately 90% of the cases. Failures are mainly caused by a difficult access to the papilla because of anatomical variations or previous gastroduodenal surgery. Ampullary tumors or impacted stones creating a bulging papilla can also impair the approach to the papillary orifice or deep ductal cannulation. For these cases lifting the roof of the papilla with the adjustable tip of the sphincterotome and use of a hydrophilic guidewire are helpful in selective cannulation and controlled cutting (Figs 12.5A, 12.5B). When cannulation fails, a variety of additional techniques including precut sphincterotomy and rendezvous procedures have been established. Their appropriate use allows access to the biliary system in nearly all cases. However, the risk of complications increases in particular when “access” papillotomy is performed, which should therefore be limited to experienced endoscopists. Availability and local expertise will determine how long to persist in difficult biliary cannulation and when to switch to precut techniques.6 Details are described in Chapters 8 and 9. After deep cannulation has been confirmed by contrast injection, a guidewire should be advanced to the proximal biliary system in order to secure ductal access for subsequent maneuvers and exchange of accessories. The tip of the sphincterotome is then slightly bowed so that it is in contact with the roof of the papilla. Not more than 5 mm of the cutting wire should be inside the papilla so that only a small amount of tissue will be cauterized. This approach improves the cutting action and avoids a rapid large incision (“zipper”) which can occur when pure cutting current is used. Newer electrosurgical generators have largely eliminated this complication. Most sphincterotomes have endoscopically visible markers at the distal part of the catheter which allow one to determine the depth of insertion of

Chapter 12 Biliary Sphincterotomy

A

B

C

D

E

F

G

H

Fig. 12.5 A Bulging papilla due to an impacted bile duct stone. B The orifice of the papilla is located at the distal, bottom of the bulging papilla: the roof is lifted by bending the sphincterotome after tip insertion into the orifice, the cutting wire is bowing towards 3 o’clock. C Fluoroscopy indicating a short, straight position of the duodenoscope corresponding to the endoscopic image of Figure 12.5B. D Fluoroscopy after rotation of the dial of the duodenoscope to the left while advancing the scope slightly toward the long scope position; the corresponding endoscopic view is seen in Figure 12.5E. E Due to the maneuver shown in Figure 12.5D the papilla has been placed to the left side and the cutting wire is bowing towards 11 o’clock; only a few millimeters of cutting wire are inside the papilla indicating an excellent position for cutting. F Sphincterotomy with sequential cutting by use of the “ENDO-CUT” mode; the cut can be extended a few more millimeters to the visible junction between the duodenal wall and the intraduodenal portion of the papilla; the lumen of the common bile duct can already be seen above the black marker of the sphincterotome. G Fluoroscopy showing balloon extraction of a small bile duct stone. The balloon is positioned just above the stone. The stone is removed by pulling downwards in the direction of the long axis of the common bile duct. H Endoscopic view after extraction of the intact bile duct stone (located at the right side of the papilla). The papilla is edematous after previous stone impaction.

the cutting wire into the bile duct (Fig. 12.1). It is generally believed that orientation of the cutting wire in the range between the 11 o’clock and 1 o’clock position, reduces the likelihood of bleeding and perforation. In spite of great efforts by the accessory manufacturers to develop sphincterotomes with cutting wires that automatically cut along these directions, sphincterotomes may still orient in the 3 o’clock direction (Fig. 12.5B, 12.5C). To overcome this problem, the papilla has to be placed on the left side and along the 10 or 11 o’clock position. This maneuver can be achieved by rotating the left-right dial to the left while advancing the duodenoscope slightly into the “long” endoscope position (Fig. 12.5D, 12.5E). The choice of electrosurgical current for EST is a source of controversy. The combination of high cutting current blended with a low coagulation current is most frequently used. Creation of edematous, extensively whitened or blackened tissue during EST is evidence of suboptimal cutting and may predispose to post-procedural pancreatitis or sphincter scarring. A previous trial indicated that pure-cut electrocautery current is safer than blended current in terms of post-ERCP pancreatitis without increasing the bleeding rate.7 Similar results were obtained in a prospective, controlled trial which found an incidence of mild post-EST pancreatitis in 3.2% of patients who underwent EST with pure-cutting current compared to 12.9% in groups randomized to EST with blended current or purecutting current initially followed by blended current.8 These differences were statistically different, although the study has been criticized because of the extraordinarily high incidence of pancreatitis after standard EST with blended current. In contrast, a recent randomized, controlled trial in 246 patients did not demonstrate a significant difference in the frequency of post-procedural pancreatitis between those patients who underwent EST with pure-cutting current or blended current.9 There was a significant increase in minor bleeding episodes in the pure-cut group with equal numbers of delayed episodes of bleeding in each arm. In another series, the incision was begun using cutting current and finished using blended current but was not associated with a decrease in the risk of postERCP pancreatitis.10 An alternative electrocautery option is the use of the “ENDO CUT” mode of the ERBE electrosurgical generator in which cutting and coagulation current are alternated by the intrinsic software. A potential advantage of this method is a stepwise cutting action which allows precise control of the direction and length of the incision. This replaces the technique whereby current is applied in short pulses controlled by foot pedal activation, and which is recommended for pure-cut or blended current to reduce the risk of a “zipper” cut. A large retrospective analysis suggested that the microprocessor-controlled EST is associated with a significantly lower frequency of intra-procedural bleeding but had no impact on clinically evident hemorrhage.11 The size of EST can vary and depends on the diameter of the distal portion of the common bile duct as well as the indication for sphincterotomy. During cutting, pressure on the papillary roof is provided by upward lifting of the slightly bowed sphincterotome. EST should be continued only when the wire can be clearly seen and when it is directed between the 11 and 1 o’clock position. Guidance and repositioning of the device should be mainly controlled with the tip and the shaft of the endoscope which is maneuvered with the right hand of the operator like the handle of a knife. A small incision seems to be appropriate for placement of an endoprosthesis in malignant biliary obstruction whereas complete splitting of the sphincter should be attempted for treatment of bile duct stones and sphincter of Oddi dysfunction (SOD) to decrease the risk of 111

SECTION 2 TECHNIQUES

A

B

A B

C Fig. 12.6 A Papilla in a patient with bile duct stones; slight bulging of the roof suggests that the proximal border of the intraduodenal portion is above the mucosal fold. B After completion of EST the lumen of the common bile duct can be seen above the inserted guidewire; there does not appear to be any residual roof of the papilla and further extension of cutting could cause duodenal perforation.

recurrences and EST-related stenosis of the papilla. However, the correlation between the length of cutting and the incidence of early or late complications of EST has not been determined in formal trials. Biliary sphincterotomy should be limited to the junction between the duodenal wall and the intraduodenal portion of the papilla of Vater which is sometimes difficult to determine since there is no reliable endoscopic “landmark.” The incision should be also finished if the inner lumen of the bile duct is completely visible or the bended tip of the sphincterotome can be pulled through the papilla without any resistance (Figs 12.5F–12.5H, 12.6A, 12.6B). In view of modern techniques of lithotripsy, a large hazardous EST is rarely required. If a wide opening to the common bile duct is needed it may be safer to perform a small to moderate sized incision and then dilate the incision with a balloon catheter rather than to increase the size of the opening by cutting (Figs 12.7A–12.7D) (see Chapter 11). Compared with other indications, the risk of complications of EST is usually low in patients with a dilated common bile duct and in the presence of ductal stones, especially when the papilla is large and protruding due to an impacted stone. Extension of a previous biliary sphincterotomy may be required for the treatment of recurrent bile duct stones or recurrence of symptoms after SOD. The technique of EST in this setting does not differ from that when EST is performed initially. Data from anecdotal reports and small case series were controversial regarding the risk of hemorrhage after extension of a previous EST and suggested that the incidence of bleeding was increased during a post-sphincterotomy period of approximately one week due to a resultant increased vascularity. However recent large prospective studies did not find that extension of a previous EST is an independent risk factor for hemorrhage.12,13

EST in patients with difficult anatomy Juxtapapillary duodenal diverticula are found in 10–15% of patients undergoing ERCP. Depending on the location of the papilla, cannulation of the bile duct can be difficult and may require special techniques such as insertion of the tip of the endoscope into the diverticulum, use of sphincterotomes with a long nose or pulling the papilla out of a diverticulum with biopsy forceps or a second catheter. After successful deep cannulation it is strongly recommended that EST is performed over a guidewire. This approach facilitates 112

D

Fig. 12.7 A Papillary orifice after EST in a patient with multiple giant bile duct stones. Mechanical lithotripsy was required followed by removal of large fragments. B Balloon dilation of the papilla after EST using an 18 mm diameter balloon. C Fluoroscopy corresponding to Figure 12.7B showing the fully inflated balloon filled with diluted contrast media. D Smooth extraction of large stone fragments with a basket catheter through the widely open sphincterotomy orifice.

cutting in the direction of the bile duct which may otherwise be difficult to determine due to the altered anatomy. Moderate bending of the tip of the sphincterotome with a few millimeters of the cutting wire inside the papilla exposes the papillary roof to allow for a controlled incision. Any direction of the cutting wire towards the base of the diverticulum should be avoided (Figs 12.8A, 12.8B). Data from a recent large, retrospective analysis suggested that bleeding after EST was an independent risk factor associated with juxtapapillary duodenal diverticula.14 The approach to patients with post-surgical anatomy is discussed further in Chapter 24. Use of a duodenosope in patients with Billroth II anatomy allows a better visualization of the papillary roof and improves the maneuverability of accessories because of the availability of the elevator. Precurved sphincterotomes should not be used for initial cannulation of the bile duct in these patients because they direct the tip of the catheter towards the pancreatic duct orifice. This is because the papilla is rotated 180 degrees as compared to native anatomy. A straight, new ERCP cannula and a straight guidewire with a hydrophilic tip aim in the direction of the bile duct and facilitate entry into the biliary orifice. After successful placement of guidewire, a rotatable, push-type or sigmoid shaped sphincterotome can be used for EST. In spite of use of these special accessories the correct direction of the cutting wire towards the desired 5 o’clock position (in this situation) can remain difficult because of the reversed anatomic orientation. It is usually easier to place a 7 Fr biliary endoprosthesis and to sever the papillary roof with a needle knife incision using the endoprosthesis as a guide. A similar approach is required when performing EST in the setting of

Chapter 12 Biliary Sphincterotomy

A

B

Fig. 12.8 A Papilla at a 6 o’clock position on the rim of a juxtapapillary diverticulum; the bridge above the papilla inside the diverticulum represents the papillary roof; there is no clear landmark of the proximal border of the intraduodenal portion. B The blue marker of the sphincterotome is visible during EST and indicates that only a few millimeters of the cutting wire are inside the papilla; passing the sphincterotome over a guidewire and inserting only a small amount of cutting wire into the duct during EST allows precise control of cutting; the correct direction alongside the bridge will avoid cutting towards the base of the diverticulum; slight bulging of the papillary roof above the wire indicates that the incision can be extended just beyond the mucosal fold.

loop gastrojejunostomy in patients with duodenal or pyloric obstruction. Reaching the papilla with a duodenoscope in patients with a Roux-en-Y anatomy can be very difficult. The approach can be better achieved with a pediatric colonoscope, a push enteroscope or a double-balloon endoscope. However therapeutic interventions are impaired because of the limited transmission of manipulations via the long insertion tube and the limited array of available accessories for these endoscopes. If the papilla is inaccessible due to altered anatomy or can not be cannulated even after precut techniques, the rendezvous method should be considered. A percutaneous transhepatic tract is established with placement of a 7 Fr catheter into the common bile duct. Thereafter duodenoscopy is repeated. A percutaneously inserted 400 cm long guidewire is passed antegrade through the papilla and grasped endoscopically with a snare passed through the endoscope. In cases where there is a long afferent loop this technique allows one to pull the tip of the endoscope towards the papilla by applying percutaneous tension on the guidewire while simultaneously applying tension on the wire exiting the endoscope. The sphincterotome is passed over the guidewire for subsequent EST. In selected cases, the sphincterotome can be passed percutaneously for the performance of antegrade sphincterotomy under endoscopic retrograde visualization.15 In rare cases, even the rendezvous method does not allow one to endoscopically reach the papilla. Antegrade sphincterotomy under percutaneous transhepatic cholangioscopic and fluoroscopic guidance can be performed, though this technique is potentially hazardous and should be restricted to centers with large expertise in percutaneous transhepatic interventions.

Alternatives to EST Balloon sphincteroplasty is discussed in detail in Chapter 11. Compared with EST, endoscopic balloon dilation of the biliary sphincter (EBD) offers the theoretical advantage of sphincter preservation in particular in young patients with bile duct stones. A meta-analysis of several randomized, controlled trials of EBD versus EST for biliary stones showed no significant difference between the success rates (94.3% vs 96.5%) and overall complication rates (10.5% vs 10.3%) of

either technique.16 Compared to EST, EBD caused less bleeding (0% vs 2.0%, p = 0.001) but a higher rate of post-ERCP pancreatitis (7.4% vs. 4.3%, p = 0.05). In addition, patients undergoing EBD were more likely to require mechanical lithotripsy for bile duct clearance (20.9% vs 14.8%, p = 0.014). This meta-analysis was performed prior to a recent publication of a large prospective US multicenter randomized trial comparing EBD with EST for extraction of bile duct stones.17 The success rates were comparably high in both groups but the overall morbidity (17.9% vs 3.3%) and severe morbidity (6.8% and 0%) were significantly higher in patients who had undergone EBD. There were two deaths (1.7%) due to pancreatitis following dilation and none for sphincterotomy. The complication rate of EBD was higher in the US trial than in previous series, which may be explained by a selection of younger patients who had a mean age of 47 years. Technical details of EBD may also influence the clinical outcome. The procedure has not yet been standardized in terms of the inflation pressure, the duration of inflation, and the number of dilations. The biliary sphincter function may be preserved but the clinical relevance of this potential advantage remains undetermined. There are limited data on the long-term outcome after EBD. According to a recent trial the frequency of stone recurrence was higher after EBD compared to EST at mid-term evaluation, but over the long term the estimated probability of stone recurrence tended to be higher in patients who had undergone EST.18 Based on these data, EBD can not be recommended as a routine procedure at this time. However, it should be considered as a valuable alternative to EST in patients with coagulopathies and those in whom the endoscopic approach is difficult (e.g. Billroth II anatomy or a duodenal diverticulum).19 For each individual patient, the risks of pancreatitis and bleeding must be weighed when choosing between EBD and EST, especially in younger patients.

INDICATIONS Well-established indications for EST are common bile duct stones, acute cholangitis, severe acute biliary pancreatitis, palliation of ampullary malignancies, facilitation of biliary stent placement, and treatment of SOD (Box 12.1). A variety of randomized, controlled 113

SECTION 2 TECHNIQUES

BOX 12.1 INDICATIONS FOR BILIARY ENDOSCOPIC SPHINCTEROTOMY Common bile duct stones Palliation of obstruction due to malignant ampullary neoplasm as alternative to stent placement (selected cases) Facilitation of biliary stent placement (especially multiple stents) for malignant or benign common bile duct obstruction Sphincter of Oddi dyskinesia (SOD), benign papillary stenosis Biliary leaks Miscellaneous conditions (choledochocele, sump syndrome, biliary parasites) Access for peroral choledochoscopya During endoscopic resection of ampullary neoplasmsa Access for cannulation of the pancreatic duct after failure of standard cannulation techniquesa a

Poor evidence to support sphincterotomy for these indications.

trials demonstrated the efficacy and safety of EST for these biliary diseases. Choledocholithiasis is still one of the major indications for biliary sphincterotomy in order to allow endoscopic stone extraction using basket or balloon catheters. The success rate of ductal clearance for standard procedures is approximately 90% depending on patient selection. Adjunctive techniques for intracorporeal or extracorporeal lithotripsy further increase the clearance rates.20 A recent trial demonstrated that EST can be safely and effectively performed for the treatment of bile duct stones even in patients 90 years of age or older.21 Previous restrictions of EST to elderly patients or those with previous cholecystectomy are, however, no longer valid. In a prospective, US multicenter trial on EST a group of 487 patients underwent sphincterotomy for bile duct stones within 30 days of laparoscopic cholecystectomy. They were significantly younger (on average 51 versus 64 years) and the common bile duct was smaller in diameter (8.7 mm vs 10.0 mm) compared to a group of 1113 patients with their gallbladder in situ or with previous cholecystectomy who received EST for the same indication. The complication rate of EST was significantly lower in the former group (4.9% versus 9.5%).12 These results demonstrate that EST can be safely performed in young patients with bile duct stones shortly before or after laparoscopic cholecystectomy. Acute cholangitis due to choledocholithiasis or ductal stenosis can be effectively treated by EST in conjunction with additional procedures such as removal of ductal stones or placement of drainage catheters or endoprostheses. Early EST has also been established in patients with severe acute biliary pancreatitis (see Chapter 31). A recent meta-analysis of four randomized, controlled trials showed significantly lower morbidity and mortality rates in patients who underwent EST compared to those who were treated conservatively.22 According to this trial 8 patients need to be treated by EST to avoid one severe complication and 26 to prevent one death. Another established indication of EST is biliary sphincterotomy as an initial therapeutic step before dilation and stent placement for palliation of malignant biliary obstruction. However sphincterotomy is not obligatory for this indication unless multiple large bore stents are inserted (see Chapter 16). Nevertheless a small cut seems to be 114

safe and is frequently performed to facilitate access to the biliary system for scheduled exchanges of plastic prostheses. Biliary sphincterotomy has become the method of choice for treatment of patients with documented SOD (see Chapter 34). Cannulation and cutting can be more difficult in patients with SOD compared to other indications for sphincterotomy due to small size of the papilla and a narrow orifice. Atraumatic cannulation of the papilla, careful manipulation of accessories, and precise control of the sphincterotomy incision while cutting over a guidewire is mandatory to minimize trauma of the tissue. For these reasons, and because of the increased risks, only experienced endoscopists should perform EST for SOD. The level of evidence is lower for a variety of other indications for EST that are listed in Box 12.1. Most of these indications have been established on the basis of prospective, uncontrolled trials or appropriate retrospective analyses. Randomized, controlled trials seem to be difficult to perform for many of these biliary disorders for a variety of reasons.23,24

CONTRAINDICATIONS Contraindications to ERCP and EST include an uncooperative or unstable patient, inability of the patient to provide informed consent, uncorrected coagulopathy, and a newly created gastrointestinal anastomosis. Contrast hypersensitivity is not considered as a contraindication to EST, but prophylactic intravenous application of corticosteroids may be considered. Preprocedure coagulation studies are strongly recommended and coagulopathy must be corrected before sphincterotomy. The presence of liver cirrhosis and use of aspirin or other nonsteroidal anti-inflammatory drugs do not appear to be important predictors of bleeding.12 However antiplatelet drugs such as clopidogrel and ticlopidin should be interrupted for at least seven days before elective sphincterotomy depending on the individual clinical risks. EST using a pull sphincterotome should not be performed if proper positioning of the sphincterotome with its tip in the bile duct can not be documented. Cutting should be avoided if the position of cutting wire can not be seen or if the tip of the sphincterotome is bowing in a the wrong direction because of difficult anatomy. If these problems can not be resolved with changing the position of the device or other maneuvers, then balloon dilation of the biliary sphincter should be considered as an alternative to EST. The indication for EST should be reconsidered for the individual case if the level of evidence is fair or poor.

COMPLICATIONS AND THEIR MANAGEMENT Chapter 6 covers complications of ERCP in detail. A large, prospective US multicenter trial was published on early complications following EST (Table 12.1). In this trial Freeman et al. reported a total complication rate of 9.8% in 2347 patients.12 Acute pancreatitis was the most frequent major complication of EST and was seen in 5.4% of all cases. Hemorrhage, perforation, cholangitis and cholecystitis occur less frequently and may have decreased compared with previous reports. Other prospective, multicenter trials of ERCP and related risk factors have been published, though in contrast to the study by Freeman et al. diagnostic procedures were also included. The reported data do not allow a separate analysis of the EST-related morbidity.25–27 Various risk factors, prophylactic measurements, early recognition and appropriate treatment should be considered in order to

Chapter 12 Biliary Sphincterotomy

Type of complication

Incidence (%)

Severe complications

Fatal complications

Pancreatitis Hemorrhage Perforation Cholangitis Cholecystitis Miscellaneous Total

5.4 2.0 0.3 1.0 0.5 1. 1 9.8

0.4 0.5 0.2 0.1 0.1 0.3 1 .6

<0.1 0.1 <0.1 <0.1 <0.1 0.2 0.4

Adjusted odds ratioa (95% CI) Anticoagulation ≤3 days after EST Coagulopathy before EST Cholangitis before EST

5.1 (1.6–16.7) 3.3 (1.5–7.2) 2.6 (1.4–4.9)

Mean case volume of the endoscopist ≤1 EST / week 2.2 (1.1–4.2) Bleeding during EST 1.7 (1.2–2.7)

Table 12.3 Risk factors for EST-related hemorrhage12 a

Table 12.1 Complications of biliary endoscopic sphincterotomy in 2347 patients12

Adjusted odds ratioa (95% CI) Suspected SOD Precut EST Difficulty of cannulation Younger age Repeated pancreatic duct injection

5.1 (2.7–9.2) 4.3 (1.7–10.9) 2.4 (1.1–5.4) 2.1 (1.4–3.3) 1.4 (1.0–1.8)

Table 12.2 Risk factors for EST related pancreatitis12 a

Significant in a multivariate analysis.

Authors

Freeman et al. (12)

Rabenstein et al. (31)

Patients for EST

2347

1335

Complication rates Endoscopist’s case volume Low (≤1 per week) 11.1%a High (>1 per week) 8.4%a

9.3%b 5.6%b

Table 12.4 Complications related to endoscopists’ case volume a,b

p < 0.05.

Significant in a multivariate analysis.

decrease the risks of EST. In an individual patient it may be difficult to determine if complications were caused by EST, by bile duct cannulation or by adjunctive therapeutic interventions.

EST-related pancreatitis

The definition of pancreatitis varies between different studies.12,25,26 According to a consensus definition, ERCP-related pancreatitis is diagnosed in patients with new or worsened abdominal pain and a serum amylase or lipase that is three or more times the upper limits of normal 24 hours after the procedure and requires at least two days of hospitalization.28 In most series the reported rates of post-ERCP pancreatitis range from 1% to 7%.25–27 EST-related risk factors for pancreatitis that were identified in a multivariate analysis of the study by Freeman et al. are summarized in Table 12.2.12 These parameters and preventive measurements should be considered when patients are selected for EST to reduce the risk of unnecessary pancreatitis. Pharmacologic prophylaxis may be considered in high-risk candidates for ERCP. Data from a recent meta-analysis suggests that the incidence of pancreatitis after ERCP can be reduced by the administration of either somatostatin or gabexate mesilate.29 In spite of these results pharmacologic prophylaxis is rarely performed in clinical practice because of its limited efficacy and high costs. In addition, a high number of cases have to be treated to avoid one case of pancreatitis. A variety of electrophysical factors can influence the efficacy and safety of EST. They include different waveforms and power settings of modern electrosurgical generators but also the cutting wire contact length. The clinical relevance of these factors is less clear as was previously discussed in this chapter. In view of conflicting results the selection of electrosurgical current for biliary EST should be based primarily on endoscopist preference. The impact of prophylactic pancreatic stent placement on prevention of post-ERCP pancreatitis was recently studied in a meta-

analysis of five controlled trials. A total of 481 patients were included who had at least one of the following risk factors for pancreatitis: suspected and/or confirmed SOD, difficult cannulation, or EBD for stone extraction within the same procedure. The incidence of postERCP pancreatitis was significantly lower in patients who had received a temporary pancreatic stent compared to those in whom a stent was not placed (5.8% vs 15.5%, p = 0.003).30 The analysis indicated that 10 patients have to be treated to avoid one case of pancreatitis. Although these data do not allow a separate analysis for EST, pancreatic stent placement is strongly recommended for patients undergoing EST with risk factors for post-ERCP pancreatitis. Treatment of EST-related pancreatitis does not differ from the management of pancreatitis of other etiologies. It includes shortterm parenteral nutrition, antibiotics in cases of pancreatic necrosis determined by CT scan, analgesia, and management of related complications. Repeat ERCP should be considered in patients with residual bile duct stones, ongoing obstructive jaundice or cholangitis.

EST-related hemorrhage Clinically relevant hemorrhage can be defined as the presence of melena, hematochezia, or hematemesis associated with a hemoglobin decrease of at least 2 g/dl or the need for blood transfusions. The incidence of EST-related bleeding in prospective trials ranges from 0.8% to 2%.12,25,26 In approximately half of the cases hemorrhage is delayed and occurs at 24 hours, though it can occur up to one week or more after EST. Risk factors for hemorrhage include coagulopathy before EST, anticoagulation within three days after EST, cholangitis before EST, and bleeding during EST (Table 12.3).12 In addition, EST performed by endoscopists who perform less than approximately one EST per week is associated with a higher rate of bleeding as compared to those performed by endoscopists with higher EST volumes. The impact of the expertise of the endoscopist on the procedure-related morbidity was also reported in a recent retrospective analysis of 1335 ESTs (Table 12.4).31 A multivariate analysis of an 115

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Italian multicenter trial found precut procedures and obstruction of the papillary orifice were risk factors for EST-related hemorrhage.25 The pattern of bleeding following EST during the procedure did not seem to predict the risk of late bleeding.32 Oozing bleeding after EST frequently stops spontaneously and further therapeutic interventions can usually be performed without treatment of bleeding. However, ongoing hemorrhage and/or pulsatile bleeding, which arises from an aberrant branch of the retroduodenal artery, require endoscopic hemostasis. Repeated duodenal irrigation is mandatory for endoscopic localization of the bleeding site and to facilitate application of appropriate hemostatic interventions. The cutting wire of a sphincterotome can be used to apply pure coagulation to the apex of the bleeding site. Endoscopic injection of saline-epinephrine solution or fibrin glue at the proximal edge of the incision site is usually effective in achieving hemostatis in the setting of severe hemorrhage.33,34 Multipolar or bipolar electrocoagulation is another option to treat hemorrhage but should be carefully performed at an appropriate distance from the pancreatic orifice; alternatively pancreatic drainage can be secured with a pancreatic duct stent. Placement of conventional hemoclips through a side-viewing endoscope is technically difficult but can be performed with a therapeutic channel duodenoscope.35 Bending of the tip and lifting of the elevator of the instrumentation channel should be minimized to allow release of the clips from the rigid applicator tip. Placement of a biliary endoprosthesis or a nasobiliary drain should be considered if interventions used to treat bleeding cause obstruction of the common bile duct. In rare cases endoscopic management of EST-related hemorrhage fails; angiographic transcatheter embolization or even laparotomy may be required, though the latter is associated with significant morbidity and mortality.

Fig. 12.9 Plain abdominal x-ray showing air in the retroperitoneal space parallel to the spine; perforation was caused by a forceful stone extraction after fracture of a basket during mechanical lithotripsy; the distal part of the broken basket can be seen in the common hepatic duct; filling of the biliary system and the duodenum with contrast injection via a nasobiliary probe demonstrates no leakage and justifies a conservative therapeutic approach.

EST-related perforation Perforation of the bile duct or the pancreatic duct with the sphincterotome, guidewire, balloon, or other accessories can usually be managed by endoscopic or percutaneous placement of drainage catheters or stents into the bile duct and pancreatic duct. EST-related retroduodenal perforations are uncommon and mainly caused by “zipper cutting” which can be avoided by limited insertion of the cutting wire into the papilla and use of modern controlled-cut electrosurgical generators. Perforation occurs when EST is performed beyond the duodenal wall. Reported perforation rates for ERCP are 0.3% to 0.6% and those related specifically to EST are 0.3%.12,36,37 A univariate analysis of a recent retrospective trial indicated that EST, SOD, a dilated common bile duct and biliary stricture dilation are risk factors for perforation.37 Most cases are diagnosed during the ERCP procedure by the finding of free intra-abdominal or retroperitoneal air on fluoroscopy, or post-procedurally on plain abdominal x-rays. Clinical presentation is variable and can be mild. Perforation should be considered in case of ongoing abdominal pain, signs of peritonitis, fever, leukocytosis, and an elevated C-reactive protein. Abdominal CT scan with luminal contrast into the duodenum is the method of choice for the diagnosis and stratification for management. Conservative treatment with temporary parenteral nutrition and administration of antibiotics is appropriate if an ongoing leak is excluded. Otherwise an interdisciplinary approach should be undertaken.38 A nasoduodenal tube and a nasobiliary or percutaneous transhepatic drain are useful to prevent gastric, pancreatic, and biliary fluid from entering into the retroperitoneal space (Fig. 12.9). Percutaneous drainage with large-bore tubes is indicated in cases of 116

abscess formation in the retroperitoneum. Laparotomy is usually required when these measurements fail and/or there is evidence of sepsis or peritonitis.

EST-related cholangitis Prophylactic administration of antibiotics to prevent cholangitis is recommended in patients with incomplete biliary drainage, particularly those patients with proximal stenoses due to hilar tumors. Nasobiliary catheters or endoprostheses should be placed if there is any evidence of incomplete bile duct clearance after EST or adjunctive interventions for biliary stones. Repeated ERCP may be needed in those cases of delayed cholangitis due to biliary obstruction. Continuous bile duct irrigation via nasobiliary drains may be useful for management of patients with purulent cholangitis.

Long-term consequences of EST Five studies comprising a large number of patients, a high follow-up rate, and follow-up periods of more than six years after EST, were recently reviewed.39 The overall rate of late symptoms which can be attributed to EST ranges from 6% to 24%, with the rate being nearly 10% in three of the five trials. Common bile duct stones and papillary stenosis were the most common complications. Stones can usually be removed after extension of the previous EST or after balloon dilation. Papillary stenosis can be managed by extension of the sphincterotomy. Cautery-induced distal bile duct strictures can be managed by balloon dilation and placement of one or more biliary stents.40 Cholangitis caused by reflux of duodenal contents into the

Chapter 12 Biliary Sphincterotomy

biliary system is rare but can occasionally require creation of a surgery for a biliodigestive anastomosis. A correlation between the size of EST and these late complications can not be determined from the current literature. Concerns about long-term biliary carcinogenic risks following sphincterotomy were not demonstrated in a large case controlled Scandinavian study.41

RELATIVE COSTS The cost–benefit ratio of EST depends on its indication. In view of high success rates, low procedure-related morbidity, and frequent

avoidance of surgery EST seems to be cost-effective. The choice of reusable or disposable sphincterotomes can have a significant impact on procedural cost but this practice varies from institution to institution and country to country.4 The use of simple and inexpensive devices is not necessarily cost-effective if these devices have a high failure rate and need to be exchanged for sphincterotomes that allow more options such as guidewire insertion and contrast injection. Depending on the local situation limiting therapeutic ERCP to high volume centers should be cost-effective because of the associated higher success rates and lower complication rates.12,31

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Laasch HU, Tringali A, Wilbraham L, et al. Comparison of standard and steerable catheters for bile duct cannulation in ERCP. Endoscopy 2003; 35:669–674. Schwacha H, Allgaier HP, Deibert P, et al. A sphincterotomebased technique for selective transpapillary common bile duct cannulation. Gastrointest Endosc 2000; 52:387–391. Cortas GA, Mehta SN, Abraham NS, et al. Selective cannulation of the common bile duct: a prospective randomized trial comparing standard catheters with sphincterotomes. Gastrointest Endosc 1999; 50:775–779. Canard JM, Cellier C, Houcke P, et al. Prospective multicenter study comparing a standard reusable sphincterotome with a disposable triple-lumen sphincterotome. Gastrointest Endosc 2000; 51:704–707. Lella F, Bagnolo F, Colombo E, et al. A simple way of avoiding post-ERCP pancreatitis. Gastrointest Endosc 2004; 59:830–834. Tang SJ, Haber GB, Kortan P, et al. Precut papillotomy versus persistence in difficult biliary cannulation: a prospective randomized trial. Endoscopy 2005; 37:58–65. Elta GH, Barnett JL, Wille RT, et al. Pure cut electrocautery current for sphincterotomy causes less post-procedure pancreatitis than blended current. Gastrointest Endosc 1998; 47:149–153. Stefanidis G, Karamanolis G, Viazis N, et al. A comparative study of postendoscopic sphincterotomy complications with various types of electrosurgical current in patients with choledocholithiasis. Gastrointest Endosc 2003; 57:192–197. MacIntosh DG, Love J, Abraham Ns. Endoscopic sphincterotomy by using pure-cut electrosurgical current and the risk of postERCP pancreatitis: a prospective randomized trial. Gastrointest Endosc 2004; 60:551–556. Gorelick A, Cannon M, Barnett J, et al. First cut, then blend: a electrocautery technique affecting bleeding at sphincterotomy. Endoscopy 2001; 33:976–980. Perini RF, Sadurski R, Cotton PB, et al. Post-sphincterotomy bleeding after the introduction of microprocessor-controlled electrosurgery: does the new technique make the difference? Gastrointest Endosc 2005; 61:53–57. Freeman ML, Nelson DB, Sherman S, et al. Complications of endoscopic biliary sphincterotomy. NEJM 1996; 335: 909–918. Mavrogiannis C, Liatos C, Papanikolaou IS, et al. Safety of extension of a previous endoscopic sphincterotomy: a prospective study. Am J Gastroenterol 2003; 98:72–76. Zoepf T, Zoepf DS, Arnold JC, et al. The relationship between juxtapapillary duodenal diverticula and disorders of the biliopancreatic system : analysis of 350 patients. Gastrointest Endosc 2001; 54:56–61.

15. Born P, Sandschin W, Rösch T. Percutaneous antegrade sphincterotomy under endoscopic retrograde control: report of two cases. Endoscopy 2002; 34:512–513. 16. Baron TH, Harewood GC. Endoscopic balloon dilation of the biliary sphincter compared to endoscopic biliary sphincterotomy for removal of bile duct stones during ERCP: a metaanalysis of randomized, controlled trials. Am J Gastroenterol 2004; 99:1455–1460. 17. DiSario JA, Freeman ML, Bjorkman DJ, et al. Endoscopic balloon dilation compared with sphincterotomy for extraction of bile duct stones. Gastroenterology 2004; 127:1291–1299. 18. Tanaka S, Sawayama T, Yoshioka T. Endoscopic papillary balloon dilation and endoscopic sphincterotomy for bile duct stones: long-term outcomes in a prospective randomized controlled trial. Gastrointest Endosc 2004; 59:614–618. 19. Bergman JJGHM, van Berkel AM, Bruno MJ, et al. Is endoscopic balloon dilation for removal of bile duct stones associated with an increased risk for pancreatitis or a higher rate of hyperamylasemia? Endoscopy 2001; 33:416–420. 20. Neuhaus H. Endoscopic and percutaneous treatment of difficult bile duct stones. Endoscopy 2003; 35:S31–S43. 21. Sugiyama M, Atomi Y. Endoscopic sphincterotomy for bile duct stones in patients 90 years of age and older. Gastrointest Endosc 2000; 52:187–191. 22. Sharma VK, Howden CW. Metaanalysis of randomized controlled trials of endoscopic retrograde cholangiography and endoscopic sphincterotomy for the treatment of acute biliary pancreatitis. Am J Gastroenterol 1999; 94:3211–3214. 23. Costamagna G, Pandolfi M, Mutignani M, et al. Long-term results of endoscopic management of postoperative bile duct strictures with increasing numbers of stents. Gastrointest Endosc 2001; 54:162–168. 24. Bergman JJGHM, Burgemeister L, Bruno MJ, et al. Long-term follow-up after biliary stent placement for postoperative bile duct stenosis. Gastrointest Endosc 2001; 54:154–161. 25. Masci E, Toti G, Mariani A, et al. Complications of diagnostic and therapeutic ERCP : a prospective multicenter study. Am J Gastroenterol 2001; 96:417–423. 26. Loperfido S, Angelini G, Benedetti G, et al. Major early complications from diagnostic and therapeutic ERCP: a prospective multicenter study. Gastrointest Endosc 1998; 48:1–10. 27. Freeman ML, DiSario JA, Nelson DB, et al. Risk factors for postERCP pancreatitis: a prospective, multicenter study. Gastrointest Endosc 1998; 48:1–10. 28. Cotton PB, Lehman G, Venes J, et al. Endoscopic sphincterotomy complications and their management: an attempt at consensus. Gastrointest Endosc 1991; 37:383–393. 117

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29. Andriulli A, Leandro G, Niro G, et al. Pharmacologic treatment can prevent pancreatic injury after ERCP: a meta-analysis. Gastrointest Endosc 2000; 51:1–7. 30. Singh P, Das A, Isenberg G, et al. Does prophylactic pancreatic stent placement reduce the risk of post-ERCP acute pancreatitis? A meta-analysis of controlled trials. Gastrointest Endosc 2004; 60:544–550. 31. Rabenstein T, Schneider HT, Nicklas M, et al. Impact of skill and experience of the endoscopist on the outcome of endoscopic sphincterotomy techniques. Gastrointest Endosc 1999; 50:628–636. 32. Wilcox CM, Canakis J, Mönkemüller MD, et al. Patterns of bleeding after endoscopic sphincterotomy. The subsequent risk of bleeding, and the role of epinephrine injection. Am J Gastroenterol 2004; 99:244–248. 33. Vàsconez C, Llach J, Bordas JM, et al. Injection treatment of hemorrhage induced by endoscopic sphincterotomy. Endoscopy 1998; 1:37–39. 34. Matsushita M, Hajiro K, Takakuwa H, et al. Effective hemostatic injection above the bleeding site for uncontrolled bleeding after endoscopic sphincterotomy. Gastrointest Endosc 2000; 51:628–636.

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35. Baron TH, Norton ID, Herman L. Endoscopic hemoclip placement for post-sphincterotomy bleeding. Gastrointest Endosc 2000; 52:662. 36. Mallery JS, Baron TH, Dominitz JA, et al. Complications of ERCP. Gastrointest Endosc 2003; 57:633–638. 37. Enns R, Eloubeidi MA, Mergener K, et al. ERCP-related perforations: risk factors and management. Endoscopy 2002; 34:293–298. 38. Stapfer M, Selby R, Stain S, et al. Management of duodenal perforation after endoscopic retrograde cholangiopancreatography and sphincterotomy. Ann Surg 2000; 232:191–198. 39. Prat F. The long term consequences of endoscopic sphincterotomy. Acta Gastro-Enterologica Belgica 2000; 63:395–396. 40. Pozsar J, Sahin P, Laszlo F, et al. Endoscopic treatment of sphincterotomy-associated distal common bile duct strictures by using sequential insertion of multiple plastic stents. Gastrointest Endosc 2005; 62:85–91. 41. Karlson BM, Ekbom A, Arvidsson D, et al. Population based study of cancer risk and relative survival following sphincterotomy for stones in the common bile dcut. Br J Surg 1997; 84:1235–1238.

SECTION 2

Chapter

13

TECHNIQUES

Stone Extraction Suyi Chang and Joseph W. Leung

INTRODUCTION Following endoscopic sphincterotomy, the majority of stones <1 cm will pass spontaneously.1 Nonetheless, it is current standard practice to attempt stone extraction and clear the bile duct to avoid stone impaction and subsequent risk of cholangitis. Extraction of stones can usually be achieved with balloon catheter or wire basket. However, large stones, particularly those over 2 cm, may be difficult to remove and will require stone fragmentation prior to removal with baskets and/or balloons. Methods of stone fragmentation include mechanical lithotripsy, intraductal electrohydraulic or laser lithotripsy, and extracorporeal shock wave lithotripsy (ESWL). In the case where endoscopic stone extraction fails, surgery or chemical dissolution of the stone2–5 should be considered. Permanent stenting can be used as an alternative for biliary drainage in cases of large unextractable stones to prevent cholangitis.6–11 Initial cholangiograms are usually obtained using 60% (normal) contrast, and early filling images should be carefully analyzed for stones, which are often seen as filling defects with a meniscus sign (Fig. 13.1A, 13.1B). However, if the bile duct is dilated, 30% (half normal) contrast should be used as a large amount of dense contrast can mask the small stones in a dilated bile duct. In patients with suspected intrahepatic stones or stone above a stricture, an occlusion cholangiogram may be necessary to inject contrast above the stricture/obstruction to visualize the stone(s) (Fig. 13.1C). There is however a risk of causing cholangitis if contrast is injected into an obstructed system increasing the intrabiliary pressure. In order to achieve successful stone extraction, it is of prime importance to assess the stone size relative to the size of the sphincterotomy and distal common bile duct (i.e. the exit passage). The sphincterotomy should be of adequate size to allow passage of the stone. One method of gauging sphincterotomy size is to pull a fully bowed sphincterotome across the cut papilla. A generous sphincterotomy should allow easy passage of the bowed sphincterotome. In addition, appropriate accessories should be available to handle any foreseeable complications. Dilation of a bile duct stricture (see Chapter 30) may be necessary for stones that occur above a bile duct stricture or intrahepatic stones. This can be achieved using Gruntzig type balloons, which are low compliance balloons that can be inflated to a fixed diameter. Dilute contrast should be used for inflating the balloon to a predetermined pressure as recommended by the manufacturer. The balloon has radiopaque markers that help with the positioning, and the maximum diameter of the balloon used should be gauged based on the diameter of the normal portion of the bile duct. The balloon is inflated and the presence or disappearance of the waist formation on the balloon is noted. This will determine the ease of stone extrac-

tion through the stricture. If the stricture cannot be opened, stone fragmentation is necessary prior to removal. Balloon dilation or sphincteroplasty after a small initial sphincterotomy has been used to facilitate removal of a large stone and to avoid the risk of bleeding and perforation from a large sphincterotomy.

BALLOON STONE EXTRACTION Key points • Bile duct stones may be removed by inflating a balloon catheter above the stone and pulling back the catheter until the stone reaches the ampulla. The stone is then expelled by traction and downward deflection of scope tip. • Ensure that an adequate sphincterotomy is performed for ease of stone extraction. • If indicated, size the exit passage before attempted stone extraction to avoid stone impaction • Monitor balloon size during traction removal of the stone. • Avoid overinflating the balloon to minimize false resistance.

Indications/contraindications • Common bile duct stones and intrahepatic stones may be removed using a balloon catheter. • Useful for removing small to medium stones. • Large stones may be difficult to remove with a balloon and may result in stone impaction.

Complications • Balloon rupture may occur. • Impacted stone due to relative inadequacy of the sphincterotomy.

Introduction Extraction balloons are available in different sizes, ranging from 8 to 15 mm. The size of the balloon can be adjusted by injecting a varying amount of air to fill the balloon and regulating the volume with a two-way stopcock (Fig. 13.2A). It may be helpful also to size the exit passage prior to stone extraction in order to avoid stone impaction. The balloon is inflated to the widest diameter of the common bile duct below the stone and pulled back gently to determine if there is any resistance to traction removal of the balloon, noting any significant deformity of the balloon at the same time. In cases of chronic pancreatitis where the retropancreatic portion of the bile duct may be compressed or fixed, the balloon may deform or become “sausage” shaped rather than retaining its rounded appearance. This may indicate likely resistance to stone passage. Triple lumen balloon allows the catheter to go over a guidewire and maintain access to the biliary system, in addition to injection of contrast (Fig. 13.2B). However, triple-lumen balloon shafts may be stiffer than regular double-lumen balloons. The tip of the balloon catheter 119

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A

B

C

Fig. 13.1 A Irregular distal bile duct stone, seen as a filling defect. Denser contrast below stone demonstrates a good meniscus sign. B Distal common bile duct stone formed around a surgical clip. C Occlusion cholangiogram showing inflated balloon in midCBD, normal gallbladder and a segment of right hepatic duct filled with stones.

A

may be curled gently before introduction into the scope to facilitate cannulation.

Description of technique

B

Fig. 13.2 A Variable diameter stone extraction balloon. Balloon (courtesy of Boston Scientific, Natick, MA) is inflated to 12 mm in diameter and held in position with 2-way stopcock. B Triple lumen stone extraction balloon (courtesy of Cook Endoscopy, Winston-Salem, NC) showing balloon inflated and held in position with two-way stopcock, with a separate lumen for injection of contrast and passage of guidewire. 120

Once the catheter is within the bile duct, the balloon is inflated above the stone and pulled back gently until the stone is at the level of the papilla. The scope should be aligned so that the axis of traction is in the same axis as the bile duct. The tip of the scope is then angled upwards against the sphincterotomy. While maintaining gentle traction on the balloon catheter at the level of the biopsy valve, the tip of the scope is deflected downwards, expelling the stone from the sphincterotomy (Fig. 13.3). If there is resistance, the tip of the scope is again angled upwards with steady traction applied to the catheter, and the flip down movement is repeated to remove the stone. It may be necessary to maintain the traction on the balloon as the stone is slowly eased out of the bile duct. If necessary, the scope tip can be angled downwards and rotated to the right to exert more traction force to expel the stone. It is important to remember that an overinflated balloon may give rise to resistance as it is being pulled down, and it may be necessary to deflate the balloon slowly to conform to the size of the bile duct. If a number of stones are present, it would be appropriate to remove the most distal stone first and then work up the bile duct. Care should also be taken to avoid overinflating the balloon in the bile duct as this will stretch the bile duct and cause pain to the patient. The balloon should be inflated or deflated accordingly to adjust the size to fit the diameter of the bile duct. In cases where the balloon goes over a short guidewire which is locked to the scope, excessive scope movement during stone extraction may dislodge the wire. It may be necessary to pull the balloon gently and avoid excess tip deflection of the scope to prevent dislodging the guidewire. An alternative is to insert more guidewire into the bile duct to maintain

Chapter 13 Stone Extraction

Fig. 13.4 Impacted ampullary stone. Note bulging distal bile duct. Initial precut is followed by standard sphincterotomy, resulting in spontaneous expulsion of stone after completion of sphincterotomy.

indwelling stent or a nasobiliary drain to avoid subsequent cholangitis if the stone is not removed.

Relative cost Fig. 13.3

Stone extracted with a balloon.

Balloons range in price from US$100 to $150 (list price), depending on the manufacturer and whether they are double-lumen or triplelumen catheters.

BASKET STONE EXTRACTION Key points access before stone extraction. Nonetheless, it should be easy to recannulate the bile duct in the presence of an adequate sphincterotomy.

Indications/contraindications The advantage of using an extraction balloon is that the inflated balloon fully occludes the lumen of the bile duct, facilitating removal of small stones and debris. In addition, an occlusion cholangiogram can be performed at the same time to ensure complete clearance of the bile duct. Furthermore, the balloon catheter can be inserted over a guidewire, allowing access to the intrahepatic ducts and removal of intrahepatic stones.

Complications and management Complications may arise with using the balloon. If the balloon is pulled too hard against the stone, rupture of the balloon may occur. If the stone is too large for the sphincterotomy, the balloon may deform and slip out, leaving the stone impacted at the lower end of the common bile duct or at the level of the papilla. In order to free an impacted stone, it may be necessary to push it back using a stiffer accessory, including a biopsy forceps. Alternatively, it may be possible to extend the sphincterotomy if a standard sphincterotome can be inserted past the stone. Another option is to use a needle knife to cut onto the bulging intraduodenal portion of the distal bile duct and papilla in order to free the stone (Fig. 13.4). A balloon may also be inflated below an impacted stone in the distal duct and contrast injected under pressure to push the stone back up the proximal duct. In the event that the stone is impacted within the bile duct, it is important to ensure drainage of the biliary system by placing an

• The basket should be filled with dilute contrast to facilitate localization of stone. Avoid injecting excess contrast to reduce risk of displacing stone upwards into the intrahepatic system. • Open basket above the stone and pull back to engage the stone. • Half close the basket to facilitate traction removal of stone. • Avoid using basket to engage the stone in intrahepatic system as this may further displace the stone. • Use an occlusion balloon over a guidewire to pull an intrahepatic stone back into the common duct for ease of stone engagement and extraction. • If extraction fails, be prepared to free the engaged stone or proceed with mechanical lithotripsy to avoid basket and stone impaction.

Indications/contraindications • Medium to larger size stones may be more easily removed with a basket.

Complications • Migration of stones into intrahepatic ducts. • Impaction of stone and basket.

Introduction Wire baskets are frequently used for stone extraction. A variety of baskets are available in different sizes and configurations, which allow engagement of stones varying from 5 mm up to 3 cm. However, stones larger than 2 cm often cannot be extracted intact and will require fragmentation prior to removal. The 4-wire Dormia basket is the most commonly used type (Fig. 13.5). It is hexagonal in shape and made of braided steel wires or nitinol wires. The stone is engaged between the wires when the basket is closed, and the stone removed by traction removal of the basket. However, small stones sometimes 121

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Fig. 13.5 Opened wire-guided basket (Olympus America, Lehigh Valley, PA) with the guidewire. Note the much larger gaps between the wires. Fig. 13.7

Opened helical basket (Cook Endoscopy).

A

B

with the help of a special crank handle that is used to tighten the basket wires around the stone to break the stone. In general, contrast can be injected through the basket to outline the stones in the bile duct. When a single lumen basket is used, the basket should be opened slightly to allow free flow of dilute contrast. A double-lumen basket allows both injection of contrast through the basket channel and passage of a guidewire through a separate channel. Alternatively, the basket can be advanced over a previously positioned guidewire. This is especially helpful for the removal of intrahepatic stones or stones that may have migrated into the intrahepatic ducts.

Description of technique

Fig. 13.6 A An opened flower basket (Olympus America, Lehigh Valley, PA). Note the smaller mesh size on the upper part of the basket. B Partially closed flower basket showing smaller mesh size, which is better for trapping small stones.

are difficult to capture with standard baskets which have large gaps between the wires. The Olympus flower basket has a modified design in that the top part of the basket is further divided into eight wires, giving rise to smaller mesh size for improved stone engagement. Small stones are thus more easily trapped than with the regular 4-wire basket (Fig. 13.6). Spiral baskets are also available and may be used to remove relatively small stones (Fig. 13.7). In the spiral configuration, the wires spring close around the stone as the basket is pushed open. However, spiral baskets are not designed for lithotripsy. Other larger and stronger baskets are available which are made for mechanical lithotripsy and are designed to engage large stones. The basket wires are much stronger and can be used to mechanically crush a large stone. Traction or tension can be applied to the wires either manually or 122

After the stones are visualized on the cholangiogram, a closed basket is inserted into the bile duct and advanced beyond the stone. After a fresh sphincterotomy or balloon sphincteroplasty, it is important that the basket be inserted in the correct axis in the bile duct to avoid dissecting a false plane, which may result in submucosal trauma or even a perforation. Once in the bile duct, the basket is opened gently above the stone. If necessary, the basket can be opened in the intrahepatic duct and pulled back to engage the stone. Care should be taken to avoid opening the basket below the stone, as the opened basket wires may push the stone further up the bile duct or into the intrahepatic system. The opened basket is pulled back gently and jiggled alongside the stone to engage it. After the stone is trapped, the basket is closed gently to avoid losing the stone (Fig. 13.8A). The scope is then pushed further into the second and third part of the duodenum to straighten the axis of the basket and the bile duct to ensure proper stone engagement. Steady traction is applied to the basket catheter at the level of the biopsy valve and the basket is withdrawn together with the stone until it reaches the distal bile duct or at the level of the sphincterotomy. Traction is applied to the basket catheter and at the same time, the tip of the scope is angled down and rotated gently to the right, pulling the stone out of the bile duct (Fig. 13.8B). In most situations, small to medium-sized stones can be removed easily. If the stone does not come out immediately, it is worth repeating the same maneuver while maintaining steady traction on the basket to ease the stone out of the bile duct. During stone extraction, pulling with an opened basket is less effective, as the loose basket wires tend to cut across the sphincter-

Chapter 13 Stone Extraction

may occur if the stone is too large to be removed and the trapped stone cannot be freed from the basket.

A

Indications/contraindications The advantage that the wire basket offers over the extraction balloon is that it provides more effective traction and therefore is helpful for removing medium size to large stones. However, smaller stones or stone fragments may not be easily engaged by the wires. In addition, intrahepatic stones may be difficult to access due to the smaller caliber of the intrahepatic ducts and constraints in opening the basket. In these situations, use of an extraction balloon is preferred.

Complications and management During basket stone extraction, the stone(s) may migrate up into the intrahepatic duct. Catching a migrated stone within the intrahepatic duct can be challenging. The best method is to avoid using the basket. A balloon and guidewire may be used to selectively cannulate the respective segment containing the stone. The balloon is advanced over the guidewire beyond the stone and inflated. The stone is then pulled back into the common hepatic duct or the common bile duct before further attempts are made to remove the stone, either using the same balloon catheter or exchanging for a basket. Use of a wire-guided basket is also helpful in removing stones from the intrahepatic ducts, although these baskets tend to be rather stiff and manipulation in the intrahepatic ducts can be somewhat difficult. If basket stone extraction fails, it may be necessary to free the engaged stone to avoid basket and stone impaction. This may be achieved by gently advancing the basket and stone up towards the bifurcation and opening the basket so that the wires bend back on themselves. In this fashion, the wires are opened and the stone can be dropped from the basket. The basket is then closed slowly above the stone to avoid re-engaging it when the opened basket is pulled back. Once the basket is closed, it can be removed. Further stone extraction may require extension of the sphincterotomy or stone fragmentation using a mechanical lithotripter. One potential complication that may arise is impaction of the basket and stone within the bile duct or at the level of the papilla due to large stone size and inadequate sphincterotomy or inability to enlarge the sphincterotomy. In rare instances, stone and basket impaction have occurred at the level of the head of the pancreas due to a narrowed distal common duct. In these cases, emergent mechanical lithotripsy may be attempted using a Soehendra lithotripter.

B

Relative cost Fig. 13.8 A Stone engaged within a basket. with a wire basket.

B Stone removed

List prices for baskets vary from $150–$350, depending on the design. Some are disposable while others are reusable.

MECHANICAL LITHOTRIPSY otomy rather than along the axis of the common bile duct. This also tends to pull the stone against the sphincterotomy and results in bruising the tissue. Closing the basket gently allows the wires to come together, allowing more effective extraction force to be transmitted along the basket catheter for stone removal. However, the basket should not be closed too tightly around the stone to avoid embedding the wires onto the surface of the stone. This is especially important in the case of a large stone, as stone and basket impaction

Key points • Always have a device available in case of unexpected stone/basket impaction. • The stone is captured within a wire basket and the metal sheath is advanced over the basket up to the stone. Closing the basket crushes the stone against the tip of the metal sheath. • Ensure that the tip of the metal sheath is in contact with stone before lithotripsy. 123

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Fig. 13.10 The Soehendra lithotripter (courtesy of Cook Endoscopy, Winston-Salem, NC) consists of a 10 Fr metal sheath that goes through the instrument channel of the duodenoscope and a selflocking crank handle.

A

B

C

D

Fig. 13.9 Failed basket stone extraction. Three large stones in common bile duct. Basket is too small for the stones.

• Turn the crank handle slowly and allow time for the basket wires to cut through the stone and to avoid breaking the basket.

Indications/contraindications • Mechanical lithotripsy is used when there is failure of standard balloon or basket stone extraction due to large stones. • May also be used in the case of impacted stone and basket.

Complications • Excess traction on the wires against a very hard stone may lead to breakage of the basket wires. • Failure can occur if there is stone impaction that prevents proper opening of the large basket around the stone.

Introduction When standard balloon or basket stone extraction fails (Fig. 13.9), fragmentation of the stone within the bile duct may become necessary, particularly if the stone is larger than 2 cm, or if there is a discrepancy between the stone size and the exit passage, i.e., distal common bile duct stricture, small sphincterotomy, or after balloon sphincteroplasty. In some cases, extension of the sphincterotomy is not feasible and may increase the risk of bleeding and perforation. It may be possible to use balloon dilation of a partially cut sphincterotomy in order to gain a bigger opening to facilitate removal of large stones. Mechanical lithotripsy is accomplished by capturing a stone within a wire basket and advancing a metal sheath over the basket catheter up to the stone. The stone is then crushed by forceful traction of the basket wires and stone against the metal sheath.

Description of technique Several lithotripters are available, but they fall into two main categories. One requires cutting of the basket handle and removal of the endoscope prior to lithotripsy, and is frequently used on an emergency basis when unexpected stone and basket impaction occurs (life saver). The Soehendra lithotripter (Cook Endoscopy, Winston124

Fig. 13.11 For demonstration purpose, an artificial stone is used. A Stone is engaged in the basket. The basket handle is cut and Teflon sheath is then removed. B Metal sheath of the Soehendra lithotripter inserted over basket wire. C The metal sheath is inserted through the scope channel and advanced to the level of the stone. The cut end of the basket wires is inserted through the shaft of the crank handle. D The basket wires are tied to the shaft of the crank handle and tension is applied as the handle is slowly wound to crush the stone.

Salem, NC) consists of a 14 Fr metal sheath and a self-locking crank handle (Fig. 13.10). The apparatus is compatible with standard extraction baskets or large lithotripsy baskets with stronger wires. It requires cutting of the basket handle to allow removal of the duodenoscope. The metal sheath is then inserted over the basket catheter. There are grooves at the tip of the metal sheath and to avoid the bare basket wires from getting stuck, a tape may be applied to the end of the metal sheath. This also helps to avoid injury to the posterior pharynx during insertion. It is helpful to retain the Teflon sheath initially to facilitate passage of the wires through this 14 Fr metal sheath before removing it. The metal sheath is advanced all the way up to the stone under fluoroscopy control. The Teflon sheath is removed and the cut ends of the basket wires are then inserted into the shaft of the crank handle. The metal sheath is attached to the handle by a luer lock. The wires are then tied to the handle and traction applied slowly by winding the crank handle. The basket is closed and drawn into the metal sheath as forceful traction is applied, crushing the stone against the tip of the metal sheath in the process (Fig. 13.11). It is important to remember that standard baskets are

Chapter 13 Stone Extraction

Fig. 13.12 A Large stone engaged in BML lithotripsy basket. B In a separate case, a BML lithotripsy basket is used to engage the stone. C The metal sheath of the lithotripter is advanced over the Teflon sheath, and basket wires tightened around the stone in mid CBD for stone fragmentation.

B A

C

not designed for lithotripsy, and if traction is applied too quickly the basket wires may break rather than the stone. Winding the crank handle slowly and allowing time for the basket wires to cut through serves to break up the stone and avoid the complication of a broken basket and stone impaction. The latest improvement in design for the Soehendra lithotripter involves using a smaller 10 Fr sheath, which can be inserted through the scope channel over the basket wires after cutting off the basket handle. In this case, it is not necessary to remove the duodenoscope. It is used specifically with the Webb basket (Cook Endoscopy), which has smaller wires. This through-the-scope set-up may not be compatible with other standard baskets. However, unlike other TTS lithotripsy baskets, the basket cannot be reused for repeat stone fragmentation because the handle is cut. The other type of lithotripter is specifically designed to be used through-the-scope (TTS) without the need for scope removal, such as the BML lithotripsy baskets (Olympus Co., Tokyo, Japan) or the Trapezoid basket (Microvasive, Boston Scientific, Natick, MA). These are used in a more elective setting, when a large stone, above a stricture or difficult stone removal is anticipated. The BML lithotripter is a three-layer device consisting of a strong four-wire basket within a Teflon sheath and an overlying metal sheath. The larger lithotripsy basket or BML-3Q equivalent (BML201) has a slightly thicker metal sheath and requires a scope with a 4.2 mm working channel. It allows injection of contrast because of the larger diameter. The smaller basket or BML-4Q equivalent (BML202, 203) goes through a 3.2 mm channel, but injection of contrast

A

B

Fig. 13.13 A Through-the-scope BML lithotripter (courtesy of Olympus America Inc., Melville, NY) consists of a wire basket within a Teflon catheter, an overlying metal sheath, and the crank handle. B With the stone engaged in the basket, the metal sheath is advanced over the Teflon catheter up to the basket. Basket is closed by turning the wheel and the stone is crushed against the metal sheath.

is more difficult. The BML lithotripter has a reusable version and a disposable version. The reusable system is assembled by inserting the Teflon sheath through the metal sheath, then loading the basket into the Teflon catheter. The wires are soldered together onto a shaft that is connected to the crank handle. Contrast can be injected via the Teflon catheter. The opening and closing of the basket is controlled with the handle. Stone engagement is performed initially with the Teflon catheter and basket. The metal sheath is then advanced over the Teflon catheter up to the level of the stone only when lithotripsy is required (Figs 13.12, 13.13). 125

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A

126

B

A

B

Fig. 13.14 A The wires of a lithotripsy basket can be deformed as a result of crushing a hard stone. B It is necessary to reshape the basket wires to ensure they open properly for repeat stone engagement.

Fig. 13.15 A Opened trapezoid basket (courtesy of Boston Scientific, Natick, MA) with handle. Note the plastic-covered metal sheath. The plastic handle can be fitted to a cranking device if lithotripsy is required. B Opened trapezoid basket inserted over a guidewire.

Although a general shaking and jiggling movement of the basket can be tried to engage the stone, very often the large stone(s) may compress the basket wire making stone engagement difficult. It may be useful to rotate the basket wires around the stone by rotational movement of the tip of the scope (even with the help of the metal sheath to transmit a stronger force) in order to engage the stone. There is a locking mechanism (notches on the metal handle) for the metal sheath to ensure proper engagement of the stone before lithotripsy. It is very important to make sure that the metal sheath is locked in the correct position. This is done by keeping the device straight and avoiding any looping. If the metal sheath is not locked properly, i.e. with a short segment of the Teflon catheter exposed between the stone and the tip of the metal sheath, mechanical lithotripsy will not be effective. If there is recoil or a clicking noise heard when turning the control wheel, lithotripsy is not working, and the position of the metal sheath will need to be adjusted. With the stone properly engaged in the basket and the metal sheath correctly positioned, traction is applied to the wires by turning the control wheel to crush the stone. As the control wheel does not have a built-in self-locking mechanism, traction should be applied slowly and continuously to allow time for the wires to cut through the stone. The reusable system can be taken apart after lithotripsy for cleaning and sterilization. The disposable version comes with the lithotripsy basket, Teflon catheter and metal sheath all built into one and is meant for use in one patient session only. If a large and hard stone is crushed, always remove the basket to examine the wires as they are often deformed due to stone breakage (Fig. 13.14). It is necessary to reshape the basket wire either by hand or with a pair of hemostats to ensure subsequent proper basket opening to trap the stone fragments for repeat lithotripsy. As a large stone will give rise to large fragments, these will still require further fragmentation before they can be removed easily. In general, mechanical lithotripsy is very effective in breaking large stones. Repeated stone fragmentation may be required in the case of a very large stone. The reported success rate of mechanical lithotripsy for large stones has ranged from 85% to 90%.12–16 The Trapezoid basket (Microvasive, Boston Scientific) is made of nitinol wire and comes with a coated and rather flexible metal sheath (Fig. 13.15). The design of the basket also allows it to go over a guidewire inserted through a separate channel. This is especially handy with the Rapid Exchange system (Boston Scientific). The flexibility of the sheath also allows free cannulation with the basket for stone engagement. If stone fragmentation is not necessary, stone extraction can be done in the usual manner because of the flexible sheath. When

stone fragmentation is indicated, the handle of an insufflator (similar to a caulk gun design) can be fitted to the handle of the basket and traction is then applied to the basket wires to break the stone. This design offers the benefit of having selective cannulation over a guidewire and the potential option for stone fragmentation.

Indications/contraindications When stones are too large to be removed with standard balloons or wire baskets, mechanical lithotripsy is indicated for stone fragmentation prior to removal. It is also a useful tool in the case of stone and basket impaction.17

Complications and management The Soehendra lithotripter may be used as a “lifesaver” measure in cases of stone and basket impaction. However, the wires of the standard basket are relatively soft, and may break in the duodenum resulting in retained broken basket and stone in the bile duct. Surgical exploration may be needed to remove the impacted stone and basket. The Olympus TTS lithotripsy basket set-up is designed to break at the connection between the basket and the crank handle and alternatively, the basket wires are also designed to break at the tip to prevent having a broken basket around an impacted stone in the bile duct. In the unexpected event of the basket breaking at the connection point, Olympus has developed a special metal sheath that resembles the Soehendra set-up. This metal sheath can be inserted over the broken basket after removal of the endoscope. Stone fragmentation can be performed as with the Soehendra lithotripter. It is not advisable to use the Cook Endoscopy Soehendra lithotripter handle and adapt it onto a broken Olympus lithotripsy basket as it is not truly compatible. If that is necessary, it is important to retain the Teflon catheter around the basket wires to offer support for the metal sheath. The design of the metal sheath with the disposable BML system is different and if tension is applied to the wires without the Teflon catheter, the coils of the metal sheath buckle thus making lithotripsy ineffective. TTS mechanical lithotripsy is successful in the majority of cases because these baskets are stronger. Over 80% of large (>2 cm) stones have been fragmented in reported series giving a common duct clearance rate of over 95%. The main reason for failure is the stone is too large for the size of the basket but even then, if part of the stone can be engaged, stone fragmentation can be attempted to reduce the size of the stone allowing for proper engagement for complete stone fragmentation. Mechanical lithotripsy fails when there is stone impaction or if there is not enough room within the

Chapter 13 Stone Extraction

bile duct to open the basket to engage the stone. In this situation, temporary stenting can be tried to insure drainage of the biliary system. Subsequent spontaneous stone fragmentation has been observed in 30% of cases possibly due to the friction between the stone and the stent or to possible dissolution effects of improved bile flow. Although relatively uncommon, perforation of the bile duct may occur due to the relative stiffness of the basket when the wires are tightened. In addition, pancreatitis may result from forceful removal of an impacted stone and basket, causing injury to the pancreatic orifice.

INTRADUCTAL ELECTROHYDRAULIC LITHOTRIPSY Key points • It is preferable to use the mother and baby scope system for direct visual control of intraductal lithotripsy. • Despite the angulations control, positioning of the baby scope is coordinated by the operator manipulating the mother scope. • Both stone and probe are immersed in fluid medium (normal saline), and with the probe directly against the stone, electrical discharge from the probe generates shock waves which result in stone fragmentation. • An adequate sphincterotomy is necessary to allow drainage from the bile duct while the baby scope is in position to avoid raising the intra-biliary pressure. • Use an indwelling nasobiliary catheter to flush the bile duct to improve visualization and to remove stone fragments during lithotripsy.

Indications/contraindications • May be used in the setting of failed lithotripsy due to large or impacted stone.

Complications • Bile duct injury and perforation.

Introduction Mechanical lithotripsy is so effective and successful that there is less and less need for intraductal lithotripsy except in very special circumstances, and the set-up is mostly available only in academic units. Intraductal lithotripsy can be conducted under fluoroscopy using a special balloon that centers the probe in the bile duct, or alternatively under direct visual control using the mother and baby scope system.

Description of technique There are two forms of intraductal lithotripsy (IDL)—electrohydraulic (EHL)18–20 or laser lithotripsy.21,22 Each of these types of intraductal lithotripsy is best performed under direct visual control using the mother and baby scope system. An older Olympus system consists of a jumbo size duodenoscope with a 5.5 mm channel and the baby scope is 4.7 mm in diameter with a 1.7 mm channel. The larger instrument channel allows easier passage of the lithotripsy probe. The newer baby scope is smaller with a 3.2 mm diameter and a 1 mm instrument channel. This can be inserted through a therapeutic duodenoscope of 4.2 mm instrument channel. However, because of the small instrument channel, it can only accommodate the small lithotripsy probe or the smaller laser probe.

After an adequate sphincterotomy or combined sphincterotomy and balloon sphincteroplasty, the baby scope is introduced into the common bile duct with the help of the mother scope. Despite the two way (up/down) tip deflection of the baby scope, most of the positioning of the baby scope is achieved by manipulating the mother scope (see Chapter 21). Two endoscopists are required to conduct this examination and it is best to project the image of both scopes onto two monitors to facilitate the coordination between the two operators. A fluid medium (normal saline) is required for electrohydraulic lithotripsy and this can be introduced through the channel of the baby scope. However for practical purposes, we prefer to insert a nasobiliary catheter which allows more efficient filling and also flushing of the system with saline to remove the stone fragments and debris generated as a result of stone fragmentation. The electrohydraulic lithotripter consists of a power generator (e.g. Walz, Germany) by which the power or energy can be preset based on the size of the probe (3 or 4.5 Fr) used (see Chapter 21). The tip of the probe has a pair of bipolar electrodes, which when activated in a fluid medium, will generate a shock wave to fragment the stone. The frequency of discharge of the shock wave can be preset on the machine and activated by a foot switch either as a single pulse or continuous discharge. Depending on the instrument channel of the baby scope, two sizes of probes (3 Fr and 4.5 Fr) can be used. For the more floppy 3 Fr probe, it may be helpful to preload this before inserting the baby scope into the bile duct. Examination with the baby scope is facilitated by filling the bile duct with saline. Care is taken not to overfill the system to avoid the risk of cholangitis. The probe is placed in contact with the stone, under direct visualization with the baby scope as well as on fluoroscopy. The stone and probe are immersed with saline filled through the nasobiliary catheter using an infusion pump. The foot switch is activated and stone fragmentation is performed under direct visual control. Stone fragments generated during lithotripsy can obscure the view and this can be cleared by flushing more saline and suctioning with the mother scope. Effective stone fragmentation can be demonstrated under fluoroscopy by injecting contrast into the bile duct. Subsequent stone extraction is performed with basket after removal of the baby scope, followed by an occlusion cholangiogram to document ductal clearance. Since stone fragments are generated during lithotripsy, it may be helpful to insert the stone extraction basket deep in the bile duct and irrigate the duct with saline flushed through the basket (while applying suction with the scope). This helps to remove the remaining stone fragments from the common duct. If the jumbo size duodenoscope is used for mother and baby examination, it may be useful to change back to a regular therapeutic scope for ease of manipulation. In most cases, it may be advisable to insert an indwelling stent or nasobiliary catheter to decompress the biliary system and to allow the stone fragments to settle and avoid the risk of stone impaction and cholangitis. A repeat ERCP is performed to remove remaining stone fragments for complete duct clearance.

Indications/contraindications When mechanical lithotripsy fails to remove the stone, particularly large stones that are difficult to capture with the lithotripsy basket, or an impacted stone, intraductal electrohydraulic lithotripsy is an effective option. The reported success rates in these cases are excellent.18–20 However, the cost of the equipment, the lack of general availability of mother-baby scope system, and the requirement for two endoscopists with expertise in the use of the equipment can be prohibitive for general use. 127

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Complications and management Although highly effective, one of the major problems is difficulty with targeting of the shock waves and inadvertent bile duct injury and perforation. The procedure should be performed under direct endoscopic and fluoroscopic guidance by endoscopists with experience in the use of the equipment.

CONCLUSION It is customary to clear the bile duct of stones because of the risk of obstruction, cholangitis and pancreatitis. Sphincterotomy and

sphincteroplasty facilitate access into the biliary system. Basket and balloon catheters are useful to remove stones up to 1.5 cm in diameter. The use of wire-guided basket or balloon catheters allows proper access into the intrahepatic system to remove intrahepatic stones or migrated stones. Stones above a bile duct stricture will require balloon dilation of the stricture prior to successful removal. The use of mechanical lithotripsy to break up the stones facilitates duct clearance of large stones or stones above a stricture. Mechanical lithotripsy is very effective in achieving common duct clearance and the use of intraductal lithotripsy is limited to 5% of very difficult ductal stones.

REFERENCES 1.

2.

3.

4.

5. 6.

7.

8.

9.

10.

11.

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Lauri A, Horton RC, Davidson BR, et al. Endoscopic extraction of bile duct stones: management related to stone size. Gut. 1993; 34:1718–1721. Palmer KR, Hoffman AF. Intraductal monooctanoin for the direct dissolution of bile duct stones. Experiences in 343 patients. Gut 1986; 27:196–202. Kaye GL, Summerfield JA, McIntyre N, et al. Methyl tert butyl ether dissolution therapy for common bile duct stones. J Hepatol 1990; 10:337–340. Neoptolemos JP, Hall C, O’Connor HJ, et al. Methyl tert butyl ether for treating bile duct stones: the British experience. Br J Surg 1990; 77:32–35. Stock SE, Carlson GL, Lavelle MI, et al. Treatment of common bile duct stones using monooctanoin. Br J Surg 1992; 79:653–654. Cotton PB, Forbes A, Leung JWC, et al. Endoscopic stenting for long-term treatment of large bile duct stones: 2- to 5-year followup. Gastrointest Endosc 1987; 33:411–412. Foutch PG, Harlan J, Sanowski RA. Endoscopic placement of biliary stents for treatment of high-risk geriatric patients with common duct stones. Am J Gastroenterol 1989; 84:527–529. Van Steenbergen W, Pelemans W, Fevery J. Endoscopic biliary endoprosthesis in elderly patients with large bile duct stones: long-term follow-up. J Am Geriatr Soc 1992; 40:57–60. Siegel JH, Yatto RP. Biliary endoprosthesis for the management of retained common bile duct stones. Am J Gastroenterol 1984; 79:50–54. Maxton DG, Tweedle DE, Martin DF. Retained common bile duct stones after endoscopic sphincterotomy: temporary and longterm treatment with biliary stenting. Gut 1995; 36:446–449. Peters R, Macmathuna P, Lombard M, et al. Management of common bile duct stones with a biliary endoprosthesis. Report on 40 cases. Gut 1992; 33:1412–1415.

12. Riemann JF, Seuberth K, Demling L. Clinical application of a new mechanical lithotripter for smashing common bile duct stones. Endoscopy 1982; 14:226. 13. Riemann JF, Seuberth K, Demling. Mechanical lithotripsy of common bile duct stones. Gastrointest Endosc 1985; 31:207–210. 14. Schneider MU, Matek W, Bauer R, et al. Mechanical lithotripsy of bile duct stones in 209 patients—Effect of technical advances. Endoscopy 1988; 20:248–253. 15. Chung SCS, Leung JWC, Leong HT, et al. Mechanical lithotripsy of large common bile duct stones with a basket. Br J Surg 1991; 78:1448–1450. 16. Shaw MJ, Mackie RD, Moore JP, et al. Results of a multicenter trial using a mechanical lithotripter for the treatment of large bile duct stones. Am J Gastroenterol 1993; 88:730–733. 17. Schutz SM, Chinea C, Friedrichs P. Successful endoscopic removal of a severed, impacted Dormia basket. Am J Gastroenterol 1997; 92:679–681. 18. Leung JW, Chung SC. Electrohydraulic lithotripsy with peroral choledochoscopy. BMJ 1989; 299:595–597. 19. Siegel JH, Ben-Avi JS, Pullano WE. Endoscopic electrohydraulic lithotripsy. Gastrointest Endosc 1990; 36:134–136. 20. Hixson LJ, Fennerty MB, Jaffee PE, et al. Peroral cholangioscopy with intracorporeal electrohydraulic lithotripsy for choledocholithiasis. Am J Gastroenterol 1992; 87:296–299. 21. Ell C, Hochberger J, May A, et al. Laser lithotripsy of common bile duct stones. Gut 1988; 29:746–751. 22. Neuhaus H, Hoffmann W, Gottlieb K, et al. Endoscopic lithotripsy of bile duct stones using a new laser with automatic stone recognition. Gastrointest Endosc 1994; 40:708–715.

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Chapter

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Pancreatic Sphincterotomy Jonathan M. Buscaglia and Anthony N. Kalloo

INTRODUCTION

ENDOSCOPIC PANCREATIC SPHINCTEROTOMY

Since its initial application in 1974, endoscopic biliary sphincterotomy has revolutionized the approach to patients with biliary tract diseases.1 Using biliary sphincterotomy in conjunction with other techniques such as stent placement, balloon and basket extraction of stones, and stricture dilatation, biliary sphincterotomy has become the standard of care for problems that were once only remedied by surgical procedures. Endoscopic therapy for pancreatic disorders has not advanced quite as rapidly, however. The main reason for this seems to be the longstanding fear of inducing pancreatitis in an organ that frequently expresses its dislike for simple manipulation of the papilla and sphincter alone.2 Historically, pancreatitis and its associated complications have prevented some endoscopists from attempting to apply therapeutic techniques similar to those used in treating biliary tract disorders. In addition, clear-cut indications for endoscopic therapy of the pancreas have been much more difficult to define due to a paucity of well-designed clinical trials justifying its use. Most of the techniques that have been used in previous studies were performed on small numbers of patients, and in expert centers only. The majority of studies have been retrospective in design without control groups. There has been a deficiency in studies that utilize randomization and directly compare endoscopic therapy with either surgical or medical therapy.2 It is on this background that we begin to discuss endoscopic pancreatic sphincterotomy. This technique is the cornerstone of endoscopic therapy of the pancreas, and it provides initial access to the main pancreatic duct.3 Once access to the duct is obtained, it may be used as a single therapeutic maneuver (e.g. to treat pancreatic type sphincter of Oddi dysfunction), or in series with other endoscopic therapeutic techniques such as the placement of a stent across a ductal stricture.4 In chronic pancreatitis, for example, pancreatic sphincterotomy not only decreases pressure within the main pancreatic duct, but it may be used to help facilitate the extraction of calculi and protein plugs.1 The ensuing chapter will focus on the endoscopic techniques and the equipment used by most experts who regularly perform pancreatic sphincterotomy. The indications and contraindications for this technique as well as the evidence that supports its basiswill also be discussed. Furthermore, the complications associated with pancreatic sphincterotomy and their management strategies will be outlined. Lastly, we will briefly discuss any existing literature associated with the costs and cost savings of pancreatic sphincterotomy.

Preparation As with all endoscopic procedures, it is imperative to obtain valid informed consent before beginning.5 This becomes of paramount importance when discussing with patients and their families the potential risks involved in performing an ERCP with pancreatic sphincterotomy, as the complication rates are greater when compared with routine upper endoscopy. Routine blood work, including a CBC and coagulation parameters are usually verified before the procedure. Aspirin, NSAIDs, warfarin, and other anticoagulants are withheld for several days before and after the procedure, if possible.5 Antibiotics are frequently given 30–60 minutes before the procedure in an effort to prevent procedure-related infection such as biliary sepsis. The data supporting antibiotic prophylaxis prior to pancreatic or biliary sphincterotomy is sparse and very limited. Only a few studies have attempted to investigate this issue, and most of them have had small numbers with poorly defined endpoints.6 Nonetheless, many endoscopists will utilize antibiotic prophylaxis before (and frequently following) a planned endoscopic sphincterotomy. Coverage with a second- or third-generation cephalosporin appears sufficient. Broader spectrum antibiotics such as piperacillin/tazobactam, or vancomycin and gentamicin if there is a penicillin allergy, may be warranted in some instances.

Equipment Pancreatic sphincterotomy, like biliary sphincterotomy, is performed with a standard side-viewing duodenoscope, the appropriate sphincterotome (papillotome), and an electrosurgical generator.7 There are a variety of options in terms of commercially available electrosurgical generators. Most have both monopolar and bipolar options, and they offer pure cutting, pure coagulation, and blended (cut/coag) current modes.5 These are the same generators that are used when performing polypectomies. Newer models even allow for cutting options that incrementally splice the sphincter muscle in 1 mm segments, while informing the endoscopist with an audible alarm at the end of each segment. This attempts to ensure that the sphincterotomy is performed in a careful, stepwise fashion without producing an unintentional exaggerated cut. However, there is no data that verifies the effectiveness of this method. There is little evidence supporting the use of one current mode over the others during a sphincterotomy. Some data, however, suggests that pure cutting current may be associated with less postERCP pancreatitis when compared to blended current.8 Also, the 129

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pure cutting technique is thought to cause less fibrosis, thus helping to diminish the chance of developing future papillary stenosis. As a result, some endoscopists advocate using only the pure cutting mode when performing a pancreatic sphincterotomy. It is unclear as to whether or not there are truly more bleeding complications associated with this option, as some have suggested. An enormous variety of sphincterotomes and guidewires are now commercially available for use in pancreatic sphincterotomy. For a more detailed description of all endoscopic guidewires and ERCP accessories, refer to Chapter 4. The original Demling-Classen or Erlangen pull-type sphincterotome (bowstring design) is still the most popular choice for performing a pancreatic sphincterotomy (Fig. 14.1). There are several variations in this type of sphincterotome; they are all based upon differences in the length of the exposed cutting wire, the number of additional lumens, and differences in the length of the “nose” of the instrument.5,7 A shorter nose (5– 8 mm beyond the wire) is sometimes more convenient for cannulation of the major papilla prior to sphincterotomy. It allows for easier engagement between the sphincterotome tip and the papilla without much interference from the cutting wire. Once the tip is positioned inside the papillary orifice, tension on the wire may be used to bow the tip into the correct axis and correctly align the instrument for eventual sphincterotomy.7 Sphincterotomes with longer noses (2– 5 cm beyond the wire) lose their ability to bow since most of the cutting wire is retained inside the duodenoscope until deep cannulation is attained. The advantage of this type of sphincterotome is the ability to maintain cannulation while the wire is being withdrawn during sphincterotomy. However, now with triple-lumen cannulas and soft, flexible tip guidewires which cause less injury to the pancreatic duct, a guidewire can be easily left in place within the pancreatic duct in order to maintain cannulation while performing a pancreatic sphincterotomy (wire-guided sphincterotomy). Standard sphincterotomes have a 5 Fr to 7 Fr catheter tip that can accept a 0.035-inch guidewire.9 Use of a triple-lumen cannula allows for the placement of a preloaded guidewire and simultaneous contrast injection without having to remove the guidewire. When

Wire pulled

A Pull type

B Needle knife

Fig. 14.1 Standard sphincterotomes used in pancreatic sphincterotomy. (Reproduced by permission of Division of Gastroenterology and Hepatology, Johns Hopkins Hospital.) 130

manipulating the papilla and the most proximal portions of the main pancreatic duct prior to sphincterotomy, many endoscopists prefer an ultra-tapered catheter tip (5 Fr-4 Fr-3 Fr) for easier cannulation. These sphincterotomes utilize smaller caliber guidewires; frequently down to 0.018-inch in diameter. Conversely, a special 3F cannula can be passed down through the channel of a standard sphincterotome to produce the effect of a tapered tip catheter.9 Endoscopic pancreatic sphincterotomy is performed after deep cannulation of the main pancreatic duct with a guidewire.10 There are several different types of commercially available guidewires that may be used to perform this technique. Such configurations of guidewires include conventional, nitinol, hydrophilic, and “hybrid.” The range in wire diameter is from 0.018-inch to 0.035-inch.11 When performing a wire-guided pancreatic sphincterotomy, the hydrophilic-coated wires with soft and floppy tips may be helpful in preventing trauma to the main pancreatic duct or its side branches.10 As mentioned above, this deep wire-guided technique in pancreatic sphincterotomy has obviated longer-nose sphincterotomes. Maintaining adequate cannulation of the papilla in this manner is less traumatic and more secure.

The endoscopic technique The main principles involved in pancreatic sphincterotomy are very much like those of biliary sphincterotomy. They involve wire-guided cannulation of the duct prior to cutting, and they utilize a slow and stepwise approach that relies on accurate identification of anatomical landmarks. There are essentially two different types of techniques that are used by most expert endoscopists when performing this procedure. The first approach, and the more popular one, is performed while using a standard pull-type sphincterotome. The second approach uses an endoscopic needle-knife to cut the sphincter muscle after placement of a pancreatic duct stent. Both techniques have their advantages and disadvantages, and the details surrounding each approach will be discussed below. In addition, we will briefly describe the technique of precut or “access” pancreatic sphincterotomy in those instances when the endoscopist is faced with a difficult pancreatic cannulation. Sphincterotomy of the minor papilla will be discussed separately in Chapter 15. As with both biliary and pancreatic sphincterotomy, the key to success starts with accurate cannulation of the correct duct. This is, at times, the greatest hurdle for novice therapeutic endoscopists. In general, selective cannulation of the pancreatic duct is easier than that of the biliary duct, assuming there has not been a previous sphincterotomy. The reason for this is directly related to the anatomical axis of each duct in relation to the wall of the duodenum. Although the main pancreatic duct may be tortuous with multiple side branches, the most proximal portion of the duct courses away from the papilla at a 90° angle from the duodenal wall (Fig. 14.2). It then runs more towards the right and straight inside.12 The most distal part of the common bile duct, on the other hand, assumes more of an acute angle in its relationship with the duodenal wall. It extends in an upward and leftward direction from the papillary orifice. This provides for a more difficult cannulation, depending on how acute the angle of take-off is from the papilla. One must remember that a cross-sectional view of the inner portion of the ampulla of Vater (the part furthest from the duodenal lumen) is similar to a “double-eyed onion,” with each duct running off in its own unique direction.12 The most proximal portion of the ampulla, however, is a single orifice that leads from the lumen of the duodenum into a common channel. This common channel then

Chapter 14 Pancreatic Sphincterotomy

Fig. 14.2 Position of the main pancreatic duct and the distal common bile duct in relation to the major papilla. The pancreatic duct runs 90 degrees perpendicular from the duodenal side wall. (Reproduced by permission of Division of Gastroenterology and Hepatology, Johns Hopkins Hospital.)

merges with the so called “double-eyed onion.” The length of this channel is variable, but usually ranges between 1 and 10 mm.7 Within this channel are several folds of papillary mucosa that may often act as obstacles to selective cannulation with the sphincterotome. Therefore, accurate cannulation depends on finding the correct axis with the catheter tip before the guidewire can be pushed all the way out into the main pancreatic duct. Approaching the papillary orifice with the right orientation allows the endoscopist to find the correct axis. When aiming for the pancreatic duct, the catheter should enter the orifice perpendicular to the duodenal wall. Then, in order to traverse the correct plane, the catheter tip should be advanced along the floor of the orifice to find the pancreatic duct. This is in contrast to biliary cannulation, in which the catheter tip is aimed at the roof of the papillary orifice to find the distal common bile duct.7 The only way to ultimately assure correct cannulation is to inject contrast and verify one’s position fluoroscopically. In order to limit the risk of pancreatitis, as little contrast as possible should be used in this situation. The importance of correct ductal axis is paramount. When faced with a difficult cannulation of the pancreatic duct, one may have to lower the catheter tip even further once advancing along the floor of the papillary orifice. This can be achieved by lowering the elevator on the duodenoscope, thus pressing down on the floor.7 The injection of contrast is done simultaneously in an effort to correctly identify the pancreatic duct.

Pull-type sphincterotomy After successful pancreatic cannulation and advancement of the guidewire into the main pancreatic duct, confirmation of position is usually obtained with a contrast pancreatogram. Assuming a clear indication for sphincterotomy has been established, this part of the procedure is most often performed with a pull-type sphincterotome (as mentioned above). Like biliary sphincterotomy, the incision should be “hot and slow.”7 It should be directed towards the 1 to 2 o’clock position with the very distal part of the cutting wire.5,10 In other words, most of the cutting wire should be visible outside the papillary orifice. Note that the direction of the cut is very different from that of a biliary sphincterotomy (Fig. 14.3a–14.3d). In biliary sphincterotomy, the cutting direction is in the 11 o’clock to 1 o’clock position (preferably the 12 o’clock position). The sphincterotome is slightly bowed while the cutting wire is “walked up” the roof of the papilla in a stepwise fashion.7 In pancreatic sphincterotomy, the same principles apply, but the direction is more towards the right, guiding the cutting wire along the floor of the papillary orifice. The actual incision should be performed using the pure cutting current with the electrosurgical generator. This prevents further damage to the pancreas and limits the possible future development of fibrosis and papillary stenosis.10,13 The length of the cut is generally between 5 and 10 mm. Larger diameter ducts require longer cuts in order to achieve the largest possible access. Once the sphincterotomy has been completed, a temporary pancreatic stent is usually left in place for a short period of time in order to help facilitate 131

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Fig. 14.3 A View of the major papilla before pancreatic sphincterotomy. towards the 2 o’clock position.

132

B Sphincterotomy performed with the cutting wire angled

Chapter 14 Pancreatic Sphincterotomy

Fig. 14.3 Continued C Placement of a pancreatic stent following sphincterotomy. D Completion of the sphincterotomy with the stent in good position. (Reproduced by permission of Division of Gastroenterology and Hepatology, Johns Hopkins Hospital.)

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adequate drainage from the duct. The edema that ensues following a pancreatic sphincterotomy can cause ductal obstruction and eventual pancreatitis.14 This policy of placing a pancreatic stent after every pancreatic sphincterotomy, however, is not universal. Some expert endoscopists do not feel the need to perform this step. Moreover, the types of stents that are chosen and the desired duration of use have also been debated.15 Early in the era of pancreatic sphincterotomy, many endoscopists advocated always performing this procedure in concert with a prior biliary sphincterotomy. Biliary sphincterotomy done immediately before pancreatic sphincterotomy is felt by some to allow for easier identification of clear anatomical landmarks, thus making it a safer and more effective procedure. It may provide better exposure of the pancreaticobiliary septum, and therefore allow improved access to the desired pancreatic tissue.16 Also, this technique prevents the rare possibility of biliary complications following a primary pancreatic cut.1 This includes inadvertent damage to the distal bile duct, as well as possible biliary obstruction due to edema adjacent to the biliary duct orifice. Many expert endoscopists recommend a biliary sphincterotomy before a pancreatic sphincterotomy in cases of cholangitis or obstructive jaundice, a common bile duct diameter >12 mm, or an alkaline phosphatase level > twice normal.10 It may also be done when it is needed to obtain better access to the main pancreatic duct.17 When performing a pancreatic sphincterotomy after a biliary sphincterotomy, the anatomical landmarks are different. Part of the papilla has already been filleted open for this procedure, and so the pancreatic orifice is usually seen at the 5 o’clock position near the rightward margin of the sphincterotomy.1 Transient opening of the pancreatic duct will allow for better visualization and more accurate cutting. This may be achieved by gently sucking air into the duodenum with the scope. Once the orifice is correctly identified and cannulated, the sphincterotomy can be carried out in a similar fashion as described above. See Box 14.1.

Needle-knife sphincterotomy An alternative method to pancreatic sphincterotomy utilizes an endoscopic needle-knife instead of a standard pull-type sphincterotome (Fig. 14.1).16 Cutting with the needle-knife is done only after

BOX 14.1 THE PULL-TYPE SPHINCTEROTOME TECHNIQUE • Direction of the incision is along the 1–2 o’clock position • Pure cutting current should be used • Incision should be “slow and hot” • Majority of the cutting wire should be outside the papillary orifice • Length of the incision is generally between 5 and 10 mm • A pancreatic duct stent is inserted after completion • May or may not be preceded by a biliary sphincterotomy

134

placement of a pancreatic duct stent. The tip of the needle-knife is placed at the most proximal portion of pancreatic sphincter tissue that is overlying the stent. While using the stent as a guide to direct the cut along the plane of the pancreatic duct, the needle-knife tip is advanced over the top of the stent and down its longitudinal axis (Fig. 14.4a–14.4b). Incision length is similar to that of sphincterotomy with a pull-type sphincterotome; that is, the length is generally between 5 and 10 mm. Many experts believe that a prior biliary sphincterotomy is especially helpful before utilizing this needleknife technique.16 Good exposure of the pancreaticobiliary septum allows for better tissue access and more effective “septotomy.” There are a few limitations to this technique, however. The absolute prerequisite of pancreatic duct stent placement makes it a technique that may not be feasible if a stent cannot be placed. For example, in chronic pancreatitis, it may be very difficult to insert a stent without first removing ductal calculi.10 Furthermore, utilizing the pull-type sphincterotome technique allows a more complete assessment of sphincterotomy completeness. The endoscopist can reassess the incision and extend the cut, if necessary, with the sphincterotome wire. This is not possible with the needle-knife and stent technique. Lastly, many endoscopists find it simpler and faster to perform the sphincterotomy without having to first place a pancreatic stent (see Box 14.2). Despite the fact that pancreatic sphincterotomy is performed by only two different techniques, survey questionnaires show that there is truly a lack of expert consensus in terms of which is the better approach. A recent survey of 14 expert endoscopists in nine US centers showed that six of the 14 gastroenterologists either “always” or “often” use the pull-type sphincterotome technique, while 7 out of 14 “always” or “often” use the needle-knife technique.15 Eight physicians “always” perform a biliary sphincterotomy prior to pancreatic sphincterotomy, and only two of 14 use pure cutting current during the procedure (Table 14.1). Almost all endoscopists insert a pancreatic stent after sphincterotomy, as it lowers the likelihood of post-ERCP pancreatitis.14 However, which types of stents are used and how long to leave them in place is quite variable among those who perform pancreatic sphincterotomy on a regular basis.15 Questions surrounding these differences among techniques can only be answered with future randomized trials that examine both the shortterm and long-term outcomes of each. See Box 14.3.

Precut pancreatic sphincterotomy The precut pancreatic sphincterotomy refers to an endoscopic technique that allows one to gain access to the pancreatic duct without performing prior deep cannulation. It is usually done when access to the duct is blocked in some manner (e.g. an impacted stone).9,12 Once the pancreatic duct is finally accessed, conventional pancreatic sphincterotomy is then able to be performed. Generally, this technique is not utilized as often as the precut biliary sphincterotomy since a difficult pancreatic duct cannulation is encountered far less often than a difficult biliary cannulation. The pancreatic precut is done in a manner which is very similar to that of the biliary precut sphincterotomy (see Chapter 12). Most endoscopists will use a freehand needle-knife to perform the precut, although there are several options for this technique.9,18 In the case of a stone that is obstructing the pancreatic orifice, for example, a needle-knife can be used to cut the papillary mucosa lying directly over the stone. Once the stone is released and the obstruction is relieved, the pancreatic duct can be cannulated in the usual manner to prepare for a conventional pancreatic sphincterotomy.

Chapter 14 Pancreatic Sphincterotomy

Fig. 14.4 A Sphincterotomy performed with a needle-knife sphincterotome. A pancreatic stent is placed before the sphincter tissue is cut. The stent acts as a guide, directing the cut along the plane of the pancreatic duct. Notice the angle of the cut is in the 2 o’clock position down towards the stent. B Completion of the needle-knife sphincterotomy. (Reproduced by permission of Division of Gastroenterology and Hepatology, Johns Hopkins Hospital.)

INDICATIONS FOR PANCREATIC SPHINCTEROTOMY Unlike endoscopic biliary sphincterotomy, literature that describes and validates the indications for pancreatic sphincterotomy is sparse.

There are several reasons for this disparity. First, pancreatic sphincterotomy appears to be mainly performed at specialized referral centers. Physicians performing this procedure usually have years of experience in therapeutic biliary and pancreatic endoscopy. In order to perform these advanced endoscopic procedures with adequate proficiency, the endoscopist must typically practice in an environ135

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BOX 14.2 THE NEEDLE-KNIFE TECHNIQUE • A pancreatic duct stent is always inserted beforehand • The needle-knife is advanced over the top of the stent • Pure cutting current should be used • Length of incision is between 5 and 10 mm • Frequently preceded by a biliary sphincterotomy

PTS NK EBS PC BC PS

Always

Often

Sometimes

Never

3 1 8 2 12 12

3 6 4

7 5 1

1 2 1

Table 14.2 Indications for endoscopic pancreatic sphincterotomy (EPS)

2

Table 14.1 Differences in technique of pancreatic sphincterotomy based on a survey of 14 expert endoscopists. Modified from Alsolaiman et al.15 with permission PTS = pull-type sphincterotome, NK = needle-knife technique, EBS = endoscopic biliary sphincterotomy before pancreatic sphincterotomy, PC = pure cutting current, BC = blended current, PS = pancreatic stent placement afterwards.

BOX 14.3 CONTROVERSIES SURROUNDING PANCREATIC SPHINCTEROTOMY • Pull-type sphincterotome technique vs. needle-knife technique • Biliary sphincterotomy before pancreatic sphincterotomy? • Blended current vs. pure cutting current • Pancreatic stent vs. no stent after sphincterotomy • If stent, what type of stent? How long should the stent stay in place?

ment which yields a relatively high volume of ERCP (a workload volume which is not seen at most centers). This is usually a larger academic or referral center capable of handling all the possible complications associated with this procedure. Furthermore, it is the relatively high likelihood of complications seen with pancreatic sphincterotomy that creates a general uneasiness among endoscopists, thus contributing to an overall decreased number of physicians performing this technique. As a result, there have been fewer published studies over the years that outline the indications, outcomes, and safety of pancreatic sphincterotomy. It is on this background that we discuss the indications for this technique. 136

1. EPS as primary therapy • sphincter of Oddi dysfunction (SOD) – pancreatic SOD – biliary SOD unresponsive to biliary sphincterotomy • chronic pancreatitis with papillary stenosis/stricture • pancreas divisum (EPS of the minor papilla) 2. EPS to facilitate a further intervention • chronic pancreatitis with ductal strictures or stones treated with pancreatic stents and/or stone removal • pancreatic pseudocysts treated with transpapillary drainage • resection of an ampullary adenoma • pancreatic fistula treated with stent placement • pancreatic disease due to malignancy – primary pancreatic cancer causing strictures, stones, pseudocysts – metastatic disease to the pancreas causing strictures, stones, pseudocysts

Pancreatic sphincterotomy may be indicated for a variety of diseases and disease-related manifestations that involve the pancreas. In general, it is easiest to think about the indications for pancreatic sphincterotomy in terms of primary therapy and secondary therapy (Table 14.2). In other words, this technique may be performed by itself as the primary treatment modality (i.e. for the treatment of pancreatic sphincter of Oddi dysfunction); or it may be utilized as a secondary treatment modality to facilitate a further intervention (i.e. better access to the main pancreatic duct before dilating a downstream dominant stricture). Overall, there is far more data available regarding the use of pancreatic sphincterotomy in conjunction with an additional intervention (secondary therapy) than for using this technique alone (primary therapy).4 Much of the following will concentrate on the indications of pancreatic sphincterotomy as a primary therapy.

Pancreatic sphincterotomy as primary therapy

Pancreas divisum and sphincter of Oddi dysfunction Most of the literature describing pancreatic sphincterotomy as the primary endoscopic therapy of choice is concentrated on the area of pancreas divisum and sphincterotomy of the minor papilla. This topic is covered at length in Chapter 15. Pancreatic sphincterotomy has been shown to provide primary therapeutic benefit in patients with pancreatic-type sphincter of Oddi dysfunction (SOD). A brief review of this disorder is necessary in order to better understand the role of pancreatic sphincterotomy as its main treatment modality. SOD is a benign obstruction to the flow of bile or pancreatic juice at the level of the pancreaticobiliary junction.19 It is due to functional dyskinesia or hypertension of the biliary and/or pancreatic portion of the sphincter. It results in transient noncalculous obstruction, causing abdominal pain or pancreatitis. It can be seen at any age, but it is most commonly encountered in middle-aged women. SOD should always be suspected in those patients who are postcholecystectomy and experiencing biliary-type abdominal pain and/or bouts of acute recurrent pancreatitis. At the present moment, the goldstandard from making the diagnosis of SOD is biliary or pancreatic sphincter manometry (Fig. 14.5A–14.5B). Sphincter of Oddi manometry involves passing a pressure-sensing catheter through a duode-

Chapter 14 Pancreatic Sphincterotomy

Fig. 14.5A–B Pancreatic sphincter of Oddi manometry. The tip of the pressure-sensing catheter lies within the proximal pancreatic (B) and bile (B’) ducts. (Reproduced by permission of Division of Gastroenterology and Hepatology, Johns Hopkins Hospital.)

noscope into the bile duct or pancreatic duct. Pressures can be measured from both portions of the sphincter (biliary and pancreatic) as the catheter is slowly pulled back and positioned within each one of the sphincter zones (Fig. 14.6).19 Elevated pressures may be due to either sphincter muscle dyskinesia or structural stenosis. In pancreatic-type sphincter of Oddi dysfunction, there are essentially three criteria used in making the diagnosis: (a) pancreatic-type pain, (b) amylase/lipase >1.5–2.0 times normal, (c) pancreatic duct diameter >6 mm in the head, or >5 mm in the body (Table 14.3). Type 1 pancreatic SOD has all three components. Type 2 SOD has pancreatic-type pain, plus (b) or (c). Type 3 SOD has just pancreatic-

type pain. In terms of biliary-type SOD, the criteria are very similar but involve the use of serum liver function tests and delayed drainage of contrast from the biliary tree during ERCP (Table 14.4). Isolated pancreatic-type SOD may be seen in 15–20% of all patients with acute recurrent pancreatitis of unknown etiology.19 It has been estimated to occur in 25% of all patients undergoing manometry for suspected SOD. The overall clinical response rate of endoscopic sphincterotomy for SOD (biliary and pancreatic) ranges between 55 and 95%. Patients with Type 1 pancreatic SOD are most likely to benefit from a pancreatic sphincterotomy. Several studies have shown that these patients may experience a significant reduc137

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Fig. 14.6 Biliary sphincter of Oddi manometry. (Reproduced by permission of Gastroenterology and Hepatology, Johns Hopkins Hospital.) (a) pancreatic-type pain (b) amylase/lipase >1.5–2.0 X’s normal (c) pancreatic duct diameter >6 mm in the head, or >5 mm in the body • Type 1 pancreatic-type SOD = (a), (b), (c) • Type 2 pancreatic-type SOD = (a), plus (b) or (c) • Type 3 pancreatic-type SOD = (a) only

Table 14.3 Modified Milwaukee classification for pancreatic-type sphincter of Oddi dysfunction. Adapted from Novak and AlKawas19 by permission of BC Decker Inc.

(a) biliary-type pain (ROME criteria) (b) abnormal AST or alkaline phosphatase >2 X’s normal, on two or more occasions (c) delayed drainage of contrast from the common bile duct on ERCP >45 minutes, and a dilated common bile duct >12 mm • Type 1 biliary-type SOD = (a), (b), (c) • Type 2 biliary-type SOD = (a), plus (b) or (c) • Type 3 biliary-type SOD = (a) only

Table 14.4 Milwaukee classification of biliary-type sphincter of Oddi dysfunction. Adapted from Novak and Al-Kawas19 by permission of BC Decker Inc. tion in pain and clinical episodes of pancreatitis. Type 2 pancreatic SOD may also achieve benefit from a pancreatic sphincterotomy, but most experts prefer to document abnormal pancreatic manometry before undertaking sphincterotomy. In addition, more recent studies have suggested a clinical benefit from pancreatic sphincterotomy in 138

those patients who have persistent pain despite prior biliary sphincterotomy.20

Chronic pancreatitis A pancreatic sphincterotomy alone is frequently used as the primary treatment modality in moderate to severe chronic pancreatitis. The rationale for treating chronic pancreatitis with endoscopic therapy is based on the principle of decreasing pancreatic intraductal pressure. In moderate to severe disease, the development of ductal stones, protein plugs, and ductal strictures may occur. Each of these can cause partial or complete obstruction to the flow of pancreatic juice out into the duodenum, resulting in permanent alterations to the duct morphology (Figs 14.7A–14.7B, 14.8A–14.8B). Ductal obstruction leads to tissue hypertension, and thus tissue ischemia. Karanja et al. demonstrated a reduction of pancreatic blood flow after ligation of the main pancreatic duct (thereby producing intraductal hypertension) in a feline model of pancreatitis.21 The reduction of blood flow was partially reversed after relief of the main duct obstruction. It is strongly believed that the symptom of pain in chronic pancreatitis is directly due to this parenchymal ischemia.1 Another consequence of obstruction of the main pancreatic duct is secondary obstruction of the smaller side branch ducts. This ultimately causes parenchymal atrophy. As the tissue begins to atrophy, the pancreas loses its ability to perform both its endocrine and exocrine functions. A therapeutic intervention that could minimize intraductal pressure might help to prevent this dangerous cascade of events, thus diminishing pain and preserving pancreatic function. This is the basis behind sphincterotomy in chronic pancreatitis. Few studies have specifically examined the role of pancreatic sphincterotomy as the sole endoscopic therapy in chronic pancreati-

Chapter 14 Pancreatic Sphincterotomy

Fig. 14.7 Changes to the ductal morphology seen in moderate severity chronic pancreatitis. (Reproduced by permission of Division of Gastroenterology and Hepatology, Johns Hopkins Hospital.)

Fig. 14.8a–b Changes to the ductal morphology seen in severe chronic pancreatitis. (Reproduced by permission of Division of Gastroenterology and Hepatology, Johns Hopkins Hospital.)

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tis. Most studies that have investigated this topic have done so in the context of additional endoscopic interventions. That is, the sphincterotomy is often performed in conjunction with a further intervention (i.e. stent placement or stricture dilatation). Studies in this area need to be examined closely in order to separate those patients who received a sphincterotomy alone versus those who received a sphincterotomy in concert with an additional endoscopic technique. This is often difficult, especially if the authors have not clearly distinguished between the two groups. Nonetheless, several studies have attempted to evaluate the safety and long-term results of pancreatic sphincterotomy in chronic pancreatitis. Ell et al. described pancreatic sphincterotomy in 118 patients with chronic pancreatitis.22 Eighty percent of the patients underwent a standard pull-type sphincterotomy, while 20% underwent a needleknife technique. Overall, 98% of the sphincterotomies performed were successful, and the complication rate was only 4.2% (four cases of moderate pancreatitis, one case of severe bleeding). The results in terms of pain relief were not examined in this study, however. Okolo et al. retrospectively analyzed 55 patients who had a pancreatic sphincterotomy.23 Forty patients (73%) underwent the procedure for the indication of symptomatic chronic pancreatitis. The goal of the study was to assess the long-term efficacy of sphincterotomy with pain relief being the primary endpoint. After a median followup of 16 months, 60% of all patients reported a significant improvement in their pain scores. Papillary stenosis appears to be a clear-cut indication for pancreatic sphincterotomy alone in those patients with symptomatic chronic pancreatitis. Without significant ductal abnormalities distal to the papilla that require some additional form of intervention, sphincterotomy can be confidently utilized as the primary endoscopic therapy of choice in these patients. Similarly, mucinous ductal ectasia involving the proximal main pancreatic duct for pancreatic sphincterotomy has also been proposed as potentially efficacious in patients with recurrent pancreatitis.4

Pancreatic sphincterotomy as secondary therapy Pancreatic sphincterotomy is commonly performed in concert with other endoscopic techniques such as stent placement or balloon dilatation of the main duct. In this setting, the purpose of the sphincterotomy is to help facilitate the primary therapy (i.e. removal of stones from the duct or dilatation of a ductal stricture). There are several diseases and conditions in which pancreatic sphincterotomy is used in this manner (Table 14.2). The decision to cut the sphincter in these situations is based on sound clinical judgment by the endoscopist, and whether or not he feels that the risk of a sphincterotomy is outweighed by the potential benefit that may be gained by aiding the primary therapy. In moderate to severe chronic pancreatitis, ductal strictures and stones are often times the norm. Frequently, their location within the main duct may be very distal to the papilla. Therefore sphincterotomy alone may not be sufficient. Stone removal or stricture dilatation may therefore be the main goal of ERCP for certain patients. Pancreatic sphincterotomy may be needed before the procedure for better access to the duct (precut), or it can be used simply to help reduce intraductal hypertension and allow for easier flow of juice and calculous debris into the duodenum. This also holds true, for example, when treating pancreatic pseudocysts by means of a transpapillary approach. For those pseudocysts that communicate with the main pancreatic duct, a stent is placed within the duct in order to bridge the fistulous connection.24 A pancreatic sphincterotomy in 140

this setting also helps to reduce intraductal pressures and facilitate flow out towards the papilla. Other clinical scenarios for which sphincterotomy has been proposed as secondary therapy include stent placement prior to surgery for mucinous ductal ectasia, as well as stent placement in the treatment of a pancreatic fistula.4 Pancreatic sphincterotomy may also be used in concert with a pancreatic stent following the resection of an ampullary adenoma. Here, the purpose of the sphincterotomy (and the stent) is to reduce the risk of post-procedural pancreatitis due to periampullary edema. Finally, sphincterotomy is often indicated for the palliative treatment of strictures, stones, and pseudocysts in malignant obstruction of the pancreas.

COMPLICATIONS OF PANCREATIC SPHINCTEROTOMY Although the first endoscopic pancreatic sphincterotomy was performed almost 30 years ago, the technique has not been used nearly as often as biliary sphincterotomy.25 The reason for this is partly due to past uncertainty about its indications, and also concerns over the relatively high likelihood of complications related to this procedure.26 When discussing the complications associated with pancreatic sphincterotomy, it must be remembered that studies which have evaluated this topic are generally small in number and have a small number of participants. They are usually performed at expert referral centers only, and they most often do not have control groups.2 Furthermore, most of the studies report on pancreatic sphincterotomy as it is used to facilitate other endoscopic maneuvers, such as pancreatic stent placement, balloon dilatation, or stone removal. Therefore it is often difficult to decipher which maneuver is truly responsible for the complication. For example, is the resultant pancreatitis due to the stricture dilatation alone, or the sphincterotomy that was first required to access the duct? These are the types of issues that complicate the literature in this area of study. It is on this background in which we discuss the complications that are associated with pancreatic sphincterotomy. In general, there are essentially three different types of complications associated with pancreatic sphincterotomy: early, late, and stent-related complications (Table 14.5).26 Early complications are usually recognized within the first 72 hours after the procedure, but

Early complications (<3 months, typically <72 hours) Pancreatitis Severe bleeding Perforation Pancreatic and/or biliary sepsis Late complications (>3 months) Papillary stenosis Proximal pancreatic duct strictures Stent-related complications (variable timing) Ductal and parenchymal changes Stone formation Infection Ductal perforation Stent migration Stent occlusion Duodenal erosion

Table 14.5 Complications of pancreatic sphincterotomy

Chapter 14 Pancreatic Sphincterotomy

Author (ref )

n

Pancreatitis

Total complications

Kozarek et al.17 Esber et al.27 Parsons et al.28

56 236 31

4 (7.1%) 33 (14%) 1 (3.2%)

6 (10.7%) 37 (15.7%) 1 (3.2%)

Table 14.6 Recent studies reporting early complications of pancreatic sphincterotomy. Adapted from Sherman and Lehman26 with permission

often within the first few hours. They include pancreatitis, severe bleeding, perforation, and pancreatic or biliary sepsis. Late complications are encountered at least three months after the procedure, and this category mainly consists of papillary stenosis and proximal ductal strictures. On the other hand, there are several complications that are stent-related. The timing of their occurrence is variable. They include pancreatic ductal and parenchymal changes, stone formation, infection, ductal perforation, stent migration, stent occlusion (causing pain and/or pancreatitis), and duodenal erosion. Within the last 12 years, there have been three major studies that have examined the rates of complication associated with pancreatic sphincterotomy (Table 14.6).17,27,28 In a study by Kozarek et al. 56 patients underwent a pancreatic sphincterotomy. Fifty-four (96%) patients had chronic pancreatitis and two patients had acute recurrent pancreatitis. The indications for the sphincterotomy were as follows: obstructing ductal calculi,26 ductal disruption and leak,12 sphincter stenosis,10 and dominant stricture.8,17 Forty-seven patients had a pull-type sphincterotomy, and 33 of these patients also had a pancreatic stent placed after the sphincterotomy. Nine patients had a needle-knife sphincterotomy over an existing pancreatic stent. Early complications occurred in 10.7% of the patients, and they included pancreatitis (four patients, or 7.1%) and cholangitis (two patients, or 3.6%). Late complications, however, occurred in 30% of the patients; 14% with papillary stenosis and 16% with asymptomatic ductal changes (thought to be due to the stent placement). Esber et al. reported the complications of pancreatic sphincterotomy in 236 consecutive patients.27 A pull-type sphincterotomy was performed in 123, and 87 patients in this group also had a stent placed following the sphincterotomy. Needle-knife sphincterotomy over a pancreatic stent was performed in 113 patients. Seventy-four percent of the patients had a sphincterotomy for the purposes of treating pancreatic-type SOD, while 26% had chronic pancreatitis and the procedure was performed to facilitate an additional endoscopic maneuver such as removal of stones, stricture biopsy, etc. Overall, post-ERCP pancreatitis occurred in 14% (mild in 76%, moderate in 21%, and severe in 3%). Other various complications occurred in only 1.7% of the cases. The rate of pancreatitis was 15.5% in the patients with pancreatic-type SOD and 9.7% in patients with chronic pancreatitis. It was suggested that the lower rate of post-ERCP pancreatitis in chronic pancreatitis patients was due to all the periductal fibrosis and scarring. In other words, the limited amount of nearby healthy pancreatic parenchyma offers some protection against the injury that occurs after a pancreatic sphincterotomy.17,26 Parsons et al. evaluated the complication rate of performing a stentless pancreatic sphincterotomy.26 In 31 patients, sphincterotomy was done with a pull-type sphincterotome followed by the placement of a nasopancreatic tube. All the tubes were removed within 24 hours of placement. Post-ERCP pancreatitis was observed in one patient (3.2%), and there were no other complications seen such as perforation, bleeding, or sepsis.

Overall, the rate of pancreatitis following a pancreatic sphincterotomy appears to be approximately 10–12%, with a total early complication rate (perforation, bleeding, etc.) between 10% and 15%. Pancreatitis occurs more frequently in those patients with pancreatic-type SOD, rather than those who have it performed for problems associated with chronic pancreatitis. Thorough data concerning the use of pancreatic stents in the prevention pancreatitis following a pull-type sphincterotomy is somewhat lacking. Sherman et al. showed that a pancreatic stent used with needle-knife sphincterotomy may limit the frequency of post-procedural pancreatitis in SOD patients.29 The problem, however, is that if the stent is left in place for too long, it may begin to induce unwanted ductal and parenchymal changes itself. Also, patients must undergo an additional procedure to have this endoprosthesis removed unless a 3 Fr prosthesis is routinely employed. Pancreatitis is the most concerning potential complication for those endoscopists who perform pancreatic sphincterotomy. This is mainly because it appears to be the complication over which we have the least amount of control, and also because its effect may be very severe and sometimes lethal. The decision to place a stent following sphincterotomy is made on a case-by-case basis. Factors weighed in the decision include the perceived risk of early pancreatitis versus the potential for late complications and the need for an additional procedure.

THE COST OF PANCREATIC SPHINCTEROTOMY There is little published information regarding the cost and cost savings of pancreatic sphincterotomy. We assume that endoscopic therapy for diseases such as chronic pancreatitis and sphincter of Oddi dysfunction ultimately reduce long-term costs by decreasing the frequency of hospitalizations and the number of required surgical interventions; yet there is truly a lack of data in the current medical literature pertaining to this area of interest. The reason for this may be the enormity and complexity of such a study. In order to yield useful and effective information, it would need to be conducted over many years, and preferably in several different centers. Studies with such difficult endpoints and complex variables are less likely to be initiated by the majority of investigators. There are some studies, however, that have examined the ability to safely perform endoscopic pancreatic sphincterotomy on an outpatient basis. Presumably, the importance of this idea centers around the reduction of unnecessary overnight observational admissions; thereby reducing the overall costs associated with therapeutic pancreatic endoscopy. Tham et al. reviewed 190 patients undergoing planned outpatient therapeutic ERCP.30 Five patients had a pancreatic sphincterotomy alone, and 28 patients had pancreatic stent insertion. Admission was necessary in 31 patients (16%). Five of the 31 patients (3% overall) were admitted from home following a median interval of 24 hours after discharge. The other 26 patients (13% overall) were admitted directly from the endoscopy unit because of obvious, discernable post-procedural complications. In the 219 consecutive inpatients undergoing ERCP, there was an overall complication rate of 13%. The authors claim that “a policy of selective outpatient therapeutic ERCP, with admission reserved for those with established or suspected complication, appears to be safe and reduces health care costs.”30 More studies in this area are needed to assess issues of cost and safety in outpatient therapeutic pancreatic endoscopy. 141

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REFERENCES 1.

2. 3.

4.

5.

6.

7.

8.

9. 10.

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Cremer M, Deviere J. Chronic pancreatitis. In: Testoni PA, Tittobello A, eds. Endoscopy in pancreatic disease: diagnosis and therapy. Chicago: Mosby-Wolfe; 1997:99–112. Mergener K, Kozarek RA. Therapeutic pancreatic endoscopy. Endoscopy 2005; 37(3):201–207. Howell DA, Holbrook RF, Bosco JJ, et al. Endoscopic needle localization of pancreatic pseudocysts before transmural drainage. Gastrointest Endosc 1993; 39:693–698. Elton E, Howell DA, Parsons WG, et al. Endoscopic pancreatic sphincterotomy: indications, outcomes, and a safe stentless technique. Gastrointest Endosc 1998; 47(3):240–249. Shields SJ, Carr-Locke DL. Sphincterotomy techniques and risks. In: Cotton PB, Hawes RH, eds. Gastrointestinal endoscopy clinics of North America. Philadelphia: Saunders; 1996:17–42. Batovsky M, Valko L, Paulen P, et al. Prophylactic effects of ceftriaxone in patients after endoscopic papillosphincterotomy. Bratisl Lek Listy 1999; 100(3):164–167. Cotton PB, Williams CB. Therapeutic ERCP. In: Practical gastrointestinal endoscopy, 3rd edition. London: Blackwell; 1990:118–156. Elta GH, Barnett JL, Brown KA. Pure cut electrocautery current for sphincterotomy causes less post-procedure pancreatitis than blended current (abstr). Gastrointest Endosc 1995; 41:A400. Freeman ML, Guda NM. ERCP cannulation: a review of reported techniques. Gastrointest Endosc 2005; 61(1):112–125. Delhaye M, Matos C, Deviere J. Endoscopic management of chronic pancreatitis. In: Chuttani R, Pleskow DK. Gastrointestinal clinics of North America. Philadelphia: Saunders; 2003:717–742. Jacob L, Geenan JE. ERCP guide wires. Gastrointest Endosc 1996; 43:57–60. Maydeo A, Borkar D. Techniques of selective cannulation and sphincterotomy. Endoscopy 2003; 35(S1):S19–S23. Deviere J, Delhaye M. Pancreatic duct stones management. Gastrointest Endosc Clin N Am 1998; 8:163–179. Sherman S, Lehman GA, Hawes RH, et al. Pancreatic ductal stones: frequency of successful endoscopic removal and improvement in symptoms. Gastrointest Endosc 1991; 37:511–517. Alsolaiman M, Cotton P, Hawes R, et al. Techniques of pancreatic sphincterotomy: lack of expert consensus. Gastrointest Endosc 2004; 59(5):AB210. Kozarek RA, Ball TJ, Patterson DJ, et al. Endoscopic pancreatic duct sphincterotomy: indications, technique, and analysis of results. Gastrointest Endosc 1994; 40(5):592–598.

17. Kim MH, Myung SJ, Kim YS, et al. Routine biliary sphincterotomy may not be indispensable for endoscopic pancreatic sphincterotomy. Endoscopy 1998; 30:697–701. 18. Freeman ML. Precut (access) sphincterotomy. Techniques in Gastrointestinal Endoscopy 1999; 1:40–48. 19. Novack DJ, Al-Kawas F. Endoscopic management of bile duct obstruction and sphincter of Oddi dysfunction. In: Bayless TM, Diehl AM, eds. Advanced therapy in gastroenterology and liver disease. Hamilton: B.C. Decker; 2005:766–773. 20. Touli J, Roberts-Thompson IC, Kellow J, et al. Mannometry based randomized trial of endoscopic sphincterotomy for sphincter of Oddi dysfunction. Gut 2000; 46:98–102. 21. Karanja N, Widdison AL, Leung F, et al. Compartment syndrome in experimental chronic pancreatitis: effect of decompressing the main pancreatic duct. Br J Surg 1994; 81:259–264. 22. Ell C, Rabenstein T, Schneider HT, et al. Safety and efficacy of pancreatic sphincterotomy in chronic pancreatitis. Gastrointest Endosc 1998; 48(3):244–249. 23. Okolo PI, Pasricha PJ, Kalloo AN. What are the long-term results of endoscopic pancreatic sphincterotomy? Gastrointest Endosc 2000; 52(1):15–19. 24. Buscaglia JM, Jagannath SB. Endoscopic decompression of pancreatic pseudocysts. Practical Gastro 2005; 29(3):74–83. 25. Cremer M, Deviere J, Delhaye M, et al. Non-surgical management of severe chronic pancreatitis. Scand J Gastroenterol 1990; 25(S175):77–84. 26. Sherman S, Lehman GA. Complications of endoscopic pancreatic sphincterotomy. In: Testoni PA, Tittobello A, eds. Endoscopy in pancreatic disease: diagnosis and therapy. Chicago: Mosby-Wolfe; 1997:167–171. 27. Esber E, Sherman S, Earle D, et al. Complications of major papilla pancreatic sphincterotomy: a review of 236 patients. Gastrointest Endosc 1995; 43:405A. 28. Parsons WG, Howell DA, Qasseem T, et al. Pancreatic duct sphincterotomy without stenting. Gastrointest Endosc 1995; 41:427A. 29. Sherman S, Eversman D, Earle D, et al. Sphincterotomy by needle knife over pancreatic stent technique lowers the post-procedure pancreatitis frequency and severity in sphincter of Oddi dysfunction patients. Gastrointest Endosc 1996; 43:413A. 30. Tham TC, Vandervoort J, Wong RC, et al. Therapeutic ERCP in outpatients. Gastrointest Endosc 1997; 45(3):225–230.

SECTION 2

Chapter

15

TECHNIQUES

Minor Papilla Endoscopic Sphincterotomy James L. Watkins and Glen A. Lehman

INTRODUCTION The decision to perform a minor papilla endoscopic sphincterotomy is a serious one. This chapter assumes indications, patient selection, pre-ERCP evaluation and informed consent have all been appropriately addressed. The largest category of candidate patients will be those with idiopathic recurrent chronic pancreatitis and pancreas divisum.1 Endoscopic visualization aspects of ERCP have improved greatly in the past decade. This now makes minor papilla and minor papilla orifice identification a simpler task. Accessory tools for cannulation and sphincterotomy have similarly advanced. Before addressing minor papilla therapy, usually diagnostic ventral (major papilla) pancreatography and dorsal pancreatic ductography via minor papilla cannulation will have been done as described in Chapter 8. This chapter is oriented toward minor papilla therapy of pancreas divisum or incomplete pancreas divisum. The same techniques apply if minor endoscopic sphincterotomy is needed in patients with normal main duct/accessory duct anatomy. The opinions here are based mainly on our team experience gained from greater than 700 minor papilla sphincterotomies. Where other case series or scientific data exist, these will be discussed.

after administration. This Secretin effect usually lasts greater than 30 minutes. Methylene blue (Faulding Puerto Rico, Inc., Aguadillia, Puerto Rico) should be available to identify the minor papilla or its orifice. It should also be in the endoscopy room for all pancreas cases.2

ACCESSORIES/GUIDEWIRES In general, similar accessories are used for major and minor papilla endoscopic sphincterotomy, i.e. pull sphincterotome or needle-knife. The exception may be in the very small (or stenotic) minor papilla orifice which requires dilation with a highly tapered push catheter (e.g. 3-4-5 Fr, Cook Endoscopy, Winston-Salem, NC) (Fig. 15.3) before passage of a pull sphincterotome. Minor papilla deep cannulation usually requires an 0.018–0.021″ diameter guidewire (e.g. RoadRunner, Cook Endoscopy, WinstonSalem, NC). A very soft tip guidewire is preferred for atraumatic deep cannulation. The guidewire is preferably passed to the mid body of the dorsal duct of the pancreas (4–6 cm into the duct) before even touching the minor papilla with the catheter or sphincterotome. This helps to avoid minor papilla orifice trauma which makes subsequent cannulation even more difficult.

Pull-type sphincterotome

INDICATIONS/CONTRAINDICATIONS TO MINOR PAPILLA SPHINCTEROTOMY Indications for minor papilla sphincterotomy are similar to indications for major papilla sphincterotomy (Table 15.1). Most patients who need minor papilla sphincterotomy will have pancreas divisum. Table 15.2 reviews contraindications to minor papilla therapy. The clinician is reminded that errors in patient selection and technique may cause serious complications including pancreatitis, perforation, or stricture formation.

SEDATION AND SUPPLEMENTAL DRUGS Sedation/analgesia for minor papilla cases is the same as for more difficult or long duration major papilla cases. Approximately 7% of our cases are done with general anesthesia. Minor papilla cases are more tedious and a quiet cooperative patient is mandatory. Drugs to stop motility are needed. Glucagon is routinely given in 0.25–0.5 mg increments and repeated as often as needed. Secretin (ChiRhoClin, Inc., Silver Spring, MD) needs to be readily available (in room, not a pharmacy trip away). Currently available Secretin gives vigorous pancreatic juice flow approximately 5–10 minutes

Any standard wire-guided sphincterotome can be used if the papilla is first dilated with a push catheter. We use a 4–5 Fr diameter short tipped (2–3 mm tip extending beyond cutting wire) sphincterotome and prefer a 20–25 mm length cutting wire, but a 30 mm long wire is acceptable (Fig. 15.4).

Needle-knife We prefer a needle-knife with a 0.012″ diameter cutting wire. The retractable wire extends 4 mm beyond a 3 Fr insulated coating (Fig. 15.5). Needle-knives with large diameter cutting wires are discouraged as they coagulate too much and cut slowly, which may contribute to stenosis of the pancreatic duct. A needle-knife can be converted from any commercially available endoscopic pull sphincterotome by cutting off the plastic tip at the point where the distal cutting wire inserts into the sphincterotome. This frees the residual bare wire which is then used for cutting.

Cautery unit There are no studies which address optimal cautery features for minor papilla sphincterotomy.3 Our personal experience has favored use of ERBE model ICC350 (ERBE USA Inc., Marietta, GA) with setting of Effect 3 and watt setting of 150. If pure cutting current is 143

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• Pancreas divisum with recurrent or disabling symptoms (to improve dorsal ductal juice flow). • Pancreas divisum with dorsal duct dilation and parenchymal atrophy (even though without pancreatic symptoms). • Provide access to dorsal ductal system, e.g. for stone removal; biopsy. • Permit placement of stents larger than 5 French. • Facilitate mucus exiting minor papilla, e.g. mucinous tumor (Figure 15.1). • To aid guidewire passage out major papilla (guidewire passage into minor papilla and then out major papilla back into the duodenum) in patient with failed cannulation of major papilla and anticipated need for major papilla/main duct at major papilla/pancreatic therapy.

Table 15.1 Indications for minor papilla sphincterotomy

• Pancreas divisum with minimal or vague symptoms (especially when associated with normal dorsal duct diameter on CT scan or MRCP) • Coagulopathy • Inadequate endoscopic view of minor papilla and surrounding duodenal wall (Figure 15.2) • Operator inexperience • Inadequate informed consent

Fig. 15.2 Minor papilla seen at 6 o’clock position (arrow) of diverticulum. Minor papilla endoscopic sphincterotomy was not attempted.

Table 15.2 Contraindications to minor papilla sphincterotomy

Fig. 15.3 Various tapered-tip catheters and guidewires used in minor papilla therapy.

Fig. 15.1 Widely patent minor papilla associated with intraductal mucin producing neoplasm. Minor papilla sphincterotomy done to facilitate mucus flow. Clinical pancreatitis did not recur while patient awaited resective surgery. Fig. 15.4 desired, the setting is Effect 1 with the computer regulated “endocut” feature (which alternates cutting and coagulation current) being shut off. Pure cutting current may induce less scar formation after sphincterotomy but this has not been evaluated in prospective trials. Pure cutting current has not decreased pancreatitis rates when used for major papilla work.4 144

Short-nosed pull-type sphincterotome.

Stents associated with minor papilla sphincterotomy Nearly all needle-knife sphincterotomies are done over a previously inserted plastic pancreatic stent. Although we have used a variety of stents ranging from 3 to 7 Fr in diameter,5 we strongly recommend

Chapter 15 Minor Papilla Endoscopic Sphincterotomy

Fig. 15.5 Typical taper-tipped guidewire used in minor papilla therapy. Needle-knife with 4 mm long cutting wire. Needle-knife sphincterotome.

initial use of 3 Fr stents as they adequately decompress the dorsal duct and induce minimal ductal reaction.6–8 Unflanged stents are routinely used and spontaneously pass out of the minor papilla in 90% of cases over two weeks. Larger diameter stents are now discouraged as they are unnecessary for prevention of post-ERCP pancreatitis and are more hazardous to the dorsal duct.

Fig. 15.6 Guidewire in minor papilla. Note major papilla in left lower photo. Planned minor papilla sphincterotomy should progress along 10–11 o’clock course to the junction of papillary mound and flat wall.

Choosing between pull sphincterotome and needle-knife sphincterotome A pull sphincterotome is preferred if (1) the angle of approach to the minor papilla is difficult for any reason, e.g. duodenal inflammation, variant anatomy; (2) duodenal motility is difficult to control; (3) Insertion of multiple pancreatic stents is desired after endoscopic sphincterotomy. Needle-knife sphincterotomy performed over a pancreatic stent has several advantages over the pull sphincterotomy method. The needle-knife method has the ability to cut more delicately and precisely without the restriction incurred by the pull sphincterotome. We suggest that the application of excessive cautery to the terminal pancreatic duct is less likely (but unproven) with needle-knife technique. Pull sphincterotomy more commonly passes >5 mm cutting wire into the orifice and extends the thermal effect into the pancreas, not just the duodenal wall “sphincter zone.” However, a recent database review from our unit showed that >80% of the last 100 minor papilla sphincterotomies were done by the pull technique.

Minor papilla endoscopic sphincterotomy technique—pull type Once a 0.018–0.025 inches guidewire is securely advanced intraductally to at least the mid body of the dorsal duct, the sphincterotome is advanced with the cutting wire oriented toward the 10–11 o’clock position. This is often the unadjusted orientation after sphincterotome passage. Alternatively, this may require the “long scope” position. The pull back “short scope” position tends to cut more toward the 11–12 o’clock position. The latter cut tends to produce more coagulation and probably results in an overall smaller orifice. The papilla is positioned in the lower to mid visual field on the video monitor (Figs 15.6–15.7). This allows for better view of the target tissue. The pull endscopic sphincterotome is then positioned with 3–4 mm of cutting wire into the orifice. The cut is initiated with 2–3 half-second taps on the cautery activation foot pedal. If cutting

Fig. 15.7 Minor papilla sphincterotomy in setting of redundant folds. The cut was in the 11–12 o’clock direction. The upper margin of the papillary mound is less certain.

begins, the foot pedal is continuously activated until the cut is nearly complete. The last 1 mm cut is performed again with 1–2 taps on the cautery activation foot pedal. If no cutting is initiated (only white char) after 2–3 taps followed by 1 second of continuous activation, then all cutting is stopped and the remainder of the sphincterotomy is performed using the needle-knife method. The cut is extended into the 10–11 o’clock direction as directed by the intraductal wire. Pulling back on the bowed sphincterotomy helps expose the available cutting space (Fig. 15.8). The sphincterotome is bowed so as to achieve moderate tension on the tissue. This allows more rapid cutting with less char. Inadequate wire contact results in inadequate cutting and may result in excess coagulation. Precise cutting requires a relatively “dry” field. Repeated fluid aspiration may be required. Excessive bile, pancreatic juice or other fluid in contact with the cutting wire will divert current away from the target tissue (Fig. 15.9). Such a pool of fluid may boil and broadly coagulate the surrounding tissue. This may result in 145

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A

B

Fig. 15.8 A Pulling out (back) on pull sphincterotome helps to better delineate papillary mound and cutting zone. B Pull out view accentuating the minor papilla mound and better defining the safe cutting zone.

Fig. 15.10 Minor papilla sphincterotomy by pull technique sequence. With placement of 5 French stent, our current recommendation is to use small caliber stents, e.g. 3 French.

Fig. 15.9 Minor papilla after ~80% of mound has been cut toward the 10–11 o’clock position. After suctioning bilious fluid, the upper rim of mound was cut.

serious stricture formation. Fluid pooling is especially problematic if secretin was given to aid orifice identification. Pancreatic stent placement with juice diversion and needle-knife sphincterotomy are then recommended. The goal is to cut to the upper rim of the minor papilla mound per se. Alternatively, some of our team members prefer to stop 1 mm short of the minor papilla-flat wall junction (Figs 15.10, 15.11). We attempt to orient the cutting wire perpendicular to the duodenal wall. This helps to limit excessive thermal effect to the intramural portion and avoid ductal injury. If the minor papilla mound is very small, the cut may extend 1–2 mm cephalad to the mound. With a small minor papilla, the “completed cut” minor papilla allows an approximately 1/4–1/3 bowed sphincterotome to pull through the sphincter. For a larger papilla, a 1/3–1/2 bowed 25 mm wire sphincterotome will pull through the sphincterotomy with only mild resistance. To view the ductal lumen per se is usually only possible with “large” papilla cases. After pull endoscopic sphincterotomy, a temporary pancreatic stent is placed in nearly all cases. Occasionally, in advanced chronic pancreatitis, with very dilated dorsal pancreatic duct (>8 mm), stent 146

Fig. 15.11 View of minor papilla 19 months after endoscopic sphincterotomy. Note no papillary mound remains. The cut extended up to the flat wall.

placement is not needed. Over the last 15 years, stent experience has now led to preferred use of very small diameter (3 Fr) 6–8 cm long polyethylene stents with no intraductal barb.5 We prefer a 3/4 pigtail for the duodenal end but double barbs in duodenum are acceptable. The intraductal length serves as a friction anchor (without barb) yet the small diameter causes less “ductitis” than larger diameters. We have abandoned 2–3 cm 5 Fr stents as the intraductal ends cause more focal ductitis (and occasionally strictures). This occurs especially when the firm stent tip abuts the wall perpendicularly at an angulation in the duct.

Chapter 15 Minor Papilla Endoscopic Sphincterotomy

A follow-up plain abdominal x-ray must be obtained in approximately two weeks to confirm spontaneous stent passage. Residual intraductal stents (5–10% of patients) require endoscopy with stent extraction. Patients who refuse follow-up are problematic. For patients who are predicted to be unreliable at follow-up, alternatives include: (1) hospitalization and stent removal 2–3 days later (if not passed spontaneously), or (2) placement of a nasopancreatic catheter for a duration of 2–3 days. The minimal interval for effective post sphincterotomy protective pancreatic stenting has not been defined but we suspect it is 2–3 days.

Needle-knife sphincterotomy over pancreatic duct stent After wire passage deep into the dorsal duct, a pancreatic stent is placed as noted above. Care is taken during final stent delivery (final guidewire withdrawal) to maneuver the pigtail toward the descending duodenum (downward) (Fig. 15.12). This aids minor papilla viewing during cutting and at times lifts the minor papilla up for easier cutting. For cutting, the minor papilla is positioned in the lower to mid visual field on the video screen. This allows better view of the upper rim of the minor papilla. The needle-knife should be maneuvered over the cutting zone of the minor papilla orifice to the upper extent of the minor papilla mound in a “dry run” fashion being sure that the accessory channel

A

B

elevator permits a full extent excursion of this distance. The cut is then initiated (usually start at orifice then cephalad) by lightly hooking (embedding) the terminal 1–2 mm of needle-knife wire into the minor papilla orifice (Fig 15.13). Light, but definite cephalad tension is placed on the wire and current activation done. We generally use continuous foot pedal activation with the ERBE cautery generator while sweeping the needle-knife cephalad over nearly the full extent of the minor papilla mound. This sequence is repeated cutting another 1–2 mm deeper into the mound and exposing more intramural stent. The cut tissue tends to retract exposing the deeper tissue. The cut is extended cephalad until the upper mm of the minor papilla mound is divided. The needle-knife catheter (with needle retracted) is then passed alongside the stent into the pancreatic duct. If the orifice does not permit this, cutting 1–2 mm of the tissue touching the upper rim of the stent is done until cannulation permitted. The above cutting is done in the 10–11 o’clock direction—precisely over the stent. An alternative cutting method is to start at the apex of the anticipated cut and cut downward onto the stent. This more precisely defines the most cephalad extent of the cut. Unintentionally cutting more cephalad than desired can more easily be avoided.

PRECUT SPHINCTEROTOMY TECHNIQUE Precutting refers to cutting the minor papilla without prior deep cannulation, wire passage, or stent placement (Fig. 15.14). Precutting is more risky than the above techniques because if cannulation fails there is no protective pancreatic duct stent. Careful risk:benefit analysis should therefore precede any decision to initiate precut sphincterotomy. Three subcategories exist: (1) minor papilla orifice evident; (2) no minor papilla orifice seen; (3) Santorinicele present.

Precut minor papilla—orifice seen

Fig. 15.12 A Pigtail stent placement with downward placement of pigtail. This facilitates cephalad view of cutting space. B Cutting with needle-knife over stent.

In such cases, the orifice usually can be entered 1–2 mm even if not deeply cannulated. In most cases, Secretin (ChiRhoClin, Inc. Silver Spring, MD) 0.2 mcg/kg IV has already been given to aid orifice identification. The needle-knife cutting wire is extended 1– 2 mm and impacted in the orifice cephalad rim. Cutting is then done toward the 10–11 o’clock direction in identical fashion as to needleknife over stent. We prefer to cut all the way to the rim of the papilla. A second cut is then made 1–2 mm deeper into the base of the first incision or slightly left or right of the first incision. If secretin was

Fig. 15.13 Diagram of needle-knife over pancreatic stent technique.

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A

B

C

D

Fig. 15.14 A Minor papilla with orifice seen (arrow) as pink dot in blue background. Secretin was given 10 minutes prior to aid orifice identification. B After precut minor papilla sphincterotomy. C Deep cannulation achieved and sphincterotomy completed by pull technique. D 3 French plastic stent placed after sphincterotomy.

Fig. 15.16 Santorinicele. Dorsal ductogram showing saccular dilation of downstream terminal end of duct.

attempted with a soft tip guidewire (e.g. Metro 0.021–0.025 inches or a blunt tip guidewire such as 0.035 Teflon-coated stainless steel coil wrapped wire (Cook Endoscopy, Winston-Salem, NC)). Gentle probing is mandatory and helps avoid bleeding, which may obscure landmarks. Probing should be toward the 10–11 o’clock direction varying from 45 to 90 degrees (perpendicular) to the wall. If cannulation fails and the precut area maintains a clear view, additional shallow cuts of 3–4 mm length and 1–2 mm depth can be made on each side of the original cut or into the base of the first cuts. Secretin use and gentle probing continue until successful ductal entry or termination of the procedure. With ductal entry, completion sphincterotomy is done with either pull technique or needle-knife over stent technique as needed above. If no ductal entry is achieved, repeat cannulation attempt is best delayed at least 4 weeks until complete healing of the precut area is achieved, if the clinical conditions permit such waiting time.

Precut—no orifice seen When considering precutting and no orifice (and usually no juice flow) can be identified, review carefully whether pancreas divisum or need for minor papilla therapy really exists. If suspicion/need remains high, proceed as follows: Precut identically as above except start on the lower rim of the minor papilla or the point on the minor papilla that the orifice seems most likely. Cut 2–3 mm length, or preferably to the upper rim of the minor papilla. Make 1or 2 cuts, probe gently, administer Secretin if needed, apply methlylene blue, cut 1–2 more shallow incisions, etc. All other aspects are as described in the preceding section above. Occasionally, flaps of tissue between incisions will need removal with small biopsy forceps.

Precut—with Santorinicele Fig. 15.15 Initially minor papilla not found. The duodenum was then washed with a methylene blue solution. Dot of pancreatic juice seen at minor papilla orifice after Secretin stimulation (arrow).

not previously given, or its effect has worn off, repeat dosing is done and the surface of the precut area is washed with a solution of 1 ml methylene blue in 9 ml water with a few drops of simethicone solution (antifoaming properties). Pancreatic juice flow, if present, will be seen as a tiny clear fluid spot or stream amidst the blue stained background mucosa (Fig. 15.15). Deep cannulation is then gently 148

Approximately 15% of minor papillae have saccular dilation of the terminal dorsal duct beneath the duodenal mucosa and papillary mound (Fig. 15.16).8 This has been named a Santorinicele (after the accessory duct of Santorini). In such cases, the mound (bulge) is usually prominent, especially after contrast filling of the dorsal ductal system or after Secretin stimulation. Five to ten minutes after Secretin, the bulge is usually maximal and may have a bluish color. The wall thickness, (distance between the duodenal lumen and saccular lumen) is usually less than 2 mm. Therefore a 2–3 mm long 1–2 mm deep needle-knife incision over the dome (center) of the bulge will usually enter the ductal lumen. Occasionally a second deeper incision is needed. Completion sphincterotomy can be done

Chapter 15 Minor Papilla Endoscopic Sphincterotomy

A

B

Fig. 15.17 A Major and minor papilla orifices two years after sphincterotomies. Slit-like minor papilla orifice (upper arrow) seen with no residual mound. B Due to recurrent pancreatitis episode, a 4 mm balloon dilation done and minimal further cutting done.

Fig. 15.19 Standard 5 Fr triple lumen aspiration type manometry catheter (courtesy of Cook Endoscopy, Winston-Salem, NC) used to measure minor papilla “sphincter” pressure in this re-evaluation case. Prior sphincterotomy was 2 years ago.

pressure9 (Fig. 15.19). The rationale for use of the same cut-off values is that the pancreatic parenchyma probably does not tolerate secretion against a barrier >40 mmHg, whether through the major or minor papilla. Alternatively, the orifice can be probed with a 5, 6, and 7 Fr tapered catheter over a guidewire. If more than minimal resistance to passage is detected (similar to passage of esophageal dilators) by the 6 Fr catheter, the manometry will usually detect >40 mmHg basal sphincter pressure.

OUTCOMES Fig. 15.18 Re-do minor papilla sphincterotomy case. After pull sphincterotome extension of cut to the flat duodenal wall, two 5 French internally unflanged plastic stents placed.

by pull or needle-knife technique. The final sphincterotomy length is often larger (5–8 mm long) if the bulge was large.

Re-do minor papilla sphincterotomy Re-do cases—in which there has been a previous minor papilla sphincterotomy—are more difficult, as the papillary mound has usually been nearly or fully ablated (Fig. 15.11). If residual cutting space is clearly present, we proceed with sphincterotomy—either pull or needle-knife. If there is no obvious residual cutting space seen, we prefer to dilate the orifice using a push dilator to 7 Fr (or larger if the dorsal duct is >4 mm) or with a 4 mm balloon. After dilation, a small cut zone may become evident. If intramural cutting space is then seen, pull or needle-knife sphincterotomy extensions can be done with the cut extending 1–2 mm up onto the flat wall (Fig. 15.17). In re-do cases we commonly place two stents of 3–5 Fr diameter, then cut 2–3 mm further from the upper rim (Fig. 15.18). Care is taken to cut tissue and coagulate minimally. Excess coagulation current probably contributes to scar formation and re-stenosis. The optimal follow-up duration of stenting is unknown. We prefer unflanged stents and check for passage one to two months later using a plain abdominal radiograph. If there is no cutting space, dilation followed by stenting alone is done. Precise methods to detect when the minor papilla orifice is still “too tight” have not been defined. We often use manometry techniques identical to those for the major papilla and use a pressure of 40 mmHg as the cut-off for upper limits of normal for basal sphincter

Efficacy of minor papilla therapy is variable according to the underlying disease state10–15 (Table 15.3). Patients with acute recurrent pancreatitis are most likely to benefit from minor papilla intervention with 77% of 164 patients in Table 15.3 followed up for more than two years having no or fewer hospitalizations from pancreatitis flares. We offer minor papilla therapy to patients with a clinical course of acute recurrent pancreatitis if they have had at least two hospitalizations. Therefore, we usually do not offer minor papilla therapy after a single bout of pancreatitis (unless the CT scan shows evidence of dorsal duct dilation/obstruction/or stones). Long-term (10–20 years) outcomes are awaited. Patients with chronic pain alone (but often with endoscopic ultrasound evidence of chronic pancreatitis) and patients with chronic pancreatitis changes by ERCP or computed tomography have improvement rates of 30–40% (Table 15.3). These latter patients are often disabled and on chronic narcotics. Such “desperate” patients make us more willing to offer trial therapy even if results are suboptimal. Preliminary results from a prospective randomized trial of medical vs endoscopic therapy for “pain only” patients with pancreas divisum has been reported.16 This trial is ongoing.

Complications of minor papilla sphincterotomy Acute complications of minor endoscopic sphincterotomy are similar to major endoscopic sphincterotomy except perforations are less frequent. Pancreatitis rates are similar to other high-risk groups such as idiopathic pancreatitis and sphincter of Oddi dysfunction. Table 15.4 summarizes our large series. Management of complications is nearly identical to that of major papilla sphincterotomy. We have little experience with management of perforations, but would expect most to be small size and easily 149

SECTION 2 TECHNIQUES

Author/year

Therapy

Mean follow-up (mo)

Coleman/1994 Sherman/1994 Kozarek/1995 Heyries/2002 Bierig/2003 Linder/2003 Borak/2005

MiES/stent MiES MiES/stent MiES/stent MiES MiES MiES

23 28 20 39 19 NG (range 1–120) 44

Total

28

ACUTE RECURRENT PANCREATITIS

PAIN ONLY

CHRONIC PANCREATITIS

n

% improved*

n

% improved*

n

% improved*

9 0 15 24 16 38 62

78 — 73 92 94 58 89

5 16 5 0 7 12 29

0 44 20 — 43 0 69

20 0 19 0 16 4 23

60 — 32 — 38 25 43

164

77

74

33

82

41

Table 15.3 Selected series of endoscopic minor papilla therapy for pancreas divisum MiES = Minor papilla sphincterotomy. % of patients improved assessed by overall clinical status. NG = Not given. W:P:MiPaRxPD

Pancreatitis Mild Moderate Severe Bleeding Mild Moderate Severe Perforationc Mild Moderate

Total

13.2%

10.9% 1.9% 0.4% Total

1.0%

.6% .1% .3% Total

.2%

.1% .1%

Table 15.4 Complicationsa of a minor papilla sphincterotomyb in 778 procedures in pancreas divisum (from reference no. 17 with permission) a

Definitions per reference—Cotton et al.17 Database search of 12 year experience at Indiana University Medical Center. c Intraprocedure only (does not include delayed stent induced perforations).

b

managed with pancreatic stent and nasoduodenal decompression. Immediate bleeding during cutting will resolve spontaneously in >80% of cases. If bleeding occurs during needle-knife over stent technique, the pancreatic duct is already stented and protected. This allows use of epinephrine 1 : 10 000 injection (0.5–2 ml/injection) into/around the bleeding site. If bleeding persists, bipolar coaptive cautery is done at setting of 15–20 watts. Care is taken to cauterize focally (not diffusely) in order to limit subsequent scar formation. Persistent bleeding is usually a reflection of a coagulopathy which may then need correction. Pancreatic stenting has decreased (but not eliminated) the frequency and severity of post-ERCP pancreatitis, including for minor papilla settings. If pancreatitis occurs after a stent is placed, pancreatitis is mild and resolves in 1–3 days. More severe pancreatitis warrants a CT scan to exclude simultaneous post-sphincterotomy perforation or stent-related ductal perforation. Such stent perforations may occur at sharp angulations of the main duct or out a side branch. Such stents need urgent endoscopic stent removal or pull back. Pancreatitis may occur with early (>24 hr) spontaneous stent passage. In this situation we do not usually replace the stent but are 150

aware of one center which does so (without published supportive data). The most important long-term complication of minor papilla sphincterotomy is re-stenosis. This occurred in nearly 20% of one tallied series.18 Whether this represents natural healing of a congenitally small orifice or scar formation after cautery and manipulation is unknown. Such re-stenosis can be difficult to manage, as the stenotic zone may extend 2–5 mm outside the duodenal wall and into the head of the pancreas. A randomized trial of steroid injection (20 mg triamcinolone) into the sphincterotomy zone numerically (not statistically significantly) decreased the re-stenosis rate from 23 to 15% over a mean follow-up period of 47 months.18 Cutting space is often not present for either extension of the sphincterotomy or surgical sphincteroplasty. We offer such patients a series of sequential plastic stents or surgical decompression (usually lateral pancreaticojejunostomy).19 Our goal is to progressively dilate the narrowing until at least two 6 French stents can be placed side by side, left in situ for 1–2 months, and subsequently removed (if not passed spontaneously). Outcome from a series of such patients has not yet been tallied. Trials of pure cutting current sphincterotomy to prevent re-stenosis are awaited.

SUMMARY The techniques of minor papilla sphincterotomy have been derived largely from biliary and major papilla pancreatic sphincterotomy. Therapeutic efficacy and complication rates are similar to major papilla techniques. It is recommended that these techniques be performed by endoscopists at referral centers with large ERCP volumes. Long-term outcomes from such intervention and comparative randomized trials with stenting alone20 or surgical sphincteroplasty would be of interest.

Acknowledgement The authors are grateful to Joyce Eggleston for the technical compilation of this document.

Chapter 15 Minor Papilla Endoscopic Sphincterotomy

REFERENCES 1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

Fischer M, Fogel EL, McHenry L, et al. ERCP/manometry in 1108 idiopathic pancreatitis patients. Gastrointest Endosc 2005; 61:190A. Park S-H, de Bellis M, McHenry L, et al. Use of methylene blue to identify the minor papilla or its orifice in patients with pancreas divisum. Gastrointest Endosc 2003; 57:358–363. Alsolaiman M, Cotton, P, Hawes R, et al. Techniques for pancreatic sphincterotomy: Lack of expert consensus. Gastrointest Endosc 2004; 59:AB210. Gorelick A, Cannon M, Barnett J, et al. First cut, then blend: an electrocautery technique affecting bleeding at sphincterotomy: Randomized controlled trial. Endoscopy 2001; 33(11):976–980. Rashdan A, Fogel EL, McHenry L, et al. Improved stent characteristics for prophylaxis of post-ERCP pancreatitis. Clin Gastrointest Hepatol 2004; 2:322–329. Smith M, Ikenberry S, Uzer M, et al. Alterations in pancreatic ductal morphology following pancreatic stent therapy. Gastrointest Endosc 1996; 44:268–275. Sherman S, Alvarez C, Robert M, et al. Polyethylene pancreatic duct stent-induced changes in the normal dog pancreas. Gastrointest Endosc 1993; 39:658–664. Eisen G, Schutz S, Metzler D, et al. Santorinicele: new evidence for obstruction in pancreas divisum. Gastrointest Endosc 1994; 40:73–76. Fogel EL, Sherman S, Kalayci C, et al. Manometry in native minor papillae and post minor papilla therapy: experience at a tertiary referral center. Gastrointest Endosc 1999; 49:187A. Coleman SD, Cotton PB. Endoscopic accessory sphincterotomy and stenting in pancreas divisum. Gastrointest Endosc 1993; 39:312.

11. Linder JD, Bukeirat FA, Geenen JE, et al. Long-term response to pancreatic duct stent placement in symptomatic patients with pancreas divisum. Gastrointest Endosc 2003; 57:208A. 12. Lehman GA, Sherman S, Nisi R, et al. Pancreas divisum: results of minor papilla sphincterotomy. Gastrointest Endosc 1993; 39:1–8. 13. Heyries L, Barthet M, Delvasto C, et al. Long-term results of endoscopic management of pancreas divisum with recurrent acute pancreatitis. Gastrointest Endosc 2002; 55:376–381. 14. Bierig L, Chen YK, Shah RJ. Patient outcomes following minor papilla endotherapy (MPE) for pancreas divisum (PD). Gastrointest Endosc 2006; 63:313A. 15. Borak G Alsolaimon M, Holt E, et al. Pancreas divisum: long-term follow up after endoscopic therapy. Gastrointest Endosc 2005; 61:149A. 16. Sherman S, Hawes R, Nisi R, et al. Randomized controlled trial of minor papilla sphincterotomy (MiES) in pancreas divisum (Pdiv) patients with pain only. Gastrointest Endosc 1994; 40:125A. 17. Cotton PB, Lehman GA, Vennes J, et al. Endoscopic sphincterotomy complications and their management: an attempt at consensus. Gastrointest Endosc 1991; 37(3):383–393. 18. Toth TG, Sherman S, Fogel EL, et al. Does intrapapillary steroid injection improve the efficacy of minor sphincterotomy in pancreas divisum? Gastrointest Endosc 2001; 53:60A. 19. Madura JA, Canal DF, Lehman GA. Wall stent-enhanced lateral pancreaticojejunostomy for small-duct pancreatitis. Arch Surg 2003; 138:644–650. 20. Ertan A. Long-term results after endoscopic pancreatic stent placement without pancreatic papillotomy in acute recurrent pancreatitis due to pancreas divisum. Gastrointest Endosc 2000; 52:9–14.

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SECTION 2

Chapter

16

TECHNIQUES

Plastic Pancreatic and Biliary Stents: Concepts and Insertion Techniques Todd H. Baron and Jeffrey L. Ponsky

INTRODUCTION AND SCIENTIFIC BASIS The use of plastic biliary stents for drainage of the bile duct was described over two decades ago1 and plastic stents are now used in the biliary tree for a variety of therapeutic indications.2 Applications in pancreatic disease have also developed.2 These stents are used for malignant and benign conditions and have proven reliable and safe in decompression of the biliary tree. Palliative insertion of biliary stents relieves distal biliary obstruction as effectively as surgical bypass.3 Plastic stents are available in a variety of configurations and lengths and are composed of Teflon, polyethylene, or polyurethane (Tables 16.1 and 16.2).2 Common configurations are straight, single pigtail, or double pigtail (Fig. 16.1A–16.1B). All plastic stents have limited patency due to occlusion with debris and biofilm (Fig. 16.2)4–6 and require periodic replacement when long-term drainage is required. Nearly all stents of the same diameter have similar patency rates. One 10Fr stent with a unique double layer design (Fig. 16.3) was shown in one study to have prolonged patency as compared to standard stent design.7 Plastic stents have been demonstrated to be easy to insert, effective for decompression, and inexpensive to use. Almost all plastic stents are hollow tubes. Side holes are present to a variable degree, but uniformly present in pancreatic duct stents to allow side branches to drain (Fig. 16.4). Recently, a star-shaped stent with a limited central lumen (Fig. 16.5) has become available for both biliary8 and pancreatic insertion (Viaduct, GI Supply®, Camp Hill, PA).9 The central lumen allows only a guidewire and is inserted without an inner guiding catheter even at 10 Fr diameter (see stent systems below). A new S-shaped pancreatic stent has been introduced which may have less potential for migration and a prolonged patency.10 Finally, a new biliary stent with an antireflux valve (wind-sock) has recently become available to prevent stent occlusion due to food and vegetable material (Cook Endoscopy, WinstonSalem, NC) (Fig. 16.6). This stent may have improved patency over conventional large bore 10 Fr stents.11

STENT SYSTEMS A variety of stent systems are available as discussed in Chapter 4. Stents of less than 8.5 Fr diameter are placed directly over a guidewire using a pusher tube or sphincterotome. Stents of greater than 8.5 Fr diameter typically come with an inner guiding catheter which passes over the guidewire (Fig. 16.7); the stent and pusher tube are then passed over the inner guiding catheter (Fig. 16.8). The inner guiding catheter promotes stability and rigidity which are necessary in passing through tight strictures.

Endoscope requirements For stents of 7 Fr in diameter a diagnostic channel endoscope can be used. However, nearly all modern duodenoscopes are equipped with a therapeutic channel (4.2 mm) which can accommodate stents up to 11.5 Fr in diameter.

Description of technique: biliary Because 10 Fr stents have a patency that is superior to 7 Fr stents, it is recommended that all patients with malignant disease who are undergoing plastic stent placement receive 10 Fr stents, if possible, so as to limit the number of endoscopic procedures required for long-term palliation.

Distal biliary obstruction The approach to distal biliary strictures is slightly more straightforward than for hilar tumors and will be discussed separately. After successful deep cannulation of the biliary tree contrast is introduced to clearly elucidate the margins of the stricture to allow the appropriate stent length to be chosen. The stricture is traversed with a guidewire. It is important to pass the wire well proximal to the stricture to prevent wire loss and to provide mechanical advantage. In general, a biliary sphincterotomy is not required for successful single 10 Fr stent insertion.12 If multiple stents are to be placed, however (for example in patients with benign disease in whom multiple stents are required), a biliary sphincterotomy is required. The guidewire is left in place. For placement of a single 10 Fr stent across a distal biliary stricture it is rarely necessary to dilate the stricture, since the mechanical advantage is great enough to overcome resistance. In cases of uncertainty, a 10 Fr dilating catheter (e.g. Soehendra dilator, Cook Endoscopy, Winston-Salem, NC) can be passed. If it traverses the stricture, then a 10 Fr stent will also traverse the stricture. Otherwise, hydrostatic balloon dilation can be performed. When the insertion of multiple stents is planned, stricture dilation is essential. In this setting, additional guidewires may be placed prior to placement of the first stent or may be passed alongside the first stent after its placement. When multiple stents are placed, it may be useful to place a slightly longer stent first as the friction of the second stent insertion may result in upward movement of the stent. If the first stent is too short it may disappear into the duct. This is usually of no consequence assuming that the stent is still across the stricture. The stent’s length should be selected based upon the distance from the papilla to the proximal edge of the stricture plus an additional 2 cm. Excessively long stents should be avoided as migration tends to occur until the proximal end of the stent impacts the top of the stricture; meanwhile, the distal end of the stent may then 153

SECTION 2 TECHNIQUES

MANUFACTURER/SHAPE ConMed ACS Size (F)a 5 6 7 8.5 10 11.5 12 Length (cm) 1 2.5 3 4 4.5 5 6 6.5 7 8 8.5 9 10 10.5 11 12 12.5 13 14 15 >15 Material Nylon Polyethylene Polyurethane Teflon Two layer Operator centered system Price Stent With delivery system With operator centered system

DP

Hobbs Medicalb ACS DP

√

√

√

√

√

√

√

√

√ √ √ √ √

√

√ √

Microvasive ACS DP

√

√

√

√

√

√

√ √

√

√ √

√

√

√

√

√

√

√

√

√

√

√

√

√

√

√ √ √

√c

√

√ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √

√ √

No 60 115–130 N/A

No 40 86 N/A

Yes 69 119–159 139

DP

√

√

√ √

Olympus ACS

Yes 45–47 117–198 N/A

Cook Endoscopy ACS DP

√ √ √ √

√ √ √ √

√ √ √

√

√

√

√ √ √ √

√

√ √

√

√ √

√ √

√ √

√

√ √ √ √

√

√ √ Yes 57 123 123

Table 16.1 Plastic biliary stents (from reference no. 2 with permission) ACS, Angled, curved, or straight; DP, double pigtail. a Stents >10 Fr require a 4.2 mm channel duodenoscope. b Hobbs Medical did not disclose their stent material for this review. c Covered with hydromer coating.

impact the opposite duodenal wall causing perforation (Figs. 16.9A and 16.9B). As a rule of thumb, most pancreatic cancers producing biliary obstruction will be adequately managed with 5 or 7 cm long stents. Measuring of the stricture can be achieved in several ways. One way is during withdrawal of the initial cannulating catheter. When the catheter is at the proximal end of the stricture, the endoscopist holds the catheter just outside of the biopsy port; the catheter is then withdrawn until it is seen just outside of the papilla. The

154

distance from the endoscopist’s fingers to the biopsy port is measured, which is the minimal length of stent required to cross the lesion. Another way is to use the radiograph to “measure” the length from the top of the stricture to the tip of the endoscope when pressed against the papilla; the diameter of the endoscope serves as the comparison measuring point to account for the magnification factor. The following equation can be used to solve for the unknown (stricture length, Figure 16.10A–16.10B):

Chapter 16 Plastic Pancreatic and Biliary Stents: Concepts and Insertion Techniques

MANUFACTURER/SHAPE

Feature Size (F) 3 4 5 7 Length (cm) 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Material Price ($) (stent/preloaded)

GI Supply S

SP

Hobbs Medical S SP

√ √

√ √

√

√

√

√

√

√

√

√

√

√

√

√

Polyurethane 58

√ √

√

√

√

SP

Cook Endoscopy S SP √ 5, 7, 9

√ √

√ √

Olympus S

Not availablea 40

√ √ √ √ √ √ √

Polyethylene 49

√ 3–15 √

√ √ √ √ √ √ √ √ √ √ √ √ √

√ √ √ √ √ √ √ √ √ √ √ √ √

Polyethylene 57/123

Table 16.2 Pancreatic stents (from reference no. 2 with permission) S, Straight; SP, single pigtail. a Hobbs Medical did not disclose their stent material for this review.

A

B

Fig. 16.2 Endoscopic photo of occluded 10 Fr stent exiting the bile duct.

Fig. 16.1 Various stents: A Straight 10 Fr biliary stent (courtesy of Olympus America Inc., Melville, NY). B Double pigtail 10 Fr stent (courtesy of Cook Endoscopy, Winston-Salem, NC).

155

SECTION 2 TECHNIQUES

Fig. 16.3

Double-layer design (Olympus).

Fig. 16.7 Cook Endoscopy stent system showing typical 10 Fr design. Inner guiding catheter (arrows), stent (blue) and pusher tube (arrowheads) are seen.

Actual stricture length (X) Actual endoscope diameter = Measured stricture length Measured endoscope diameter

Fig. 16.4 Pancreatic duct stent, Cook Endoscopy. Note side holes.

Fig. 16.5 Magnified photograph of a sagittal section of a Viaduct stent. The flow is through the six channels (C) rather than through the central guidewire lumen (L).

Fig. 16.6 Antireflux stent (MarathonTM, Cook Endoscopy). The antireflux wind sock (white) is seen at the end of the stent. 156

Finally, fluoroscopic markers separated by a known distance are available on some catheters and guidewires and used as a reference point to the stricture and papilla. At this point, the stent is placed. The tapered end is the proximal end. Depending on the type of stent system, either the inner guiding catheter alone or the inner guiding catheter with the stent, are advanced over the guidewire. It is important not to allow the wire to pass too proximally into the biliary tree during this advancement, since this could cause hepatic capsule or intrahepatic ductal injury. On the other hand, excessive traction on the wire may result in wire loss. The stent is then advanced over the guide catheter by advancing the pusher tube, which is a somewhat larger bore and stiffer catheter which approximates the diameter of the stent. During advancement, the elevator should remain closed. When the stent impacts the elevator, the elevator is opened slightly to allow it to emerge from the endoscope channel. The elevator is closed to direct the stent upward and into the papilla. It is imperative to maintain a short endoscope position as close as possible to the papilla to maintain maximal mechanical advantage. Using a series of small movements in which the elevator is sequentially lowered to allow advancement of the stent, and then closed to advance the stent in a “ratchet-like” manner, the stent is advanced into the bile duct. Upward tip deflection as well as withdrawing the endoscope to further shorten it also provides forward motion to the stent. It is important to not allow more than a minimal amount of the stent to be advanced out of the endoscope into the duodenum; excessive length between the endoscope tip and papillary orifice decreases the mechanical advantage to forward advancement. To facilitate forward movement of the stent, the endoscopy assistant must provide traction on the inner guiding catheter. Once optimal stent position is achieved, the inner guiding catheter and guidewire are removed while the endoscopist maintains forward pressure with the pusher tube against the stent to prevent distal dislodgement. If additional contrast is needed to assess drainage or intrahepatic anatomy above the stent, the guidewire is removed prior to removing the inner guiding catheter to allow the injection. The guide catheter and pusher tube are then removed as described above. The process is repeated for additional stent placement.

Chapter 16 Plastic Pancreatic and Biliary Stents: Concepts and Insertion Techniques

Fig. 16.8 Illustration of 10 Fr stent system with stent placed for relief of malignant distal biliary obstruction.

A

B

the duct is then cannulated alongside the first stent with the second stent, guidewire, and inner guiding catheter. The process is continued until all stents are deployed. Alternatively, the stents can be placed one by one alongside each stent (Fig. 16.12). Newer stent delivery systems such as the Fusion (Cook Endoscopy) facilitate placement of multiple stents, since they allow intraductal exchange whereby the wire remains across the stricture between stent placements.

Stents for irretrievable bile duct stones Fig. 16.9 Endoscopic photos of distally migrated 11.5 Fr biliary stent impacted against the duodenal wall opposite the major papilla. A Before removal and B after removal, a small defect is seen.

In patients with short, distal bile strictures in whom multiple stents are to be placed (for example chronic pancreatitis with biliary stricture, post-sphincterotomy papillary stenosis) three to four 10 Fr 5 cm stents can be placed at one time on the inner guiding catheter. Once the first stent is in place (Fig. 16.11), the inner guiding catheter and guidewire are withdrawn just enough to release the first stent;

In the absence of a stricture, pigtail stents (Fig. 16.1b) may be preferable to straight stents when placed in a dilated biliary tree because they are less likely to migrate distally and completely out of the bile duct. Pigtail stents are placed slightly differently than straight stents in that if the distal end of the stent is against the papilla, too much stent has been advanced into the duct to allow the pigtail to form in the duodenum. The stent should be advanced until the portion of the stent that is just proximal to the distal pigtail (identified by applying indelible marker prior to placement if a visible marker is not already on the stent) is visible. The stent is then advanced while simultaneously withdrawing the endoscope so that the pigtail is deployed into the duodenum. 157

SECTION 2 TECHNIQUES

B A

Fig. 16.12 Additional stent insertion. Passage of the catheter alongside the initial stents in order to recannulate and place additional stents. Fig. 16.10 Measurement on the radiograph to calculate stent length. A The measurement from the top of the stricture to endoscope tip when positioned at the papilla (bracket) compared to the diameter of the endoscope (arrowheads) was 7 : 1. B Since the diameter of the endoscope was 11.5 mm, a 9 cm stent was placed.

A

B

be adequate to cross the stricture but too short to be “anchored” in the intrahepatic system are more prone to migrate distally. If it is determined that bilateral stents are to be placed, there are two options for guidewire placement. One way is the placement of two wires, one in each intrahepatic system, prior to placing either stent (Fig. 16.1). The other way is to place the first stent, recannulate the bile duct alongside this stent, and pass the guidewire into the opposite intrahepatic system. There are proponents of both methods, with advantages being the lack of friction within the endoscope channel between the first stent (if 10 Fr) and its larger pusher tube and the “second” guidewire within the endoscope channel. This can be overcome by using a 0.025″ guidewire as the “second wire.” It is important to note that it may not be possible to place bilateral 10 Fr stents during the first session. In that case it may be best to place two 7 Fr stents or one 10 Fr and one 7 Fr stent, then upsize one or both at the second session one month later.

Pancreatic duct stent insertion Fig. 16.11 Insertion of Multiple 10 Fr stents. A The first stent (1) is being pushed by the second stent (2) since the actual pusher tube is still well above the multiple stents loaded onto the catheter. B Final result of four 10 Fr stents, all placed with one passage of the stent introducer system.

Hilar biliary obstruction Hilar biliary obstruction differs from distal obstruction in two ways. Although a sphincterotomy is not needed for placement of a unilateral biliary stent, limited data suggest that hilar stent placement for obstruction carries a higher risk of pancreatitis than for distal obstruction, and pancreatitis, which may be prevented by performing a biliary sphincterotomy.13 Secondly, stricture dilation is frequently required because of the loss of mechanical advantage as the resistance of the stricture is away from the tip of the endoscope. Both of these maneuvers become mandatory when bilateral stents are placed (Fig. 16.13A–16.13C). In general, stents used for hilar tumors are 12–15 cm in length, since the average distance to the bifurcation is 9 cm. Stents that may 158

Pancreatic duct stent placement does not usually require the performance of a pancreatic sphincterotomy, especially since these stents have a small caliber (3–7 Fr). Rarely, 10 Fr stents are placed and even then a sphincterotomy for stent placement alone is usually unnecessary. The diameter of the stent chosen is dependent on the indication as well as the size of the main pancreatic duct. As mentioned previously, smaller diameter stents are passed over the guidewire without an inner guiding catheter. Similar to the biliary stenting process, the site of the pathology is identified, a wire passed into the tail and dilation performed, if necessary. The stent is selected and advanced into place with a pusher tube over the guidewire, although most 5, 6, or 7 Fr stents can be pushed into place using a standard 5 Fr catheter or sphincterotome. The wire is removed while keeping the pusher tube in position as mentioned. The pusher tube is then removed, leaving the end of the stent extruding from the papilla. Single pigtail stents with the pigtail in the duodenum are commonly employed in the pancreatic duct to avoid inward migration, which can be difficult to retrieve. Small caliber plastic stents (3–5 Fr) are now typically used for prevention of post-ERCP pancreatitis in patients at high risk (e.g. sphincter of Oddi dysfunction, ampullectomy) and/or the perfor-

Chapter 16 Plastic Pancreatic and Biliary Stents: Concepts and Insertion Techniques

A

B

C

Fig. 16.13 Bilateral stent placement for hilar cholangiocarcinoma. A Malignant stricture involves left (arrowhead) and right hepatic (arrow) ducts. B Balloon dilation is performed of left hepatic duct stricture (arrowhead); note wire is in right intrahe-patic (arrow). C Successful bilateral stent placement.

mance of high-risk interventions (precut biliary sphincterotomy, pancreatic sphincterotomy)14 (Fig. 16.14). These stents are expected to pass spontaneously within 14 days and thereby minimize pancreatic ductal injury.

Drainage of pancreatic fluid collections Double pigtail stents are placed transgastrically or transduodenally when transmural drainage of pancreatic fluid collections is undertaken.15 Usually two stents are placed across the wall into the collection (Fig. 16.15). Although straight stents can be used, they may be

a source of delayed bleeding as the end within the collection impacts the wall as the collection collapses.16 Therefore double pigtail stents are preferred. They are inserted as mentioned above for the biliary tree. It is important to note that the proximal ends of some of the 10 Fr stents are tapered and do not allow an inner guiding catheter to pass. The tapered portion may need to be severed to allow an inner guiding catheter pusher tube to pass through the stent. In addition, one must be especially careful that an excessive length of stent is not passed into a pseudocyst since the entire stent can be “lost” during deployment. 159

SECTION 2 TECHNIQUES

Fig. 16.14 3 Fr pancreatic duct stent placed for prevention of postERCP pancreatitis. Arrows denote ends of stent. Fig. 16.16 Plastic biliary stent (arrowhead) passed through occluded metal biliary stent (arrows) which had been placed for palliation of pancreatic carcinoma.

Fig. 16.15 Two 10 Fr stents placed transduodenally to drain a pancreatic pseudocyst.

Indications and contraindications Biliary indications

Malignant biliary obstruction is the most frequent indication for the use of plastic stents. Distal obstruction is most commonly due to pancreatic carcinoma. Mid to proximal malignant obstruction may be due to primary cancer of the biliary tree (gallbladder or cholangiocarcinoma) or from invasion or obstruction of the duct by adjacent malignant metastatic lymph nodes. Plastic stents may be used to relieve obstruction of previously placed metal stents17 (Fig. 16.16). In general, distal bile duct tumors are more effectively palliated with plastic stents than are hilar tumors. Benign strictures can frequently be managed by the use of plastic stents. Causes of benign obstruction include post-sphincterotomy stenosis, chronic pancreatitis, post-surgical injury, ischemia, and anastomotic strictures after liver transplantation. Indeed, in addition to acute relief of obstruction, serial stenting and dilation with increasing numbers of stents appears to be more effective than single stents for such pathology18–20 (Fig. 16.17). Biliary leaks and fistulae after biliary surgery, cholecystectomy, or trauma are also effectively treated by short-term stent placement across the papilla21 (Fig. 16.18). In most of these latter indications short-length stents are effective and do not need to cross the leak site. The elimination of sphincter pres160

Fig. 16.17 Fluoroscopic image after placement of five stents for treatment of benign distal bile duct stricture.

sure promotes flow away from the leak into the duodenum, promoting closure. For more complex leaks and major leaks of the common bile duct, it may be necessary to traverse the leak site.

Pancreatic indications Plastic stents have been used for relief of pancreatic duct obstruction in the setting of chronic pancreatitis. In this setting there may refractory pain or pancreatic leaks, with resultant pancreatic ascites or pseudocysts.22 Occasionally malignant pancreatic duct obstruction will result in pancreatitis or contribute to disabling pain. Placement of pancreatic stents may be effective in this setting (Fig. 16.19).23 As previously mentioned, temporary stent placement is useful in the prevention of post-ERCP pancreatitis in selected patients. In the setting of severe acute pancreatitis, pancreatic duct leaks and disrup-

Chapter 16 Plastic Pancreatic and Biliary Stents: Concepts and Insertion Techniques

A B

C

Fig. 16.18 Placement of biliary stent for treatment of post-cholecystectomy cystic duct leak. A Active leak is seen. B Fluoroscopic image taken immediately after placement of 10 Fr biliary stent. C Follow-up cholangiogram several weeks later showing closure of leak.

Fig. 16.19 Placement plastic pancreatic stent in patient with unresectable pancreatic cancer, intractable pain, fever, and hyperamylasemia. A Stricture (arrowheads) and dilated main pancreatic duct (arrows). B Immediately after placement of stent. Significant improvement in pain was achieved.

B A

C

A B

Fig. 16.20 Placement of pancreatic stent for treatment of post-splenectomy pancreatic duct leak. A Active leak is seen. B Fluoroscopic image taken immediately after placement of 7 Fr pancreatic stent to tail. C Follow-up pancreatogram several weeks later showing closure of leak.

tions may contribute to the poor outcome of these patients; pancreatic stent placement may improve the clinical course in a subset of these patients.24 In patients with traumatic pancreatic ductal injury, plastic stents may be effective in bridging the injured duct and permitting resolution of the leak. Post surgical pancreatic duct

leaks (distal pancreatectomy, inadvertent surgical injury) can occur and are effectively treated with pancreatic stents (Fig. 16.20).25 Finally, a variety of plastic stent configurations have been useful in transpapillary and transmural drainage of pancreatic fluid collections (see Chapter 45).15 161

SECTION 2 TECHNIQUES

Complications When sphincterotomy is performed to facilitate stent insertion, complications such as hemorrhage (Fig. 16.21) or perforation may occur.26 When placed into the bile duct, problems caused by the stent itself include cholangitis, frequently due to stent occlusion, and cholecystitis as a result of cystic duct obstruction.27 Occlusion of a biliary stent secondary to deposition of bacterial biofilm and/or plant material (Fig. 16.2) is the most commonly encountered complication of plastic stents and occurs in about 30% of cases with resulting jaundice and cholangitis. When placed into the pancreatic duct, stent occlusion may cause pancreatitis. Stent migration, into or out of the bile duct, occurs in up to 5% of cases and may result in recurrent obstruction and cholangitis. Pancreatic stent migration into the duct can be difficult to retrieve due to their small diameter and the small size of the pancreatic duct. If not retrieved, permanent ductal damage can occur. Even when left in for a few weeks in a planned situation, pancreatic duct stents can induce ductal damage similar to chronic pancreatitis.28 (Figs 16.22A–16.22C). Uncommon complications include perforation of the duodenum if distal migration occurs (Fig. 16.9);29 such perforations may be occult until the stent is removed

A

Fig. 16.21 Endoscopically visible vessel (arrow) identified from post-sphincterotomy bleeding following biliary stent placement. Heater probe therapy was applied and no further bleeding ensued.

B C

Fig. 16.22 Pancreatic duct stent-induced ductal damage after treatment of post-tail resection pancreatic duct leak. A Active leak is seen at tail (arrow). B Fluoroscopic image taken immediately after placement of short 7 Fr pancreatic stent. C Follow-up pancreatogram several weeks later showing stricture (arrow) at site where the stent end was in contact with the duct.

and the hole opened. A variety of rare complications have been reported following migration completely out of the bile duct, such as bowel obstruction,30 and intestinal perforation.31

Relative cost Plastic stents provide rapid palliation of biliary obstruction, and shorten hospital stay when compared to surgical bypass. In many cases, stent placement obviates major surgical intervention. The cost of a plastic stent is less than $100 and is far less than an expandable

metal stent, the cost of which may exceed $1800 contingent upon manufacturer and presence or absence of a covering. Metal stents have a significantly longer patency than plastic stents, although if the patient does not survive long enough, this benefit will not be realized. Therefore, in patients with distal malignancy who have an anticipated life expectancy less than three to four months, plastic stents are more cost-effective.3,32 CPT codes and ambulatory payment classifications in the US for placement and/or removal of plastic biliary stents are available in a recent review.2

REFERENCES 1.

Soehendra N, Reynders-Frederix. Palliative bile duct drainage- a new endoscopic method of introducing a transpapillary drain. Endoscopy 1980; 12:8–11. 2. Somogyi L, Chuttani R, Croffie J, et al. Biliary and pancreatic stents. Gastrointest Endosc. 2006 June; 63(7):910–919. 3. Moss AC, Morris E, Mac Mathuna P. Palliative biliary stents for obstructing pancreatic carcinoma. Cochrane Database Syst Rev. 2006 Apr 19(2):CD004200. 162

4. van Berkel AM, van Marle J, Groen AK, et al. Mechanisms of biliary stent clogging: confocal laser scanning and scanning electron microscopy. Endoscopy. 2005 Aug; 37(8):729–734. 5. Farnbacher MJ, Voll RE, Faissner R, et al. Composition of clogging material in pancreatic endoprostheses. Gastrointest Endosc. 2005 June; 61(7):862–866. 6. Weickert U, Venzke T, Konig J, et al. Why do bilioduodenal plastic stents become occluded? A clinical and pathological investigation

Chapter 16 Plastic Pancreatic and Biliary Stents: Concepts and Insertion Techniques

7.

8.

9.

10.

11.

12.

13.

14.

15.

16.

17. 18.

on 100 consecutive patients. Endoscopy. 2001 Sep; 33(9):786–790. Tringali A, Mutignani M, Perri V, et al. A prospective, randomized multicenter trial comparing DoubleLayer and polyethylene stents for malignant distal common bile duct strictures. Endoscopy. 2003 Dec; 35(12):992–997. Raju GS, Sud R, Elfert AA, et al. Biliary drainage by using stents without a central lumen: a pilot study. Gastrointest Endosc. 2006 Feb; 63(2):317–320. Raju GS, Gomez G, Xiao SY, et al. Effect of a novel pancreatic stent design on short-term pancreatic injury in a canine model. Endoscopy. 2006 Mar; 38(3):260–265. Ishihara T, Yamaguchi T, Seza K, et al. Efficacy of s-type stents for the treatment of the main pancreatic duct stricture in patients with chronic pancreatitis. Scand J Gastroenterol. 2006 June; 41(6):744–750. Reddy DN, Banerjee R, Choung OW. Antireflux biliary stents: are they the solution to stent occlusions? Curr Gastroenterol Rep. 2006 Apr; 8(2):156–160. Giorgio PD, Luca LD. Comparison of treatment outcomes between biliary plastic stent placements with and without endoscopic sphincterotomy for inoperable malignant common bile duct obstruction. World J Gastroenterol. 2004 Apr 15; 10(8):1212–1214. Tarnasky PR, Cunningham JT, Hawes RH, et al. Transpapillary stenting of proximal biliary strictures: does biliary sphincterotomy reduce the risk of postprocedure pancreatitis? Gastrointest Endosc. 1997 Jan; 45(1):46–51. Singh P, Das A, Isenberg G, et al. Does prophylactic pancreatic stent placement reduce the risk of post-ERCP acute pancreatitis? A meta-analysis of controlled trials. Gastrointest Endosc. 2004 Oct; 60(4):544–550. Baron TH. Endoscopic drainage of pancreatic fluid collections and pancreatic necrosis. Gastrointest Endosc Clin N Am. 2003 Oct; 13(4):743–764. Cahen D, Rauws E, Fockens P, et al. Endoscopic drainage of pancreatic pseudocysts: long-term outcome and procedural factors associated with safe and successful treatment. Endoscopy. 2005 Oct; 37(10):977–983. Tham TC, Carr-Locke DL, Vandervoort J, et al. Management of occluded biliary Wallstents.Gut. 1998 May; 42(5):703–707. Baron TH. Endoscopic therapy with multiple plastic stents for benign biliary strictures due to chronic calcific pancreatitis: the good, the bad, and the ugly. J Clin Gastroenterol. 2004 Feb; 38(2):96–98.

19. Pozsar J, Sahin P, Laszlo F, et al. Endoscopic treatment of sphincterotomy-associated distal common bile duct strictures by using sequential insertion of multiple plastic stents. Gastrointest Endosc. 2005 Jul; 62(1):85–91. 20. Kuzela L, Oltman M, Sutka J, et al. Prospective follow-up of patients with bile duct strictures secondary to laparoscopic cholecystectomy, treated endoscopically with multiple stents. Hepatogastroenterology. 2005 Sep–Oct; 52(65): 1357–1361. 21. Kaffes AJ, Hourigan L, De Luca N, et al. Impact of endoscopic intervention in 100 patients with suspected postcholecystectomy bile leak. Gastrointest Endosc. 2005 Feb; 61(2):269–275. 22. Delhaye M, Arvanitakis M, Bali M, et al. Endoscopic therapy for chronic pancreatitis. Scand J Surg. 2005; 94(2): 143–153. 23. Costamagna G, Mutignani M. Pancreatic stenting for malignant ductal obstruction. Dig Liver Dis. 2004 Sep; 36(9):635–638. 24. Lau ST, Simchuk EJ, Kozarek RA, et al. A pancreatic ductal leak should be sought to direct treatment in patients with acute pancreatitis. Am J Surg. 2001 May; 181(5):411–415. 25. Le Moine O, Matos C, Closset J, et al. Endoscopic management of pancreatic fistula after pancreatic and other abdominal surgery. Best Pract Res Clin Gastroenterol. 2004 Oct; 18(5):957–975. 26. Freeman ML, Nelson DB, Sherman S, et al. Complications of endoscopic biliary sphincterotomy. N Engl J Med. 1996 Sep 26; 335(13):909–918. 27. Dolan R, Pinkas H, Brady PG. Acute cholecystitis after palliative stenting for malignant obstruction of the biliary tree. Gastrointest Endosc. 1993 May–June; 39(3):447–449. 28. Kozarek RA. Pancreatic stents can induce ductal changes consistent with chronic pancreatitis. Gastrointest Endosc. 1990 Mar–Apr; 36(2):93–95. 29. Melita G, Curro G, Iapichino G, et al. Duodenal perforation secondary to biliary stent dislocation: a case report and review of the literature. Chir Ital. 2005 May–June; 57(3):385–388. 30. Simpson D, Cunningham C, Paterson-Brown S. Small bowel obstruction caused by a dislodged biliary stent. J R Coll Surg Edinb. 1998 June; 43(3):203. 31. Storkson RH, Edwin B, Reiertsen O, et al. Gut perforation caused by biliary endoprosthesis. Endoscopy. 2000 Jan; 32(1):87–89. 32. Levy MJ, Baron TH, Gostout CJ, et al. Palliation of malignant extrahepatic biliary obstruction with plastic versus expandable metal stents: An evidence-based approach. Clin Gastroenterol Hepatol. 2004 Apr; 2(4):273–285.

163

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Chapter

17

TECHNIQUES

Expandable Stent Insertion Ann Marie Joyce and Gregory G. Ginsberg

Introduction Expandable biliary stents are used primarily for the palliation of malignant biliary obstruction. There are two main categories of biliary stents: fixed-diameter plastic stents (FDPS) and self-expanding metallic stents (SEMS). FDPS, introduced in 1980, preceded their SEMS counterparts and are discussed in detail in Chapter 16. While FDPS are a safe and effective means to overcome biliary stenoses, they eventually become occluded.1 Stent occlusion is attributed to biofilm formation such that under even ideal circumstances, FDPS occlusion occurs in 30% and 50% of patients within three and six-months, respectively.2 Bile flow rate is impacted on by the stent lumen diameter. The internal diameter of an FDPS is limited by the accessory channel size of the duodenoscope. Because the diameter of the accessory channel of a “therapeutic” duodenoscope is 3.2 mm, FDPSs are available with internal diameters up to 12 Fr. SEMS were developed to overcome this limitation as they deliver a larger diameter stent (10 mm) via a small diameter (7.5 Fr) delivery device. Because malignant biliary obstruction is typically associated with a survival of less than one year, SEMS are intended to yield “lifelong” palliation of obstructive symptoms.3–5 This chapter reviews the indications for SEMS placement, SEMS selection, types of SEMS available, techniques for SEMS placement, SEMS-related complications, and complication avoidance and management.

INDICATIONS SEMS are indicated for palliation of malignant biliary obstruction. The most common cause of malignant biliary obstruction is pancreatic adenocarcinoma arising in the head or genu region of the pancreas. The management of distal biliary obstruction is discussed in more detail in Chapter 27 by Barkun. Other causes of malignant biliary stenoses are cholangiocarcinoma, ampullary carcinoma, gallbladder cancer, and extrinsic compression associated with lymphadenopathy due to lymphoma and metastatic carcinoma. Patients with malignant biliary obstruction typically present with jaundice. Left unchecked, biliary obstruction may lead to the development of pruritis, pain, cholangitis, hepatic synthetic dysfunction, and malabsorption. Without therapy the mean survival for patients presenting with malignant biliary obstruction is less than 200 days. Because most patients have advanced disease at the time of presentation, operative resection with curative intent is only possible in 10–15% of cases.6,7 Therefore, palliation of symptoms is a major component of management in the majority of patients with malignant biliary obstruction.

Options for palliation of malignant biliary obstruction include operative bypass, percutaneous drainage, and/or endoscopic stenting. In a prospective, randomized trial of endoscopic stenting with FDPSs versus operative bypass the two compared equivalently with respect to alleviation of obstruction and relief of jaundice, and favorably with respect to hospital stay and procedure-related complications and mortality.8 However, late recurrence of jaundice occurred more commonly in the FDPS group owing to stent occlusion. Versus percutaneous drainage, endoscopic stenting compares equivalently for alleviation of jaundice, and superiorly with respect to procedurerelated morbidity and 30-day mortality.9 Both FDPS and SEMS can be used for the palliation of malignant biliary obstruction. FDPSs are safe and effective. They are relatively less expensive compared to SEMS, and can be removed and replaced if they become occluded. To restate, the main drawback of FDPS is their variable rate of occlusion. Symptoms of stent occlusion include recurrence of jaundice and/or ascending cholangitis. Two strategies have been employed related to FDPS occlusion: (1) prophylactic exchange, and (2) expectant management. The former involves elective stent removal and exchange at three-month intervals in order to reduce the risk of cholangitis and need for emergency exchange while the latter relies on watchful waiting and nimble responsiveness should stent occlusion occur. Further discussion on FDPS can be found in Chapter 16 (Baron and Ponsky). SEMS are intended, owing to their larger internal diameter, to extend the duration of patency, thereby reducing the need for and frequency of reintervention. As such, their increased cost may be offset by a reduction in episodes of cholangitis and need for elective and emergency interventions, including hospitalization. A multicenter randomized study that compared a SEMS (Wallstent) to 10 Fr FDPS was performed by the US Wallstent study group10 (Table 17.1). Early stent occlusion occurred in about 3% of the FDPS group as compared to none in the Wallstent group. Early occlusion was attributed to sludge accumulation in the plastic stent groups. During long-term follow-up, the probability of stent occlusion was 2.8 times greater for plastic stents than for Wallstents. Tumor ingrowth or overgrowth contributed to about 14% of the Wallstent occlusions, but this did not affect the plastic stent group. The overall complication rate was significantly lower in the Wallstent group than in the FDPS group (20% vs 31%, p < 0.05). In the plastic stent group there was a higher number of procedures performed which resulted in a higher cost as compared to the Wallstent group. Another prospective, randomized trial was performed to compare the patency and determine the cost-effectiveness of SEMS versus FDPS.4 This study demonstrated that the median period of patency was longer for the metal stent group (33%) after a median of 273 days compared with 54% after a median of 126 days (p = 0.006). Two subsequent prospective, randomized trials11,12 also reported longer duration of patency with Wallstents compared to 165

SECTION 2 TECHNIQUES

Author

No. of patients FDPS SEMS

Drainage (%) FDPS SEMS

Davids (4) Carr-Locke (10) Knyrim (5) Kaassis (11)

49 78 31 59

95 95 100

56 86 31 59

96 98 100

Occlusion on rate (%) FDPS SEMS

Stent patency (days) FDPS SEMS

p value

54 13 36 63

126a 62a 140a 165a

p = 0.006

33 13 22 20

273a 111a 189b Not reached

p = 0.035 p = 0.007

Table 17.1 Randomized trials comparing FDPS versus SEMS for palliation of malignant strictures of the bile duct a

median. mean.

b

COMPLICATIONS Author, year (reference)

No. of pts

Stent occlusion

Smits et al. 1995 (20) Born et al. 1996 (21) Miyayama et al. 1997 (22) Rossi et al. 1997 (23) Hausegger et al. 1998 (24) Shim et al. 1998 (25) Nakamura et al. 2002 (26) Han et al. 2002 (27) Isayama et al. 2002 (28) Schoder et al. 2002 (29) Bezzi et al. 2002 (30) Han et al. 2003 (31) Isayama et al. 2004 (32) Miyayama et al. 2004 (33) Nakai et al. 2005 (34) Kahaleh et al. 2005 (35)

22 10 19 21 30 21 13 10 21 42 26 13 57 22 69 80

2 3 1 7 11 2 1 0 3 6 4 3 8 3 7 12

Tumor in growth 0 0 4 2 2 0 0 0 0 2 0 0

Migration

Cholecystitis

Pancreatitis

Cholangitis

1 1 1

1 (related to tumor)

0

2 4

0 2 3 3 0 2 3 4 3

0 1 1 0 0 5

1 3 0 0 0 1 4 5

4 5

1 5

Table 17.2 Review of available studies of the complications of covered SEMS

FDPS. Along with the extended patency rate with Wallstents there were fewer accumulated hospital days in this group (p < 0.05). Conventionally, the use of SEMS is limited to patients with confirmed, non-operable, malignant biliary obstruction. Our practice, and the practice of many, has been to place FDPS for initial management of suspected malignant biliary obstruction. We have relatively deferred the use of SEMS until there was evidence of occlusion of the initially placed FDPS, a performance status suggesting a greater than 6-month survival, a confirmed tissue diagnosis, and completed staging to confirm non-operability. Our most common application of SEMS has been in patients with biopsy proven, inoperable malignant biliary obstruction that have developed occlusion of a previously placed FDPS with a life-expectancy of greater than 3–6 months. However, recent studies suggest broader application for SEMS. Concerns about the use of SEMS prior to confirming a tissue diagnosis of cancer and affirming unresectability have been contested. In patients with potentially resectable pancreatic cancer, patients have improved survival with neoadjuvant chemotherapy followed by operative resection.13–17 In a small group of patients, Wasan et al. demonstrated that SEMS can be useful for relief of biliary obstruction in resectable pancreatic carcinoma.18 While there had been concern about SEMS complicating operative resection, this 166

has not been borne out in clinical practice. One cost analysis concluded that initial SEMS placement provided equal or superior efficacy and reduced overall costs compared to FDPS placement.19 Covered SEMS share the same indications as their uncovered precursors, though they are not used in hilar or intrahepatic ducts because of blockage to the contralateral intrahepatic system if ipsilateral intrahepatic branches. The anticipated advantage of covered SEMS is the retardation of tissue (malignant or hyperplastic) in-growth contribution to stent occlusion. However, there is considerably less published and unpublished experience with covered SEMS. Limited studies of covered SEMS have raised concerns of higher rates of stent migration, cystic duct obstruction, and pancreatitis (Table 17.2)20–36 Covered stents may be particularly well suited for reconstitution of an occluded indwelling uncovered SEMS. Because they are considered non-removable SEMS have generally been considered contraindicated for management of benign biliary strictures. While SEMS remain patent longer than FDPS, the durability of their biotolerance is not indefinite. Endoscopic removal of occluded uncovered SEMS cannot be reliably achieved as compared with covered SEMS.37 Long-term results from ongoing trials evaluating the application of covered SEMS in the management of benign bile duct disease are awaited with interest.38,39

Chapter 17 Expandable Stent Insertion

TYPES OF SELF-EXPANDING STENTS There are a variety of SEMS used in the palliation of malignant biliary obstruction (Table 17.3). Commercially available SEMS vary moderately in design, delivery, configuration, and sizes. There are few studies comparing the different stents. The available uncovered stents include: Wallstent (Boston Scientific, Natick, MA), Zilver stent (Cook Endoscopy, Winston-Salem, NC), Diamond stent (Boston Scientific, Natick, MA), and Flexxus stent (ConMed, Billerica, MA). Covered stents include the covered Wallstent (Boston Scientific, Natick, MA) and Viabil stent (W.L. Gore, Flagstaff, AZ). To decrease the occlusion of expandable stents by tumor ingrowth covered stents have been introduced. These stents vary slightly but all are deployed through a duodenoscope.

Wallstent The Wallstent is the original SEMS and is considered the industry standard (Fig. 17.1). Most of the published literature on SEMS applies to the biliary Wallstent. It is a braided stainless steel mesh with soft barbed ends. The Wallstent is available in 40, 60 and 80mm lengths. The available diameters of the fully expanded Wallstent are 8 and 10 mm. The delivery device has an outside diameter of 7.5 Fr and consists of an 0.035-inch guidewire compatible introducer catheter, on which the compressed SEMS is constrained by a hydrophilic-coated outer sheath. The delivery device has a tapered

tip to allow ease of passage. The SEMS is deployed by withdrawing the outer sheath releasing the SEMS in the desired location. The Wallstent is radiopaque and there are four radiopaque markers on the delivery device to guide precision deployment. The stent can be recaptured, if need be, and repositioned up until 90% of full stent release. Wallstents can be deployed entirely within the bile duct or in transpapillary position. There is 33% foreshortening of the Wallstent post-deployment. Transpapillary positioned uncovered Wallstents may be reliably removed within 12 to 24 hours after insertion. Subsequently, the stent becomes embedded into the bile duct wall and it is more difficult, if not impossible, to remove.

Diamond Ultraflex stent The Ultraflex Diamond stent is made of nitinol, a nickel-titanium alloy that provides a high degree of flexibility (Fig. 17.2). It is constructed as a laser-welded single knitted wire. The interstices of the lattice work are larger compared to those of the Wallstent. This may more easily permit cannulation of the interstices and dilation for placement of another stent to create a “Y” configuration; this may be potentially helpful in the palliation of hilar strictures. The delivery device is similar to that of the Wallstent. The outer sheath measures 3 mm (8.5 Fr) in diameter. The stent is available in 4, 6, and 8 cm in length and 10 mm in diameter. Once the deployment has commenced the stent cannot be recaptured. There is little foreshortening. There are radiopaque markers to assist with the accurate positioning of the stent, however; the stent itself is less visible

Type

Delivery system (Fr)

Metal

Length (cm)

Diameter (mm)

List price

Wallstent Diamond Ultraflex stent Gianturco-Rosch “Z” stent Spiral Z stent Za stent Zilver stent Flexxus Covered Wallstent Viabil

7.5 9.25 12 8.5 8.5 7 7.5 8 10

Steel Nitinol Stainless steel Stainless steel Nitinol Nitinol Nitinol Steel Nitinol

4,6,8 4,6,8 4,6,8 5.7,7.5 4,6,8 4,6,8 4,6,8,10 4,6,8 4,6,8,10

8,10 10 10 10 10 6,8,10 8,10 8,10 8,10

$1450 $1300 N/A N/A N/A $1250 $1525–$1735 $1650

Table 17.3 Characteristics of SEMS

Fig. 17.1

Wallstent

Fig. 17.2

Diamond Ultraflex stent 167

SECTION 2 TECHNIQUES

radiographically compared to the Wallstent. Radial expansion forces are purportedly similar. Four studies have been published which compared the Ultraflex Diamond stent with Wallstent for palliation of malignant biliary strictures.40–43 While one reported equivalency, three others reported inferior performance of the Ultraflex Diamond as compared to the Wallstent.

Z stent There have been multiple iterations of the Z stent. The original Gianturco-Rosch “Z” stent was a stainless steel wire bent in a continuous Z shaped pattern forming a cylinder. This was modified by stringing together individual cages by adding small eyelets making the stent more flexible and compressible. This is known as the Spiral Z stent The introducer is similar in diameter to the Wallstent but the stent lengths vary. The Spiral Z stent is available in 5.7 cm and 7.5 cm lengths and 10 mm in diameter. There are silver radiopaque markers along the length of the stent. Another iteration of the design, the Za-stent, incorporates nitinol in place of stainless steel making the stent more flexible. The available lengths of the Za-stent are 4, 6 and 8 cm with a diameter of 10 mm. There are gold radiopaque markers in the middle and at the end of the Za-stent for fluoroscopic visualization. The Zilver stent (Fig. 17.3) is one piece of nitinol compared to many pieces of nitinol threaded together (Za). The gold radiopaque markers are at the proximal and distal end of the stents. The introducer diameter is 7 Fr, which is the smallest on the market. The release mechanism is similar to that of the Wallstent. All forms of the Z stent including the newest edition, Zilver stent, are non-shortening facilitating accurate deployment. A multi-center trial comparing the Wallstent with Spiral Z stent was performed by Shah et al. and included 145 patients.44 There were 64 patients in the Z stent group and 68 in the Wallstent group. There was a 100% success in the placement of the stents. There were 8 occlusions in the Z-stent group and 13 in the Wallstent group (p = 0.3). The calculated median patency rates for the Z-stent and the Wallstent were 152 days and 154 days, respectively (p = 0.9). According to this study, the two stents appeared comparable.

Fig. 17.3 168

Zilver stent

Flexxus The Flexxus stent (formerly Memotherm and Luminexx) is a highly flexible nitinol stent with flared ends (Fig. 17.4). The stent is a lasercut single piece of nitinol. Similar to the Diamond stent, the interstices of the lattice work are large enough to permit cannulation of the interstices and dilation for placement of another stent to create a “Y” configuration for palliation of hilar strictures. There are four Tantalum markers on each end to provide improved fluoroscopic imaging. The predeployment delivery diameter is 7.5 Fr and the post-deployment diameters are 8 and 10 mm with lengths of 40 mm, 60 mm, 80 mm, and 100 mm. The release mechanism is unique and employs a pistol-grip handle which withdraws the constraining sheath and allows stepwise, controlled release. During deployment, there is no foreshortening and the stent cannot be re-constrained. There are no studies available to compare the Flexxus with the other stents previously mentioned.

Covered SEMS SEMS have a longer patency rate as compared with plastic stents but they may still eventually become occluded. Plastic stents typically become occluded with sludge and/or biofilm whereas SEMS become occluded with tumor overgrowth or ingrowth, ingrowth of benign epithelial hyperplasia, and/or sludge accumulation. Covered SEMS

Fig. 17.4

Flexxus stent

Chapter 17 Expandable Stent Insertion

were developed to overcome ingrowth through the SEMS interstices. The covered Wallstent has a polyurethane covering (Fig. 17.5). The delivery system and deployment are the same as the uncovered version, though the predeployment diameter is slightly larger at 8 Fr. The initial stents were completely covered but modifications have been made so that 5 mm of each end is uncovered to allow embedding into the tissue to decrease the rate of migration. Published studies of the covered Wallstent have yielded mixed results with respect to improvement in patency rates (Table 17.4).20–36 Furthermore, complications from covered Wallstents included adherent debris, migration (6%) and cholecystitis (12%). Another covered stent for use is the Viabil (Fig. 17.6). The nonporous polytetrafluoroethylene (ePFTE) and fluorinated ethylene propylene (FEP) covering prevents tumor ingrowth. Outside this lining there is a nitinol stent with radiopaque rings on either end. There are anchoring fins along the nitinol stent to prevent migration. The stent is available with or without holes in the covering. The holes are along the proximal end of the stent to prevent occlusion of other duct branches. The stent is available in a variety of sizes with a 10 Fr delivery system and is available through ConMed (Billerica, MA, USA).

TECHNIQUES FOR SEMS PLACEMENT Duodenoscope We preferentially use a therapeutic duodenoscope (accessory channel—4.2mm) for most ERCP. Standard diagnostic duodenoscopes with a 3.2 mm accessory channel do permit insertion of most

Other SEMS Obscure, pirated, and boutique stents have been developed and marketed to limited extents around the globe. However these are not readily available in most markets. The “Y Stent” (Fig. 17.7) is an example, intended for palliation of hilar strictures.

Fig. 17.6 Viabil stents: without holes (top) and with holes (bottom).

Fig. 17.5

Fig. 17.7

Polyurethane covered Wallstent

Author (reference)

No. of pts U

C

Shim et al. 1998 (25) Nakamura et al. 2002 (26) Miyayama et al. 2004 (33) Isayama et al. 2004 (32) Smits et al. 1995 (20)

26 10 19 55 24

21 13 22 57 22

Median stent patency U C 233 >402

267 >470

193a

225a

Stent occlusion U C 6 2 14 21 3

2 1 3 8 2

Y stent

Tumor ingrowth U C 6 2

2 0

16 2

0 0

Migration U C

0 0

1 1 1 1

Cholecystitis U C

Pancreatitis U C

1 1 0

1

0

1

5

0 2 2

Table 17.4 Covered (C) vs uncovered (U) SEMS studies a

mean.

169

SECTION 2 TECHNIQUES

SEMS. In patients with pending or existing gastric outlet or duodenal obstruction, a forward-viewing endoscope may be necessary for initial inspection and stricture dilation. When considering dual enteral and biliary stenting, we place the biliary SEMS first, followed by enteral stent placement.

Cholangiogram A good quality cholangiogram using undiluted contrast will define the length, localization, and configuration of the biliary obstruction and is important for selection of the appropriate stent. MRCP or CT scan with pancreaticobiliary protocol may be valuable in the preERCP evaluation of suspected hilar obstruction when selected unilateral drainage versus bilateral or multisegmental drainage may be indicated, as discussed in Chapter 27.45

Sphincterotomy A biliary sphincterotomy is not obligatory for SEMS placement in either the supra- or transpapillary positions. Assertions that transpapillary SEMS placement without preplacement biliary sphincterotomy increases the risk of pancreatitis are unfounded, and avoidance of sphincterotomy may reduce the risk of procedure-related complications.

Dilation Routine stricture dilation to facilitate SEMS placement is not required. SEMS radial forces are sufficient to permit full or near-full expansion within 48 hours; therefore post-deployment dilation is also not routinely performed. In rare instances the stricture may need to be dilated to allow the passage of the SEMS delivery device.

SEMS shortening needs to be taken into consideration to enhance precision of placement.

Use of guidewire Guidewires are commonly used to traverse malignant bile duct strictures, facilitate catheter insertion, and maintain access during device exchange. The SEMS delivery device is passed over the guidewire and positioned within the stricture. Larger diameter (0.035″), nitinol, hydrophilic coated wires are preferred as they enhance device exchange. If two or more stents are going to be placed to palliate a hilar stricture in a side-by-side fashion, multiple guidewires are used to maintain access to the specific segments.

SEMS positioning Biliary SEMS may be placed in a suprapapillary or transpapillary position. This positioning is at the discretion of the endoscopist. In a suprapapillary position (Fig. 17.8) the sphincter of Oddi remains intact, assuming sphincterotomy was not performed. The potential advantage of this approach is that it prevents free reflux of the duodenal contents into the bile duct which may contribute to stent occlusion. However, there is insufficient data to support this notion for SEMS46 and when this concept was tested with FDPS, no difference in stent occlusion rates was observed. Suprapapillary SEMS placement is most commonly performed for strictures of the hilar region or common hepatic duct with which SEMS length is insufficient to traverse the ampulla. In a study of 59 patients, Liu et al.47 demonstrated that an “inside-stent” was possible in onethird of patients presenting with malignant obstructive jaundice. In

Stent selection The endoscopist and technician should be sufficiently familiar with the delivery and deployment mechanisms and post-deployment performance characteristics of a SEMS when considered for use. This includes guidewire and accessory channel compatibility, device preparation, insertion and deployment mechanisms, radiographic markings, SEMS shortening, recapture and reposition capabilities, and a shared communications terminology. Size matters. While the 10 mm diameter SEMS is used most commonly, SEMS length selection is individualized and dependent on the length and location of the stricture and the intention of supra- or transpapillary placement. Careful measurements best ensure optimal outcomes. Deployed and fully expanded SEMS should extend a minimum of 10 mm beyond the proximal and distal aspects of the stenosis to retard tumor overgrowth. One should prevent placement of the stent where the ends of the SEMS butt up against the bile duct side wall. The SEMS length should be determined at the time of the ERCP cholangiography. Experienced endoscopists commonly estimate the length based on the dimensions of the superimposed duodenoscope diameter (see Chapters 3 and 16). The length of the stricture may also be determined during the out exchange of a catheter or guidewire. The catheter tip is positioned at the desired proximal extent of the stent. Demarcating this position with the fingers on the catheter sheath at the accessory channel port, the catheter is then withdrawn until the tip is positioned at the desired distal extent of the SEMS. The distance is then determined by the length of catheter withdrawn from the accessory channel port. Catheters and guidewires with designated length markings can also be used. The degree of 170

Fig. 17.8

Suprapapillary placement of SEMS

Chapter 17 Expandable Stent Insertion

this patient group there was 2 cm between the papilla and the distal end of the stricture. The potential disadvantage of suprapapillary SEMS placement is that, should it be required for management of SEMS occlusion, recannulation of the stent lumen may prove challenging. Transpapillary SEMS placement (Fig. 17.9) is typically used for common bile duct obstruction. Transpapillary placed SEMS should extend 5–10 mm into the duodenal lumen. This extent permits ease of subsequent recannulation. Transpapillary SEMS that extend much further increase the risk for mechanical trauma to the opposing duodenal wall with potential for development of ulceration, bleeding and perforation. Transpapillary SEMS placement does not promote pancreatic duct obstruction or pancreatitis.

Endoscopic and fluoroscopic guides Once access has been obtained and the appropriate stent selected then the SEMS can be delivered and deployed. One or both ports of the stent introducer (depending on the stent) should be lubricated with a flush of normal saline to ease advancement over the guidewire and withdrawal of the outer sheath. The tip of the duodenoscope should remain in close proximity to the papilla and thus minimal wire is seen endoscopically. This “close” position helps to prevent accidental loss of guidewire access when the rather stiff SEMS introducer catheter is being inserted into the ampullary orifice. The stent is passed over a guidewire into the bile duct and advanced through the stricture. In a coordinated effort between the endoscopist and the assistant, the guidewire is maintained stationary while the introducer catheter is inserted over it. The arrangement and designation

of endoscopic and fluoroscopic marking vary between commercially available SEMS and the endoscopist and assistant must be familiar with these representations. Fluoroscopic markings commonly designate the predeployment and approximate post-deployment proximal and distal ends of the SEMS. If the stent will be placed transpapillary, the distal margin of the SEMS can be seen endoscopically and positioned so as to deploy with the desired length extending from the ampulla. We generally maintain fluoroscopic and endoscopic guidance throughout deployment to ensure accurate SEMS placement. It should be noted that during deployment, SEMS may have a tendency to move upstream. To counter this, during deployment, the endoscopist may need to apply resistance to or graded withdrawal of the introducer catheter in order to achieve precise placement.

Deployment With the SEMS introducer apparatus in the desired position, the outer sheath is incrementally withdrawn by the technician to release the stent. The proximal end (with respect to the liver) of the stent will gradually open as the outer sheath is withdrawn (Fig. 17.10). The stent position may be adjusted distally by withdrawing the entire apparatus. For more proximal position readjustment, the partially released SEMS must be recaptured, if possible, by advancing the outer sheath. The extent of deployment to which the stent may be recaptured varies between products. Withdrawing the outer sheath fully deploys the SEMS. The introducer catheter and guidewire are then removed. Care should be taken to ensure that the obturator tip of the introducer catheter does not catch the SEMS

A

B

Fig. 17.9

Transpapillary SEMS placement 171

SECTION 2 TECHNIQUES

B A

Rendezvous technique When ERCP cannulation of the bile duct cannot be achieved, SEMS placement may be performed in a coordinated effort between the endoscopist and interventional radiologist. A guidewire is placed into the bile duct through the percutaneous transhepatic approach. The guidewire is advanced into the duodenum. The guidewire is grasped in the duodenum by a biopsy forceps or snare and pulled through the accessory channel of the duodenoscope. A catheter or stent introducer is then advanced over the guidewire through the accessory channel and eventually into the bile duct. This combined technique has been successful in 80% of patients with malignant bile duct obstruction.48

Hilar stricture

C

D

Fig. 17.10 Deployment of SEMS. A Cholangiogram demonstrating a markedly dilated proximal bile duct with a distal stricture. B SEMS introducer advanced over the wire with the proximal end of the stent above the proximal end of the stricture. C Initial withdrawal of the outer sheath. D Full deployment of the SEMS.

risking displacement. When using SEMS for palliation of tight stenosis, incomplete radial expansion of the deployed stent is not uncommonly observed. Incomplete expansion may resist withdrawal of the introducer catheter, particularly at the level of the obturator tip, risking dislodgement or malpositioning of the SEMS. To overcome this, the outer sheath may be incrementally re-advanced over the introducer catheter as it is withdrawn. This permits withdrawal of the stent delivery system while applying resistance to the deployed SEMS thereby avoiding unintended dislodgement. The elevator lever should be relaxed during deployment to allow smooth withdrawal of the outer sheath. Post-deployment SEMS cannot be readjusted proximally. A rat-tooth forceps may be used to adjust the position more distally. 172

Management of hilar tumors is also discussed in Chapter 28. Cholangiocarcinoma, gallbladder carcinoma, and portal hepatic lymph nodes can lead to an obstruction of the bile duct at the level of the hilum of the liver. These tumors are associated with poor prognoses and death is usually caused by cholangitis or liver failure. This patient population tends to present with advanced disease; as such, most of the tumors are unresectable. Palliation of hilar obstructions provides a greater challenge than common bile duct lesions. While unilateral stenting is effective for the relief of jaundice, bilateral stenting may be required to palliate cholangitis. In a prospective study of 61 patients with hilar strictures, unilateral stent placement was achieved in 97% of patients.49 Jaundice resolved in 86.9% of patients. Cholangitis developed in three patients within the first week of the stent placement but all of these patients were successfully treated with antibiotics. There was one patient that developed a liver abscess and required percutaneous interventions on the contralateral side.50 It is now generally recommended that both the left and right intrahepatic ducts be drained during the procedure if both sides are opacified during a cholangiogram (Fig. 17.11). A preprocedure MRCP may help to plan selective drainage with metallic stents.45 If there is one dominant side identified by MRCP then selective cannulation with a catheter and a guidewire should be attempted with intentional avoidance of pressure injection of contrast. Once the catheter is in the desired location then measured cholangiography should be performed. If only one side is opacified then single stent can be placed. If there is opacification of both the right and left biliary systems, bilateral stenting should be pursued. Bilateral SEMS may be placed alongside one another or the second SEMS may be deployed through the mesh of the initial SEMS (Fig. 17.12). Two wires are used to maintain access to the right and left biliary systems while placing bilateral stents in a side-by-side fashion. Those wires must remain separated and secure while placing the stents. It can sometimes be difficult to place the second stent beside the first stent. Hookey demonstrated that the placement of a tem-porary plastic stent in the CBD prevents the full expansion of the first stent to facilitate placement of the second SEMS.51 When a second stent is being placed through the interstices of the first stent, sometimes the interstices need to be balloon dilated. If obstructed intrahepatic ducts remain inadequately drained then percutaneous drainage may be required adjunctively.

Duodenal obstruction Up to 10–20% of patients with pancreatic and ampullary tumors develop duodenal or gastric outlet obstruction.52 Enteral stenting is an effective means of palliation of malignant gastroduodenal obstruction symptoms.53–57 Most of these patients have concurrent or

Chapter 17 Expandable Stent Insertion

A

B

D

E

C

Fig. 17.11 Bilateral SEMS for a hilar stricture. A Cholangiogram revealed dilated left and right intrahepatic ducts with a hilar stricture. B Wire placed in the left intrahepatic system. C Catheter placed in right intrahepatic system to facilitate placement of a second wire. D SEMS placed over wire into the right intrahepatic system with a wire in the left intrahepatic system. E Stents placed in both the left and right intrahepatic ducts. The stent in the left intrahepatic duct was placed in a suprapapillary position. A

Fig. 17.12 Positioning of SEMS in hilar strictures. A Side by side placement of stents. B One stent through the interstices of another stent creating a “Y” formation. Redrawn from Ahmad NA, Ginsberg GG. Gastrointestinal Endoscopy 2001;3(2):93– 102 with permission.

B

pending bile duct obstruction and many will already have a bile duct stent in place. Owing to their prolonged patency, a biliary SEMS is recommended prior to placement of an enteral stent. This may be performed at the same setting. While feasible in individual cases, it is apt to be more difficult to place a biliary stent through the interstices of a previously placed enteral stent. Sequential placement of biliary and enteral SEMS was reported on 17 patients. The duodenal stricture was traversed with the duodenoscope after dilation. All patients had resolution of jaundice and 16 of the 17 patients had relief of nausea and vomiting. During the follow-up two patients had recurrence of biliary obstruction and two different patients had recurrence of duodenal obstruction. Three cases were secondary to tumor ingrowth and the fourth case was secondary to migration of the duodenal stent.58

COMPLICATIONS SEMS are generally safe and effective for the palliation of malignant biliary obstruction. The complications related to SEMS include those associated with ERCP and immediate and delayed SEMS malfunction. The generic ERCP associated complications include perforation, pancreatitis, and sedation-related cardiorespiratory compromise and are discussed in more detail in Chapter 6. Immediate causes of SEMS malfunction include device failure, deployment failure, and malpositioning of the stent. Failure to adequately lubricate the delivery device channels may inhibit withdrawal of the outer sheath. Excessive articulation of the elevator lever may similarly retard withdrawal of the outer sheath and has led to separation of the delivery apparatus. 173

SECTION 2 TECHNIQUES

Malpositioning of the SEMS is usually attributable to operator error. If the location of the stent is not satisfactory then a second stent may be placed at the same setting. When in the transpapillary position, another option is to completely remove the stent. Recently placed SEMS may be repositioned more distally or completely removed with a grasping forceps or a snare. For SEMS removal, the stent should be grasped and pulled to the tip of the endoscope, and the endoscope withdrawn under fluoroscopic guidance. The stent should be not pulled into the accessory channel of the duodenoscope because the sharp ends can damage the channel. This is best accomplished within 48 hours of insertion as tissue hyperplasia leads to embedding of the stent within the bile duct wall. Covered SEMS may be more readily removed remote to the time of insertion.37 Other early complications, as defined as occurring within one week of the stent placement, include cholangitis, hemobilia, and perforation. Ineffective drainage of segments opacified during cholangiography increases the risk of cholangitis. Patients with malignant hilar strictures or coexisting primary sclerosing cholangitis are at greatest risk. Administration of prophylactic antibiotics may be beneficial to prevent or manage cholangitis in selected patients. Persistent evidence of cholangitis while on antibiotics requires repeat instrumentation either through a retrograde or antegrade approach. SEMS placement into friable bile duct tumors may induce hemobilia. This bleeding is typically not clinically significant and resolves spontaneously. However, retained clot may result in recurrence of biliary obstruction. The retained blood clot may be cleared with catheter irrigation or a stone retrieval balloon. A malpositioned SEMS may perforate the bile duct wall or produce ulceration, bleeding, and perforation of the opposing duodenal wall. There are reports of using argon beam plasma coagulation to shorten stents of excessive length within the duodenum that have caused complications.59 Studies in animals suggest this is safe to surrounding tissues.60 The most common late complication related to SEMS is stent occlusion. The stent may become occluded by tumor ingrowth or overgrowth, tissue hyperplasia or biliary sludge. Biliary sludge is the most common cause of occlusion of plastic stents but this occurs less commonly with SEMS given their larger diameter. With SEMS, the most common cause of occlusion is tumor ingrowth. The tumor grows through the interstices of the stent. There have been two studies that have investigated the management of an occluded stent. Tham et al.61 performed a multicenter trial that included 38 patients with occluded stents. Occlusions were managed by insertion of another metallic stent in 19, insertion of a plastic stent in 20 and mechanical cleaning in 5. There was no statistical difference in revised stent patency among the different treatment groups. It was noted that it is more cost-effective to place a plastic stent for the management of an occluded metallic stent. A similar single-center

study was performed by Bueno et al.62 In this study, placement of a second Wallstent or plastic stent was equally effective. A covered Wallstent may be chosen for the management of an occluded SEMS. Patient outcome was better if they had a distal bile duct occlusion as opposed to a proximal bile duct occlusion. The means of SEMS revision should be individualized and take into consideration the overall prognosis of the patient. Once deployed, migration of non-covered SEMS is rare. Migration of covered SEMS occurred in 6% of patients in the study by Kahaleh et al.35 Initial iterations of covered stents were 100% covered which appeared to increase the risk of SEMS migration. Subsequent modifications have left the proximal and distal ends of the stent uncovered. This allows some degree of embedding into the bile duct wall to retard migration. Cholecystitis has occurred in 2.9% to 12% of patients with covered biliary SEMS owing to cystic duct obstruction.35

COST SEMS vs Plastic Overall biliary SEMS have longer patency than FDPS. The major limiting factor to SEMS is the higher cost. The cost-effectiveness of the SEMS becomes apparent when multiple FDPS exchanges need to be performed. A randomized, prospective study by Kaassis et al.11 demonstrated that the number of additional days of hospitalization, days of antibiotics and the number of ERCPs performed on the group with the FDPS was higher compared to the group that received the SEMS. Davids et al.4 demonstrated a 28% reduction in ERCPs per patient with the use of SEMS. From those two studies as well as two studies using decision analysis with Markov modeling,63,64 initial SEMS placement is cost-effective in patients with survival of greater than six months. In Kaassis, et al.11 patients with liver metastases had a poorer prognosis with less than six months to live so would be an ideal group for the placement of plastic stents.

CONCLUSION Malignant pancreaticobiliary disease presents at an advanced stage and has a poor prognosis. Endoscopic palliative techniques have largely replaced surgical bypass. SEMS are effective for the palliation of malignant biliary obstruction. SEMS have more durable patency versus FDPS. While the upfront cost is greater for SEMS, compared to FDPS, they require few reinterventions which make SEMS more cost-effective. Covered SEMS have been more recently introduced and have been shown to decrease the rate of tumor ingrowth as compared to uncovered SEMS, however, they have been associated with increased frequency of complications. Covered SEMS are being studied for non-malignant applications.

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Chapter 17 Expandable Stent Insertion

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26. Nakamura T, Hirai R, Kitagawa M, et al. Treatment of common bile duct obstruction by pancreatic cancer using various stents: single-center experience. Cardiovasc Intervent Radiol 2002; 25:373–380. 27. Han YM, Hwang SB, Lee ST, et al. Polyurethane-covered selfexpandable nitinol stent for malignant biliary obstruction: preliminary results. Cardiovasc Intervent Radiol 2002; 25:381–387. 28. Isayama H, Komatsu Y, Tsujino T, et al. Polyurethane-covered metal stent for management of distal malignant biliary obstruction. Gastrointest Endosc 2002; 55:366–370. 29. Schoder M, Rossi P, Uflacker R, et al. Malignant biliary obstruction: treatment with ePTFE-FEP-covered endoprostheses-initial technical and clinical experiences in a multicenter trial. Radiology 2002; 225(1):35–42. 30. Bezzi M, Zolovkins A, Cantisani V, et al. New ePTFE/FEP-covered stent in the palliative treatment of malignant biliary obstruction. J Vasc Interv Radiol 2002; 13:581–589. 31. Han YM, Jin GY, Lee SO, et al. Flared polyurethane-covered selfexpandable nitinol stent for malignant biliary obstruction. J Vasc Interv Radiol 2003; 14:1291–1301. 32. Isayama H, Komatsu Y, Tsujino T, et al. A prospective randomized study of “covered” versus “uncovered” diamond stents for the management of distal malignant biliary obstruction. Gut 2004; 53:729–734. 33. Miyayama S, Matsui O, Akakura Y, et al. Efficacy of covered metallic stents in the treatment of unresectable malignant biliary obstruction. Cardiovasc Intervent Radiol 2004; 27:349–354. 34. Nakai Y, Isayama H, Komatsu Y, et al. Efficacy and safety of the covered Wallstent in patients with distal malignant biliary obstruction. Gastrointest Endosc 2005; 62:742–748. 35. Kahaleh M, Tokar J, Conaway MR, et al. Efficacy and complications of covered Wallstents in malignant distal biliary obstruction. Gastrointest Endosc 2005; 61:528–533. 36. Yoon WJ, Lee JK, Lee KH, et al.. A comparison of covered and uncovered Wallstents for the management of distal malignant biliary obstruction. Gastrointest Endosc 2006; 63(7):996–1000. 37. Familiari P, Bulajic M, Mutignani M, et al. Endoscopic removal of malfunctioning biliary self-expandable metallic stents. Gastrointest Endosc 2005; 62:903–910. 38. Kahaleh M, Brock A, De La Rue SA, et al. Temporary placement of covered self expandable metal stents (SEMS) in benign biliary strictures: preliminary data. Gastrointest Endosc 2005; 61:AB208. 39. Baron TH, Poterucha JJ. Insertion and removal of covered expandable metal stents for closure of complex biliary leaks. Clin Gastroenterol Hepatol 2006; 4(3):381–386. 40. Dumonceau JM, Cremer M, Auroux J, et al. A comparison of Ultraflex Diamond stents and Wallstents for palliation of distal malignant biliary strictures. Am J Gastroenterol 2000; 95:670–676. 41. Rajiman I, Amin V, Siddique I, et al. The use of the Diamond stent (DS) in the treatment of malignant bile duct stricture. Gastrointest Endosc 1999; 49:AB235. 42. Seecoomar LF, Cohen SA, Kasmin FE, et al. Preliminary experience with the Ultraflex Diamond stent for management of malignant biliary obstruction. Gastrointest Endosc 1999; 49:AB236. 43. Siqueira E, Martin JA, Vargas, et al. Prospective evaluation of a new metal stent for treating malignant biliary obstruction. Gastrointest Endosc 1999; 49:AB236. 44. Shah RJ, Howell DA, Desilets DJ, et al. Multicenter randomized trial of the spiral Z-stent compared with the Wallstent for malignant biliary obstruction. Gastrointest Endosc 2003; 57:830–836. 45. Freeman ML, Overby C. Selective MRCP and CT-targeted drainage of malignant hilar biliary obstruction with self-expanding metallic stents. Gastrointest Endosc 2003; 58:41–49. 46. Pedersen FM, Lassen AT, Schaffalitzky de Muckadell OB. Randomized trial of stent placement above and across the

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47.

48.

49.

50.

51.

52.

53.

54.

55.

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sphincter of Oddi in malignant bile duct obstruction. Gastrointest Endosc 1998; 48:574–579. Liu Q, Khay G, Cotton PB. Feasibility of stent placement above the sphincter of Oddi (“inside-stent”) for patients with malignant biliary obstruction. Endoscopy 1998; 30:687–690. Dowsett JF, Vaira D, Hatfield AR, et al. Endoscopic biliary therapy using the combined percutaneous and endoscopic technique. Gastroenterol 1989; 96:1180–1186. Deviere J, Baize M, de Toeuf J, et al. Long term follow-up of patients with hilar malignant stricture treated by endoscopic internal biliary drainage. Gastrointest Endosc 1988; 34:95–101. DePalma GD, Pezzullo A, Rega M, et al. Unilateral placement of metallic stents for malignant hilar obstructions: A prospective study. Gastrointest Endosc 2003; 58:50–53. Hookey LC, Le Moine O, Deviere J. Use of a temporary plastic stent to facilitate the placement of multiple self-expanding metal stents in malignant biliary hilar strictures. Gastrointest Endosc 2005; 62(4):605–609. Watanapa P, Williamson RC. Surgical palliation for pancreatic cancer: developments during the past two decades. Br J Surg 1992; 102:608–613. Maetani I, Ogawa S, Hoshi H, et al. Self-expanding metal stents for palliative treatment of malignant biliary and duodenal stenosis. Endoscopy 1994; 26:701–4. Soetikno RM, Carr-Locke DL. Expandable metal stents for gastric outlet, duodenal, and small intestinal obstruction. Gastrointest Endosc Clin North A 1999; 9:447–458. Soetikno RM, Lichtenstein DR, Vadervoort J, et al. Palliation of malignant gastric outlet obstruction using an endoscopically placed Wallstent. Gastrointest Endosc 1998; 47:267–270.

56. Yates III MR, Morgan DE, Baron TH. Palliation of malignant gastric and small intestinal strictures with self-expandable metal stents. Endoscopy 1998; 30:266–272. 57. Yim HB, Jacobson BC, Saltzman JR, et al. Clinical outcome of the use of enteral stents for palliation of patients with malignant upper GI obstruction. Gastrointest Endosc 2001; 53:329–332. 58. Kaw M, Singh S, Gagneja H. Clinical outcome of simultaneous self-expandable metal stents for palliation of malignant biliary and duodenal obstruction. Surgical Endoscopy 2003; 17:457–461. 59. Vanbiervliet G, Piche T, Caroli-Bosc FX, et al. Endoscopic argon plasma trimming of biliary and gastrointestinal metallic stents. Endoscopy 2005; 37(5):434–438. 60. Chen YK, Jakribettuu V, Springer EW, et al. Safety and efficacy of argon plasma coagulation trimming of malpositioned and migrated biliary metal stents: a controlled study in the porcine model. Am J Gastroenterol 2006; 101:1–6. 61. Tham TCK, Carr-Locke DL, Vandervoort J, et al. Management of occluded biliary Wallstents. Gut 1998; 42:703–707. 62. Bueno JT, Gerdes H, Kurtz RC. Endoscopic management of occluded biliary Wallstents: a cancer center experience. Gastrointest Endosc 2003; 58:879–884. 63. Arguedas MR, Heudebert GH, Stinnett AA, et al. Biliary stents in malignant obstructive jaundice due to pancreatic carcinoma: a cost effective anaylsis. Am J Gastroenterol 2002; 97:897–904. 64. Yeoh KG, Zimmerman MJ, Cunningham JT, et al. Comparative costs of metal versus plastic biliary stent strategies of malignant obstructive jaundice by decision analysis. Gastrointest Endosc 1999; 49:466–471.

SECTION 2

Chapter

18

TECHNIQUES

Stent Removal: Migrated and Non-Migrated Tiing Leong Ang, Stefan Seewald and Nib Soehendra

BOX 18.1 SUMMARY OF KEY TECHNIQUES Techniques that do not maintain duct access: • Direct grasping with a basket, rat-tooth forceps or snare • Use of an inflated balloon catheter to provide lateral traction Techniques that maintain duct access: The occluded or proximally migrated stent is first cannulated using a guidewire and catheter. The stent is then retrieved with retrieval devices such as: • Soehendra® stent retriever: The retriever is inserted over the guidewire and pushed into close proximity with the stent. Its screw-tip is then rotated into the distal end of the stent, thus anchoring the stent retriever. The stent is then pulled out through the accessory channel with continued duct access maintained by the guidewire. • Other techniques: 1. A partially opened small snare is passed over the guidewire. The snare is fully opened around the distal tip of the stent which is grasped over the distal flaps. The stent is removed through the accessory channel while the guidewire is maintained in position. 2. A 4 mm diameter, 2.5 cm long dilating balloon is advanced over the guidewire into the stent (size > 10 Fr) and inflated. The stent is withdrawn by pulling the inflated balloon.

INTRODUCTION AND SCIENTIFIC BASIS Plastic endoprostheses have become an established therapy for a variety of biliary and pancreatic disorders (see Chapter 16). Endoscopic biliary stent placement is used for indications such as drainage of malignant or benign biliary obstruction, biliary stricture dilatation and biliary leakage. Pancreatic stents are used for transpapillary drainage of pseudocysts, treatment of pancreatic fistulae, relief of pancreatic duct obstruction from stricture or malignancy, as well as prophylaxis against post-ERCP pancreatitis.1 These stents may be temporary, such as in the case of stricture dilatation or prevention of post-ERCP pancreatitis, or intended for long-term treatment. Stent removal will be required once the therapeutic endpoint is achieved, and when stent occlusion or migration occurs because

of complications such as cholangitis, pancreatitis, duodenal wall injury or perforation. Self-expandable metallic stents (SEMS) are increasingly being used for palliative treatment of malignant biliary obstruction. As compared to plastic stents, the duration of stent patency is longer because of the larger luminal diameter. SEMS have also been shown to be more cost-effective compared to plastic stents for patients who survive more than 4–6 months.2 The placement of uncovered SEMS is generally regarded as permanent due to the fact that they become deeply embedded in the bile duct wall and induce a marked tissue reaction making endoscopic removability difficult, if not impossible. Covered SEMS were developed primarily to extend stent patency by preventing tumor ingrowth. The covering prevents deep embedding of the stent into the biliary wall, which, although increasing the risk of migration, allows them to be potentially endoscopically removable. SEMS are generally only used for palliation of malignant biliary stenosis with intent to remain in place permanently. SEMS placement in benign biliary strictures has been described3 but it is not generally accepted. Although uncovered SEMS are generally not removable, cases of successful extraction have been reported.4 Plastic stents may be removed by directly grasping them with accessories such as rat-tooth forceps, polypectomy snares, or stone retrieval baskets. Other methods of direct removal involve cannulation of the stent lumen with a guidewire followed by insertion of retrieval devices such as the Soehendra® stent retriever or a dilating balloon. Plastic stents can also be removed indirectly by providing lateral traction force, such as with the use of a stone retrieval or dilating balloon. SEMS extraction is more difficult than plastic stents. Covered SEMS can be removed by directly snaring the distal end within the duodenum, whereas uncovered SEMS can be removed by grasping and breaking individual wire filaments in order to unravel the stent, though this is not always technically feasible.

INDICATIONS/CONTRAINDICATIONS OF STENT REMOVAL

BOX 18.2 INDICATIONS AND CONTRAINDICATIONS Indications: • Occluded stents • Migrated stents

177

SECTION 2 TECHNIQUES

• Therapeutic endpoint achieved • To facilitate duct access for further endoscopic treatment Contraindications: • Presence of severe co-morbid illnesses such that endoscopy cannot be safely performed • In situations such as terminal malignancies where the clinical outcome would not be altered • Uncovered self-expandable metallic stents (relative contraindication)

Indications

1. Occluded stents: Occluded biliary stents need to be removed and replaced in order to facilitate continued biliary drainage. Occluded stents lead to jaundice and cholangitis. If occluded pancreatic duct stents are not replaced, acute pancreatitis may result. If not removed in a timely fashion chronic pancreatic duct changes may also occur. 2. Migrated stents: Completely distally migrated biliary and pancreatic stents usually pass spontaneously and uneventfully out of the gastrointestinal tract into the stool. However, if distal migration of a stent is incomplete, injury to the contra-lateral duodenal wall may arise; duodenal wall perforation has been reported in this context. Usually a distally migrated stent may be simply grasped and removed. Frequently, the distal end is too far to be reached with a snare or basket and can be grasped with a rat-tooth forceps at the point where the stent is exiting the papilla. 7 Fr stents can be grasped with a diagnostic forceps while a therapeutic forceps is required to grasp 10 Fr stents. Grasping the flap is usually not effective, since it usually breaks away from the stent. Proximal migration has been reported to occur at an incidence rate of 4.9% and 5.2% for biliary and pancreatic stents, respectively.5 Unlike distally migrated stents, proximally migrated stents are more difficult to retrieve since they cannot be directly endoscopically visualized; guidance is provided by fluoroscopy which does not provide three-dimensional orientation. 3. Therapeutic purpose achieved: When the treatment endpoint has been achieved, such as after successful dilatation of benign biliary strictures including anastomotic strictures following liver transplantation,6 those due to chronic pancreatitis,7 and after resolution of biliary8 or pancreatic9 fistula, the stent should be removed. Temporary pancreatic stents placed after endoscopic papillectomy or pancreatic duct sphincterotomy require removal if they do not pass spontaneously. 4. To provide access for further endoscopic interventions: In some situations stents are inserted for temporary ductal drainage and require removal before definitive treatment can be carried out. For example, insertion of a temporary biliary stent may be performed if bile duct calculi cannot be extracted. Stents require removal in order to perform additional interventions such as mechanical lithotripsy or electrohydraulic lithotripsy. Temporary stents have also been inserted to facilitate healing of biliary and pancreatic fistulae; if these fistulae are persistent, sealing may be attempted with the help of N-butyl-2-cyanoacrylate.10,11 In these instances, in order to provide adequate duct access for the passage of accessory devices, the temporary stents must first be removed. 178

Contraindications

1. Severe comorbid illnesses: In the presence of severe comorbid medical illnesses, hemodynamic instability, or pulmonary insufficiency, where sedation is hazardous or the patient is unstable, ERCP and stent removal are contraindicated. In terminally ill patients, with a migrated stent but who are asymptomatic, attempted ERCP and stent removal should probably be avoided since it will not be expected to influence the clinical course of the patient. 2. Self-expandable metallic stent: The placement of an uncovered SEMS is generally regarded as permanent. Uncovered SEMS may occlude because of tumor ingrowth and/or tissue hyperplasia. Attempted removal of uncovered SEMS may lead to complications such as bleeding and perforation because they become deeply embedded into the tissue soon after placement. Hence, removal of uncovered SEMS is considered a contraindication, though in certain circumstances the benefits of removal outweigh the potential risks. The presence of a coagulopathy, however, is considered a contraindication to removal of uncovered SEMS.

TECHNIQUES OF STENT REMOVAL Plastic stents

Overview of techniques for plastic stent removal These techniques include direct grasping with an accessory device such as rat-tooth forceps, stone retrieval basket, or polypectomy snare. Indirect techniques utilize traction with an inflated occlusion or dilating balloon that has been advanced alongside the stent followed by withdrawal. Direct traction techniques involve cannulation of the stent lumen with a guidewire followed by insertion of a dilating balloon or screw extractor. These latter methods allow access to the biliary tree to be maintained as the stent is withdrawn facilitating subsequent insertion of a new stent or performance of other therapeutic maneuvers. Maintaining duct access with a guidewire is crucial if the intent is to replace the stent, especially if selective duct cannulation or traversal of a stricture was initially difficult to achieve. Migrated stents are generally more difficult to remove compared to non-migrated stents. With distal migration, the end may be impacted against the contra-lateral duodenal wall or out of reach of the endoscope. Much of the published data on removal of proximally migrated stents consist of case reports. Three larger case series have been reported. In these series successful stent removal was achieved in 85–90% of cases (Table 18.1).12–14 In addition, novel techniques for the removal of migrated stents have also been described.15,16

Common accessories used In general, a therapeutic duodenoscope with a working channel of 4.2 mm diameter is preferred. This allows withdrawal of the retrieved stents (up to 10 Fr) through the accessory channel without having to withdraw the endoscope. Endoscopic accessories that are commonly used for stent removal include the following: polypectomy snare (e.g. ReSnare® (a reusable polypectomy snare), Cook Endoscopy), rat-tooth forceps (e.g. FG-14P-1, FG-8L-1; Olympus Optical Co, Tokyo, Japan), Dormia basket (e.g. FG-22Q-1, Olympus Optical Co, Tokyo, Japan), biliary dilatation balloon (e.g. CRETM wire guided biliary balloon dilators, Boston Scientific, Natick, MA, USA; BB-1, Olympus Optical Co, Tokyo, Japan; QBIDTM, Cook Endoscopy), extraction balloon catheters (e.g. B5-2Q, Olympus Optical Co, Tokyo, Japan; DASH® extraction balloon, Cook Endoscopy), Teflon coated

Chapter 18 Stent Removal: Migrated and Non-Migrated

1st author 12

Tarnasky 1995

Biliary stent

Pancreatic stent

44

0

13

33

26

14

41

0

118

26

Lahoti 1998

Chaurasia 1999

Total

Success rate of endoscopic retrieval

Management of failed retrieval

38/44 (86%)

Radiological Surgery Follow-up

Biliary: 28 (85%) Pancreatic: 21 (80%)

Insertion of 2nd stent Surgery Follow-up

37/41 (90%)

Insertion of 2nd stent

124/144 (86%)

Table 18.1 Results of endoscopic removal of proximally migrated stents

Fig. 18.1 Soehendra® Stent Retriever (courtesy of Cook Endoscopy, Winston-Salem, NC, USA).

Fig. 18.3 basket.

Fig. 18.2 Soehendra® Stent Retriever with extended curved plastic tip facilitating cannulation of the stent (courtesy of Cook Endoscopy, Winston-Salem, NC, USA).

stainless steel and nitinol tracer guidewires (Cook Endoscopy, Winston-Salem, NC, USA), Zebra® wire (Boston Scientific, Natick, MA, USA), Soehendra® universal catheter and Soehendra® stent retriever (Cook Endoscopy, Winston-Salem, NC, USA) (Figs 18.1 and 18.2). Most of these accessories are readily available from a variety of medical device companies (Chapter 4).

SPECIFIC TECHNIQUES 1. Direct grasping of stent The standard method of removing non-migrated or distally migrated stents involves grasping the distal intra-duodenal portion of the stent with a polypectomy snare, stone retrieval basket (Fig. 18.3) or rattooth forceps (Fig. 18.4), followed either by withdrawing the endoscope completely out of the patient or by depositing the stent in the stomach for subsequent removal at the end of the procedure. Alternatively, the stent may be withdrawn through the accessory channel of the endoscope, if the diameter of the stent allows. For example,

Grasping an occluded biliary stent with a Dormia

if a diagnostic duodenoscope with a 2.8 mm accessory channel is used, a 7 Fr stent (2.3 mm diameter) may be extracted through the channel, but a 10 Fr stent (3.3 mm) cannot; similarly, if a therapeutic duodenoscope with a 4.2 mm accessory channel is used, a 10 Fr stent may be extracted through the endoscope if it is captured at its distal end, but if caught in mid-shaft, it tends to fold upon itself, such that the total diameter is 6.6 mm; in this scenario, the duodenoscope would have to be withdrawn. If the distally migrated stent has penetrated the duodenal wall, then neither stone retrieval baskets nor snares are suitable and a rat-tooth forceps would be required. This technique of direct grasping may also be utilized for proximally migrated stents, but in the presence of non-dilated ducts, passage of accessories may be difficult and the forceps may not have enough room to adequately open. A rat-tooth forceps can be used to grasp the distal end of the proximally migrated stent. In addition, a basket or snare can be used to capture the stent from either the proximal or distal end initially, but on removal only the distal end should be grasped in order to avoid perforation.17 If subsequent stent replacement is required, or if the access to the duct needs to be maintained, the biliary or pancreatic duct must be cannulated with a guidewire and the stent removed leaving the wire in place.

2. Indirect technique using balloon traction To retrieve a proximally migrated stent there are two variations of this indirect technique in which either a single or double lumen balloon catheter is passed over a guidewire that has been passed alongside the stent. Either a stone extraction balloon or a dilatation 179

SECTION 2 TECHNIQUES

Fig. 18.4 forceps.

Retrieving an occluded biliary stent with a rat-tooth

balloon may be used. The balloon is advanced so that it is located alongside and at the midpoint of the stent. The balloon is then inflated and gradually withdrawn. The indirect traction provided by the balloon catheter causes the stent to pass distally (Fig. 18.5). An alternative is to pass the balloon catheter to a point just above the proximal end of the stent. The balloon is then inflated and the stent retrieved by gradually pulling the balloon catheter distally. The size of the balloon used depends on the size of the duct; for instance, in a dilated common bile duct, one may be able to use an 8 or 11.5 mm dilating balloon, whereas in a non-dilated pancreatic duct, a smaller size dilatation balloon (4 mm) is used.18

Fig. 18.5 Removal of proximally migrated biliary stent using a dilating balloon. The dilating balloon (arrow) and distal end of the stent (arrowhead) can be seen.

3. Techniques utilizing stent cannulation A variety of techniques which utilize stent cannulation may be used for stent retrieval. The stent lumen is cannulated with a guidewire loaded into a catheter or sphincterotome; the latter allows for upward deflection into the stent. When applying this technique to proximally migrated stents, the lumen can be difficult to cannulate; use of a hydrophilic guidewire may be helpful to access the stent lumen. The Soehendra® stent retriever was developed to maintain duct access during stent removal. This is especially useful when replacing stents in patients in whom the initial cannulation and stent placement were very difficult, such as in the case of perihilar cholangiocarcinoma and multiple stents (Figs 18.6–18.12). It can also be used to retrieve a proximally migrated stent upon initial guidewire cannulation of the stent (Figs 8.13–8.21). It is a wire-guided metal spiral retrieval device 200 cm long with a screw tip 3 to 4 mm long that is rotated into the inner lumen of the stent.19 Exact alignment of the inner lumen of the stent with the retrieval device is needed for this device to self-thread into the stent. Once the stent retriever is securely anchored to the end of the stent, the 180

Fig. 18.6 A patient with perihilar cholangiocarcinoma. Four biliary stents were inserted in order to drain different liver segments; the insertion of two of these stents required a rendezvous procedure after initial unsuccessful ERCP. The figure shows initial cannulation of one of the occluded stents using a 7 Fr universal catheter.

Chapter 18 Stent Removal: Migrated and Non-Migrated

Fig. 18.7 A guidewire had been successfully inserted through the occluded stent.

Fig. 18.8 The catheter was withdrawn and the guidewire left within the stent.

Fig. 18.10 The screw tip of Soehendra® stent retriever was rotated into the distal end of the stent.

Fig. 18.9 Insertion of the Soehendra® stent retriever over the guidewire.

Fig. 18.11 The occluded stent was then removed by the Soehendra® stent retriever. 181

SECTION 2 TECHNIQUES

Fig. 18.12 After the stent had been retrieved, the guidewire was left in place to facilitate subsequent reinsertion of a new stent.

Fig. 18.15 The glidewire was used to direct the tip of the universal catheter into the distal end of the migrated stent.

Fig. 18.13

X-ray picture of a proximally migrated biliary stent.

Fig. 18.16 The glidewire had been withdrawn, and the tip of the universal catheter was inserted in the distal end of the migrated stent.

Fig. 18.14 Cannulation of the proximally migrated biliary stent using Terumo glidewire guided by a universal catheter. 182

Fig. 18.17 A standard guidewire was then inserted through the universal catheter into the lumen of the migrated stent.

Chapter 18 Stent Removal: Migrated and Non-Migrated

Fig. 18.18 The universal catheter was then withdrawn leaving the guidewire in place.

Fig. 18.21 The migrated stent had now been pulled out through the major papilla.

Fig. 18.19 The Soehendra® stent retriever had been inserted over the guidewire and its tip had been rotated into the end of the proximally migrated stent.

Fig. 18.20 X-ray picture of the stent being withdrawn by the Soehendra® stent retriever.

stent is withdrawn through the biopsy channel. The guidewire is maintained during exchange as when any device is exchanged. Depending on the size of the stent, one would need to select an appropriately sized stent retriever. Plastic stents made of polyethylene become softer after a few months and so the tip of the retriever may not anchor firmly into the end of the stent, resulting in failure of stent retrieval. In such a situation, a larger size stent retriever (e.g. 11.5 Fr retriever for a 10 Fr stent) should be used. Newer stents such as the Viaduct (GI Supply®, Camp Hill, PA) and the Marathon antireflux stent (Cook Endoscopy, Winston-Salem, NC) (Chapter 16) are not amenable to this type of removal. Another method of stent removal using the stent cannulation technique is passage of a 4 mm standard biliary dilating balloon into the stent (Fig. 18.22). The balloon is advanced over the guidewire into the stent and inflated. The amount of inflation necessary to provide enough traction is less than for stricture dilatation; 4 atmospheres of pressure is usually adequate. The balloon inflation port is then locked and the stent is withdrawn by withdrawing the balloon while the wire is kept in place. This method can only be used for stents 10 Fr and larger.20 For removal of proximally migrated 5 Fr pancreatic stents, interventional cardiology dilating balloons, such as a 3 mm angioplasty balloon mounted on 2.5 Fr catheter, can be used.15 Yet another technique of removal over the wire utilizes a standard polypectomy snare (Figs 18.23–18.25).21–22 The stent lumen is cannulated with a standard guidewire as mentioned above. A partially opened snare (e.g. 5 Fr mini-snare, snare diameter 5 mm, snare length 1.5 cm, WCMSR-1; Cook Endoscopy, Winston-Salem, NC) is then passed over the guidewire and through the accessory channel. Once in view, the snare is fully opened and advanced to encircle the distal tip of the stent. The snare is closed to grasp the stent and the stent is withdrawn through the biopsy channel while the guidewire position is maintained.22 183

SECTION 2 TECHNIQUES

A

B

Fig. 18.23 This was a patient with pancreas divisum who had been treated with pancreatic stenting due to dorsal duct disruption following pancreatitis. A guidewire had already been inserted through the stent, and a partially opened snare was being advanced over the guidewire toward the stent. 184

Fig. 18.22 Balloon over the guidewire technique. A guidewire was first inserted into the stent. Next a balloon catheter was inserted over the guidewire into the stent. The balloon would then be inflated (either at the proximal end of the stent A or within the stent lumen B) and used to pull the stent down, while keeping the guidewire in place for subsequent stent reinsertion.

Fig. 18.24 The distal end of the pancreatic stent was then captured by the snare.

Chapter 18 Stent Removal: Migrated and Non-Migrated

4. Novel techniques In addition to the use of a rat-tooth forceps, the “lasso” technique had also been reported as a means of retrieving distally migrated plastic stents which have impacted against and perforated the contralateral duodenal wall.23 A 0.035 inch guidewire was passed behind the stent and the tip of the guidewire grasped by a polypectomy snare in front, thus looping the stent. The stent is then winched into close proximity with the endoscope and the entire apparatus retrieved together with the stent (Fig. 18.26). Instead of a snare, a retrieval basket had also been used for this purpose.16 In a case report the removal of proximally migrated 10 Fr biliary stent in which the distal end had become embedded in the wall of the common bile duct was described. A 0.035-inch Glidewire (Boston Scientific Corp, Natick, Mass.) was advanced beyond the proximal end of the stent within the common hepatic duct and then looped at the bifurcation with the tip of the guidewire returning toward the papilla. A snare was inserted through the accessory channel with the wire passing through the loop of the snare. The end of the Glidewire protruding from the papilla was grasped with the snare, tightening the wire and lassoing the stent. With further traction, the stent could be kinked and withdrawn.24 Some patients undergoing liver transplantation have a T-tube inserted across the choledochocholedochostomy to ensure anasto-

motic patency. A stent modified from a 5 Fr latex urinary catheter may be used intraductally to maintain anastomotic patency, and being without flaps, it is intended to pass spontaneously within weeks. A case had been reported in which such a latex stent did not pass spontaneously and was found to be folded back on itself within the bile duct. In this instance, ERC was performed and a guidewire was inserted without performing papillotomy. A rotatable rat-toothed forceps (Olympus America Corp, Lehigh Valley, PA) was inserted through the working channel and manipulated around the guidewire such that the guidewire was entrapped in the notch when the forceps was closed. The forceps was then introduced easily into the common bile duct in tandem with the guidewire, then disengaged, allowing the catheter to be grasped and removed without disrupting the architecture of the papilla.25

Special considerations Newer plastic stents that have become available such as the Viaduct stent and antireflux stent (Chapter 16) may pose special problems for removal. The Viaduct has a small central lumen that only allows passage of a guidewire; thus balloon passage and stent retriever passage into the lumen are not possible. With proximal migration, they may be more difficult to grasp. In patients with the antireflux stent, the wind-sock on the distal end makes it nearly impossible to cannulate the stent lumen. In addition in the event of proximal migration, the wind-sock may tear if grasped with a rat-tooth forceps.

SELF-EXPANDABLE METALLIC STENTS Overview of techniques for metallic stent removal Unlike plastic stents, the techniques used for removal of SEMS involve direct grasping of the stent. For removal of uncovered SEMS embedded into the mucosa, initial fragmentation of the individual wires in order to cause the stent to collapse may be required. Covered stents may be removed by grasping the stent with a snare.

Specific techniques Fig. 18.25 The pancreatic stent was then removed by the snare while the guidewire remained in place.

For an uncovered SEMS which is embedded in the bile duct mucosa, snare removal will be impossible. An option then would be the initial extraction of individual wire filaments from the distal end of the

A

B

Duodenoscope

Snare over stent and guidewire underneath

A lasso is formed as the snare grasps the guidewire, and is used to winch the tip of the stent from the duodenal wall

Fig. 18.26 The “lasso” technique for removing a distally migrated stent that had impacted against the contralateral duodenal wall. A A snare was inserted over the stent while a guidewire was inserted below the stent. B The guidewire was then captured by the snare, creating a “lasso” over the distal end of the stent which was then winched into close proximity with the endoscope, thus freeing the impacted distal end. 185

SECTION 2 TECHNIQUES

SEMS using a “hot” biopsy forceps so that the stent architecture is destroyed, thus allowing the stent to collapse. Once the stent has collapsed, it may then be possible to extract it using a snare. It may be necessary to coagulate the lumen within the stent first before stent extraction in order to reduce the risk of bleeding. If a SEMS has migrated distally and impacted upon the opposite duodenal wall, it may be necessary to attempt cutting the stent with argon plasma coagulation first before extraction with a snare. In one series SEMS removal was successful in 17 out of 18 patients. Among these successfully removed SEMS, 13 were covered and 4 uncovered stents.4 In a larger series, endoscopic removal of 39 SEMS (13 uncovered and 26 covered) was attempted. It was successful in 29 SEMS (74.3%). Covered SEMS were effectively removed more frequently than uncovered ones: 24 of 26 (92.3%) and 5 of 13 (38.4%), respectively (p < 0.05). No major complications were recorded. The presence of a stent covering was the only factor predictive of successful stent extraction. The presence of diffuse and severe ingrowth was the main feature limiting SEMS removal.26 For removal of covered SEMS in which the distal end is lying free in the duodenum beyond the papilla, the distal end is grasped with a polypectomy snare as far proximally as possible based upon the amount of stent remaining within the duodenum. The snare is then closed, such that the distal end of the SEMS becomes compressed, whereupon the SEMS elongates and collapses over a short distance from the point of compression. Either the entire stent can be withdrawn, or the stent can be withdrawn through the accessory channel of the endoscope without injury to the patient or damage to the instrument. In rare situations SEMS can migrate proximally above the stricture and may be “free floating.” Stent retrieval may be possible with either a basket27 or a rat-tooth forceps.28 An interesting method of removal of distally migrated covered Wallstent which had impacted on the contralateral duodenal wall had been reported. A closed biopsy forceps (FB-21K-1, Olympus Optical Co. Ltd, Tokyo, Japan) was advanced through the stent mesh and opened within the stent to form an anchor. The endoscope was then withdrawn together with the opened forceps. During endoscope withdrawal, the stent folded upon itself in the mid-body and was easily transported from the duodenum to the stomach. Once inside the stomach one end of the stent was caught with a snare and the stent was removed by complete withdrawal of the endoscope.29

COMPLICATIONS AND THEIR MANAGEMENT BOX 18.3 COMPLICATIONS AND CONTROVERSIES Complications: • General complications related to endoscopy and ERCP • Duct injury with bleeding or perforation during retrieval of proximally migrated stents • Injury to the cardia and distal esophagus when the unprotected stent is pulled out simultaneously with the endoscope

186

Failure of stent extraction: Options include insertion of another stent to maintain duct drainage, surgical removal of the stent and observation in the context of an asymptomatic patient. Controversies: The placement of a SEMS is generally regarded as permanent. This is due to the metallic mesh being deeply embedded in the biliary wall. Attempted removal may be technically impossible, or may result in bleeding and perforation. Reports of successful endoscopic removal of SEMS have been published, especially of the covered type. Hence the presence of SEMS should no longer be viewed as an absolute contraindication for stent removal.

General complications The usual complications of sedation, cardiopulmonary events, perforation and pancreatitis may occur. Proper patient selection prior to performing the procedure and close clinical monitoring during the procedure are important in reducing the risk of complications.

Complications related specifically to stent removal Although guided by fluoroscopy, the retrieval of a proximally migrated plastic stent is essentially a blind procedure. When accessories such as forceps are used, there is a possibility of accidentally grasping the ductal epithelium instead of the stent which may cause ductal injuries such as bleeding and perforation. In addition, if the stent is grasped at its proximal end instead of its distal end, it may kink and rotate during withdrawal and potentially cause ductal injury. Thus it is important to capture the distal end of the stent before applying traction. In the very rare event of bile duct perforation during stent removal, the insertion of a new biliary stent may allow the perforation to close. One must be careful if the stent and endoscope are withdrawn together because the distal end of the stent may tear the cardia or esophageal wall. The elevator of the working channel must be completely opened. In addition, when using a stone retrieval basket or snare, allowing a sufficient length between the captured end of the stent and the distal tip of the duodenoscope will allow a more flexible and smooth retrieval, as the axis of the snare may be aligned with that of the esophageal lumen. The removal of an uncovered SEMS, if it is possible, is associated with an increased risk of bleeding and perforation. Therefore in patients with uncovered SEMS one should seriously consider whether removal is absolutely necessary. Options to manage the stent include placement of another stent, be it a plastic stent or a SEMS, through the occluded stent. In the event that endoscopic stent removal is not possible, management options include surgical removal, insertion of another stent (if continued duct drainage is required), or observation if the patient remains asymptomatic. Surgical removal should be considered in healthy patients with proximally migrated pancreatic duct stents to minimize the possibility of irreversible ductal injury.

Chapter 18 Stent Removal: Migrated and Non-Migrated

RELATIVE COSTS AND CHOICE OF TECHNIQUE There are no studies that have compared one technique of stent removal to another. In addition, there are no cost-effectiveness studies. It is unlikely that such studies will be done. All of the accessories mentioned in this chapter are likely already available and their use for stent removal should not lead to increased costs. The choice

of a particular technique depends on the specific circumstances requiring stent removal. In patients in whom the goal is to remove and not replace a plastic stent, one should simply grasp the stent with a polypectomy snare, rat-tooth forceps, or stone retrieval basket. If the intent is to replace a stent it is advisable to initially cannulate the stent with a guidewire and remove the stent while maintaining duct access by leaving the guidewire in place.

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Soehendra N, Binmoeller KF, Seifert H, et al. Therapeutic endoscopy: color atlas of operative techniques for the gastrointestinal tract. 2nd edn. Stuttgart: Georg Thieme Verlag; 2005:30–155. Arguedas MR, Heudebert GH, Stinnett AA, et al. Biliary stents in malignant obstructive jaundice due to pancreatic carcinoma: a cost-effectiveness analysis. Am J Gastroenterol 2002; 97:898–904. Dumonceau JM, Deviere J, Delhaye M, et al. Plastic and metal stents for postoperative benign bile duct strictures: the best and the worst. Gastrointest Endosc 1998; 47:8–17. Kahaleh M, Tokar J, Le T, et al. Removal of self-expandable metallic Wallstents. Gastrointest Endosc 2004; 60:640–644. Johanson JF, Schmalz MJ, Geenen JE. Incidence and risk factors for biliary and pancreatic stent migration. Gastrointest Endosc 1992; 38:341–346. Shah JN, Ahmad NA, Shetty K, et al. Endoscopic management of biliary complications after adult living donor liver. transplantation. Am J Gastroenterol. 2004; 99:1291–1295. Draganov P, Hoffman B, Marsh W, et al. Long-term outcome in patients with benign biliary strictures treated endoscopically with multiple stents. Gastrointest Endosc. 2002; 55:680–686. Costamagna G, Mutignani M, Ingrosso M, et al. Endoscopic treatment of postsurgical external pancreatic fistulas. Endoscopy. 2001; 33:317–322. Sherman S, Shaked A, Cryer HM, et al. Endoscopic management of biliary fistulas complicating liver transplantation and other hepatobiliary operations. Ann Surg. 1993; 218:167–175. Seewald S, Groth S, Sriram PV, et al. Endoscopic treatment of biliary leakage with N-butyl-2 cyanoacrylate. Gastrointest Endosc. 2002; 56:916–919. Seewald S, Brand B, Groth S, et al. Endoscopic sealing of pancreatic fistula by using N-butyl-2-cyanoacrylate. Gastrointest Endosc. 2004; 59:463–470. Tarnasky PR, Cotton PB, Baillie J; et al. Proximal migration of biliary stents: attempted endoscopic retrieval in forty-one patients. Gastrointest Endosc 1995; 42:513–519. Lahoti S, Catalano MF, Geenen JE, et al. Endoscopic retrieval of proximally mgrated biliary and pancreatic stents: experience of a large referral center. Gastrointest Endosc 1998; 47:486–491. Chaurasia OP, Rauws EAJ, Fockens P, et al. Endoscopic techniques for retrieval of proximally migrated biliary stents: the Amsterdam experience. Gastrointest Endosc 1999; 50:780–785. Baron TH, Dean LS, Morgan DE, et al. Proximal migration of a pancreatic duct stent: endoscopic retrieval using interventional cardiology accessories. Gastrointest Endosc 1999; 50:124–125.

16. Mergener K, Baillie J. Retrieval of distally migrated, impacted biliary endoprostheses using a novel guidewire/basket “lasso” technique. Gastrointest Endosc 1999; 50:93–95. 17. Sharara AI, Leung JW. Endoscopic extraction of proximally migrated biliary endoprostheses using a grasping rat-tooth forceps. Gastrointest Endosc 1995; 41:619–620. 18. Horwhat JD, Jowell P, Branch S, et al. Proximal migration of a 3 French pancreatic stent in a patient with pancreas divisum: suggested technique for successful retrieval. JOP. J Pancreas (Online) 2005; 6:178–184. 19. Soehendra N, Maydeo NA, Eckmann B, et al. A new technique for replacing obstructed biliary endoprostheses. Endoscopy 1990; 22:271–272. 20. Martin DF. Wire-guided balloon assisted endoscopic biliary stent exchange. Gut 1991; 32:1562–1564. 21. Sherman S, Hawes RH, Uzer MF, et al. Endoscopic stent exchange using a guidewire and snare. Gastrointest Endosc 1993; 39:794–799. 22. Bohorfoush AG, Ballinger PJ, Hogan WJ. A new method for exchange of endoprostheses in the biliary and pancreatic ducts. Gastrointest Endosc 1993; 39:799–802. 23. Smith FC, O’Connor HJ, Downing R. An endoscopic technique for stent recovery used after duodenal perforation by a biliary stent. Endoscopy 1991; 23:244–245. 24. Vandervoort J, Carr-Locke DL, Tham TCK, et al. A new technique to retrieve an intrabiliary stent: a case report. Gastrointest Endosc 1999; 49:800–802. 25. Mulcahy HE, Cunningham JT. A guidewire-assisted technique for removing retained biliary stents with rat-toothed forceps during endoscopic retrograde cholangiography. Gastrointest Endosc 2001; 53:386–387. 26. Familiari P, Bulajic M, Mutignani M, et al. Endoscopic removal of malfunctioning biliary self-expandable metallic stents. Gastrointest Endosc. 2005 Dec; 62(6):903–910. 27. Mo LR, Tsai CC, Yueh SK, et al. Endoscopic retrieval of a selfexpanding stainless steel stent from the common bile duct. Endoscopy 1994; 26:562–563. 28. Baron TH, Blackard WG, Morgan DE. Endoscopic removal of a “floating” biliary Gianturco Z stent five years after placement for a benign anastomotic stricture in a liver transplant patient. Gastrointest Endosc 1997; 46:80–82. 29. Matsushita M, Takakuwa H, Nishio A, et al. Open biopsy forceps technique for endoscopic removal of distally migrated and impacted biliary metallic stents. Gastrointest Endosc 2003; 58:924–927.

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Chapter

19

TECHNIQUES

Papillectomy/Ampullectomy Ann M. Chen and Kenneth F. Binmoeller

INTRODUCTION

• Using a duodenoscope, endoscopic ampullectomy is performed in a similar manner to snare polypectomy.

Ampullary tumors Tumors of the ampulla of Vater include adenocarcinomas, lymphomas, neuroendocrine tumors, lipomas, fibromas, leiomyomas, and hamartomas, but adenomas are the most common. Ampullary adenomas are premalignant neoplasms and occur sporadically in about 0.04 to 0.12% of the general population based on autopsy series.1,2 The incidence is increased among patients with hereditary polyposis syndromes, such as familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC). In patients with FAP, 40–100% will develop duodenal adenomas and the relative risk of papillary cancer is over 100 times that of the general population.3

Surgical treatments Surgical treatment of ampullary tumors includes transduodenal local resection (LR) and pancreaticoduodenectomy (PD). For PD, the possible benefit of a low recurrence rate is weighed against a high risk of complications. Surgical-related morbidity of PD can be as high as 50–63% and mortality ranging from 0–9% with the higher rates reported in patients with malignant disease.4–7 Although LR is generally associated with lower morbidity (14–27%)4–6 and mortality rates (0–4%),5–7 recurrence rates can be as high as 17–32%4–8 and thus endoscopic surveillance after surgery is still required.

Endoscopic ampullectomy/papillectomy

Endoscopic ampullectomy was described in 1983 by Suzuki et al.9 and the first large case series was reported in 1993 by Binmoeller et al.10 Over the last decade, many more studies have been published showing high success rates with low morbidity and mortality risks. Endoscopic therapy is therefore gaining increasing acceptance for the treatment of ampullary tumors.

TECHNIQUE

BOX 19.1 SUMMARY OF THE TECHNIQUE • Staging of ampullary tumors and definition of the biliary and pancreatic ductal anatomy are achieved with high accuracy by endoscopic ultrasound. • Endoscopic retrograde cholangiopancreatography prior to ampullectomy is indicated if there is suspicion of intraductal involvement.

• Thermal ablation may be used as adjunctive therapy. • Although not definitive, current data supports prophylactic biliary sphincterotomy and pancreatic stent placement to prevent ductal stenosis, cholangitis, and pancreatitis. • Local tumor recurrences do occur and therefore follow-up surveillance duodenoscopy is essential.

Endoscopic evaluations

1. Conventional endoscopy Evaluation of the ampulla of Vater requires a high degree of suspicion and is best performed with a duodenoscope. Large periampullary diverticula can hinder endoscopic exam (Fig. 19.1). Tumors of the major ampulla can vary in appearance from slight enlargement to granular or polypoid, with or without ulceration (Fig. 19.2). Unfortunately, the presence or absence of malignant transformation cannot be determined by appearance alone and endoscopic biopsies are notorious for missing carcinomatous foci harbored within papillary adenomas.5,11,12 Rattner et al.6 found a sensitivity of only 42% for detection of malignancy by endoscopic biopsies and a specificity of 79% with a poor positive predictive value of 50% and negative predictive value of 73%. Therefore a negative biopsy does not rule out presence of cancer and a minimum of six biopsies to increase histologic yield has been recommended.10,13 It is important to be aware that frequency of malignant foci in an adenoma of the papilla figures around 26–30%.4,14

2. Endoscopic ultrasound Endoscopic ultrasound (EUS) should be performed whenever possible. It is useful in assessing tumor size, depth of invasion relative to the duodenal wall layers, and involvement of the pancreatic or biliary ducts (Fig. 19.3). The radial scanning echoendoscope has been shown to be valuable for identifying patients with disease localized to the muscularis propria in whom endoscopic resection may be appropriate for cure. In one study,6 EUS correctly staged preoperatively 9 of 12 ampullary lesions (3 of 5 villous adenomas, 3 of 3 adenocarcinomas, 1 carcinoid, and 2 of 2 adenocarcinomas arising in a villous adenoma). Size of the lesion did not correlate with the presence of malignancy. Cannon et al.15 reported similar N-stage accuracy by EUS (68%) compared to CT (59%) and MRI (77%) but superior T-stage accuracy (78% for EUS vs 24% and 46% for CT and MRI, respectively). Prior sphincterotomy and the presence of a 189

SECTION 2 TECHNIQUES

transpapillary endobiliary stent, however, can decrease EUS T-stage accuracy. One group16 found intraductal ultrasound to be even better than conventional EUS for T-staging (87% vs 63%) but more studies are needed to confirm these results.

3. Endoscopic retrograde cholangiopancreatography Endoscopic retrograde cholangiopancreatography (ERCP) is helpful in detecting intraductal tumor extension not visualized by computed tomography (CT) scan (Fig. 19.4). Opacification of both the pancreatic and common bile duct should be attempted and surgical referral should be considered if evidence of ductal involvement is found. In addition, pancreatography can define the presence of pancreas divisum and obviate the need for pancreatic stent placement. While EUS is generally performed before resection to increase staging accuracy, ERCP is performed at the time of ampullectomy to exclude intraductal tumor involvement, to perform sphincterotomy, and to place a pancreatic duct stent. If EUS is not available or the findings are equivocal, then ERCP should be performed before ampullectomy to assess for intraductal extension.

Endoscopic ampullectomy There is currently no consensus as to how endoscopic ampullectomy should be performed. Randomized trials are lacking. In general, ampullectomy is accomplished in a manner similar to snare polypectomy using a standard duodenoscope (JF-140, TJF-140; Olympus America, Inc., Leigh Valley, PA). The application of adjuvant thermal therapy, sphincterotomy, and prophylactic stent placement is variable (Table 19.1) and will be discussed further later in this section.

A

B

C A

D

B

Fig. 19.1 Ampullary mass obscured by periampullary diverticulum. Ampullary adenoma hidden in a diverticulum A can be appreciated after eversion of the surrounding mucosa B.

A

B

Fig. 19.2 Endoscopic appearances of tumors of the ampulla of Vater. A Villous adenoma with granular surface. B Bilobed tubular adenoma in a patient with FAP. C T1 submucosal carcinoid tumor seen as a prominent polypoid mass. D Well-differntiated ampullary adenocarcinoma with bleeding and superficial ulcerations. FAP, Familial adenomatous polyposis.

C

Fig. 19.3 EUS examination of ampullary tumors. A Large ampullary mass with tumor extension into a dilated common bile duct. B Hyperechoic stage T2 ampullary mass (black arrow) is seen invading into the wall of the duodenum with extension (white arrow) into the muscularis mucosa (black arrowheads denote intact muscularis). C Large ampullary adenoma. As compared to b, the muscularis is intact (arrowheads). 190

Chapter 19 Papillectomy/Ampullectomy

Although no data exist on prophylactic antibiotics for endoscopic ampullectomy, the procedure is similar to other submucosal resections and we routinely give antibiotics prior to and for three days after the procedure.

1. Snare excision Various types of standard monopolar diathermic polypectomy snares have been used. We prefer a more rigid snare such as the 20 mm oval snare with spiral wires (SnareMaster, Olympus America Inc., Lehigh Valley, PA). In our experience, a stiffer wire can be more easily positioned parallel to the plane of dissection and perpendicular to the catheter for a uniform excision to the level of the muscularis propria (Fig. 19.5). Blended cut is more commonly used than pure cut current to decrease the risks of bleeding. No studies have shown a decreased incidence of tumor recurrence when en bloc (Fig. 19.6) rather than piecemeal endoscopic

A1

ampullectomy is performed. However, as a general rule of oncologic surgery, en bloc resection is preferred because of higher likelihood of complete tumor excision and improved histologic analysis of the resected margins. The downside of en bloc resection is that it can be technically more difficult to perform and may incur higher risks of bleeding and perforation, especially when lesions are large or extremely sessile. Piecemeal excision is therefore sometimes necessary, although complete tumor removal may require several sessions. Vital dye staining with indigocarmine or methylene blue may help to delineate the tumor margins prior to resection (Fig. 19.7).

Common bile duct

Pancreatic duct

A2

Ampulla of Vater

B

Major duodenal papilla

Fig. 19.5 Snare ampullectomy. Schematic drawing showing the ideal plane of dissection during snare ampullectomy.

A

Fig. 19.4 ERCP examination of ampullary tumors. A1 Routine endoscopic visualization of the ampulla after prior sphincterotomy did not reveal obvious residual adenomatous tissue but balloon sweep of the bile duct during ERCP A2 showed intraductal adenomatous growth. B Intraductal filling defect after contrast injection of the common bile duct seen here is consistent with ampullary ductal tumor extension. ERCP, endoscopic retrograde cholangiopancreatography.

Author, y (reference no.)

N

Binmoeller, 1993 (10) Desilets, 2001 (27) Zadorova, 2001 (29) Norton, 2002 (26) Catalano, 2004 (22) Cheng, 2004 (30)

25 13 16 26 103 55

B

Fig. 19.6 En bloc ampullectomy. A Ampullary adenoma ensnared in entirety with gentle pressure on the catheter before snare closure. B Appearance of same lesion after resection.

FAP

Sphincterotomya (biliary, pancreatic)

Thermal therapy, (APC/E/YAG)

Pancreatic stent, size (Fr)

Biliary stent, size (Fr)

NA 7 (54%) 1 (6%) 15 (58%) 31 (30%) 14 (25%)

9 (36%), 0 13 (100%), 13 (100%) 16 (100%), 8 (50%) 26 (100%), 2 (8%) NA 2 (4%), 0

NA 7 (54%), (5/2/0) 3 (19%), (3/0/0) 12 (46%), (2/10/0) 35 (34%), (18/14/3) NA

1 (4%), 7 11 (85%), 5 6 (38%), 7 10 (38%), 5 91 (88%), 5–7 41 (75%), 3–5

0 3 (23%), NA 3 (19%), 10 NA 34 (33%), 7-10 NA

Table 19.1 Techniques of endoscopic ampullectomy in published series

FAP, Familial adenomatous polyposis; NA, not available; APC, argon plasma coagulation; E, electrocautery; YAG, YAG laser. a Pre- or post-ampullectomy.

191

SECTION 2 TECHNIQUES

A1

A2

B1

B2

Fig. 19.7 Vital dye staining. A1 Ampullary adenoma with indistinct borders. A2 Same lesion with well-defined borders after methylene blue staining. B1 A small recurrent adenoma after prior ampullectomy is better visualized with B2 Indigocarmine staining.

The role of submucosal injection with saline or dilute epinephrine prior to ampullectomy remains unclear. Extrapolating from the practice of submucosal injection prior to mucosectomy, there is the theoretical benefit of a reduction in risk of perforation and bleeding. The inability to obtain a cleavage plane with saline injection may be useful in predicting the presence of malignancy in ampullary neoplasia.17 However, ampullary tumors differ from mucosal neoplasms in that the bile and pancreatic ducts are embedded in the tissue. A submucosal injection will fail to raise the tissue at the site of ductal insertion. Furthermore, submucosal injections may increase the risk of procedure-induced pancreatitis. We concur with the findings of Harewood et al.18 that submucosal lifts deter complete resection of ampullary adenomas down to the sphincteric musculature and hinder subsequent access to both pancreatic and biliary ducts. In our practice we do not perform submucosal injection prior to ampullectomy. Recently novel techniques to facilitate endoscopic ampullectomy have been proposed. Aiura et al.19 reported successful en bloc resection of ampullary tumors less than 2 cm in size with the use of an intraductal balloon-catheter for traction. Another group in Korea20 inserted a guidewire into the pancreatic duct preampullectomy to maintain ductal access for stent placement immediately after snare resection. More study is needed to confirm feasibility and safety of these inventive methods. The retrieval of all resected specimens for surgical pathology is essential for detection of small malignant foci. Specimens should be retrieved immediately after resection with a snare, basket, or net (Fig. 19.8). Glucagon administered just before resection may be helpful in preventing loss of tissue downstream due to small bowel peristalsis. While some authors suggest pinning the specimen on polystyrene plates for orientation, our pathologists have not found this to be necessary. 192

Fig. 19.8 Retrieval of specimen with a net after en bloc ampullary resection.

2. Thermal ablation Although thermal ablation was initially used as primary therapy with acceptable success,21 it is now more commonly applied as adjunctive treatment. When used alone, thermal ablation precludes complete histopathologic evaluation and may risk incomplete treatment. Catalano et al.22 reported similar overall success rates among patients who had adjunctive ablation compared with those who did not (81%, 30 of 37 vs 78%, 52 of 66, respectively). However adjunctive thermal ablation has not been addressed consistently in most studies, so its absolute benefit is inconclusive. Thermal modalities to achieve ablation include the Nd:YAG laser,23–25 bipolar and monopolar coagulation,23,25–27 photodynamic therapy,24 and argon plasma coagulation.25–29 We use argon plasma coagulation only when visible residual adenomatous tissue remains after snare excision. Treatment can also be palliative for patients with non-operable neoplasms. We apply a 7 Fr argon plasma probe at a power of 60W and flow rate of 1.2–1.8 L/ml for ablation. For intraductal lesions, a multipolar probe is used at a power of 25–30W. If placement of pancreatic and biliary stents is to be performed, both should be placed before thermal ablation to potentially decrease complications of stenosis by protecting the exposed pancreatic and biliary epithelia (Fig. 19.9).

3. Preresection sphincterotomy There are no data to support any beneficial effect of sphincterotomy, either biliary or pancreatic, prior to ampullectomy. It has been argued that biliary sphincterotomy may allow a more complete excision of the ampulla by facilitating access to tissues in the biliary orifice and thereby increase diagnostic accuracy.24,27 It has also been proposed that biliary and pancreatitic sphincterotomy may decrease the risks of cholangitis and pancreatitis, respectively. Arguments

Chapter 19 Papillectomy/Ampullectomy

A

B

Fig. 19.9 Adjuvant thermal therapy. A Pancreatic and biliary stents placed after endoscopic ampullectomy and before thermal ablation B with APC. APC, argon plasma coagulation.

against preresection sphincterotomy include increased risks of bleeding, perforation, and tumor seeding. The resultant thermal injury from sphincterotomy may impede accurate histopathologic interpretation of the resected specimen. Moreover, if a biliary or pancreatic stent is placed routinely after preresection sphincterotomy, ensuing ampullectomy will likely be in piecemeal fashion rather than en bloc.

4. Postampullectomy sphincterotomy and stent placement After ampullectomy, separate orifices for the biliary and pancreatic ducts can usually be readily identified. Mixing contrast with methylene blue during pancreatography prior to ampullary resection or administering secretin after resection may facilitate the identification of the ductal orifice in cases where localization is difficult. Cholangiopancreatography is performed to define the ductal anatomy as described perviously. The role of prophylactic sphincterotomy to minimize complications such as pancreatitis, cholangitis, and papillary stenosis remains controversial. Sphincterotomy will expose the opening to the distal duct and may thereby allow the detection of intraductal involvement. This benefit will need to be weighed against the risks of bleeding and perforation. Our protocol is to perform a biliary sphincterotomy in all patients, and pancreatic sphincterotomy in patients with any suspicion for pancreatic duct involvement. Pancreatic stent placement after ampullectomy may be performed to minimize the risk of post-ERCP pancreatitis but supportive data is not definitive. A retrospective study by Norton et al.26 found pancreatitis developed in 2 of 10 (20%) patients with pancreatic duct stent placement and 2 of 18 (11%) patients without a stent, but this difference was not statistically significant (p = 0.5). In a larger study using 5–7 Fr pancreatic stents, Catalano et al.22 also found that both acute pancreatitis and papillary stenosis occurred more frequently in patients without stents (17% vs 3% for pancreatitis and 8% vs 3% for stenosis). However, the overall number of patients with pancreatitis (5 of 103) and papillary stenosis (3 of 103) was small and no randomization was done, making interpretation of the results difficult. Similarly, Cheng et al.30 reported 4 of 41 patients (10%) with 3–5 Fr pancreatic stents placed prophylactically developed pancreatitis compared to 1 of 4 (25%) patients without stents. This was again

Fig. 19.10 Prophylactic 5 Fr pancreatic stent placement and biliary sphincterotomy after endoscopic ampullectomy.

not statistically significant (p = 0.33). Furthermore, the only two patients in this study who developed biliary and pancreatic stenosis were among those who had undergone both prophylactic biliary sphincterotomy and pancreatic stent insertions. The only prospective, randomized controlled trial of prophylactic pancreatic stent placement after endoscopic ampullectomy was reported by Harewood et al.18 All patients underwent biliary sphincterotomy, and pancreatic stents were inserted immediately after ampullectomy without pancreatic sphincterotomy. Results showed that single-flanged, 3 or 5 cm long, 5 Fr stents reduced pancreatitis (3 of 19 patients in the unstented group vs 0 of 10 patients in the stented group, p = 0.02). The study was terminated early in response to institutional review board concerns about the risk of pancreatitis in the unstented group. It is important to note that the number of patients enrolled was smaller than the intended 25 patients in each arm for a power of 80% to detect a 25% difference in rates of pancreatitis, hence a single episode of pancreatitis in the stented group would have resulted in a nonsignificant p value.31 Also of interest is that pancreatic stents were endoscopically removed after 24 hours which is much sooner than the general practice of allowing spontaneous stent migration over 1 to 2 weeks and further raises questions regarding the role of stents in these patients. Further larger scale prospective studies are needed to prove prophylactic pancreatic stenting decreases complications of endoscopic ampullectomy, nonetheless current data from difficult or invasive ERCP does support empiric stent placement. In our earlier practice,10 pancreatic stents were inserted only if delayed drainage was noted. We have subsequently changed to routine stenting after observing a high rate of postampullectomy pancreatitis in patients without stenting. Typically a 5 cm long, 5–7 Fr polyethylene stent without an intraductal flange is used (Fig. 19.10). An abdominal x-ray is obtained 1–2 weeks 193

SECTION 2 TECHNIQUES

later to confirm spontaneous stent migration. A stent that remains in situ is removed endoscopically without need for ductography. In contrast to pancreatitis, cholangitis after endoscopic ampullectomy is a rare occurrence and therefore biliary stenting is not routinely performed. One exception is in the event that thermal therapy is required, biliary stent placement should be considered to ensure adequate drainage and to minimize the risk of stenosis of the biliary orifice. We also place a 10 Fr biliary stent if there is evidence of poor bile duct drainage despite biliary sphincterotomy.

• Contraindications to ampullectomy include lesions with advanced intraductal involvement or local metastasis. Patients unwilling to undergo postresection surveillance should also be advised against the procedure. • With improvements in technique and increasing experience, indications for endoscopic ampullectomy will likely expand and continue to be modified.

Postampullectomy surveillance Surveillance duodenoscopy applies predominately to adenomatous tumors, but the same principle can be used to monitor for the recurrence of rare non-adenomatous lesions. Duodenoscopy should be performed with multiple biopsies from the site of the resected ampulla, even in the absence of macroscopic recurrence. There are no standard guidelines regarding appropriate intervals for postampullectomy surveillance. Generally, small (<3 cm) sporadic benign adenomas with clean resection margins are re-evaluated at 3 months initially, then at 6 to 12 months intervals for at least 2 years if eradication is confirmed.10,27,30 Some authors recommend extending initial examinations to 6 months intervals for at least 2 years and then only when clinically indicated if two consecutive biopsies have shown no residual adenomatous tissue.22 In patients with FAP who require routine surveillance for duodenal polyps, duodenoscopy should be performed indefinitely every year after initial negative biopsies at 6 and 12 months.22,28 For large (>3 cm) sporadic adenomas excised in a piecemeal fashion and for lesions with involved resected margins, repeat ampullectomy with possible thermal ablation as well as ERCP should be performed at 2 to 3 month intervals until ablation is complete.10,22 Subsequently, follow-up duodenoscopy with biopsies and ERCP should be performed every 6 months for a minimum of 2 years. Surgery should be considered if intraductal tumor extension is suspected or if invasive carcinoma is found on biopsies.

Appropriate therapeutic strategy for ampullary tumors is determined by the patient’s general health, tumor characteristics, and experience of the endoscopist. In general, patients with benign ampullary tumors are candidates for endoscopic mucosectomy. Exclusion criteria10,27,30 for endoscopic resection include: 1. histologic documentation of coexistent carcinoma; 2. suspected intraductal tumor extension on EUS or ERCP; 3. tumor size >4 cm; 4. endoscopic findings suspicious for malignancy (i.e. indurated mass, presence of ulceration, excessive friability, or spontaneous bleeding); 5. poor patient compliance with follow-up; 6. absence of endoscopic expertise. It is important to note that the above list of exclusion criteria is not absolute and may be modified as more studies are published. Ampullary adenomas up to 7 cm in diameter29 and lesions with intraductal growth32 have been successfully managed by snare resection. Cases of early T1 ampullary adenocarcinoma have also been treated endoscopically.33 Patients who are poor candidates for surgery or who refuse surgery may also be considered for endoscopic resection and/ or ablation despite unfavorable tumor characteristics.

COMPLICATIONS

INDICATIONS AND CONTRAINDICATIONS BOX 19.3 COMPLICATIONS BOX 19.2 INDICATIONS AND CONTRAINDICATIONS • In general, endoscopic resection is indicated in patients who have benign ampullary lesions less than 4 cm in size without evidence of intraductal involvement. These criteria may be changing, however, as successful resection of larger lesions and lesions with early intraductal invasion and/or malignant transformation is increasingly reported in recent literature.

194

• Complications occur in between 8% and 35% of reported cases but are usually mild and managed endoscopically. These include acute pancreatitis, cholangitis, bleeding, papillary stenosis, and perforation. • Death as a result of endoscopic ampullectomy is very rare.

BOX 19.4 CONTROVERSIES

• Endoscopic therapy may be considered in patients with ampullary malignancies who refuse surgery or are not surgical candidates.

• Controversy exists regarding adequate endoscopic treatment of a lesion with potential for malignant transformation and possible undetected neoplastic foci.

• Endoscopic ampullectomy should be performed by appropriately trained and experienced endoscopists because of potential serious complications.

• Currently, there is no randomized, controlled, prospective study comparing surgery with endoscopic resection for ampullary tumors.

Chapter 19 Papillectomy/Ampullectomy

• The rates of submucosal injection prior to ampullectomy, thermal ablation of resection margins post-ampullectomy, sphincterotomy, and prophylactic stent placement remain debatable.

bringing the elevator down again when deploying or closing the hemoclip (again blindly).

• Optimal strategy for postampullectomy surveillance is also unknown.

Complete tumor eradication is achieved in greater than 85% of endoscopic ampullectomies for benign adenomas, although several treatment sessions may be necessary (Fig. 19.11 and Table 19.3). Recurrences, however, do occur and average around 20% in reported case series. Recurrent lesions are usually benign and most can be retreated endoscopically. Outcome is influenced by tumor histology, size, and genetic disposition. In a retrospective case series, Catalano et al.22 reported higher overall success rates for endoscopic treatment of sporadic lesions compared to genetically determined lesions (86%, 63 of 72 vs 67%, 20 of 31). Age greater than 48 years, lesion size of 24 mm or less, and male gender were also associated with higher rates of successful resection. The presence of intraductal

SUCCESS

Overall complications of endoscopic ampullectomy range between 8 and 35%. Most commonly, mild cases of acute pancreatitis (5–15%) and bleeding (0–16%) are reported (Table 19.2). Perforations26,30 and orifice stenosis26,30 are much less common, and death17,25,34 from ampullary resection is rare. Patients with FAP and those with severe dysplasia or adenocarcinoma may have higher complication rates. In a prospective study35 of 25 patients with FAP and routine pancreatic stenting after ampullectomy, 14% developed pancreatitis. However, all of these patients had adjunctive thermal ablation and some patients had intraductal ablation of adenomatous tissue so that meaningful conclusions can not be made from this data. In most case series, complications were managed without surgical intervention. Pancreatic and biliary stenosis resulting from endoscopic ampullary resections can be treated with sphincterotomy,26 stents,22 and/or balloon dilation.30 Acute pancreatitis usually resolves with conservative therapy while postampullectomy bleeding can be controlled with endoscopic epinephrine injection, electrocautery, or hemoclips and rarely requires blood transfusions or embolizations. Norton et al.26 described one patient with duodenal perforation who was treated endoscopically with a hemoclip. Applying clips through a duodenoscope is technically challenging owing to the angulation at the end of the working channel. The key points to remember are to keep the elevator down when opening the clip (thus opening the clip blindly), lifting the elevator to bring the opened clip into view for proper positioning at the target site, then

Author, y (reference no.)

N

Pancreatitisa

Binmoeller, 1993 (10)

25

Desilets, 2001 (27)

A

B

Fig. 19.11 Eradication with endoscopic ampullectomy. A Large 3.5 cm benign extraductal adenoma. B Same lesion after 4 endoscopic resections. Multiple biopsies of the ampulla resection site revealed benign duodenal tissue. Scarring from previous excisions can be seen near the orifice.

Bleeding; management (n)

Perforation; management (n)

Papillary stenosis; management (n)

3 (12%)

2 (8%); epinephrine injection

0

0

5 (20%)

0%

13

1 (18%)

0

0

0

1 (8%)

0%

Zadorova, 2001 (29)

16

2 (13%)

2 (13%); epinephrine 0 injection

0

4 (25%)

0%

Norton, 2002 (26)

26

4 (15%)

2 (8%); epinephrine injection

1 (4%); hemoclip

2 (8%) sphincterotomy

9 (35%)

0%

Catalano, 2004 (22)

103 5 (5%)

2 (2%) electrocautery (1) and hemoclip (1)

0

3 (3%) sphincterotomy and stent (2), surgery (1)

10 (10%)

0%

Cheng, 2004 (30)

55

9 (16%); nonspecified endoscopic (6) transfusion only (3)

1 (2%); conservative

2 (4%); sphincterotomy and dilation

17 (31%)

0%

5 (9%)

Overall morbidity

mortality

Table 19.2 Complications of endoscopic ampullectomy in published series a

All cases of pancreatitis were mild to moderate and managed.

195

SECTION 2 TECHNIQUES

N

FAP

Mean Mean follow-up procedures Malignant (mos) per patient foci

Binmoeller, 1993 (10)

25

NA

37

1.1

0

2

NA

6/23a (26%)

4/6 (67%)

benign adenomas, 1 with intraductal growth

Desilets, 2001 (27)

13

7 (54%) 19

2.7

0

1

12/13 (92%)

0/12a (0%)

—

—

Zadorova, 2001 (29)

16

1 (6%)

1.4

0

0

16/16 (100%)

3/16 (19%)

2/3 (67%)

benign adenomas, 1 with intraductal growth

Norton, 2002 (26)

26

1.1

1

0

NA

2/20b (10%)

2/2 (100%)

extraductal benign adenomas

Catalano, 2004 (22)

103 31 (30%) 36

1.8

6

0

93/103c (90%)

21/103c (20%)

11/21 (52%)

NA

Cheng, 2004 (30)

55

1.3

7

6

37/39d (95%)

9/27d (33%)

7/7 (100%)

extraductal benign adenomas

Author, y (reference no.)

NA

15 (58%) 9

13 (33%) 30

Intraductal growth

Complete eradication

Recurrences managed by Recurrences endoscopy

Recurrence type

Table 19.3 Outcome of endoscopic ampullectomy in published series

FAP, Familial adenomatous polyposis; NA, not available. a Excludes lesions with ductal (all sent to surg). b Excludes lesion with malignant foci and 5 missing follow-up data. c Includes lesions with malignant foci (n = 6). d Excludes ductal extension, malig foci, and nl histology (n = 3). Recurrence rate also excludes 12 missing follow-up data.

tumor extension also affects outcome. In a prospective study of benign tumors excised endoscopically, Bohnacker et al.32 found comparable recurrence rates between patients with and without intraductal growth (14%, 4 of 31 vs 15%, 11 of 78). However, long-term success rate was significantly higher in the group without ductal involvement (83% vs 46%, p < 0.001).

RELATIVE COST SAVINGS Mean length of hospital stay ranges from 11–13 days following surgical transduodenal LR and 15–23 days following PD.5,6 By comparison, endoscopic ampullectomy is usually performed using conscious sedation alone and on an outpatient basis with two hours of postprocedure observation before discharge. As described earlier, the rates of morbidity and mortality after endoscopic therapy are significantly lower than those of surgical alternatives and recurrence rates are similar to those after LR. Complete eradication after endoscopic resection of ampullary adenomas is eventually successful in greater

than 85% and the number of procedures required range from only 1.1 to 2.7 per patient (Table 19.3) which still translates to significant savings over surgery. Finally, in patients with FAP, recurrence rates are high even after surgical excision36 and these patients will still require lifelong surveillance duodenoscopy for evaluation of duodenal polyps. There is currently no definitive data suggesting improvement in overall survival outcome when small ampullary adenomas in the setting of FAP are aggressively resected. In a study36 of FAP patients surveyed by duodenoscopy with biopsy for >10 years, the histological grade of dysplasia increased in only 3 of 12 subjects who initially had adenoma suggesting that the natural history of these adenomas may be rather static. However, given that endoscopic biopsy surveillance is known for high false-negative detection rates for malignant foci and that there are currently no factors stratifying patients who are likely to progress to ampullary adenocarcinoma, small ampullary adenomas should probably still be resected when found in patients with FAP.

REFERENCES 1.

Baker H, Caldwell D. Lesions of the ampulla of Vater. Surgery 1947; 21:523–531. 2. Shapiro P, Lifvendahl R. Tumors of the extrahepatic bile ducts. Ann Surg 1931; 94:61–79. 3. Offerhaus G, Giardiello F, Krush A, et al. The risk of upper gastrointestinal cancer in familial adenomatous polyposis. Gastroenterology 1992; 102:1980–1982. 196

4. Cahen D, Fockens P, de Wit L, et al. Local resection or pancreaticoduodenectomy for villous adenoma of the ampulla of Vater diagnosed before operation. Br J Surg 1997; 84(7):948–951. 5. de Castro S, van Heek N, Kuhlmann K, et al. Surgical management of neoplasms of the ampulla of Vater: Local resection or pancreatoduodenectomy and prognostic factors for survival. Surgery 2004; 136(5):994–1002.

Chapter 19 Papillectomy/Ampullectomy

6. Rattner D, Fernandez-del Castillo C, Brugge W, et al. Defining the criteria for local resection of ampullary neoplasms. Arch Surg 1996; 131(4):366–371. 7. Beger H, Treitschke F, Gansauge F, et al. Tumor of the ampulla of Vater: Experience with radical resection in 171 consecutively treated patients. Arch Surg 1999; 134(5):526–532. 8. Farnell M, Sakorafas G, Sarr M, et al. Villous tumors of the duodenum: Reappraisal of local versus extended resection. J Gastrointest Surg 2000; 4:13–21. 9. Suzuki K, Kantou U, Murakami Y. Two cases with ampullary cancer who underwent endoscopic excision. Prog Dig Endosc 1983; 23:236–239. 10. Binmoeller K, Boaventura S, Ramsperger K, et al. Endoscopic snare excision of benign adenomas of the papilla of Vater. Gastrointest Endosc 1993; 39:127–131. 11. Seifert B, Schulte F, Stolte M. Adenoma and carcinoma of the duodenum and papilla of Vater: a clinicopathologic study. Am J Gastroenterol 1992; 87:37–42. 12. Yamaguchi K, Enjoji M, Kitamura K. Endoscopic biopsy has limited accuracy in the diagnosis of ampullary tumors. Gastrointest Endosc 1990; 36:588–592. 13. Shemesh E, Nass S, Czerniak A. Endoscopic sphincterotomy and endoscopic fulguration in the management of adenoma of the papilla of Vater. Surg Gynecol Obstet 1989; 169:445–448. 14. Heidecke C, Rosenberg R, Bauer M, et al. Impact of grade of dysplasia in villous adenomas of Vater’s papilla. World J Surg 2002; 26:709–714. 15. Cannon M, Carpenter S, Elta G, et al. EUS compared with CT, magnetic resonance imaging, and angiography and the influence of biliary stenting on staging accuracy of ampullary neoplasms. Gastroentest Endo 1999; 50(1):27–33. 16. Menzel J, Hoepffner N, Sulkowski U, et al. Polypoid tumors of the major duodenal papilla: preoperative staging with intraductal US, EUS, and CT—a prospective, histopathologically controlled study. Gastroentest Endo 1999; 49(3):349–357. 17. Kahaleh M, Shami V, Brock A, et al. Factors predictive of malignancy and endoscopic resectability in ampullary neoplasia. Am J Gastroenterol 2004; 99:2335–2339. 18. Harewood G, Pochron N, Gostout C. Prospective, randomized, controlled trial of prophylactic pancreatic stent placement for endoscopic snare excision of the duodenal ampulla. Gastrointest Endosc 2005; 62(3):367–370. 19. Aiura K, Imaeda H, Kitajima M, et al. Balloon-catheter-assisted endoscopic snare papillectomy for benign tumors of the major duodenal papilla. Gastrointest Endosc 2003; 57(6):743–747. 20. Moon J, Cha S, Cho Y, et al. Wire-guided endoscopic snare papillectomy for tumors of the major duodenal papilla. Gastrointest Endosc 2005; 61(3):461–466.

21. Saurin J, Chavillon A, Napoleon B, et al. Long-term follow-up of patients with endoscopic treatment of sporadic adenomas of the papilla of Vater. Endoscopy 2003; 35:402–406. 22. Catalano M, Linder J, Chak A, et al. Endoscopic management of adenoma of the major duodenal papilla. Gastrointest Endosc 2004; 59(2):225–232. 23. Ponnudurai R, Martin J, Haber G, et al. Endoscopic snare ampullectomy for resection of benign ampullary neoplasm in 25 patients. Gastroentest Endo 2000; 51(4):part 2:AB2213. 24. Ponchon T, Berger F, Chavaillon A, et al. Contribution of endoscopy to diagnosis and treatment of tumors of the ampulla of Vater. Cancer 1989; 64:161–167. 25. Martin J, Haber G, Kortan P, et al. Endoscopic snare ampullectomy for resection of benign ampullary neoplasms [abstract]. Gastrointest Endosc 1997; 45:AB458. 26. Norton I, Gostout C, Baron T, et al. Safety and outcome of endoscopic snare excision of the major duodenal papilla. Gastrointest Endosc 2002; 56:239–243. 27. Desilets D, Dy R, Ku P, et al. Endoscopic management of tumors of the major duodenal papilla: refined techniques to improve outcome and avoid complications. Gastrointest Endosc 2001; 54(2):202–208. 28. Martin J, Haber G. Ampullary adenoma: clinical manifestations, diagnosis, and treatment. Gastrointest Endoscopy Clin N Am 2003; 13:649–669. 29. Zadorova Z, Dvorak M, Hajer J. Endoscopic therapy of benign tumors of the papilla of Vater. Endoscopy 2001; 33:345–347. 30. Cheng C, Sherman S, Fogel E, et al. Endoscopic snare papillectomy for tumors of the duodenal papillae. Gastrointest Endosc 2004; 60:757–764. 31. Baille J. Endoscopic ampullectomy: does pancreatic stent placement make it safer? Gastrointest Endosc 2005; 62(3):371–373. 32. Bohnacker S, Seitz U, Nguyen D, et al. Endoscopic snare resection of benign ampullary tumors of the duodenal papilla without and with intraductal growth. Gastrointest Endosc 2005; 62(4):551–560. 33. Ito K, Fujita N, Noda Y, et al. Case of early ampullary cancer treated by endoscopic papillectomy. Dig Endosc 2004; 16(2):157–161. 34. Churrani R, Cretu D, Pleskow D, et al. Efficacy, safety, and outcome of endoscopic snare ampullectomy for 31 ampullary adenomas. Gastrointest Endosc 2002; 55(5):AB166. 35. DiSario J, Giampaolo A, Samowitz W, et al. Endoscopic management of ampulla of Vater lesions in familial adenomatous polyposis. Gut 2002; 51:A278. 36. Heiskanen I, Kellokumpu I, Jarvinen H. Management of duodenal adenomas in 98 patients with familial adenomatous polyposis. Endoscopy 1999; 31:412–416.

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Chapter

20

TECHNIQUES

Pancreatoscopy Tadashi Kodama, Yoshihide Tatsumi and Tatsuya Koshitani

INTRODUCTION AND SCIENTIFIC BASIS Various techniques imaging the pancreas have recently been developed. Among those methods such as computed tomography (CT), magnetic resonance imaging (MRI) and transabdominal or endoscopic ultrasonography, magnetic resonance cholangiopancreatography (MRCP) has emerged as an alternative diagnostic technology, yielding images at times comparable to endoscopic retrograde cholangiopancreatography (ERCP). Although ERCP is one of the established gold standards for the diagnosis of pancreatic cancer, it, as well as MRCP, may fail to differentiate the origin of a filling defect or a stenosis in the main pancreatic duct, because of inability to directly visualize the duct lumen. This desire of direct vision of the main pancreatic duct gave birth to the idea of direct pancreatoscopy. The pancreatoscope was first developed by the Japanese group of Takekoshi et al. in 1975.1 It was a small caliber fiberscope (baby scope) that could pass through the accessory channel of a duodenoscope (mother scope). Although the idea was very attractive and a few investigators studied its feasibility, pancreatoscopy was unpopular because of instrument fragility and suboptimal visibility as well as its relatively large diameter relative to the duodenal papilla. The description of intraductal papillary mucinous tumor (IPMT) by another Japanese investigator, Ohashi et al.,2 made an impact on pancreatoscopy in the early 1980s. Since then, the pancreatoscope has been reassessed as a useful method to diagnose IPMT by virtue of characteristic endoscopic findings resembling salmon eggs. Initial pancreatoscope prototypes had only optic image fiber bundles without any channel or tip deflection. Subsequent devices of more than 3 or 4 mm in diameter were then developed with oneor two-way tip deflection and with an accessory channel. To insert the scope into a non-dilated pancreatic duct, an ultrathin pancreatoscope (0.8 mm in diameter) was also developed by decreasing the number of optical fibers. These thin or ultrathin fiberoptic scopes had the same problem of low visibility to different degrees, contingent upon the numbers of optical bundles. Recently a peroral electronic pancreatoscope (PEPS), the smallest known electronic endoscope, was developed using the latest high quality television technology. With the above advancements in technology and imaging, peroral pancreatoscopy has been assessed and considered to be a useful technique, although most cases continue to be performed in Advanced Centers of Endoscopic Excellence.

DESCRIPTION OF TECHNIQUE Equipment

Pancreatoscope To date, there are two types of commercially available fiberoptic pancreatoscopes.3 These scopes can be purchased from several endo-

scopic manufactures. Video pancreatoscopes manufactured by Olympus Medical Systems (Tokyo, Japan) are commercially available in Japan. The most commonly used fiberoptic pancreatoscope has an outer diameter of more than 3 mm. It has both tip angulation and an accessory channel (more than 1.2 mm diameter) which allows biopsy and lithotripsy under direct visualization.4–6 Pentax Co. (Tokyo, Japan) offers a 2.7 mm-miniscope with tip angulation, but its small 0.75 mm forceps channel is not large enough to reliably allow biopsy and brush cytology. A much smaller scope lacking an angulation mechanism, with an outer diameter of 1.67 mm and 0.55 mm accessory channel, has also been reported.7 A second type of device is known as the ultrathin pancreatoscope. This fiberscope has an outer diameter of 0.75 or 0.8 mm and contains 3000–6000 bundles of image fibers.4,6,8 Since the ultrathin pancreatoscope can be inserted through the usual ERCP catheter, it can be applied easily at the time of ERCP. Although it has no tip angulation or accessory channel, cytology sampling as well as injection and aspiration of saline are available through the outer cannula (Figs 20.1A, 20.1B).9 Specifications for representative fiberoptic pancreatoscopes in Japan are compared in Table 20.1, although a number of other scopes are available from other manufacturers. The peroral electronic pancreatoscope (PEPS) was first described by Kodama et al. in 1999.10 A new prototype was developed with a newly designed 50 000-pixel interline charge-coupled device (CCD) (about 1 mm square in size) (Matsushita Electronics, Osaka, Japan) in cooperation with Olympus Optical Co. (Tokyo, Japan). The prototype PEPS (XPF-22EY) has an outer diameter of 2.1 mm and a bidirectional angle function without an accessory channel. After its prototype success, Olympus has developed an enhanced version that has an accessory channel (XCHF-BP240).11 At present, Olympus offers two types of commercial electronic pancreatoscopes in Japanese markets. The first type (CHF-BP260) is a commercial model of XCHF-BP240 with a small 0.5 mm accessory channel for a guidewire (Figs 20.2A–20.2E). The second type (CHF-B260) is a larger scope with a larger accessory channel with use for biopsy and lithotripsy under direct visualization. These scopes use a field sequential imaging system. Both types of electronic pancreatoscopes using a simultaneous imaging system have also been developed in the US, but they are not commercially available. The specifications for the prototypes and these new commercial electronic pancreatoscopes are compared in Table 20.2.

Mother scope Direct pancreatoscopy can be safely performed by means of a “mother-baby” method. A “baby scope” with an outer diameter less than 3.1 mm can be inserted through the channel of a standard therapeutic duodenoscope. Since larger baby scopes (e.g. with an 199

SECTION 2 TECHNIQUES

B

A

Fig. 20.1 An ultrathin fiberoptic pancreatoscope, PF-8P (Olympus) and guide catheter. A Overview. a guide catheter inserted through an accessory channel of duodenoscope (TJF-240).

CHF-BP30 PF-8P FCP-9P FCP-8P

B Ultrathin pancreatoscope with

Manufacturer

Tip diameter (mm)

Channel (mm)

Angulation up/down (degrees)

View (degrees)

Olympus Olympus Pentax Pentax

3.1 0.8 (1.8a) 3.0 2.7

1.2 None 1.2 0.75

160/130 none 90/90 90/90

80 80 90 90

Table 20.1 Specifications of representative fiberoptic pancreatoscopes in Japan a

Outer diameter of guide catheter.

XPF-22EY (not commercially available) XCHF-BP240 (not commercially available) CHF-BP260 CHF-B260

Imaging

Tip diameter (mm)

Channel (mm)

Angulation up/down (degrees)

View (degrees)

Simultaneous

2.1

None

120/120

80

Field sequential

2.6

0.5

90/90

90

Field sequential Field sequential

2.6 3.4

0.5 1.2

70/70 70/70

90 90

Table 20.2 Specifications of prototype and commercially available electronic pancreatoscopes PEPS, Peroral electronic pancreatoscope. All electronic pancreatoscopes are manufactured by Olympus Medical Systems Co. at present.

200

outer diameter more than 4 mm) require a special mother scope which proved expensive and hard to control; they are no longer commercialized.

tial color television system that is utilized in another ultrathin video endoscope adapted for upper GI endoscopy (e.g. GIF-N230; Olympus).12

Light source and image processor

Image converter for fiberoptic pancreatoscope

Direct pancreatoscopy requires a second light source for a baby scope as well as one for a mother scope. Video pancreatoscopes also need suitable processors. The prototype (XPF-22EY) works with a processor modified from a CV-140 processor, using a simultaneous color television system. Both new commercial electronic pancreatoscopes (CHF-BP260 and CHF-B260) and XCHF-BP240 work with a CV-240 or CV-260 processor (Fig. 20.3) using a sequen-

Connecting a special video converter (OVC-200) (Fig. 20.4) with a processor (CV-200 or later) to the head of a conventional fiberoptic pancreatoscope facilitates the endoscopic procedure and improves imaging.8 This converter enables viewing the image on a television monitor as a sequential electronic endoscope image, although its image quality is inferior to that of the electronic pancreatoscope. In the US markets, this video converter is also available as OVC-140

Chapter 20 Pancreatoscopy

A

B

C

D

E

Fig. 20.2 Peroral electronic pancreatoscope with a small accessory channel, CHF-BP260 (Olympus). A Overview. B Control section with an up/down angulation control knob and accessory channel port. C Deflection part of pancreatoscope. D Distal chip of pancreatoscope (note channel). E Deflection section of pancreatoscope entirely out of an accessory channel of a duodenosocpe (TJF-240).

201

SECTION 2 TECHNIQUES

with CV-160 (Olympus America), processor using a simultaneous imaging system.

ENDOSCOPIC PROCEDURE Procedure timing In our institutions, MRCP is preferable for the initial diagnostic evaluation of the pancreatic duct. MRCP is usually followed by ERCP and selective pancreatoscopy when a pancreatic lesion is suspected. Enough preparation time for direct pancreatoscopy should be considered if it is undertaken at the time of an initial diagnostic ERCP, since its application requires significant time.

Dilatation of the duodenal papilla prior to insertion When baby scopes with an outer diameter of more than 2.5 mm are utilized, endoscopic sphincterotomy (EST) of the pancreatic sphincter is usually needed. EST may be skipped, if the papilla is dilated in the pathological situation like IPMT (Figs 20.5A, 20.5B). Intravenous administration of a nitric oxide donor such as isosorbide dinitrate (5 mg/hr) can facilitate the insertion of the scope without EST even with some larger pancreatoscopes. With the prototype electronic pancreatoscope (XPF-22EY; outer diameter 2.1 mm) and the enhanced version with an accessory channel (XCHF-BP240; outer diameter 2.6 mm), insertion of the scope has been performed without sphincterotomy with relatively high success rates.10,11 However, the success rate of XCHF-BP240 appears to be inferior to that of XPF-22EY as a consequence of larger outer diameter.

Insertion of the scope Fig. 20.3 CHF-BP260 with a CV-260 processor (Olympus America), using a sequential color television system.

Fig. 20.4 A special video converter, OVC-200 (Olympus) that enables viewing the image of fiberoptic pancreatoscope on a television monitor. OVC-200 connected with the head part of the ultrathin fiberoptic pancreatoscope, PF-8P (Olympus).

202

All pancreatoscopes need a careful insertion procedure because of their fragility. They are easily damaged by acute angulation over the elevator of the duodenoscope. After introduction of a mother scope into the second portion of the duodenum, the main duodenal papilla is viewed and conventional pancreatography performed. Pancreatoscopes without an accessory channel are inserted directly through the papilla, at times alongside of a previously placed guidewire. Cooperation of two experienced endoscopists for the mother and baby scope, using a combination of tip angulation and movement of the duodenoscope, is the key for successful deep insertion (Fig. 20.6).10 Pancreatoscopes which have an accessory channel usually are inserted over a guidewire placed into the main pancreatic duct. However, when using the enhanced PEPS with an accessory channel (XCHF-BP240, CHF-BP260), direct insertion through the papilla is needed, because it cannot be inserted over any available guidewire, to date. However, once inserted into the main pancreatic duct, a thin guidewire through the accessory channel of the instrument can facilitate deep insertion to the targeted point like other scopes with an accessory channel (Fig. 20.7)11 Another type of commercial pancreatoscope, CHF-B260, can be inserted over a 0.035 inch guidewire. An ultrathin pancreatoscope is inserted through the guide cannula. In this setting, a cannula is advanced over a guidewire under fluoroscopy deep into the main pancreatic duct. The guidewire is then removed and an ultrathin pancreatoscope is inserted through the cannula. After the scope has emerged several millimeters from the tip of the cannula, the image of the pancreatic duct is obtained. Observation should be done only during withdrawal of the cannula of the scope from the duct. Pushing the ultrathin pancre-

Chapter 20 Pancreatoscopy

A

B

Fig. 20.5 Observation of intraductal papillary mucinous tumor (IPMT) in the main pancreatic duct by visualized PEPS. A Abundant mucin in dilated papilla. B Filling defects in the dilated main pancreatic duct were observed at ERCP. PEPS was easily inserted without dilatation procedure of papilla.

Fig. 20.6 Electronic pancreatoscopy with a second experienced endoscopist who handles the baby scope.

Fig. 20.7 Endoscopic image obtained with XCHF-BP240 (Olympus) during insertion over a guidewire.

atoscope system may damage both scope and mucosa. If investigation at the distal part of the duct is needed again, the cannula should be advanced again over a guidewire without the scope.8

ability to obtain clear images even with remarkably thick and mucinous pancreatic juice as seen in some cases of IPMT. The XCHF-BP240 pancreatoscope is significantly superior to the XPF22EY when washing under direct visualization (Figs 20.8A–C).11 With any debriding, care must be taken not to use excessive force with irrigation, resulting in acinar rupture and procedural pancreatitis. With an ultrathin pancreatoscope, washing can be also performed under direct visualization through the narrow lumen between the ultrathin scope and the guide catheter. However, saline flow is sometimes too weak to wash out thick mucus. If thick mucus precludes visualization, irrigation through the guide catheter is preferable after temporary removal of the pancreatoscope.

Improving visualization To obtain a clear image, washing with saline is necessary during every procedure. Techniques to wash the pancreatic duct lumina are different for each pancreatoscope mentioned above. When a pancreatoscope without an accessory channel like XPF-22EY is used, washing is needed through an ERCP catheter prior to direct pancreatoscopy, if necessary.10 This method has some limitation when abundant mucus fills the lumen. Secretin (100 clinical units) has also been injected intravenously to stimulate the exocrine function of the pancreas and thus improve visualization with the initial cases utilizing the XPF-22EY miniscope.13 However, this method cannot be utilized in Japan at present, because the drug is currently not available from domestic pharmaceutical companies. When using a pancreatoscope that has an accessory channel, washing with saline in the pancreatic duct can be done through the channel under direct vision. The advantage of this method is the

Biopsy and cytology sampling A sample of pancreatic juice for cytology can be obtained under direct vision when the pancreatoscope has an accessory channel. With an ultrathin pancreatoscope, sampling can be also performed under direct visualization through the narrow lumen between the ultrathin scope and the guide catheter. The diagnosis of in situ carcinoma of the pancreas has been reported by sampling under direct 203

SECTION 2 TECHNIQUES

A

B C

Fig. 20.8 Endoscopic images of intraductal papillary mucinous tumors (IPMT) obtained with XCHF-BP240 (Olympus). Note the effect of washing under direct visualization. Rinsing with saline is sufficient to wash out abundant mucin. After rinsing, an image of egg-shaped tumor of the pancreatic duct was clearly visualized. A Before washing. B During washing. C After washing. Reprinted from Gastrointest Endosc, 59, Kodama T et al., Initial experience with a new peroral electronic pancreatoscope with an accessory channel, 895–900, 2004 with permission from American Society for Gastrointestinal Endoscopy.

vision using the ultrathin scope.9 However, when the juice is extremely turbid or mucinous, it is often impossible to collect a pancreatic juice sample through the narrow lumen of the ultrathin scope system or the 0.5 mm channel of an XCHF-BP240.11 Brush cytology catheters and biopsy forceps can be used if the pancreatoscope has a relatively large accessory channel of 1.2 or 1.7 mm.4,5 When ultrathin pancreatoscopes or other pancreatoscopes with smaller channels are used for examination, transpapillary brush cytology or biopsy is needed under fluoroscopy after baby scope removal. In such cases, the pancreatoscopic findings are referred to decide the target point in the main pancreatic duct.

PROCEDURAL SUCCESS RATES It is important to select a scope prior to examination contingent upon the diameter of the duct and purpose of the study. Most endoscopists will not have access to multiple instruments. With a peroral electronic pancreatoscope (PEPS), a high resolution image is obtained by an ultra-miniature interline charge-coupled device (CCD). Olympus XPF-22EY, XCHF-BP240 and CHF-BP260 electronic baby scopes are designed to be inserted through the papilla without pancreatic duct sphincterotomy. They can be inserted deep into the tail of the non-dilated pancreatic duct unless the duct is too crooked or small in its previously noted diameter. The CHFB260 is designed to function for biopsy and lithotripsy under direct visualization. However, its application requires a pancreatic sphincterotomy and it cannot be inserted into a non-dilated or extremely angulated pancreatic duct. Kodama et al.13 reported the initial use of the XPF-22EY inserted into the pancreatic duct without sphincterotomy. It was successfully inserted into the predetermined target point and the pancreatic duct lesion could be visualized in 42 (75%) of 56 cases. Of the 42 cases, the PEPS reached the pancreatic head in 10 cases, the pancreatic body in 15 cases, and the pancreatic tail in 17 cases. In the 14 remaining cases, 6 failures were related to failure to intubate the papilla and the other 8 to passing the pancreatoscope beyond 204

the genu of the pancreatic duct. In our preliminary experience, the XCHF-BP240 could be inserted successfully into the pancreatic or bile duct without sphincterotomy in 9 of the 11 patients (82%). Observation of a predetermined target and juice collection with direct visualization was successful in 8 of 9 patients (89%).11 With the 3.1 mm fiberoptic pancreatoscope, angulation of the endoscope facilitates the visualization of the pancreatic duct and target biopsy or brush cytology is possible. However, this instrument cannot be inserted into a non-dilated or angulated pancreatic duct. Sphincterotomy of the pancreatic sphincter is usually needed unless the orifice of the papilla is patulous. The 3.1 mm pancreatoscope has been reported to perform successful pancreatoscopy after a pancreatic duct sphincterotomy in 16 (89%) of 18 cases by Riemann et al.4 Two failures occurred because of tight strictures in the setting of calcific pancreatitis. In this study, 5 cases of intraductal cystadenoma and 2 cases of pancreatic adenocarcinoma were all diagnosed by pancreatoscopic images. Histologic confirmation of the above cases was successfully obtained by biopsy under direct visualization. Two cases of segmental pancreatitis were also diagnosed by pancreatoscopic images (smooth strictures in conjunction with negative cytology). With a comparably small sized pancreatoscope, Jung et al.5 also reported that the pancreatic duct lesion could be observed in 15 (83%) of 18 patients with various pancreatic disorders. The author had a comment on the limitation of biopsy with this instrument, specifically, that angulation in a narrow pancreatic duct often precluded passage of a small biopsy forceps. With an ultrathin pancreatoscope, a screening examination is possible for a non-dilated pancreatic duct without sphincterotomy, but lack of angulation of the endoscope limits the visualization of the pancreatic duct. Cytology under direct visualization of the pancreatic duct is possible. Tajiri et al.8 have reported that an ultrathin pancreatoscope was able to reach a predetermined target point and the pancreatic duct lesion noted at ERCP could be observed in 42 (81%) of 52 cases examined. In the 10 inadequate studies, 5 were related to failure to

Chapter 20 Pancreatoscopy

intubate the papilla and the other 5 to failure to pass the pancreatoscope beyond the genu of the pancreatic duct. Yamao, et al.6 also reported with the same type scope that 22 of the 35 pancreatic cancer cases (63%) were observed, although insertion was successful in all cases. The failure to diagnose 13 cases was because of tapering stenosis or obstruction of the main pancreatic duct with asymmetrical deviation. The observation rate was increased to 75% when pancreatic cancers were less than 2 cm. On the other hand, an observation rate of benign stenoses of the pancreatic duct and IPMT were reported to be 16 of 20 (80%) and 57 of 60 (95%), respectively.

ELECTRONIC PANCREATOSCOPIC FINDINGS IN THE VARIOUS TYPES OF PANCREATIC DISEASES With electronic pancreatoscopes, various pancreatic diseases were diagnosed from the endoscopic findings more precisely compared with previous reports using fiberoptic scopes. Furthermore, fine capillary vessels on the surface of the pancreatic duct mucosa was first clearly observed by PEPS.

Fig. 20.9 Endoscopic image of the pancreatic duct of a healthy control subject obtained with PEPS system. Network of fine vessels clearly visualized. Reprinted from Gastrointest Endosc, 49, Kodama T et al., Pancreatoscopy for the next generation: development of the peroral electronic pancreatoscope system, 366–371, 1999 with permission from American Society for Gastrointestinal Endoscopy and Elsevier.

A

B

With PEPS, in normal cases, smooth pancreatic duct walls with white to pink color, and clear confluences of side branches, are observed. Fine capillary vessels are clearly visualized on the surface of the pancreatic duct (Fig. 20.9). In cases with chronic pancreatitis, protein plugs and calcified stones are clearly observed in the main pancreatic duct (Figs 20.10, 20.11A, 20.11B). On the mucosal surface of the pancreatic duct, whitish, rough, scar-like, or erythematous mucosa is observed. Fine capillary vessels on the surface of the pancreatic duct are frequently blurred (Figs 20.12A, 12B). Smooth ductal stenoses with scar formation are also observed (Figs 20.13A, 20.13B). In cases with advanced cancers, friable mucosa with erythema and erosive changes around the stenosis (Fig. 20.14) are observed as diagnostic findings of pancreatic cancer, while in some cases a compressed pancreatic duct wall covered with normal epithelium is observed. In IPMT cases, the characteristic finding of papillary tumors reported by other investigators is visualized with extreme clarity as are mucosal excrescences resembling clustered salmon eggs. Endoscopic findings of IPMT are further discussed in the Indications section of this chapter.

Fig. 20.10 Endoscopic image of the pancreatic duct of a patient with chronic pancreatitis obtained with PEPS system. Fine protein plugs within the pancreatic duct. Reprinted from Gastroenterol Endosc, 44, Kodama T, Present and future of the peroral electronic pancreatoscope (PEPS), 3–10, 2002 with permission from Japan Gastroenterological Endoscopy Society and Elsevier.

Figs. 20.11A, B Endoscopic images of the pancreatic duct of a patient with chronic pancreatitis obtained with PEPS system. A white stone within the pancreatic duct. The fine detail of the texture of the stone is clearly seen. “Reprinted from Gastrointest Endosc, 49, Kodama T et al., Pancreatoscopy for the next generation: development of the peroral electronic pancreatoscope system, 366–371, 1999 with permission from American Society for Gastrointestinal Endoscopy and Elsevier.

205

SECTION 2 TECHNIQUES

A

Figs. 20.12A, B Endoscopic images of the pancreatic duct in a patient with chronic pancreatitis obtained with PEPS system. Vague network of fine vessels on the rough-surfaced pancreatic duct. Reprinted from Gastrointest Endosc, 49, Kodama T et al., Pancreatoscopy for the next generation: development of the peroral electronic pancreatoscope system, 366–371, 1999 with permission from American Society for Gastrointestinal Endoscopy and Elsevier.

B

Fig. 20.13 Endoscopic image of the pancreatic duct of a patient with chronic pancreatitis obtained with PEPS system. A Remarkable stenosis in the main pancreatic duct was observed in ERCP image. B Smooth stenosis of the main pancreatic duct was noted with the PEPS.

B

A

INDICATIONS Necessary indications

Fig. 20.14 Endoscopic image of the pancreatic duct of a patient with pancreatic cancer obtained with PEPS system. Friable mucosa with erythema and erosive changes around the stenosis of the pancreatic duct clearly visualized. Reprinted from Gastroenterol Endosc, 44, Kodama T, Present and future of the peroral electronic pancreatoscope (PEPS), 3–10, 2002 with permission from Japan Gastroenterological Endoscopy Society and Elsevier. 206

Major indications for direct pancreatoscopy include filling defects on ERCP of uncertain etiology and duct cut-off or stricture of uncertain origin. Direct pancreatoscopy can improve the diagnosis of IPMT from its characteristic endoscopic findings. Direct pancreatoscopy can also differentiate pancreatic cancers from chronic pancreatitis if the cancerous lesion is within the main pancreatic duct. However, final diagnosis should be assured by virtue of directed histology or cytology. Intraoperative pancreatoscopy is very useful in some cases of IPMT to determine the resection line of the pancreas, although frozen section of the margin remains mandatory. The high quality image of PEPS has the potential to improve diagnostic accuracy of IPMT or pancreatic cancer. It also has the potential to improve visual detection of tumor invasion within the pancreatic duct.

Intraductal papillary mucinous tumor (IPMT) The investigation of possible IPMT cases is one of the best indications for pancreatoscopy. IPMT has been recently recognized as a unique pancreatic tumor with an indolent biologic behavior and

Chapter 20 Pancreatoscopy

favorable prognosis. The tumor spreads along the pancreatic duct replacing the normal epithelium and includes a broad spectrum of histopathologic disorders such as hyperplasia, adenoma, and adenocarcinoma. The possible diagnosis of IPMT is usually established by ERCP or MRCP findings.14 They include dilated, mucus-filled papilla, filling defects in the main pancreatic duct, and dilated main and branch pancreatic ducts in the absence of remarkable obstructing ductal strictures. CT and transabdominal or endoscopic ultrasonography are also useful for detecting cystic lesions and tumors within the cysts.15 However, definite diagnosis of IPMT is possible if the characteristic appearance of papillary tumors are observed during pancreatoscopy. A biopsy to differentiate various kinds of histology can be taken from lesions under direct vision when a pancreatoscope with an accessory channel is used. Even without biopsy, pancreatoscopy has been reported to be useful in the differentiation of benign IPMT of the pancreas from more dysplastic lesions. It is often combined with intraductal ultrasonography (IDUS) which can measure the size of papillary lesions and define potential invasion. Hara, et al. classified the endoscopic findings of IPMT into 5 groups and described a fish-egg-like type with prominent vessels, villous type and vegetative type, as often malignant.16,17 Pancreatoscopy also provides valuable information in assessing the extent of the lesion and multicentric lesions. It is helpful at selecting the best surgical procedure in IPMT. Kaneko, et al.18,19 reported that intraoperative pancreatoscopy of IPMT was useful in determining the surgical resection line. These findings were more clearly confirmed by investigators using PEPS.20 With this instrument the characteristic appearance of papillary tumors can be visualized with unsurpassed clarity, even though the distance between each element of the tumor and the distal end of the endoscope varied. PEPS made it possible to make a more detailed morphologic assessment of the tumor and its grade of malignancy. In the case of adenocarcinoma, PEPS revealed a variety of tumors, from granular or nodular tumors to higher villous tumors with dilatation of capillary vessels (Figs 20.15A, 20.15B). Papillary tumors resembling salmon eggs with reddish inner color (venous dilatation) were also observed with adenocarcinoma (Fig. 20.16), while papillary tumors resembling salmon eggs with whitish inner color were recognized in adenomas (Fig. 20.17A). These findings supported the results of the previous studies concerning papillary adenoma or adenocarcinoma in IPMT. PEPS information on the extent of the intraductal growth of the tumor was also reported to be better than conventional pancreatoscopy.20 PEPS clearly visualized even small papillary projections near larger tumors, and the border of the lesion with the normal mucosa was well identified (Figs 20.17A, 20.17B). In a single case of branch-duct type of IPMT, where the main tumor existed in a dilated branch duct off the main pancreatic duct, the PEPS visualized papillary tumors spreading from the orifice of the dilated branch duct.

Differentiation of stenosis of the main pancreatic duct (benign or malignant) From the initial prototype of pancreatoscopy, many trials have been performed to distinguish focal or chronic pancreatitis from pancreatic cancer. Many investigators have described smooth stenoses with or without scar formation or mucosal edema observed in chronic pancreatitis, while lesions with friable erythematous mucosa and erosive changes are more common in pancreatic cancer. Our PEPS findings of pseudotumorous pancreatitis that was differentiated

A

B

Fig. 20.15 Endoscopic images of the pancreatic duct of a patient with intraductal papillary mucinous tumors (IPMT) obtained with PEPS system. Various shapes of tumors were observed inside the dilated pancreatic duct. This case proved to be adenocarcinoma histologically. A numerous tumors with taller villous projections and dilatation of capillary vessels. B granular or nodular tumors. Reprinted from Gastrointest Endosc, 52, Koshitani T et al., Clinical application of the peroral electronic pancreatoscope for the investigation of intraductal mucin-hypersecreting neoplasm, 95–99, 2000 with permission from American Society for Gastrointestinal Endoscopy and Elsevier.

Fig. 20.16 Endoscopic images of the pancreatic duct of a patient with intraductal papillary mucinous tumors (IPMT) obtained with PEPS system. Papillary tumors resembling salmon eggs with dilatation of capillary vessels. This case was proved to be adenocarcinoma. Reprinted from Gastroenterol Endosc, 44, Kodama T, Present and future of the peroral electronic pancreatoscope (PEPS), 3–10, 2002 with permission from Japan Gastroenterological Endoscopy Society and Elsevier.

207

SECTION 2 TECHNIQUES

A

B

from pancreatic cancer is supportive of this consensus.21 However, smooth stenoses without friable erythematous mucosa and erosive changes do not always imply a benign lesion. Yamao et al.6 reported that the sensitivity and specificity of coarse mucosa or friability for pancreatic cancer were 59% and 88% (coarse mucosa), and 50% and 100% (friability), respectively, in 38 cases that were followed up for more than 2 years. A compressed pancreatic duct wall covered with normal epithelium can be observed with an extrinsic malignancy that does not involve the epithelium of the pancreatic duct at the distal site of the stenosis. Miyakawa et al.22 classified endoscopic cancerous changes into two groups: superficial and compressed. They reported that malignant cells were detected histopathologically in 41% of the superficial type and in none of the compressed type, based on transpapillary biopsy or brush cytology. Although pancreatic duct compression by an extrinsic pancreatic cancer is steeper than compression in chronic pancreatitis, the necessity of surgical treatment cannot be decided from the pancreatoscopic findings alone. Clinical diagnosis of pancreatic cancer should be carefully considered with other multiple imaging modalities if biopsy or cytology is negative.

Appropriate indications Using an ultrathin pancreatoscope, the usefulness of direct pancreatoscopy for the early detection of pancreatic cancer has been reported in small series. Detection of pancreatic cancer using PEPS is being investigated,23 looking for early stages of pancreatic cancer. Direct pancreatoscopy with PEPS image quality may be considered in patients who are suspected of having chronic pancreatitis, equivocal by other imaging modalities including endoscopic ultrasound in this setting. Pancreatoscopic images obtained by PEPS could suggest the clinical diagnosis of chronic pancreatitis from its characteristic endoscopic findings.

Early detection of pancreatic cancer Because most pancreatic cancers are derived from pancreatic duct epithelium, pancreatoscopy can contribute to the diagnosis of early pancreatic cancer if located within the main pancreatic duct. However, reports of in situ carcinoma of the pancreas found by pancreatoscopy are very rare except for that associated with IPMT. 208

Fig. 20.17 Endoscopic images of the pancreatic duct of a patient with intraductal papillary mucinous tumors (IPMT) obtained with PEPS system. A Papillary tumors resembling salmon eggs with whitish inner color. B Small papillary projections near larger tumors. Reprinted from Gastrointest Endosc, 52, Koshitani T et al., Clinical application of the peroral electronic pancreatoscope for the investigation of intraductal mucin-hypersecreting neoplasm, 95–99, 2000 with permission from American Society for Gastrointestinal Endoscopy and Elsevier.

This is partly because the detection of early pancreatic cancer by pancreatoscopy is a limited method for advanced centers of endoscopic excellence. Moreover, it is uncertain how frequently ductal adenocarcinoma begins its growth in the main pancreatic duct. Uehara et al.9 reported diagnosis of in situ carcinoma of the pancreas using the ultrathin peroral pancreatoscope and pancreatoscopic cytology. Out of 11 cases of in situ carcinoma diagnosed in the surgically resected specimen, they observed endoscopic findings of irregular, nodular or papillary mucosa of the main pancreatic duct in 10 cases. They also collected pancreatic juice from abnormal sites of the pancreatic duct seen by peroral pancreatoscopy through the narrow lumen between the scope and the guide catheter. They diagnosed all the 10 cases as carcinoma by this pancreatoscopic cytology. They concluded that pancreatoscopic cytology was useful for locating and diagnosing in situ carcinoma when compared to pancreatic juice cytology obtained by catheter at the time of ERCP. However a more comprehensive study in high-risk patients could reveal the sensitivity and specificity for diagnosing minute pancreatic cancer with pancreatoscopy in the future.

Further investigation of chronic pancreatitis Endoscopic findings of protein plugs and calcified stones floating in turbid pancreatic juice or scar formation on the mucosa have been reported by many investigators in patients with chronic pancreatitis.24 These findings were further studied with PEPS in 36 patients with chronic pancreatitis who were classified as having equivocal to marked ductographic changes by ERP according to the Cambridge criteria.25 With the high quality image of PEPS, these plugs consisted of fine granular or thread-like protein floating in the lumen or coating the epithelium on occasion. In equivocal cases, ductal contents were turbid and calculi co-existing with protein plugs appeared to be relatively soft, while in advanced chronic pancreatitis calculi had a rough surface and were generally calcified. Although the vascular markings in the pancreatic ductal mucosa were clearly observed in normal patients, those in chronic pancreatitis were generally indistinct. However, the vascular markings tended to be visible again in advanced stages of chronic pancreatitis. Normal patients had smooth capillary reticulation markings, whereas changes in the visible vascular net such as disruption, stenosis, irregularity, rearrangement and stretching were observed in chronic pancreatitis.

Chapter 20 Pancreatoscopy

Whitish mucosa co-existing with a rough surface and scar formation of the ductal wall were observed in advanced subjects with vascular changes, while the vascular markings had disappeared and edematous white mucosa was observed in equivocal cases. From these findings, PEPS images appear to be particularly helpful with a patient complaining of symptoms consistent with chronic pancreatitis, whose ERCP image is equivocal relative to the Cambridge criteria of chronic pancreatitis. Further study may establish new diagnostic criteria for chronic pancreatitis by PEPS images.26

Management of complications

Inappropriate indications When the lesion is limited to a side branch of the pancreatic duct, direct pancreatoscopy cannot reach the lesion. Alternative diagnostic modalities in such a case are endoscopic or intraductal ultrasonography (EUS or IDUS) combined with pancreatic juice cytology.27 Multiple molecular biological analyses of the pancreatic juice, including K-ras oncogene mutations and telomerase activity, are being investigated as an adjunct to cytology.28

COMPLICATIONS Acute pancreatitis occurring with or without sphincterotomy is the main complication of pancreatoscopy. Reported complications of pancreatoscopy are relatively low (0–12%), partially because the procedure is usually undertaken at Advanced Centers of Endoscopic Excellence. Moreover, patients with chronic pancreatitis are less susceptible to endoscopic complications than patients with normal pancreatic ducts. Mild pancreatitis after sphincterotomy was reported by Riemann et al.4 in 1 of 16 cases (6%) in one series using the 3.1 mm pancreatoscope. This pancreatitis rapidly improved with standard therapy. In this study, the total complication rate of pancreatoscopy was reported to be 2.6%, including 20 cases studied with an ultrathin pancreatoscope which is probably less invasive. Yamao et al.,6 in turn, reported that using the 3.4 mm pancreatoscope and ultrathin pancreatoscope, mild pancreatitis (lasting 1–2 days) occurred in 4 of 33 patients (12%). In 3 of these 4 patients, transpapillary biopsy specimens or cytology specimens (brushings) were obtained as well as pancreatoscopic investigation. With use of an ultrathin pancreatoscope, Tajiri et al.8 reported that 2 of 52 patients (4%) developed acute pancreatitis. Clinical symptoms and biochemical abnormalities improved completely within 7 days. With use of 3.2 mm or 1.67 mm pancreatoscopes, Hara et al.17 reported that mild to moderate pancreatitis occurred in

CHF-BP30 PF-8P FCP-9P FCP-8P CHF-BP260 CHF-B260 Video Converter CV-140 Processor CV-160

4 of 60 patients (7%). All patients recovered with conservative treatment. Using the XPF-22EY PEPS, 1 of 56 patients developed moderate acute pancreatitis with abdominal pain and elevation of serum amylase after the procedure. Pancreatitis improved with standard therapy, thus giving a total complication rate of 1.8%.13 With the enhanced version, XCHF-BP240, our preliminary experiences in 9 cases, including 2 cases of cholangioscopy, revealed no significant complications.11

To avoid possible complications, patients are usually hospitalized for one day after the procedure and receive peri-procedural intravenous antibiotics. Drugs (gabexate mesilate, nafamostat mesilate, ulinastatin) which inhibit the activation of pancreatic enzymes are also used in Japan to minimize procedurally related pancreatitis.13 A pancreatic duct stent is sometimes placed following endoscopic procedure to prevent acute pancreatitis, especially after sphincterotomy. Standard therapy of intravenous antibiotics and pancreatic enzyme inhibitors is usually enough to treat the mild acute pancreatitis which occasionally occurs after a pancreatoscopy procedure.

RELATIVE COST Pancreatoscopes are relatively expensive instruments for special usage in the pancreatobiliary area. Comparison of prices for pancreatoscopes, video converter and the image processor in US markets are summarized in Table 20.3. CHF-BP30, FCP-9P, FCP-8P, CHFBP260 and CHF-B260 need a therapeutic duodenoscope (channel diameter 4.2 mm) as a mother scope, whereas PF-8P can be used through an ERCP catheter and can be used with a diagnostic duodenoscope. Since all pancreatoscopes are fragile, they require careful insertion procedures. Inspection of the scope before and after the procedure should be performed to find minor damage of the scope as early as possible. In the case of electronic pancreatoscopes, the deflection part is covered with only one layer of very thin rubber to make the diameter small. This is the most fragile part which needs to be checked after each use. It is also important to check that this fragile part is entirely out of the accessory channel of the mother scope when the elevator of the duodenoscope is lifted (Fig. 20.2e). In our experience, the XPF-22EY and XCHF-BP240 needed repairs of the deflection part after about 5 procedures. Even with the most careful procedure, significant maintenance costs can be expected for all miniscopes.

Imaging

Diameter (mm)

Channel (mm)

Price (US dollars)

Fiberoptic Fiberoptic Fiberoptic Fiberoptic Field sequential Field sequential Simultaneous Simultaneous

3.1 0.8 3.0 2.7 2.6 3.4 — —

1.2 None 1.2 0.75 0.5 1.2 — —

20,900 not available 23,700 23,700 not available not available 9,500 19,700

Table 20.3 Comparison of prices of pancreatoscopes and processors in US marketsa a

Prices are based on data, September 2005.

209

SECTION 2 TECHNIQUES

CONCLUSION Although the problem of suboptimal visualization has finally been resolved by development of electronic pancreatoscopes, other problems such as instrument fragility and relative large diameter remain

problematic in the search for the ideal scope.23,29 Continued research into the design of the pancreatoscope, which could improve durability and success rates, may make this technology more popular in the future.

REFERENCES 1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

11.

12.

13.

14.

210

Takekoshi T, Maruyama M, Sugiyama N. Retrograde pancreatic cholangioscopy [in Japanese]. Gastroenterol Endosc 1975; 17:678–683. Ohashi K, Murakami Y, Maruyama M, et al. Four cases of “mucous secreting” cancer of the pancreas on specific findings of the papilla Vater [in Japanese]. Prog Dig Endosc 1982; 20:348–351. Technology Committee of American Society for Gastrointestinal Endoscopy. Technology status evaluation: duodenoscope-assisted cholangiopancreatoscopy. Gastrointest Endosc 1999; 50: 943–945. Riemann JF, Kohler B. Endoscopy of the pancreatic duct: value of different endoscope types. Gastrointest Endosc 1993; 39:367–370. Junk M, Zipf A, Schoonbroodt D et al. Is pancreatoscopy of any benefit in clarifying the diagnosis of pancreatic duct lesions? Endoscopy 1998; 30:273–280. Yamao K, Ohashi K, Nakamura T et al. Efficacy of peroral pancreatoscope in the diagnosis of pancreatic diseases. Gastrointest Endosc 2003; 57:205–209. Özkan H, Saisho H, Yamaguchi T et al. Clinical usefulness of a new miniscope in the diagnosis of pancreatic disease. Gastrointest Endosc 1995; 42:480–485. Tajiri H, Kobayashi M, Niwa H, et al. Clinical application of an ultrathin pancreatoscope using a sequential video converter. Gastrointest Endosc 1993; 39:371–374. Uehara H, Nakaizumi A, Tatsuta M. Diagnosis of carcinoma in situ of the pancreas by peroral pancreatoscopy and pancreatoscopic cytology. Cancer 1997; 79:454–461. Kodama T, Sato H, Horii Y, et al. Pancreatoscopy for the next generation: development of the peroral electronic pancreatoscope system. Gastrointest Endosc 1999; 49:366–371. Kodama T, Tatsumi Y, Sato H, et al. Initial experience with a new peroral electronic pancreatoscope with an accessory channel. Gastrointest Endosc 2004; 59:895–900. Technology Committee of American Society for Gastrointestinal Endoscopy. Technology status evaluation: ultrathin endoscopes esophagogastroduodenoscopy. Gastrointest Endosc 2000; 51:786–789. Kodama T, Koshitani T, Sato H, et al. Electronic pancreatoscopy for the diagnosis of pancreatic diseases. Am J Gastroenterol 2002; 97:617–622. Telford JJ, Carr-Locke DL. The role of ERCP and pancreatoscopy in cystic and intraductal tumors. Gastrointest Endosc Clin N Am 2002; 12:747–757.

15. Yamao K, Okubo K, Sawaka A, et al. Endoluminal ultrasonography in the diagnosis of pancreatic diseases. Abdom Imaging 2003; 28:545–555. 16. Yamaguchi T, Hara T, Tsuyuguchi T, et al. Peroral pancreatoscopy in the diagnosis of mucin-producing tumors of the pancreas. Gastrointest Endosc. 2000; 52:67–73. 17. Hara T, Yamaguchi T, Ishihara T, et al. Diagnosis and patient management of intraductal papillary-mucinous tumor of the pancreas by using peroral pancreatoscopy and intraductal ultrasonography. Gastroenterology 2002; 122:34–43. 18. Kaneko T, Nakao A, Nomoto S, et al. Intraoperative pancreatoscopy with the ultrathin pancreatoscope for mucinproducing tumors of the pancreas. Arch Surg 1998; 133:263–267. 19. Kanazumi N, Nakao A, Kaneko T, et al. Surgical treatment of intraductal papillary-mucinous tumors of the pancreas. Hepatogastroenterology 2001; 48:967–971. 20. Koshitani T, Kodama T, Sato H, et al. Clinical application of the peroral electronic pancreatoscope for the investigation of intraductal mucin-hypersecreting neoplasm. Gastrointest Endosc 2000; 52:95–99. 21. Kodama T, Abe M, Sato H, et al. A case of pseudotumorous pancreatitis that presented unique pancreatoscopic findings with the peroral electronic pancreatoscope. J Gastroenterol Hepatol 2003; 18:108–111. 22. Miyakawa H, Suga T, Murashima Y, et al. The role of peroral pancreatoscopy. [in Japanese]. Endosc Dig 1993; 5:943–948. 23. Kozarek RA, Kodama T, Tatsumi Y. Direct cholangioscopy and pancreatoscopy. Gastrointest Endosc Clin N Am 2003; 13:593–607. 24. Kozarek RA. Direct pancreatoscopy in chronic pancreatitis. Dig Endosc 1990; 2:1–5. 25. Kodama T, Imamura Y, Satoh H, et al. Feasibility study using a new small electronic pancreatoscope: description of findings in chronic pancreatitis. Endoscopy 2003; 35:305–310. 26. DiMagno MJ, DiMagno EP. Chronic pancreatitis. Curr Opin Gastroenterol 2003; 19:451–457. 27. Fujita N, Noda Y, Kobayashi G, et al. Endoscopic approach to early diagnosis of pancreatic cancer. Pancreas 2004; 28:279–281. 28. Myung SJ, Kim MH, Kim YS, et al. Telomerase activity in pure pancreatic juice for diagnosis of pancreatic cancer may be complementary to K-ras mutation. Gastrointest Endosc 2000; 51:708–713. 29. Kodama T, Tatsumi Y, Kozarek RA, et al. Direct pancreatoscopy. Endoscopy 2002; 34:653–660.

SECTION 2

Chapter

21

TECHNIQUES

Cholangioscopy Peter B. Kelsey

INTRODUCTION The prospect of visualizing the biliary tree during ERCP has allured gastroenterologists for decades.1 Significant mechanical challenges have resulted in a design evolution of both rigid and flexible endoscopes employing fiberoptic and video technology. The nomenclature has likewise evolved through a spectrum of descriptive terms including cholangioscopy, cholangioscopy, duodenoscope-assisted cholangiopancreatoscopy, and peroral cholangioscopy. The duct can now be accessed through a variety of approaches: percutaneously through a transhepatic route, through a choledochotomy, or the cystic duct created intraoperatively, or through the papilla of Vater via a duodenoscope. This chapter will specifically review the duodenoscope assisted approach to cholangioscopy. In this two endoscope system, the supporting duodenoscope and the cholangioscope are often referred to as the mother and baby scope, respectively.

DESCRIPTION OF THE TECHNIQUE Preprocedure room set-up If cholangioscopy is to become a truly meaningful adjunct for the interventionalist, the equipment needs to be readily available as the indications arise. A giant stone may be encountered that is simply too large to fragment by standard techniques or a stricture suspicious for malignancy may require direct visualization for tissue sampling. Under these circumstances, the ability to perform cholangioscopy as an adjunct to ERCP may both clarify the diagnosis, and facilitate appropriate therapy. The result may both optimize patient care quality and minimize the need for reintervention. For many years, prototype cholangioscopes have been sited in various academic institutions around the world. Currently, in the United States, the limited assortment of cholangioscopes available for purchase is listed in Table 21.1. In general, the smaller the outer diameter of the cholangioscope, the greater the maneuverability within the bile duct. The smaller size, however, leaves less room for important features such as a sufficiently large working channel. The optimal ERCP suite design places the cholangioscope, its power supply, and accessories in close proximity to the endoscopist. Because of the intimate spatial working relationships between the mother and baby scope, the cholangioscope components are set up on or adjacent to the ERCP processor cart. These components include the light generator and image processor as well as the flushing and suctioning equipment. Depending on the manufacturer and the model, the light source, image processing hardware and air/fluid pump are available either as individual components or combined in a single unit (Fig. 21.1).

Likewise strategic placement of the monitors is critical to permit simultaneous viewing of the video images from the mother scope, the baby scope and fluoroscopic unit during cholangioscopy. Ideally, the three monitors are clustered and mounted at eye level in front of the endoscopist. In new unit designs, these three monitors are mounted on articulating arms to maximize the operators’ comfort and ergonomics. Toggle switches or footpedals permit easy switching between other video output sources such as EUS, or a microscopy unit. Extra monitors are positioned for the assisting staff. Digital recording of the cholangioscopic exam provides a permanent record of the exam and most importantly permits post-procedure review of the findings (Box 21.1). A variety of accessories are used during routine cholangioscopy. A special adapter is attached to the opening of the mother scope’s instrument channel through which the cholangioscope is passed. This adapter is designed to prevent crimping of the baby scope as it is maneuvered during the procedure. As copious flushing and suctioning is routine during cholangioscopy, the saline irrigant, connector tubing, stopcocks, and syringes need to be available. Some processors are equipped with irrigation and suctioning components. Finally, there are a variety of accessories specific to cholangioscopy such as cytology brushes, biopsies forceps, snares, and electrohydraulic lithotripsy accessories that need to be organized and readily available.

TECHNIQUE: DIAGNOSTIC The step up from basic interventional ERCP to cholangioscopy requires the development of several new skills. One major challenge of cholangioscopy is the coordination and handling of the twoendoscope system using either the single or the two operator technique. The two person technique requires two experienced endoscopists to be present during the exam, one to handle the mother scope and the other to operate the baby scope with all of its accessories. Alternatively, the single operator technique requires a single interventionalist who manages both endoscopes. The endoscopist’s left hand is used to control the mother duodenoscope scope. The baby scope is secured to the endoscopist by a breast plate (see Fig. 21.2). The endoscopist’s right hand is then free to manage the controls and accessories of both the baby scope as well as the mother scope. The single operator technique has several advantages over the dual operator technique. First, cholangioscopy requires a carefully choreographed coordination of movement between the two endoscopes to both successfully maneuver the baby scope and to minimize the likelihood of damage due to crimping at its insertion into the mother scope. This coordination is more easily performed by a single person than by two trying to synchronize their motions. Second, obligating two physicians to be present during an entire exam is an inefficient use of manpower, especially when the exam can be performed 211

SECTION 2 TECHNIQUES

Feature

Olympus

Pentax

Pentax

Model

CHF BP 30

FCP—9N

FCP—8P

Working Channel

1.2 mm

1.2

0.75

Guidewire size

0.035 in

0.035

0.025

Outer Diameter

3.4 mm

3.1

2.8

“Mother Scope” Channel Diameter

4.2 mm

4.2

3.8

Field of View

90°

90°

90°

Depth of Field

1-50

1-50

1-50

Tip Deflection

160° up/ 130° down

160°/130°

160°/130°

Working Length

187 cm

190

190

Table 21.1 Cholangioscopes available in the US Fig. 21.2 The baby scope secured to the endoscopist by a breast plate.

mother scope and can be immobilized to a breastplate or waistband strapped to the endoscopist.

CANNULATION

Fig. 21.1

Cholangioscopy set-up for routine use.

BOX 21.1 ROOM SET-UP REQUIREMENTS FOR CHOLANGIOSCOPY Cholangioscope Light source and video Processor Breastplate (for single operator technique) Accessories Cytology brush Biopsy forceps Electrohydraulic Lithotripsy EHL power source EHL probes Monitors (2) for cholangioscopic image

efficiently by one physician alone. Finally, since the cholangioscope functions more as a catheter than as a true endoscope, the baby scope handle remains essentially motionless during the cholangioscopy. Most of the steering and maneuvering of the baby scope actually comes from the mother. Since the baby scope is not designed to tolerate torque, its position should remain fixed relative to the 212

There are three considerations when cannulating the ampulla; the need for a papillotomy, the need for guidewire assistance, and the actual maneuvering required to advance the baby scope up the bile duct without injury to the instrument or the patient. First, in almost all cases, the presence of a papillotomy greatly facilitates the ease of the exam. In many instances, however, a papillotomy will have already been performed before the decision has been made to refer the patient for cholangioscopy. The patient with giant, recalcitrant choledocholithiasis has often already undergone one or more failed prior attempts during which a papillotomy has been performed to either remove smaller debris or to permit the use of balloons or lithotripsy catheters. Cholangioscopy has been successfully performed following balloon ampullary dilation without papillotomy.2 Likewise the development of the ultrathin caliber endoscopes permits scope passage through supporting catheters without the need for a sphincterotomy.3 These ultrathin scopes, still not widely used, do not have an instrument channel for tissue sampling or for interventions. The papilla can, however, be dilated using either catheter or balloon dilators to permit passage of the larger cholangioscopes over a guidewire into the biliary tree. Balloon dilation of the papilla carries a defined risk of pancreatitis. Cannulation can be performed either over a guidewire or free hand. The guidewire technique is recommended until the endoscopist becomes experienced with cholangioscopy. Once the guidewire is passed up the bile duct, the cholangioscope is back-loaded over the wire using caution not to damage the channel as it angles and exits near the scope handle. A straw or other similar device can be used to intercept the advancing wire to safely deflect the wire tip out of the scope. The wire now acts as a rail over which the cholangioscope can be passed out from the mother scope and up through the papillotomy. As the cholangioscope approaches the papilla, the assistant provides gentle traction on the guidewire to pull the baby scope upward and into the papillary orifice. This upward deflection minimizes the need to raise the elevator. It is the lifting up of the elevator that causes the most damage to these fragile scopes either by tearing

Chapter 21 Cholangioscopy

the bending rubber at the distal end of the insertion tube or by actually crimping the insertion tube. Once the baby scope tip penetrates the ampullary orifice, it can be further advanced up the bile duct by gently tugging back on the mother scope. There is often a soft pop as the baby scope moves up the biliary tree. The baby scope can then be advanced up the bile duct in one to two centimeter increments followed by a gentle lifting of the elevator. This sequence of motions, similar to the technique used to advance a biliary stent, is repeated until the scope is in a desired and secured position. The free hand cannulation technique can be accomplished, in most cases, by first positioning the mother scope close to the ampulla. The baby scope tip is then advanced through the mother scope elevator. With the tip turned upward, and using the mother scope elevator, the baby scope is lifted up to the papillotomy site. The large dial of the mother scope is turned fully towards the endoscopist which lifts the tip of the mother scope upward and introduces the baby scope into the papilla. Once the tip of the baby scope is fully committed into the papillary orifice, a gentle tugging back on the mother scope, pulling it slightly outward from the patient’s mouth, will often pop the baby scope up through the papillary region and into the free biliary lumen. Fluoroscopy is employed during cannulation to observe both the angle of the cholangioscope’s deflecting tip and the trajectory of its insertion tube as it passes up the bile duct. The cholangioscope’s deflecting tip should not knuckle or bow as it heads up the bile duct. Ideally, the trajectory of the tip and the insertion tube should be straight and should point towards the bifurcation. This will lessen the likelihood of inadvertent cannulation of the pancreatic duct. Fluoroscopic observation is also used to guide the depth of the cholangioscope’s insertion.

Preparing the bile duct for observation With the cholangioscope positioned in the biliary system and the guidewire removed, the lumen of the bile duct comes into view. This view is often obscured by bile, mucus, and debris. Clearing the duct of this debris is necessary for an accurate diagnostic exam and usually requires several minutes of irrigation using a saline lavage. Irrigation with volumes from 5 to 25 cc saline can be used with each flush, depending on the duct diameter. Because of the small caliber of the cholangioscope’s working channel, the viscosity of bile, and the frequent presence of small particles of stone and other debris, suctioning of the irrigant from the duct is a tedious but necessary process. Lavaging the bile duct until it is clear facilitates optimal visualization and is necessary prior to any therapeutic maneuvers. During this cleaning process, fluid and debris tend to accumulate in the intestinal lumen and track up into the stomach. Comparing the amount of lavage fluid instilled to that amount suctioned will help minimize the aspiration risk. When this difference approaches 100 cc, the endoscopist might consider removal of the baby scope and withdrawing the mother scope into the stomach to aspirate the fluid that has accumulated there. Constant suctioning of this fluid from the duodenum should be performed through the mother scope during the procedure. This is a counter-intuitive maneuver for most experienced interventionalists who are trained to constantly insufflate the duodenal lumen with air to maintain good luminal visualization.

Maneuvering the cholangioscope Once positioned in the bile duct and with the guidewire removed, inspection can begin. Optimal visualization occurs under an aqueous

medium and thus saline is constantly pulsed or infused during the procedure. Sterile water can likewise be used safely.4 The amount of irrigant used should be sufficient to permit clear visualization carefully avoiding high pressure injections and excess accumulation of irrigant in the intestinal lumen. The cholangioscope is advanced up the bile duct with the same technique used to advance a biliary stent. With the elevator lowered, the cholangioscope is advanced 2–3 cm. The elevator is raised slightly and the endoscopist’s left thumb turns the mother scope’s large dial towards the endoscopist lifting up the tip of the mother scope towards the ampulla, thus pushing the baby scope up the bile duct. The elevator is then lowered, the large dial turned away, and the process is repeated. The challenge at this point is to keep the baby scope centered in the duct lumen, permitting good visualization. The baby scope tends to slide along the bile duct wall, smearing the mucosa across the viewing lens, thus obscuring the view. The crux of cholangioscopy is the challenge of maintaining a centered position of the baby scope within the bile duct. The insertion tube of the baby scope is not designed to respond to torque, and thus little control actually comes from manipulating the baby scope itself. Most of the baby scope control comes from the handling of the mother scope. Several principles may help the beginner cholangioscopist. Once the cholangioscope is maneuvered up the bile duct, fine tuning of its position lengthwise in the duct is best achieved by slight movements of the mother scope up and down the duodenum past the ampulla. These position changes will similarly move the cholangioscope up and down the bile duct. Lateral movements within the bile duct are more difficult. Rolling and torquing the mother scope and use of the duodenoscope’s small dial will translate into some baby scope lateral movement. Pulling or pushing on the mother scope will affect how straight or curved the baby scope lies within the bile duct and will alter its orientation. The baby scope tip deflection dial offers additional positioning changes.

INDICATIONS FOR CHOLANGIOSCOPY The primary indications for cholangioscopy include the evaluation and management of biliary strictures, filling defects, and difficult choledocholithiasis (Table 21.2).

Evaluation of bile duct lesions Conventional ERCP has an excellent track record in the diagnosis and management of well-defined bile duct abnormalities such as choledocholithiasis and bile leaks. This technique has fared less well in the accurate diagnosis of two, not so well-defined classes of bile duct lesions: biliary strictures and biliary filling defects. Though there is some overlap between these two findings, it may be useful to consider them separately. A filling defect relates to

ERCP Diagnosis

Cholangioscopy offers

Strictures

Improved diagnostic accuracy Tissue acquisition under visualization

Filling defects

Improved diagnostic accuracy Definitive therapy

Stones, refractory

EHL Duct clearance

Table 21.2 Indications for cholangioscopy 213

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Fig. 21.3

Intraluminal filling defects due to stones.

the fluoroscopic appearance of something that actually lies within the bile duct lumen such as a stone or a polypoid tumor. Conversely, a stricture implies a narrowing of the duct lumen due to either thickening of the wall or compression from extrinsic pathology. The increased wall thickening can be intrinsic to the wall such as with a cholangiocarcinoma and might therefore have some associated mucosal defects that could be detected by direct visualization. Compression, on the other hand, due to extrinsic disease, such as nodal metastasis may result in a narrowing of the lumen, but the epithelial lining of the bile duct wall in the region of the stricture may retain a normal appearance. Cholangiocarcinoma, for example, can spread through the biliary tree in the submucosal layers and obstruct by compression. The overlying mucosa, however, may have a completely unremarkable appearance. It has now been clearly established that cholangioscopy can improve the accuracy in the diagnosis of biliary filling defects.5–7 One recent experience examined the impact of cholangioscopy on the diagnostic accuracy of ERCP when there was uncertainty in the ERCP diagnosis.8 Patients were excluded if they had obvious stone disease or classic biliary obstruction due to malignancy in the head of the pancreas. In this study, 91 consecutive patients were evaluated by ERCP supplemented by biopsy/brush cytology when indicated. There were 76 strictures and 21 filling defects in the study group. Of the patients with the 21 filling defects, ERCP with biopsy or brush cytology was able to correctly identify the 8 malignant lesions and the 9 benign tumors. ERCP did not, however, correctly diagnose the four cases of stone disease. In these patients, the stones were adherent to the bile duct wall and had the appearance of a mass. Cholangioscopy, on the other hand was able to make the correct diagnosis using direct visualization alone in all 21 patients. The four patients with stone disease were easily identified and treated with stone removal (Fig. 21.3). While the cholangioscopic differentiation between stone and tissue appears straightforward, the same is not true in the ability to differentiate malignant from benign strictures on the basis of direct visualization alone. Early cholangioscopic experience reported morphologic characteristics that claimed to distinguish malignant from benign tissue with an accuracy that approached 95%.9 Several features were identified as being accurate predictors of malignancy including tumor neovascularization, a dense papillary pattern, and friable nodularity. It was observed that bile duct adenocarcinomas had three patterns: nodular, papillary, and infiltrative. Nodular lesions were bulky and eccentric with an overlying friable mucosa (Fig. 21.4). There was often neovascularization with tissue friability and oozing. The papillary type (Fig. 21.5) was identified by a high density pattern of papilla or fish egg type mucosa. There is often luminal mucin, and blood obscuring the visual field. The third type 214

Fig. 21.4

Nodular lesion with friable mucosa.

Fig. 21.5

Papillary mucinous epithelium.

of bile duct adenocarcinoma is the infiltrating type. This is the most difficult to diagnose because of the paucity of specific cholangioscopic characteristics. The overlying mucosa is bland and whitish with minimal neovascularization. The authors described several other less common bile duct tumors including biliary papillomatosis, mucin-hypersecreting cholangiocarcinoma, and biliary cyst adenocarcinoma. Biliary papillomatosis looks similar to the papillary adenocarcinoma except that it is a multifocal disease with areas of normal intervening mucosa. The mucin-hypersecreting cholangiocarcinoma is similar to the papillary type adenocarcinoma except that according to the authors, the biliary ducts may be dilated and mucin filled. These cholangioscopic criteria for malignancy were tested prospectively on 76 patients with biliary strictures of unknown type and compared to the accuracy of ERCP with biopsy alone. In this study, ERCP with tissue sampling had a sensitivity of 58% and a specificity of 100% (Fig. 21.6). The addition of cholangioscopy to this group of patients did increase the sensitivity to100% but dropped the specificity to 87%. The loss of specificity was due to the incorrect diagnosis of malignancy in 5 patients on the basis of the cholangioscopic appearance of neovascularization and the presence of a tumor vessel. These five false positives were found instead to have chronic pancreatitis in two patients and one patient each with primary sclerosing cholangitis, autoimmune pancreatitis, and a peri-biliary cyst. Another potential advantage of cholangioscopy in the evaluation of biliary strictures is the opportunity to obtain pathologic material under direct observation. Brushings and biopsy forceps can be

Chapter 21 Cholangioscopy

Fig. 21.6

Tissue sampling under direct visualization.

steered directly onto the area of suspicion and the sample obtained under visual guidance. Whether this approach actually increases the yield of correct diagnosis has not been studied. Though it may seem advantageous to obtain tissue in this fashion, there are several recognized difficulties. First, is the issue of access. Negotiating the angulation and turns of the bifurcation and the small biliary radicals remains a challenge given the limitation of maneuverability and steerability of the current cholangioscopes. Once in a tight space, it may not be possible to deflect the scope tip to obtain a specimen from abnormal appearing tissue off to one side. And finally, the cups on the biopsy forceps are quite small, approximately 1 mm in diameter and thus the tissue yield is likewise small and frequently insufficient when biopsying hard or fibrotic tissue. Brush cytology, however, is often feasible. This can be performed by removing the polyethylene sleeve from any inexpensive, disposable brush, and passing the unsheathed brush through the cholangioscope’s channel. After obtaining the specimen, the brush can be withdrawn 1–2 cm inside the baby scope. With the baby scope then removed from the duodenoscope, the brush is advanced out of the cholangioscope’s tip and the specimen swiped on to frosted slides as per routine.

Electrohydraulic lithotripsy Fragmentation of giant or recalcitrant stones is one of the primary indications for interventional cholangioscopy. Candidate stones are usually too large to be trapped in a mechanical lithotripsy basket or are adherent to the bile duct wall and thus can not be easily manipulated. In these circumstances, fragmentation using electrohydraulic lithotripsy (EHL) is an efficient and highly successful technique. Traditionally, endoscopists have been resigned to longterm stenting of large, recalcitrant stones. It has been recently demonstrated, however, that when compared to stone removal using EHL, long-term stenting is associated with higher long-term complications such as cholangitis,10 and thus most patients with such stone burden should be considered for definitive fragmentation therapy. EHL was originally designed as an industrial mining tool. The modification for endoscopy employs a fiber with two embedded electrodes. A power generator delivers a high voltage electrical

current creating a spark across the two electrodes at the tip of the fiber. High frequency discharges cause rapid expansion of the fluidstone interface generating shock waves that fragment the stone. This technique has been successfully applied using percutaneous, surgical and transampullary routes to the bile duct using either cholangioscopic or fluoroscopic guidance. To perform EHL, the cholangioscope must be first positioned in front of the target stone. Achieving a satisfactory position is critical to the safe deployment of the probe. When the EHL probe projects from the cholangioscope, it must hit directly on the target stone and not touch or travel adjacent to the biliary epithelium. In addition, the contact interface between the probe and the stone must be in an aqueous environment for the shock wave to be transmitted and effect fragmentation. In patients with a capacious bile duct and a generous papillotomy, the bile duct may drain too rapidly to perform EHL. The patient must then be rolled to place the biliary tree in a dependent orientation. Before firing, the probe tip should be in close apposition to the stone. The duct is lavaged to sweep away fragmented debris to maintain good visualization. The probe should be aimed at a single target on the stone, chipping away at a focus until the stone cleaves. Often the outer coating of a stone is more durable and requires more EHL pulses. Once chipped, continued firing at the same spot rapidly enlarges the defect and fragments the stone. As the target stone mass is reduced in size, the cholangioscope is advanced up the duct to the next target. Fragmentation is then repeated until all of the target stones are fragmented or the visual field is obscured by debris. It is common to overestimate the degree of fragmentation that has occurred during a round of EHL discharges. With the cholangioscope removed from the bile duct, the stone fragments are swept out using standard balloon and basket techniques. Often, by simply fragmenting the lower stones in a packed duct, the remaining stones can then be more easily removed by standard maneuvers. The second round of EHL, if needed, proceeds more quickly as the duct is less tightly packed and there is more room to maneuver the cholangioscope. Once the bile duct has been cleared of debris and stones, the baby scope can be reintroduced into the bile duct to check for large retained fragments and for unsuspected strictures. The success of EHL has been reported in a number of series.11–13 In one large study, the power generator (Lithotripter Elgin, Il) was configured at settings of 100 watts, a frequency of 6 shots per second and 8 shots per pulse.13 In the management of recalcitrant stone disease that has failed standard ERCP techniques, cholangioscopic directed EHL is 90–100% successful in complete stone eradication.14 While the number of procedures required to achieve this success has ranged broadly from 1 to 13 exams, the experienced cholangioscopists can expect to achieve complete duct clearance in one exam of under 2 hours’ duration in the majority of patients.13

Cholangioscopy without fluoroscopy Occasionally, urgent biliary exploration is indicated when fluoroscopy is either unavailable or not practical. The ability to examine the bile duct without fluoroscopy has proven useful in three clinical situations: in morbidly obese patients whose features may not conform to standard fluoroscopy units, in patients during their first trimester of pregnancy and finally in those patients too critically ill to be transported to a fluoroscopy unit. The technique of cholangioscopy without fluoroscopy requires few modifications from the technique described above. Routine biliary cannulation is performed using a papillotome and a wire. 215

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Once a duct has been deeply cannulated, the guidewire is removed. The observation of bile tracking up the lumen of the papillotome as the guidewire is withdrawn confirms the position of the papillotome in the bile duct. The guidewire is then advanced back up through the papillotome into the biliary system. Sphincterotomy is performed and the papillotome is removed leaving the wire in the biliary tree. The cholangioscope is passed down through the mother scope over the guidewire and a wire-guided cannulation of the bile duct is performed. Once the baby scope is positioned in the region of the bifurcation, the guidewire is removed. Bile and debris can then be flushed from the duct allowing inspection of the biliary tree. Several important interventional manipulations of the biliary tree can be performed without the use of fluoroscopy. Small stones can be removed under direct visualization using either a balloon or a wire-guided basket. Large stones are usually stented, to be more definitively managed at a later date when the patient has stabilized. Cholangioscopic directed EHL without the use of fluoroscopic assistance has not yet been reported, but may become feasible as baby scope technology evolves. Mass lesions encountered during cholangioscopy without fluoroscopy can be brushed or biopsied under direct visualization. Stenting of strictures or obstructing lesions in the common hepatic duct or common bile duct requires a modification from the standard stenting procedure. In determining the appropriate stent length, it is necessary to first pass the baby scope above the level of the obstruction. A guidewire is passed into the free space above the obstruction. The baby scope is slowly withdrawn down the length of the bile duct to the level of the ampulla, carefully measuring this length as it is pulled out of the instrument channel of the mother scope; this defines the appropriate stent length. With the guidewire positioned above the stricture, the cholangioscope is removed, and the plastic biliary stent is passed up the guidewire. Direct visualization of the guidewire is lost as the stent passes out of the working channel of the mother scope. Care must be taken at this point to prevent accident removal of the guidewire to a level below the obstructing lesion. The observation at this point of bile flow through the stent is reassuring of correct stent placement although this finding can also be occasionally observed if the stent has been accidentally placed up the cystic duct (Fig. 21.7).

Therapy of malignant bile duct lesions There is increasing interest in the targeting of therapy against a variety of malignant and pre-malignant bile duct lesions using cholangioscopic assistance. Photodynamic therapy of cholangiocarcinoma has been performed by both the percutaneous15,16 and per-oral route.17 The technique appears safe with minimal complications but its long-term clinical effectiveness remains to be evaluated in multicentered trials. In general, these patients still require stenting to maintain duct patency and the goal of the PDT therapy is likely palliative rather than curative. Biliary papillomatosis is an uncommon condition of multifocal papillary lesions of the bile duct. Patients can present with obstruction and may require transplantation. Transhepatic cholangioscopy using a variety of ablative therapies has been successful in controlling disease progression.18,19

216

Fig. 21.7

Cholangioscopy without fluoroscopy.

CONTRAINDICATIONS TO CHOLANGIOSCOPY Cholangioscopy can be performed in most situations where ERCP is indicated. While there are no absolute contraindications to cholangioscopy, there are several noteworthy areas of caution. Coagulopathic patients may not safely undergo sphincterotomy, thus preventing passage of many of the currently employed cholangioscopes. The risk of bleeding due to EHL induced tissue injury might be increased. In patients with ascending cholangitis, the risk of inducing bacteremia during cholangioscopy might be increased.

COMPLICATIONS The reported complications of cholangioscopy include bacteremia, aspiration, bleeding, and pancreatitis. Bacteremia as determined by serial blood cultures in the minutes following cholangioscopy can be demonstrated to occur in 15% of patients, but cholangitis is clinically relevant in only a minority of these situations.20 Prophylactic antibiotics do not appear to be of benefit following cholangioscopy and stone removal in the surgical setting.21 Bacteremia can result from over-distention of the biliary tree during irrigation. This may be more likely if the ampulla forms a tight seal around the insertion tube of the cholangioscope, preventing the venting of excess irrigant into the duodenum. As a rule, irrigation can be safely performed with a volume equal to or less than that amount of bile aspirated from the obstructed ductal system. Patients suspected of having cholangitis should receive peri-procedure antibiotics. Aspiration occurs as a consequence of the irrigating fluid that accumulates in the stomach.22 Aspiration of these contents can be prevented by frequent suctioning of the gastric contents The reported complications following EHL stone fragmentation during cholangioscopy include cholangitis, bleeding, pancreatitis,23 and perforation. Self-limited bleeding occurs when the EHL pulses are discharged in close apposi-

Chapter 21 Cholangioscopy

tion to the bile duct wall.24 There are no reports of uncontrolled bleeding. Bile duct leaks due to EHL injury have been reported. Perforation can occur at either the papillotomy site or at the site of an errant EHL discharge.

RELATIVE COST There are no published cost comparisons between the technique of cholangioscopy and alternative techniques.

SUMMARY Cholangioscopy is an important adjunct to interventional ERCP. It has been documented to improve the diagnostic accuracy in the assessment of biliary strictures. Cholangioscopy in conjunction with electrohydraulic lithotripsy can fragment and eradicate stones refractory to standard interventional ERCP techniques. There are few complications.

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Kozarek RA. Direct cholangioscopy and pancreatoscopy at time of endoscopic retrograde cholangiopancreatography. Am J Gastroenterol 1988; 83:55–57. Minami A, Nakatsu T, Uchida N, et al. Papillary dilation vs sphincterotomy in endoscopic removal of bile duct stones. A randomized trial with manometric function. Dig Dis Sci 1995; 40:2550–2554. Soda K, Shitou K, Yoshida Y, et al. Peroral cholangioscopy using new fine-caliber flexible scope for detailed examination without papillotomy. Gastrointest Endosc 1996; 43:233–238. Sheen-Chen SM, Chou FF. Is sterile water irrigation safe during postoperative cholangioscopy? A prospective trial. Eur J Surg 1996; 162:801–804. Siddique I, Galati J, Ankoma-Sey V, et al. The role of cholangioscopy in the diagnosis and management of biliary tract diseases. Gastrointest Endosc 1999; 50:67–73. Seo DW, Kim MH, Lee SK, et al. Usefulness of cholangioscopy in patients with focal stricture of the intrahepatic duct unrelated to intrahepatic stones. Gastrointest Endosc 1999; 49:204–209. Seo DW, Lee SK, Yoo KS, et al. Cholangioscopic findings in bile duct tumors. Gastrointest Endosc 2000; 52:630–634. Fukuda Y, Tsuyuguchi T, Sakai Y, et al. Diagnostic utility of peroral cholangioscopy for various bile-duct lesions. Gastrointest Endosc 2005; 62:374–382. Nimura Y, Kamiya J, Hayakawa N, et al. Cholangioscopic differentiation of biliary strictures and polyps. Endoscopy 1989; 21 Suppl 1:351–356. Hui CK, Lai KC, Ng M, et al. Retained common bile duct stones: a comparison between biliary stenting and complete clearance of stones by electrohydraulic lithotripsy. Aliment Pharmacol Ther 2003; 17:289–296. Adamek HE, Maier M, Jakobs R, et al. Management of retained bile duct stones: a prospective open trial comparing extracorporeal and intracorporeal lithotripsy. Gastrointest Endosc 1996; 44:40–47. Binmoeller KF, Bruckner M, Thonke F, et al. Treatment of difficult bile duct stones using mechanical, electrohydraulic and extracorporeal shock wave lithotripsy. Endoscopy 1993; 25:201–206.

13. Farrell JJ, Bounds BC, Al-Shalabi S, et al. Single-operator duodenoscope-assisted cholangioscopy is an effective alternative in the management of choledocholithiasis not removed by conventional methods, including mechanical lithotripsy. Endoscopy 2005; 37:542–547. 14. Arya N, Nelles SE, Haber GB, et al. Electrohydraulic lithotripsy in 111 patients: a safe and effective therapy for difficult bile duct stones. Am J Gastroenterol 2004; 99:2330–2334. 15. Shim CS, Moon JH, Cho YD, et al. The role of extracorporeal shock wave lithotripsy combined with endoscopic management of impacted cystic duct stones in patients with high surgical risk. Hepatogastroenterology 2005; 52:1026–1029. 16. Wiedmann MW, Caca K. General principles of photodynamic therapy (PDT) and gastrointestinal applications. Curr Pharm Biotechnol 2004; 5:397–408. 17. Harewood GC, Baron TH, Rumalla A, et al. Pilot study to assess patient outcomes following endoscopic application of photodynamic therapy for advanced cholangiocarcinoma. J Gastroenterol Hepatol 2005; 20:415–420. 18. Gunven P, Gorsetman J, Ohlsen H, et al. Six-year recurrence free survival after intraluminal iridium-192 therapy of human bilobar biliary papillomatosis. A case report. Cancer 2000; 89:69–73. 19. Meng WC, Lau WY, Choi CL, et al. Laser therapy for multiple biliary papillomatosis via cholangioscopy. Aust N Z J Surg 1997; 67:664–666. 20. Chen MF, Jan YY. Bacteremia following postoperative choledochofiberscopy—a prospective study. Hepatogastroenterology 1996; 43:586–589. 21. Sheen-Chen SM, Chou FF. Postoperative cholangioscopy: is routine antibiotic prophylaxis necessary?—A prospective randomized study. Surgery 1994; 115:170–175. 22. Schebesta AG, Sporr D, O’Leary J, et al. Gastric aspiration associated with operative cholangioscopy. Anaesth Intensive Care 1983; 11:257–258. 23. Sheen-Chen SM, Eng HL. Acute pancreatitis following choledochoscopic stone extraction for hepatolithiasis. Med Sci Monit 2003; 9:CS13–CS15. 24. Fan ST, Choi TK, Wong J. Electrohydraulic lithotripsy for biliary stones. Aust N Z J Surg 1989; 59:217–221.

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TECHNIQUES

ERCP in Children Victor L. Fox

INTRODUCTION Endoscopic retrograde cholangiopancreatography (ERCP) was introduced into pediatric medicine in the mid to late 1970s following initial experience in adult patients. It is now routinely used for the diagnosis and treatment of biliary tract and pancreatic diseases in children who are referred to major medical centers worldwide.1–3 Although expertise remains concentrated among endoscopists with advanced training in adult medicine, pediatric specialists collaborate closely in patient selection, in pre- and post-procedural management, and in the periodic appraisal of the role of ERCP in current pediatric practice.4 In high volume tertiary pediatric referral centers, ERCP is sometimes performed by expert pediatric endoscopists working alone or in consultation with adult medicine colleagues. Major differences between adult and pediatric ERCP relate to alternative approaches to patient preparation and sedation, to technical constraints of equipment that is not optimally designed for small children and infants, and to the rarity of biliary and pancreatic pathology in children.

DESCRIPTION OF TECHNIQUE Procedure setting In modern practice, most patients undergo ERCP with the potential for immediate therapeutic intervention. Therefore, the setting in which the procedure is conducted should include appropriate equipment and staff to proceed with available therapies and support for complications that might arise. Although interventional ERCP can be performed safely on an ambulatory basis in children, overnight hospital admission for observation is often advisable given the risk for post-procedure pancreatitis, and rarer complications of bleeding, infection, or cardiorespiratory compromise. Immediate access to subspecialty consultation by pediatric anesthesiologists, surgeons, and radiologists is essential to provide optimal and comprehensive team management. Ideally, recovery nurses with experience in postoperative recognition and management of complications that occur in children should be available to expedite supportive interventions.

Endoscopist Pediatric ERCP is best performed by an endoscopist with advanced technical skills and sufficient breadth of clinical experience to achieve an optimal outcome for the child. This may require a collaborative effort involving both adult and pediatric medicine specialists. Therapeutic ERCP requires that an endoscopist achieve selective deep cannulation of the desired (biliary or pancreatic) duct with >90% success to enable essential interventions including dilation,

stent placement, sphincterotomy, and stone extraction. Since experience with >200 cases is required by the average trainee to achieve this rate of technical success5 and the volume of pediatric cases is relatively small even in tertiary care facilities, pediatric specialists usually require either supplemental training with adult patients or a very long training period to achieve initial competence. The volume of cases required to maintain competence is less well studied in endoscopists specializing in pediatrics than those specializing in adults. Complication rates in the latter have been shown to correlate with case volume and complexity.6 While advanced endoscopic skills reside most often within adult medicine centers of excellence, technical skill alone does not benefit children in the absence of specialized clinical knowledge and experience, since technical success does not necessarily equate with optimal clinical outcome. Both adult and pediatric medicine trained endoscopists must consider these factors and the availability of alternative management options before embarking on ERCP in pediatric patients.

Sedation Most pediatric gastroenterologists prefer general anesthesia or deep sedation for technically challenging procedures in children. There has also been a trend toward more frequent use of deep sedation in adults undergoing particularly uncomfortable or lengthy endoscopic procedures. Although ERCP may be performed successfully with intravenous (IV) sedation in children, especially in cooperative adolescents, general anesthesia with endotracheal intubation affords safer airway management with assured analgesia and hypnosis for as much time as is necessary to complete a potentially lengthy or difficult procedure.

Fluoroscopy Fluoroscopy for pediatric ERCP may be performed using a fixed table in a dedicated fluoroscopy suite or a portable C-arm in a separate procedure room. The advantages of the C-arm device are portability, lower cost, and easier oblique imaging. Modern digital devices provide excellent image quality. The x-ray equipment should be adjusted to accommodate the smaller body of a young child and reduce the radiation dose rate. Shielding of reproductive organs is important and should be performed in all patients. Good fluoroscopic technique by the examiner can minimize radiation exposure to the child and to personnel (see also Chapter 3). The following rules or principles will help advance this goal: (1) position the child so that the beam takes the shortest distance through the body, i.e. avoid unnecessary oblique projection; (2) position the image intensifier or receptor above the patient; (3) minimize the distance of the intensifier and maximize the distance of the x-ray tube to the child’s body; (4) use the least magnification necessary and utilize field collimators to focus on areas of interest; (5) avoid the use of a grid; (6) minimize beam-on time and use the slowest pulse rates that produce 219

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acceptable imaging for a given task. The assistance of a radiation technologist with pediatric experience for equipment set-up and the availability of a radiologist with pediatric training for consultation can be very important in achieving the goals outlined above. Either low osmolar, non-ionic, or high osmolar water soluble contrast media in the range of 150 to 300 mg per ml may be used.

Supplemental medications Drug dosing for children is usually based on units per kilogram body weight ranging up to maximum adult doses. In addition to endocarditis prophylaxis, antibiotics are generally used in the setting of high-grade biliary or pancreatic duct obstruction, biliary or pancreatic duct disruption, and pancreatic pseudocyst. Ampicillin/sulbactam (100–200 mg/kg/d IV divided every 6 hours, maximum 4 grams sulbactam/d) or a broad spectrum cephalosporin such as cefazolin (50–100 mg/kg/d IV divided every 8 hours, maximum 6 grams/d), or a fluoroquinolone such as ciprofloxacin (20–30 mg/kg/d IV divided every 12 hours, maximum 800 mg/d) are usually adequate. Intravenous glucagon can be used to briefly reduce duodenal contractions during cannulation. A dose of 0.5 mg IV is appropriate for most ages and can be repeated. Intravenous secretin 0.2 mcg/kg may be used to facilitate successful cannulation of the minor papilla.

Endoscopic equipment Children of all ages and sizes, including full-term neonates, can undergo diagnostic and therapeutic ERCP using duodenoscopes that are commercially available. Standard diagnostic duodenoscopes with insertion tube diameters in the range of 11–12 mm can be used effectively in children older than 2 years and with difficulty between 1–2 years of age.7 These endoscopes generally have operating channels that will accommodate catheters and stents up to 7–8 Fr, which is adequate for most interventions. While “therapeutic” duodenoscopes containing operating channels in excess of 4 mm are needed to place 10 Fr stents, such large endoprostheses are rarely needed in young children. These larger endoscopes are easily used in adolescents. Neonates and infants require a small diameter instrument in the range of 7–8 mm that will pass easily through the pylorus and allow effective positioning of the tip adjacent to the major papilla.8 Currently, only two duodenoscopes are available specifically for use in small infants: the PJF 160 (Olympus America, Inc Lehigh Valley, PA) and the ED-2370K (Pentax Medical Company, Montvale, NJ). Both endoscopes have a maximum distal tip diameter of approximately 7.5 mm, an operating channel diameter of approximately 2.0 mm, and an elevator. Most diagnostic and therapeutic maneuvers are possible with these endoscopes, although the repertoire of available accessories that will fit through the small operating channel is quite limited. Sphincterotomy, stone extraction, and temporary stent placement have all been successfully performed in very young infants using these endoscopes9 (Fox, unpublished) (Fig. 22.1). Catheter tips that taper to a diameter of 3–4 Fr are helpful in order to selectively cannulate biliary and pancreatic ducts in infants. Deep advancement of commercially available catheters into these ducts is not always physically possible in young infants with normal anatomy due to the fine caliber of these structures at this age (Fig. 22.2).

Technique The techniques for ERCP in children are the same as for adult patients. The procedure can be conducted with the child either prone or supine on the examining table, although prone positioning is 220

Fig. 22.1 Placement of nasobiliary stent in 4-month-old infant following sphincterotomy for impacted stone.

most comfortable for the endoscopist. The basic endoscopic maneuvers are more technically challenging in children because sideviewing endoscopes and accessories have not been optimally designed to work in a narrow lumen and through a narrow operating channel, respectively. In small children and infants the endoscope tip is forced into a position in close proximity to the papilla, allowing very little of the cannula to extend out into view and increasing the difficulty of achieving optimal position for selective bile duct cannulation. Although pre-curved cannulas tapering to 3 Fr at the tip are available (Glo-Tip, GT-5-4-3, Cook Endoscopy, Winston-Salem, NC), selective biliary cannulation is more easily achieved using a double-lumen tapered tip, pull type sphincterotome with a short, 20 mm cutting wire (Mini-tomeTM pc, MT-20, Cook Endoscopy). Tightening the short cutting wire increases angulation of the catheter tip within a short working distance. Also, by starting the procedure with a sphincterotome, the endoscopist can proceed directly with therapy when indicated. The UTS-15 (Cook Endoscopy), a 5 Fr sphinctertome that tapers to 4 Fr at the tip, accepts a 0.021″ diameter wire guide, and has a 15 mm braided cutting wire, may be used for infants. Wire-guided access, using a soft-tipped, hydrophilic, narrow gauge wire, may be used if free cannulation proves too difficult (Fig. 22.2). Stiff catheters such as those used for stricture dilation or stone retrieval are more likely to require wire-guided entry. Also, in young infants a soft-wire retrieval basket (Memory® Baskets, MSB5-2x4, Cook Endoscopy) will enter the duct more easily if partially opened since the basket wires are more flexible when extending out from the stiffer plastic sheath. Alternatively, the endoscope can be placed in the long position, which may achieve a more favorable position in front of the major papilla, similar to the technique used for cannulation of the minor papilla. Tip control is not optimal, however, with the endoscope in this position. Although ultra thin duodenoscopes have 2.0 mm operating channels that will accept accessory catheters of 5 Fr diameter, the

Chapter 22 ERCP in Children

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Fig. 22.2 Former 28-week gestation neonate, now a 3-month-old, 3 kg infant with severe cholestasis. A Transabdominal ultrasound showed fusiform distension of the CBD containing debris suggestive of choledochal cyst. B–C Endoscopic views of major and minor papillae. D–F Initial and completed sphincterotomy and emerging sludge. G Tiny normal pancreatic duct. H Wire-guided access for deep bile duct cannulation. I–J Cholangiogram during and after basket extraction of sludge.

catheters tend to bind in the channel when the endoscope is bent. In addition, air and fluid cannot be evacuated easily when an accessory is within the channel. These ultrathin endoscopes are also less apt to maintain a stable scope position due to increased flexibility. Assistance is sometimes needed to maintain torque on the insertion tube.

Another caveat to consider when instrumenting a small child or infant is the fragility of the soft tissues. Repeated impaction of catheters or wire guides against a small papilla in a young infant can render the structure unrecognizable due to traumatic edema. Also, a false tract can be created using surprisingly little force while advancing a catheter or wire into the ampulla of Vater or into the minor papilla. 221

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INDICATIONS AND CONTRAINDICATIONS Diagnostic and therapeutic indications While the necessity of diagnostic ERCP has been diminished by advances in magnetic resonance cholangiopancreatography (MRCP), early or subtle diagnostic findings are still best resolved with direct contrast injection. This is particularly true for young children who cannot cooperate with breath-holding sequences required for MRI or high-resolution CT in the setting of conditions that may require fine spatial resolution such as early sclerosing cholangitis, bile duct paucity syndromes and neonatal biliary atresia, anomalous junction of the biliary and pancreatic ducts, and pancreas divisum. Continued improvement in non-invasive imaging techniques may eventually remove this limitation. The main indication for ERCP in children, as in adults, is for potential therapeutic intervention of known or suspected structural abnormalities in order to relieve obstruction, divert leakage, or drain a collection.

Biliary indications

Neonatal cholestasis Neonatal cholestasis is the only biliary condition unique to pediatrics in which purely diagnostic cholangiography has a role. The most common causes of neonatal cholestasis are idiopathic neonatal hepatitis and total parenteral nutrition, both of which are frequently encountered in neonates compromised by premature birth, congenital abnormalities requiring surgical intervention, or other acute illnesses of the newborn. These conditions are characterized by intrahepatic features of hepatocellular and canalicular dysfunction rather than bile duct obstruction. However, they can sometimes be difficult to distinguish from ductal obstruction due to inspissated bile (seen with cystic fibrosis or idiopathic causes), bile duct paucity (e.g. Alagille’s syndrome), or obliteration of the duct due to biliary atresia (BA). Of these conditions, the correct diagnosis is most urgently needed for BA since surgical intervention by portoenterostomy (Kasai procedure), substantially reduces long-term morbidity and mortality if undertaken early (less than 8 weeks). If left untreated, BA leads to liver failure and organ transplantation or death by 1–2 years of age. The role of ERCP in the diagnosis of BA remains controversial and is most helpful when the diagnosis is thought to be unlikely but cannot be definitely excluded without cholangiography (Fig. 22.3). In this situation, an unnecessary exploratory laparotomy can be avoided. A specialized ultra thin diameter duodenoscope must be used in neonates. The endoscopic findings that suggest BA include: absence of visible bile within the duodenum, partial filling of the bile duct with abnormal termination, and failure to fill the bile duct despite filling of the pancreatic duct (Fig. 22.4).10 A high level of skill and confidence in technical proficiency is required to make this diagnosis with certainty. In the largest neonatal series of suspected biliary atresia, ERCP predicted the correct diagnosis in all but 2 of 147 infants in whom biliary cannulation was successful.11 Complete filling of the bile duct definitely excludes the diagnosis of BA. However, most pediatric gastroenterologists and hepatologists rely on a combination of clinical presentation, serum chemistry profile, ultrasonography, biliary scintigraphy, and liver histology rather than ERCP to select infants with cholestasis for surgical exploration, intraoperative cholangiography, and anticipated portoenterostomy. 222

Fig. 22.3 Normal intrahepatic and extrahepatic bile ducts and small gallbladder in 10-week, 4.3 kg infant who has cholestasis and cystic fibrosis. Biliary atresia was suspected based on nonexcreting biliary scintigraphy and liver biopsy with suggestive histopathology.

Cholelithiasis and choledocholithiasis Choledocholithiasis, usually associated with cholelithiasis, is the predominant indication for ERCP in children. Black pigment bilirubinate material is usually found in infants and young children with cholelithiasis while light-colored cholesterol stones are more typical in adolescent patients without an underlying hemolytic disorder such as sickle cell disease or spherocytosis. Stringer and colleagues recently reported detailed analysis of the chemical composition of gallstones in a series of 20 children ranging in age from 0.3 to 13.9 years.12 Ten had black pigment stones, 2 had cholesterol stones, 1 had brown pigment stones, and 7 (35%) had calcium carbonate stones, a form uniquely found in children. Asymptomatic neonatal cholelithiasis may resolve spontaneously13 and even symptomatic choledocholithiasis can clear without the need for aggressive intervention.14 Therefore, a brief period of supportive care with dietary fasting, IV fluids, and antibiotics can be justified to avoid unnecessary invasive therapy. Otherwise, symptomatic small stones and impacted sludge can be definitively treated endoscopically without resorting to surgical intervention or more involved percutaneous transhepatic techniques. Sphincterotomy with removal of stone and/or sludge material can be undertaken even in very young infants with appropriate equipment9 (Fig. 22.5). Balloon sphincteroplasty rather than sphincterotomy might seem an appealing alternative in young children since the long-term effects of sphincterotomy performed in childhood are unknown. However, there are no data beyond individual case reports on the outcome of balloon sphincteroplasty in children and there is no reason to expect a lower rate of complications from this technique in children compared with adults.15,16

Chapter 22 ERCP in Children

Fig. 22.4 Schematic representation of cholangiographic patterns in infants with biliary atresia. Light green indicates nonopacified or atretic segments (adapted from reference 11 with permission of Taylor and Francis).

Type 1

Type 2

Type 3A

Type 3B

Some pediatric surgeons advocate intraoperative cholangiography and laparoscopic CBD exploration at the time of cholecystectomy for primary therapy of choledocholithiasis, thereby avoiding potential complications of ERCP.17–19 With this approach, therapeutic ERCP is reserved for situations in which intraductal calculi cannot be easily cleared at the time of surgery. However, there are no data to support routine cholecystectomy in young children with choledocholithiasis, especially if there are no residual stones within the gallbladder. Small residual gallstones are expected to pass spontaneously after endoscopic sphincterotomy alone. In this situation, a team approach is needed to offer a thoughtful and coordinated management plan to the family.

Choledochal anomalies Choledochal anomalies include cystic malformations of the bile duct and anomalous junctions between the bile duct and pancreatic duct and these conditions often co-exist. Choledochal cyst (described in more detail in Chapters 36 and 42) is a descriptive term used when there is segmental rounded or fusiform distension of the bile duct. An anatomic classification scheme proposed by Todani20 subcategorizes the condition into types 1 through 5 depending on the shape and location. Distal CBD obstruction in infants due to choledocholithiasis can induce fusiform distension mimicking Type I choledochal cyst (Figs 22.2 and 22.6). ERCP is, therefore, important in

this situation to clarify the diagnosis and render therapy that relieves the obstruction, avoiding unnecessary surgical resection of the bile duct. When anomalous pancreatobiliary union (APBU) accompanies a cystic deformity of the bile duct, stenosis at the junction is often present and surgery becomes a more reasonable treatment option for definitive decompression and to reduce the long-term risk of later onset biliary cancer (Fig. 22.7). APBU may also be found incidentally without associated cystic changes in the bile duct or in association with acute recurrent pancreatitis.

Biliary strictures and leaks Most pediatric biliary strictures are due to sclerosing cholangitis. However, patients with advanced changes of PSC with a dominant stricture that is amenable to therapeutic endoscopic dilation are the exception rather than the rule. The typical picture is one of subtle, diffusely irregular intrahepatic ducts with alternating thin and thick caliber. Since the bile duct epithelium is diffusely inflamed extending to the papilla, there is often minimal dilation of the CBD due to mild functional papillary obstruction (Fig. 22.8). A characteristic observation when PSC is present is underfilling of the intrahepatic ducts despite deep cannulation to the level of the common hepatic duct. Injection through an inflated balloon catheter permits optimal filling of the intrahepatic branches. Sclerosing cholangitis in children is associated with chronic inflammatory bowel disease (ulcer223

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A

B

C

D

E

F

Fig. 22.5 A 4-month-old, 4.8 kg infant presenting with acholic stool and jaundice 6 weeks after surgery for complex congenital heart disease. Endoscopic views of a darkened bulging papilla, cannulation with sphincterotome, removal of impacted soft pigment stone, and retrieval basket within completed sphincterotomy are seen A–D. Cholangiograms showing dilated intra- and extraheptic ducts and small filling defects within common bile duct E, and retrieval basket open within common bile duct F.

ative colitis and Crohn’s disease) and is the most common hepatic complication of primary immunodeficiency disorders.21 Patients with PSC may present with clinical features that are indistinguishable from autoimmune hepatitis and the distinction is identified during cholangiography.22 Although the “double duct sign” is considered ominous for the presence of malignancy when seen in adults, it is usually due to a 224

benign process when seen in children. Imaging with CT or EUS is recommended in order to exclude a rare tumor within the pancreatic head. When the “double duct sign” is present in children, the head of the pancreas appears either normal or slightly swollen due to acute or subacute pancreatitis. Patients present with pain and obstructive jaundice due to extrinsic compression of the distal common bile duct as it traverses the head of the pancreas (Fig. 22.9).

Chapter 22 ERCP in Children

A

B

Fig. 22.6 A Two-year-old child presenting with pancreatitis, obstructive jaundice, and cystic dilation of CBD on ultrasound. B Cholangiogram shows dilation of the CBD extending to the ampulla. Biliary sphincterotomy and stone extraction resolved the problem. Fig. 22.7 Four-year-old child presenting with recurrent pancreatitis and biliary obstruction. Cholangiogram shows an anomalous pancreatobiliary union, distal biliary stricture, and dilated CBD. This was successfully treated with bile duct resection and Roux-en-Y anastomosis.

A

B

Fig. 22.8 16-year-old female with Crohn’s disease and PSC confirmed by liver biopsy. A Cholangiogram shows slightly dilated common bile duct and poor filling of intrahepatic ducts despite deep cannulation. B Contrast injected proximal to inflated balloon catheter fills intrahepatic ducts revealing diffusely irregular pattern.

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Fig. 22.9 Stricturing of the CBD and pancreatic duct within the pancreatic head due to subacute pancreatitis in an 11-year-old male with autism who presented with jaundice.

Dilation of the stenosis and placement of one or more temporary 7 Fr stents will relieve the obstruction while awaiting resolution of the pancreatitis. Biliary brush cytology and/or bile duct biopsy may be helpful to assess for malignancy, although the yield is quite low. Biliary strictures following pediatric liver transplantation are frequently inaccessible by endoscopic cholangiography since few children undergo whole organ transplantation with duct-to-duct anastomosis. For example, in the case of biliary atresia, the most common indication for liver transplantation in childhood, a biliary enterostomy is created. Many other children receive a split organ graft due to a shortage of age-matched whole organ donors and the use of living related donor grafts. Strictures at the biliary enteric anastomoses are usually due to ischemia and require radiologic or surgical intervention. Anastomotic strictures after duct-to-duct anastomosis are managed the same as in adult patients using dilation and stent therapy (Fig. 22.10). Strictures near the junction of the main left and right hepatic ducts have been reported rarely in children and are presumed to be congenital in origin (Fig. 22.11).23 These have been successfully managed both surgically and endoscopically. Biliary leaks occur in children with laceration of the liver after blunt abdominal trauma and also after abdominal surgery such as cholecystectomy. ERCP can be used to simultaneously confirm the source and to treat the leak by transpapillary stent placement (Fig. 22.12).24 The diameter of the stent is based upon the ductal diameter.

Fig. 22.10 Choledochal anastomotic stricture and impacted stone in an adolescent male following liver transplantation.

Unusual biliary infections Human immunodeficiency virus (HIV)-associated cholangiopathy has been described in children.25 As in adults, the biliary abnormalities include irregularities of contour and caliber of the intrahepatic and extrahepatic ducts and papillary stenosis. The changes may result from concomitant infection with opportunistic organisms such as cytomegalovirus and Cryptosporidium parvum. Ascariasis infestation may be the most prevalent biliary infection worldwide, although concentrated within tropical climates. Among 214 children admitted to hospital in northern India for management of hepatobiliary and pancreatic ascariasis, 20 (9%) underwent endoscopic and 7 (4%) surgical intervention.26 226

Fig. 22.11 Presumed congenital stricture of the common hepatic duct presenting with advanced cirrhosis and portal hypertension in a 10-year-old child.

Sphincter of Oddi dysmotility Sphincter of Oddi dysmotility is sometimes considered in children with unexplained biliary colic-like pain. Although no normal manometric values have been established for children, some experts apply adult normal data and perform interventions such as

Chapter 22 ERCP in Children

biliary sphincterotomy when basal pressure exceeds 40mm Hg. Improvement following sphincterotomy has been reported in small numbers of patients but no controlled outcome data exist for children.2,27

Pancreatic indications Acute pancreatitis

ERCP is rarely indicated in the setting of acute pancreatitis. As in adults, ERCP is most helpful in the setting of biliary pancreatitis when there is evidence of choledocholithiasis and severe cholangitis.

A

Biliary pancreatitis is a commonly seen but underreported entity in childhood.28–30 Drainage of the bile duct may abruptly improve the child’s condition without necessarily improving the pancreatitis. Another acute indication for ERCP is known or suspected pancreatic trauma, where disruption of the pancreatic duct is questioned. In this case, urgent ERCP is recommended to investigate the integrity of the main duct and attempt to place a transpapillary stent that crosses a site of free duct leakage31 (Fig. 22.13). Endoscopic therapy is not indicated for contained intraparenchymal leaks, which usually heal spontaneously (Fig. 22.14). In tropical countries, parasites,

B

Fig. 22.12 A Contrast leaking from cystic duct stump in 15-year-old female with biliary leak after laparoscopic cholecystectomy. healed after temporary placement of short transpapillary biliary stent.

A

B Leak

B

Fig. 22.13 A Laceration at junction of head and body of the pancreas in 8-year-old boy after fall from a go-cart. B Pancreatogram reveals free extravasation from a disruption that could not be crossed with a wire guide. A distal pancreatectomy was performed after complete pancreatic transection was confirmed during exploratory laparotomy. 227

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Fig. 22.14 Pancreatogram shows faint intraparenchymal extravasation of contrast in head of pancreas in 9-year-old girl after a lap belt injury that occurred during an automobile accident.

Fig. 22.15 Anomalous pancreatobiliary union with long common channel treated with sphincterotomy in 14-year-old girl presenting with recurrent acute pancreatitis. primarily Ascaris lumbricoides, are an important cause of acute pancreatitis in children.26 Endoscopy is indicated to remove obstructing worms that fail to pass after drug therapy.

Persistent, recurrent, and chronic pancreatitis ERCP is an important investigative procedure in children with pancreatitis that is unrelenting after initial onset or recurs without an identifiable cause. However, a careful history and comprehensive medical evaluation along with non-invasive imaging should precede the performance of ERCP in order to avoid unnecessary risk. Occult drug exposures, underlying metabolic and autoimmune disorders, and newly recognized genetic disorders may be revealed and obviate the need for direct pancreatography. Increasingly, children previously labeled with the diagnosis of idiopathic relapsing pancreatitis have been reassigned a specific diagnosis without the need for invasive testing. Complete analysis of the genes for CFTR, SPINK1, and PRSSI, which can identify mutations associated with recurrent and chronic pancreatic disease, has recently become possible using commercially available assays (Ambry Genetics, Aliso Viejo, CA). The finding of mutations in one or more of these genes may call into question formerly assigned diagnoses such as pancreas divisum or sphincter of Oddi dysfunction, for which causality to pancreatitis remains controversial. Developmental anomalies involving the pancreas have been reported in association with recurrent attacks of pancreatitis. These include complete and partial pancreas divisum, anomalous pancreaticobiliary junction (Fig. 22.15), and enteric duplications (Fig. 22.16). Reports of endoscopic therapy with sphincterotomy of the minor and major papillae, respectively for the first two entities in children are limited but indicate potential beneficial outcomes. Communication of the pancreatic duct with cystic duplications may be confirmed endoscopically and help guide surgical intervention.

228

Fig. 22.16 18-month-old infant presenting with recurrent acute pancreatitis and persistent pancreatic cyst. Pancreatogram revealed intestinal duplication cyst in continuity with main pancreatic duct that was surgically excised and histologically confirmed.

Sphincter of Oddi dysfunction has been reported as a cause of recurrent pancreatitis in children, and improves after endoscopic pancreatic sphincterotomy.2,27,32 As with biliary manometry, basal pressures considered normal for adults have been used for normal baseline values in children. There are no controlled studies comparing endoscopic sphincterotomy to sham or placebo therapy in children. The largest series to date2 has not yet reported outcome data. Altered morphology of the main pancreatic duct and its side branches is seen with the progressive disease of chronic pancreatitis from various causes (Fig. 22.17). The range of changes is the same

Chapter 22 ERCP in Children

A

B

Fig. 22.17 Repeat pancreatograms six years apart showing progressive dilation of the main duct in a child with chronic pancreatitis.

as seen in adult patients including ectatic side branches, contour irregularities and dilation of the main duct, and occasional filling defects consisting of protein plugs and stones. Pancreatic sphincterotomy has been advocated in the setting of a dilated main pancreatic duct in symptomatic children who have failed to respond to medical therapy. There are no controlled studies, but short-term improvement following sphincterotomy has been reported. Pseudocysts that are causing clinical symptoms due to compression of adjacent structures may be drained endoscopically using transpapillary, transmural, or combination approaches, as discussed in Chapter 45. Experience in children is limited to case reports and small series.33,34

tion occur rarely in the larger pediatric ERCP series.2,4 Rates of complications after sphincterotomy in children appear comparable to those in adults.37 Cheng et al.2 reported minor acute bleeding treated with epinephrine injection in 5 patients in their series of 245 therapeutic ERCPs in children less than 18 years of age, including 100 selective biliary and 22 dual biliary and pancreatic sphincterotomies. The incidence of delayed complications following sphincterotomy in early childhood has not been reported. Complications of sedation or anesthesia, although relatively rare, especially when administered by an anesthesiologist, must also be considered as part of the total risk to children undergoing ERCP.

COMPLICATIONS

RELATIVE COSTS

Pancreatitis is the most common complication of ERCP in children. Rates have ranged from 3% to 17% with higher rates associated with therapeutic procedures.35,36 The highest rates of post-ERCP pancreatitis in children were reported by Cheng and colleagues2 in patients who underwent sphincterotomy for SOD: 30% with biliary sphincterotomy alone, 25% with biliary sphincterotomy followed by placement of a temporary pancreatic duct stent, and 20% with pancreatic sphincterotomy followed by placement of a pancreatic duct stent. Other complications such as bleeding, perforation, and infec-

There are no published data comparing the cost of ERCP with alternative diagnostic and therapeutic approaches such as percutaneous transhepatic cholangiography and direct surgical exploration. Anesthesia contributes a large fraction of the total cost for each approach. Surgical fees likely exceed those of either endoscopy or interventional radiology. The expense of maintaining costly specialized endoscopes and a reasonable inventory of accessories can be prohibitive for many pediatric facilities. Sharing equipment and accessories with a busy adult medicine service is most cost-effective.

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Pfau PR, Chelimsky GG, Kinnard MF, et al. Endoscopic retrograde cholangiopancreatography in children and adolescents. J Pediatr Gastroenterol Nutr 2002 Nov; 35(5):619–623. Cheng CL, Fogel EL, Sherman S, et al. Diagnostic and therapeutic endoscopic retrograde cholangiopancreatography in children: a large series report. J Pediatr Gastroenterol Nutr 2005 Oct; 41(4):445–453. Keil R, Snajdauf J, Stuj J, et al. Endoscopic retrograde cholangiopancreatography in infants and children. Indian J Gastroenterol 2000 Oct–Dec; 19(4):175–177. Fox VL, Werlin SL, Heyman MB. Endoscopic retrograde cholangiopancreatography in children. Subcommittee on Endoscopy and Procedures of the Patient Care Committee of the North American Society for Pediatric Gastroenterology and Nutrition. J Pediatr Gastroenterol Nutr 2000 Mar; 30(3):335–342. Jowell PS, Baillie J, Branch S, et al. Quantitative assessment of procedural competence: a prospective study of training in retrograde cholangiopancreatography. Ann Intern Med 1996; 125:983–989. Freeman ML, Nelson DB, Sherman S, et al. Complications of endoscopic biliary sphincterotomy. N Engl J Med 1996; 335:909–918. Teng R, Yokohata K, Utsunomiya N, et al. Endoscopic retrograde cholangiopancreatography in infants and children. J Gastroenterol 2000; 35(1):39–42. Rocca R, Castellino F, Daperno M, et al. Therapeutic ERCP in paediatric patients. Dig Liver Dis 2005 May; 37(5):357–362. Wilkinson ML, Clayton PT. Sphincterotomy for jaundice in a neonate. J Pediatr Gastroenterol Nutr 1996; 23:507–509. Guelrud M, Jaen D, Mendoza S, et al. ERCP in the diagnosis of extrahepatic biliary atresia. Gastrointest Endosc 1991 Sep–Oct; 37(5):522–526. Guelrud M, Carr-Locke DL, Fox VL. ERCP in Pediatric Practice: Diagnosis and Treatment. Oxford: Isis Medical Media Ltd; 1997. Stringer MD, Taylor DR, Soloway RD. Gallstone composition: are children different? Journal of Pediatrics 2003; 142:435–440. Brown DL, Teele RL, Doubilet PM, et al. Echogenic material in the fetal gallbladder: sonographic and clinical observations. Radiology 1992; 182:73–76. St-Vil D, Yazbec S, Luks FI, et al. Cholelithiasis in newborns and infants. Journal of Pediatric Surgery 1992; 27:1305–1307. Baron TH, Harewood GC. Endoscopic balloon dilation of the biliary sphincter compared to endoscopic biliary sphincterotomy for removal of common bile duct stones during ERCP: a metaanalysis of randomized, controlled trials. Am J Gastroenterol 2004 Aug; 99(8):1455–1460. Disario JA, Freeman ML, Bjorkman DJ, et al. Endoscopic balloon dilation compared with sphincterotomy for extraction of bile duct stones. Gastroenterology 2004 Nov; 127(5):1291–1299. Bonnard A, Seguier-Lipszyc E, Liguory C, et al. Laparoscopic approach as primary treatment of common bile duct stones in children. J Pediatr Surg 2005 Sep; 40(9):1459–1463. Mah D, Wales P, Njere I, et al. Management of suspected common bile duct stones in children: role of selective intraoperative cholangiogram and endoscopic retrograde cholangiopancreatography. J Pediatr Surg 2004 June; 39(6):808– 812; discussion -12. Vrochides DV, Sorrells DL, Jr., Kurkchubasche AG, et al. Is there a role for routine preoperative endoscopic retrograde

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cholangiopancreatography for suspected choledocholithiasis in children? Arch Surg 2005 Apr; 140(4):359–361. Todani T, Watanabe Y, Narusue M, et al. Classification, operative procedures and review of thirty seven cases including cancer arising from choledochal cyst. Am J Surg 1977; 134:263–269. Rodrigues F, Davies EG, Harrison P, et al. Liver disease in children with primary immunodeficiencies. J Pediatr 2004 Sep; 145(3):333–339. Gregorio GV, Portmann B, Karani J, et al. Autoimmune hepatitis/ sclerosing cholangitis overlap syndrome in childhood: a 16-year prospective study. Hepatology 2001 Mar; 33(3):544–553. Chapoy PR, Kendall RS, Fonkalsrud E, et al. Congenital stricture of the common hepatic duct: an unusual case without jaundice. Gastroenterology 1981; 80:380–383. Sharpe RP, Nance ML, Stafford PW. Nonoperative management of blunt extrahepatic biliary duct transection in the pediatric patient: case report and review of the literature. J Pediatr Surg 2002 Nov; 37(11):1612–1616. Yabut B, Werlin SL, Havens P, et al. Endoscopic retrograde cholangiopancreatography in children with HIV infection. J Pediatr Gastroenterol Nutr 1996 Dec; 23(5):624–627. Malik AH, Saima BD, Wani MY. Management of hepatobiliary and pancreatic ascariasis in children of an endemic area. Pediatr Surg Int 2006 Feb; 22(2):164–168. Varadarajulu S, Wilcox CM. Endoscopic management of sphincter of Oddi dysfunction in children. J Pediatr Gastroenterol Nutr 2006; 42:526–530. Sutton R, Cheslyn-Curtis S. Acute gallstone pancreatitis in childhood. Ann R Coll Surg Engl 2001 Nov; 83(6):406–408. Akel S, Khalifeh M, Makhlouf Akel M. Gallstone pancreatitis in children: atypical presentation and review. Eur J Pediatr 2005 Aug; 164(8):482–485. Nowak A, Kohut M, Nowakowska-Dulawa E, et al. Acute biliary pancreatitis in a 9-year-old child treated with endoscopic sphincterotomy. Dig Liver Dis 2003 Sep; 35(9):656–659. Canty TG, Sr., Weinman D. Management of major pancreatic duct injuries in children. J Trauma 2001 June; 50(6):1001–1007. Guelrud M, Morera C, Rodriguez M, et al. Sphincter of Oddi dysfunction in children with recurrent pancreatitis and anomalous pancreaticobiliary union: an etiologic concept. Gastrointest Endosc 1999 Aug; 50(2):194–199. Haluszka O, Campbell A, Horvath K. Endoscopic management of pancreatic pseudocyst in children. Gastrointest Endosc 2002 Jan; 55(1):128–131. Cahen D, Rauws E, Fockens P, et al. Endoscopic drainage of pancreatic pseudocysts: long-term outcome and procedural factors associated with safe and successful treatment. Endoscopy 2005 Oct; 37(10):977–983. Brown CW, Werlin SL, Geenen JE, et al. The diagnostic and therapeutic role of endoscopic retrograde cholangiopancreatography in children. J Pediatr Gastroenterol Nutr 1993 Jul; 17(1):19–23. Guelrud M, Mujica C, Jaen D, et al. The role of ERCP in the diagnosis and treatment of idiopathic recurrent pancreatitis in children and adolescents. Gastrointest Endosc 1994 Jul–Aug; 40(4):428–436. Varadarajulu S, Wilcox CM, Hawes RH, et al. Technical outcomes and complications of ERCP in children. Gastrointest Endosc 2004 Sep; 60(3):367–371.

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23

TECHNIQUES

ERCP in Pregnancy William M Outlaw and John Baillie

OVERVIEW Fear of causing fetal and maternal injury or death by procedurerelated pancreatitis delayed the introduction of ERCP for biliary complications of pregnancy until 1990. Since then, there have been seven case series (total of 57 patients) and numerous (>30) single case reports of ERCP in pregnancy. No case of severe ERCP-related pancreatitis (or other severe complication of the procedure) has been reported, and all but one reported case has been successful. PostERCP pancreatitis (PEP) and bleeding were reported in 8% and 4% of the 57 case series patients, while pre-eclampsia, premature birth and spontaneous abortion were observed in 4%, 2% and 2% of these same patients. The physiologic changes of pregnancy have profound implications for many aspects of ERCP, ranging from the type of drugs than can be used for sedation to positioning the patient and shielding the fetus from ionizing radiation. Single cases successfully managed by ERCP during pregnancy include spontaneous bile duct rupture with bile peritonitis and relief of obstructive jaundice from pancreatic adenocarcinoma have been reported. Overall, ERCP with biliary sphincterotomy and clearance of bile duct stones has an acceptably low morbidity in pregnant women, with no reported maternal mortality. It is not clear if one reported spontaneous abortion and two premature labors noted in the case series literature were causally related. ERCP can be recommended for managing the complications of bile duct stones in pregnancy. However, balloon dilation of the papilla (balloon sphincteroplasty) should be avoided due to its tendency to cause pancreatitis.

INTRODUCTION Endoscopic retrograde cholangiopancreatography (ERCP) rapidly advanced as a therapeutic specialty in 1974 with the advent of endoscopic sphincterotomy (ES), reported simultaneously by Kawai1 and Classen.2 However, acceptance of ERCP during pregnancy occurred later than other therapeutic interventions. Based on dated surgical literature which suggested a significant spontaneous abortion rate when laparotomy was performed in the first trimester of pregnancy, endoscopists were frightened to attempt ERCP during pregnancy in any clinical situation. It was felt that a severe attack of pancreatitis following ERCP might result in fetal, and possibly even maternal, death. There was also significant concern about the teratogenicity of fluoroscopy during the first trimester of pregnancy. In 1990, however, a group from Duke University Medical Center (including one of us (JB)) reported its experience of ERCP during pregnancy in five patients. These ERCPs allowed the avoidance of surgery.3 All five procedures were uncomplicated, the pregnancies lasted to full term, and five healthy babies were born. This landmark paper emboldened

other endoscopists to perform ERCP in pregnant women, and this is now considered accepted practice. Moreover, a recent case series4 comparing medical and surgical treatment of biliary stones in pregnancy failed to support the concern about fetal loss following surgery in pregnancy. Cholelithiasis and choledocholithiasis (Fig. 23.1) in pregnancy are common, and their complications, including biliary obstruction, cholangitis and gallstone pancreatitis (Fig. 23.2) are appropriately and safely managed by ERCP with ES. To the best of this author’s knowledge, no pregnant woman has died as a result of ERCP. There have been no studies comparing standard endoscopic sphincterotomy with so-called balloon sphincteroplasty (Fig. 23.3) in pregnant women, nor are there likely to be given the propensity of the latter to cause pancreatitis. It is the authors’ opinion that balloon sphincterotomy should never be used in pregnancy. Biliary obstruction in the setting of uncorrectable coagulopathy in a pregnant woman is more appropriately—and safely—managed by stenting to ensure drainage (Fig. 23.4). Elective sphincterotomy can be performed at a later date, when normal coagulation has been restored.

INDICATION The indication for ERCP during pregnancy must be well-established as necessary and critical to the safety of the mother and fetus: pregnancy is not the appropriate time to be assessing possible Type III sphincter of Oddi dysfunction by biliary manometry. Table 23.1 lists the ASGE’s recommendations regarding Indications for Endoscopy in pregnancy. Table 23.2 lists the ASGE’s Guiding Principles for Endoscopy in Pregnancy. Although choledocholithiasis (Fig. 23.1) is the commonest biliary pathology requiring ERCP in pregnancy, in certain parts of the world parasites (e.g. Fasciola, Clonorchis, Ascaris) can cause biliary obstruction and pancreatitis. These parasites are best treated by a combination of ERCP with ES for duct clearance and specific chemotherapeutic agents5 (see below).

RADIATION PROTECTION Considerable attention has been devoted to shielding the fetus from ionizing radiation during ERCP. Radiation protection is also discussed in Chapter 3. Three types of radiation exposure occur: primary, secondary and “leakage.”6 The primary radiation beam is focused and directed through the area of interest. Personnel (doctors, nurses, technicians) in the procedure room are exposed to secondary (or “scatter”) radiation. “Leakage” is leakage radiation from the radiation source itself. It has been estimated that the typical radiation dose to the fetus during ERCP is 3.1 mGy.7 This compares with 1.75 mGy for an upper GI contrast series, 7.8 mGy for a PET scan, 15.4 mGy for a pelvic CT scan and 37.0 mGy for an intravenous urogram (IVU). Protecting the first and second trimester fetus from irradiation is usually straightforward; a lead apron is applied to the 231

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Fig. 23.1 Endoscopic retrograde common bile duct stones.

cholangiogram

showing

Fig. 23.3 papilla

Dilation (balloon sphincteroplasty) of the duodenal

Fig. 23.4 Plastic stent draining purulent bile from the bile duct in a patient whose severe coagulopathy was a contraindication to endoscopic sphincterotomy

Fig. 23.2 Duodenal papilla obstructed by a stone in a patient with gallstone pancreatitis.

appropriate part, shielding the mother’s abdomen. The endoscopist must confirm which direction the x-rays travel in the fluoroscopy system being employed to ensure that the shielding is appropriately applied; this may dictate placing a lead apron or mat underneath the patient. In the third trimester—especially close to term—it may be impossible to avoid exposing the fetus to a small amount of radiation from screening, but we have no data to suggest that this has caused any detectable harm, especially since the fetus is well-formed by then. As a rule, taking “hard copy” fluoroscopic images should be 232

Significant or continuing GI bleeding Severe or refractory nausea and vomiting or abdominal pain Dysphagia or odynophagia Strong suspicion of a colonic mass Severe diarrhea with negative evaluation Biliary pancreatitis, choledocholithiasis or cholangitis Biliary or pancreatic ductal injury

Table 23.1 Indications for endoscopy in pregnancy (ASGE)

avoided, as this significantly increases radiation exposure. Fluoroscopy time is kept to an absolute minimum; short “bursts” of fluoroscopy are used to confirm the seating of the papillotome in the bile duct and confirmation of the underlying pathology followed by as little contrast injection as possible. Typically, less than 60 seconds

Chapter 23 ERCP in Pregnancy

• Always have a strong indication, particularly in high-risk pregnancy • Defer endoscopy to the second trimester whenever possible • Use the lowest effective dose of sedative medication • Whenever possible, use category A or B drugs • Minimize procedure time • Position pregnant patients in left pelvic tilt or left lateral position to avoid vena caval or aortic compression • The presence of fetal heart sounds should be confirmed before sedation is begun and again at the end of the procedure • Obstetric support should be available in the event of a pregnancy-related complication • Endoscopy is contraindicated in the presence of obstetric complications, such as placental abruption, imminent delivery, ruptured membranes or eclampsia

Table 23.2 General principles guiding endoscopy in pregnancy

of fluoroscopy time are required. However, published reports cite fluoroscopy time ranging from 8 seconds8 to 3.2 minutes.9 A standard radiation dosimeter is applied to the abdominal wall overlying the fundus of the gravid uterus to check that the fetus has been adequately shielded. Radiation doses are typically negligible. Reported measured fetal exposures range from 40 to 310 mrad (4– 31 mGy)—well within established safe limits.9,10 (Note: 1 mGy = 100 mrad.) One novel method of ERCP that avoids radiation exposure altogether was described by Simmons et al.11 This technique involves wire-guided bile duct cannulation without fluoroscopic guidance. Once the wire has passed proximally, the catheter is advanced and entry into the presumed duct is confirmed by aspirating bile into the catheter. After a biliary sphincterotomy is performed stone retrieval is achieved using a stone retrieval balloon. The ballon is passed proximally into the bile duct, inflated, and swept through the sphincterotomy. Using this technique, successful ERCP and stone extraction were described in six cases.11 Neither fluoroscopy nor spot radiographs (“hard copy” images) were used during these procedures. The mean ERCP time was 16 minutes (range 10–25 minutes). Though useful, it is likely that this technique will be used by only the most experienced endoscopists and for straightforward cases.

POSITIONING Positioning the pregnant mother is rarely a problem. However, women in the later stages of pregnancy cannot lie prone, the standard position for ERCP imaging. A semi-prone or left lateral position is acceptable in such circumstances (Fig. 23.5). The endoscopist performing the procedure should be familiar with the altered endoscopic and radiologic appearances when pregnant patients are so positioned. The supine position is not acceptable in the third trimester of pregnancy: the “supine hypotensive syndrome” occurs in 15– 20% of pregnant women at term.12 Uterine blood flow is compromised in the supine position due to inferior vena cava (IVC), and sometimes aortic, compression by the gravid uterus. This phenomenon is exacerbated by the use of vasodilators. As amniotic fluid can conduct electrical current to the fetus,13 it is recommended that the grounding pad for electrocautery should

Fig. 23.5 The patient is lying in the left semi-prone position with lead mats below her and a lead apron draped over the lower abdomen. A dosimeter (not seen) is placed over the fundus of the uterus on the mother’s abdomen to measure fetal radiation exposure.

be placed in such a way as to avoid interposing the uterus on an imaginary line between the electrical device and the pad. Bipolar electrocautery is preferred to minimize the risk of stray currents.

PHYSIOLOGIC CHANGES OF PREGNANCY Although endoscopists rarely consider the physiologic changes of pregnancy, these are important and impact directly on sedation, positioning, fluid balance, prevention of gastroesophageal reflux disease (GERD), etc.14 Pregnancy causes a hypercoagulable state; cardiac output increases 50% during pregnancy; oncotic pressure is reduced, making pulmonary edema more likely in the setting of fluid overload; oxygen consumption increases 60% and functional residual (lung) capacity is reduced 20% at term, due to the presence of the large gravid uterus in the abdomen (this reduction in lung capacity is reduced a further 30% in the supine position); renal blood flow increases 75% (glomerular filtration rate 50%) during pregnancy, which has implications for drug clearance; loss of tone in the lower esophageal sphincter (LES) during pregnancy occurs in 22% of women in the first trimester and increases to nearly 80% in the third trimester. Due to the risk of gastroesophageal reflux and aspiration of gastric contents, it is recommended that pregnant women undergo rapid induction for general anesthesia with cricoid pressure and endotracheal intubation.

SEDATION The sedation used for ERCP in pregnancy is similar to that used for moderate (“conscious”) sedation and general anesthesia, except that benzodiazepines are generally avoided due to their long half-life.15 Sustained use of diazepam in early pregnancy has been associated with cleft palate.16 In later pregnancy, it has been suggested that diazepam use may result in neurobehavioral disorders.17 Midazolam has not been reported to be associated with congenital abnormalities. However, due to concerns about benzodiazepines in general, midazolam is usually avoided, especially in the first trimester. Pro233

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pofolTM (DiprivanTM and others, 2,6-bis(1-methylethyl-phenol)) is considered safe in pregnancy. However, if PropofolTM is used, it should be noted that this agent has no analgesic effect. The fetal heart rate should be assessed before and after ERCP to ensure that the fetus remains viable and undistressed by the procedure. Standard monitoring (i.e. pulse oximetry, automated blood pressure monitoring, and capnography) is employed for the mother. The safety of commonly used medications for endoscopy during pregnancy is covered in more detail in the ASGE Guideline for Endoscopy in Pregnant and Lactating Women.18

OUTCOMES Table 23.3 summarizes the collective outcome of case series consisting of = 3 patients. Reports of one or two cases, and those lumping together ERCP and non-ERCP endoscopy in pregnancy,11,19–24 have been excluded. Seven case series3,9–11,15,19 comprising a total of 57 patients undergoing ERCP during pregnancy have been reported. The median stage of pregnancy in which these patients presented with symptomatic choledocholithiasis (the main indication for ERCP) was mid-to-late second trimester. Complications were postERCP pancreatitis (PEP) 8%, post-sphincterotomy bleeding (4%), and pre-eclampsia (4%). There were two premature births (at 35 weeks, one with severe growth retardation and pulmonary immaturity) (4%) and one spontaneous abortion (2%).

MANAGEMENT OF RELATED BILIARY DISORDERS OF PREGNANCY Thaggard et al.25 reported a rare case of spontaneous bile duct rupture during pregnancy leading to bile peritonitis that was managed endoscopically. Allmedinger et al.26 describe the use of percutaneous cholecystostomy to manage acute cholecystitis in two women during the third trimester of pregnancy. Both delivered normal babies at term and underwent uneventful laparoscopic

cholecystectomy (LC) within 3 months. Sungler at al.,27 and Friedman and Friedman,28 report the combination of ERCP and LC for managing gallstone disease in seven pregnancies, all with successful outcome. Diettrich et al.29 identified 34/1100 pregnant women patients who underwent laparotomy within 6 weeks of delivery. Twenty-six patients had spontaneous vaginal deliveries (SVDs) and eight had Cesarian sections. There were no complications resulting from any of these procedures. Blackbourne et al.30 reported a most unusual case of a patient diagnosed with pancreatic adenocarcinoma at 17 weeks gestation in whom a biliary stent was successfully placed to relieve biliary obstruction. The patient subsequently underwent pancreaticoduodenectomy (Whipple procedure). Hewitt et al.31 described their experience of managing three patients with choledochal cysts (CDC) during pregnancy. One CDC that was conservatively managed ruptured, with fetal loss and a prolonged hospitalization. Based upon this case proactive drainage of CDC should be considered in order to limit the risk of spontaneous rupture in the peripartum period. Routine “worming” of women of childbearing age is recommended in areas where Ascaris is endemic. Despite this, Shah et al.32 describe an interesting experience of 15 cases of symptomatic biliary Ascariasis seen over a 10-year period. Ten of these patients were in their third trimester of pregnancy. The condition was most reliably diagnosed by transabdominal ultrasound. Nine of the 15(60%) patients responded to conservative treatment. Among the remaining six cases, endoscopic extraction of Ascaris worms was successful in four cases and open biliary surgery was required in two cases. Of the pregnant patients, one suffered a spontaneous abortion at 12 weeks and another went into premature labor. In summary, ERCP is a safe and effective modality primarily for the management of choledocholithiasis.33–36

Acknowledgement The authors are grateful to Dr Dick Kozarek (Seattle, WA) for his helpful critique of the first draft of this manuscript.

Author

Number of pts

Mean gestation (weeks)

Complications/outcomes

Kaleleh (ref 12)

17

18.6

PEP-1, Bleed-1 Pre-eclampsia-2

Gupta (ref 10)

18

17

PEP-1, Bleed-1 Preterm delivery-1

Jamidar (ref 16)

23 (6 centers; total of 29 ERCPs)

15-1st trimester 8-2nd trimester 6-3rd trimester

PEP-1 Spontaneous abortion 3 months after ERCP

Tham (ref 11)

15

28.9

None

Baillie (ref 6)

5

1-1st trimester 4-2nd trimester

None

Barthel (ref 20)

3

n/a

PEP-1

Simmons (ref 21)

6

6-30 weeks

2 premature births

Total

57

mid-late 2nd trimester

PEP-4 (8%) Bleed-2 (4%) Pre-eclampsia-2 (4%) Spontaneous abortion 1 (2%) Premature birth 2 (4%)

Table 23.3 ERCP during pregnancy: series of ≥2 patients PEP-post-ERCP pancreatitis.

234

Chapter 23 ERCP in Pregnancy

REFERENCES 1.

2.

3.

4.

5. 6. 7. 8.

9. 10. 11.

12.

13.

14.

15.

16. 17.

18.

19.

Kawai K, Akasaka Y, Murakami K, et al. Endoscopic sphincterotomy of the ampulla of Vater. Gastrointest Endosc 1974; 20:148–151. Classen M, Demling L. Endoscopic sphincterotomy of the papilla of Vater and extraction of stones from the choledochal duct. Dtsch Med Wochenschr 1974; 99(11):496–497. Baillie J, Cairns SR, Putnam WS, et al. Endoscopic management of choledocholithiasis during pregnancy. Surg Gynecol Obstet 1990; 171(1):1–4. Lu EJ, Curet MJ, El-Sayed YY, et al. Medical versus surgical management of biliary tract disease in pregnancy. Am J Surg 2004; 188(6):755–759. Shah OJ, Robanni I, Khan F, et al. Management of biliary Ascariasis in pregnancy. World J Surg 2005; 29(10):1294–1298. http://www.sgna.org/resources/guidelines/guideline2_print.html. http://brighamrad.harvard.edu/education/fetaldose/diagexposure.html. Gupta R, Tandan M, Lakhtakia S, et al. Safety of therapeutic ERCP in pregnancy—an Indian experience. Indian J Gastroenterol 2005; 24(4):161–163. Tham TC, Vandervoort J, Wong RC, et al. Safety of ERCP during pregnancy, Am J Gastroenterol 2003; 98(2):308–311. Kahaleh M, Hartwell GD, Arseneau KO, et al. Safety and efficacy of ERCP in pregnancy. Gastrointest Endosc 2004; 60(2):287–292. Simmons DC, Tarnasky PR, Rivera-Alsina ME, et al. Endoscopic retrograde cholangiopancreatography (ERCP) in pregnancy without the use of radiation. Am J Obstet Gynecol 2004; 190(5):1467–1469. Holmes F. Incidence of supine hypotensive syndrome in late pregnancy. A clinical study of 500 subjects. J Obstet Gynaecol Br Emp 1960; 67:254–258. Einarson A, Bailey B, Inocencion G, et al. Accidental electric shock in pregnancy: a prospective cohort study. Am J Obstst Gynecol 1997; 176:678–681. Cappell MS. Sedation and analgesia for gastrointestinal endoscopy during pregnancy. Gastrointest Endosc Clin N Am 2006; 16(1):1–31. Jamidar PA, Beck GJ, Hoffman BJ, et al. Endoscopic retrograde cholangiopancreatography in pregnancy. Am J Gastroenterol 1995; 90(8):1263–1267. Ornoy A, Arnon J, Shectman S, et al. Is benzodiazepine use during pregnancy really teratogenic? Reprod Toxicol 1998; 12:511–515. Laegreid L, Olegard R, Wahlstrom J, et al. Teratogenic effects of benzodiazepine use during pregnancy. J Pediatr 1989; 114:126–131. ASGE Standards of Practice Committee. Guidelines for endoscopy in pregnant and lactating women. Gastrointest Endosc 2005; 61(3):357–362. Barthel JS, Chowdhury T, Miedema BW. Endoscopic sphincterotomy for the treatment of gallstone pancreatitis in pregnancy. Surg Endosc 1998; 12(5):394–399.

20. Rahmin MG, Hitscherich R, Jacobson IM. ERCP for symptomatic choledocholithiasis in pregnancy. Am J Gastroenterol 1994; 89(9):1601–1602. 21. Uomo G, Manes G, Picciotto FP, et al. Endoscopic treatment of acute biliary pancreatitis in pregnancy. J Clin Gastroenterol 1994; 18(3):250–252. 22. Cohen SA, Kasmin FE, Siegel JH. ERCP during pregnancy. Am J Gastroenterol 2003; 98(2):237–238. 23. Goldschmidt M, Wolf L, Shires T. Treatment of symptomatic choledocholithiasis during pregnancy. Gastrointest Endosc 1993; 39(6):812–814. 24. Quan WL, Chia CK, Yim HB. Safety of endoscopical procedures during pregnancy. Singapore Med J 2006; 47(6):525–528. 25. Thaggard WG, Johnson PN, Baron TH. Endoscopic management of spontaneous bile duct perforation and bile peritonitis complicating term pregnancy (case report). Am J Gastroenterol 1995; 90(11):2054–2055 (case report). 26. Allmendinger N, Hallisey MJ, Okhi SK, et al. Percutaneous cholecystostomy of acute cholecystitis of pregnancy. Obstet Gynecol 1995; 86(4 pt 2):653–654. 27. Sungler P, Heinerman PM, Steiner H, et al. Laparoscopic cholecystectomy and interventional endoscopy for gallstone complications of pregnancy. Surg Endosc 2000; 14(3):267–271. 28. Friedman RL, Friedman IH. Acute cholecystitis with calculous biliary obstruction in the gravid patient. Management by ERCP, papillotomy, stone extraction and laparoscopic cholecystectomy. Surg Endosc 1995; 9(8):910–913. 29. Diettrich NA, Kaplan G. Surgical considerations in the contemporary management of biliary tract disease in the postpartum period. Am J Surg 1998; 176(3):251–253. 30. Blackbourne LH, Jones RS, Catalano CJ, et al. Pancreatic adenocarcinoma in the pregnant patient: case report and review of the literature. Cancer 1997; 79(9):1776–1779. 31. Hewitt PM, Krige JE, Bornmann PC, et al. Choledochal cyst in pregnancy: a therapeutic dilemma. J Am Coll Surg 1995; 181(3):237–240. 32. Shah OJ, Robanni I, Khan F, et al. Management of biliary ascariasis in pregnancy. World J Surg 2005; 29(10):1294–1298. 33. Axelrad AM, Fleischer DE, Strack LL, et al. Performance of ERCP for symptomatic choledocholithiasis during pregnancy: techniques to increase safety and improve patient management. Am J Gastroenterol 1994; 89(1):109–112. 34. Baillie J. ERCP during pregnancy. Am J Gastroenterol 2003; 98(2):237–238. 35. Menees S, Elta G. Endoscopic retrograde cholangiopancreatography during pregnancy. Gastrointest Endosc Clin N Am 2006; 16(1):41–57. 36. Cappell MS. The fetal safety and clinical efficacy of gastrointestinal endoscopy during pregnancy (review). Gastrointest Endosc Clin North Am 2003; 32(1):123–179 (review).

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24

TECHNIQUES

ERCP in Surgically Altered Anatomy Simon K. Lo

ERCP is generally considered the technically most difficult endoscopic procedure. But it can be made more challenging if the gastrointestinal or pancreaticobiliary anatomy is modified. A thorough understanding of a surgically altered anatomy is essential to minimize complications and to enhance the chance of a successful outcome. In virtually all these cases, careful preprocedure planning is mandatory (Table 24.1).

SURGERY THAT MAY IMPACT THE PERFORMANCE OR INTERPRETATION OF ERCP Many operations reroute the upper gastrointestinal tract and may require a special equipment or extreme familiarity in order to reach the pancreatic and biliary systems. Some surgery removes or alters a portion of the bile duct or pancreas but does not create any hardship to performing ERCP. Conversely, there are those improbable surgical consequences that would not allow any endoscopic access of the biliary tract regardless of experience, skill and equipment. We will explain most of these operations and attempt to bring up relevant points pertaining to ERCP.

ESOPHAGEAL RESECTION Mostly done for esophageal neoplasm or pre-malignant conditions, up to 22% of esophageal resections may be accompanied by high esophageal anastomosis strictures.1 Additionally, small diverticuli can form proximal to these anastomoses. In passing a duodenoscope, care must be taken to avoid forcing it through a diverticulum or an anastomotic stricture. If resistance is encountered, an end-viewing upper endoscope should be used to inspect the esophageal anatomy carefully. Esophageal resections also result in the stomach being brought up above the diaphragm and turned into a tubular sack that ends with a pyloroplasty. Once the duodenoscope has passed through the pylorus, the approach to the major papilla requires slightly more clockwise rotation or a longer insertion of the endoscope than usual. This is because of the more proximal location of the duodenum and the lack of a competent pylorus to hold the endoscope in place.

GASTRIC RESECTION There are many forms of gastric resection, ranging from a Billroth I where there is very little loss of the volume of the stomach to a total gastrectomy. As a result, the impact of gastric resection on ERCP can be either minimal or profound.

Billroth I In a Billroth I surgery, only the antrum and pylorus are removed and the stomach is attached to the duodenum along its greater

curvature (Fig. 24.1). Scope passage into the duodenum is typically easier than usual, but the papilla is harder to visualize. As expected, both the major and minor papillae are more proximally located than usual. In the short-scope position, the papilla is seen following an exaggerated clockwise rotation of the endoscope. However, anchoring of the endoscope is difficult without the pylorus and achieving a stable scope position for deliberate cannulation can be quite difficult. In this situation, working in the long-scope position may be more desirable for bile duct cannulation because the papillary orifice is better visualized and the scope is more stably situated.

Billroth II Before proton pump inhibitors were introduced, peptic ulcer surgery was common. A Billroth II operation involves an antrectomy and creation of a gastrojejunostomy. The result is an end (stomach)-toside (jejunum) anastomosis with an afferent and an efferent limb (Figs 24.2A, 24.2B) next to each other beyond the line of anastomosis. The afferent limb travels proximally and ends at the duodenal stump whereas the efferent limb restores continuity with the rest of the gastrointestinal tract. The major papilla is obviously located near the duodenal stump and is seen with the papillary orifice facing the endoscope. There are several challenges that the endoscopist has to deal with when performing ERCP in a patient with Billroth II anatomy. It begins with the choice of endoscope. Once it was believed that end-viewing endoscopes were best used to navigate the small bowel and pass cannulas into the biliary orifice. Many experienced biliary endoscopists switched to using the side-viewing duodenoscopes to take advantage of the elevator and better viewing of the papilla. But in a prospective randomized study of 45 patients in Korea, no difference was noted between the side-viewing and endviewing endoscopes in success of cannulation and sphincterotomy.2 In fact, the end-viewing endoscopes were safer to use. Regardless of what endoscope to use, Billroth II ERCP is one of the more difficult procedures. In a study involving 185 Billroth II ERCP procedures, the failure rate was 34%.3 The afferent lumen cannot be identified by visual inspection alone, though it is commonly believed that it is the more awkwardly located orifice. The afferent limb can be attached to the stomach along either the lesser (antiperistaltic) (Fig. 24.2A) or greater (isoperistaltic) curvature (Fig. 24.2B). Scope passage with an end-viewing device is rather intuitive, and the major challenge is in visualizing and cannulating the papilla. Even though data suggests there is no difference in technical success between side-viewing and endviewing, endoscopies, in reality it is far easier to perform cannulation and therapies using a duodenoscope. When using a duodenoscope, the difficulty starts with gaining entry into the afferent lumen. It is even more difficult if the afferent limb is sutured to the lesser curvature after it has exited the 237

SECTION 2 TECHNIQUES

Understand the prior surgery thoroughly Choose the proper endoscope Standard therapeutic duodenoscope Thin-caliber diagnostic duodenoscope Pediatric duodenoscope Diagnostic upper endoscope Therapeutic upper endoscope Pediatric (variable stiffness) colonoscope Therapeutic colonoscope Push enteroscope Double balloon enteroscope Linear EUS scope Position the patient properly Prone Supine Left lateral Left oblique Prepare accessories Standard accessories Non-precurved catheters Nasobiliary drains Specialty accessories (e.g. for Billroth II) Long-length accessories Anesthesia Conscious sedation Propofol anesthesia General anesthesia

Table 24.1 Pre-procedure planning in situations that involve surgically altered anatomy A

Fig. 24.1 Billroth I gastrectomy. Antrectomy is followed by connection of the stomach to the duodenum in the end-to-end fashion. The lesser curvature side of the cut end of the stomach is closed to allow creation of the gastroduodenostomy.

B

Fig. 24.2 A Billroth II gastrectomy with an antiperistaltic gastrojejunostomy anastomosis. In this case, the afferent limb is accessed through the stomal orifice located near the lesser curvature. B Billroth II gastrectomy with an isoperistaltic anastomosis, where the afferent limb is attached to the greater curvature. 238

Chapter 24 ERCP in Surgically Altered Anatomy

gastrojejunostomy, as this form of operation creates a fixed and significantly angulated point of entry4 (Figs 24.3A, 24.3B). When a duodenoscope is used, the technique to enter the orifice is the same as for the pylorus. When the lumen can only be visualized in the retroflexed position, gliding the scope along gently toward it rarely works. Suctioning out excess gastric air may make the gliding a little easier. Once the tip of the scope has reached the orifice, the scope should be gradually pulled back and straightened in order to advance further. There is the technique of entering the lumen by rotating the scope 180 degrees at the orifice and pointing the tip of the scope down until the small bowel lumen is clearly in sight. This technique A

can theoretically be done with the scope facing the opening rather than “backing in.” However, the endoscope would be blinded by mucosal lining and visual inspection during the maneuvering would become impossible. Hand compression of the mid-abdomen or extending a polypectomy snare into the intended lumen has been reported to add to the success of intubation of a difficult intestinal orifice.5 Even in a tertiary biliary center, failure to enter the afferent limb has been reported to be as high as 10%.3 Once the side-viewing duodenoscope has securely engaged in a jejunal lumen, passage forward is safe and effective by constantly orientating the bowel in the 6 o’clock position (Figs 24.4A). This

B

Fig. 24.3 A Endoscopic appearance of a typical Billroth II gastrojejunostomy. Viewing from the stomach, the two jejunal limbs are located at the extreme right and left of this image. B Billroth II gastrectomy with the greater curvature side of the stomach attached to the jejunum in an end-to-side fashion. The lesser curvature side of the stomach is closed surgically. Some surgeons choose to suture the jejunum onto this area to protect the suture line. If the afferent limb is tagged down in this manner, then endoscope entry into this limb may be quite difficult. A

B

Fig. 24.4 A The typical view of the jejunal lumen when a side-viewing duodenoscope is being advanced. Note the upper half of the lumen should always be kept in the 6 o’clock position. B A similar duodenoscopic view of the distal lumen in the 6 o’clock position. Note the upper lumen always represents a retroflexed view. An attempt to pass the scope toward the 12 o’clock direction would cause either perforation or the scope to fold backward.

239

SECTION 2 TECHNIQUES

would simulate the view of driving a car in a long tunnel. It is common to see two lumens when a duodenoscope is partially retroflexed and it creates confusion regarding where to advance the endoscope. A good rule of thumb is to orientate the two lumens along the vertical midline and the lower lumen is the one that the endoscope should enter (Fig. 24.4B). Natural intestinal redundancy and tortuosity rarely allow unimpeded forward advancement. Rather, successful passages require a combination of gentle rotation, dial redirection, pulling and pushing. Care must be taken to minimize sudden or forceful manipulations, as perforation may result. In one series, perforation occurred in 5% and was mainly from manipulations in the afferent limb.3 In another study, 18% of the cases were complicated by jejunal perforation.2 Usage of a small caliber and soft, older duodenoscope may reduce the chance of traumatizing the intestinal wall. Minimizing air insufflation helps keep the lumen straight and the bowel wall soft and stretchable. Rotating the patient is occasionally effective in getting around seemingly improbable turns. These measures all may contribute to a safe and successful procedure. With experience and special care, an acceptable risk of perforation can be achieved.6 After passing some distance, it is wise to take a fluoroscopic picture to confirm that the scope has passed or is passing though the transverse duodenum (Fig. 24.5). If the scope is in the pelvis, then it is likely to be in the efferent limb and should be withdrawn to search for the other intestinal orifice. Some afferent limbs seem to be longer and more tortuous to reach the papilla than others. This impression is indeed correct, as the afferent loop may be created in the antecolic fashion over the transverse colon (Figs 24.6A, 24.6B). On the way to the proximal duodenum, an anastomosis that connects the afferent to the efferent limbs may be encountered. This Braun procedure is a modification of the Billroth II operation to reduce bile reflux into the stomach or to lessen the chance of duo-

Fig. 24.5 Fluoroscopy shows the duodenoscope is facing the right direction and crossing the transverse duodenum. 240

A

B

Fig. 24.6 A Retrocolic construction of the Billroth II gastrojejunostomy. The afferent limb is relatively short in this case. B Antecolic Billroth II gastrojejunostomy. The afferent limb is significantly longer than that in 24.6a.

Chapter 24 ERCP in Surgically Altered Anatomy

denal obstruction (Fig. 24.7). It should not influence the endoscopic passage other than by creating confusion to the endoscopist. On some occasions the duodenal stump appears as a blind sac with a distinctly flat and smooth mucosa and is reached without the major papilla being noticed. The minor and then major papilla should be readily identified upon gradual withdrawal of the endoscope (Figs 24.8A–24.8C). The major papilla is almost always found near the 12 o’clock position of the duodenum when a duodenoscope is used (Fig. 24.8C). If the intestinal lumen is kept in view ahead of the endoscope, then the bile duct leads away from the endoscope straight ahead or slightly to the right (Figs 24.9A, 24.10). In order to keep the cannulating catheter or guidewire tangentially to the duodenal wall for biliary access, the papilla should not be approached up close (Fig. 24.8C). Rather, the scope should be pulled back slightly with its elevator partially lowered for catheter passage. Conversely, the pancreatic duct is easier to cannulate by advancing the scope close to the papilla and keeping the elevator in a lifted position (Fig. 24.8B). Some endoscopists prefer to use straight-tip catheters for biliary cannulation,5 while others like to use straight guidewires. However, perhaps the most effective way in entering the bile duct is to use a catheter that has been bent in an S-shape (Fig. 24.9B). A cap-assisted approach has been described to improve cannulation of a Billroth II papilla when an end-viewing endoscope is used7 (Fig. 24.11). On some occasions when pancreas divisum is suspected, the minor papilla should be correctly identified for cannulation. As a general rule, it is located slightly further away from (cephalad to) and to the left of the major papilla (Figs 24.8A, 24.10). Biliary sphincterotomy is accomplished either by the use of a Billroth II sphincterotome or a needle-knife to cut over a biliary stent. A Billroth II push sphincterotome is designed virtually opposite to a conventional traction sphincterotome. The cutting wire is loosened to form a half loop over a straight sphincterotome catheter. The wire loop is then pushed forward to cut the papilla hood along the 12 o’clock position. Sphincterotomy done in this manner is slightly less well controlled than in the normal setting because of the pushing motion and suboptimal visualization of the proximal edge of the papillary mound. A modified sphincterotome that forces its tip into an S-shape when the cutting wire tightens may also be used to

A

B

perform sphincterotomy in this setting.8 However, most endoscopists seem to prefer needle-knife sphincterotomy over a biliary stent because it avoids injury to the pancreatic sphincter and allows gradual, unhurried tissue cutting.4,9 Balloon sphincter dilation, commonly done with an 8 mm balloon, is technically easy to perform. A randomized study showed balloon sphincter dilation was as effective as sphincterotomy to facilitate stone extraction and had fewer com-

Fig. 24.7 A Braun modification of a Billroth II operation. Here the afferent and efferent limbs are connected via a side-to-side anastomosis.

C

Fig. 24.8 A The minor papilla, which is quite prominent in this case, is located more cephalad to and to the left side of the major papilla. Further up the afferent lumen is the duodenal stump. B As the scope is pulled back from the duodenal stump, the major papilla is seen up close and perpendicular to the duodenoscope. This position favors cannulation of the pancreatic duct. C The duodenoscope is pulled back further and farther away from the major papilla. This position favors cannulation of the bile duct. 241

SECTION 2 TECHNIQUES

A

Fig. 24.9 A The major papilla is usually located at the 12 o’clock position. Here the guidewire points in the direction of the bile duct. B This S-shaped biliary cannula is best used for intubating the bile duct.

B

Minor papilla

Major papilla

Fig. 24.10 A schematic illustration of the relationship of the major and minor papillae and the directions of the bile duct (yellow arrow) and pancreatic duct (blue arrow).

Fig. 24.12

A typical Roux-en-Y gastrojejunostomy.

plications.9 Additionally, there was no more pancreatitis with this treatment than sphincterotomy.

Roux-en-Y gastrectomy Fig. 24.11 A balloon dilator is being used to perform sphincteroplasty using an end-viewing endoscope. Note a short, soft cap has been fitted to the tip of the scope. This cap is believed to improve the ability to cannulate the papilla. 242

Created to reduce reflux of pancreatic and biliary fluids into the stomach following a partial gastrectomy, the gastric outlet is constructed similar to that of a Billroth II surgery. However, this endto-side anastomosis leads to a very short blind stump and a long, efferent limb (Fig. 24.12). The jejunum of the efferent limb extends

Chapter 24 ERCP in Surgically Altered Anatomy

around 40 cm before a jejunojejunostomy anastomosis is found. At this point two or three lumens (Figs 24.13A, 24.13B) will be identified, depending on whether the two jejunal limbs are connected end-to-side (Fig. 24.13C) or side-to-side (Fig. 24.13D). If done sideto-side, one of the three outlets is a short, blind stump. If the afferent limb is correctly entered, the endoscope will travel up the proximal jejunum, the ligament of Treitz, transverse duodenum and finally the descending duodenum. This long distance to travel makes it nearly impossible for a 125 cm-long duodenoscope to reach the major papilla. Many longer-length endoscopes have been used to perform ERCP in this setting, including pediatric or adult versions of colonoscopes and push enteroscopes.10 A special oblique-viewing endoscope has been reported to be potentially useful for this purpose.11 Double-balloon enteroscopes can reach as far as the cecum per-orally and were introduced in the United States in 2004 (Figs 24.14A–D). ERCP, including therapeutic maneuvers, has been reported to be successful in 5 of 6 patients when using this new form of enteroscope.12 The challenge of performing ERCP in a Roux-en-Y gastrectomy lies not just in traveling a great length and recognizing the proper intestinal lumen but also in selectively cannulating the bile duct and pancreatic duct. All end-viewing endoscopes have the inherent difficulty in identifying the major papilla because of its location along

A

C

B

the interior aspect of the duodenal C-loop. Even when it is seen, cannulation is extraordinarily difficult because of awkward orientations and unstable positioning for cannulation (Figs 24.15A–C). In the hands of ERCP experts, the success rate is a mere 67%.13 Yamamoto and colleagues reported the success of performing diagnostic and therapeutic ERCP with a double-balloon enteroscope in five patients.12 Interestingly, the authors fitted a small plastic cap on the tip of the enteroscope to enable cannulation. It is uncertain if and how this plastic cap helps with the procedure. Given the difficulty and frequent failure of performing ERCP in this postoperative anatomy, it is best to refer this type of cases to a tertiary biliary center or choose an alternative method such as a transhepatic study. Performing ERCP with the intent to evaluate and treat a pancreatic condition is particularly problematic as a transhepatic procedure is ineffective. An intraoperative transjejunal ERCP method has been reported to overcome this difficulty. At laparotomy, an enterotomy is made at 20 cm distal to the ligament of Treitz to allow passage of a gas-sterilized duodenoscope to advance up the afferent limb.14

Total gastrectomy Done usually for treatment of gastric cancer, a total gastrectomy leads to the creation of an end-to-side esophagojejunostomy. One

Fig. 24.13 A A schematic illustration of 3 lumens at the point of a jejunojejunostomy anastomosis. The single distal lumen on the same side of the anastomosis is either the efferent or a blind limb. One of the two lumens on the other side of the anastomosis is a blind stump or the efferent limb while the other is the afferent limb. In either case, the afferent limb has to cross the line of anastomosis. B Endoscopic picture of the two lumens seen beyond an anastomosis. One of these two orifices should lead to the afferent limb. C Illustration of an end-toside jejunojejunostomy anastomosis. D Illustration of a side-to-side jejunojejunostomy anastomosis.

D

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B A

D

C

Fig. 24.14 The double-balloon system consists of a balloon on the tip of a thin endoscope A and a balloon on an overtube B. C Both balloons are inflated. D Balloon inflation device that controls air insufflation, deflation, pressure reading, and an alarm with a yellow-light indicator of excessive pressure.

A

B

C

Fig. 24.15 A The major papilla seen with an end-viewing endoscope. Note it is a very tangential view with an awkward position for cannulation. B After rotating the end-viewing endoscope, the major papilla appears to be optimally positioned for cannulation. The papilla is still tangentially located and it is difficult to maintain this view for long. C A catheter has been successfully inserted into the bile duct with this end-viewing endoscope. 244

Chapter 24 ERCP in Surgically Altered Anatomy

Fig. 24.16 A total gastrectomy with a Roux-en-Y esophagojejunostomy. In spite of the significant distance, a side-viewing duodenoscope is usually long enough to reach the papilla.

lumen of the esophagojejunostomy is a blind end, whereas the other is the efferent jejunal limb (Fig. 24.16). In a short distance down this limb is a side-to-side or end-to-side jejunojejunostomy to receive pancreatic and biliary contents. Similar to the Roux-en-Y gastrectomy, the endoscope has to enter the afferent limb and pass through the proximal jejunum and most of the duodenum. But unlike Rouxen-Y partial gastrectomy, a duodenoscope actually can reach the major papilla on a more regular basis. Once the major papilla is identified with the duodenoscope, the approach to ERCP cannulation and therapy is quite similar to that for a Billroth II anatomy. But if a duodenoscope is too short to reach the descending duodenum, then an end-viewing long endoscope has to be used. In that case, the challenge lies in cannulating and treating disease processes without the benefits of an elevator and the side-viewing capability.

tomy is usually located along the dependent portion of the stomach. However, it may be slightly off to the anterior or posterior wall along the greater curvature (Figs 24.17A, 24.17B). While most anastomoses for bypass of obstructive diseases are expected to be large, some of these gastrojejunostomy openings appear to be quite small. Immediately through the rim of anastomosis two jejunal orifices will be found, and either opening can be the one that leads to the afferent limb. If it is the more distal orifice, then it is an antiperistaltic connection and the afferent limb is relatively short. But this distance becomes longer if the surgery is done in the antecolic fashion because the intestine has to drape over the transverse colon. This limb may become even longer if the gastrojejunostomy is created in the isoperistaltic manner. On some occasions a second anastomosis is noted beyond the gastrojejunostomy. This Braun procedure (Fig. 24.17B) is done to add further bypass of contents between the afferent and efferent limbs to reduce alkaline biliary reflux into the stomach or to provide a safety net to minimize the chance of an afferent limb obstruction. If the scope passes through a Braun anastomosis, it has a 50% chance of returning to the stomach via the other limb of the gastrojejunostomy. Since the major papilla is intact in this setting, a duodenoscope is preferred for ease of inspection and cannulation unless it is proven to be too short. In practice, reaching the descending duodenum is often not the key issue. Instead, inspection and cannulation is a bigger challenge because most of these cases have a highly stenotic duodenum that has led to the gastrojejunostomy. Fortunately, duodenal obstruction from pancreatic head cancer is frequently located proximal to the major papilla leaving sufficient room to carry out an ERCP. In the event of an inadequate space, balloon dilation of the duodenal stricture can be perform but the resultant mucosal trauma and hemorrhage may add even more obstacles to the procedure. A transhepatic approach to biliary drainage is frequently necessary in this situation. Alternatively a rendezvous procedure, in which a transhepatic catheter or guidewire is passed across the biliary sphincter, can be done for endoscopic access. There are occasions when the bypass surgery is done for gastroparesis and performing an ERCP in the usual antegrade fashion is preferred. In this situation the duodenoscope has to be slightly rotated, when gliding along the greater curvature, to skip around the gastrojejunostomy to reach the pylorus.

Duodenal bypass

UPPER GI BYPASS SURGERY WITHOUT RESECTION

Duodenal perforations are occasionally treated by a duodenojejunostomy. Even though this form of operation is uncommon, the finding of two or more intestinal lumens beyond the pylorus or at the descending duodenum may create confusion to the endoscopist. If there is no associated duodenal narrowing, the procedure is straightforward and the key is to carefully inspect each lumen until the major papilla is found. If a mildly to moderately stenotic duodenal lumen is found, gentle balloon dilation may be attempted to ease the scope passage. Alternatively, a pediatric ERCP scope with a 7.5 mm outer diameter and 2.0 mm instrument channel can be used. But the small endoscope channel allows only limited therapeutic possibilities such as sphincterotomy, basket stone extraction and placement of a 5-French stent.

Gastrojejunostomy

BARIATRIC SURGERY

The indications for gastrojejunostomy without resection of any part of the stomach include large pancreatic head mass, benign chronic duodenal obstruction and unresectable malignant duodenal stricture. When inspecting the stomach during ERCP, the gastrojejunos-

There are many forms of bariatric operations to induce weight reduction, but about 70% of them in the US are Roux-en-Y gastric bypass. Biliopancreatic diversion (12%), vertical banded gastroplasty (7%) 245

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A

B

Fig. 24.17 A Gastric bypass with an anteriorly located gastrojejunostomy. B Gastric bypass with a posteriorly located gastrojejunostomy. Note a Braun procedure that connects the afferent and efferent jejunal limbs.

and gastric banding (5%) constitute the remaining practices of bariatric surgery today.15 Interestingly, morbidly obese patients are most likely to have bariatric surgery done in the northeastern United States than the rest of the country.16 As obesity affects more Americans, more weight-reduction operations are being performed. Since gallstone disease and abdominal pain are common issues in obese individuals, biliary and pancreatic evaluations are in increasing demand. At the same time, this group of patients are the most difficult to perform ERCP on because of the need to pass through the extremely long intestine to get to the proximal duodenum. Variation of techniques and surgeons’ preferences add further confusion to this difficult ERCP arena.

Malabsorptive-jejunoileal bypass This form of weight-reduction surgery is mentioned here primarily for the historical purpose. It is neither practiced today nor does it affect the performance of ERCP. Rarely, a consultation for ERCP may be requested for a patient with a prior jejunoileal bypass surgery because of jaundice. In this case, the cause of jaundice is more likely due to hepatic failure rather than biliary tract disease. This operation, popular prior to 1980, consists of transecting and connecting a large jejunoileal segment to the distal colon. Alternatively, the proximal jejunum is transected and connected to the distal ileum in an endto-side manner, excluding a long jejunum and ileum from contact 246

with intestinal nutrients (Fig. 24.18). The result of this form of operation is a very short functioning small bowel that causes weight loss by malabsorption and maldigestion. Chronic diarrhea, stone diseases and fatal liver dysfunction are reasons why all patients who have undergone this surgery should have a jejunoileal bypass reversed.17

Biliopancreatic diversion and duodenal switch There are two other forms of malabsorptive operations that are still practiced today. Metabolic complications are reportedly less often seen than in jejunoileal bypass. Both operations require resection of most of the stomach and connection of either the duodenum or the stomach remnant to the distal ileum (250 cm proximal to the ileocecal valve) (Figs 24.19A, 24.19B). The excluded block of duodenumjejunum-ileum is then hooked up to the distal ileum at around 100 cm proximal to the ileocecal valve. ERCP is not a possibility whether it is biliopancreatic bypass or duodenal switch because the descending duodenum can only be reached by passing through most of the small intestine.

Restrictive surgery There are two forms of this operation that aim to restrict food intake by creating a mere 15 ml proximal gastric pouch and a small pouch outlet of roughly 1 cm in diameter. Vertical band gastroplasty,

Chapter 24 ERCP in Surgically Altered Anatomy

Fig. 24.18 Jejunoileal bypass. This surgery does not interfere with the performance of ERCP.

popular in 1980s, consists of cutting off the fundus with staples and limiting the pouch outlet with a 5 cm circumferential Marlex band17 (Fig. 24.20A). A more modern alternative is the laparoscopic adjustable gastric banding procedure, done with placement of a silicone band that wraps around the gastric cardia (Fig. 24.20B). Tightness of this band can be modified following surgery by inserting a needle into a reservoir embedded in the abdominal wall. Restrictive gastric surgery is easily recognized endoscopically because of the tiny gastric pouch that leads to a small firm outlet that barely allows the passage of an upper endoscope. The channel length is usually only 1–2 cm. If this surgery is suspected in advance of the ERCP, it is best to start the procedure with a standard upper endoscope to inspect the tightness of the outlet. If difficulty passing a duodenoscope is anticipated, then dilating the ring outlet with a 13.5 mm balloon can be safely done. Once the duodenoscope has reached the distal stomach, no special technique is needed to accomplish an ERCP procedure. In patients who have regained their weight after a vertical band gastro-

plasty, their stomachs may appear normal with minimal evidence of any restriction or have two outlets from the pouch that lead to the rest of the stomach. This loss of physical restriction is either due to breakage of the gastric band or development of a gastric pouchgastric fundus fistula.

Gastric bypass This is the most commonly done surgical procedure to induce weight reduction today. It works by both restricting food intake with a small (<50 ml) gastric pouch and creating malabsorption with a proximal small bowel bypass. This is the most difficult form of Roux-en-Y surgical anatomy for performance of ERCP. In order to reach the papilla, the endoscope has to travel through 40 cm of the esophagus, a tiny gastric pouch, a 75–150 cm Roux limb followed by a variable-length afferent limb (Fig. 24.21). After arriving at the descending duodenum, the tip of the endoscope has to be flexible enough to visualize the major papilla and sufficiently still to perform 247

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B

A

Fig. 24.19 A Biliopancreatic diversion. The long efferent and afferent limbs prevent any chance of performing ERCP in this case. B Duodenal switch procedure. Very similar to the biliopancreatic diversion surgery, it is not possible to perform ERCP in this situation.

cannulation. Even a 250 cm-long push enteroscope is usually too short because of looping and stretching of the intestine. Working with long accessories to perform ERCP in this setting posts additional technical challenges that even elite endoscopists consider overwhelming. There are several ways of performing ERCP in this very difficult situation (Table 24.2). The simplest, but most likely method to fail is to use the longest endoscope available and cannulate the papilla with extra-long accessories. A more logical alternative is to use a double-balloon enteroscope, which is thinner, more flexible and 248

able to travel long segments of the intestine. Indeed, there is preliminary evidence that they can be used to carry out the procedure successfully in most cases.12 If cannulation is not possible in spite of successful scope advancement, then it is possible to perform a percutaneous endoscopic gastrostomy (PEG) by inserting the double-balloon enteroscope retrograde into the stomach. After the large bore fistula has matured, a duodenoscope can be inserted through the gastric fistula to perform ERCP. A similar alternative is to have a surgical gastrostomy tube placed and then perform ERCP after maturation of the tract.18 It is also possible to perform either

Chapter 24 ERCP in Surgically Altered Anatomy

A

B

Fig. 24.20 A Vertical banded gastroplasty, with a small aperture that allows food passage. This channel may have to be dilated in order to pass a duodenoscope. B Laparoscopic adjustable gastric banding. The degree of constriction in the proximal stomach is adjustable externally.

Per-oral with a long scope: Colonoscope (therapeutic, pediatric) Duodenoscope (not advisable) Push enteroscope (need special long accessories) Double-balloon enteroscope (need special long accessories) Via a mature gastrocutaneous fistula Fistula created at surgery Fistula created by retrograde PEG Fistula created by percutaneous gastrectomy Rendezvous approach with a long scope Intra-operative via a stoma using a sterilized endoscope Gastric stoma Proximal jejunal stoma

Table 24.2 Methods of performing ERCP in gastric bypass patients

an open surgical gastrostomy or a laparoscopic gastrostomy duodenoscope insertion in one setting.19 Alternatively, a transjejunal operative approach to advance a duodenoscope at 20 cm below the ligament of Treitz may be attempted.14 Of course, the Rendezvous procedure that involves placement of a percutaneous transhepatic guidewire into the duodenum/jejunum may help passage of the endoscope as well as gaining access into the bile duct. Finally, not all biliary diseases require endoscopic manipulations and a solely

transhepatic approach may be sufficient to manage these conditions without involving the endoscopist.

PANCREATIC RESECTION Conventional Whipple procedure The most well-known pancreatic surgery is the Whipple operation or pancreaticoduodenectomy, done for resection of malignant or benign pancreatic head lesions. While the concept of resection is simple, the multiple anastomoses in this operation create a great deal of confusion to the non-surgeons. Since bile duct, pancreatic duct and duodenum are interrupted, at least three separate connections are made to re-establish pancreatic, biliary and intestinal continuity. When an endoscope is passed into the mid-stomach, two small bowel orifices are seen in the conventional Whipple (Fig. 24.22A). One gastrojejunostomy ascends up the afferent limb and joins the bile duct and eventually the pancreatic duct. The other orifice leads to the efferent limb and the rest of the gastrointestinal tract. Since the usual challenge of cannulating an intact papilla is absent, ERCP can be readily performed with either an end-viewing or a side-viewing endoscope. It is possible to start this procedure with a diagnostic upper endoscope to take advantage of its small caliber and flexibility. If a gastric loop prevents the endoscope from reaching the biliary anastomosis, a scope-stiffening stylet may be inserted into the gastroscope instrument channel. If a diagnostic 249

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be seen at either the very proximal end of the afferent limb (invagination of the pancreatic remnant into the end lumen of the intestine) (Figs 24.22A and 24.22C) or slightly before the surgically closed stump is reached (end-to-side, mucosa-to-mucosa, pancreaticojejunostomy) (Figs 24.22D and 24.22E).

Pylorus-preserving Whipple procedure Aimed to minimize the gastric emptying problem and other surgery related morbidity, a pylorus-preserving Whipple is different from the conventional Whipple by preserving the full stomach and a tiny segment of the proximal duodenal bulb (Fig. 24.22D). However, this presumed advantage of keeping the antrum and pylorus has not been proven.20 When performing an ERCP, the stomach and pylorus appear normal. Immediately past the pylorus are two jejunal lumens, with either one possibly leading to the biliary and pancreatic anastomoses. However, the efferent limb is frequently pointing directly away from the pylorus.

Pancreaticogastrostomy A pancreaticoduodenectomy can be further modified to have the main duct of the body and tail of the pancreas implanted into the posterior wall of the stomach21 (Fig. 24.23). In this case, the bilioenteric anastomosis is found along the afferent limb in the usual manner. However, the pancreatic orifice is no longer seen near the end of the proximal jejunal stump. Rather, it is located along the posterior gastric wall as a small opening. Finding the anastomosis among the gastric rugal folds can be difficult; but parenteral injection of secretin and spraying a color dye on the gastric mucosa may help with the identification.

Other pancreatic resective surgery

Fig. 24.21 Gastric bypass surgery for weight reduction that combined restrictive and malabsorptive principles. This increasingly common operation is one of the most challenging surgically altered anatomies for performance of ERCP. upper endoscope is too short, then a pediatric colonoscope should be able to get to the bilioenteric and even the pancreaticoenteric anastomosis (Fig. 24.22B–C). A 120 cm, therapeutic channeled, oblique-viewing prototype endoscope was successful in treating a post-Whipple case that had failed other attempts with existing endoscopes.11 However, more clinical experience with this scope is necessary to reveal the true value of this oblique-viewing endoscope in this setting. Fluoroscopy may occasionally be of benefit to confirm if the endoscope is within the afferent limb because it should be located in the right upper quadrant. Fluoroscopy may also help to locate the anastomosis as it is always coming off the most cephalad portion of the bowel gas in the right upper quadrant. A patent hepaticojejunostomy should also allow pneumobilia to be visualized. Endoscopically, a normal bile duct anastomosis is readily identified as a round orifice with bile existing. The opening is frequently located eccentrically or retracted behind an intestinal fold. It is usually a subjective opinion in diagnosing a mild or moderate hepaticojejunostomy narrowing. In severe stenosis, the opening can appear as a pinhole or be covered completely by a film of whitish scar tissue. The pancreaticoenteric anastomosis is notoriously difficult to identify and cannulate. It can 250

Resection of the tail of the pancreas does not alter gastric, duodenal or pancreaticobiliary anatomy. Injection of contrast across the pancreatic sphincter would obviously discover a shortened duct. Midpancreatic resections for benign diseases may result in a normal anatomy in the head of the pancreas and a very short pancreatic duct. The tail of the pancreas is usually drained into a piece of jejunum. Studying the pancreaticojejunostomy in this setting is difficult. When the tail of the pancreas is connected to the posterior wall of the stomach, the possibility of accessing the pancreatic duct becomes much greater.22

PANCREATIC DUCT DRAINAGE PROCEDURES Puestow procedure This longitudinal pancreaticojejunostomy procedure is favored by most pancreatic surgeons for decompression of a dilated pancreatic duct for relief of pain from chronic pancreatitis. The procedure involves opening the pancreatic duct from the head to the tail of the pancreas and creating a side-to-side anastomosis between the open edges of the pancreatic duct and those of a piece of jejunum.23 There is obviously no anatomical alteration in the upper gastrointestinal tract as a result of the surgery and ERCP can be done in the usual manner. Contrast injection into the main pancreatic sphincter should identify the Wirsung duct followed by immediate opacification of the jejunum. While determining if there is a stricture between the Wirsung duct and the jejunum is relatively easy, there is no certainty if the duct beyond that point is fully decompressed by the surgery.

Chapter 24 ERCP in Surgically Altered Anatomy

A B

D

C

E

Fig. 24.22 A Conventional Whipple procedure. Note the pancreatic duct is found at the upper end of the afferent limb. B A cholangiogram obtained through a hepaticojejunostomy anastomosis with a pediatric colonoscope. C A pancreaticogram of a markedly dilated pancreatic duct following a Whipple procedure. D Pylorus-preserving Whipple procedure with an intact stomach and a very short duodenal bulb before the lumen splits into the afferent and efferent limbs. Note the pancreaticojejunostomy is fashioned on the side of the proximal afferent limb before the intestinal lumen ends in this case. A corresponding radiograph (E) showing the relationship between the endoscope and a tortuous and markedly dilated pancreatic duct due to stenosis of the pancreaticojejunostomy. The afferent jejunum ends a few centimeters straight away from the tip of the endoscope.

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anastomosis is made in a side-to-side fashion between the proximal duodenum and the mid-bile duct (Fig. 24.24A). However, this procedure may be complicated by recurrent fever, abdominal pain, liver abscess, pancreatitis or cholangitis. Bile duct impaction due to trapped debris distal to a choledochoduodenostomy is referred to as the sump syndrome (Figs 24.24B,C,F). Interestingly, symptoms of sump syndrome usually occur 5–6 years after the surgery is performed.25 Inspection of biliary complaints in this situation should aim at studying the bile duct via the major papilla. However, the biliary sphincter is frequently stenotic and may not allow access through it. Therefore, contrast injection via the anastomosis may become necessary. Identification of the orifice, which is normally about 0.5 to 1 cm in diameter, is difficult because it is often located in the posterior aspect of the proximal descending duodenum (Fig. 24.24D). Nonetheless, careful inspection and gentle rotation of the duodenoscope should reveal this opening. A biliary sphincterotomy may provide relief from sump syndrome for up to several years.25 Jaundice and recurrent cholangitis may also occur as a result of stenosis of the choledochoduodenostomy; balloon dilation and stenting through the strictured anastomosis is necessary in this situation.

Roux-en-Y hepaticojejunostomy

Fig. 24.23 Pancreaticogastrostomy. The arrow points to the pancreatic duct that is directly anastomosed to the posterior wall of the stomach. Endoscopic pancreatography is possible if this gastric anastomosis is identified.

Frey’s procedure This is a procedure that combines a longitudinal pancreaticojejunostomy (see Puestow procedure above) and duodenum-preserving, local removal of pancreatic tissue within the head of the pancreas.24 Similar to the Puestow procedure, injection of contrast should identify a Wirsung duct that drains into the intestine. In spite of the resection of a big portion of the head of the pancreas, the pancreatic duct is not interrupted and therefore should show no altered anatomy or the appearance of any anastomosis.

Duval procedure One of the original pancreatic duct drainage procedures, this surgery involves resection of the tail of the pancreas and the spleen and creation of an end-to-end pancreaticojejunostomy. The principal function of this surgery is to allow backward drainage of an obstructed pancreatic duct into the jejunum rather than through the obstruction at the head of the pancreas. However, this operation has a high incidence of treatment failure and is rarely practiced today. A pancreatogram should reflect a slightly shortened pancreatic duct that connects to an intestinal lumen in this situation.

BILIARY SURGERY Choledochoduodenostomy This is a simple form of surgery to provide mid-bile duct drainage for a benign condition such as a distal bile duct stricture or recurrent choledocholithiasis. There is usually no ductal transection, and the 252

The hepatic duct is surgically connected to the jejunum in a variety of conditions, including recurrent biliary stones, benign distal biliary strictures, cholangiocarcinoma, choledochal cyst, liver transplantation and iatrogenic bile duct injury. In stone disease and benign biliary stasis, continuity of the entire biliary tract may be kept and the biliojejunal anastomosis is constructed side-to-side. ERCP can be carried out in the usual way by accessing the major papilla (Fig. 24.25A). The clue to this surgery is continuous spillage of contrast into the jejunal lumen, located near the duodenal bulb. Quality cholangiograms can be obtained only by injection of contrast superior to the hepaticojejunostomy or by occluding the common hepatic duct with a stone-retrieval balloon. Most of the time a hepaticojejunostomy is created with transection of the mid-bile duct. In this situation a cholangiogram via the major papilla should show a complete blockage at the proximal common bile duct (Fig. 24.25B). If this is known in advance, performing a standard ERCP via the major papilla to study the biliary tract is unnecessary and raises the risk of otherwise negligible chance of pancreatitis. Sometimes the surgically ligated stump is misinterpreted as tight biliary stricture and perforation may occur due to aggressive probing of the blind end. Studying the biliary system proximal to the transected bile duct is a rather difficult task. It requires a long endoscope that can travel through the entire duodenum, ligament of Treitz, proximal jejunum, jejunojejunostomy and the afferent limb. A variable-stiffness pediatric colonoscope is the ideal endoscope for this purpose, although a push enteroscope, therapeutic colonoscope or double balloon enteroscope may also be used. Since there is no major papilla involved, accessing the bile duct is relatively straightforward once the proximal afferent limb is reached. Nonetheless, searching for the hepaticojejunostomy or choledochojejunostomy anastomosis may take some experience. It is frequently hidden behind a sharp turn or a recessed fold. Viewing is often difficult because it may only be partially visible near the edge of an endoscopic image. Cannulation may be possible with the use of a guidewire in this situation. An immediate bifurcation may be noted if the anastomosis is created in

Chapter 24 ERCP in Surgically Altered Anatomy

A

B

D

C

F

Fig. 24.24 A A choledochojejunostomy without interruption of the bile duct. The bile duct can be accessed either through the major papilla or the choledochoduodenostomy. B A pigmented stone (thin arrow) and a large piece of fresh vegetable (large arrow) was swept into the duodenum after a sphincterotomy. C More foreign body-like biliary debris was extracted from the bile duct of the same patient. This material appears to have been in the bile duct for a long duration. D A schematic illustration of the usual relationship between the choledochoduodenostomy and the major papilla. Finding the anastomosis can be quite difficult because of its usual location in the posterior wall of the proximal descending duodenum. E A biliary stent was visualized through a choledochoduodenostomy as expected. F A cholangiogram typically seen in a sump syndrome. The open arrow points towards the choledochoduodenostomy where biliary contrast escapes laterally into the duodenum. Thin arrows show filling defects throughout the dilated bile duct.

E

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A

B

Fig. 24.25 A Roux-en-Y hepaticojejunostomy without transection of the bile duct. ERCP is done in the usual fashion and contrast is seen flowing outside of the bile duct via the biliary bypass into the jejunum. B Roux-en-Y hepaticojejunostomy without biliary continuity. In this case, the only possible way to study the bile duct is by passing a long endoscope through the proximal jejunum and up the afferent jejunal limb. Injection of the major papilla to evaluate the bile duct should be avoided to prevent causing pancreatitis.

the proximal hepatic duct. On rare occasions, two separate orifices may be identified when the bilioenteric anastomosis is created very high up the bile duct. When the anastomosis is severely stenosed, a seemingly complete closure by a film of whitish scar tissue may be observed. It is essential to look for a fully opacified intrahepatic cholangiogram. If a part of the intrahepatic distribution is missing, then a ductal stricture or an occluded separate orifice should be suspected.

Cholecystojejunostomy This operation was once commonly employed to bypass the bile duct obstructed by an obviously unresectable pancreatic head cancer. However, this form of surgery is an unreliable means to decompress the bile duct because of the potential of tumor extension to involve the cystic duct. The surgery is a very simple one whereby a distended gallbladder is opened up and anastomosed to a jejunal limb (Fig. 24.26). Today, this operation is mostly reserved for the intra-operative finding of an unresectable and obstructing cancer 254

that is too large to allow access to the proximal bile duct to create a hepaticojejunostomy. This surgery does not alter the upper GI anatomy and poses no additional difficulty to the regular ERCP. In fact, the result of this surgery is not readily recognized unless the bile duct is overfilled with contrast.

Liver transplantation The bile duct anastomosis in liver transplantation is usually a ductto-duct connection or choledochocholedochostomy. There is no special technical challenge to the performance of ERCP in this situation. When the transplantation is done for primary sclerosing cholangitis or other conditions in which the distal bile duct cannot be used, then a Roux-en-Y choledochojejunostomy or hepaticojejunostomy is constructed (Fig. 24.25b). Some living donor liver transplantation cases also utilize Roux-en-Y hepaticojejunostomy because of difficulty in matching up the native bile duct with the donor right hepatic duct. As mentioned before, a long endoscope is mandatory for a successful ERCP study in this situation.

Chapter 24 ERCP in Surgically Altered Anatomy

Fig. 24.26 A schematic drawing of a partially exposed proximal afferent jejunum to illustrate biliary decompression through a patent cystic duct. This form of surgery does not interfere with the performance of ERCP and may not even be recognized if only a small amount of contrast is injected above an obstructed distal bile duct.

Hepaticocutaneous jejunostomy This form of biliary surgery is rarely encountered in the US but is occasionally done in Asia, where recurrent pyogenic cholangitis is prevalent. This is essentially a Roux-en-Y hepaticojejunostomy with an extension of the afferent limb to the abdominal wall as a permanent stoma or to be concealed in the subcutaneous tissue. The persistent nature of recurrent pyogenic cholangitis mandates an easy access to the bile duct for periodic clearance of intrahepatic biliary stones.26 Via this stoma a choledochoscope, bronchoscope or a pediatric upper endoscope can be inserted into the intrahepatic ducts for stricture dilation and stone extraction. This cutaneous stoma provides a highly convenient means of biliary access without having to perform numerous difficult ERCP and per-oral choledochoscopies. It should significantly reduce the risks of post-ERCP cholangitis, cumulative radiation exposure and repeated prolonged sedation.

ENDOSCOPIC TECHNIQUES COMMONLY EMPLOYED FOR ERCP IN SURGICALLY ALTERED ANATOMY Performing a Rendezvous procedure There is no single Rendezvous technique adopted by all gastroenterologists for endoscopic biliary access through the use of a percutane-

ous transhepatic biliary guidewire or catheter. Most of these procedures are done in two steps and possibly in two locations of a hospital.27 An interventional radiologist would first insert a needle into a dilated peripheral intrahepatic duct. A guidewire, between 250 cm and 450 cm in length, is then passed through the needle into the bile duct and eventually into the duodenum or jejunum if there is a biliojejunal anastomosis. The external end of the guidewire is then secured onto the abdominal wall with heavy dressing. Some radiologists prefer to slide a thin-caliber biliary catheter over the guidewire to protect liver and biliary tissue from slicing injuries from a thin, tightly wound, wire.27 The patient is then transferred to an endoscopic suite where ERCP is performed. If endoscope passage is met with technical difficulty, such as in the case of a long afferent limb of a Whipple procedure, the guidewire can be floated down the intestinal lumen under fluoroscopy guidance until it is seen endoscopically. The guidewire is grasped with a snare and pulled up the endoscope channel until it can be secured externally. With a slight traction on the guidewire, the endoscope may be advanced along the lumen. However, the assumption that an externally placed wire may readily pull an endoscope up the afferent tract is inaccurate. In fact, excessive tension on a tightly drawn wire can injure the intestine or liver tissue and must be avoided. For the most part, the rendezvous procedure is done for traversing a difficult papilla or a tight stricture. The free end of the wire is 255

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snared and pulled up the channel of the endoscope until it can be secured externally. During the guidewire manipulation, the external end must be secured with a clamp to prevent it from being drawn into the intestine. Once the guidewire has been pulled outside of the instrument channel a sphincterotome, balloon dilator or biliary stent is readily passed over the guidewire into the bile duct to complete the ERCP procedure. Alternatively, a needle-knife sphincterotomy can be done over the transhepatic guidewire or catheter to create a space on the papilla for subsequent biliary cannulation. Yet another way to complete a Rendezvous procedure is to slide a catheter directly onto the free end of the guidewire that is barely exposed through the papilla to perform a sphincterotomy, stricture dilation or stenting. Finally, a two-step procedure that combines transhepatic placement of an 8 Fr external-to-duodenal biliary catheter with a subsequent ERCP session to cannulate the bile duct alongside the biliary drain has been described.28

Choosing an intestinal anastomotic opening to enter It is often confusing when the endoscope reaches an anastomosis with more than one exiting lumen. Additionally, correctly finding the afferent limb amongst several orifices at an anastomosis is a difficult and time-consuming task. There is no quick solution other than examining the anatomy carefully and systematically. A thorough understanding of small bowel surgery may minimize the frustration. Recognizing which lumen has been examined is crucial so that there is no wasted time by entering the same lumen over and over. Some endoscopists use India ink to mark the examined lumen, whereas others take superficial biopsies or leave cautery marks. It is important to know that there are either two or three lumens at any given anastomosis, depending on whether they are the results of a side-to-side (3 lumens) or end-to side (2 lumens) reconstruction (Figs 24.13A–D). It is equally important to know that the afferent limb is usually not a direct extension of the Roux limb. Therefore, it is important to observe where the suture line is. The afferent limb should be one of the lumens that crosses the suture line. An exception is when a Braun procedure is found but this should be suspected whenever a second anastomosis in a series is noted. Since many of these procedures have to be repeated in the future, it is important to construct a roadmap by carefully documenting how the afferent limb and papilla or bilioenteric anastomosis are found.

On rare occasions, fluoroscopic examination may visualize a redundant gastric or jejunal loop that can be gently straightened before making further advancement. Some highly angulated intestine behaves like a blind pouch. The downstream lumen may be identified only by probing with a hydrophilic wire or infusion of contrast into the intestinal lumen. Finally, it is important to be willing to stop a procedure if repeated attempts fail to lead to any forward progress.

ERCP ACCESSORIES Billroth II gastrectomy may be the most common surgically altered anatomy encountered in an ERCP. All commercially available ERCP accessories can be used; however, they may have to be modified in order to gain access into the tangentially and upside-down oriented bile duct (Fig. 24.27A). Sphincterotomes are also specially made to accommodate the distorted anatomy (Fig. 24.27B). The techniques of using these catheters and sphincterotomes are intuitive, but can be difficult with the first few uses. In spite of the concern for severe pancreatitis,29 balloon sphincter dilation is an important therapeutic option if the endoscopist is unfamiliar with performing sphincterotomy in this setting. In fact, a small study showed no disadvantage in employing balloon dilation to remove biliary stones in Billroth II cases.9 When a colonoscope is used, most diagnostic and therapeutic

A

B

Navigating through the small intestine Passing through the small intestine is similar to navigating the lumen of a tortuous colon; simply pushing an endoscope would not get far. Whether it is using a side-viewing or end-viewing endoscope, gentle rotation and intermittent shortening are essential maneuvers. But handling a side-viewing duodenoscope requires very careful manipulations to avoid causing perforation. When a duodenoscope is used, the scope should constantly be adjusted so that the intestinal lumen is situated at the 6 o’clock position before it can be advanced forward. Sudden rotation and forceful pulling should be avoided to prevent trauma to the intestine. Minimizing air insufflation is equally important, as it reduces bowel tortuosity and allows stretching room so there is less chance of traumatizing the intestinal wall. When repeated passages result in paradoxical movements, hand compression of the abdomen may have positive effects similar to maneuvers used in passing a colonoscope. Rotating the patient may straighten out a segment of the intestine and allow further passage. 256

Fig. 24.27 A Three types of diagnostic instruments are commonly used for cannulating the Billroth II bile duct. A tapered ERCP catheter bent into an S-shape is probably the most useful instrument. Some endoscopists prefer to use a catheter with a straight hydrophilic wire. Still other endoscopists find it helpful to start with a straight, uncurved cannula. B Sphincter-cutting accessories include a push-type sphincterotome with a protruding loop when the cutting wire is loosened, a sphincterotome with the cutting wire at the very tip, an S-shape sphincterotome, and the needle-knife.

Chapter 24 ERCP in Surgically Altered Anatomy

ERCP accessories may be sufficiently long to use. For instance, all plastic biliary stenting can be carried out. On the other hand, most biliary balloon dilators are too short. However, colonic balloon dilators can be used instead. Some, but not all, sphincterotomes are sufficiently long for use through a colonoscope. Each endoscopy unit should consult with its ERCP accessory manufacturers to put together a complete set of supplies for this purpose. It is far more challenging to find the right accessories for use through a push enteroscope or double-balloon enteroscope. With lengths of 200 to 250 cm, these endoscopes are too long for most commercially available ERCP instruments. Cook Medical Inc. (Winston Salem, North Carolina) does make available a selection of extra-long supplies that include diagnostic cannulas, retrieval balloons, over-the-wire dilators and sphincterotomes. However, exchanges of these instruments are more difficult than usual because of added friction and inadequate lengths of guidewires. Even 450 cmlong guidewires are too short to perform exchanges of 300 cm length catheters. Since it is difficult to perform ERCP in a Roux-en-Y anatomy, every effort has to be made to reduce the necessity of

repeating the procedure. Therefore, nasobiliary drainage catheters are more likely to be used in this setting than ordinary ones.

CONCLUSION Performing ERCP in a surgically-altered anatomy is a uniquely challenging experience. Preprocedure planning, stocking of appropriate accessories and knowledge of surgical procedures are as important as good endoscopic skills in achieving success. ERCP in Billroth II predisposes to a high risk of perforation and should be done only by those with a record of acceptable safety. Accessing the bile duct through the afferent limb of a Roux-en-Y anatomy, once considered an improbability, is increasingly accomplished by expert endoscopists. However, the bar of technical difficulty has been raised by the recent dramatic rise in bariatric surgery. Other than an occasional case of favorably short Roux and afferent limbs, the gastric bypass surgery makes ERCP far too challenging a procedure to perform. Whether a double-balloon enteroscope offers a solution to this problem remains to be seen.

REFERENCES 1.

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Briel JW, Tamhankar AP, Hagen JA, et al. Prevalence and risk factors for ischemia, leak, and stricture of esophageal anastomosis: gastric pull-up versus colon interposition. J Am Coll Surg 2004; 198:536–542. Kim MH, Lee SK, Lee MH, et al. Endoscopic retrograde cholangiopancreatography and needle-knife sphincterotomy in patients with Billroth II gastrectomy: a comparative study of the forward-viewing endoscope and the side-viewing duodenoscope. Endoscopy 1997; 29:82–85. Faylona JM, Qadir A, Chan AC, et al. Small-bowel perforations related to endoscopic retrograde cholangiopancreatography (ERCP) in patients with Billroth II gastrectomy. Endoscopy 1999; 31:546–549. Feitoza AB, Baron TH. Endoscopy and ERCP in the setting of previous upper GI tract surgery. Part I: Reconstruction without alteration of pancreaticobiliary anatomy Gastrointestinal Endoscopy 2001; 54:743–749. Lin LF, Siauw CP, Ho KS, et al. ERCP in post-Billroth II gastrectomy patients: emphasis on technique. Am J Gastroenterol 1999; 94:144–148. Swarnkar K, Stamatakis JD, Young WT. Diagnostic and therapeutic endoscopic retrograde cholangiopancreaticography after Billroth II gastrectomy–safe provision in a district general hospital. Ann R Coll Surg Engl 2005; 87:274–276. Lee YT. Cap-assisted endoscopic retrograde cholangiopancreatography in a patient with a Billroth II gastrectomy. Endoscopy 2004; 36:666. Hintze RE, Veltzke W, Adler A, et al. Endoscopic sphincterotomy using an S-shaped sphincterotome in patients with a Billroth II or Roux-en-Y gastrojejunostomy. Endoscopy 1997; 29:74–78. Bergman JJ, van Berkel AM, Bruno MJ, et al. A randomized trial of endoscopic balloon dilation and endoscopic sphincterotomy for removal of bile duct stones in patients with a prior Billroth II gastrectomy. Gastrointest Endosc 2001; 53:19–26. Elton E, Hanson BL, Qaseem T, et al. Diagnostic and therapeutic ERCP using an enteroscope and a pediatric colonoscope in longlimb surgical bypass patients. Gastrointest Endosc 1998; 47:62–67. Law NM, Freeman ML. ERCP by using a prototype obliqueviewing endoscope in patients with surgically altered anatomy. Gastrointest Endosc 2004; 59:724–728.

12. Sato H, Tamada K, Kita H, et al. Application of double-balloon endoscopy for afferent limb lesions of Roux-en-Y surgical anastomoses. Gastrointest Endosc 2005; 61:AB238. 13. Byron E, Wright BE, Cass OW, et al. ERCP in patients with longlimb Roux-en-Y gastrojejunostomy and intact papilla. Gastrointest Endosc 2002; 56:225–232. 14. Mergener K, Kozarek RA, Traverso LW. Intraoperative transjejunal ERCP: case reports. Gastrointest Endosc2003; 58:461–463. 15. Neligan PJ, Williams N. Nonsurgical and surgical treatment of obesity. Anesthesiol Clin North America 2005; 23:501–523, vii. 16. Poulose BK, Holzman MD, Zhu Y, et al. National variations in morbid obesity and bariatric surgery use. J Am Coll Surg 2005; 201:77–84. 17. DeMaria EJ, Jamal MK. Surgical options for obesity. Gastroenterol Clin N Am 2005; 34:127–142. 18. Baron TH, Vickers SM. Surgical gastrostomy placement as access for diagnostic and therapeutic ERCP. Gastrointest Endosc 1998; 48:640–641. 19. Pimentel RR, Mehran A, Szomstein S. Laparoscopy-assisted transgastrostomy ERCP after bariatric surgery: case report of a novel approach. Gastrointest Endosc 2004; 59:325–328. 20. Stojadinovic A, Brooks A, Hoos A, Jaques DP, Conlon KC, Brennan MF. An evidence-based approach to the surgical management of resectable pancreatic adenocarcinoma. J Am Coll Surg 2003; 196:954–964. 21. Aranha GV, Hodul, PJ, Creech S, et al. Zero Mortality after 152 Consecutive Pancreaticoduodenectomies with Pancreaticogastrostomy. J Am Coll Surg 2003; 197:223–231. 22. Sugiyama M, Abe N, Ueki H, et al. Pancreaticogastrostomy for reconstruction after medial pancreatectomy. J Am Coll Surg 2004; 199:163–165. 23. Steer ML. Townsend: Sabiston Textbook of Surgery, 17th edn, 2004 Saunders. 24. Frey CF, Amikura K. Local resection of the head of the pancreas combined with longitudinal pancreaticojejunostomy in the management of patients with chronic pancreatitis. Ann Surg 1994; 220:492–507. 25. Caroli-Bosc FX, Demarquay JF, Peten EP, et al. Endoscopic management of sump syndrome after 257

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choledochoduodenostomy: retrospective analysis of 30 cases. Gastrointest Endosc 2000; 51:180–183. 26. Fan ST, Mok F, Zheng SS, et al. Appraisal of hepaticocutaneous jejunostomy in the management of hepatolithiasis. Am J Surg 1993; 165:332–335. 27. Calvo MM, Bujanda L, Heras I, et al. The rendezvous technique for the treatment of choledocholithiasis. Gastrointest Endosc 2001; 54:511–513.

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28. Dickey W. Parallel cannulation technique at ERCP rendezvous. Gastrointest Endosc—2006; 63:686–687. 29. DiSario JA, Freeman ML, Bjorkrnan DJ, et al. Endoscopic balloon dilation compared to sphincterotomy (EDES) for extraction of bile duct stones: preliminary results. Gastrointest Endosc 1997; 45: AB129.

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25

APPROACH TO CLINICAL PROBLEMS

Dilated Bile Duct Geoffrey Spencer and Michael L. Kochman

BACKGROUND The dilated bile duct is a commonly encountered phenomenon in the daily practice of clinical medicine and is often generally felt to represent a pathologic obstructive process limiting the flow of bile. The indication and goal of any further evaluation would, therefore, be to diagnose and treat an unrecognized obstructive lesion. Developing an approach to the evaluation of the dilated bile duct requires definition of the normal limit of bile duct size, developing predictive markers for an obstruction, and consideration of the accuracy of the various imaging modalities for defining the etiology of an obstruction. Developing a definition for biliary dilation depends on the site of measurement. Dilation may be present in the intra or extrahepatic biliary systems or both. Assuming that this dilation is a manifestation of obstruction then a distal lesion would lead to diffuse dilation as compared to a more proximal lesion giving rise to focal intrahepatic dilation. Intrahepatic ducts as small as 1–2 mm are seen as scattered and non-confluent on abdominal computed tomography or ultrasonography, but become confluent and more easily imaged as they move centrally with diameters exceeding 2 mm in size (Fig. 25.1).1 Abnormal intrahepatic ducts are present when duct diameter exceeds 40% of the diameter of the adjacent intrahepatic portal vein and when they appear as parallel tubes coursing together.1 An increase in diameter of the extrahepatic bile ducts, in particular the common hepatic duct (CHD) or common bile duct (CBD), is often referred to as biliary dilation. The normal size of the duct varies at different levels, for example, at the confluence of the hepatic ducts and at the union of the CBD and cystic duct, and it varies from person to person.1,2 Numerous potential causes have been elucidated which may affect the diameter of the extrahepatic ducts. First, the imaging modality used to evaluate the biliary system can influence the reported duct diameter. Extracorporeal ultrasonography measures the internal diameter of the duct (Fig. 25.2).2,3 These measurements of the CHD are typically obtained at the level of the hepatic artery in the porta hepatis, anterior to the main or right portal vein or more distally of the CBD.1,4 Most ultrasound (US) studies have placed the upper limit of normal for the diameter of the CBD at 6–8 mm and that of the CHD at 6 mm.1,4–7 However, on computed tomography (CT), it is more common to accept values of 8–10 mm for the CBD.1,2 This difference is in part due to measurements performed at different locations along the duct. Unlike US, CT can more easily image the mid to distal portions of the CBD which are often larger in diameter.1 It also more readily identifies the fat around the duct and measurements include the duct wall (Fig. 25.3). Evaluation of the biliary system with cholangiogram, by endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC) may also yield results different than with other imaging techniques. A study of 135 patients who underwent imaging of their

extrahepatic bile ducts with US and ERCP or PTC demonstrated duct size of up to 4 mm by US versus 10.4 mm and 10.6 mm by ERC and PTC respectively.8 This was likely a result of radiographic magnification of the cholangiogram and may also reflect distention from contrast injection. Measurements of bile duct caliber have not all been uniform even when using the same imaging modality. For example, a study using US to measure CBD diameters recorded normal values up to 8– 10 mm in completely asymptomatic patients.5 This study noted a trend towards increasing diameters in older-age individuals supporting a belief that the duct size may increase with age. This thought has generated principles including adding 0.4 mm to the upper limit of normal for duct size for each decade of life or 1 mm per decade of life after age 60 years.7,9,10 However, a large US study of 1018 asymptomatic adults demonstrated a slight trend toward an increase in duct size with age, but not as large as had been previously reported, with a mean diameter of 3.6 mm at age 60 years and 4 mm at 85 years.7 In this study, 99% of the patients had a CBD diameter less than 7 mm. Patient characteristics other than age can affect the upper limit of normal for the CBD. Since Oddi first predicted the phenomenon in 1887, dilation of the CBD after cholecystectomy has remained controversial.11 Several prospective studies found no ductal dilation on US in patients before and after cholecystectomy.12,13 However, other studies have demonstrated a slight trend towards ductal dilation post-cholecystectomy which was statistically significant over time.14–17 In a study of 234 patients undergoing cholecystectomy, the CBD increased after surgery from a mean of 5.9 mm before cholecystectomy to 6.1 mm at an average of 393 days postcholecystectomy.17 As in other studies, the patients who had dilation of the CBD after surgery, the increase in diameter was of the order of 1–2 mm in the majority of patients and it has been suggested that the upper limit of normal based on US be adjusted up to 8 mm in such patients.15 In a study of 24 patients undergoing elective cholecystectomy, two asymptomatic patients with normal laboratory results were noted to have an increase in ductal diameter of 4 mm or more with duct diameters of >9 mm and >10 mm at 5 years postcholecystectomy.16 Though most patients have minor if any dilation post-cholecystectomy, there are clearly those that may manifest a more profound asymptomatic dilation of the ducts. Variation of normal extrahepatic bile duct size due to extrinsic factors such as time of day, respiration, or patient positioning, have all been shown to affect the caliber of the CBD.18–20 Given all the possible circumstances that may affect the measurement of the extrahepatic biliary system, it is difficult to define an absolute measurement that will by itself yield satisfactory predictive values for obstruction as a cause of duct dilation. Instead, the duct diameter should be interpreted in the context of potential causes of obstructive biliary dilation so that any pertinent findings from the clinical 263

SECTION 3 APPROACH TO CLINICAL PROBLEMS

Fig. 25.1 Transabdominal ultrasound examination demonstrating intrahepatic ductal dilation (arrowheads).

Fig. 25.3 Abdominal CT demonstrating a dilated CBD (arrow) in a patient with choledocholithiasis.

without evidence of an obstructing lesion (Fig. 25.4).23 These numbers are similar to other studies that have demonstrated the general results in order of decreasing prevalence: choledocholithiasis, pancreatic cancer, ampullary carcinoma, and cholangiocarcinoma as causes of biliary dilation.6 Assessing the a priori likelihood of a particular disease given the clinical scenario should influence the choice of the subsequent diagnostic evaluation.

EVALUATION

Fig. 25.2 Transabdominal ultrasound examination demonstrating a dilated CBD (arrowheads) and dilated CHD (arrows).

presentation or biochemical tests may be considered in the decision to pursue further diagnostic evaluation.

ETIOLOGY Identifying the level of biliary obstruction is important in developing a differential diagnosis. Common causes of obstruction include both neoplastic and benign causes such as choledocholithiasis (Table 25.1).1,21,22 Less common in the United States, but more common worldwide would be infectious etiologies such as parasitic disease. A study on the use of EUS in the evaluation of a dilated biliary tree in 90 patients with an unrevealing abdominal US found 40 patients with choledocholithiasis, 13 with tumor, 8 with benign stricture, 2 choledochal cysts, 1 with infection with ascaris, and 24 dilated ducts 264

Though there is a strong correlation between a dilated bile duct and the presence of an obstruction, as previously discussed, there is a broad interpretation of what is considered dilated. Many of the techniques used for biliary imaging are based on anatomic measurements and are not a functional demonstration of flow within the ducts as may be evident on cholangiography or scintigraphy. It is therefore important that decisions to proceed with further evaluation include both a clinical and biochemical assessment for obstruction in addition to consideration of the initial imaging results (Fig. 25.5).

Clinical evaluation The clinical presentation should be assessed for any signs or symptoms relating to biliary obstruction or its cause. For example, the history should elicit any symptoms such as abdominal pain, fever, weight loss, jaundice, pruritus, acholic stools, dark urine, or steatorrhea. The physical exam may be limited in its utility, but special attention should be paid to the presence of an abdominal tenderness or mass, hepatomegaly, jaundice, or lymphadenopathy. A positive history or physical examination may serve to lower the threshold for further diagnostic evaluation in those patients with an equivocal duct size on initial imaging. In the era of laparoscopic cholecystectomy, studies have attempted to develop models of these clinical

Chapter 25 Dilated Bile Duct

SITES OF BILIARY OBSTRUCTION Intrahepatic

Porta hepatis

Suprapancreatic

Intrapancreatic

Primary sclerosing cholangitis Space occupying liver lesion

Cholangiocarcinoma

Pancreatic carcinoma

Pancreatic carcinoma

Primary sclerosing cholangitis Gallbladder carcinoma Hepatocellular carcinoma

Cholangiocarcinoma Metastatic disease Direct extension of gastric/colon/ gallbladder Carcinoma Pancreatitis

Pancreatitis Choledocholithiasis Ampullary stenosis/carcinoma

Malignant lymph nodes Liver metastases

Duodenal carcinoma Cholangiocarcinoma

Table 25.1 Common obstructive causes of biliary dilation

Fig. 25.4 Radial EUS examination demonstrating a longitudinal view of a dilated CBD (arrows).

features in addition to biochemical values to predict choledocholithiasis prior to surgery. Some of these studies have demonstrated an increased likelihood for choledocholithiasis with jaundice or fever at presentation, acholic stools, dark urine, or an older patient age.24–27 However, it is difficult to draw a clear conclusion from these studies as they differ in methodology and results.

Biochemical evaluation Integral to the biochemical evaluation of obstruction are the bilirubin and liver associated enzymes (LAEs), commonly referred to as liver function tests. These generally include alkaline phosphatase (AP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). The principal markers of cholestasis are bilirubin and AP.28–30 The total bilirubin present in the serum represents a balance between input from production and hepatobiliary removal. In obstructive jaundice, the serum bilirubin is principally in the conjugated form (water soluble). Hepatobiliary AP is present on the apical membrane of the hepatocyte and in the luminal bile duct epithelium. Increases in AP result from increased synthesis and release into the serum. As a result, levels may not rise until one to two days after biliary obstruction occurs. In addition, the enzyme has a half-life of a week and the

level may therefore remain elevated for several days even after the resolution of biliary obstruction. Levels of AP up to three times normal are relatively nonspecific and occur in a variety of liver diseases. However, higher elevations are more specific for biliary obstruction (intra- or extrahepatic) and infiltrating liver diseases. As AP can be produced in sources outside of the liver, it may be necessary in certain instances to use other biochemical tests such as the AP isoenzymes or the gamma-glutamyl transpeptidase or 5’-nucleotidase to confirm the hepatobiliary etiology of an elevated AP. The serum aminotransferases include AST and ALT. Transient elevations occurring rapidly (within one to two days) and with levels into the thousands may occur in acute CBD obstruction, from trauma or more commonly from choledocholithiasis, Subsequent levels rapidly decline.28–30 Aminotransferase levels may also rise from other subacute or chronic obstructions but typically remain less than 500 IU/dl. It is difficult to interpret the predictive models using these markers in evaluating obstruction from choledocholithiasis as the results vary among studies.24–27 In general, there is increased likelihood for stones with abnormalities in bilirubin, AP, and transaminase levels. With these studies in mind, one can predict that it would be unusual for a lesion to cause biliary obstruction and dilation without clinical or biochemical abnormality. This is not universal, however, and there have been case reports of patients with normal LAEs despite having dilated ducts and choledocholithiasis.31

Imaging Imaging of the biliary tract continues to evolve with the enhancement of non-invasive techniques for cross-sectional evaluation and biliary reconstruction. There are numerous radiographic and invasive modalities now available to the clinician to image the anatomy of the biliary system. These include US, CT and CT cholangiography, magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography (MRCP), EUS, and ERCP. Each has advantages and disadvantages as well as limitations in the evaluation of the biliary system. The goal of any radiologic procedure evaluating the dilated bile duct is to confirm the presence of obstruction and to define its location, extent, and cause.

Ultrasound US is often the first line imaging technique in the evaluation of the bile ducts, gallbladder and right upper quadrant and is usually the test initially demonstrating dilation of the bile ducts. US is noninvasive, inexpensive and is a quick procedure that may be done at the bedside. It does, however, require experience in technique and interpretation and may be limited due to interference from gas 265

SECTION 3 APPROACH TO CLINICAL PROBLEMS

External bile duct diameter

Initial imaging

Ultrasound MRI

CT/Cholangiogram

Bile duct measurement <8 mm

≥8 mm

≤10 mm

>10 mm

Biochemical/ clinical assessment (–) No further evaluation indicated.

Fig. 25.5

(+) Indeterminate, obstruction possible. Follow labs and imaging.

(–) Indeterminate, consider patient characteristics such as age or cholecystectomy.

(+) Further evaluation indicated.

No further evaluation indicated.

(+) Indeterminate, obstruction possible. Follow labs and imaging.

(–) Indeterminate, consider patient characteristics such as age or cholecystectomy.

(+) Further evaluation indicated.

Algorithm for assessment of the external bile ducts for obstruction.

within the surrounding bowel. US has been shown to be one of the most accurate imaging studies in the evaluation of cholelithiasis with both a sensitivity and specificity of up to 99%.4,32–34 It is also highly sensitive for detecting dilation of the biliary tree as a whole with a sensitivity greater than 90%.4,35 The ability of ultrasound to define the site and cause of biliary obstruction is slightly less reliable. A review of the literature with more than 700 patients demonstrated that ultrasound has a sensitivity of 71% in delineating the level of obstruction, a sensitivity of 57% in defining the etiology, and a sensitivity for choledocholithiasis of 32%.32 However, there is great variation with sensitivities ranging from 27% to 95% for the correct level of obstruction and 23–81% for the correct cause of obstruction.36–39 Some of this limitation may result from a relative inability to image the distal CBD due to bowel gas. This area is well visualized in only 40–50% of patients.4 Clearly the ease of use, widespread availability, and few contraindications place US early on the algorithm for evaluation of the biliary tract or abdominal pain, but it typically leads to further studies as it is often inconclusive and does not provide adequate staging or surgical information in the setting of suspected neoplasms.

Computed tomography Similar to ultrasound, abdominal CT may be the initial test demonstrating dilation of the bile ducts or can also be considered as a test to further evaluate suspected biliary pathology. Multidetector CT can obtain images at thin 1.25–2.5 mm intervals that can be reformatted with high resolution into views to reproduce the biliary tree.1,40,41 This, in conjunction with careful review of axial images, can provide a complete evaluation of the bile ducts. Infusion of intravenous contrast agents is necessary to provide vascular landmarks and organ opacification maximizing the visualization of the bile ducts.40 Unenhanced scans can highlight the presence of calcifications and aid in visualization of choledocholi266

(–)

thiasis. Water is often used as an oral contrast agent when biliary tract abnormalities are suspected so as not to obscure potential pathology at the level of the ampulla of Vater.40 CT cholangiography has been evaluated in the United States and is used extensively in Asia and Europe. This employs the administration of IV contrast material to highlight the biliary tree. The fact that obstruction limits contrast excretion into the bile ducts and the higher incidence of adverse reactions to the contrast agents has limited the role of CT cholangiography.42 However, with new contrast agents and multidetector CT this may be the preferred imaging technique in the future. In a study evaluating the presence of biliary obstruction, defined as extrahepatic bile duct diameter >8 mm, the sensitivity and specificity of CT for diagnosing dilated ducts was 96% and 91% respectively.40 CT is also accurate at defining the level of obstruction in 88–97% of cases as well as the cause of obstruction in 70–95% of cases.39,40,43,44 Though CT is a readily available test that can accurately identify a dilated CBD as well as provide important details as to the level and cause of obstruction, there are limitations as well. It requires intravenous contrast to optimize the images, which may lead to adverse reactions including potential nephrotoxicity. CT also lacks sensitivity for a common cause of obstruction, choledocholithiasis, which is likely responsible for the lower rates of detection of the etiology of obstruction; approximately 20–25% of biliary stones are isoattenuating with bile making them difficult to detect on CT.1,40 Sensitivity of CT for choledocholithiasis ranges from 70% to 94% depending on the use of indirect signs of obstruction that typically coincide with choledocholithiasis.1,45,46

Magnetic resonance imaging Since it was first introduced in 1991, MRCP has gained popularity as a non-invasive imaging modality of the biliary system. MRCP

Chapter 25 Dilated Bile Duct

Fig. 25.6 MRCP image demonstrating markedly dilated bile ducts proximal to a Klatskin-type bile duct tumor.

Fig. 25.7

exploits the differences between fluid filled structures in the abdomen and adjacent soft tissues. The static or slow-moving fluid within the pancreatic and biliary system produces a different signal than solid tissue.21,22 Images can be obtained without use of IV contrast and are routinely performed in the axial and coronal planes. MRCP has a high accuracy in detecting the level and cause of biliary obstruction (Fig. 25.6). It has been shown to have a sensitivity of 91–97% and specificity of up to 99% for the diagnosis of biliary obstruction.47–49 Unlike US and CT, which can be limited in their ability to correctly identify the level and etiology of an obstructed biliary system, MRCP can more accurately define these parameters, similar to the use of direct cholangiography. The level of obstruction can be determined with MRCP in 87–98% of cases.47,48,50,51 The etiology of obstruction was determined in roughly 84% of cases with a malignant process and 94% in cases of a benign process.47,48 This was corroborated by a large meta-analysis demonstrating a sensitivity and specificity of MRCP of 92% and 97% respectively for cholelithiasis and 88% and 95% respectively for malignant causes (Fig. 25.7).47 However, the reported accuracy in discerning benign from malignant obstruction has varied from 30% to 98% across studies, with a mean accuracy of 88% reported in the meta-analysis. Addition of conventional T1 and T2 weighted images to MRCP allows for evaluation of extraductal soft tissue increasing the diagnostic accuracy by demonstrating tumor extension, lymph nodes, or metastatic disease.51,52 In one study, this increased the sensitivity, specificity, and accuracy 17–20% for differentiation of benign and malignant causes of biliary obstruction.53 This, however, comes with increased cost and time of exam. The major advantages of MRCP over other imaging techniques include the avoidance of invasive procedures, IV contrast, ionizing radiation, and the ability to visualize the biliary system above and below an obstruction. MRCP does have limitations. Its non-invasive nature means an inability to perform therapeutic intervention. Tech-

nical and interpretive difficulties can simulate or miss pathologic conditions of the biliary system. Static images demonstrating a contraction on the distal CBD can simulate a stenosis for example.54 Other drawbacks include the high cost of the test, extended time to perform an exam leading to patient intolerance, and contraindications such as magnetic objects.

MRCP demonstrating choledocholithiasis (arrow).

Endoscopic ultrasound EUS has emerged as a significant advance in gastrointestinal endoscopy since its introduction in 1987. It allows for both diagnostic evaluation of the pancreaticobiliary system with high resolution images as well as for therapeutic procedures. EUS is performed utilizing a specialized endoscope with a radial or linear ultrasound transducer at the tip.55,56 Images of the biliary system are obtained from transgastric or transduodenal locations. Unlike transabdominal ultrasound, EUS allows for better visualization of the extrahepatic biliary tree without interference of bowel gas as the CBD passes posterior to the duodenal bulb. Additionally, EUS offers accurate and systematic visualization of the wall of the duodenum including the papillary region (Fig. 25.8). EUS has been studied extensively in a variety of disorders that can lead to dilation of the CBD. In the setting of choledocholithiasis, EUS has consistently demonstrated sensitivities of >90% and specificities up to 100%.57–59 EUS may be particularly useful for detecting microlithiasis (stones <3 mm) though such small stones would be less likely to lead to biliary obstruction and dilation (Fig. 25.9).60 The close proximity of the stomach and duodenum to the pancreas allows for sensitive evaluation of pancreatic lesions such as neoplasms and cyst formation which may lead to obstruction. EUS has demonstrated greater sensitivity in the detection of pancreatic carcinoma with sensitivities in the range of 90% and above when compared to other imaging modalities (Fig. 25.10).61–63 This superiority is particularly evident with respect to smaller lesions (<3 cm). EUS 267

SECTION 3 APPROACH TO CLINICAL PROBLEMS

Fig. 25.8 Radial EUS demonstration of ampullary adenoma (arrows).

Fig. 25.10 Radial EUS demonstration of a pancreatic head carcinoma (arrowheads).

Cholangiography

Fig. 25.9 Radial (arrowheads).

EUS

demonstration

of

microlithiasis

has the further advantage of allowing for biopsy and diagnosis. Overall, EUS has been shown to provide an accurate explanation of biliary dilation in greater than 90% of patients.23 The limitations of EUS for the evaluation of biliary dilation include poor visualization of obstructive lesions located more proximally in the biliary system such as in the hilum or in the right hepatic duct. Poor visualization of the distal CBD also occurs when the pancreas is markedly calcified, during an episode of acute pancreatitis, when there is altered anatomy such as previous gastric surgery or presence of air within the biliary tract. Complications from diagnostic EUS are uncommon with a major complication rate of around 0.5%.64 This rate is the same as upper endoscopy with similar risks of perforation, bleeding, and sedation. 268

Cholangiography is generally performed using ERCP, but can be performed percutaneously (PTC). Each route provides both an anatomic view of the bile ducts as well as a functional assessment of whether bile can freely drain through the ducts. With the advent of recent advances in biliary imaging, particularly MRCP, the diagnostic indications for ERCP have been significantly challenged. For example, detection rates for choledocholithiasis using ERCP, MRCP, and EUS are comparable at over 90%; though microlithiasis may be masked by contrast medium and better imaged with EUS.22,60 In the diagnosis of pancreatic cancer, ERCP was shown to have a sensitivity of 70% versus 84% with MRCP (Fig. 25.11).51 Evaluation of perihilar biliary obstruction, the most common location for cholangiocarcinoma, with both ERCP and MRCP demonstrated to be very effective in detecting the presence of obstruction with a sensitivity of 100%.65 However, MRCP was superior in its investigation of the cause and anatomic extent of disease when compared with ERCP in part because it displayed the biliary tree cephalad to the obstruction and the character of the intraductal filling defect. A substantial downside to performing ERCP in patients with suspected hilar cholangiocarcinoma is the introduction of contamination into several segments of the biliary tree which, if left undrained, may lead to severe cholangitis. However, ERCP remains the best means of diagnosing ampullary cancers due to direct visualization and the ability to biopsy.34,56 Common complications of ERCP include pancreatitis with a rate of 1–7%, as well as hemorrhage, perforation, and infectious complications (see Chapter 6).66 It is therefore recommended that ERCP be reserved for patients with a reasonable likelihood of need for therapeutic intervention.66,67 For example, retrieval of stones and clearance of the duct is successful in over 90% of cases and in the setting of acute suppurative cholangitis can improve the clinical course and be life-saving.56 ERCP can also be used for palliation of obstructive lesions in nonsurgical patients or for obtaining tissue for diagnosis.

Chapter 25 Dilated Bile Duct

When a drainage procedure is indicated these rates increase to 2.5% for sepsis, 2.5% for hemorrhage, 1.2% for infection, and 1.7% for death. With the advent of enhanced imaging techniques, PTC should be employed for patients who warrant therapeutic biliary intervention, but are not candidates for ERCP or who have failed endoscopic biliary access.

Biliary scintigraphy Scintigraphy employs the administration of intravenous radioisotopes to evaluate the biliary system. The radioisotopes are taken up by the hepatocytes and excreted into the bile with concentration in the gallbladder. The sensitivity and specificity for biliary obstruction in jaundiced patients are 97% and 89%, respectively, based on the duration of time until the appearance of radiotracer in the duodenum.70 This test may help elucidate if obstruction is present in the setting of a dilated bile duct, but little if any information is gained regarding the etiology of obstruction.

APPROACH TO THE PATIENT WITH A DILATED DUCT Fig. 25.11 ERCP demonstration of a “double-duct” sign in pancreatic carcinoma with proximal biliary dilation (arrows) and dilated pancreatic duct (arrowheads).

Fig. 25.12 PTC demonstration of a proximal bile duct stricture in a patient with hilar cholangiocarcinoma. The arrows demonstrate the proximal extent of the tumor in the right and left intrahepatic ducts and the arrowheads demonstrate the distal extent of the tumor in the CHD. PTC is also an invasive technique of imaging the biliary system. It requires insertion of a needle into a dilated bile duct followed by opacification of the bile ducts with an injection of contrast. PTC has close to 100% sensitivity and specificity for identifying the site and cause of biliary obstruction (Fig. 25.12).68 However, this procedure is invasive and requires sedation. Complication rates vary with patient status but include major complications such as sepsis, cholangitis, bile leak, hemorrhage, or pneumothorax at a rate of 2%.69

Developing an algorithm on the approach to the dilated bile duct must incorporate the many variables described to this point. The first step in this process is to determine the clinical probability that an underlying obstructive lesion is present that requires further evaluation. This decision is based on the anatomic information from the initial imaging study and the clinical and biochemical assessment of the patient. US and CT are common initial radiographic tests demonstrating a bile duct abnormality. Dilation of intrahepatic ducts will become evident when the diameter exceeds 40% of the adjacent intrahepatic portal vein and the ducts become confluent throughout the liver. If isolated dilation of all or a portion of the intrahepatic ducts cannot be explained based on patient characteristics described above it warrants further investigation. The approach to dilation of the extrahepatic ducts is more challenging. The heterogeneity of results in defining an upper limit of normal for duct size makes it difficult to assign a value representing pathologic or obstructive dilation. Patient characteristics such as age and history of cholecystectomy as well as imaging modality must be considered when defining an abnormal duct size. On US, extrahepatic ducts with diameters greater than 7 mm can be considered abnormal since it has been shown that 99% of the non-obstructed population has ducts equal to or less than 7 mm. Values up to 10 mm should be considered normal for CT. However, outliers exist with larger ducts and no pathologic obstruction. Therefore, duct size must be correlated with clinical and biochemical features suggesting obstruction. In the absence of any such abnormalities, it is unlikely that obstruction is present even when duct diameter if greater than 7 mm. In these patients, most likely no further evaluation is necessary. It is important to note that obstruction may still be present with an extrahepatic duct measuring 7 mm or less. Dilation may not yet have occurred in response to obstruction or the size represents a change from a previously smaller duct. Again clinical and biochemical features may be helpful in determining an underlying process. Once it is determined that dilation of a bile duct likely represents obstruction, the next decision is how to proceed with further evaluation (Fig. 25.13). Again this approach must be individualized based on the clinical scenario with consideration of the underlying etiology. Generally, the algorithm should start with less invasive tests. 269

SECTION 3 APPROACH TO CLINICAL PROBLEMS

Probable biliary obstruction Symptoms of cholangitis (+)

(–)

ERCP or PTC for biliary drainage

MRI/MRCP or CT*

Further therapeutic or diagnostic procedures Cause still unknown, consider for imaging

EUS/FNA

ERCP/brushing or biopsy

* Choice of CT over MRI/MRCP based on contraindications to MR procedure, patient characteristics and availability.

Fig. 25.13

Algorithm for the evaluation of an obstructed bile duct.

However, patients presenting with obstruction and signs and symptoms of cholangitis may require diagnostic and therapeutic intervention acutely, in which case ERCP is an appropriate initial procedure. Patients without emergent indication for biliary drainage will require cross-sectional imaging with either a CT, if not performed initially, or an MRI/MRCP. Availability of testing, cost, patient characteristics, and probability of the underlying cause must be considered when choosing between these tests. Scant useful direct comparative data exist when comparing these tests and attempting to control for etiology, but some trends can be observed. Considerations in the decision process include contraindications to IV CT contrast, potential intolerance of MRI, and presence of metal objects which preclude MRI. CT has a high accuracy for defining many of the common etiologies of biliary obstruction, but has a

lower sensitivity for choledocholithiasis. MRCP with cross-sectional imaging has the highest sensitivity for defining obstructing lesions and should be the test of choice. Though higher in cost, a missed diagnosis with CT would lead to further testing and more expense. Based on the findings from subsequent imaging, more invasive procedures such as EUS or ERCP may be needed to obtain tissue for definitive diagnosis. In conclusion, the approach to the patient with a dilated bile duct is less than straightforward. First, the clinician must predict the possibility of an obstructing lesion that requires further evaluation based on duct size, clinical presentation, and biochemical assessment. Next further imaging modalities must be chosen based on both test and patient characteristics. Finally, definitive diagnosis with biopsy and treatment can be considered.

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Baron RL, Tublin ME, Peterson MS. Imaging the spectrum of biliary tract disease. Radiol Clin North Am 2002; 40(6):1325–1354. Adkins RB Jr, Chapman WC, Reddy VS. Embryology, anatomy, and surgical applications of the extrahepatic biliary system. Surg Clin North Am 2000; 80(1):363–379. Sauerbrei EE, et al. The discrepancy between radiographic and sonographic bile-duct measurements. Radiology 1980; 137(3):751–755. Cohen SM, Kurtz AB. Biliary sonography. Radiol Clin North Am 1991; 29(6):1171–1198. Wu CC, Ho YH, Chen CY. Effect of aging on common bile duct diameter: a real-time ultrasonographic study. J Clin Ultrasound 1984; 12(8):473–478. Niederau C, et al. Extrahepatic bile ducts in healthy subjects, in patients with cholelithiasis, and in postcholecystectomy patients: a prospective ultrasonic study. J Clin Ultrasound 1983; 11(1):23–27. Perret RS, Sloop GD, Borne JA. Common bile duct measurements in an elderly population. J Ultrasound Med 2000; 19(11):727–730; quiz 731.

8. Niederau CA, Sonnenberg A, Mueller J. Comparison of the extrahepatic bile duct size measured by ultrasound and by different radiographic methods. Gastroenterology 1984; 87(3):615–621. 9. Mahour GH, Wakim KG, Ferris DO. The common bile duct in man: its diameter and circumference. Ann Surg 1967; 165(3):415–419. 10. Rumack CM, Wilson SR. The gallbladder and bile ducts. 2nd edn 1998; St. Louis: Mosby-Yearbook:206–207. 11. Oddi R. D’une disposition a sphincter speciale de ‘ouverture du canal choledoque. Arch Ital Biol 1887; 8:317–322. 12. Graham MF, et al. The size of the normal common hepatic duct following cholecystectomy: an ultrasonographic study. Radiology, 1980; 135(1):137–139. 13. Mueller PR, et al. Postcholecystectomy bile duct dilatation: myth or reality? AJR Am J Roentgenol 1981; 136(2):355–358. 14. Chung SC, Leung JW, Li AK. Bile duct size after cholecystectomy: an endoscopic retrograde cholangiopancreatographic study. Br J Surg 1990; 77(5):534–535.

Chapter 25 Dilated Bile Duct

15. Reinus WR, et al. Ultrasound evaluation of the common duct in symptomatic and asymptomatic patients. Am J Gastroenterol 1992; 87(4):489–492. 16. Hunt DR, Scott AJ. Changes in bile duct diameter after cholecystectomy: a 5-year prospective study. Gastroenterology 1989; 97(6):1485–1488. 17. Feng B, Song Q. Does the common bile duct dilate after cholecystectomy? Sonographic evaluation in 234 patients. AJR Am J Roentgenol 1995; 165(4):859–861. 18. Wachsberg RH. Respiratory variation of extrahepatic bile duct diameter during ultrasonography. J Ultrasound Med 1994; 13(8):617–621. 19. Lorenzon G, Corsi M. [Ultrasonic study of the dimensions of the common bile duct in various postures]. Radiol Med (Torino) 1990; 80(4):455–462. 20. Raptopoulos V, et al. Daytime constancy of bile duct diameter. AJR Am J Roentgenol 1987; 148(3):557–558. 21. Siegelman EAS, Body MRI. 1st ed. 2005. Philadelphia: Elsevier: 63–77. 22. Soto JA, Barish MA, Ferrucci JT. Magnetic resonance imaging of the bile ducts. Semin Roentgenol 1997; 32(3):188–201. 23. Songur YG, Temucin G, Sahin B. Endoscopic ultrasonography in the evaluation of dilated common bile duct. J Clin Gastroenterol, 2001; 33(4):302–305. 24 Prat F, et al. Prediction of common bile duct stones by noninvasive tests. Ann Surg 1999; 229(3):362–368. 25. Barkun AN, et al. Useful predictors of bile duct stones in patients undergoing laparoscopic cholecystectomy. McGill Gallstone Treatment Group. Ann Surg 1994; 220(1):32–39. 26. Abboud PA, et al. Predictors of common bile duct stones prior to cholecystectomy: a meta-analysis. Gastrointest Endosc 1996; 44(4):450–455. 27. Trondsen E, et al. Prediction of common bile duct stones prior to cholecystectomy: a prospective validation of a discriminant analysis function. Arch Surg 1998; 133(2):162–166. 28. Limdi JK, Hyde GM. Evaluation of abnormal liver function tests. Postgrad Med J 2003; 79(932):307–312. 29. Green RM, Flamm S. AGA technical review on the evaluation of liver chemistry tests. Gastroenterology 2002; 123(4):1367–1384. 30. Reddy KR. Hepatobiliary tract and pancreas. 1st ed. The requisites in gastroenterology, ed. A Rustgi 2004; Philadelphia: Mosby: 1–17. 31. Goldman DE, Gholson CF. Choledocholithiasis in patients with normal serum liver enzymes. Dig Dis Sci 1995; 40(5):1065–1068. 32. Blackbourne LH, et al. The sensitivity and role of ultrasound in the evaluation of biliary obstruction. Am Surg 1994; 60(9):683–690. 33. Harvey RT, Miller WT Jr. Acute biliary disease: initial CT and followup US versus initial US and follow-up CT. Radiology 1999; 213(3):831–836. 34. Stroszczynski C, Hunerbein M. Malignant biliary obstruction: value of imaging findings. Abdom Imaging 2005; 30(3):314–323. 35. Laing FC, et al. Biliary dilatation: defining the level and cause by real-time US. Radiology 1986; 160(1):39–42. 36. Haubek A, et al. Dynamic sonography in the evaluation of jaundice. AJR Am J Roentgenol 1981; 136(6):1071–1074. 37. Koenigsberg M, Wiener SN, Walzer A. The accuracy of sonography in the differential diagnosis of obstructive jaundice: a comparison with cholangiography. Radiology 1979; 133(1):157–165. 38. Honickman SP, et al. Ultrasound in obstructive jaundice: prospective evaluation of site and cause. Radiology 1983; 147(2):511–515. 39. Baron RL, et al. A prospective comparison of the evaluation of biliary obstruction using computed tomography and ultrasonography. Radiology 1982; 145(1):91–98.

40. Baron RL. Computed tomography of the bile ducts. Semin Roentgenol 1997; 32(3):172–187. 41. Kim HC, et al. Three-dimensional reconstructed images using multidetector computed tomography in evaluation of the biliary tract. Abdom Imaging 2004; 29(4):472–478. 42. Stockberger SM, Sherman S, Kopecky KK. Helical CT cholangiography. Abdom Imaging 1996; 21(2):98–104. 43. Pedrosa CS, et al. Computed tomography in obstructive jaundice. Part II: The cause of obstruction. Radiology 1981; 139(3):635–645. 44. Pedrosa CS, Casanova R, Rodriguez R. Computed tomography in obstructive jaundice. Part I: The level of obstruction. Radiology 1981; 139(3):627–634. 45. Neitlich JD, et al. Detection of choledocholithiasis: comparison of unenhanced helical CT and endoscopic retrograde cholangiopancreatography. Radiology 1997; 203(3):753–757. 46. Baron RL. Common bile duct stones: reassessment of criteria for CT diagnosis. Radiology 1987; 162(2):419–424. 47. Romagnuolo J, et al. Magnetic resonance cholangiopancreatography: a meta-analysis of test performance in suspected biliary disease. Ann Intern Med 2003; 139(7):547–557. 48. Magnuson TH, et al. Utility of magnetic resonance cholangiography in the evaluation of biliary obstruction. J Am Coll Surg 1999; 189(1):63–71; discussion 71–72. 49. Guibaud L, et al. Bile duct obstruction and choledocholithiasis: diagnosis with MR cholangiography. Radiology 1995; 197(1):109–115. 50. Georgopoulos SK, et al. Comparison of magnetic resonance and endoscopic retrograde cholangiopancreatography in malignant pancreaticobiliary obstruction. Arch Surg 1999; 134(9):1002–1007. 51. Adamek HE, et al. Pancreatic cancer detection with magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography: a prospective controlled study. Lancet 2000; 356(9225):190–193. 52. Barish MA, Soto JA. MR cholangiopancreatography: techniques and clinical applications. AJR Am J Roentgenol 1997; 169(5):1295–1303. 53. Kim MJ, et al. Biliary dilatation: differentiation of benign from malignant causes—value of adding conventional MR imaging to MR cholangiopancreatography. Radiology 2000; 214(1):173–181. 54. David V, et al. Pitfalls in the interpretation of MR cholangiopancreatography. AJR Am J Roentgenol, 1998; 170(4): 1055–1059. 55. Ingram M, Arregui ME. Endoscopic ultrasonography. Surg Clin North Am 2004; 84(4):1035–1059, vi. 56. Ahmad NA, Shah JN, Kochman ML. Endoscopic ultrasonography and endoscopic retrograde cholangiopancreatography imaging for pancreaticobiliary pathology: the gastroenterologist’s perspective. Radiol Clin North Am 2002; 40(6):1377–1395. 57. Canto MI, et al. Endoscopic ultrasonography versus cholangiography for the diagnosis of choledocholithiasis. Gastrointest Endosc 1998; 47(6):439–448. 58. Palazzo L, Levy P, Bernades P. Usefulness of endoscopic ultrasonography in the diagnosis of choledocholithiasis. Abdom Imaging 1996; 21(2):93–97. 59. Amouyal P, et al. Diagnosis of choledocholithiasis by endoscopic ultrasonography. Gastroenterology 1994; 106(4):1062–1067. 60. Liu CL, et al. EUS for detection of occult cholelithiasis in patients with idiopathic pancreatitis. Gastrointest Endosc 2000; 51(1):28–32. 61. Akahoshi K, et al. Diagnosis and staging of pancreatic cancer by endoscopic ultrasound. Br J Radiol 1998; 71(845):492–496. 62. Muller MF, et al. Pancreatic tumors: evaluation with endoscopic US, CT, and MR imaging. Radiology 1994; 190(3):745–751.

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63. Snady H, Cooperman A, Siegel J. Endoscopic ultrasonography compared with computed tomography with ERCP in patients with obstructive jaundice or small peri-pancreatic mass. Gastrointest Endosc 1992; 38(1):27–34. 64. Yusuf TE, Bhutani MS. Role of endoscopic ultrasonography in diseases of the extrahepatic biliary system. J Gastroenterol Hepatol 2004; 19(3):243–250. 65. Yeh TS, et al. Malignant perihilar biliary obstruction: magnetic resonance cholangiopancreatographic findings. Am J Gastroenterol 2000; 95(2):432–440. 66. Mallery JS, et al. Complications of ERCP. Gastrointest Endosc 2003; 57(6):633–638.

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67. NIH state-of-the-science statement on endoscopic retrograde cholangiopancreatography (ERCP) for diagnosis and therapy. NIH Consens State Sci Statements 2002; 19(1):1–26. 68. Gold R, Casarella WJ, Stern G. Transhepatic cholangiography: The radiologic method of choice in suspected obstructive jaundice. Radiology 1979; 133:39–44. 69. Burke DR, et al. Quality improvement guidelines for percutaneous transhepatic cholangiography and biliary drainage. J Vasc Interv Radiol 2003; 14(9 Pt 2):S243–246. 70. Lee AW, et al. Technetium-99m BIDA biliary scintigraphy in the evaluation of the jaundiced patient. J Nucl Med 1986; 27(9):1407–1412.

SECTION 3

Chapter

26

APPROACH TO CLINICAL PROBLEMS

Ampullary Neoplasm Ellert J. van Soest and Paul Fockens

INTRODUCTION Malignant tumors of the ampulla of Vater are rare. One person per 80.000 inhabitants older than 40 years will be diagnosed with ampullary cancer each year in the United States.1 Fifteen times more prevalent than ampullary cancer is the heterogeneous group of malignancies of the periampullary region, which include mainly tumors of the pancreas, but also less prevalent tumors of the distal bile duct, the periampullary duodenum, and the ampulla of Vater. Prior to surgical resection, the origin of these tumors is often difficult to differentiate. However, survival rates after Whipple’s resection differ significantly between the different periampullary cancers, in favour of ampullary tumors (Fig. 26.1).2 This chapter will focus on neoplasms arising from the ampulla of Vater itself. Adenoma is the most common benign ampullary tumor. Since an adenoma-carcinoma sequence has been documented at this level, all adenomas must be resected upon their detection. In short, many adenomas are suitable for endoscopic therapy (see also Chapter 19), whereas adenocarcinomas should primarily be resected surgically.

in 16%, jaundice in 15%, pancreatitis in 9%, and miscellaneous symptoms were present in 15%.3 Presentation with severe acute gastrointestinal bleeding is rare, but has been described with adenomas, carcinomas and mesenchymal tumors of the ampulla, when the overlying mucosa has become eroded.4 There are no specific laboratory findings that accompany ampullary tumors. Usually, because of disturbed biliary outflow, alkaline phosphatase and bilirubin are elevated; sometimes elevated aminotransferases and iron deficiency anemia are seen. Abnormal liver function tests can be the only presenting feature. Tumor markers are used mostly as a prognostic rather than a diagnostic tool. In a study of 56 patients with ampullary carcinoma, CA 19-9 had a sensitivity of 78% in detecting cancer, and CEA only 33%. Specificity of both CA 19-9 and CEA is low.5 Gene expression analysis of ampullary adenocarcinoma has identified other tumor markers, such as serum osteopontin, which in the future may also aid in the early detection and differential diagnosis of patients with periampullary lesions.6

DIAGNOSTIC WORK-UP AND STAGING

SYMPTOMS AND SIGNS Endoscopy Patients with ampullary tumors frequently develop symptoms early in the course of the disease, when the tumor is still relatively small. These early symptoms are caused by its typical anatomical location at the junction of the bile duct and pancreatic duct, impeding biliary and/or pancreatic outflow. Jaundice is the presenting symptom in the majority of patients. Unlike the jaundice observed with cancer of the pancreas, jaundice produced by ampullary cancers may fluctuate, especially early in the course of the obstructive process. In addition, nonspecific symptoms such as weight loss, abdominal discomfort, nausea and vomiting are often seen. Obstructive jaundice, anemia due to gastrointestinal blood loss, and a palpable, nontender gallbladder (Courvoisier sign) make up the classic triad of an ampullary carcinoma. Acute pancreatitis and cholangitis can occur as the result of obstruction of the pancreatic or bile duct. Benign ampullary tumors present less often with jaundice, reflecting the smaller tumor size and the absence of tissue invasion. Nondescript abdominal pain is common. An increased incidence of common duct calculi, observed in both benign and malignant tumors of the ampulla, due to bile stasis, may account for some of the abdominal pain and jaundice observed with these lesions. A significant subset of ampullary adenomas are found during surveillance for adenomas in patients with Familial Adenomatous Polyposis (FAP), or as an incidental finding at upper gastrointestinal endoscopy in patients with symptoms that are not attributable to the ampullary lesion. In a relatively large series of 55 ampullary adenomas, 45% of patients were asymptomatic, abdominal pain was seen

Endoscopy for the assessment of an ampullary tumor should be done with a high quality side-viewing duodenoscope. Regular forwardviewing endoscopy will miss abnormalities of the papilla in a significant number of cases. Endoscopy visualizes the site of the lesion, its size, and macroscopic appearance, as well as extension beyond the limits of the ampulla. More important, the value of endoscopy lies in its ability to obtain tissue for histology. A wide variation exists in the endoscopic appearance of the normal major duodenal papilla. Recognition of adenomas can therefore be difficult. Grossly, ampullary tumors may manifest in one of four welldescribed appearances (Figs 26.2 and 26.3):7 • Macroscopically normal papilla: suspicion of an ampullary process arises when unexplained common bile duct (and/or pancreatic duct) dilatation to the level of the ampulla is seen on CT scan. Completely intra-ampullary tumors may only become apparent after endoscopic sphincterotomy, but can often be visualized with endoscopic ultrasound (EUS) nowadays. • Intramural protrusion: A bulge underneath a normal-appearing papilla (“prominent infundibulum”). • Exposed protrusion: Neoplastic-appearing tissue extending out from an otherwise normal or abnormal-appearing papilla. • Ulcerating tumor: This situation is very suspicious for malignancy (Fig. 26.5a). A characteristic appearance distinguishing benign from malignant disease is the presence of an ulcerating tumor mass. Failure to achieve a cleavage plane with submucosal injection during ampul273

SECTION 3 APPROACH TO CLINICAL PROBLEMS

A

B

C

D

100 90 80

Survival (%)

70 60 50 40 30

Ampulla Duodenum Distal bile duct Pancreas

20 10 0

0

No. at risk Ampulla Distal bile duct Duodenum Pancreas

6

24 30 36 12 18 Time after diagnosis (months)

88 78 41 30 13 7 419 207

67 17 5 95

57 13 3

49

42

45

37

32

Fig. 26.2 Different appearances of ampullary adenomas. A Macroscopic almost normal papilla, containing adenoma at biopsy in a FAP-patient. B Adenoma with granular surface C Exposed protrusion of villous adenoma. D Large polypoid mass at the papilla.

Fig. 26.1 Survival curves for 561 patients with periampullary tumors, stratified by site of origin (Redrawn from reference no. 2 with the permission of John Wiley & Sons Ltd on behalf of the British Journal of Surgery Society Ltd.) A

C

B

Fig. 26.3 Adenocarcinoma of the ampulla of Vater. Although multiple biopsies yielded only adenoma, the ampullectomy specimen showed adenocarcinoma. Patient underwent a pancreaticoduodenectomy afterwards. lectomy is also a strong predictor of malignancy.8 Other signs that indicate malignancy are induration and friability with easy bleeding. Ulceration located on the roof of the ampulla, separated from the papilla by normal mucosa, indicates a lesion invading the duodenal submucosa.9 In a series of 52 patients with biopsy-proven ampullary adenomas or carcinomas, Ponchon et al. noted a normal endoscopic appearance of the papilla in 37% of patients. In these patients the intra-ampullary tumors only became apparent after endoscopic sphincterotomy.7 274

Most sporadic lesions are solitary, while there is almost always macroscopic evidence of adenomatous transformation elsewhere in the duodenum in FAP-patients.

ERCP Since the introduction of MRCP and EUS, ERCP has limited application as a diagnostic test because of its associated morbidity and possible mortality. However, in case of an ampullary tumor, ERCP is performed when biliary drainage is required.

Chapter 26 Ampullary Neoplasm

Sphincterotomy can be performed to biopsy deeper within the ampulla. Furthermore, ERCP is helpful when performing an ampullectomy, to establish the presence or absence of intraductal tumor in the bile- or pancreatic duct. Some centers use cholangioscopy for this purpose.10 Other fluoroscopic findings of ampullary cancer at ERCP include bile- and pancreatic duct dilatation in most cases, a defect in the ampulla, delayed drainage of contrast, and common bile duct stones in a minority of patients.

Forceps biopsy Endoscopic forceps biopsy specimens, taken from the surface of a tumor, can be falsely negative for malignancy in a considerable number of patients. Carcinomatous changes inside adenomas are found in 25–30%, and percentages up to 56% have been reported in older series, depending on the size of the adenoma.11,12 Despite these limitations, recent endoscopic series show an acceptable percentage of only 6–8% carcinomas in ampullectomy specimens in patients who were treated for presumed benign ampullary tumors.10,13 This is probably the result of improved patient selection before performing an ampullectomy. To improve diagnostic yield, it is essential to obtain a large number of biopsies (at least six) from an ampullary neoplasm to minimize sampling error. Even then, negative biopsies do not rule out the presence of cancer. Larger biopsies with a diathermic snare improve the quality of samples, but also carry more risk of complications. In some patients, sphincterotomy with deeper biopsies from within the incised papilla may be considered. Biopsies are more reliable when obtained 10 days or more after sphincterotomy, as sphincterotomy can cause coagulation effects that can be misinterpreted.14 Endoscopic ultrasound-guided fineneedle aspiration biopsy (EUS-guided FNAB) seems to be accurate in the assessment of suspected primary ampullary masses. In the only published report on this subject, the reported sensitivity and specificity were 82% and 100%, respectively. However, adenomas were underrepresented in this study (2 out of 35 patients), so the role of EUS-guided FNAB for ampullary adenomas needs to be determined.15

detection of ampullary lesions (respectively 95–100% versus 15% and 20–30%).16–18 However, lesions of 10 mm or smaller can be difficult to demonstrate with EUS.17 Secondly, EUS can be used in the assessment of the cause of an endoscopically abnormal looking ampulla. EUS should ideally be able to differentiate an ampulla with a (pre-) malignant lesion in it, from other conditions, such as a an enlarged inflammatory papilla or normal-variant protruding papilla. From the sparse literature on this subject it seems that the specificity of EUS in the diagnosis of an ampullary mass is less impressive than its sensitivity, and lies arround 75%.21 A false positive result is primarily caused by a swollen papilla as a consequence of stone migration (Fig. 26.4). In summary, EUS should be considered an important tool in clarifying the cause of an abnormal papilla, but only biopsies can reliably confirm the diagnosis.

Staging advanced ampullary cancer EUS is helpful with staging of ampullary cancers, according to the TNM system (Table 26.1). Pretherapeutic staging is essential for making therapeutic decisions and to determine prognosis of the patient. EUS has been proven to be the most reliable modality for preoperative T-staging, compared to CT and MRI.18,22 In the largest series of 50 consecutive patients with ampullary neoplasms, EUS was found to be more accurate (78%) than CT (24%) and MRI (46%) compared with surgical-pathologic staging in the assessment of the T stage. The main limitation of EUS in T-staging is its relative inaccuracy in differentiating stage T2 from T3. Overstaging of true T2 carcinomas can be caused by peritumoral pancreatitis. The presence

A

B

C

D

Transabdominal ultrasound, CT and MRI Obstructive jaundice is usually initially analysed with transabdominal ultrasound (US) or a CT scan. If biliary obstruction is attributable to an ampullary neoplasm, dilatation of the entire biliary tree is typically demonstrated. The tumor itself is not seen in the majority of cases, however. Sensitivity of CT for detecting ampullary tumors is only around 20–30%, but increases with larger tumor size.16–18 If no mass is depicted with CT, endoscopic ultrasound should be considered (see below). In the setting of ampullary carcinoma with a clear mass, CT plays an important role in predicting resectability, by depicting both vessel infiltration and distant metastasis.19 MRI with MRCP has not been studied extensively for ampullary tumors, but its role in periampullary tumors is promising.20

Endoscopic ultrasonography (EUS) When evaluating patients with ampullary pathology, EUS can be used for different purposes.

Diagnosing an ampullary tumor EUS can be used in the primary detection of an ampullary tumor in patients with obstructive jaundice, without a mass on US or CT. Studies in patients with ampullary cancer have clearly shown a higher sensitivity of EUS when compared to US and CT for the

Fig. 26.4 Enlarged inflammatory papilla (“odditis”) due to gallstones. A Swollen papilla (with a stent in situ), suspicious for a tumor with intramural protrusion. B Therefore a sphincterotomy was performed to biopsy deeper. Biopsies showed only inflammation. C Gallstones were removed. D Normalization of the papilla two months later. 275

SECTION 3 APPROACH TO CLINICAL PROBLEMS

T1 T2 T3 T4 N0 N1 M0 M1

Tumor limited to the ampulla of Vatera Tumor invades duodenal wall (muscularis propria) Tumor invasion into the pancreas <2 cm Tumor invasion into the pancreas >2 cm or into adjacent organs or vessels No regional lymph node metastasis Regional lymph node metastasis No distant metastasis Distant metastasis

Table 26.1 TNM staging system for ampullary carcinomas a

Some divide T1 tumors in d0 (limited to Oddi’s sphincter) and d1 (tumor invading the duodenal submucosa). Sobin LH, Wittekind Ch (eds) International union against cancer (UICC): The TNM classification of malignant tumors. 6th ed. New York: Wiley; 2002.

A

B

C

D

relatively long distance from the mesenteric and other major vessels, vascular involvement is uncommon. EUS can obtain adequate visualization of the portal venous system from the the duodenal bulb, and celiac vessels can be scanned from the gastric fundus. EUS is a very sensitive modality in demonstrating vascular tumor involvement.24,25 Liver metastasis and ascites can be evaluated with EUS, but distant metastasis should be exluded with CT scan as well, before considering a surgical resection.

Staging early ampullary lesions When local endoscopic or surgical resection is considered, EUS Tstaging becomes of vital importance. Endoscopic resection is mainly reserved for benign lesions since early cancers already have a 10% risk of lymph node metastases and should be treated with radical surgery (pancreaticoduodenectomy). EUS cannot distinguish between benign adenoma and ampullary cancer, unless infiltrative growth exists, such as infiltration in the duodenal muscularis propria. In case of benign biopsies, exclusion of infiltrating tumors deeper in the lesion is the primary goal of EUS. The accuracy of EUS to assess that the T stage > T1 is high, and has been reported to be between 87 and 94%.17,22,24,26 Subdivision of stage T1 in d0 and d1 further refines staging. T1d0 tumors are limited to Oddi’s sphincter and T1d1 tumors invade the duodenal submucosa. Local resection of ampullary tumors is appropriate when there are no signs of malignancy macro- and microscopically, and staging is T1d0. For this subdivision intraductal ultrasonography (IDUS) seems to be the best imaging modality (see below). Ingrowth in the common bile- and pancreatic duct is regarded as a (relative) contraindication for endoscopic treatment of ampullary adenomas, a condition that can be visualized by either EUS or IDUS.

Intraductal ultrasound (IDUS)

Fig. 26.5 T2N1 adenocarcinoma of the ampulla of Vater. A Endoscopic appearance. B EUS showing the polypoid tumor, C a dilated common bile duct and pancreatic duct, D and a lymph node metastasis.

of endobiliary stents also may decrease the accuracy of EUS in staging ampullary tumors, mainly by understaging T2/T3 carcinomas. Nevertheless, this differentiation is not mandatory as the same surgical treatment is applied in T2 and T3 tumors. No significant difference in N-stage accuracy has been noted between CT, MRI and EUS. Metastatic regional lymph nodes are detected by EUS with an accuracy of around 65% (Fig. 26.5).22,23 Locoregional lymph node involvement usually does not influence the surgical treatment plan. Currently, suspicion of lymph node metastasis should always be confirmed by EUS-guided FNAB when treatment decisions are dependent on it. Resectability of ampullary tumors depends mainly on vessel involvement, and on distant metastasis. Since ampullary cancer causes symptoms early in the course of the disease and originates a 276

IDUS is a promising imaging modality in staging ampullary tumors. Ultrasound catheter probes are inserted during ERCP and advanced over a guidewire into the bile duct and/or pancreatic duct. Intraductal catheter probes have a higher frequency (20 MHz) than standard EUS, resulting in better resolution. In the largest prospective study on this subject, IDUS was significantly superior to EUS and CT in terms of tumor visualization, especially in depicting small lesions.17 IDUS is the only modality that distinguishes the sphincter of Oddi as a distinct layer.26 Potentially, IDUS could be performed in every patient with seemingly benign tumors of the ampulla. The decision to perform endoscopic resection would then be taken only if no submucosal ingrowth or intraductal extension was detected with IDUS. Larger prospective series are needed to validate this policy.

Colonoscopy There are reports in the literature that the risk of colonic adenoma and carcinoma is increased in patients with adenomas of the ampulla, not only as part of hereditary polyposis syndromes.27,28 In one study of 16 patients with adenomas of the ampulla, 10 colonoscopies were performed, and colonic adenomas were found in four cases, and one patient turned out to have FAP.29 The group of Saurin and Ponchon has also described positive findings in approximately half the colonoscopies that they performed in 13 patients with “sporadic” ampullary adenomas, including one patient who had eight colonic adenomas, and one patient found to have a sigmoid carcinoma.30 Although these studies are small, the significant percentage of

Chapter 26 Ampullary Neoplasm

detected colon adenomas/carcinomas mandate a colonoscopy in all patients with “sporadic” adenomas of the ampulla.

PATHOLOGY Only 5% of all tumors of the ampulla are not adenomas or adenocarcinomas. These 5% of cases comprise a wide range of benign and malignant disease. Most ampullary tumors develop sporadically, and some occur in connection with cancer syndromes, as summarized in Table 26.2.

Adenoma The ampulla of Vater is a complex anatomic site, and is composed of the common channel, the intraduodenal portion of the common bile duct and pancreatic duct, and duodenal mucosa. The common channel is probably the site from which most ampullary tumors derive, as shown in histologic studies and autopsy series.31 A pathophysiological role of bile and pancreatic juice in its carcinogenesis has been hypothesised, but, to date, has not been convincingly demonstrated. Ampullary adenomas are histologically very similar to their colonic counterparts and are classified as tubular, tubulovillous, or villous, in order of increasing malignant potential. As in the colon, progressive dysplastic changes may occur, including eventual transformation to cancer. This adenoma-carcinoma sequence is supported by the following observations: • In patients who had been operated on for benign ampullary tumors in the past, a significant percentage presented later with ampullary cancer.7 • Adenomatous remnants, with histological transitions of adenoma into carcinoma, have been found in the vicinity of ampullary adenocarcinoma.7,32,33 • Histological progression has been demonstrated during follow-up of ampullary adenomas in FAP patients.34 • A genetic alteration model delineating ampullary tumor development has been described, and is similar to that seen in colonic carcinogenesis.35 Some cancers have no detectable adenomatous component. Either tumor extension has already destroyed the adenomatous tissue, or certain cancers develop without going through an adenoma stage. The finding in autopsy series that atypical epithelium occurs without adenomatous growth supports the latter theory.31

type.36 The intestinal type resembles tubular adenocarcinoma of the colon and originates from the ampulloduodenal mucosa; the pancreaticobiliary type originates from the common channel, or from bile- or pancreatic duct epithelium. Carcinomas of the intestinal and pancreaticobiliary types may develop via different mechanisms, and demonstrate different molecular biological characteristics.37 There are conflicting reports whether survival differs between types; some suggest survival is better in the intestinal type.32,36

Neuroendocrine tumors (NET) For many years, disseminated neuroendocrine neoplasms of the gastrointestinal tract have been subsumed as “carcinoids.” Currently, the World Health Organization (WHO) recommends using the term neuroendocrine tumor. The WHO distinguishes (i) welldifferentiated neuroendocrine tumors (carcinoids); (ii) well-differentiated neuroendocrine carcinomas (malignant carcinoids); and (iii) poorly differentiated neuroendocrine carcinomas. These tumors are morphologically and biologically diverse, with a broad spectrum of subtypes. Ampullary NETs are rare. Between 100 and 200 cases have been reported in the international literature. NETs that arise at the ampulla of Vater are mainly somatostatinomas, but gangliocytic paragangliomas and other NETs can occur also (Figs 26.6 and 26.7). The majority of ampullary NETs are nonfunctional: there is production of peptides when examined immunocytochemically, but plasma hormone levels are not elevated and they do not produce a clinical syndrome.38 There is a strong relationship with neurofibromatosis (von Recklinghausen disease): approximately one quarter of all reported patients with ampullary NETs had neurofibromatosis.39 Jaundice is the predominant presenting symptom. The correct diagnosis is frequently made only after operation, because the submucosal location hinders adequate tissue sampling with forceps biopsies.40 In contrast to carcinoid tumors at other gastrointestinal sites, the tumor size of ampullary carcinoids does not correlate with either the metastatic potential or prognosis.39,40 For assessment of tumor extension, the same imaging modalities are used as described above for ampullary adenocarcinomas. In addition, somatostatin receptor (octreotide) scintigraphy can be helpful.38 Pancreaticoduodenectomy is the standard treatment for ampullary, welldifferentiated carcinoids >2.0 cm and for ampullary neuroendocrine

Carcinoma Carcinoma of the ampulla can be classified histopathologically and immunohistochemically as either an intestinal or pancreaticobiliary

FAP HNPCC Neurofibromatosis type 1 Muir-Torre syndrome

Table 26.2 Cancer syndromes associated with ampullary carcinoma • Hereditary nonpolyposis colorectal carcinoma (HNPCC) is weakly associated with ampullary carcinoma. • Neurofibromatosis seems to be a predisposition of both somatostatinomas and carcinomas of the ampulla of Vater. • Muir-Torre syndrome is a condition characterized by the association of multiple sebaceous tumors and kerato-acanthomas with internal malignancies, including ampullary carcinomas.

Fig. 26.6

Carcinoid at the papilla. 277

SECTION 3 APPROACH TO CLINICAL PROBLEMS

A

B

C

D

A

B

Fig. 26.8 Metastasis of a melanoma to Vater’s ampulla. A Patient with a history of a melanoma was admitted because of cholangitis. ERCP showed a bulging papilla. B Easy bleeding during cannulation. Endoscopic ultrasound-guided fine-needle aspiration biopsy confirmed the suspicion of a metastasis of melanoma.

Benign disease

Fig. 26.7 Periampullary gangliocytic paraganglioma. A Large, stalked polyp. B Indentification of the orifice of the papilla. C Cannulation. D Snare resection just under the papilla, after placing an “endoloop.”

carcinomas.40 Local surgical, or endoscopic resection can be considered for smaller carcinoids without evidence of metastases. Generally, the prognosis of ampullary carcinoids after resection is good, with a five-year survival period of 90%.40 Poorly differentiated neuroendocrine carcinomas have an aggressive clinical behaviour, however, with early metastases, and often, a fatal outcome.

Lymphoma

Lymphomas of the biliary system are rare, but should be considered in the differential diagnosis of malignant strictures of the common bile duct. The ampulla is even more rarely the site of origin of these tumors. Four types of primary lymphomas of the ampulla of Vater have been described: • Primary ampullary MALT lymphoma arise from the mucosaassociated lymphoid tissue of the duodenum. Similar to MALT lymphomas in the stomach, ampullary MALT lymphomas are sometimes controlled by eradication of Helicobacter pylori. In other cases, tumor regression is accomplished only with more aggressive forms of therapy, such as radio- or chemotherapy.41 • Diffuse largeB-cell lymphoma. Together with MALT lymphomas, diffuse large B-cell lymphomas seem to be the most prevalent lymphomas in the periampullary region. Their absolute incidence is low, however.42 • Follicular lymphomas are infrequently limited to the ampulla. Surgery can be avoided, if a proper diagnosis is made before operation, as chemotherapy is reported to be effective.43 • T-cell lymphomas very rarely infiltrate the sphincter of Oddi and cause jaundice.44 Association with celiac sprue has been described. 278

Adenoma Carcinoid GIST Lipoma Leiomyoma Hamartoma (Peutz-Jeghers polyp) Schwannoma Lymphangioma Hemangioma Fibroma Neurofibroma Granular cell tumor Adenomyoma Eosinophilic gastroenteritis Duodenal duplication Choledochocele Heterotopic pancreas Heterotopic gastric mucosa Brunner’s gland hyperplasia Inflammatory nonneoplastic lesions: odditis/papillitis (e.g. due to lithiasis) Large, but normal variant ampulla

Table 26.3 Differential diagnosis of tumors and pseudotumors of the ampulla of Vater

Gastrointestinal stromal tumor (GIST) There are few reports of gastrointestinal stromal tumors of the ampulla. Most patients have been treated with a pancreaticoduodenectomy. Treatment with imatinib mesylate has shown to improve outcome in unresectable, metastatic or recurrent disease.45,46

Metastasis Metastasis to the ampulla is extremely unusual. It may arise from a variety of primary lesions including renal cell carcinomas, melanomas, and ovarian-, breast-, esophagus- and larynx cancer (Fig. 26.8).47

Miscellaneous The ampulla of Vater can harbour a variety of other neoplasms, and an extended overview is given in Tables 26.3 and 26.4.

Chapter 26 Ampullary Neoplasm

Malignant disease (Adeno)carcinomaa Neuroendocrine carcinoma Malignant GIST Lymphoma Pancreatoblastoma Leiomyosarcoma Neurofibrosarcoma Kaposi sarcoma Angiosarcoma Malignant schwannoma Rhabdomyosarcoma (only described in children) Metastasis to the ampulla

Table 26.4 Differential diagnosis of malignant tumors and pseudotumors of the ampulla of Vater a

• Mixed cellular populations of carcinoma have been described, such as: ° Sarcomatoid carcinomas, an intermixture of carcinomatous and sarcomatous elements. ° Adenocarcinoid tumors, an intermixture of adenocarcinoma and carcinoid tumor • Ampullary carcinomas with unusual patterns of differentiation, such as papillary carcinomas, Paneth cell carcinomas and signet-ring cell carcinomas are also included.

Points

1

2

3

Polyp number Polyp size (mm) Histology Dysplasia

1–4 1–4 Tubular Mild

5–20 5–10 Tubulovillous Moderate

>20 >10 Villous Severe

Table 26.5 Staging system for the severity of duodenal polyposis in FAP: the Spigelman classification (Reproduced from reference no. 49 with permission.)

effectively prevents cancer, it is questionable whether all stage IV patients should be exposed to this procedure in view of its considerable morbidity, and mortality.52 An alternative would be to follow these patients regularly with upper endoscopy. Unfortunately, endoscopic surveillance seems not to detect all carcinomas, as has been shown in the study by Björk et al.51 This was potentially related to the use of forward-viewing, rather than forward- and side-viewing endoscopes. Alternatively, endoscopic biopsies may not have been sensitive enough, or disease may have progressed rapidly between screening intervals. In spite of these limitations, upper gastrointestinal endoscopic surveillance is recommended for all FAP patients, with special attention for the periampullary region. Adenomas of the major duodenal papilla are more likely to undergo malignant transformation than an adenoma arising elsewhere in the duodenum, reflecting the fact that the occurrence of dyplasia in the periampullary region has been reported to be as high as 66–74%.27,34,49 Surveillance intervals of 3 years are recommended by experts for less severe disease; those with stage IV disease should be examined every 6 months to 1 year.53 Biopsies should be taken routinely, also from normal appearing papillae, as a normal appearing papilla can harbour an adenoma in more than 50% of cases (Fig. 26.2A).34 The role of endoscopic treatment of ampullary lesions in FAP is not yet clearly defined. Randomized trials of the different surgical and endoscopic modalities are lacking. Endoscopic therapy has not been studied in large prospective studies yet, but the available literature on this subject seems promising.13,54 Endoscopic treatment of (peri) ampullary lesions in FAP does not differ from therapy for “sporadic” ampullary lesions, although one should take into account that recurrence of adenomas is more common in FAP patients.13

TREATMENT

0 points = Stage 0; 1–4 = Stage I; 5–6 = Stage II; 7–8 = Stage III; 9–12 = Stage IV

Familial adenomatous polyposis (FAP) FAP syndrome and its variants (Gardner’s syndrome and Turcot syndrome) afflict approximately 1 in 20 000 people (data from Denmark).48 Duodenal cancer, mainly in a (peri) ampullary location, is the leading cause of cancer death in patients with FAP who have undergone prophylactic colectomy.48 Patients with FAP have a cumulative lifetime risk of over 90% for developing duodenal adenomas, and a lifetime risk of 4–10% for developing periampullary or duodenal adenocarcinoma.48–51 The risk of adenocarcinoma of the major duodenal papilla has been estimated to be greater than 100 times that of the general population.50 In an attempt to prevent cancer, screening programmes have been developed using a welldefined staging system to detect those patients most at risk, as shown in Table 26.5. Patients with stage IV disease have a 10–30 times higher chance of developing carcinoma, as compared to patients at a lower stage.51,52 How to treat patients with Spigelman stage IV remains controversial. Around 25% of patients with stage IV periampullary adenomas developed cancer in a large Scandinavian study.51 It is our impression however, that the use of current high resolution endoscopes and chromoendoscopy leads to upstaging of patients in the Spigelman classification. This upstaging will probably diminish the cancer risk in stage Spigelman IV. Although (pancreatico) duodenectomy

Optimal therapy results in a radical excision of all neoplastic tissue, minimizes the chance of recurrence, and has an acceptable procedure-related morbidity and mortality.

Adenomas Pancreaticoduodenotomy has been the traditional treatment of ampullary adenomas for years. This procedure effectively eliminates all adenomatous tissue, but has been associated with considerable morbidity (25–65%), and with mortality (0–10%). Two strategies have been developed to diminish complications: transduodenal local surgical resection (surgical ampullectomy) and endoscopic therapy. Postoperative morbidity is definitely lower with local surgical resection (0–25%), and mortality is low to absent (0–5%), but recurrence of adenomas occurs in 5–30% of operated patients. Endoscopic surveillance is therefore indicated after this type of surgery.12,55,56 Since 1983, reports have been published on the endoscopic treatment of ampullary adenomas, using snare resection and laser photocoagulation.57–59 Later, with the results of snare removal of the entire ampulla as a single specimen, described by Binmoeller, it became clear that endoscopic snare resection in selected patients provides an excellent alternative to traditional surgery (Figs 26.9 and 26.10) (for indications, see Chapter 19).60 Controlled studies comparing endoscopic and surgical strategies have not (yet) been conducted. The published reports on this subject are case series from surgical and endoscopic centers, and vary considerably in 279

SECTION 3 APPROACH TO CLINICAL PROBLEMS

A

B

A

B

C

D

C

D

Fig. 26.9 En bloc resection of a tubulovillous adenoma. A Periampullary polypoid mass. B Indentification and cannulation of the papilla. C Snare resection. D Result after ampullectomy, and sphincterotomy of the common bile duct.

Fig. 26.10 Piecemeal resection of a large tubulovillous adenoma. A Large polyp with orifice of the papilla on top. B Twisted stalk. C Piecemeal resection. D Result after two months.

100 90 80 70 Survival (%)

patient selection and demographics, thus making comparison difficult. Table 26.6 summarizes the literature on endoscopic therapy. The choice on how to treat ampullary adenomas is highly dependent on local expertise. In our opinion, because of its favourable outcome, its low morbidity and absent mortality in most case series, endoscopic snare resection as the initial treatment is justified in centers with experience in this type of endoscopic interventions. An additional advantage is that this treatment can be performed on an outpatient basis.

Carcinomas Standard surgical management of invasive ampullary carcinoma is resection by pancreaticoduodenectomy. Local surgical therapy for pT1 carcinoma is questionable, as the resection is often limited,61 and a reduced survival has been reported compared to pancreaticoduodenectomy.62 Conversion to pancreaticoduodenectomy is indicated when pathological examination of an ampullectomy specimen identifies invasive carcinoma. The subsequent operation does not seem to increase morbidity when compared to initial pancreaticoduodenectomy.63 For high grade dyplasia/carcinoma in situ, radically removed endoscopically or with local surgical excision, there is insufficient evidence that a subsequent operation (i.e. lymphadenectomy) is beneficial. Lymph node metastasis in such cases seems to be absent.64 A “wait and see” policy may be justified, but opinions are divided on this issue. Survival after resection in a relatively recent, large, single center study is summarized in Figure 26.11. Operative mortality has diminished over time, with no postoperative death in this and in other studies.2 Factors predictive of improved survival in ampullary carci280

60 50 40 30 20

T1 T2 T3

10 0

No. at risk T1 T2 T3

0

24 30 12 18 Time after resection (months)

6

18 32 20

17 30 17

17 28 12

15 24 11

13 23 11

12 18 8

36

11 16 5

42

10 18

Fig. 26.11 Survival curves for 70 patients after resection of ampullary carcinoma, stratified by tumor stage. Patients with T3 tumors had poorer survival than those with T1 or T2 disease (P = 0.05). (Redrawn from reference no. 2 with the permission of John Wiley & Sons Ltd on behalf of the British Journal of Surgery Society Ltd.)

2005

2005

2005

Harewood

Bohnacker

Han

Retrospective Prospective

Prospective

Retrospective

n = 14

n = 19

n = 106 (109 lesionsb)

n = 22

0

0

Intraductal growth

Snare excision

0

Snare excision 31 and/or electrocoagulation

Snare excision (RCT of prophylactic pancreatic stent placement)

Snare excision

Retrospective/ Prospective Technique

b

Median number of 3 therapeutic sessions to achieve complete destruction of adenomatous tissue. Synchronous tumors of the major and minor papillae.

a

Table 26.6 Summary of the literature on endoscopic resection of ampullary tumors

2006

Number of Year of patients publication included

Katsinelos

First author

NR: Not reported

Bleeding 5%, perforation 5%, papillary stenosis 5%, cholangitis 5%, cholestasis 5%

Pancreatitis 12%, bleeding 3%

Pancreatitis 33% without pd stent, vs 0% with pd stent. Cholestasis 5%

Pancreatitis 7%, bleeding 7%

Complications

NR

NR

28 79% months

15 adenoma 8 86% (3 with months HGD), 2 carcinoma, 1 carcinoid, 3 inflammatory lesion, 1 lymphangioma

NR

19%

NR

21%

5%

18%

NR

18%

Complete Follow- endoscopic up resection Surgery Recurrence

92 adenoma 43 73% (18 with months HGD), 4 carcinoma, 12 inflammatory lesion, 1 lymphangioma

NR

11 adenoma, 3 carcinoma

Histology

Recurrence: recurrence of adenoma (or adenocarcinoma) after complete endoscopic resection (patients lost to follow-up are excluded).

Surgery (percentage per total number of patients) includes the need of surgery for malignant disease, for persistent adenoma, for complications, and for recurrences that could not be treated endoscopically.

Complete endoscopic resection (percentage per total number of patients): total clearance of adenoma in one or more treatment sessions, without the need for surgery (this includes recurrences that could be treated endoscopically).

Complication rate (percentage per total number of patients): Only clinically evident bleeding that occurred after completion of the procedure was regarded as a complication. Pancreatitis and perforation were managed conservatively in the majority of patients.

Inclusion: Studies published from 1990, and with more than 5 patients included, on endoscopic treatment of ampullary tumors with benign features.

Chapter 26 Ampullary Neoplasm

281

282

2004

2004

2003

2002

2001

2001

2000

2000

1993

Cheng

Catalano

Saurin

Norton

Desilets

Zádarová

Vogt

Park

Binmoeller

Table 26.6 Continued

2005

Moon

Prospective

Retrospective

Retrospective

Retrospective

Retrospective

Retrospective Retrospective Retrospective Retrospective Prospective

n=6

n = 55

n = 103

n = 24

n = 26 (28 lesionsb)

n = 13

n = 16

n = 18

n=6

n = 25 Snare excision

Snare excision

Snare excision

Snare excision

Snare excision (piecemeal)a

Snare excision

Mainly laser photodestructiona

Snare excision

Snare excision (wire-guided endoscopic papillectomy).

2

NR

NR

NR

0

0

0

0

6

0

13 adenoma (1 with HGD)

25 adenoma, 1 carcinoma, 1 inflammatory lesion, 1 normal histology

Pancreatitis 12%, bleeding 8%

25 adenoma (1 with HGD)

4 adenoma, 2 carcinoma

Pancreatitis 11%, bleeding 11%, 18 adenoma stent dysfunction 6% Pancreatitis 33%

36 80% months

30 74% months

7 100% months

100%

37 92% months

21 67% months

75 100% months

NR

19 92% months

9 96% months

Forcepsbiopsies: 81 67% 24 months adenoma (10 with HGD)

97 adenoma (14 with HGD), 6 carcinoma

45 adenoma (7 with HGD), 5 carcinoma, 2 carcinoid, 1 gastric heterotopia, 2 normal histology

6 adenoma (1 with HGD)

Pancreatitis 13%, bleeding 13% 16 adenoma

Pancreatitis 8%

Pancreatitis 15%, perforation 4%, pancreatic duct stenosis 8%

Pancreatitis 17%, bleeding 13%, perforation 4%

Pancreatitis 5%, bleeding 2%, papillary stenosis 3%

Pancreatitis 9%, bleeding 7%, perforation 2%

Late onset pancreatitis 17%, cholangitis 17%

12%

17%

17%

6%

8%

4%

17%

16%

13%

0%

26%

0%

44%

19%

0%

10%

6%

20%

33%

0%

SECTION 3 APPROACH TO CLINICAL PROBLEMS

Chapter 26 Ampullary Neoplasm

noma vary per study, and include resectability, negative margins (R0 resection), negative lymph nodes, differentiation of the tumor, and absence of pancreatic, vascular and perineural invasion.2,61 Palliative treatment for ampullary carcinoma can consist of a local resection in very frail patients with a small, pT1 tumor.64 Literature on endoscopic resection of this kind of tumor is only anecdotal.65 Furthermore, biliary- or pancreatic drainage can be achieved with ERCP by placing an endoprosthesis or by papillotomy. In case of duodenal obstruction an expandable metal stent can be placed endoscopically to palliate the gastric outlet obstruction.

varies between a local endoscopic resection in case of a benign lesion, and a radical surgical pancreaticoduodenectomy for malignant disease. The diagnostic work-up of ampullary lesions is challenging. A high index of suspicion together with careful endoscopic examination of the papilla are crucial for early detection. CT-scan and endoscopic ultrasonography are usually necessary to decide on the optimal treatment for the individual patient. Ampullary tumors are typically lesions that require close cooperation of a multidisciplinary team consisting of a gastroenterologist, radiologist, surgeon and pathologist.

CONCLUSIONS Ampullary tumors are rare lesions, but of interest. Their prognosis is generally better than that of pancreatic tumors and their treatment

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11.

12.

Urbach DR, Swanstrom LL, Khajanchee YS, et al. Incidence of cancer of the pancreas, extrahepatic bile duct and ampulla of Vater in the United States, before and after the introduction of laparoscopic cholecystectomy. Am J Surg 2001; 181(6): 526–528. Bettschart V, Rahman MQ, Engelken FJ, et al. Presentation, treatment and outcome in patients with ampullary tumours. Br J Surg 2004; 91(12):1600–1607. Cheng CL, Sherman S, Fogel EL, et al. Endoscopic snare papillectomy for tumors of the duodenal papillae. Gastrointest Endosc 2004; 60(5):757–764. Nowak A, Botdys H, Marek T, et al. Unusual cause of severe upper gastrointestinal hemorrhage treated using a simple endoloop technique. Endoscopy 2001; 33(8):733. Kau SY, Shyr YM, Su CH, et al. Diagnostic and prognostic values of CA 19-9 and CEA in periampullary cancers. J Am Coll Surg 1999; 188(4):415–420. Van Heek NT, Maitra A, Koopmann J, et al. Gene expression profiling identifies markers of ampullary adenocarcinoma. Cancer Biol Ther 2004; 3(7):651–656. Ponchon T, Berger F, Chavaillon A, et al. Contribution of endoscopy to diagnosis and treatment of tumors of the ampulla of Vater. Cancer 1989; 64(1):161–167. Kahaleh M, Shami VM, Brock A, et al. Factors predictive of malignancy and endoscopic resectability in ampullary neoplasia. Am J Gastroenterol 2004; 99(12):2335–2339. Napoléon B, Pialat J, Saurin JC, et al. Adenomas and adenocarcinomas of the ampulla of Vater: endoscopic therapy. Gastroenterol Clin Biol 2004; 28(4):385–392. Bohnacker S, Seitz U, Nguyen D, et al. Endoscopic resection of benign tumors of the duodenal papilla without and with intraductal growth. Gastrointest Endosc 2005; 62(4):551–560. Yamaguchi K, Enjoji M, Kitamura K. Endoscopic biopsy has limited accuracy in diagnosis of ampullary tumors. Gastrointest Endosc 1990; 36(6):588–592. Cahen DL, Fockens P, de Wit LT, et al. Local resection or pancreaticoduodenectomy for villous adenoma of the ampulla of Vater diagnosed before operation. Br J Surg 1997; 84(7):948–951.

13. Catalano MF, Linder JD, Chak A, et al. Endoscopic management of adenoma of the major duodenal papilla. Gastrointest Endosc 2004; 59(2):225–232. 14. Bourgeois N, Dunham F, Verhest A, et al. Endoscopic biopsies of the papilla of Vater at the time of endoscopic sphincterotomy: difficulties in interpretation. Gastrointest Endosc 1984; 30(3):163–166. 15. Defrain C, Chang CY, Srikureja W, et al. Cytologic features and diagnostic pitfalls of primary ampullary tumors by endoscopic ultrasound-guided fine-needle aspiration biopsy. Cancer 2005; 105(5):289–297. 16. Skordilis P, Mouzas IA, Dimoulios PD, et al. Is endosonography an effective method for detection and local staging of the ampullary carcinoma? A prospective study. BMC Surg 2002; 25; 2:1. 17. Menzel J, Hoepffner N, Sulkowski U, et al. Polypoid tumors of the major duodenal papilla: preoperative staging with intraductal US, EUS, and CT—a prospective, histopathologically controlled study. Gastrointest Endosc 1999; 49(3):349–357. 18. Chen CH, Tseng LJ, Yang CC, et al. The accuracy of endoscopic ultrasound, endoscopic retrograde cholangiopancreatography, computed tomography, and transabdominal ultrasound in the detection and staging of primary ampullary tumors. Hepatogastroenterology 2001; 48(42):1750–1753. 19. Schwarz M, Pauls S, Sokiranski R, et al. Is a preoperative multidiagnostic approach to predict surgical resectability of periampullary tumors still effective? Am J Surg 2001; 182(3):243–249. 20. Andersson M, Kostic S, Johansson M, et al. MRI combined with MR cholangiopancreatography versus helical CT in the evaluation of patients with suspected periampullary tumors: a prospective comparative study. Acta Radiol 2005; 46(1): 16–27. 21. Will U, Meyer F, Erhardt C, et al. Correlation of differential diagnosis between inflammatory and malignant lesions of the papilla of Vater using endosonography with results of histologic investigation [Abstract]. Gastroenterology 2003; 124 (suppl 1) A 440. 283

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22. Cannon ME, Carpenter SL, Elta GH, et al. EUS compared with CT, magnetic resonance imaging, and angiography and the influence of biliary stenting on staging accuracy of ampullary neoplasms. Gastrointest Endosc 1999; 50(1):27–33. 23. Kubo H, Chijiiwa Y, Akahoshi K, et al. Pre-operative staging of ampullary tumours by endoscopic ultrasound. Br J Radiol; 72(857):443–447. 24. Mukai H, Nakajima M, Yasuda K, et al. Evaluation of endoscopic ultrasonography in the pre-operative staging of carcinoma of the ampulla of Vater and common bile duct. Gastrointest Endosc 1992; 38(6):676–683. 25. Tierney WM, Francis IR, Eckhauser F, et al. The accuracy of EUS and helical CT in the assessment of vascular invasion by peripapillary malignancy. Gastrointest Endosc 2001; 53(2): 182–188. 26. Itoh A, Goto H, Naitoh Y, et al. Intraductal ultrasonography in diagnosing tumor extension of cancer of the papilla of Vater. Gastrointest Endosc 1997; 45(3):251–260. 27. Seifert E, Schulte F, Stolte M. Adenoma and carcinoma of the duodenum and papilla of Vater: a clinicopathologic study. Am J Gastroenterol 1992; 87(1):37–42. 28. Schneider AR, Seifert H, Trojan J, et al. Frequency of colorectal polyps in patients with sporadic adenomas or adenocarcinomas of the papilla of vater–an age-matched, controlled study. Z Gastroenterol 2005; 43(10):1123–1127. 29. Zádorová Z, Dvorák M, Hajer J. Endoscopic therapy of benign tumors of the papilla of Vater. Endoscopy 2001; 33(4):345–347. 30. Saurin JC, Chavaillon A, Napoléon B, et al. Long-term follow-up of patients with endoscopic treatment of sporadic adenomas of the papilla of Vater. Endoscopy 2003; 35(5):402–406. 31. Kimura W, Futakawa N, Zhao B. Neoplastic diseases of the papilla of Vater. J Hepatobiliary Pancreat Surg 2004; 11(4):223–231. 32. Fischer HP, Zhou H. Pathogenesis of carcinoma of the papilla of Vater. J Hepatobiliary Pancreat Surg 2004; 11(5):301–309. 33. Spigelman AD, Talbot IC, Penna C, et al. Evidence for adenomacarcinoma sequence in the duodenum of patients with familial adenomatous polyposis. The Leeds Castle Polyposis Group (Upper Gastrointestinal Committee). J Clin Pathol 1994; 47(8):709–710. 34. Burke CA, Beck GJ, Church JM, et al. The natural history of untreated duodenal and ampullary adenomas in patients with familial adenomatous polyposis followed in an endoscopic surveillance program. Gastrointest Endosc 1999; 49(3):358–364. 35. Takashima M, Ueki T, Nagai E, et al. Carcinoma of the ampulla of Vater associated with or without adenoma: a clinicopathologic analysis of 198 cases with reference to p53 and Ki-67 immunohistochemical expressions. Mod Pathol 2000; 13(12):1300–1307. 36. Kimura W, Futakawa N, Yamagata S, et al. Different clinicopathologic findings in two histologic types of carcinoma of papilla of Vater. Jpn J Cancer Res 1994; 85(2):161–166. 37. Zhao B, Kimura W, Futakawa N, et al. p53 and p21/Waf1 protein expression and K-ras codon 12 mutation in carcinoma of the papilla of Vater. Am J Gastroenterol 1999; 94(8):2128–2134. 38. Hoffmann KM, Furukawa M, Jensen RT. Duodenal neuroendocrine tumors: Classification, functional syndromes, diagnosis and medical treatment. Best Pract Res Clin Gastroenterol 2005; 19(5):675–697. 39. Makhlouf HR, Burke AP, Sobin LH. Carcinoid tumors of the ampulla of Vater: a comparison with duodenal carcinoid tumors. Cancer 1999; 85(6):1241–1249. 40. Hatzitheoklitos E, Buchler MW, Friess H, et al. Carcinoid of the ampulla of Vater. Clinical characteristics and morphologic features. Cancer 1994; 73(6):1580–1588.

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41. Toyoda H, Yamaguchi M, Nakamura S, et al. Regression of primary lymphoma of the ampulla of Vater after eradication of Helicobacter pylori. Gastrointest Endosc 2001; 54(1):92–96. 42. Yildirim N, Oksuzoglu B, Budakoglu B, et al. Primary duodenal diffuse large cell non-hodgkin lymphoma with involvement of ampulla of Vater: report of 3 cases. Hematology 2005; 10(5):371–374. 43. Nadal E, Martinez A, Jimenez M, et al. Primary follicular lymphoma arising in the ampulla of Vater. Ann Hematol 2002; 81(4):228–231. 44. Weinstock LB, Swanson PE, Bennett KJ, et al. Jaundice caused by a clinically undetectable T-cell lymphoma infiltrating the sphincter of Oddi. Am J Gastroenterol 2001; 96(11):3186–3189. 45. Matsushita M, Kobayashi Y, Kobayashi H, et al. A case of gastrointestinal stromal tumour of the ampulla of Vater. Dig Liver Dis 2005; 37(4):275–277. 46. Schubert ML, Moghimi R. Gastrointestinal Stromal Tumor (GIST). Curr Treat Options Gastroenterol 2006; 9(2):181–188. 47. Le Borgne J, Partensky C, Glemain P, et al. Pancreaticoduodenectomy for metastatic ampullary and pancreatic tumors. Hepatogastroenterology 2000; 47(32):540–544. 48. Bülow S. Results of national registration of familial adenomatous polyposis. Gut 2003; 52(5):742–746. 49. Spigelman AD, Williams CB, Talbot IC, et al. Upper gastrointestinal cancer in patients with familial adenomatous polyposis. Lancet 1989; 2(8666):783–785. 50. Offerhaus GJ, Giardiello FM, Krush AJ, et al. The risk of upper gastrointestinal cancer in familial adenomatous polyposis. Gastroenterology 1992; 102(6):1980–1982. 51. Björk J, Åkerbrant H, Iselius L, et al. Periampullary adenomas and adenocarcinomas in familial adenomatous polyposis: cumulative risks and APC gene mutations. Gastroenterology 2001; 121(5):1127–1135. 52. Bülow S, Björk J, Christensen IJ, et al. Duodenal adenomatosis in familial adenomatous polyposis. Gut 2004; 53(3):381–386. 53. Burke C. Risk stratification for periampullary carcinoma in patients with familial adenomatous polyposis: does theodore know what to do now? Gastroenterology 2001; 121(5):1246–1248. 54. Norton ID, Gostout CJ. Management of periampullary adenoma. Dig Dis 1998; 16(5):266–273. 55. Martin JA, Haber GB. Ampullary adenoma: clinical manifestations, diagnosis, and treatment. Gastrointest Endosc Clin N Am 2003; 13(4):649–669. 56. Farnell MB, Sakorafas GH, Sarr MG, et al. Villous tumors of the duodenum: reappraisal of local vs. extended resection. J Gastrointest Surg 2000; 4(1):13–23. 57. Shemesh E, Nass S, Czerniak A. Endoscopic sphincterotomy and endoscopic fulguration in the management of adenoma of the papilla of Vater. Surg Gynecol Obstet 1989; 169(5): 445–448. 58. Lambert R, Ponchon T, Chavaillon A, et al. Laser treatment of tumors of the papilla of Vater. Endoscopy 1988; 20 Suppl 1:227–231. 59. Suzuki K, Kantou U, Murakami Y. Two cases with ampullary cancer who underwent endoscopic excision. Prog Dig Endosc 1983; 23:236–239. 60. Binmoeller KF, Boaventura S, Ramsperger K, et al. Endoscopic snare excision of benign adenomas of the papilla of Vater. Gastrointest Endosc 1993; 39(2):127–131. 61. Beger HG, Treitschke F, Gansauge F, et al. Tumor of the ampulla of Vater: experience with local or radical resection in 171 consecutively treated patients. Arch Surg 1999; 134(5):526–532.

Chapter 26 Ampullary Neoplasm

62. Roggin KK, Yeh JJ, Ferrone CR, et al. Limitations of ampullectomy in the treatment of nonfamilial ampullary neoplasms. Ann Surg Oncol 2005; 12(12):971–980. 63. de Castro SM, van Heek NT, Kuhlmann KF, et al. Surgical management of neoplasms of the ampulla of Vater: local resection or pancreatoduodenectomy and prognostic factors for survival. Surgery 2004; 136(5):994–1002.

64. Yoon YS, Kim SW, Park SJ, et al. Clinicopathologic analysis of early ampullary cancers with a focus on the feasibility of ampullectomy. Ann Surg 2005; 242(1):92–100. 65. Jung S, Kim MH, Seo DW, et al. Endoscopic snare papillectomy of adenocarcinoma of the major duodenal papilla. Gastrointest Endosc 2001; 54(5):622.

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27

APPROACH TO CLINICAL PROBLEMS

Malignant Biliary Obstruction: Distal Raed M. Alsulaiman and Alan Barkun

INTRODUCTION Malignant biliary obstruction is most frequently encountered in the setting of pancreatic adenocarcinoma, but can also be due to cholangiocarcinomas, gallbladder, and ampullary neoplasms. The approach and management of distal biliary obstruction, including the role of endoscopic retrograde cholangiopancreatography (ERCP), will be discussed in this chapter. For discussions on the approach to managing patients with proximal biliary obstruction and the practical aspects of biliary stenting, readers are referred to Chapters 17 and 28.

EPIDEMIOLOGY Malignancies of the biliary and pancreatic systems are not uncommon; together they represent two of the 10 most incident cancers in North America and Europe. While the incidence of pancreatic cancer has remained stable over the last 25 years, the epidemiology of cholangiocarcinoma has changed. The incidence of intrahepatic cholangiocarcinomas seems to be rising while that of extrahepatic biliary tumors is decreasing, even though the reasons for such a change in pattern are not known.1 Because these cancers are usually diagnosed at advanced stages, when the probability of cure is very low, the mortality rate is very high. Consequently pancreatic cancer ranks as the fifth most lethal cancer in the US, and second as a cause of digestive cancer-related deaths, behind colon cancer. The incidence of pancreatic and biliary malignancies increases with age and, in fact, these tumors are rarely seen before the age of 45. Epidemiological surveys have shown that the median age of diagnosis approximates 70 years. Exceptions include genetically predisposed individuals, and those with chronic pre-malignant conditions such as primary sclerosing cholangitis.2 Pancreatic cancer is more common in males, people of Jewish and Afro-American descent. Diabetes, chronic pancreatitis, pernicious anemia, inherited disorders such as familial adenomatous polyposis, and high fat and meat intake have been cited as risk factors for pancreatic cancer.3 Although rare and confined to clusters of families, genetic disorders such as hereditary pancreatitis and familial pancreatic cancer have also been linked to pancreatic cancer; individuals with these conditions appear to have up to a 40% lifetime risk of malignant transformation.4 The majority of cases of cholangiocarcinoma have no identifiable underlying etiology. However, a number of risk factors have been implicated in its development; most factors exhibit long-standing inflammation and chronic injury of the biliary epithelium. Primary sclerosing cholangitis is an uncommon disease, more commonly seen in middle-aged males. It is characterized by stricturing, fibrosis and inflammation of the biliary tree, and is closely associated with inflammatory bowel disease, particularly ulcerative colitis. Approximately 10–20% of patients with primary sclerosing cholangitis will

develop cholangiocarcinoma. The rare congenital fibropolycystic diseases of the biliary system are associated with increased risks of cholangiocarcinoma, particularly choledochal cysts and Caroli’s disease. Choledochal cysts are associated with a 10% lifetime incidence of cholangiocarcinoma: there is a 1% per year risk which plateaus after 15–20 years.5 In the Far East, other forms of chronic inflammation associated with cholangiocarcinoma include infestation with the liver flukes Clonorchis sinensis and Opisthorchis viverinni. Cholangiocarcinoma is also rarely seen in association with cirrhosis and has been weakly linked to hepatitis C infection. Among neoplasms involving the biliary tree, carcinoma of the gallbladder has the poorest prognosis with a 5-year survival ranging between 0% and 10% in most reported series.6 Gallbladder cancer is the most incident malignant lesion of the biliary tract, and the fifth most common among malignant neoplasms of the digestive tract. It affects women two to six times more often than men, and the incidence increases with age. Although its etiology is unknown, cholelithiasis is thought to be an important risk factor for gallbladder cancer. Other risks factors such as the presence of a porcelain gallbladder, gallbladder polyps, an anomalous pancreaticobiliary junction and obesity have also been suggested in epidemiological studies.7

NATURAL HISTORY Although not always present, obstruction of the distal common bile duct (CBD) occurs during the natural evolution of most of these tumors, depending on their location and behavior. The most common malignancy causing distal biliary malignant obstruction is pancreatic cancer accounting for more than 90% of cases (2), followed by gallbladder cancer, malignant lymphadenopathy and cholangiocarcinoma, the latter being relatively uncommon in Western countries. Carcinoma of the ampulla of Vater can also obstruct the distal CBD and although rarely seen in otherwise healthy individuals, it is particularly common in patients with familial adenomatous polyposis. In fact, it is a leading cause of death in this population. Gallbladder cancer and cholangiocarcinoma involving the distal CBD may also obstruct, but represent just a small fraction of all such patients. The overall prognosis of malignancies that cause biliary obstruction is dismal. Except for extrinsic compressions caused by enlarged lymph nodes in the case of hematological malignancies such as nonHodgkin’s lymphomas and for ampullary tumors, the majority of patients found with unresectable disease have a median survival of 3–5 months.8

CLINICAL FEATURES The most common presenting symptoms of pancreaticobiliary malignancies are painless jaundice, anorexia and weight loss, and are seen in most patients. If pain occurs it is often located in the 287

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Demographic Age Gender Race Symptoms and signs Abdominal pain Jaundice Weight loss Nausea/vomiting Back pain

Palliated (N = 256)

Resected (N = 512)

64.0 ± 0.7 years 57% male 91% white

65.8 ± 0.5 years 55% male 91% white

64% 57% 48% 30% 26%

36%a 72%a 43% 18%a 2%

Ampullary adenocarcinoma Pancreatic adenocarcinoma Head Body/tail Gallbladder adenocarcinoma Cholangiocarcinoma Non-hilar Metastatic disease

Table 27.2 Most prevalent distal pancreaticobiliary malignancies

Table 27.1 Presenting symptoms and signs in patients with resectable and unresectable pancreatic cancer a P < 0.001 vs. Palliated group With permission from Sohn TA, Lillemoe KD, Cameron JL, et al. Surgical palliation of unresectable periampullary adenocarcinoma in the 1990, J Am Coll Surg 1999; 188:658–666. © 1999 The American College of Surgeons.

epigastric region or right upper quadrant, and may radiate to the back. Back pain usually indicates retroperitoneal infiltration by the tumor, and therefore, probable unresectability (Table 27.1). Other symptoms may include dark urine, pale stools and pruritus. As many as 80% of patients with pancreatic cancer will present with impaired glucose tolerance or frank diabetes mellitus. Carcinoma of the body and tail of the pancreas presents with similar features, although jaundice is usually absent or develops very late in the course of the disease. A history of inflammatory bowel disease or previously diagnosed malignancies should be sought. A complete physical examination, including assessment for abnormal lymph nodes, jaundice, hepatomegaly, palpable gallbladder, or mass should be performed. A chest radiograph may be appropriate to exclude pulmonary metastases. Obtaining serum tumor markers such as CA19-9 and CEA may be appropriate. Once there is a clinical suspicion of a pancreaticobiliary malignancy, further investigation with abdominal imaging studies is appropriate.

DIFFERENTIAL DIAGNOSIS OF DISTAL BILIARY MALIGNANCIES AND IMAGING TECHNIQUES The differential diagnosis of distal biliary malignancies is shown in Table 27.2.

Ampullary carcinoma Ampullary carcinoma is suspected based upon the demonstration of obstructive jaundice, often with dilation of the pancreatic and biliary ducts seen on abdominal imaging studies. A discrete mass may or may not be identifiable by using standard transabdominal US (TUS) or helical computerized tomography (CT) scanning. ERCP allows for direct identification and biopsy confirmation, although the diagnostic accuracy of biopsy is not 100%. MRCP may allow identification of the lesion and obviate diagnostic ERCP. Endoscopic ultrasound (EUS) allows for more accurate diagnosis and staging of these lesions than CT, and also allows for fine needle aspirate (FNA) tissue sampling.9 EUS also may facilitate the selection of patients who can undergo local resection instead of pancreaticoduodenectomy (Whipple operation). Once the lesion is identified and staged, the choice of operative resection for cure or some form of jaundice palliation are similar to treatment options for carcinoma of the pancreatic head. 288

Fig. 27.1 CT demonstrating a pancreatic carcinoma causing biliary obstruction: enlarged head of the pancreas with an irregular area of low attenuation of the tumor.

Pancreatic malignancies The approach to the patient with pancreatic carcinoma involving the pancreatic head is different than in the patient with body/tail lesions in terms of accessibility, curative potential, and palliation. Most patients with cancer of the pancreatic head present with obstructive jaundice. Radiological imaging studies are performed allowing for (a) detection of the tumor, (b) determination of tumor resectability, and (c) tissue acquisition under imaging guidance. TUS will suggest biliary obstruction by the demonstration of biliary ductal dilation. It may also identify the presence of obvious liver metastases. However, standard TUS is operator dependent and has a poor sensitivity for detecting small neoplasms of the pancreatic head. Recent advances in TUS, such as color-power Doppler US, US angiography, harmonic imaging (tissue harmonic imaging and contrast harmonic imaging), and three-dimensional US, may improve the usefulness of this modality in the staging of pancreatic cancer. Nonetheless, more information regarding staging and extent of disease, and possible nodal or vascular involvement is obtainable with other imaging modalities. Helical CT of the abdomen with fine cuts through the pancreas during the arterial and portal phases of contrast enhancement has a high sensitivity and specificity for the detection of pancreatic carcinoma (Fig. 27.1). It allows for the determination of tumor extension, liver metastases, and invasion of vascular structures, and thus, resectability. Multislice (multidetector) CT has been introduced and

Chapter 27 Malignant Biliary Obstruction: Distal

may improve on the accuracy of helical CT. If the CT findings are found to be highly suggestive of a resectable pancreatic carcinoma in the appropriate clinical setting, and the patient is felt to be an operative candidate, a reasonable approach is to then refer the patient directly for an attempt at surgical resection (pancreaticoduodenectomy) with or without further imaging (depending on local availability and expertise) or diagnostic testing. Transabdominal or CT-guided biopsy of the pancreatic mass rarely may result in tumor seeding at the needle track or within the peritoneum and has been reported to increase the risk of postoperative recurrence.10 If the CT scan reveals overt evidence of unresectable pancreatic cancer or the patient is a not an operative candidate because of co-morbid medical conditions, non-operative palliation of obstructive jaundice should be performed at ERCP. If a definitive tissue diagnosis is required for the administration of chemotherapy and/or radiation therapy, tissue acquisition can be performed at the time of the palliative ERCP. If a tissue diagnosis cannot be made at that time, then transabdominal biopsy (CT-guided or US) of the mass or metastatic disease sites (i.e. liver lesions), or EUS-guided FNA of the mass or metastatic sites should be performed. Magnetic resonance imaging (MRI) of the pancreas may include MRI, MR cholangiopancreatography (MRCP), or magnetic resonance angiography. Standard abdominal MRI appears to be an accurate modality for staging pancreatic carcinoma, though it does not appear to be more specific or sensitive than helical CT. In addition, it is more expensive and more time consuming to perform than CT11 (Fig. 27.2). If expertise in EUS is readily available, it should be used as a preoperative staging modality in patients with suspected pancreatic cancer (Fig. 27.3). This is particularly important in patients with equivocal findings on CT or those with co-morbidities and, therefore, at higher risk for intra-operative or postoperative complications. EUS allows identification of vascular invasion as well as sampling of suspicious-appearing lymph nodes, which, if positive, may change the treatment approach as it alters prognosis. EUS appears to be complementary to helical CT, with EUS better at detecting small (<3 cm) masses, staging the portal vein, and detecting lymph node metastases, while helical CT is superior for staging arterial involvement and distant metastases.12 An EUS-guided FNA biopsy specimen allows for a definitive tissue diagnosis of a pancreatic mass when results on other biopsy methods are negative but pancreatic cancer is suspected. If EUS suggests resectability, EUSguided biopsy of the mass is not necessary before proceeding with operative resection, although this point remains controversial. Advantages of needle biopsy of the mass include identification of alternative diagnoses to primary pancreatic adenocarcinoma (lymphoma, islet cell tumors, and metastatic disease). It also allows for preoperative patient counseling. Potential disadvantages of preoperative EUS-guided FNA include the risks of pancreatitis, bleeding, and, theoretically, tumor seeding.13 The latter has never been reported and appears to be inconsequential in most cases since the needle path usually lies within the resected specimen. Ideally, EUS should be performed before ERCP and stent placement since the latter may interfere with the accuracy of EUS staging and EUS findings of unresectable carcinoma allow improved patient selection for placement of a self-expanding metallic stent.14 In patients with unresectable cancer, EUS-guided celiac plexus neurolysis has been shown to control disabling abdominal pain. The near-pathognomonic findings on ERCP of a pancreatic head cancer are strictures of the bile and pancreatic ducts with proximal

Fig. 27.2 Cholangiogram at MRCP showing a pancreatic carcinoma with upstream dilation of pancreatic and common bile ducts. A plastic stent is shown within the common bile duct.

Fig. 27.3 EUS appearance of a hypoechoic lesion measuring 1.5 cm in the head of the pancreas (Grey arrow). CBD = common Bile Duct, PD = Pancreatic Duct. 289

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dilation (the “double-duct” sign) (Fig. 27.4). While ductal abnormalities are almost invariably present in patients with adenocarcinoma, other imaging modalities (CT, MR, and EUS) have supplanted ERCP in the diagnosis of pancreatic cancer. Preoperative ERCP does not add further staging information and may result in complications15 that may make operative intervention more difficult and/or may considerably delay operative intervention, resulting in a decreased potential for curative resection. Furthermore, several studies suggest postoperative complications after pancreaticoduodenectomy may be higher when a preoperative ERCP is done.16 However, if the patient suffers from cholangitis or severe pruritus, or if there is a substantial delay in operative resection, preoperative ERCP with biliary drainage should be performed. A more extensive discussion on biliary stenting follows in this chapter.

dilation without an associated pancreatic mass or pancreatic ductal dilation, and the level of obstruction usually can be localized to a level above that of the pancreatic duct. The differentiation of hilar vs non-hilar tumors is important because of implications for both operative resection and endoscopic palliation. The Bismuth classification of cholangiocarcinoma is useful for determining surgical resectability and type of surgery (Fig. 27.5). If imaging studies map the level of obstruction below the bifurcation (Bismuth type I lesions, Fig. 27.5), operative resection should be considered in fit patients without metastatic disease. If the patient is a poor operative candidate, palliation with plastic or metal stents, as with pancreatic carcinoma, should be undertaken.17 The management of patients with hilar cholangiocarcinomas is detailed in the next chapter.

Metastatic disease

Cholangiocarcinoma A primary tumor of the bile duct should be suspected based on clinical and imaging findings. Abdominal CT scans will show biliary

A variety of malignant diseases may metastasize to and around the biliary tree, resulting in obstruction. These may lead to biliary obstruction either intrinsically or extrinsically (porta hepatis involvement) anywhere from the level of the bifurcation to the ampulla. The diagnosis may be obvious, based upon known widespread malignancy, or more occult and discovered at the time of endoscopic evaluation or surgical resection. CT scan findings may mimic primary malignant disease of the bile ducts or pancreas.18 An MR examination may be useful in defining the presence of perihilar obstructive disease. If disease is widespread, palliation of obstruction is indicated as for primary malignancies. Surgical resection may be indicated in selected cases.

AN APPROACH TO THE MANAGEMENT OF PATIENTS WITH DISTAL BILIARY MALIGNANCIES

Fig. 27.4 Cholangiogram at ERCP showing a stenosis of both pancreatic and common ducts also called a “double-duct sign” as seen in pancreatic adenocarcinoma. Type I

Fig. 27.5 290

Type II

The Bismuth classification for cholangiocarcinomas.

If a pancreaticobiliary malignancy is suspected based on clinical and US findings, further imaging must be performed to obtain a diagnosis, stage the extent of the malignant process for resectability, and evaluate the appropriateness of possible palliative treatment. Identification of the level of obstruction is of great importance since the differential diagnosis and therapeutic implications differ accordingly. Conceptually, management may be stratified according to whether the biliary obstruction is proximal or distal.19 Patients with a distal CBD obstruction may be amenable to endoscopic or surgical drainage, whereas a more proximal blockage of the biliary tree may require a more complex intrahepatic anastomosis or percutaneous drainage. The optimal approach to patients with malignant biliary obstruction must take into account the performance characteristics of the different imaging modalities, the level and cause of the obstruction, the risk of cholangitis when opacifying an obstructed biliary tree, and the potential for curative versus palliative therapy. Recent data suggest that non-invasive biliary imaging

Type IIIa

Type IIIb

Type IV

Chapter 27 Malignant Biliary Obstruction: Distal

may greatly assist endoscopic drainage and diminish septic complications that occur when there is a failed attempt at unilateral or bilateral drainage.20 A proposed algorithm for the management of patients with a suspected pancreaticobiliary malignancy is shown in Figure 27.6. The roles of radiotherapy and nutritional support are not addressed in this chapter.

Curative surgery Operable patients with a distal pancreaticobiliary neoplasm and no evidence of metastatic disease or local vascular invasion should be offered curative surgical resection. Unfortunately these patients account for only 10–20% of all presenting cases. Many elderly patients are not referred for consideration of surgery as they are judged unfit for surgery due to advanced age or the presence of unrelated co-morbidities. The first step towards potential resection should be laparoscopy to determine resectability and to prevent a lengthy hospital stay and prolonged convalescence associated with an unnecessary laparotomy. Laparoscopy is used mostly to detect peritoneal carcinomatosis, liver metastases, malignant ascites, and unexpected cirrhosis. Despite an extensive preoperative work-up, 11%-53% of patients are found to be unresectable at the time of laparotomy. Most patients thus end up undergoing palliative treatment tailored to the symptomatology, i.e. either a surgical bypass (biliary or biliary and gastric), or placement of a biliary stent.21

Palliation The three most important conditions requiring treatment in patients with unresectable biliary and pancreatic cancers are cholestasis, pain, and gastrointestinal obstruction. These may be consequences of local tumor invasion into adjacent structures including the bile ducts, duodenum, and neural celiac plexus.

Endoscopic stenting The following emphasizes issues relating to an approach to the management of patients with distal malignant biliary obstruction; practical aspects of biliary endoscopic stenting and a more detailed description of the equipment are discussed in Chapters 4, 16, 17, and 28.

Background Endoscopic placement of plastic biliary stents were first described by Soehendra et al. as an alternative to surgical biliary bypass in high-risk and inoperable cancer patients.22 Self-expandable metal stents (SEMS) for use in the biliary system were introduced into clinical practice over a decade later. The ability to place a largerdiameter plastic stent is limited by the size of the endoscope accessory channel. SEMS were developed to overcome this limitation. They have the advantage of larger diameter stenting (up to 10 mm) but are more costly than plastic stents.

Indications Biliary decompression is indicated if there is cholangitis or pruritus in the face of advanced malignant biliary obstruction. Biliary stenting has also been shown to improve symptoms of anorexia and quality of life.23,24 When a patient has advanced malignant disease, drainage of the biliary system for palliation is not routinely indicated because the risk of complications related to the procedure may outweigh the potential benefit. Indeed, the best treatment for a patient with asymptomatic obstructive jaundice and liver metastases may be supportive care alone. In the preoperative setting, as jaundice itself is thought to be associated with multiple adverse systemic effects (e.g. renal failure, sepsis, and impaired wound healing), it has been postulated to improve surgical outcomes if performed before pancreaticoduodenectomy. Routine preoperative drainage of an obstructed biliary system, however, has not been shown to benefit patients who will soon undergo a surgical procedure, and may in fact be deleterious in some.15,25,26 If preoperative drainage is indicated because of cholangitis or an anticipated delay to surgery in the face of clinically significant symptoms, such as pruritus, drainage has traditionally been performed using plastic stents. A recent cost-minimization study favors the preoperative placement of a short SEMS.27

Plastic endoprostheses Plastic stents are easy to insert, and can be removed if necessary (Fig. 27.7). Their biggest advantage compared to metal stents is that their upfront cost is significantly lower (tenfold in many markets).

Fig. 27.6 An algorithm suggested by the American Society for Gastrointestinal Endoscopy for the diagnosis and management of patients with suspected pancreaticobiliary malignancies.

• Clinical suspicion of primary pancreaticobiliary malignancy OR • Transabdominal US suggestive

Helical CT or MS-CT

Suspected resectable pancreatic head, ampullary, or distal cholangio CA

Unresectable primary or metastatic disease

Suspected hilar tumor

MRCP

EUS

Resectable

Surgery

Resectable

Unresectable

Unresectable Palliation

291

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Fig. 27.7 Cholangiogram at ERCP showing a 10 French, 9 cm plastic biliary endoprosthesis inserted across a distal common bile duct stricture. A large variety of biliary plastic stents are available with internal diameters ranging from 5 to 11.5 French (Fr) gauge with lengths varying from 5 to 15 centimeters (cm). Straight plastic stents with flaps at both ends and side-holes are the most common type of stent used. The presence of flaps minimizes the risk of stent migration which is less likely to occur in pigtail stents due to their physical characteristics that allow greater anchoring inside the CBD and duodenum. Although no study has compared the occlusion and migration rates between straight and pigtail stents, animal studies suggest that straight stents may provide better bile drainage than pigtail stents.28 The main limitation of plastic stents is their shorter duration of patency and the potential for occlusion. Many studies have assessed the mechanisms of plastic stent occlusion. Although recent investigations have focused on the importance of ingested fiber matter,29 most studies have historically emphasized bacterial colonization of the prosthesis interior leading to production of a bacterial biofilm and subsequent stent clogging.30 These findings have resulted in modified stent designs or the use of adjuvant medications in the hope of prolonging stent patency. (a) Size of the internal diameter: The duration of patency for stents with an internal diameter of 10 Fr or greater is 21–32 weeks compared to 10–12 weeks for 7 or 8.5 Fr plastic stents. Additionally, there may be a lower associated incidence of cholangitis with larger gauge stents. The superior performance of large-caliber stents is attributed to improved internal flow dynamics.31 There is no conclusive evidence favoring 11.5 Fr compared to 10 Fr stents,32 and the insertion of 10 Fr stents does not require the routine perfor292

mance of a sphincterotomy. Stent length does not seem to affect patency duration. (b) Plastic-stent design: Evidence linking the presence of side holes as a contributing factor for stent occlusion prompted the development of a stent without side holes. As materials that allow a lower coefficient of friction may theoretically reduce stent clogging, the stent was made of Teflon. However these changes have not resulted in proven clinical benefits.33,34 More recently, a double layer plastic stent, combining a very smooth inner surface with an absence of sideholes, has been found in one randomized trial to display a longer patency duration than the standard polyethylene stents,40 while a pilot study has assessed a stent without a lumen, that may result in prolonged stent patency.41 (c) Position of the distal tip of the stent: Placement of plastic stent above an intact sphincter of Oddi appeared useful in animals by preventing colonization by bacteria, but did not result in demonstrable patency improvement in a human, randomized clinical trial. Moreover, stents placed above the papilla had higher stent migration rates.35 (d) Administration of choleretic agents and/or antibiotics: The role of pharmacological agents to lengthen the patency period fo plastic stents has been assessed using choleretic agents that may enhance bile flow and reduce stent occlusion. Antibiotics may also be useful by inhibiting bacterial colonization of the stent. However, both classes of drugs, alone or in combination, have failed to demonstrate improvement in the duration of stent patency.36,37 A series of metaanalyses have confirmed the negative results for all the aforementioned attempts in improving the duration of patency with plastic stents.38 In addition, no improvement in survival has been noted. A recent randomized trial of patients with malignant biliary obstruction treated by plastic stent insertion demonstrated that long-term ciprofloxacin administration initiated prior to the ERCP significantly decreased the incidence of cholangitis, and resulted in improvement of certain domains of quality of life.39

Self-expandable metal stents The idea of inserting an expandable stent has been applied to strictures of the biliary tree comparable to their use in vascular stenoses.8 SEMS are braided in the form of a tubular mesh using a surgical grade steel alloy. The elastic properties of the material allow the stent to adopt different configurations according to the site and intensity of forces applied to it. SEMS are delivered into the bile duct while completely constrained by a sheath, allowing insertion as a smallcircumference delivery system. As the constraining sheath is progressively retracted from its more distal end, the intrinsic expansile forces of the stent make it regain its original configuration. After the sheath is completely withdrawn, the end result is an expanded stent which accommodates to the shape of normal and strictured bile ducts by maintaining constant radial pressure against its bile duct wall (Figs 27.8 and 27.9). Since the initial application of Wallstents in patients with biliary malignancies, a multitude of SEMS types have been released. SEMS differ in regard to the type of delivery system, structural composition, design, length and diameter. However, all achieve a much larger internal diameter and subsequent longer patency rate compared to plastic stents (see below). The mechanisms of SEMS blockage include stent ingrowth and overgrowth by tumor, as well as mucosal hyperplasia.42 There are limited published data directly comparing different models of uncovered SEMS.43,44,44a Generally, most biliary endoscopists consider SEMS models to be equivalent. Familiarity with the

Chapter 27 Malignant Biliary Obstruction: Distal

Fig. 27.9 Endoscopic picture of metallic stent after full deployment with good bile flow from the stent.

Fig. 27.8 Cholangiogram at ERCP showing a distal common bile duct stricture caused by a pancreatic adenocarcinoma. A selfexpanding metallic stent has been inserted for palliation.

mechanical characteristics of the stent and its delivery system is important to consider when choosing a SEMS. More recently, polyurethane-covered SEMS have been developed in the hope of prolonging stent patency by presenting a physical barrier to tumor ingrowth. In the sole randomized comparative trial to date, the covered SEMS technology was associated with a significant increase in patency duration as compared to the uncovered SEMS.45 More recent non-randomized studies have questioned this finding.45a,45b However the covered SEMS may be more prone to migration, and may occlude ductal branches, leading to complications such as cholecystitis, cholangitis, and pancreatitis.45,46 Risk factors for the development of cholecystitis in this setting include gallstones and cystic duct invasion by tumor.46a SEMS are difficult to remove so they are generally reserved for patients with established, unresectable malignant disease, although recently, an increasing number of endoscopists are describing removal of covered SEMS.47 Additional complications related to biliary stenting (common to both plastic and metal stents) are much more infrequent and include upper gastrointestinal bleeding, duodenal perforation, and intestinal luminal obstruction.

Stent choices for palliation of malignant biliary obstruction The optimal stent choice for the palliation of malignant biliary obstruction is dependent on multiple factors and varies from patient to patient. The major decision that needs to be made is the type of stent to be placed (plastic or metal). Important measures for this decision include several stent-related factors, such as stent efficacy (relief of jaundice), stent patency, need for reinterventions, and

costs. Patient-related issues, such as the extent of disease and expected survival time, also need to be considered and influence the optimal and cost-effective choice of stent. Several trials have directly compared plastic stents to SEMS for the palliation of malignant biliary obstruction. Plastic stents and SEMS both provide palliation of jaundice and improve liver tests after placement in over 95% of patients; they are equivalent in this regard. These two stent types, however, significantly differ in duration of patency. Median stent patency ranges from 2 to 5 months for plastic stent, whereas it is 4 to 10 months or more for SEMS.48,49,49a The decreased patency of plastic stents seems to influence the need for additional interventions. In comparative trials, the use of plastic stents led to significantly increased repeat endoscopic interventions to re-establish biliary drainage as compared with either covered or uncovered SEMS.48,49,49b In several of these studies there were significantly increased numbers of hospitalization days associated with the use of plastic stents versus SEMS. Median patient survival ranges from 4 to 6 months after plastic or metallic stenting. There have been no associated survival benefits demonstrable that are attributable to any stent type in individual trials, although a recent metaanalysis presented in abstract form demonstrated an improvement in survival attributable to the use of SEMS compared to plastic stents in patients with distal malignant biliary obstruction. Self-expandable metal stents confer a survival advantage in palliation of distal malignant biliary obstruction.49c The recent Cochrane systematic review, however, did not conclude on any survival benefits attributable to metal versus plastic stents.49a Cost-effectiveness analyses have shown that the optimal choice of stent (plastic versus SEMS) is influenced by the ratio of the cost of stent to the cost of the ERCP, and the anticipated life expectancy of the patient.50,51 The greater the cost of the ERCP, the more likely the SEMS will be a cost-effective choice. Unfortunately, it is difficult to estimate survival in a patient with malignant biliary 293

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obstruction. Plastic stents may be preferred to SEMS in patients with large tumors (>3 cm) or liver metastases, both of which are poor predictors of survival, as plastic stents are cost-saving in patients surviving less than 3–4 months while SEMS are more cost-effective in patients expected to survive longer than 6 months.50,51 Direct cost measurements from a randomized controlled trial demonstrated similar results.52 Despite these considerations, there are no strict criteria for selecting between plastic stents and SEMS for the palliation of unresectable malignant biliary obstruction. Indeed, the decision must be individualized as patient factors must also be considered. For example, SEMS may be preferred in a patient who is non-compliant or resides in a remote area without medical access, despite an anticipated short life expectancy. Patients with difficult endoscopic biliary access from associated duodenal stenosis may benefit from early SEMS placement, and may even be candidates for endoscopic double bypass where a biliary and an enteric metallic stents are placed.52a

Fig. 27.10 Plain abdominal radiograph showing a plastic stent inserted within a blocked SEMS.

The optimal stenting strategy In addition to deciding on the optimal stent technology (plastic versus SEMS), an endoscopist must also consider the optimal stenting strategy. For example, if a plastic stent is initially inserted, should it be replaced at regular intervals to prevent stent blockage, or is it best to change the plastic stent on demand during the life of the patient? In a randomized trial, routine exchanges every 3 months were associated with longer symptom-free intervals for patients than exchanges at signs of stent occlusion, but there was no difference in overall survival.52 An extensive cost-effectiveness model suggested, in order of the most to the least cost-effective approaches, the following approaches: initial insertion of a covered SEMS, or of an uncovered metal stent, and a plastic stent with its subsequent on demand replacement (when the patient developed symptoms suggesting stent occlusion). Least cost-effective was the routine threemonthly replacement of a plastic stent.53 As discussed previously, a cost-minimization analysis suggested that the preoperative insertion of a short covered SEMS is cost saving.27 Occluded SEMS are managed by a variety of methods. The most commonly used techniques include insertion of a plastic stent within the occluded SEMS (Fig. 27.10), insertion of a second SEMS (Fig 27.11) and mechanical cleaning of the occluded stent lumen. Overall success rates for re-establishing biliary drainage are over 80%. Mechanical cleaning methods, such as catheter irrigation or the use of stone-extraction balloons, may be less successful and are associated with decreased duration of patency than repeat stenting. Given the typical short median survival at the time of the first SEMS occlusion, treatment with a plastic prosthesis seems to be the most costeffective method. Other techniques for SEMS recanalization include application of thermal energy and intaductal brachytherapy but are not widely used.

294

Percutaneous approach

Fig. 27.11 Plain abdominal radiograph showing a second SEMS inserted within an initially placed, now occluded SEMS.

Percutaneous insertion of plastic stents and SEMS is an acceptable alternative for management of distal biliary malignant obstruction not successfully treated by an endoscopic approach. Percutaneous drainage was the preferred palliative method in patients with malignant obstruction until several years ago. This procedure entails sterile catheterization of a peripheral biliary radical after percutaneous puncture. External drainage is accomplished by percutaneous transhepatic insertion of a catheter, manipulation of a guidewire and insertion of a drainage catheter through the obstructing lesion that

allows both internal and external bile flow. The technique has evolved over the years and currently insertion of an indwelling catheter without external drainage is possible; furthermore, the advent of SEMS has obviated in many cases the need for serial tract dilation. Prior to the era of metallic expandable stents, the percutaneous approach had permitted the insertion of plastic stents with larger diameters when compared to endoscopic drainage. The consequent

Chapter 27 Malignant Biliary Obstruction: Distal

benefit of a longer stent patency represented a significant advantage over the prosthesis inserted by ERCP which was historically limited by the size of the accessory channel of duodenoscopes. Also, percutaneous drainage appeared to be as effective as biliary bypass and had other inherent advantages. Bornman et al. found the overall survival to be similar in both surgical and percutaneous groups, whereas percutaneous drainage was associated with a lower procedure-related complication and 30-day mortality rate.54 The disadvantages of external biliary drainage include the risk of spontaneous catheter dislodgment, inflammation and pain around the puncture site, leak of ascitic fluid and bile around the catheter, and loss of fluid and electrolytes. The complication rate for transhepatic biliary drainage can be substantial and varies with the patient status prior to the procedure as well as the diagnosis. The presence of coagulopathy, cholangitis, stone, malignant obstruction or intrahepatic lesions are all associated with high complication rates. The advent of self-expandable metal endoprostheses, larger size accessory channels in duodenoscopes, and the complication rate observed with percutaneous drainage have changed the standard of practice. Speer and colleagues conducted a prospective, randomised study comparing percutaneous and endoscopic drainage. While overall survival was not different between either arm, 30-day mortality, both by intention-to-treat and per-protocol analysis, was significantly lower in the endoscopy group and justified the early termination of the study.55 The authors found that complications associated with the percutaneous procedure accounted for the difference in mortality and that endoscopic insertion of a stent was safer and more likely to succeed.55 In contradistinction, a recent RCT showed that patients undergoing percutaneous drainage had a longer survival than those in the endoscopy group.56 However, a number of possible confounders of outcome need to be examined: First, the authors selected not only patients with unresectable distal biliary obstruction but also subjects with more proximal obstruction including hilar tumors. The latter may be more amenable to percutaneous management. These inclusion criteria could explain the low success rate of PE stent insertion by endoscopy (58%) which, in turn, accounted for the suboptimal efficacy observed in this group. Secondly, the authors used SEMS in the percutaneous group and PE stents in the endoscopic drainage group, which biases against the endoscopic approach even though it may represent that institution’s practice. The economic evaluation of this study is also difficult to interpret as it did not include procedural costs, and may thereby have further disadvantaged the endoscopic treatment arm. At present, there is insufficient evidence in the literature to advocate the routine use of percutaneous drainage as the preferred approach in the palliation of patients with distal biliary obstruction other than for reasons of institutional expertise or availability.

Surgical palliation Historically, surgery was the favored method of palliation, but has been replaced by percutaneous and endoscopic insertion of stents.57 The 30-day mortality after surgical palliation for pancreatic cancer and cholangiocarcinoma is significant, especially in the face of advancing age and metastatic disease. Surgical biliary and gastrointestinal bypass have been advocated for patients who also suffer from chronic pain, since celiac nerve block can also be performed at the time of surgery. Whether prophylactic gastrointestinal bypass should be offered to patients with malignant obstructive jaundice, and if so, when, remains unclear. Recent studies have shown that gastrojejunostomy, in addition to biliary bypass may decrease the inci-

dence of late gastric outlet obstruction without higher morbidity or mortality.58 Surgery has the advantage of precluding multiple reinterventions, associated with less invasive procedures, namely endoscopic stenting. Three prospective randomized trials have compared open surgery to endoscopic stenting.59–61 Smith and colleagues randomized 203 patients to 10 French (Fr) plastic stents or biliary bypass (choledochoduodenostomy and choledochojejunostomy). Patients who underwent stent placement had lower procedurerelated and major complication rates as well as a shorter hospital stay than the surgical group. Most complications occurred in the first 30 days in the surgical group. In contrast to the endoscopy group, therefore numerically fewer late complications due to cholangitis or gastric obstruction. Shepherd and Andersen conducted smaller studies that have shown similar results. While overall survival did not differ between treatments, they demonstrated that endoscopic stenting had a lower rate of short-term complications than surgical treatment. Although patients in the endoscopy group had more obstructions and needed more re-interventions, the total number of days in hospital was higher in the surgical group. A meta-analysis performed with these three studies confirmed a higher likelihood of intervention in the stent group.62 The recent Cochrane systematic review by Moss et al. suggested a lower recurrent biliary obstruction rate attributable to surgery, with a higher overall complication rate, and no difference in mortality when compared to plastic biliary stenting.49a Although performed more than 10 years ago, before the advent of newer stent technologies and less invasive surgical procedures, these studies suggest that endoscopic prostheses are effective and less costly than surgery. A recent, single-center, retrospective cost-analysis in the US also revealed a striking difference between endoscopic palliation and surgery despite the need for repetitive interventions and readmissions in the endoscopic group.63 However, surgical bypass remains an excellent alternative and may be favored in patients with unresectable disease at the time of laparotomy, and for those requiring concomitant gastrointestinal bypass and/or celiac nerve block for management of chronic pain.

Adjuvant therapy While the cases of biliary obstruction due to lymphomas can be managed with stent insertion or surgical bypass, cure can only be achieved with remission of the underlying disease. Responsiveness to chemotherapy is the main predictor for outcome in these patients. In contrast, cure of tumors of epithelial origin can only be achieved with surgical resection, even though adjuvant chemotherapy has been shown to improve 1- and 5-year survival after resection of pancreatic adenocarcinoma.64 The role of chemotherapy in patients with unresectable disease is still limited. Studies have shown that 5-Fluoracil (5-FU) based regimens are superior to observation or supportive treatment in patients with unresectable adenocarcinoma of the pancreas. Unfortunately, the combination of other chemotherapeutic agents such as cisplatin with 5-FU is no better than 5-FU alone.65 In fact, this combination is associated with an increased rate of systemic toxicity, which seems to be unrelated to the biliary obstruction and inability to excrete the drug metabolites. An important breakthrough in the management of advanced pancreatic cancer occurred with the introduction of gemcitabine and other cytotoxic drugs which have been shown to improve major symptoms such as pain and weight loss, clinical benefit response, time to progression, and length of survival, but maintain an acceptable toxicity profile.66 295

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The effect of chemotherapy in the management of malignant biliary obstruction is unknown. Because tumor invasion into the biliary tree is unlikely to be relieved by chemotherapy alone, a procedure to palliate the obstruction is still necessary regardless of the administration and response to adjuvant therapy, and may in fact be required to improve liver tests and function prior to the initiation of this treatment. In contrast, addition of a chemotherapeutic regimen for the treatment of patients with unresectable disease could potentially result in an improvement in survival and influence the choice of palliation. There are no studies evaluating the effect of chemotherapy on the patency of stents. While chemotherapeutic agents are unlikely to affect the mechanisms involved in plastic stent occlusion, reduction of the tumor mass could diminish the probability of tumor ingrowth and prolong patency of SEMS. It is unknown if adjuvant chemotherapy can increase the risk of stent migration and malfunctioning as has been suggested for esophageal malignancies.67

SUMMARY Distal malignant biliary obstruction is a commonly encountered problem facing endoscopists that requires a multidisciplinary approach involving surgeons, radiologists and gastroenterologists. The optimal approach to manage this complex medical problem depends more on available expertise and resources than the evidence in the literature. Endoscopic techniques have advanced significantly over the past two decades and maintain a central role in the palliation of distal pancreaticobiliary malignancy.

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27. Chen VK, Arguedas MR, Baron TH. Expandable metal biliary stents before pancreaticoduodenectomy for pancreatic cancer: a Monte-Carlo decision analysis. Clin Gastroenterol Hepatol 2005; 3:1229–1237. 28. Scheeres D, O’Brien W, Ponsky L, et al. Endoscopic stent configuration and bile flow rates in a variable diameter bile duct model. Surg Endosc 1990; 4:91–93. 29. van Berkel AM, van Marle J, Groen AK, et al. Mechanisms of biliary stent clogging: confocal laser scanning and scanning electron microscopy. Endoscopy 2005; 37:729–734. 30. Libby ED, Leung JW. Prevention of biliary stent clogging: a clinical review. Am J Gastroenterol 1996; 91:1301–1308. 31. Speer AG, Cotton PB, MacRae KD. Endoscopic management of malignant biliary obstruction: stents of 10 French gauge are preferable to stents of 8 French gauge. Gastrointest Endosc 1988; 34:412–417. 32. Kadakia SC, Starnes E. Comparison of 10 French gauge stent with 11.5 French gauge stent in patients with biliary tract diseases. Gastrointest Endosc 1992; 38:454–459. 33. Catalano MF, Geenen JE, Lehman GA, et al. “Tannenbaum” Teflon stents versus traditional polyethylene stents for treatment of malignant biliary stricture. Gastrointest Endosc 2002; 55: 354–358. 34. van Berkel AM, Huibregtse IL, Bergman JJ, et al. A prospective randomized trial of Tannenbaum-type Teflon-coated stents versus polyethylene stents for distal malignant biliary obstruction. Eur J Gastroenterol Hepatol 2004; 16:213–217. 35. Pedersen FM, Lassen AT. Response. Gastrointest Endosc 2000; 51:117. 36. De Ledinghen V, Person B, Legoux JL, et al. Prevention of biliary stent occlusion by ursodeoxycholic acid plus norfloxacin: a multicenter randomized trial. Dig Dis Sci 2000; 45:145–150. 37. Halm U, Schiefke, Fleig WE, et al. Ofloxacin and ursodeoxycholic acid versus ursodeoxycholic acid alone to prevent occlusion of biliary stents: a prospective, randomized trial. Endoscopy 2001; 33:491–494. 38. Waschke K, da Silveira E, Toubouti Y, et al. The role of plastic stents, adjuvant therapy and metal stents in distal malignant biliary obstruction. a systematic review and series of metal-analyses. American Journal of Gastroenterology 2004; 99:AB 74. 39. Chan G, Barkun J, Barkun AN, et al. The role of ciprofloxacin in prolonging polyethylene biliary stent patency: a multicenter, double-blinded effectiveness study. J Gastrointest Surg 2005; 9:481–488. 40. Tringali A, Mutignani M, Perri V, et al. A prospective, randomized multicenter trial comparing DoubleLayer and polyethylene stents for malignant distal common bile duct strictures. Endoscopy 2003; 35:992–997. 41. Raju GS, Sud R, Elfert AA, et al. Biliary drainage by using stents without a central lumen: a pilot study. Gastrointest Endosc 2006; 63:317–320. 42. Huibregtse K, Carr-Locke DL, Cremer M, et al. Biliary stent occlusion—a problem solved with self-expanding metal stents? European Wallstent Study Group. Endoscopy 1992; 24:391–394. 43. Dumonceau JM, Cremer M, Auroux J, et al. A comparison of Ultraflex Diamond stents and Wallstents for palliation of distal malignant biliary strictures. Am J Gastroenterol 2000; 95: 670–676. 44. Shim CS, Lee YH, Cho YD, et al. Preliminary results of a new covered biliary metal stent for malignant biliary obstruction. Endoscopy 1998; 30:345–350. 44a. Shah RJ, Howell DA, Desilets DJ, Sheth SG, Parsons WG, Okolo P 3rd, Lehman GA, Sherman S, Baillie J, Branch MS, Pleskow D,

Chuttani R, Bosco JJ. Multicenter randomized trial of the spiral Z-stent compared with the wallstent for malignant biliary obstruction. Gastrointest Endosc 2003; 57(7):830–836. 45. Isayama H, Komatsu Y, Tsujino T, et al. A prospective randomised study of “covered” versus “uncovered” diamond stents for the management of distal malignant biliary obstruction. Gut 2004; 53:729–734. 45a. Park do H, Kim MH, Choi JS, Lee SS, Seo DW, Kim JH, Han J, Kim JC, Choi EK, Lee SK. Covered versus uncovered wallstent for malignant extrahepatic biliary obstruction: a cohort comparative analysis. Clin Gastroenterol Hepatol. 2006; 4(6):790–796. 45b. Yoon WJ, Lee JK, Lee KH, Lee WJ, Ryu JK, Kim YT, Yoon YB. A comparison of covered and uncovered wallstents for the management of distal malignant biliary obstruction. Gastrointest Endosc 2006; 63(7):996–1000. 46. Nakai Y, Isayama H, Komatsu Y, et al. Efficacy and safety of the covered Wallstent in patients with distal malignant biliary obstruction. Gastrointest Endosc 2005; 62:742–748. 46a. Suk KT, Kim HS, Kim JW, Baik SK, Kwon SO, Kim HG, Lee DH, Yoo BM, Kim JH, Moon YS, Lee DK. Risk factors for cholecystitis after metal stent placement in malignant biliary obstruction. Gastrointest Endosc 2006; 64(4):522–529. 47. Baron T, Poterucha J. Insertion and removal of covered expandable metal stents for closure of complex biliary leaks. Clinical gastroenterology and hepatology 2006; 4:381–386. 48. Davids PH, Groen AK, Rauws EA, et al. Randomised trial of selfexpanding metal stents versus polyethylene stents for distal malignant biliary obstruction. Lancet 1992; 340:1488–1492. 49. Kaassis M, Boyer J, Dumas R, et al. Plastic or metal stents for malignant stricture of the common bile duct? Results of a randomized prospective study. Gastrointest Endosc 2003; 57:178–182. 49a. Moss AC, Morris E, Leyden J, MacMathuna P. Malignant distal biliary obstruction: a systematic review and meta-analysis of endoscopic and surgical bypass results. Cancer Treat Rev 2007; 33(2):213–221. 49b. Soderlund C, Linder S. Covered metal versus plastic stents for malignant common bile duct stenosis: a prospective, randomized, controlled trial. Gastrointest Endosc 2006; 63(7):986–895. 49c. Waschke K, da Silveira E, Toubouti Y, Rahme E, Barkun A. Selfexpandable metal stents confer a survival advantage in palliation of distal malignant biliary obstruction. Gastrointest Endosc 2005; 61(5):T1322. 50. Arguedas MR, Heudebert GH, Stinnett AA, et al. Biliary stents in malignant obstructive jaundice due to pancreatic carcinoma: a cost-effectiveness analysis. Am J Gastroenterol 2002; 97:898–904. 51. Yeoh KG, Zimmerman MJ, Cunningham JT, et al. Comparative costs of metal versus plastic biliary stent strategies for malignant obstructive jaundice by decision analysis. Gastrointest Endosc 1999; 49:466–471. 52. Prat F, Chapat O, Ducot B, et al. A randomized trial of endoscopic drainage methods for inoperable malignant strictures of the common bile duct. Gastrointest Endosc 1998; 47:1–7. 52a. Maire F, Hammel P, Ponsot P, Aubert A, O’Toole D, Hentic O, Levy P, Ruszniewski P. Long-term outcome of biliary and duodenal stents in palliative treatment of patients with unresectable adenocarcinoma of the head of pancreas. Am J Gastroenterol 2006; 101(4):735–742. 53. da Silveira E, Waschke K, Barkun A, et al. Cost-effectiveness decision analysis comparing covered to uncovered selfexpandable metal stents to elective or on-demand polyethylene stent changes in patients with distal biliary malignant obstruction. Gastrointest Endosc 2005; 61:AB 203.

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54. Bornman PC, Harries-Jones EP, Tobias R, et al. Prospective controlled trial of transhepatic biliary endoprosthesis versus bypass surgery for incurable carcinoma of head of pancreas. Lancet 1986; 1:69–71. 55. Speer AG, Cotton PB, Russell RC, et al. Randomised trial of endoscopic versus percutaneous stent insertion in malignant obstructive jaundice. Lancet 1987; 2:57–62. 56. Pinol V, Castells A, Bordas JM, et al. Percutaneous self-expanding metal stents versus endoscopic polyethylene endoprostheses for treating malignant biliary obstruction: randomized clinical trial. Radiology 2002; 225:27–34. 57. Sharma D, Bhansali M, Raina VK. Surgical bypass is still relevant in the palliation of malignant obstructive jaundice. Trop Doct 2002; 32:216–219. 58. Lillemoe KD, Grosfeld JL. Addition of prophylactic gastrojejunostomy to hepaticojejunostomy significantly reduces gastric outlet obstruction in people with unresectable periampullary cancer. Cancer Treat Rev 2004; 30:389–393. 59. Andersen JR, Sorensen SM, Kruse A, et al. Randomised trial of endoscopic endoprosthesis versus operative bypass in malignant obstructive jaundice. Gut 1989; 30:1132–1135. 60. Shepherd HA, Royle G, Ross AP, et al. Endoscopic biliary endoprosthesis in the palliation of malignant obstruction of the

298

61.

62.

63.

64. 65.

66.

67.

distal common bile duct: a randomized trial. Br J Surg 1988; 75:1166–1168. Smith AC, Dowsett JF, Russell RC, et al. Randomised trial of endoscopic stenting versus surgical bypass in malignant low bileduct obstruction. Lancet 1994; 344:1655–1660. Taylor MC, McLeod RS, Langer B. Biliary stenting versus bypass surgery for the palliation of malignant distal bile duct obstruction: a meta-analysis. Liver Transpl 2000; 6:302–308. Martin RC, 2nd, Vitale GC, Reed DN, et al. Cost comparison of endoscopic stenting vs surgical treatment for unresectable cholangiocarcinoma. Surg Endosc 2002; 16:667–670. Shore S, Raraty MG, Ghaneh P, et al. Review article: chemotherapy for pancreatic cancer. Aliment Pharmacol Ther 2003; 18:1049–1069. Ducreux M, Rougier P, Pignon JP, et al. A randomised trial comparing 5-FU with 5-FU plus cisplatin in advanced pancreatic carcinoma. Ann Oncol 2002; 13:1185–1191. Heinemann V. Gemcitabine in the treatment of advanced pancreatic cancer: a comparative analysis of randomized trials. Semin Oncol 2002; 29:9–16. Siersema PD, Hop WC, Dees J, et al. Coated self-expanding metal stents versus latex prostheses for esophagogastric cancer with special reference to prior radiation and chemotherapy: a controlled, prospective study. Gastrointest Endosc 1998; 47:113–120.

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Chapter

28

APPROACH TO CLINICAL PROBLEMS

Malignant Biliary Obstruction: Hilar Giovanni D. De Palma

INTRODUCTION BOX 28.1 KEY POINTS 1. Review of epidemiology of malignant bile duct obstruction at the hepatic hilum. 2. Review of anatomical classification.

Epidemiology of malignant bile duct obstruction Malignant biliary obstruction at the liver hilum is caused by a heterogeneous group of tumors that includes primary bile duct cancer (the so-called Klatskin tumor), cancers that involve the confluence by direct extension (e.g., gallbladder and liver cancer), and metastatic cancer to hilar lymphatic nodes or to the liver (Table 28.1). Primary cholangiocarcinoma of the hepatic hilus affecting either the right or left main hepatic ducts or the biliary confluence was first described in 1957 by Altemeier et al. Other investigators have also documented the existence of this tumor, but it was not until 1965 that Klatskin1 reported the first comprehensive examination of the pathology, diagnosis, and management of the tumor that now bears his name. Cholangiocarcinoma is an uncommon malignancy comprising less than 2% of all cancer diagnoses. The overall rate of occurrence of cholangiocarcinoma is 1.2/100 000 individuals, with two-thirds of all cases occurring in patients more than 65 years old, and a near tenfold increased rate of occurrence in patients more than 80 years of age.2 In recent years, there has been a worldwide trend towards decreased mortality from extrahepatic tumors, particularly for females. In contrast to the observations in intrahepatic cholangiocarcinoma, the estimated annual percentage change in mortality for extrahepatic biliary tract cancers decreased in most countries, with the exception of the United Kingdom.3 Chronic biliary tract inflammation represents a major risk factor for the development of cholangiocarcinoma. The association between chronic parasitic infection of the biliary tract and cholangiocarcinoma is obvious in regions of high endemicity, such as in certain Far Eastern nations. In Western nations, primary sclerosing cholangitis is the most common risk factor identified with the development of cholangiocarcinoma.4 Extrahepatic cholangiocarcinoma has traditionally been separated into three groups, based on anatomical location. Upper third or hilar

tumors are those located in the common hepatic duct and/or the right and left hepatic ducts including their confluence. Middle third tumors occur in the region bounded by the upper border of the duodenum and extending to the common bile duct. Lower third or distal bile duct tumors arise between the ampulla of Vater and the upper border of the duodenum. Tumors at the biliary confluence of the liver are the most common and comprise 40–60% of the total. Middle third and distal third tumors comprise 17–20%, and 18–27%, respectively. A small percentage of patients (<10%) have diffuse tumors involving the entire extrahepatic bile duct.2.4,5

Anatomical classification The extent of duct involvement by perihilar tumors may be classified as suggested by Bismuth and Corlette6 (Fig. 28.1): A. type I: tumors below the confluence of the left and right hepatic ducts (ceiling of the biliary confluence is intact; right and left ductal systems communicate); B. type II: tumors reaching the confluence but not involving the left or right hepatic ducts (ceiling of the confluence is destroyed; bile ducts are separated); C. type III: tumors occluding the common hepatic duct and either the right (IIIa) or left (IIIb) hepatic duct; D. type IV: multicentric tumors or tumors involving the confluence and both hepatic ducts, the right one and the left one.

MANAGEMENT STRATEGIES FOR HILAR TUMORS BOX 28.2 KEY POINTS 1. Understanding the role of imaging studies. 2. Review of the management strategies for resectable tumors. 3. Review of the pros and cons of alternative palliative techniques.

Hilar tumors have proven to be a challenge to treat and manage because of their poor sensitivity to conventional therapies and our inability to prevent or to detect early tumor formation. Untreated patients usually die within six months to a year of diagnosis. The range of therapeutic modalities varies from a curative approach by performing extensive liver resections—in some 299

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cases even total hepatectomy and liver transplantation—to a more palliative approach in which a surgical bypass or even percutaneous or endoscopic stent insertion is undertaken, with or without radiotherapy. All patients should be fully evaluated for resectability before any type of intervention is performed because stent-associated inflammation or infection often makes assessment more difficult. Patients being evaluated for resectability must at first be physiologically suitable for a potential operative resection that may include a partial hepatectomy. The patient’s nutritional status and risk of postoperative liver failure are important factors to consider before proceeding to exploration for resection. A retrospective review of resected hilar cholangiocarcinoma cases demonstrated that a preoperative serum albumin level <3 g/dl and a total bilirubin level >10 mg/dl were both associated with poorer survival.7 All available data must be used to distinguish resectability (localized cancers) from unresectability (Table 28.2). The preoperative evaluation of a patient with suspected hilar tumors is directed toward the following three primary objectives: (1) an assessment of the extent and level of biliary tract and portal vein involvement; (2) an assessment of the liver status to detect evidence of lobar atrophy or concomitant liver pathology; (3) an evaluation of the presence and extent of nodal disease and/or distant metastases.

Radiological studies Radiographic studies are essential in therapeutic planning of patients with hilar cholangiocarcinoma.8–11 Most jaundiced patients undergo initial transabdominal ultrasound (US) before being referred to a hepatobiliary specialist. In patients with hilar lesions US typically demonstrates intrahepatic bile duct dilation and normal diameter of extrahepatic ducts, or dila-

Malignant

Non-malignant

Cholangiocarcinoma Gallbladder carcinoma Nodal mets at porta hepatis Hepatocellular carcinoma Hepatic metastases Metastase to biliary tree

Sclerosing cholangitis Inflammatory strictures Post operative Post radiation – chemotherapy Caroli’s disease Retroperitoneal fibrosis AIDS

Table 28.1 Hilar strictures

Type I

Type II

Type IIIa

tion of both intrahepatic and extrahepatic ducts in more distal lesions. Centers with expertise in duplex ultrasound have found that this method is an accurate predictor of vascular involvement and resectability. Duplex ultrasonography can identify the site of biliary obstruction, as well as the presence or absence of portal venous involvement, with 93% sensitivity and 99% specificity. Contrast CT is sensitive to detect bile duct tumors, the level of biliary obstruction, and the presence of liver atrophy. In addition, CT may also permit visualization of the pertinent nodal basins. Performance of a triple-phase helical CT will detect essentially all cholangiocarcinomas greater than 1 cm. However, CT may only be able to establish resectability in approximately 60% of patients. Dilation of the intrahepatic bile ducts in a single, small hepatic lobe with hypertrophy of the contralateral lobe suggests the atrophy-hypertrophy complex, as seen with tumors chronically obstructing a single lobe and invading the ipsilateral portal vein. Bilobate dilated intrahepatic ducts and a normal or collapsed gallbladder and common bile duct suggest a perihilar tumor. At the present time magnetic resonance (MR) is the optimal initial investigation for suspected hilar cholangiocarcinoma. MR permits excellent visualization of hepatic parenchymal abnormalities, as well as the visualization of the biliary tree and vascular structures. MR with the use of ferrous oxide and gadolinium yields information similar to that yielded by CT, cholangiography, and angiography combined (Fig. 28.2). MR cholangiopancreatography (MRCP), has the capability to evaluate the bile ducts both above and

• Medical co-morbidities limiting the patient’s ability to undergo major surgery • Significant underlying liver disease prohibiting liver resection necessary for curative surgery based on preoperative imaging • Bilateral tumor extension to secondary biliary radicals • Encasement or occlusion of the main portal vein • Lobar atrophy with contralateral portal vein involvement • Contralateral tumor extension to secondary biliary radicals • Evidence of metastases to N2 level lymph nodesa • Presence of distant metastases

Table 28.2 Criteria for unresectability in patients with hilar cholangiocarcinoma a N2 lymph nodes, metastasis in the peripancreatic (head only), paraduodenal, periportal, celiac, superior mesenteric, and/or posterior pancreaticoduodenal lymph nodes.

Type IIIb

Type IV

Type IV

Fig. 28.1 Schematic representation of Bismuth classification of hilar cholangiocarcinoma. Type I: tumors below the confluence of the left and right hepatic ducts (ceiling of the biliary confluence is intact; right and left ductal systems communicate); type II: tumors reaching the confluence but not involving the left or right hepatic ducts (ceiling of the confluence is destroyed; bile ducts are separated); type III: tumors occluding the common hepatic duct and either the right (IIIa) or left (IIIb) hepatic duct; type IV: multicentric tumors or tumors involving the confluence and both hepatic ducts, the right one and the left one. 300

Chapter 28 Malignant Biliary Obstruction: Hilar

A

B

Fig. 28.2 Contrast enhanced MR A and MRCP B showing tumor involving the confluence and both hepatic ducts, the right one and the left one. Courtesy of Mainenti P., MD, and Maurea S., MD. Dipartimento di Scienze Biomorfologiche e Funzionali; University of Naples Federico II, School of Medicine.

below a stricture. The efficacy of MRCP as a non-invasive means of acquiring reliable and precise information about the anatomy of both the intrahepatic and the extrahepatic biliary tree, has been well documented and has almost totally replaced percutaneous and endoscopic cholangiography. EUS has not been proven to offer more than using other imaging modalities in patients with suspected hilar cholangiocarcinoma. One small series suggests that EUS may allow a definitive histological diagnosis to be made in patients with hilar tumors.12 Intraductal US (IDUS), at the time of ERCP, may add useful information in the patient with a suspected pancreaticobiliary malignancy, especially cholangiocarcinoma. However, there are limited data to date, the exact role has not been defined yet, and the availability of this technology is limited to specialized centers. Positron emission tomography (PET) using the radionucleotide tracer 18-fluorodeoxyglucose (FDG) can reliably detect cholangiocarcinomas as small as 1 cm. A recent study has demonstrated that preoperative staging using FDG PET detected distant metastatic disease that was not suspected based on other radiological studies in 30% of patients.13 PET may be useful to detect primary cholangiocarcinoma in patients with PSC.

Preoperative histological confirmation The diagnosis of malignant biliary strictures depends on the identification of tumor cells obtained by ultrasound or CT-guided percutaneous fine needle aspiration, bile sampling, endobiliary brushings, or bile duct biopsies. Percutaneous needle biopsies are reliable only if US or CT identify a malignancy (sensitivity of 50%). Bile samples, obtained through a percutaneous or endoscopic stent, contain cancerous cells in 30–40% of cases of cholangiocarcinoma. The use of brush biopsy and cytologic examination may increase the yield to 40–70%. Unfortunately, even percutaneous or endoscopic biopsy not infrequently yields non-diagnostic tissue because of the desmoplastic nature of the lesion. There are currently many problems with tissue sampling during ERCP. Despite combination sampling with brush cytology, FNA, and biopsy, the sensitivity for all three combined is only 62% with a negative predictive value of 39%.14,15 Additionally, multiple sampling requires considerable time and technical expertise and there is a risk of losing guidewire access across the biliary stricture. Finally,

forceps biopsy generally requires a sphincterotomy, which adds a small risk of bleeding and perforation and is not required for subsequent stent placement. As a result of time and technical considerations, most practitioners perform brush cytology alone, which has sensitivity as low as 30%. Whereas the vast majority of extrahepatic strictures, particularly hilar strictures, are the result of a cholangiocarcinoma, histological diagnosis is not mandatory before exploration. At the present time, particularly if preoperative biliary stents are placed, distinguishing between alternative diagnoses can be difficult, if not impossible, even intraoperatively. In the absence of clear evidence of unresectability, all suspected lesions should be considered for resection.

Surgery for localized cancer Surgery remains the only intervention offering the possibility of a cure. The main treatment goal should be complete excision with negative margins. Several studies have concluded that radical excision of the lesion offers the best treatment option with respect to long-term survival.16,17 However, curative resections are difficult to achieve owing to the unfavorable location of the tumor, its tendency to grow into the perineural tissue, and to infiltrate proximally into the biliary tree and the liver. A significant number of patients have peritoneal implants or locoregional lymph node involvement that is not easily detected on preoperative imaging studies. The surgical treatment of perihilar cholangiocarcinoma depends on the Bismuth class. Most authors report that about one-third of patients can undergo curative resection, but some suggest that up to two thirds of patients should undergo resection with curative intent. En bloc resection of the extrahepatic bile ducts and gallbladder, regional lymphadenectomy, and Roux-en-Y hepaticojejunostomy are recommended for type I and II tumors, and that treatment plus hepatic lobectomy is recommended for type III tumors. The intent is to achieve a tumor-free proximal margin of at least 5 mm. Because type II and III tumors often involve the ducts of the caudate lobe, caudate lobectomy is recommended to improve local control and survival for patients with type II or III tumors. However, extended resection has shown an increased surgical risk with higher morbidity (overall up to 45%) and mortality rates of 3–33%.13,18

Liver transplantation Orthotopic liver transplantation (OLT) has been performed for both resectable and unresectable cholangiocarcinomas. Liver transplantation is currently contraindicated because it is usually associated with rapid recurrence of disease and death within three years.19 In pilot studies, OLT following preoperative chemoirradiation for unresectable cholangiocarcinoma has resulted in long-term survival of carefully selected patients and may be appropriate within clinical trials.20

Surgery for unresectable cancer Palliative options include operatively placed trans-tumoral stents, or the performance of an operative bilioenteric bypass. Several surgical techniques have been described for intrahepatic biliary bypass. The two most common approaches are bypass to the segment III duct and the right sectoral hepatic ducts. The first one, because of the more constant anatomy and long extrahepatic course of the left hepatic duct, is technically easier and preferred. However, the type of bypass is usually dictated by the location of the tumor. In general, segment III bypass is performed unless the left lobe is atrophic or 301

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A B

Fig. 28.3 Percutaneous drainage. A X-ray showing internal-external drainage of Bismuth type-IV hilar stricture secondary to colonic hepatic metastases (recurrence after liver resection) (courtesy of Iaccarino V, MD, UOC of Radiology. University of Naples Federico II, School of Medicine). B Endoscopic view of duodenal end of internal-external prosthesis.

heavily involved with tumor or if the primary lesion extends to the umbilical fissure of the liver.

Percutaneous approach (see Fig. 28.3) Distinction should be made between three transhepatic procedures: (1) external drainage; (2) external-internal drainage—a long catheter is placed through the obstruction into the duodenum, so that bile can flow internally, but the proximal end still exits through the skin for flushing, cholangiography and exchange; (3) internal drainage— a prosthesis is placed by the percutaneous route without subsequent external access. Adjuvant therapy At this time, there is no effective adjuvant therapy for cholangiocarcinoma. No prospective randomized trials that demonstrate a therapeutic role for chemotherapy, brachytherapy, or external beam radiation have been published. However, given the poor prognosis associated with this diagnosis, patients should be encouraged to enroll in phase I or II clinical trials. Recently, photodynamic therapy has been used in the palliative management of extrahepatic cholangiocarcinoma with promising results.21–23

ENDOSCOPIC APPROACH TO MALIGNANT STRICTURES AT THE HEPATIC HILUM BOX 28.3 KEY POINTS 1. Understanding the role of endoscopic management. 2. Review of the current techniques for stent implantation.

302

3. Identifing the criteria for stent selection (plastic versus metal stent).

Endoscopic drainage of malignant hilar obstruction Endoscopic stent drainage has been proposed as an alternative to biliary-enteric bypass surgery and percutaneous drainage to palliate malignant biliary obstruction. In addition, alternative approaches to biliary stent placement have been compared with particular interest in determining optimal stent material, design, and placement strategies.24–29 Prosthetic palliation of patients with malignant hilar stenoses poses particular difficulties, especially in advanced lesions (type II lesions or higher). The risk of cholangitis after contrast injection into the biliary tree in cases where incomplete drainage is achieved is well known. Retention of contrast and subsequent segmental cholangitis is a risk associated with endoscopic attempts to treat advanced hilar lesions and this has prompted some to question the role of endoscopic drainage in this situation.30 Some studies suggest that patients undergoing stent placement for malignant low bile duct obstruction had significant improvement in abdominal discomfort, weight loss, or anorexia and sleep patterns, in addition to the expected improvement in pruritus and jaundice.31 Similar studies would be needed to confirm that endoscopic stent placement of hilar obstruction is associated with an improved quality of life and can be justified by economic considerations. Although, metabolic and immune parameters appear improved with biliary drainage, there has been no evidence that endoscopic stent placement translates into prolonged survival.

Chapter 28 Malignant Biliary Obstruction: Hilar

Patients (n) Successful drainage (%) Complications (%) 30-day mortality (%) Duodenal bypass (%) Recurrent jaundice (%) Median survival (days)

Shepherd (1988) surgery stent

Andersen (1989) surgery stent

Smith (1994) surgery stent

19 84 na na 0 16 100

25 92 40 20 0 2 125

103 91 28 17 1 3 150

25 96 na na 0 28 84

23 91 22 9 0 17 152

101 94 10 7 6 18 150

Table 28.3 Treatment outcomes: comparison of endoscopic stent placement versus surgical bypass (randomized controlled trials) na = not available

The success rate of plastic stent insertion is around 80% in patients with proximal tumors. Relief of symptoms can be achieved in nearly all patients successfully stented. Failure of endoscopic drainage may be due to previous gastric surgery, presence of periampullar diverticulum, duodenal obstruction, failure of cannulation of the common bile duct, or inability to pass a guidewire or push a stent through the stricture.

Endoscopic drainage compared with alternative techniques (a) Endoscopic stenting versus surgical bypass Prospective comparisons between surgery and stents do not exist for proximal bile duct obstruction. There have been three prospective studies comparing biliary stents with surgical bypass for distal bile duct obstruction (Table 28.3). These studies demonstrate that surgery is associated with greater early morbidity and mortality but greater long-term patency and a lower incidence of recurrent jaundice. There was no long-term survival advantage for either technique. Neither of the randomized trials looked at cost. Two retrospective studies both found lower cost for the endoscopic approach.32,33 A meta-analysis suggested that patients who live less than six months would be best served with endoscopic stent placement, whereas those who live longer would benefit most by surgical bypass. Unfortunately, there were insufficient data in existing trials to draw any firm conclusions.34 There have also been no randomized comparative studies of endoscopic stent placement with expandable metal stents and surgery.

(b) Endoscopic versus percutaneous stenting No direct comparative studies exist between endoscopic and percutaneous placement of biliary stents for proximal bile duct obstruction. Percutaneous transhepatic stent placement has been compared with endoscopic stent placement showing significant advantages for the endoscopic approach (higher success in relieving jaundice and lower complication rate).35 These studies were carried out in the era of large, plastic stents, which are clearly disadvantageous for the transhepatic route. With the introduction and widespread use of smaller expandable metal stents, percutaneous placement is now associated with fewer risks and complications including hemorrhage, cholangitis, and pneumothorax. Studies with metal stent technology have not been reported primarily because it is now accepted that endoscopic access is less invasive than the percutaneous transhepatic route, offers the advantage of favorable fluid and

electrolyte homeostasis, more satisfactory cosmetic results, and greater psychological acceptance.

Preoperative stenting The role of preoperative stenting is controversial. It is generally accepted that preoperative biliary instrumentation is associated with an increase in the bile colonization rate and an increase in perioperative infectious complications, although mortality is not increased. Most surgeons will agree that those patients with renal impairment, cholangitis, or significant pruritis (where an operation cannot be scheduled in reasonable time) should undergo preoperative drainage. In cases of preoperative stenting, use of metal stents should be avoided because initial insertion of an expandable metal stent makes subsequent surgery more difficult as these stents cannot readily be removed surgically.

Technique of stent implantion The options include draining only the left hepatic system, draining only the right hepatic system, or draining both systems. The decision whether to place a single biliary stent or multiple stents depends initially on the location of the stricture in the biliary tract. In patients who have strictures that do not involve the confluence of right and left hepatic ducts (Bismuth type I hilar strictures), jaundice can be palliated completely with a single biliary stent because both the right and left intrahepatic ductal systems are in communication (Fig. 28.4). In patients who have more complex strictures (Bismuth type II to IV strictures) the central question is whether adequate palliative relief of obstruction requires the placement of two endoprostheses (Fig. 28.5), one to drain the left system and one to drain the right, or if one prosthesis placed in either system will suffice. Palliation of jaundice generally requires drainage of 1/4 to 1/3 of a healthy liver, or proportionally more in those with underlying dysfunction. Hence unilateral drainage is usually adequate, and many studies have reported good results using a single stent in about 80% of patients with type II and III tumors. No difference in efficacy has been shown between single stent placement in the left or the right system. Really, the necessity to ensure the drainage of both systems, including additional endoscopic or percutaneous stent, if necessary, pertains more to the prevention of procedure-induced cholangitis caused by contrast injection in undrained biliary branches than to effective palliation. Generally, if both lobes are imaged with contrast 303

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B

A

C

Fig. 28.4 Unilateral stent implantation. A ERCP showing Bismuth type I hilar stricture. B A guidewire and a guide-catheter advanced through the stricture in the left hepatic duct. C Post-ERCP x-ray image showing single 10 Fr plastic stent in place.

A

B

C

E D

Fig. 28.5 Bilateral stent implantation. (a) ERCP showing Bismuth type-II hilar stricture. (b) Endoscopic view of two guidewires respectively inserted in the right and left hepatic duct. (c) Endoscopic view of second stent insertion. (d) Two stents have been selectively placed into each major hepatic duct. (e) Endoscopic view of the two stents in place.

during cholangiography bilateral stenting reduces the potential sequelae of cholangitis in contaminated but undrained areas. If contrast does not contaminate both sides then unilateral stenting should be sufficient.30,36–39 Patients with multiple intrahepatic strictures may not benefit from any type of drainage procedure if several segments (>1/4) always remain undrained (Fig. 28.6). In the absence of intractable symptoms, these patients should not undergo further endoscopic measures, as the risk of inducing cholangitis outweighs any benefits realized from the establishment of endoscopic drainage. 304

Patient preparation The patients should have an intravenous line for administration of sedatives, antibiotics and hydration. Antibiotic coverage is mandatory, particularly in those patients with more complex strictures (Bismuth type III and IV). Prophylaxis can be given as a single, adequate dose shortly before the procedure and should be continued for 4–5 days after the procedure. Escherichia coli, and to a lesser extent, Klebsiella spp. (gram-negative bacteria) and gram-positive Enterococcus spp. are the most common organisms in bile. Therefore, antibiotics should be aimed mainly at gram-negative bacteria with good penetration in liver tissue and bile. Ciprofloxacin is

Chapter 28 Malignant Biliary Obstruction: Hilar

the guidewire passes through the stricture in the desired direction, it is advanced as deeply as possible into that lobe. Then a catheter is advanced over the guidewire and through the stricture as far as possible, the guidewire is removed, and as much bile as possible is aspirated to decompress the accessed duct. Contrast is injected with the catheter and the unilateral cholangiogram is completed. Subsequently, a stiff guidewire is substituted for the initial guidewire and the catheter removed, leaving the guidewire in that duct for the remainder of the procedure until final stent deployment. Thereafter, if necessary, dilation of the malignant stenosis is performed using either balloon catheters or bouginages. If histological diagnosis is not already established, sampling is performed with a biopsy forceps and cytology brush. Finally a plastic or a metal stent is inserted to decompress the proximal ductal system. If bilateral stent placement was planned, immediately after insertion of the first guidewire a second guidewire is inserted into the contralateral side, stents are placed sequentially into the left and then the right hepatic ducts over dual guidewires.

Fig. 28.6 strictures

ERCP showing patient with multiple intrahepatic

currently the first choice of antibiotic. In case of cholangitis, the addition of amoxicillin or a switch to piperacillin/tazobactam is advisable, Patients should be routinely sedated with diazepam or midazolam, sometimes combined with fentanyl or pethidine. The patients should be monitored by an assistant and by mechanical methods including pulse oximetry. Supervision by an anesthetist may be required.

MRCP and CT-guided stent implantation (Fig. 28.7) Recent reports describe the utility of MRCP or CT imaging to guide selection of the target lobe for subsequent endoscopic stenting, often without use of contrast.37,39 MRCP or CT images are used to confirm the diagnosis of Klatskin tumor to exclude other biliary diseases (Fig. 28.1) and to demonstrate the stenoses as well as dilation of proximal liver segments. The left or right main hepatic duct is chosen for stent insertion, depending on the number of drainable liver segments. Subsequent to MRCP selective endoscopic retrograde contrast injection is deliberately limited to the distal end of the malignant tumor stenosis. Thereafter, sphincterotomy is generally performed, the papillotome or a catheter is advanced to the distal margin of the stricture and a guidewire (hybrid or hydrophilic, with a torquable angle-tip if necessary) is advanced, under fluoroscopic guidance, in the direction of the duct preselected for drainage based on prior imaging. Once

Unilateral random stent implantation (Figs 28.8–28.9) MRCP images are used to confirm the diagnosis of Klatskin’s tumor, to exclude other biliary diseases, and to demonstrate the stenoses, as well as dilation of proximal liver segments. Contrast injection at ERCP is deliberately limited to the extrahepatic bile duct distal to the tumor. Then, sphincterotomy is performed in all cases, and a guidewire is subsequently advanced through the malignant stenosis into the duct that is technically easiest to access. A catheter is then passed over the guidewire and through the stenosis, and, after removal of the guidewire, a unilateral cholangiogram is completed. Finally, a single plastic or metallic stent is deployed.36,38

Contrast-free stent implantation (Fig. 28.10) Stents are placed in these patients under fluoroscopic guidance as follows: the stent assembly is passed over the guidewire above the suspected site of stricture (Fig. 28.10A) and the stent is deployed at the desired site.40

Rendezvous technique An interventional radiologist passes a guidewire transhepatically down the bile duct and into the duodenum; this wire is then grasped by the endoscopist to place stents in the bile duct. The combined percutaneous-endoscopic approach has been reported by many groups. The rationale is that the complications should be lower than those with a purely percutaneous approach, since only small catheters are passed through the liver, and rather briefly. However, the complication rates are not negligible. The overall morbidity, including the initial failed endoscopic attempts, proved to be 62% and 27% in one series of 74 patients.

Plastic versus metal stents Theoretically, a metal stent should result in better drainage than plastic stent in hilar strictures. Metal stents have two advantages over the plastic stents: they do not occlude side branches because of the mesh; furthermore, because most hilar tumors are firm and scirrhous, tumor ingrowth probably occurs less frequently. Metallic stents offer longer but still limited stent patency duration of about 4–6 months compared with a patency duration of 2–4 months for plastic stents (Table 28.4). 305

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A

B

C

D

E

Fig. 28.7 MRCP-targeted unilateral implantation of SEMS. A Contrast enhanced MR showing hilar cholangiocarcinoma causing marked dilation of the bile ducts in the lateral segments of the right lobe. B MRCP image showing tumor occluding the common hepatic duct and the right (IIIa) hepatic duct (same patients as in Fig. 28.5A). (A and B courtesy of Mainenti P, MD, and Maurea S, MD. Dipartimento di Scienze Biomorfologiche e Funzionali; University of Naples Federico II, School of Medicine.) C The stent is advanced over the guidewire into dilated right hepatic duct as planned. D The SEMS has been deployed. E Post-ERCP x-ray image showing SEMS in place providing drainage.

306

Chapter 28 Malignant Biliary Obstruction: Hilar

A

B

C

Fig. 28.8 Retrograde cholangiograms illustrating unilateral contrast injection and unilateral stent deployment. A Contrast injected into distal common duct distal to stenosis. Stenosis itself and the more proximal bile duct regions are deliberately not opacified. B Guidewire is advanced through tumor stenosis toward left hepatic duct under fluoroscopic control. A minimal contrast injection into dilated left hepatic ductal system shows correct position of the guidewire and guiding catheter. Injection of contrast into right hepatic duct system has been avoided. C Stent advanced through stenosis into dilated left hepatic duct.

A B

C

Fig. 28.9 Retrograde cholangiograms illustrating unilateral stent deployment in a patient with type IV Bismuth hilar stricture. A ERCP showing dilated biliary tree with high-grade stricture affecting the distal common bile duct, caused by carcinoma of the pancreas. Narrowed common hepatic duct and dilation of proximal biliary tree are compatible with metastatic disease producing obstruction at the bifurcation. B A guidewire and a guide-catheter advanced through the stricture in the left hepatic duct. C Single 10 Fr plastic stent advanced through stenosis.

In contrast to plastic stents, metallic stents are not removable after the first few days of deployment, as the stent becomes embedded in the tumor tissue which may grow into each individual mesh opening. Thus, metallic stents should be used in patients with proven unresectable malignancies, because initial insertion of an expandable metal stent makes subsequent surgery more difficult as these stents cannot readily be removed surgically. The main disadvantage is the cost of the metallic stent (US$ 900–1200), and identification of patients who are likely to outlive their first plastic stent, and warrant a metal stent, is a major challenge for the managing clinician. Cost analysis showed that metallic stents were advantageous versus plastic stents in patients surviving more than six months and very costly when patients survived less

than three months. Therefore, the use of metal stents should be restricted to those patients with unresectable tumors who will, in all probability, live longer than three months. Unfortunately there is no a good way to predict life expectancy at this time. Tumor size (>3 cm), evidence of diffuse liver metastases, and general condition of the patient could guide the choice of stent. An additional indication for the use of metal stents is the small group of patients who suffer rapid and repeated obstruction of plastic stents. These patients have not been well studied and presently cannot be identified at the start. This group constitutes patients who will also benefit from a metal stent. All patients, who need a stent exchange because of clogging of a plastic stent within 1 month after insertion are good candidates for metal stent insertion. 307

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30-days Patients Drainage mortality Occlusion (N) (%) (%) (%)

A

Davids (1992) Metal 49 Plastic 56 Carr-Locke (1993) Metal 86 Plastic 78 Knyrim (1993) Metal 31 Plastic 31

Patency (days)

96 95

14 4

33 54

372 126

98 95

5 5

13 13

111 62

100 100

13 9

22 43

— —

Table 28.4 Treatment outcomes: comparison of plastic versus metal stents for low bile duct obstruction (randomized controlled trials)

B

Fig. 28.11 Duonenal perforation by guidewire in a patient with high-grade stricture affecting common hepatic duct and dilation of proximal biliary tree.

Fig. 28.10 Contrast-free deployment of stent. A A guidewire is passed above the suspected site of stricture, deeply in the left hepatic duct. B Stent is passed over the guidewire above the stricture.

COMPLICATIONS BOX 28.4 KEY POINTS 1. Review of the complications of the endoscopic approach. 2. Identifying strategies to reduce complications and their management.

308

Early and late complications of stent insertion Immediate complications of attempted and successful stent placement are similar to those of other ERCP procedures. Pancreatitis can be provoked. A small sphincterotomy, when performed, rarely results in direct complications, such as bleeding or perforation (Fig. 28.11). In contrast, post-ERC bacterial cholangitis in patients with Klatskin tumors occurs in 17–49%.5,23 Bacterial cholangitis is caused by infected bile and inflammation of ductal epithelium. In animal studies bacterial reflux from bile to blood is enhanced by increased intrabiliary pressure.16 This suggests that increased intrabiliary pressure during ERC is the main reason for increased bacterial access to the blood. The major late complication is clogging of the prosthesis, occurring in 21–36% of cases. Much higher rates of 21–54%

Chapter 28 Malignant Biliary Obstruction: Hilar

are reported in prospective randomized studies, with an overall incidence of 42%. Stents placed for hilar obstruction appear to occlude faster than stents placed for more distal obstruction.41 The problem with stent occlusion has been studied intensively but attempts at altering bile composition using choleretic agents, reducing bacterial load with antibiotics, or influencing mucin production with aspirin have failed to prolong stent patency. Prophylactic stent changes have been advocated by many authorities: However, nearly 50% of patients undergoing stenting with 10 or 11.5 French plastic stents die prior to stent occlusion. Thus, not all patients will require stent changes and a watchful waiting remains a reasonable option if a good follow-up system is in place. Other late complications are unusual and include migration into the more proximal bile duct or bowel, duodenal or bile duct perforation and acute cholecystitis.

How to reduce the risk of acute cholangitis All patients undergoing evaluation and therapy should receive antibiotics before and after ERCP. The antibiotic chosen should penetrate an obstructed biliary tree (see patient preparation). For Bismuth type II and III strictures, good endoscopic techniques are paramount. Minimal contrast medium should be injected only into the duct to be drained. Once access is obtained to the obstructed segment, the pressure in the system should be reduced before more complete filling, by aspirating bile. If possible, manipulation of ducts that will not be drained should be avoided. A single stent into an obstructed segment that drains at least 25% of the liver should be placed. There does not seem to be any advantage to choosing one lobe of the liver over the other. If cholangitis occurs, ERCP or a percutaneous approach to drain the obstructed lobe of the liver should be performed promptly.36,38,42

Complications specific to metal stents Incomplete removal of the covering membrane, failure of stent expansion and inability to remove the inner catheter after stent release are rare technical problems. About 10–15% of metal stents eventually get occluded because of tumor ingrowth through the wire mesh or tumor overgrowth above or below the stent. The problem can be solved by inserting another stent, either plastic or metal, through the occluded stent (Figs 28.12–28.13).

A

B

Fig. 28.12 Tumor ingrowth: endoscopic treatment. A ERCP showing a case of tumor ingrowth in a SEMS. B A plastic stent inserted through the SEMS.

A

B

Fig. 28.13 Stent clogging: endoscopic treatment. A Endoscopic view showing the distal end of stent completely occluded. B Insertion of new SEMS through the occluded stent.

COSTS There are no economic analyses which compare various palliative options in patients with malignant biliary obstruction of the hepatic hilum. A “cost-effectiveness” study previous reported a tabulation of hospital charges comparing surgical bypass with endoscopic stenting in patients with distal malignant biliary obstruction. The study reported total costs per patients of 25 000 US$ for patients treated with surgical bypass, and 5000 US$ per patient treated with endoscopic stent.43 The cost-effectiveness of palliation with endoscopic stent is enhanced when metal stents are used. Studies have demonstrated that the cost for both treatment strategies are different only because of stent price. Cost analysis has concentrated on patency rates, repeat ERCPs, and total length of hospital stays. Of critical importance in determining cost-efficiency is the length of survival of each patient. Because occlusion rates are dependent on survival, the longer a patient survives, the more likely a metal stent will be beneficial (as plastic stents occlude earlier than metal). Despite the initial heavy cost of expandable metal stents (30–40 times that of the plastic stents), in patients surviving over than 4–6 months, metal stents ultimately (because of longer patency periods) prove to be the least expensive method of relieving biliary obstruction.44,45

SUMMARY 1. The evaluation of patients with suspected malignancy of the hepatic hilum should include helical or multislice CT of the abdomen. An MRCP should be obtained to assess for resectability. 2. If the disease is resectable and the patient is fit, surgical resection of the lesion should be performed. 3. Preoperative ERCP should be avoided unless there is cholangitis or significant delay in surgery and the patient is symptomatic. 4. If the lesion is unresectable or the patient is unfit for surgery, then endoscopic palliation of jaundice should be performed by using MRCP as a guide for unilateral drainage to minimize cholangitis. 309

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5. If cholangitis occurs, ERCP or a percutaneous approach to drain the obstructed lobe of the liver should be performed promptly. 6. The use of metal stents should be restricted to those patients who will, in all probability, live longer than 3 months.

Acknowledgments I thank Francesca Salvatori, MD, for the English text revision and Pietro Addeo, MD, for the bibliographic research.

REFERENCES 1.

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Klatskin G. Adenocarcinoma of the hepatic duct at its bifurcation within the porta hepatis: an unusual tumor with distinctive clinical and pathological features. Am J Med 1965; 38:241–256. De Groen PC, Gores GJ, LaRusso NF, et al. Biliary tract cancers. N Engl J Med 1998, 341; 18:1368–1378. Patel T. Worldwide trends in mortality from biliary tract malignancies. BMC Cancer 2002; 2(10):1–5. Chamberlain SS, Blumgart RH. Hilar cholangiocarcinoma: a review and commentary. Annals of Surgical Oncology, 2000; 7:55–66. Michaud DS. The epidemiology of pancreatic, gallbladder, and other biliary tract cancers. Gastrointest Endosc 2002; 56(6): S195–S200. Bismuth H, Corlette MB. Intrahepatic cholangioenteric anastomosis in carcinoma of the hilus of the liver. Surg. Gynecol. Obstet. 1975; 140:170–176. Gerhards MF, van Gulik TM, de Wit LT, et al. Evaluation of morbidity and mortality after resection for hilar cholangiocarcinoma-a single center experience. Surgery 2000; 127:395–404. Han JK, Choi BJ, Kim AY, et al. Cholangiocarcinoma: pictorial essay of ct and cholangiographic findings. RadioGraphics 2002; 22:173–187. Yeh T, Jan YY, Tseng JH, et al. Malignant perihilar biliary obstruction: magnetic resonance cholangiopancreatographic findings. Am J Gastroent 2000; 95:432–440. Mortele KJ, Ji H, Ros PR. CT and magnetic resonance imaging in pancreatic and biliary tract malignancies. Gastrointest Endosc 2002; 56:S206–S212. Lee WJ, Lim HK, Jang KM, et al. Radiologic spectrum of cholangiocarcinoma: emphasis on unusual manifestations and differential diagnoses RadioGraphics 2001; 21:S97–S116. Fritscher-Ravens A, Broering DC, Sriram PVJ, et al. EUS-guided fine-needle aspiration cytodiagnosis of hilar cholangiocarcinoma: a case series. Gastrointest Endosc 2000; 52:534–540. Anderson CS, Pinson CV, Berlin J, et al. Diagnosis and treatment of cholangiocarcinoma The Oncologist 2004; 9:43–57. Gerhards MF, van Gulik TM, de Wit LT, et al. Evaluation of morbidity and mortality after resection for hilar cholangiocarcinoma—a single center experience. Surgery 2000; 127:395–404. De Bellis M, Sherman S, Fogel EL, et al. Tissue sampling at ERCP in suspected malignant biliary strictures (Part 1). Gastrointestinal Endosc 2002; 56:552–561. De Bellis M, Sherman S, Fogel EL, et al. Tissue sampling at ERCP in suspected malignant biliary strictures (Part 2). Gastrointestinal Endosc 2002; 56:720–730. Sugiura Y, Nakamura S, Iida S, et al. Extensive resection of the bile ducts combined with liver resection for cancer of the main hepatic duct junction: a cooperative study of the Keio Bile Duct Cancer Study Group. Surgery 1994; 115:445–451.

18. Smimada K, Sano T, Sakamoto Y, et al. Safety and effectiveness of left hepatic trisegmentectomy for hilar cholangiocarcinoma. World J. Surg. 2005; 29:723–727. 19. Capussotti L, Muratore A, Polastri R, et al. Liver resection for hilar cholangiocarcinoma: in-hospital mortality and longterm survival. J Am Coll Surg 2002; 195:641–647. 20. Meyer CG, Penn I, James L. Liver transplantation for cholangiocarcinoma: results in 207 patients. Transplantation 2000; 69:1633–1637. 21. De Vreede I, Steers JL, Burch PA, et al. Prolonged disease-free survival after orthotopic liver transplantation plus adjuvant chemoirradiation for cholangiocarcinoma. Liver Transpl 2000; 6:309–316. 22. Zoepf T, Jakobs R, Rosenbaum A, et al. Photodynamic therapy with 5-aminolevulinic acid is not effective in bile duct cancer Gatrointest Endosc 2001; 54:763–766. 23. Ortner MEJ, Caca K, Berr F, et al. Successful photodynamic therapy for nonresectable cholangiocarcinoma: a randomized prospective study. Gastroenterology 2003; 125:1355–1363. 24. Wiedmann M, Berr F, Schiefke I, et al. Photodynamic therapy in patients with non-resectable hilar cholangiocarcinoma: 5-year follow-up of a prospective phase II study Gastrointest Endosc 2004; 60:68–75. 25. Hawes RH. Diagnostic and therapeutic uses of ERCP in pancreatic and biliary tract malignancies. Gastrointest Endosc 2002; 56: S201–S205. 26. Strasberg SM. ERCP and surgical intervention in pancreatic and biliary malignancies Gastrointest Endosc 2002; 56:S213–S217. 27. Flamm CR, Mark DH, Aronson N. Evidence-based assessment of ERCP approaches to managing pancreaticobiliary malignancies Gastrointest Endosc 2002; 56:S218–S225. 28. Rey JF, Dumas R, Canard JM, et al. Guidelines of the French Society of Digestive Endoscopy: Biliary Stenting. Endoscopy 2002; 34:169–173. 29. ASGE Guidelines. The role of endoscopy in the evaluation and treatment of patients with pancreaticobiliary malignancy. Gastrointest Endosc 2003; 58:643–649. 30. ASGE guideline: the role of ERCP in diseases of the biliary tract and the pancreas. Gastrointest Endosc 2005; 62:1–8. 31. Chang W, Kortan P, Haber G. Outcome in patients with bifurcation tumors who undergo unilateral versus bilateral hepatic duct drainage. Gastrointest Endosc 1998; 47:354–362. 32. Abraham NS, Barkun JS, Barkun A. Palliation of malignant biliary obstruction: a prospective trial examining impact on quality of life Gastrointest Endosc 2002; 56:835–841. 33. Raiker GV, Melin MM, Ress A, et al. Cost-effective analysis of surgical palliation versus endoscopic stenting in the management of unresectable pancreatic cancer. Ann Surg Oncol 1996; 3:470–475. 34. Brandabur JJ, Kozarek RA, Ball TJ, et al. Non-operative versus operative treatment of obstructive jaundice in pancreatic cancer: cost and survival analysis. Am J Gastroenterol 1988; 83:1132–1139.

Chapter 28 Malignant Biliary Obstruction: Hilar

35. Taylor MC, McLeod RS, Langer B. Biliary stenting versus bypass surgery for the palliation of malignant distal bile duct obstruction; a meta-analysis. Liver Transpl 2000; 6:302–308. 36. Speer AG, Cotton PB, Russell RCG. Randomized trial of endoscopic versus percutaneous stent insertion in malignant obstructive jaundice. Lancet 1987; 2:57–62. 37. De Palma GD, Galloro G, Iovino P, et al. Unilateral versus bilateral endoscopic hepatic duct drainage in patients with malignant hilar biliary obstruction. Results of a prospective, randomized, and controlled study. Gastrointest Endosc 2001; 53:547–553. 38. Hintze RE, Abou-Rebyeh H, Adler A, et al. Magnetic resonance cholangiopancreatography—guided unilateral endoscopic stent placement for Klatskin tumors. Gastrointest Endosc 2001; 53:40–46. 39. De Palma GD, Pezzullo A, Rega M, et al. Unilateral placement of metallic stents for malignant hilar obstruction: a prospective study. Gastrointest Endosc 2003; 58:50–53. 40. Freeman ML, Overby C. Selective MRCP and CT-targeted drainage of malignant hilar biliary obstruction with self-expanding metallic stents Gastrointest Endosc 2003; 58:41–49.

41. Singh V, Sigh G, Verma GR, et al. Contrast-free unilateral endoscopic palliation in malignant hilar biliary obstruction: New method Journal of Gastroenterology and Hepatology 2004; 19:589–592. 42. Shermann S, Lehman G, Earle D. Are the patency rates for 10French, 11.5-French stents different for common duct obstruction and hilar obstruction? Randomized, prospective study. Gastrointest Endosc 1996; 43:396. 43. Shermann S. Endoscopic drainage of malignant hilar obstruction: Is one biliary stent enough or should we work to place two? (Editorial) Gastrointest Endosc 2001; 53:681–684. 44. Raikar GV, Melin MM, Ress A, et al. cost-effective analysis of surgical palliation versus endoscopic stenting in the management of unresectable pancreatic cancer. Ann Surg Onc 1996; 3:470–475. 45. Schmassmann A, Von Gunten E, Knuchel J, et al. Wallstents versus plastic stents in malignant biliary obstruction: effects of stent patency of the first and second stent on patient compliance and survival. Am J Gastroenterol 1996; 91:654–659.

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29

APPROACH TO CLINICAL PROBLEMS

Indeterminate Biliary Stricture Bret T. Petersen

Biliary obstruction results from diverse benign and malignant processes and patients can present acutely or chronically with signs and symptoms ranging in severity. The nature of an obstruction is often immediately clear at the time of initial investigation, while at other times obstruction is readily apparent but the nature of the pathologic process remains uncertain. No single definition exists for the term “indeterminate stricture,” but it commonly refers to biliary strictures in patients in whom cross-sectional imaging is unrevealing, i.e. without an associated mass lesion, and without pathologic confirmation. Recent experience with inflammatory pancreatic masses might prompt expansion to include all strictures, including those with associated mass lesions, prior to histological characterization. When biliary obstruction is identified, an efficient approach to early diagnostic testing and management is important for reduction of morbidity and guidance of definitive therapy. Untreated obstructive cholestasis of even moderate degree can culminate in secondary biliary cirrhosis within several months.1,2 Patients with inadequately treated strictures also risk development of acute or chronic cholangitis, particularly following invasive testing. Key steps in the assessment and management of patients with indeterminate biliary strictures include characterization of the pathogenesis of the stricture, relief of biliary obstruction and/or definitive treatment of the pathologic process—employing medical, endoscopic, percutaneous, or surgical means. Stricture characterization and relief of obstruction are not independent pursuits but are typically accomplished in unison. Stricture characterization is based upon historical features, laboratory testing, non-invasive and invasive imaging, and by the use of various tissue sampling methods (Fig. 29.1).3

HISTORICAL FEATURES Historical features may contribute to both the correct diagnosis and the management strategy for newly identified biliary strictures (Table 29.1). Prior history of ulcerative colitis, complicated biliary surgery, or chronic pancreatitis suggest PSC, postoperative strictures, and pancreatic compression of the CBD, respectively. An acute presentation in the early postoperative period or during an episode of pancreatitis suggests significant operative injury or stonerelated obstruction whereas sub-acute but early (<3 months) presentations suggest inflammatory processes that may resolve with time—hence minimally invasive and temporizing approaches may suffice. Presentation more than three months after a prior insult suggests a more fibrotic and rigid stricture which may require more aggressive or prolonged therapy. Strictures that present in an occult or delayed fashion, and those presenting without known predisposing factors all raise the specter of a malignant etiology. A waxing and waning presentation is suggestive of benignity whereas inexorable

progression of symptoms associated with weight loss suggests malignant etiologies.

LABORATORY FEATURES Laboratory features obtained at the time of presentation with a stricture may provide an assessment of the stricture’s severity and chronicity as well as the etiology. Isolated mild to moderate elevations of alkaline phosphatase, without transaminase or bilirubin elevations, imply modest impairment to bile flow due to intra or extrahepatic etiologies. Enzyme fractionation should confirm the hepato-biliary source of the elevation and cross-sectional imaging should identify when obstruction involves larger central or extrahepatic ducts. Concurrent elevations in the transaminases imply either a hepatitic process or relative acuity of onset to the obstruction. Total bilirubin values are not highly indicative of obstruction, but in the setting of complete obstruction with an otherwise healthy liver, bilirubin is said to generally peak under 20 mg/dl, whereas values beyond this imply hepatocellular injury, with or without obstruction. Chronic obstruction with deep jaundice can induce malabsorption of the fat soluble vitamins, including vitamin K, thus leading to elevated prothrombin times. Hence an INR should be checked prior to interventional techniques in these patients. Elevated pancreatic enzymes imply concurrent pancreatitis or pancreatic duct obstruction, commonly due to biliary stone disease, pancreatic carcinoma, or advanced chronic pancreatitis. Very few serologic markers contribute to characterization of the benign or malignant nature of indeterminate biliary strictures. Carbohydrate antigen 19-9 (CA19-9) is a serum moiety that is elevated in the settings of pancreatic and biliary carcinoma, cholangitis, and to a lesser degree, pancreatitis.4 Marked CA19-9 elevations above 1000 IU are seen only with cancer or florid cholangitis. Elevations above 100 IU are strongly suggestive of cancer in the absence of known pancreatitis or cholangitis. When an elevated CA19-9 is detected in the setting of cholangitis it should be reassessed following appropriate therapy of the infectious process. Immunoglobulin G, sub-fraction 4 levels are often, but not invariably, elevated in autoimmune pancreatitis, which can cause biliary strictures that mimic those that occur with chronic pancreatitis of other etiologies, pancreatic cancer, or even PSC.5 Such strictures are often amenable to therapy using corticosteroids.6

NON-INVASIVE CROSS-SECTIONAL IMAGING Ultrasonography (US), computerized tomography (CT), and magnetic resonance imaging (MR) play a primary role in confirmation of obstruction (based upon findings of duct dilation or mass lesions), identification of associated complications such as abscess or bowel obstruction, and initial characterization of the pathologic process. Settings in which ductal dilation proximal to a stricture may not be 313

SECTION 3 APPROACH TO CLINICAL PROBLEMS

Fig. 29.1 Algorithm for Evaluation of Jaundice and Suspected Biliary Obstruction. See text for discussion. (Redrawn with permission from Gastrointestinal Endoscopy 2002.)

Obstructive jaundice

Ultrasound or CT scan

Yes

Mass? ERCP with tissue sampling and stenting

No

Yes

EUS with FNA

Resectable

Biliary dilation?

No

Surgical candidate and potentially resectable

Yes

Mass?

Yes

No

No

Hepatitis screen Drugs screen Liver biopsy MRCP

ERCP with tissue sampling and stenting

Not resectable

Surgery

Tissue diagnosis not established

EUS, FNA or CT FNA

A. Historical features suggestive of benign etiologies • History of right upper quadrant surgery • Trauma • Ulcerative colitis or Crohn’s disease • Chronic pancreatitis • Difficult biliary stone disease • Stable weight • Fluctuating labs B. Historical features suggestive of malignant etiologies • Never operated abdomen • Absent history of abdominal illness • Weight loss • Short course without antecedent illness • Decompensation of known PSC

Table 29.1 Historical features and character of biliary strictures present include: early or fluctuating processes that are inadequately advanced to cause obstruction, and diseases in which the ducts and/or the liver are fibrosed and cannot dilate easily, as in sclerosing cholangitis. Transabdominal ultrasonography (TUS) is usually the first study employed in jaundiced patients to identify the presence and level of duct dilation and to look for bile duct or gallbladder stones or masses. Ultrasonography is the most sensitive of the non-invasive tests for biliary stones. US is extremely sensitive for duct dilation but less so for identifying the specific etiology of a stricture. Once a stricture is localized by cross-sectional imaging with US (or CT scanning) the next step in evaluation is highly dependent upon the clinical judgment as to whether the setting favors a benign or malignant process, the patient’s fitness for surgery, and the appar314

ent resectability of the lesion based on initial studies. Ultrasonographic evidence of a stricture, without evidence of advanced cancer, is usually followed by abdominal CT scanning to define whether a mass exists and to provide initial staging information. If ultrasonography demonstrates a distal unresectable mass, based on local-regional extension, hepatic metastasis, or associated ascites, then ERCP is usually performed for both tissue acquisition and palliation of obstructive jaundice. If US demonstrates a hilar mass, with or without evidence of unresectability, then magnetic resonance cholangiopancreatography (MRCP) is helpful to better define the level of the obstruction, assist with assessment of resectability, and guide the subsequent approach to invasive cholangiography, tissue sampling, and palliative stenting.7 An extrahepatic stricture without a mass in the setting of fever, apparent biliary pancreatitis, or gallbladder stones can often be evaluated directly with ERCP in anticipation of identifying an obstructing duct stone. Abdominal CT scanning is commonly employed in patients with associated weight loss, fever, or significant pain, as it is particularly useful for identification and staging of extra-ductal mass lesions, inflammatory processes, and bile collections or leaks (Fig. 29.2). CT is also preferred over ultrasonography in obese subjects. CT images are very familiar to most clinicians. Recently the inclusion of coronal renderings has provided clinicians with even greater understanding of the anatomic relationships between neighboring structures in the right upper quadrant and their involvement by pathology. CT cholangiography is also available but seems to be less utilized currently, in the era of MRCP. Abdominal magnetic resonance imaging yields cross-sectional information analogous to CT scanning and provides relatively sensitive cholangiographic images that usually allow determination of stricture location. MRCP is the most sensitive non-invasive

Chapter 29 Indeterminate Biliary Stricture

A

B

C

Fig. 29.2 Abdominal CT scan demonstrates distal extrahepatic obstruction, based upon traditional cross-sectional views showing dilation of the intrahepatic ducts A and proximal extrahepatic ducts B, and similar dilation plus pancreatic duct dilation and a distal mass seen on the coronal view C.

imaging test for biliary obstruction and it approaches the sensitivity of ERCP for identification of biliary strictures.8 Studies differ, however, as to whether it is inferior or equivalent to ERCP for the differentiation of benign from malignant lesions.8,9 When acquired and displayed by standard cross-sectional MR scanning information regarding extra-ductal pathology or extent of disease tends to be less readily interpreted by the non-radiologist than by CT scanning. MRCP has largely replaced diagnostic endoscopic cholangiography

when there is not a need for tissue acquisition, therapy, or dynamic measurements of motility. The primary benefit of MRCP is the avoidance of intubation, sedation, and the risk of pancreatitis. Other advantages of MRI over ERCP include the ability to display the anatomy of the ducts and the liver above a stricture even when complete obstruction is present, and the ability to generate multiple perspectives or angles of view for the same lesion. A disadvantage of MRI is that the cholangiographic display includes all ducts, 315

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without the ability to localize images to the region of interest around a stricture, as is done with “early films” acquired during initial contrast instillation during ERCP. This sometimes makes interpretation of a central or a complex stricture difficult due to overlapping peripheral ducts that are of little consequence (Fig. 29.3). Several studies have demonstrated the utility of MRCP as a guide to

Fig. 29.3 Abdominal MRCP demonstrating a distal extrahepatic stricture, analogous to that seen on CT in Figure 29.2. A

subsequent ERCP and palliative stent placement for hilar lesions7 (Fig. 29.4) as discussed in Chapter 28.

INVASIVE IMAGING TECHNIQUES Evaluation of the biliary tree can be achieved using endoscopic ultrasonography, as well as by traditional contrast-based cholangiography via percutaneous transhepatic (PTC) or endoscopic retrograde (ERCP) routes. Intraductal ultrasound (IDUS) and cholangioscopy are specialized techniques employed during performance of ERCP with a duodenoscope which will be discussed in subsequent sections. Cholangioscopy is also discussed in Chapter 21. Endoscopic ultrasonography (EUS) is useful for both diagnosis and staging of malignant biliary strictures. EUS is accomplished from the duodenal bulb, and/or the antrum, depending upon the patient’s anatomy. Radial or linear technology can be employed, but the frequent use of fine needle aspiration is driving an evolution toward predominantly linear imaging. Malignancies are identified as hypoechoic masses or thickening of the bile duct wall. In one study of 40 biliary strictures (24 malignant, 16 benign) EUS findings of a pancreatic head mass and/or an irregular bile duct were more sensitive than concurrent FNA sampling. EUS imaging alone was 88% sensitive and 100% specific for malignancy. Wall thickness >3 mm was 79% sensitive and 79% specific for malignancy. The sensitivity of FNA was 47%, with 100% specificity and positive predictive value but only 50% negative predictive value.10 In a comparative study of several modalities, EUS sensitivity and specificity (79% and 62%) were less than ERCP or MRCP but complementary to them.8 In contrast, a study evaluating EUS with FNA in 28 patients with non-diagnostic sampling of biliary strictures obtained during ERCP, PTC, or CT demonstrated 86% sensitivity, 100% specificity, 100% positive predictive value, 57% negative predictive value, and 88% accuracy for malignant lesions.11 Importantly, management B

Fig. 29.4 Cross-sectional imaging with MRCP or CT provides guidance to the preferred lobe for palliative biliary drainage during ERCP in patients with proximal biliary obstruction. A MRCP suggests access should be pursued toward the dominant right lobe. B CT in the same patient demonstrates left lobe atrophy, also suggesting access should be to the right lobe. 316

Chapter 29 Indeterminate Biliary Stricture

was influenced in 84% of patients. Some but not all studies note a greater sensitivity of EUS/FNA for pancreatic lesions than for extrahepatic cholangiocarcinoma.12 EUS and CT are complementary studies for staging and determination of resectability for distal biliary strictures due to pancreatic mass lesions.13 Hence, while not a primary imaging modality for biliary strictures, EUS with FNA is an important ancillary technique when diagnosis remains elusive and when staging for determination of resectability is sought. Cholangiography is the mainstay for diagnosis and characterization of extrahepatic biliary lesions of all types. Endoscopic and percutaneous approaches to cholangiography are complementary studies and, on occasion, both will be necessary to characterize and treat difficult biliary lesions (Table 29.2). In general, proximal lesions that appear to involve the hilar region are best investigated initially with non-invasive MRCP, as this study provides directional guidance for subsequent invasive imaging and palliation7 and avoids the risk of cholangitis that occurs with ERCP when contrast is injected into areas which may not be drainable. However, preoperative planning for hilar lesions may still require the clarity of contrast-based cholangiography (ERCP or PTC). The cholangiographic appearance of the stricture is generally inadequate for interpretation of malignancy and many strictures that are interpreted as benign prove to be malignant.14 Features suggestive of malignancy include progressive focal stricturing over time, abrupt shelf-like borders, length greater than 14 mm, intrahepatic duct dilation, and presence of intraductal polypoid or nodular areas.14,15 In the setting of background sclerosing cholangitis with dominant strictures, malignant lesions are more likely to exceed 1 cm in length, be located at the bifurcation as opposed to the common bile duct, and have irregular margins.16 Despite these criteria, cholangiography alone correctly identified only 8 of 12 (66% sensitivity) malignant lesions and 21 of 41 (51% specificity) benign lesions.16 Endoscopic retrograde cholangio-pancreatography (ERCP) has become the primary non-operative modality for both investigation and palliation of biliary strictures because it provides high quality contrast-based images of the ductal systems, access for tissue sampling, and means of therapy via internal drainage. ERCP is preferred if there is a likely need for stone extraction or stent placement in the extrahepatic ducts, when coagulopathy or ascites is present, when

the bile ducts are not dilated, and when percutaneous approaches fail. It should be undertaken only by endoscopists with the experience and ability to proceed with appropriate imaging, tissue sampling, and therapies. In inexperienced hands initial studies often yield poor stricture definition, inadequate drainage, or procedural complications. Endoscopic cholangiography in the setting of obstructive jaundice should be performed with peri-procedural antibiotic coverage and anticipation of continuing antibiotics for a brief interval, particularly if complete drainage cannot be achieved. Stent placement should be performed whenever significant contrast is instilled above a lesion that prevents spontaneous drainage. In the setting of hilar strictures intrahepatic filling of contrast should be avoided until wire access is accomplished, to ensure the ability to provide subsequent palliative drainage of the imaged segments. As noted, prior highquality CT or MRCP imaging can guide selection of optimal intrahepatic systems for wire access and stent placement. Optimal characterization and successful access for sampling and treatment require attention to imaging principles that are often not appreciated by non-radiologists. The following points apply equally to imaging of benign or malignant strictures (Table 29.3): (1) Strictures, unlike large dilated systems, are best imaged with full-strength contrast. (2) Multiple early films should be taken as contrast is first crossing the lesion, continuing the injection until the image has been obtained (Fig. 29.5). This allows later reference back to the minute details of angles or bifurcations, which may not be evident when the ducts are completely filled. (3) Coning down on an area of interest will sharpen the detail seen on hard copy. This requires at least some larger views to maintain anatomic reference. (4) Tissue sampling and therapy should be performed with the least contrast filling required to adequately demonstrate the anatomy. Excessive filling of intrahepatic ducts often obscures the bifurcation. (5) The proximal extent of duct involvement must be well demonstrated for surgical or endoscopic decision making. Following wire access,

1. 2. 3. 4. 5.

Settings favoring endoscopic approach (ERCP) Preferred in most settings Intact upper gut anatomy Anticipated need for therapeutic stenting or stone removal Need for luminal exam Ascites Coagulopathy Small caliber ducts Failed percutaneous approaches Settings favoring percutaneous approach (PTC) Altered upper gut anatomy, especially Roux-en-Y gastric bypass, +/− Whipple anatomy Complete biliary obstruction Failed endoscopic access for cholangiography or stent placement Need to better image and stage proximal end of stricture for surgical planning

Table 29.2 Indications and favored settings for endoscopic vs percutaneous cholangiographic approach to biliary strictures

6.

7.

8.

8.

9.

Use pre-procedure antibiotics and full strength contrast. Obtain multiple early images during contrast injection. Obtain selected broad views to maintain anatomic reference. Cone down on the area of interest to sharpen radiographic detail. Use the least contrast filling required to adequately demonstrate anatomy. Employ prior CT or MRCP for hilar lesions to guide intrahepatic duct selection for contrast filling and decompression. When wire access is confirmed the proximal extent of duct involvement must be well demonstrated for surgical or endoscopic decision making. Head-up and head-down positions on a tilt table can facilitate imaging of stricture extent by inducing contrast flow to the area of interest. An open hilar view is best obtained with a 20 degree oblique position using a C-arm or by rolling the prone patient rightward toward the endoscopist. After demonstrating a distal stricture, the bifurcation and central intrahepatic ducts should be filled to exclude secondary proximal obstruction (e.g. adenopathy). Some lesions can only be well characterized by percutaneous cholangiography.

Table 29.3 Pointers for stricture characterization during cholangiography 317

SECTION 3 APPROACH TO CLINICAL PROBLEMS

A

B

C

Fig. 29.5 Early A vs later B images acquired during ERCP. Note detail evident on early image is obscured by intrahepatic filling overlapping the area of interest in the subsequent view. Note improved view C with oblique imaging.

A

B

A

B

Fig. 29.6 A and B Overlapping and open views of the ducts at the hilum. B is obtained by rolling the patient rightward 15–20 degrees or by leftward rotation of a C-arm.

marked filling may be required to delineate the proximal end of the stricture. (6) Head-up and head-down positions on a tilt table can facilitate imaging of stricture extent by employing gravity to shift contrast to the area of interest. (7) An open view of the hilum, without overlapping ducts, is best seen in an oblique position, which is achieved with use of a C-arm or by rolling the prone patient rightward toward the endoscopist (Fig. 29.6). (8) After demonstrating a distal extrahepatic stricture, the central intrahepatic ducts and hepatic confluence should be filled to exclude additional proximal strictures (e.g. adenopathy) within reach of endoscopic management. (9) Some lesions can only be well characterized by percutaneous cholangiography (Fig. 29.7). (10) Limited pancreatography may aid in demonstrating or excluding a pancreatic primary lesion when biliary strictures involve the distal third of the duct. Stricture access with guidewires and subsequently other over-thewire accessories is required to accomplish cytology brushing, dilation, and palliative stenting or definitive endoscopic management. Access is usually gained with multipurpose plastic-coated guidewires or specialty hydrophilic wires that are extremely slippery, flexible, and torqueable.17 Manipulation of angled wires using simultaneous torque and advancement can be performed by the assistant, or by the endoscopist using any of several recently designed short318

Fig. 29.7 Benefit of percutaneous trans-hepatic cholangiography (PTC) for proximal evaluation of selected duct lesions. A Partial endoscopic cholangiogram demonstrating complete duct obstruction following laparoscopic cholecystectomy. B PTC-placed hepatic drain demonstrating intrahepatic ducts, confirming complete duct disruption.

wire systems. This is best done with two hands to facilitate fine wire control and maintenance of position (Fig. 29.8). Stricture dilation should be performed prior to passage of larger caliber devices. In the case of benign lesions this constitutes the first step in their therapy. For the tightest strictures that will not accept anything beyond 0.035″ guidewires, initial dilation can be accomplished with angioplasty balloons that traverse 0.018″ wires and expand up to 4 mm from their deflated 0.035″ caliber (Fig. 29.9). Rigid 4–5–7 F dilators can be passed over a 0.025 guidewire. Standard balloon dilators can then be used to expand to larger calibers. Balloon selection is based upon the size of the non-obstructed duct just distal to the stricture. Most often this calls for 4, 6, or 8 mm diameter balloons. Tight chronic strictures carry some risk for rupture or tear during dilation. Should this occur, adequate

Chapter 29 Indeterminate Biliary Stricture

stenting for drainage is mandatory and addition of a nasobiliary drain may be useful during a several-day hospital stay for parenteral antibiotics. Percutaneous transhepatic cholangiography (PTC) has similar capabilities of duct imaging, access, and palliative drainage as does ERCP; however, it is performed through a sterile prepped cutaneous field and hence cholangitis risks are lessened and drainage of filled

segments is less critical. PTC is only indicated when the proximal end of a stricture has not been adequately characterized by MRCP or retrograde methods (if this information will change management), when endoscopy fails to access and decompress an obstructed system, or altered anatomy dictates that percutaneous routes be used. When an extrahepatic stricture cannot be accessed from below, a guidewire can be advanced via PTC for subsequent retrograde access. Use of this so-called “combined procedure” to enable stent placement and decompression should have less morbidity than conversion of the entire management plan to a percutaneous approach.

TISSUE ACQUISITION AND PATHOLOGIC INVESTIGATIONS

Fig. 29.8 A view of the endoscopist’s hands during manipulation of a slippery guidewire through difficult strictures. Note that two hands are used to hold and move the wire, while the base of one hand holds the control section of the endoscope.

A

Methods of tissue acquisition and analysis for cholangiography include performance of fine needle aspiration and mucosal brushing for thin preparation cytologic exam, mucosal biopsy for standard histological analysis, and evaluation of both cytology and biopsy specimens using a variety of specialized tests for nucleic abnormalities or by-products of neoplasia. Tissue acquisition is a key element of each of these techniques. In a recent review, all available sampling techniques during ERCP were evaluated.18 Overall, the results for pathologic examination of tissues acquired at ERCP remain frustratingly low. This is due to several factors, including the scirrhous nature of many tumors, the small tissue samples acquired, difficulty in targeting the abnormality in question, and time constraints in procedures geared primarily toward palliation and less so to tissue acquisition. During cholangiography, spot film radiographic documentation should be obtained of all sampling techniques and locations.

B

C

Fig. 29.9 Dilation of a web-like anastomotic stricture with an angioplasty balloon passed over a 0.018” guidewire. This balloon dilates from an outer diameter of 0.035” to 4 mm, allowing subsequent passage of standard 5 Fr balloon catheters for dilation to 6 or 8 mm. 319

SECTION 3 APPROACH TO CLINICAL PROBLEMS

A

Fig. 29.10 Various cytology brush designs include: A metal tip brush; B brush with flexible wire leader in single lumen catheter; C brush with leader and guidewire in dual lumen catheter; and (d) large caliber brush. (With permission, from Clinical Gastrointestinal Endoscopy, Elsevier Saunders.)

B

Fig. 29.11 A Cholangiogram demonstrating an indeterminate biliary stricture. B Wire-guided brush cytology device within the stricture.

A

B

Brush cytology The yield of brush cytology for the diagnosis of strictures varies widely, with confirmation of malignancy in 15–65% of biliary strictures secondary to pancreatic cancer and in 44–80% of strictures due to cholangiocarcinoma.18,19 Combined results in over 800 patients reported sensitivity of 42%, specificity of 98% and positive predictive value (PPV) of 98% among patients with confirmed cancer.18 Studies pertaining to sampling technique note that cellular yield is improved by using a minimum of five brush passes through the stricture, removal of the catheter and brushing together while avoiding brush withdrawal through the length of the catheter, and flushing residual cells from within the catheter into the sample vial after removal of the brush.20 It is unclear whether stricture dilation improves sample cellularity. Inclusion of washings from the barb or lumen of removed plastic stents may also enhance cytology yield. A variety of brushes are available but few comparative data exist among them. One major design variant is incorporation of a leading flexible wire guide for maintenance of position both within the stricture and within the duct (Fig. 29.10). One study showed no difference between traditional biliary brushes and a new design with longer, stiffer, angled bristles.19 Both brushes yielded adequate specimens in over 80% of cases, suggesting cytologic technology itself is suboptimal for all varieties of malignant biliary lesions. Today biliary cytology brushing is most commonly employed using wire-guided devices (Fig. 29.11). The technique involves first establishing wire-access through the stricture, advancement of the cytology device over the guidewire until through the stricture, advancement of the brush beyond the end of the sheath, and withdrawal of the two together until the brush is within the stricture. The brush is then passed up and down through the stricture at least five times, using either combined movement of the sheath and the brush by the endoscopist, or movement of the brush itself by the assistant as the sheath is held in place. Those devices with a flexible wire leader ahead of the brush can be withdrawn through most of the length of the stricture and safely advanced without risking loss of access or perforation. Some tight or angled strictures can only be brushed with a downward movement or brush withdrawal, requiring repeated access with the entire assembly for each brush pass. 320

Fig. 29.12 A An indeterminate biliary stricture with a neighboring pancreatic stricture representing a double duct sign, suspicious for pancreatic carcinoma. B Forceps biopsy being performed parallel to a guidewire.

Intraductal transmucosal fine needle aspiration This FNA method was reported to yield positive or suspicious cytology in 67% of cancers in the hands of one proponent21 but cumulative data from over 220 patients in five series yielded a sensitivity of only 34%, with 100% specificity and 100% PPV.18 The technique has not gained favor as it is difficult and is optimally performed with a cytopathologist in the room.

Intraductal forceps biopsies Intraductal biopsies provide the greatest yield for detection of malignancy among the ERCP-based modalities, with a cumulative sensitivity of 56%, specificity of 97% and positive predictive value of 97% based upon 500 patients in five cumulative studies.18,20 A variety of straight, angled, and malleable forceps are available in adult (7 F) and pediatric (5–6 French) calibers for intraductal use. Passage of these devices may require performance of a biliary sphincterotomy. However, passing the forceps alongside of a guidewire without sphincterotomy is possible.22 Trocars or sheaths for transpapillary passage of biopsy cables are also available. There are limited data comparing the different biopsy devices. The technique of passing a biopsy forceps into the bile duct involves impacting the rigid leading end of the biopsy cable into the papillary os or the sphincterotomy opening from a short scope position, then advancing the endoscope several centimeters while simultaneously flexing the large ratchet backward to look upward from below the papilla, followed by upward advancement of the cable (Fig. 29.12). Alternatively one can occasionally advance the biopsy

Chapter 29 Indeterminate Biliary Stricture

A B

Fig. 29.13 Fluorescent in-situ hybridization demonstrates a single microscopic field with fluorescent probes of different colors attached to specific chromosomal loci. Two copies of each probe should be present. Presence of more than two copies represents aneuploidy in a cell. A a normal cell. B a cell from a malignant stricture in a patient with PSC.

cable directly into the papilla from a slightly longer flexed position, looking upward from below the papilla. The highest diagnostic yield for tissue sampling during ERCP is obtained when two or more of the standard modalities are combined at the same procedure. Ponchon increased the cumulative yield to 63% by combining brush cytology (43% sensitivity) and intraductal biopsy (30%).23 Combined biopsy, brushing, FNA, and stent cytology yielded positive diagnosis in 82% of patients in one study.23a Given the suboptimal diagnostic yield from standard analyses of brush cytology and tissue biopsy samples, a variety of advanced analytic techniques have been investigated. They include flow cytometry, digital image analysis (DIA), and fluorescent in-situ hybridization (FISH). In a limited number of studies, flow cytometry for DNA assessment of large cellular populations yielded improved sensitivity at the expense of significantly reduced specificity.24 Digital image analysis uses a computerized assessment of cellular DNA ploidy within a smaller number of individual cells identified on a cytology slide to estimate the relative proportion with aneuploidy, which serves as a marker of malignancy. In a recent prospective study of 100 patients with mixed benign and malignant strictures the sensitivity, specificity, and accuracy of DIA of biliary brush cytology samples was 39.3%, 77.3%, and 56%, compared to 17.9%, 97.7%, and 53% for standard cytology.25 False positive results from DIA (10 of 44, 22.7%) occurred only in patients with primary sclerosing cholangitis (PSC). The only false positive for routine cytology (1/44, 2.3%) was also in a patient with PSC. Fluorescent in-situ hybridization employs fluorescent probes that label specific portions of selected chromosomes, allowing for determination of cellular ploidy via fluorescent microscopy of specific cellular samples (Fig. 29.13). Recent studies have employed chromosomal probes that were originally designed for identification of urothelial cancers (centromeres to chromosomes 3, 7, and 17 plus chromosomal band 9p21).26 Detection of more than five cells with polysomy is considered evidence for malignancy. In preliminary

studies, the FISH technique increased the sensitivity of brush sampling for detection of malignancy from 15% to 34% (p < 0.01), with corollary non-significant reduction in specificity from 98% to 91% (p = 0.06).26 Concerns about specificity persist and confirmatory series are needed. Studies designed to identify products of other genetic mutations (p-53, k-ras) in bile or tissues have not yielded adequate sensitivity and specificity to be of clinical use for diagnosis.

ANCILLARY TECHNIQUES Intraductal ultrasonography (IDUS) employs a 20 mHz radial ultrasound probe on the leading end of a 7 French catheter that can be passed over a guidewire into the biliary and pancreatic ducts during ERCP (Fig. 29.14). IDUS has been employed for identification of residual duct stones, characterization of strictures, and staging of local cancer involvement. Following performance of cholangiography, a 0.035″ guidewire is left in the duct and the ultrasound probe is advanced over the wire with the radial crystal stationary. Imaging is then performed primarily during catheter withdrawal, to limit mechanical trauma to the mechanical drive of the probe. Acquisition of IDUS skills is less involved than acquisition of EUS skills and most experienced endoscopists should be able to adopt IDUS for the management of stone disease with limited training, and for stricture assessment with slightly greater experience. Ultrasonographic features of malignant strictures include hypoechoic asymmetric wall thickening, poorly demarcated borders and abrupt shoulders (Fig. 29.15). Benign lesions tend to be hyperechoic, have less asymmetry, sharper demarcation with surrounding tissues, preserved tissue planes, and smooth edges. IDUS interpretation is more difficult in the setting of primary sclerosing cholangitis, where widespread background inflammation and duct thickening are present. Similarly, prolonged stenting can induce more widespread duct abnormalities than were originally present at the level of the index stricture. 321

SECTION 3 APPROACH TO CLINICAL PROBLEMS

A

B

C

Fig. 29.14 A Leading end of 5 F wire-guided intraductal ultrasound (IDUS) probe. The mechanical radial ultrasound crystal is noted with an arrow. B IDUS catheter exiting from the duodenoscope. C IDUS probe within stricture in Figure 29.11.

Fig. 29.15 IDUS images from an extrahepatic cholangiocarcinoma. Note the asymmetry of wall thickening and its irregular outer boundary.

Several studies have demonstrated the superior sensitivity and accuracy of IDUS for characterization of strictures as malignant (sensitivity >90%; accuracy 88–92%) compared to standard cholangiography, with or without cytology and biopsy sampling (sensitivity 48–57%; accuracy 73–78%).27–29 In a recent prospective study in 87 patients, elevated serum CA 19-9 (>100 units), routine cytology and 322

intraductal biopsy were compared to advanced cytologic assessment with DIA, FISH and stricture assessment with IDUS. IDUS showed the greatest sensitivity (87%) and accuracy (90%), and the combination of IDUS, DIA, and FISH allowed diagnosis of malignancy in 87% of those with falsely negative routine cytology.30 Studies of IDUS for tumor staging also report utility for defining longitudinal extent as well as the extent of invasion to the pancreatic parenchyma, portal vein, and right hepatic artery.31 Periductal, nodal, and distant spread is not adequately assessed by IDUS. Cholangioscopy, or direct visual evaluation of the biliary tree, is increasingly used for visually directed sampling of indeterminate strictures and for electrohydraulic lithotripsy therapy of intractable stones. Cholangioscopy is also discussed in Chapter 21 (Fig. 29.16). It usually employs 8–10 French mini-endoscopes that are passed through the working channel of a therapeutic duodenoscope, with or without guidewire assistance. Fiberoptic cholangioscopes are commercially available; digital video-chip versions are in use but not widely available. Cholangioscopy is usually performed with the assistance of a second endoscopist to manipulate the cholangioscope controls and biopsy cables while the primary endoscopist controls the duodenoscope and the insertion of the cholangioscope. Some centers employ custom endoscope holders for the cholangioscope to enable studies by a single operating physician.32 During cholangioscopy attention must be paid to frequent or continuous flushing to clear the field of bile or debris. Fluid run-off to the stomach requires frequent aspiration, use of a nasogastric tube, or endotracheal intubation. Cholangioscopes are relatively fragile and care must be taken to avoid excessive angulation or force, particularly at the level of the elevator on the duodenoscope. Recent series demonstrate improved sensitivity and accuracy for diagnosis of malignant obstruction when cholangioscopy is employed33,34 In one study, ERCP with fluoroscopically guided tissue sampling had a sensitivity of 58% and accuracy of 78% for malignancy while addition of cholangioscopy raised these values to 100%

Chapter 29 Indeterminate Biliary Stricture

A

B

Fig. 29.16 A Radiograph of a cholangioscope advanced to the level of the proximal extrahepatic duct. B Cholangioscopic view of hepatic confluence with open left hepatic duct and tumor occluding right hepatic duct.

and 94% respectively.33 Cholangioscopy may be particularly useful in differentiating benign from malignant strictures in the setting of primary sclerosing cholangitis. One study demonstrated improved sensitivity (92% vs 66%, p = 0.25), specificity (93% vs 51%, p < 0.001), and accuracy (93% vs 55%, p < 0.001) for cholangioscopic characterization compared to radiographic characterization.16 The criteria for suspicion of malignancy in this study were the presence of an associated polypoid or villous mass or irregularly shaped ulceration. A recently developed technology employs a single-use 10 Fr multi-channeled sheath (SpyglassTM Direct Visualization System; Boston Scientific, Marlboro, MA) that attaches to the head of the duodenoscope just below the biopsy port and advances through the accessory channel for insertion into the duct (Fig. 29.17). The sheath provides 4-way steering of the tip, illumination, water flushing, a channel for passage of a 0.035” caliber fiberoptic probe for visualization of the duct (SpyScope), and another for either wire guidance or passage of therapeutic or sampling devices such as the electrohydraulic probe, biopsy cables (SpyBite), or cytology brushes. Preliminary data demonstrate utility in 18 of 20 cases for directed biopsy, stone therapy, or clarification of anatomy or pathology.35 Stent placement for biliary decompression is the major therapeutic modality used for patients with indeterminate strictures. Stenting as definitive therapy for benign lesions or as palliative therapy for malignant obstruction is discussed in Chapters 16 and 17. Plastic stents are usually employed for palliation of indeterminate strictures to ensure the ability to remove them at a later endoscopic or surgical procedure and to limit the cost of potentially brief duration stenting. When diagnosis remains indeterminate, serial procedures and repeated tissue sampling are often performed; hence shorter intervals of drainage and smaller caliber 7 and 8.5 French stents may suffice. If subsequent diagnostic investigations are chosen that employ EUS rather than ERCP or if the patient is not a surgical candidate regardless of the diagnosis, it is preferable to palliate the indeterminate lesion with larger caliber 10 French stents that remain patent longer and may minimize the number of

A

B

C

D

Fig. 29.17 The SpyGlass Direct Visualization System attached to the duodenoscope and advanced into the accessory channel. Close-up demonstrates ratchets for steering and ports for passage of guidewire, biopsy forceps, and 0.035” SpyGlass fiberoptic probe. 323

SECTION 3 APPROACH TO CLINICAL PROBLEMS

subsequent procedures. In the patient with an indeterminate stricture self-expandable metal stents (SEMS) are typically avoided due to both their permanence and their expense. Partially coated SEMS are generally removable when they are left extending into the duodenum, and fully coated variants designed specifically for removal are under investigation.36,37 Their use can be entertained in the indeterminate lesion if prolonged stenting for either treatment of benign stricture or palliation of cancer is desirable. Plastic stents

remain preferable for the patient with a mass lesion and high likelihood of resectability. Modern imaging and new analytical techniques have advanced our ability to characterize indeterminate biliary strictures. Nevertheless, in some patients with indeterminate strictures a definitive diagnosis cannot be made via minimally invasive approaches. In these instances, surgical exploration with a goal of diagnosis and resection should be considered in operable patients.

REFERENCES 1. Afroudakis A, Kaplowitz N. Liver histopathology in chronic common bile duct stenosis due to chronic alcoholic pancreatitis. Hepatology 1981; 1:65–72. 2. Lesur G, Levy P, Flejou JF, et al. Factors predictive of liver histopathological appearance in chronic alcoholic pancreatitis with CBD stenosis and increased serum alkaline phosphatase. Hepatology 1993; 18:10781–1081. 3. ASGE Standards of Practice Committee. An annotated algorithmic approach to malignant biliary obstruction. Gastrointest Endosc 2001; 53:849–852. 4. Torok N, Gores GJ. Cholangiocarcinoma. Seminars in Gastrointestinal Disease 2001; 12:125–132. 5. Klimstra DS, Adsay NV. Lymphoplasmacytic sclerosing (autoimmune) pancreatitis. Seminars in Diagnostic Pathology 2004; 21:237–246. 6. Chari ST, Smyrk TC, Levy MJ, et al. Diagnosis of autoimmune pancreatitis: the Mayo Clinic experience. Clin Gastroenterol Hepatol 2006 Aug; 4(8):1010–1016. 7. De Palma GD, Pezzullo A, Rega M, et al. Unilateral placement of metallic stents for malignant hilar obstruction: A prospective study. Gastrointestinal Endoscopy 2003; 58:50–53. 8. Rosch T, Meining A, Fruhmorgen S, et al. A prospective comparison of the diagnostic accuracy of ERCP, MRCP, CT, and EUS in biliary strictures. Gastrointestinal Endoscopy 2002; 55:870–876. 9. Domagk D, Wessling J, Reimer P, et al. Endoscopic retrograde cholangio-pancreatography, intraductal ultrasonography, and magnetic resonance cholangio-pancreatography in bile duct strictures: A prospective comparison of imaging diagnostics with histopathological correlation. American Journal of Gastroenterology 2004; 99:1684–1689. 10. Lee JH, Salem R, Aslanian H, et al. Endoscopic ultrasound and fine-needle aspiration of unexplained bile duct strictures. American Journal of Gastroenterology 2004; 99:1069–1073. 11. Eloubeidi MA, Chen VK, Jhala NC, et al. Endoscopic ultrasoundguided aspiration biopsy of suspected cholangiocarcinoma. Clinical Gastroenterology and Hepatology 2004; 2:209–213. 12. Rosch T, Hofrichter K, Fringberger E, et al. ERCP or EUS for tissue diagnosis of biliary strictures? A prospective comparative study. Gastrointestinal Endoscopy 2004; 60:390–396. 13. Wiersema MJ, Fletcher JG, Jondal ML, et al. Prospective evaluation of triple phase multidetector computed tomography, dynamic gadolinium-enhanced magnetic resonance imaging and endosonography in potentially resectable pancreatic adenocarcinoma. Gastrointestinal Endoscopy 2002 Oct; 56(4 Suppl):S123. 14. Bain VG, Abraham N, Jhangri GS, et al. Prospective study of biliary strictures to determine the predictors of malignancy. Endoscopy 2000; 14:397–402. 15. MacCarty RL, LaRusso NF, May GR, et al. Cholangiocarcinoma complicating primary sclerosing cholangitis: cholangiographic appearances. Radiology 1985; 156:43–46. 324

16. Tischendorf JJW, Kruger M, Trautwein C, et al. Cholangioscopic characterization of dominant bile duct stenosis in patients with sprimary sclerosing cholangitis. Endoscopy 2006; 38:665–669. 17. ASGE Technology Committee. Technology assessment status evaluation: guidewires in gastrointestinal endoscopy. Gastrointestinal Endoscopy 1998; 47:579–583. 18. De Bellis M, Sherman S, Fogel EL, et al. Tissue sampling at ERCP in suspected malignant biliary strictures (Part 2). Gastrointestinal Endoscopy 2002; 56:720–730. 19. Fogel EL, deBellis M, McHenry L. Effectiveness of a new long cytology brush in the evaluation of malignant biliary obstruction: a prospective study. Gastrointest Endosc 2006; 63:71–77. 20. Barkun A, Liu J, Carpenter S, et al. Update on endoscopic tissue sampling devices. Gastrointestinal Endoscopy 2006; 63:741–745. 21. Howell DA, Beveridge RP, Bosco J, et al. Endoscopic needle aspiration biopsy at ERCP in the diagnosis of biliary strictures. Gastrointestinal Endoscopy 1992; 38:531–535. 22. Lin LF, Siauw CP, Ho KS, et al. Guidewire technique for endoscopic transpapillary procurement of bile duct biopsy specimens without endoscopic sphincterotomy.Gastrointest Endosc 2003 Aug; 58(2):272–274. 23. Ponchon T, Gagnon P, Berger F, et al. Value of endobiliary brush cytology and biopsies for the diagnosis of malignant bile duct stenosis: results of a prospective study, Gastrointestinal Endoscopy 1995; 42:565–572. 23a. Jailwala J, Fogel EL, Sherman S, et al. Triple-tissue sampling at ERCP in malignant biliary obstruction. Gastrointest Endosc 2000; 51:383–390. 24. Ryan ME, Baldauf MC. Comparison of flow cytometry for DNA content and brush cytology for detection of malignancy in pancreaticobiliary strictures. Gastrointest Endosc 1994; 40: 133–139. 25. Baron TH, Harewood GC, Rumalla A, et al. A prospective comparison of digital image analysis and routine cytology for the identification of malignancy in biliary tract strictures. Clinical Gastroenterology and Hepatology 2004; 2:214–219. 26. Kipp BR, Stadheim LM, Halling SA, et al. A comparison of routine cytology and fluorescence in situ hybridization for the detection of malignant bile duct strictures. Am Journal of Gastroenterology 2004; 99:1675–1681. 27. Farrell RJ, Agarwal B, Brandwein SL, et al. Intraductal US is a useful adjunct to ERCP for distinguishing malignant from benign biliary strictures. Gastrointest Endoscopy 2002; 56:681–687. 28. Vazquez-Sequeiros E, Baron TH, Clain JE, et al. Evaluation of indeterminate bile duct strictures by intraductal US. Gastrointestinal Endoscopy 2002; 56:372–379. 29. Inui K, Miyoshi H. Cholangiocarcinoma and intraductal sonography. Gastrointestinal Endoscopy Clinics of NA 2005; 15:143–155. 30. Levy MJ, Rumalla A, Baron TH, et al. Prospective Evaluation of Intraductal Ultrasound (IDUS), Digital Image Analysis (DIA), Fluorescence in Situ Hybridization (FISH), CA 19-9, and ERCP with routine

Chapter 29 Indeterminate Biliary Stricture

cytology and intraductal biopsy in the evaluation of indeterminate bile duct strictures. Gastrointestinal Endoscopy 2006; 63:AB88. 31. Tamada K, Ido K, Ueno N, et al. Preoperative staging of extrahepatic bile duct cancer with intraductal ultrasonography. American Journal of Gastroenterology 1995; 90:239–246. 32. Farrell JJ, Bounds BC, Al-Shalabi S, et al. Single-operator duodenoscope-assisted cholangioscopy is an effective alternative in the management of choledocholithiasis not removed by conventional methods, including mechanical lithotripsy. Endoscopy 2005; 37:542–547. 33. Fukuda Y, Tsuyuguchi T, Sakai Y, et al. Diagnostic utility of peroral cholangioscopy for various bile-duct lesions. Gastrointestinal Endoscopy 2005; 62:374–382.

34. Shah RJ, Langer DA, Antillon MR, et al. Cholangioscopy and cholangioscopic forcepts biopspy in patients with indeterminate pancreaticobiliary pathology. Clinical Gastroenterology and Hepatology 2006; 4:219–225. 35. Chen YK. Results from the first human use clinical series utilizing a new peroral cholangiopancreatoscopy system (Spyglass(tm) Direct Visualization System). Gastrointestinal Endoscopy 2006; 63: AB86. 36. Familiari P, Bulajic M, Mutignani M, et al. Endoscopic removal of malfunctioning biliary self-expandable metallic stents. Gastrointestinal Endoscopy 2005; 62:903–910. 37. Petersen BT. SEMS removal: salvage technique or new paradigms. Gastrointestinal Endoscopy 2005; 62:911–913.

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Benign Biliary Strictures Guido Costamagna, Syed G. Shah and Lalit Shimpi

BOX 30.1 KEY POINTS • There are a variety of causes of benign biliary strictures • Postoperative biliary strictures are the most common benign biliary stricture • Endoscopic therapy for benign biliary strictures consists of dilation and stent placement using multiple, large-bore plastic stents • Chronic pancreatitis strictures are less responsive to endoscopic therapy • The short-term outcome following endoscopic treatment of benign strictures is excellent • Successful long-term outcome following endoscopic therapy of benign biliary strictures is comparable to surgery, and does not preclude subsequent surgical therapy in cases that fail or recur

The majority of benign bile duct strictures occur as a result of postoperative iatrogenic injury, most commonly following cholecystectomy, or occur at the site of biliary anastomosis after hepatic resection or liver transplantation. Benign strictures may also result from a variety of other causes (Table 30.1). The endoscopic management of benign biliary strictures is also covered in Chapters 31, 35, and 43. Bile duct injuries are reported to be higher during laparoscopic cholecystectomy than open surgery.1 The estimated overall incidence of biliary injuries following laparoscopic cholecystectomy has been reported to be between 0.2% and 1.7%.2,3 Misidentification of anatomic structures during dissection, presence of acute inflammation or fibrous adhesions in the gallbladder fossa, excessive use of electrocautery to control bleeding, inaccurate placement of clips or sutures, and excessive traction on the gallbladder neck are major causes.2 Bergman et al.4 described four types of postoperative bile duct injuries: Type A-cystic duct leaks or leakage from aberrant or peripheral hepatic radicles, Type B-major bile duct leaks with or without concomitant biliary strictures, Type C-bile duct strictures without bile leakage, and Type D-complete transection of the duct with or without excision of some portion of the biliary tree. Postoperative biliary strictures occur in 0.2–0.5% of patients and usually occur as a result of partial or complete transection by clipping or ligation of the bile duct, or less frequently as a result of vascular injury during dissection or cauterization. Injury to sectorial or

segmental branches may occur in patients with anatomic anomalies of the biliary tree. Approximately 10–30% of patients with chronic pancreatitis develop symptomatic biliary stenosis.5 Biliary obstruction due to compression by an edematous pancreatic head or pseudocyst usually resolves when the inflammation subsides or after resolution of the pseudocyst. However, obstruction caused by a fibrotic stricture does not resolve spontaneously and requires therapeutic intervention.

CLINICAL FEATURES Approximately 10% of postoperative bile duct strictures present within 1 week of surgery. These usually occur as a result of inadvertent clipping or ligation of the common bile duct and may or may not be associated with biliary leaks. Patients may present with abdominal pain, fever, pruritus, jaundice or biliary fistula. However, in the majority of cases presentation is delayed and 70–80% present within 6–12 months of surgery.6 The presentation is symptomatic or asymptomatic cholestasis, recurrent cholangitis, stone formation, or secondary biliary cirrhosis. Bismuth7 classified benign strictures into five types: Type 1-Low common hepatic duct (CHD) or bile duct (CHD >2 cm), Type 2-Mid common hepatic duct (CHD <2 cm), Type 3-Hilar stricture, Type 4-Destruction of hilar confluence (right and left hepatic ducts separated) and Type 5-Involvement of right hepatic branch alone or with common duct. Bismuth types 1 and 2 strictures are most frequent in reported series.8–10 The clinical presentation of biliary strictures is somewhat different in patients with chronic pancreatitis.11 In a retrospective survey of 78 patients with chronic pancreatitis, overt jaundice was found in only a minority of patients.12 No relationship was found between features of the common bile duct and severity of pancreatitis, or disease duration.

DIAGNOSIS The clinical diagnosis of postoperative biliary stricture is usually suspected by the onset of either symptomatic and/or biochemical cholestasis in the early or late postoperative period. In the first instance, ultrasound examination is performed to confirm biliary dilation and may suggest the level of biliary obstruction. MRCP is a useful, non-invasive diagnostic modality for accurately delineating the biliary anatomy and site of stenosis, and for planning definitive therapy.13

MANAGEMENT Traditionally, postoperative bile duct strictures were managed surgically and the role of ERCP was limited to the diagnosis and definition of the level and extent of the stricture.14 With the 327

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Postoperative Anastomotic Non-anastomotic Ischemia (including polyarteritis nodosa) Primary or secondary sclerosing cholangitis Post-sphincterotomy Chronic pancreatitis Radiation therapy Portal bilopathy Post-treatment of biliary lymphoma Tuberculosis Abdominal trauma Post-radiofrequency ablation Endoscopic injection sclerotherapy of duodenal ulcer bleeding

Table 30.1 Causes of benign biliary strictures increasing use of ERCP for the treatment of acute complications of cholecystectomy, therapeutic ERCP has been extensively adopted to manage postoperative strictures and other benign biliary strictures. Percutaneous transhepatic therapy with balloon dilation of the stricture is limited by low success rates, high stricture recurrence rates, and high complication rates.15,16 The high stricture recurrence rate following percutaneous transhepatic pneumatic dilation is most likely due to forceful disruption of the scar, which can add further traumatic damage to the tissue and consequential development of a new fibrotic reaction. Endoscopic treatment of a postoperative bile duct stricture is often preferred over percutaneous techniques because it avoids the need for liver puncture and access to non-dilated intrahepatic ducts is easier. Also, the endoscopic approach is more comfortable for the patient and is safer in the presence of cirrhosis, ascites, or coagulopathy. Percutaneous transhepatic techniques are now usually reserved for failed endoscopic procedures.

ENDOSCOPIC TECHNIQUE Endoscopic treatment of benign biliary strictures involves two technical steps: (1) negotiating the stricture and (2) dilation of the stricture.

Negotiating the stricture Negotiating the stricture requires continuity of the common bile duct (CBD). In cases of complete transection or ligation of the CBD, a guidewire cannot be passed across the lesion and thus endotherapy alone is not feasible. In such cases, surgical reconstruction is indicated, though a combined percutaneous endoscopic approach has been described.17 Negotiating benign biliary strictures is often much more difficult than neoplastic strictures because the stenosis, even if short, may be asymmetric. Furthermore, associated fibrosis makes them thin and tighter. It is, therefore, often necessary to use thin hydrophilic guidewires (0.021 or 0.018-inch diameter) with a straight or curved (J-shaped) tip to get across. Guidewire manipulation requires patience, skill, and optimal fluoroscopic imaging. Forceful maneuvers may create false passages and should be avoided. Pulling on an inflated stone retrieval balloon positioned just distal to the stricture results in stretching of the bile duct and modification of the axis of the guidewire. Steerable catheters or papillotomes may also be used to achieve the same result. Once the stricture is traversed, the hydrophilic guidewire is exchanged for a 328

stiffer one to facilitate dilation. Sphincterotomy is usually performed due to the necessity for repeated stent exchanges and to allow for side-by-side placement of large-bore stents. When a stricture cannot be traversed at ERCP, a combined endoscopic percutaneous approach (rendezvous) can be used.

Dilation of the stricture Stricture dilation has two objectives: (1) to reopen the CBD to achieve bile drainage and (2) to keep the stenosis open and avoid re-stricturing. Insertion of the guidewire through the stricture is followed by placement of a 6 Fr catheter over the guidewire, and by mechanical dilation with a 9.5 Fr Cunningham-Cotton sleeve (Cook Endoscopy, Winston-Salem, NC, USA) to test the caliber of the stricture prior to attempting stent insertion. Hydrostatic balloon dilation with 4, 6, and 8 mm balloons (e.g. Max Force, Boston Scientific, MA, USA) may be necessary in cases where the stricture is not amenable to mechanical dilation. Balloon dilation is usually performed to a size 1–2 mm larger than the downstream bile duct diameter. Although immediately effective, endoscopic and percutaneous balloon dilation alone, whether in single or multiple sessions, is considered inadequate and associated with a high restenosis rate (up to 47%).8,18,19 Stent placement, on the other hand, keeps the stricture open for a prolonged period to allow scar remodeling and consolidation.20 When mechanical and/or balloon dilation is unsuccessful, leaving a 5 or 6 Fr nasobiliary drainage tube in situ for 24 to 48 hours may increase the chances of subsequent endoscopic stent placement. Typically, 10 to 12 Fr polyethylene stents are placed and exchanged every 3–4 months to prevent cholangitis from stent occlusion. However, the optimal number of stents and duration of stent placement for stricture resolution has not been established.

OUTCOMES OF BILIARY STENTING Several variations in endoscopic stent protocols have been described for the treatment of postoperative benign biliary strictures with successful stricture resolution reported in 74–90% of patients.8,21 Bergman and colleagues reported on the results of endoscopic stent therapy in 74 patients with postoperative biliary strictures.22 Two 10 Fr stents were placed whenever possible, and exchanged every 3 months for a period of 1 year. Technical success of initial stenting was reported to be 80%. However, due to a variety of reasons only 59% (44 patients) of the original cohort completed the 12-month stenting period. Amongst these, endoscopic stent placement failed in 11 patients due to complete bile duct obstruction. Recurrent stenosis occurred in 9 of 44 patients (20%) after a median follow-up of 9.1 years with the majority of patients presenting within six months of stent removal (median 2.6 months, range 2 months to 15 years). Of the original cohort, 35 of 74 patients (47%) were stricture free at the end of the follow-up period. Major complications, including cholangitis, pancreatitis, bleeding and stent migration, were more common in patients who were non-compliant with the stent exchange protocol. A more aggressive biliary stent approach has been reported by our own institution.9 In 45 patients with postoperative biliary strictures, we placed as many stents as possible during each ERCP session with elective stent exchange performed every 3 months. At each exchange, all previously placed stents were removed and the maximum number of large-diameter stents inserted, as permitted by the diameter of the duct distal to the stricture and the diameter of the stricture itself. The treatment protocol was stopped when

Chapter 30 Benign Biliary Strictures

A

B

C

D

E

F

G

H

Fig. 30.1 A Bismuth type 2 stricture after laparoscopic cholecystectomy. B Guidewire negotiated across stricture. C A single largebore plastic stent has been placed. Cholangiogram shows co-existent bile leak at the site of the biliary stricture. D At repeat ERCP, two large-bore plastic stents have been placed. E Persistence of biliary stricture after removal of stents. The stricture has been traversed using a guidewire and biliary balloon dilator. F Biliary balloon dilation performed. G Post-dilation, three large-bore plastic stents have been placed. H Disappearance of the stricture after removal of the stents.

complete morphologic disappearance of the stricture was demonstrated by occlusion cholangiography after stent removal, and confirmed by subsequent cholangiography performed through a nasobiliary drain 24 to 48 hours later (Fig. 30.1). Complete disappearance of the stricture was defined as absence of any significant indentation at the site of previous narrowing. Of the 42 patients who completed the stenting protocol, a percutaneous endoscopic “rendezvous” technique was necessary for endoscopic biliary access in 3 patients, and balloon dilation was required in 40% of patients prior to stent placement. The mean number of stents placed at the first session was 1.7 ± 0.7 (range 1–4), while that at the last ERCP session was 3.2 ± 1.3 (range 1–6). Mean duration of treatment was 12.1 ± 5.3 (range 2–24) months with a mean number of 4.1 ± 1.3 (range 2–8) procedures per patient. Stents were ultimately removed from all patients. The mean follow-up was 48 months (range 24 months–11.3 years). On an intention-to-treat basis, endoscopic treatment was successful in 89% of patients. Complications occurred in 9% of patients (including three patients with cholangitis, and one with pancreatitis) and all were managed conservatively. There was no mortality. Even though the follow-up period in our

study was shorter than the Amsterdam group, it is longer than the typical period during which all the recurrences after endoscopic therapy have been described (within 2 years). These promising results with endoscopic therapy have also been replicated in a recent prospective trial involving 43 patients with post-laparoscopic cholecystectomy bile duct strictures in whom a similar protocol for endoscopic stenting was followed.23 A mean of 3.4 ± 0.6 (range 3–5) stents were placed for a period of 1 year. The authors reported a 100% success rate for stricture dilation with no stricture recurrence at a mean follow-up of 16.0 ± 11.1 (range 1–42) months after stent removal. Previously published data have shown that endoscopic therapy is at least as effective as surgical treatment for benign biliary strictures with reported success rates of approximately 80%.24 Although there are no randomized controlled trials comparing the two modalities, retrospective and case controlled studies comparing both treatment modalities have shown similar long-term results and re-stenosis rates.24–26 Surgery may, however, be associated with higher early morbidity and mortality.25,27,28 Endoscopic therapy, on the other hand, offers several advantages including relative simplicity, 329

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reversibility, and above all minimal invasiveness. An additional advantage of endotherapy is that treatment failure does not preclude subsequent surgery, whereas hepaticojejunostomy, which is the classical surgical procedure, makes future endotherapy difficult, if not impossible. The major disadvantage of endotherapy, however, is the need for multiple procedures. Most studies have employed a protocol of elective stent exchange to avoid cholestasis and/or cholangitis, secondary to stent occlusion. In case of patient non-compliance, late morbidity with endoscopic therapy may increase. Assurance of patient compliance is therefore of paramount importance to ensure successful endoscopic therapy. As with surgery, strictures at or above the main hepatic confluence are often more challenging than strictures below the hepatic confluence (Fig. 30.2). In the study by Draganov et al. a high success rate was achieved in patients with Bismuth type 1 or 2 strictures (80%), and the lowest in type 3 strictures (25%).8 The favorable results of endoscopic therapy for post-cholecystectomy biliary strictures are also reflected in the treatment of anastomotic strictures following orthotopic liver transplantation. Though poor long-term outcome has been reported with endoscopic balloon dilation alone,29 good to excellent results (74–90% clinical success rates at 3–5 years follow-up) have been reported following multiple stent insertion in patients with post-transplant anastomotic biliary strictures.30,31 Endoscopic therapy is associated with a low complication rate and may avoid the need for surgical intervention.30,32 However, surgery should be considered for those patients who are non-responsive to endoscopic therapy.31 Unlike postoperative benign biliary strictures, long-term results of endoscopic therapy for bile duct strictures associated with chronic pancreatitis have not been encouraging. Although short-term results are excellent with immediate relief of cholestasis in almost all cases, it remains unclear whether endoscopic plastic stent placement can achieve definite stricture resolution, especially in tight, fibrotic strictures.33 No prospective studies have been performed, and a number of small, retrospective studies have reported success rates ranging between 10 and 95%. Cahen et al. recently reported a success rate of only 38% for endoscopic plastic stent placement in 58 patients with distal bile duct strictures due to chronic pancreatitis.33 In this retrospective study single, large-bore (10 Fr) plastic stents were placed in the majority of patients and exchanged every 3 months, or when signs of stent dysfunction were present, for a period of 1 year. In those patients in whom stricture dilation was successful there was no evidence of recurrent biliary stricture after a median follow-up of 85 months. Concomitant acute pancreatitis was the only factor identified as predictive of a successful outcome (92% stricture resolution with concomitant pancreatitis vs 24% without pancreatitis).33 Stricture dilation beyond 1 year had no additional benefits. A more aggressive approach using multiple plastic stents has also been tried, but with little improvement in success rates.8 The poor results of endoscopic therapy for chronic pancreatitis induced biliary strictures following plastic stent placement have encouraged the use of self-expandable metal stents (SEMS). However, the majority of studies reporting on the use of uncovered SEMS have been small with variable results.34,35 Uncovered SEMS may be useful and considered in those patients who either refuse surgery, or in whom surgery is contra-indicated due to concomitant portal hypertension or patient co-morbidity. Overall, the long-term results of stenting using uncovered SEMS for all types of benign biliary strictures has been disappointing because patency is usually short term, and most stents eventually 330

obstruct due to mucosal hyperplasia, biliary sludge or calculi.26,36,37 Placing SEMS in such patients may therefore add to morbidity, require repeated endoscopic sessions to re-establish stent patency, and may preclude surgical therapy if placed too proximally. Current data does not support the routine placement of SEMS for benign biliary strictures. As opposed to uncovered SEMS, covered SEMS may have added applicability because of potential removability. One trial, published in abstract form is encouraging.38 Wallstents were placed in 55 patients for benign biliary strictures (chronic pancreatitis, n = 25; stones, n = 16; liver transplantation, n = 11; surgical bile duct injury, n = 3) and the stents could be easily removed. At a median follow-up of 3 months (range 1–11), relapse occurred in only 10% of patients. The advantage of this approach is the large “dilation” diameter which can be achieved after one endoscopic procedure. Larger studies with longer follow-up are needed to confirm these results. In addition, when the Wallstent is placed, one must be sure that the distal end is well into the duodenum so that it can be subsequently removed.39 Post-sphincterotomy distal bile duct strictures are a distinct entity that deserve mention. It is estimated that post-sphincterotomy distal biliary strictures occur in about 2% of patients when the indication is for choledocholithiasis. A recent study in 20 patients with postsphincterotomy stricture using sequential insertion of multiple plastic biliary stents was published.40 After a median of nine months of follow-up with 18 patients the success rate was 90%. Two patients developed stricture recurrences at 10 and 24 months. Complications of biliary stenting may occur at any time during the first or subsequent treatment sessions. Early complications relate to sphincterotomy, such as acute pancreatitis, perforation or bleeding, and occur with similar frequency to those encountered during therapeutic ERCP for other indications, such as removal of CBD stones. Complications arising during the course of stent therapy are mostly due to stent dysfunction, including obstruction,

BOX 30.2 INDICATIONS AND CONTRAINDICATIONS • The indications for treatment of a benign biliary stricture are symptoms and/or cholestasis. • Contraindications to endoscopic therapy are inability to traverse the stricture and severe, uncorrectable coagulopathy.

BOX 30.3 COMPLICATIONS AND CONTROVERSIES • Complications of endoscopic therapy include cholangitis, ductal or luminal perforation, pancreatitis, bleeding, and stent migration. • The use of self-expanding metal stents for treatment of benign biliary strictures is controversial.

Chapter 30 Benign Biliary Strictures

A

B

Fig. 30.2 A Bismuth type 4 bile duct stricture with two guidewires in place in the paramedian branch of the right hepatic and left hepatic ducts. B Three large-bore plastic stents have been placed. C Persistence of stricture after removal of stents. D Five largebore plastic stents have been placed. E At subsequent ERCP, eight large-bore plastic stents have been placed. F Cholangiogram showing resolution of biliary stricture after stent removal.

D C

F

E

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migration, and stent impaction. Stent dysfunction usually manifests as acute cholangitis, and requires prompt endoscopic assessment and stent replacement or repositioning to establish biliary drainage. Complications of long-term stenting include the formation of stones or biliary sludge above the stricture, which may be asymptomatic or present with cholangitis. Regular stent exchange every three months is essential in minimizing the risk of stone formation. Removal of all stones and sludge by basket and/or balloon extraction is mandatory before replacement of new stent(s) to minimize the risk of early reocclusion. In the future, novel endoscopic stents may become available which will improve the success rates of endoscopic therapy in patients with benign biliary strictures. The development of bioabsorbable stents, dedicated removable expandable stents, or drugeluting stents that may be coated with steroids or chemotherapeutic agents that inhibit endothelial growth or fibrosis (similar to coronary stents),41 could offer new possibilities for treatment. The management of primary sclerosing cholangitis (PSC) biliary strictures is discussed in Chapter 35. In general, the approach differs from that of postoperative strictures in several ways. The intra and extrahepatic bile ducts are usually small and do not lend themselves

to placement of multiple large-bore stents. The occlusion rate of large-bore stents is higher, such that shorter duration (4 weeks) stent placement has been advocated. Finally, the possibility that an underlying cholangiocarcinoma is present must always be considered. Therefore, tissue sampling is crucial during the management of PSC patients. At the present time there are no studies that have addressed cost-effectiveness of endoscopic therapy compared to surgical therapy. In conclusion, an endoscopic attempt at management of postoperative bile duct strictures should be undertaken as a first-line treatment in most instances. An aggressive approach placing multiple stents improves the results of endoscopic therapy. Surgical reconstruction should be considered for complete transection of the bile duct, when endotherapy fails, and following stricture recurrence. The role of SEMS in benign biliary strictures is not yet clearly defined due to variable results and small numbers, and is currently not recommended. In patients with biliary strictures secondary to chronic pancreatitis, SEMS may be considered as an alternative to surgery in patients who are considered to be poor surgical candidates.

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Chapter 30 Benign Biliary Strictures

25. Davids PHP, Tanka AKF, Rauws EAJ. Benign biliary strictures. Surgery or Endoscopy? Ann Surg 1993; 217:237–243. 26. Dumonceau JM, Deviere J, Delhaye M, et al. Plastic and metal stents for postoperative benign bile duct strictures: the best and the worst. Gastrointest Endosc 1998; 47:8–17. 27. Csendes A, Diaz C, Burdiles P, et al. Indications and results of hepaticojejunostomy in benign strictures of the biliary tract. Hepatogastroenterology 1992; 39:333–336. 28. Frattaroli FM, Reggio D, Guadalaxara A, et al. Benign biliary strictures: a review of 21 years of experience. J Am Coll Surg 1996; 183:506–513. 29. Schwartz DA, Petersen BT, Poterucha JJ, et al. Endoscopic therapy of anastomotic bile duct strictures occurring after liver transplantation. Gastrointest Endosc 2000; 51:169–174. 30. Morelli J, Mulcahy HE, Willner IR, et al. Long-term outcomes for patients with post-liver transplant anastomotic biliary strictures treated by endoscopic stent placement. Gastrointest Endosc 2003; 58:374–379. 31. Rossi A, Grosso C, Zanasi G, et al. Long-term efficacy of endoscopic stenting in patients with stricture of biliary anastomosis after orthotopic liver transplantation. Endoscopy 1998; 30:360–366. 32. Mahajani RV, Cotler SJ, Ulzer MF. Efficacy of endoscopic management of anastomotic biliary strictures after hepatic transplantation. Endoscopy 2000; 32:943–949. 33. Cahen DL, van Berkel AM, Oskam D, et al. Long-term results of endoscopic drainage of common bile duct strictures in chronic pancreatitis. Eur J Gastroenterol Hepatol 2005; 17:103–108.

34. Kahl S, Zimmermann S, Glasbrenner B, et al. Treatment of benign biliary strictures in chronic pancreatitis by self-expandable metal stents. Dig Dis 2002; 20:199–203. 35. van Berkel AM, Cahen DC, Van Westerloo DJ, et al. Self-expanding metal stents in benign biliary strictures due to chronic pancreatitis. Endoscopy 2004; 36:381–384. 36. O’Brien SM, Hatfield AR, Craig PI, et al. A 5-year follow-up of selfexpanding metal stents in the endoscopic management of patients with benign bile duct strictures. Eur J Gastroenterol Hepatol 1998; 10:141–145. 37. Siriwardana HP, Siriwardena AK. Systematic appraisal of the role of metallic endobiliary stents in the treatment of benign bile duct stricture. Ann Surg. 2005 Jul; 242(1):10–19. 38. Dumonceau JM. Systematic appraisal of the role of metallic endobiliary stents in the treatment of benign bile duct stricture. Ann Surg. 2006 Jul; 244(1):164–165. 39. Baron TH, Poterucha JJ. Insertion and removal of covered expandable metal stents for closure of complex biliary leaks. Clin Gastroenterol Hepatol. 2006 Mar; 4(3):381–386. 40. Pozsar J, Sahin P, Laszlo F, et al. Endoscopic treatment of sphincterotomy-associated distal common bile duct strictures by using sequential insertion of multiple plastic stents. Gastrointest Endosc. 2005 Jul; 62(1):85–91. 41. Degertekin M, Serruys PW, Foley DP. Persistent inhibition of neointimal hyperplasia after sirolimus-eluting stent implantation: long-term (up to 2 years) clinical, angiographic, and intravascular ultrasound follow-up. Circulation 2002; 106:1610–1613.

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31

APPROACH TO CLINICAL PROBLEMS

Biliary Surgery Complications including Transplantation Claudio Navarette, Eduardo Valdivieso and Jaquelina M. Gobelet

Endoscopic management of iatrogenic biliary complications continues to be technically challenging for the therapeutic endoscopist. In this area, some progress has been reported and ERCP constitutes a valuable tool. This chapter deals with the endoscopic treatment of biliary leaks after laparoscopic cholecystectomy (LC) or liver resection. Consideration of ERCP in the treatment of complications following liver transplantation is also described. The treatment of late strictures will not be discussed in detail as this particular topic is described in Chapter 30 of this textbook. Currently, medical literature does not provide much information from experimental trials, and a systematic approach to guide decisions about the use of ERCP as a treatment for biliary surgery complications has not been clearly established. Indications and contraindications of ERCP in the treatment of a biliary injury are based only on empirical evidence provided by highly experienced groups. This chapter will provide a tool to determine when and how endoscopic management could be the treatment of choice for an individual patient with a complicated biliary surgery.

PHYSIOLOGICAL BASIS OF ERCP TECHNIQUES IN TREATING BILIARY SURGERY COMPLICATIONS ERCP is useful in the treatment of biliary surgery complications by means of different physiological mechanisms:

Decreasing the pressure inside the biliary ducts The first aim of endoscopic therapy is to reduce sphincter of Oddi tone. Endoscopic sphincterotomy (ES) can achieve this, favoring transpapillary bile flow and controlling the drainage trough the leak site. As ES usually does not cut the sphincter completely, a stent is often used concomitantly, passing through the papilla in order to bypass the muscular activity of the remnant sphincter (Fig. 31.1).

Bypassing bile flow trough the leak site In addition to reducing intraductal pressure, the stent bypasses the bile toward the papilla and reduces the flow through the leak site. This fact, contributes indirectly to the closure of the leak (Fig. 31.2). Considering the low morbidity associated with stents, we recommend the combined use of ES and stenting to minimize intrabiliary pressure. Traditionally, plastic stents have been used for this purpose. However, in a recent report, bioabsorbable self-expanding stenting appears to be a promising option both because of larger diameter and elimination of need for removal.1

Nasobiliary tubes can be an alternative to stenting in the treatment of biliary leaks after laproscopic cholecystectomy (LC). Advantages include precluding need for sphincterotomy, easy removal, and interval cholangiograms to assess leak resolution.2 However, because of patient discomfort, we do not routinely use nasobiliary tubes as an alternative to stents in the treatment of biliary leaks.

Sealing the leak In case of bilio-pleural fistula, where negative pressure sucks bile into the thoracic cavity, application of sealants is often necessary to facilitate control of the abnormal flow. ERCP can be an expeditious way to apply sealants to a leak as described by Seewald, who reported his preliminary experience using endoscopically injected glue to control fistula output.3 Endoscopic cyanoacrylate glue occlusion is an effective method to occlude the lumen of a disrupted duct. As total lumenal closure is not feasible for lesions of major ducts, the use of this resource is limited to peripheral injuries of the biliary tree and may be potentially useful in peripheral pancreatic fistulas.4 However, because of potential risk of pulmonary embolism, we have used sealants to occlude biliary fistulas only for highly selected peripheral cases of bilio-pleural fistulas, or bilio-peritoneal fistulas that have been refractory to combined treatment with ES and plastic prostheses (Fig. 31.3).

Dilating the stricture and maintaining intraductal flow Benign biliary strictures require dilatation followed by multiple stent placements and exchanges. This therapy, which is described in Chapter 30, offers a minimally invasive alternative to hepaticojejunostomy in the management of postoperative biliary strictures.5 Biofilm accumulation in the prosthesis and secondary loss of patency require repeated exchanges. This constitutes a problem not only because of infection risk related to bile flow obstruction, but also because of patient discomfort and the morbidity related to repetitive procedures. In this setting, bio-absorbable biliary stents, as well as self-expanding metal prostheses, have been recently described with promising, but preliminary results.6 As noted above, there are several physiological mechanisms that are potentially efficacious for treatment of a biliary injury by means of an ERCP. Unfortunately, there are no randomized clinical trials to define the ideal mechanism or combined strategy for the successful endoscopic resolution of an injury of the biliary tree. In general, we suggest that pressure inside the biliary ducts should be 335

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BOX 31.1 PHYSIOLOGICAL BASIS FOR ENDOSCOPIC MANAGEMENT OF BILIARY SURGERY COMPLICATIONS • Decreasing pressure inside the biliary ducts • Bypassing bile flow through the leak site • Sealing the leak • Dilatation of a stricture • Maintaining bile flow

reduced as much as possible, using not only ES but also stent placement. In selected cases of peripheral leak, endoscopic cyanoacrylate application may be considered as adjunctive therapy (Box 31.1). Fig. 31.1 Endoscopic sphincterotomy and transpapillary stenting in a patient with a tear of the common bile duct. Post-stenting, the biliary drainage is improved and the pressure inside the biliary ducts is reduced.

A

B

Fig. 31.2 A Common bile duct tear in a 52-year-old woman after a laparoscopic cholecystectomy. B Final position of the stent bridging the leak site.

A

B

ERCP FOR TREATMENT OF COMPLICATIONS FOLLOWING LAPAROSCOPIC CHOLECYSTECTOMY Laparoscopic cholecystectomy has become the first choice for the treatment of symptomatic cholecystolithiasis. A different assortment of surgical complications such as leaks from the cystic duct or injuries to aberrant ducts have been described as surgical teams gain experience and classical contraindications to LC have been progressively eliminated. Strasberg classified biliary injuries during LC according to anatomical considerations and their relationship to treatment.7 We recommend this classification as it identifies lesions morphologically amenable to endoscopic management and it has been widely adopted by surgical groups (Fig. 31.4). The majority of biliary injuries are suitable for endoscopic management. They correspond to small tears and leaks that are easily misidentified during surgery. Rarely, transections of the Common Bile Duct (CBD) have been reported and are generally not amenable to endoscope therapy.8 An evidence-based approach cannot be used to determine what type of bile duct lesion is going to improve by means of an ERCP. Currently, indications and contraindications for endoscopic procedures are determined by experts, supported by factors such as: nature and magnitude of the injury, flow trough the leak, timing of the diagnosis postoperatively, presence of sterile or infected bilomas and surgical risk associated with operative repair.

Nature and magnitude of the biliary injury Fig. 31.3 68-year-old man after segmental liver resection. A Central biliary leakage treated with Hystoacryl injection. B After emptying of contrast, radiopaque cyanoacrylate is noted to occlude the injured duct. 336

Continuity of the injured bile duct is the most important factor concerning the nature and magnitude of the injury and its relation to endoscopic management. If there is continuity of the injured bile duct (Fig. 31.4 types A, C and D), ERCP is considered as primary therapy. Otherwise,

Chapter 31 Biliary Surgery Complications including Transplantation

A

>2cm

<2 cm

E1

E2

B

C

D

E3

E4

E5

Fig. 31.4 Classification of biliary injury following cholecystectomy. Type A is a transection of small bile ducts that enter the liver bed or the cystic duct. Type B and C almost always involve aberrant right hepatic ducts. Type D is a tear or burn of the CBD. Type E implies transection or resection of the CBD. Type A, C, D and some E injuries frequently cause bilomas of fistulas requiring external drainage. Type B may or may not require subsequent treatment. (Redrawn with permission from Strasberg SM, Hertl M, Soper NJ. An analysis of the problem of biliary injury during laparoscopic cholecystectomy. J Am Coll Surg 1995 Jan; 180(1):101–25 © 1995 The American College of Surgeons.)

endoscopic therapy is generally precluded for injuries with complete bile duct transection and the presence of clips at the distal stump or lack of continuity between segments (Fig. 31.4 type E).9,10 If the CBD has been resected, surgery is always necessary to establish the lost continuity of the duct. ERCP is helpful only to determine the type and extent of the injury and a complementary magnetic resonance cholangiogram is usually required to define proximal biliary anatomy. In case of complete transection without resection of the CBD, surgical reconstruction is also almost always required. Even though, we have successfully treated some patients with complete transection of the CBD by means of ERCP without the use of a simultaneous percutaneous transhepatic approach, after successful passage of a wire guide, these cases should be considered anecdotal. Complete transection of a major bile duct is a strong indication for operative repair. Only if it is possible to adequately traverse the lesion and decompress the entire biliary system with stents, should exclusive endoscopic therapy be considered.11 Aberrant ducts usually drain bile from areas of the liver directly to the gallbladder or the CBD and they uncommonly have communication to the left or right biliary system. If an aberrant damaged duct is misidentified during surgery (Fig. 31.4 type C), clinical suspicion of an iatrogenic injury will often require an ERCP. If the injured duct is visualized, it means that communication with the biliary system exists. In this case, an ERCP could be therapeutic if procedures such as ES, stenting and, occasionally, glue injection are undertaken. If the injury is not detected, other studies such as scintigraphy or magnetic resonance cholangiogram are required and resective surgery is mandatory.

Flow through the leak Clinically significant bile leak is a potentially serious complication that occurs after 0.1–0.5% of conventional open cholecystectomy. Either because of intrinsic risk or increased tendency to report complications, the shift to LC has been associated with up to a 2% incidence of bile leak. Given the large number of LC performed, the incidence of postoperative bile leaks is substantial. The most common site of leakage is the cystic duct (78%), followed by peripheral right hepatic ducts of Luschka (13%) and other sites (9%) including the common hepatic duct, CBD and T-tube insertion points.12 High output leaks were traditionally considered as an indication for surgery. However, more and more successful endoscopic treatments have been reported (Table 31.1). Shanda et al. defined a low-grade leak as a leak identified only after opacification of the intrahepatic biliary radicals with contrast and a high-grade leak as a leak observed fluoroscopically before intrahepatic opacification.12 As ERCP is generally used for diagnosis when a leak is suspected, endoscopic therapy should be attempted even for high-grade ductal leaks.

Time to diagnosis If a patient presents with a bile duct injury early or late after surgery, the treatment of choice is an endoscopic procedure. If the injury is identified during surgery, the complication should be solved during the same procedure that caused the iatrogenic lesion. 337

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Series

n

Stones

ES

Stent

ES&Stent

NT

Efficacy

Kozarek Foutch Barkum Ryan Davids Prat Himal DePalma Chow Shanda

11 23 52 50 48 26 12 64 19 204

18% 30% 22% 22% 31% 31% — 33% 16% 20%

2 4 27 6 20 15 6 25 19 75

7 6 1 13 — — — 18 — —

— 12 27 31 25 3 6 — — —

1 1 8 — 3 8 — 21 19 —

82% 100% 88% 88% 90% 70% 100% 96.9% 95% 99%

Injury

Table 31.1 Published series using an endoscopic approach to treat bile leaks n = number of patients; ES = endoscopic sphincterotomy; NT = nasobiliary tube.

However, biliary endoprostheses can be used to facilitate a correct cicatrisation of a sutured bile duct and as an alternative method of CBD drainage after a choledochorraphy.13

Collections and related septic complications The first step in the treatment of iatrogenic biliary injury is sepsis control and patient stabilization. Septic complications are mainly associated with loculated collections and their drainage is mandatory. Currently, most collections and bilomas are drained percutaneously by placing an indwelling catheter, and systemic antibiotics are administered. If percutaneous drainage is considered insufficient, minimally invasive techniques can be used to laparoscopically resolve the collection. It is important to note that the role of ERCP in the modern minimally invasive treatment of bilomas and septic collections related to biliary surgery is to diagnose and control the bile leak, while sepsis control must be the initial treatment.

Surgical risk Significant surgical risk has historically been considered to be a contraindication for conventional surgery. As a consequence, highrisk patients have helped engender the initial development of minimally invasive procedures. ERCP has not been the exception, but currently, enough evidence and experience support the safety and effectiveness of surgical endoscopy to recommend it for almost all patients in whom conventional surgery was historically considered the only alternative. Considering this complex scenario, iatrogenic lesions of the biliary tree represent serious injuries with common complications, high costs and uncertain results at late follow-up. The management of these patients is a difficult medical problem which requires the cooperation and skill-set of hepatobiliary surgeons, interventional radiologists and biliary endoscopists. It is desirable but impossible to establish a rigorous evidencebased list of indications and contraindications for ERCP in the treatment of LC complications. Instead, we propose a useful guide to identify the most appropriate clinical setting that supports the principles of endoscopic therapy and surgery in the management of iatrogenic injuries of the biliary tree. (Table 31.2). 338

Factor

ECRP

Cystic duct (Strasberg A) Luschka duct (Strasberg A) Ligated sectorial duct (Strasberg B) Non-ligated sectorial duct (Strasberg C) CBD small; tearing/burning (Strasberg D) CBD transection (Strasberg E) CBD resection (Strasberg E)

X X

Surgery

Xa Xb

X

X Xc X Xd

X X

Flow through the leak

Low-grade leak High-grade leak

Timing

Intraoperative Early postoperative Late postoperative (strictures)

X Xd

X

Associated biloma

No associated or small collection Aseptic no septated collection Infected or septated collection

X X Xe

X

Surgical risk

High-risk Non-high-risk

X Xd

X

X X

Table 31.2 Factors influencing endoscopic vs. surgical treatment of biliary tree injuries a

Absent communication to CBD branches leads to late liver resection. Only if aberrant system communicates with CBD branches. c Stenting only if continuity can be established. d ERCP seems as effective as surgery; other factors should be considered. e Drainage is priority, post-drainage, endoscopic therapy should be used. b

BOX 31.2 CONTRAINDICATIONS FOR ENDOSCOPIC TREATMENT OF COMPLICATIONS FOLLOWING LC • Injuries identified during surgery • Injuries without continuity to the CBD 1. Strasberg B 2. Strasberg C

In summary, most patients are candidates for a therapeutic ERCP if a complication from LC is suspected. As shown by our proposed algorithm (Fig. 31.5), ERCP is a widely accepted therapy for high output fistulas and low risk patients. Only type B and E lesions without continuity to the CBD, and injuries identified during surgery limit ERCP to adjuvant therapy to the classical surgical repair (Box 31.2).

ERCP AND BILIARY LEAKS AFTER HEPATIC RESECTION The true incidence of bile leaks after hepatic resection is unknown. Many series report an incidence approximating 11% but most cases correspond to minor bile leaks that often seal spontaneously. Major bile leaks are often central in origin and occur as a

Chapter 31 Biliary Surgery Complications including Transplantation

Fig. 31.5 ERCP for treatment of complications after LC. * In selected cases of septic collections and/ or biloma, open surgery is indicated as primary treatment. ** Consider open surgery only if Laparascopic management is not feasible. LC = Laparoscopic Cholecystectomy.

Biliary complication after LC

Identified during surgery

Misidentified during surgery

**

*

Septic collection/biloma

No collection

Percutaneous/ laparoscopic drainage

Failure

Success

Therapeutic ERCP

Open surgery

Failure

Success

Follow up

consequence of failure to ensure the integrity of the bile ducts at the liver hilum (Fig. 31.6). Coagulopathy is common in patients following hepatic resection. For this reason ES is sometimes avoided and cyanoacrylate is occasionally used.14 For correct occlusion with sealants, the duct must be selectively visualized by ERCP and its distal part embolized with approximately 1.5 ml of cyanoacrylate. This procedure usually effectively stops further bile leakage (Fig. 31.3). Although supported only by case reports, selective embolization is a useful adjuvant therapy to stenting procedures and its use as an exclusive treatment for stopping major bile leaks has also been described.

A

C

B

D

THE RETAINED COMMON BILE STONE A retained bile duct stone after cholecystectomy is present in up to 2.5% of LC. The effectiveness of ERCP to treat CBD stones has improved due to the increased experience of endoscopic surgeons, and the introduction of new lithotripsy devices which allow the extraction of giant and complicated stones (Fig. 31.7). To support the use of ERCP for retained CBD stones, Anward conducted a retrospective study of patients who presented with symptomatic retained stones after LC.15 The study included 25 patients who returned to the hospital with symptoms and signs suggestive of CBD stones. All 25 patients underwent ERCP and there was successful removal of stones in 16 cases, failure in five cases, and no stones in

Fig. 31.6 65-year-old male patient with a biliobronchial fistula after hydatid cyst resection treated with ES and stenting. A Biliary leakage from a left liver duct. B Leakage draining to an organized biliobronchial fistula. C Wire placed into the injured duct. D Final position of the stent. 339

SECTION 3 APPROACH TO CLINICAL PROBLEMS

A

B

Fig. 31.7 A Giant choledocholithiasis. B Multiple common bile duct stones.

four cases. A second ERCP was successful in removing retained stones in four of the five failed patients. For most patients with bile duct stones, ES continues to be the treatment of choice to facilitate extraction. We have previously described 8204 patients treated in three surgical endoscopy centers (Chile, Germany, and India); 86– 91% of all CBD stones could be extracted subsequently after ES using a Dormia basket, 4–7% required mechanical lithotripsy before removal, and 3–10% of the patients required different techniques, such as electrohydraulic lithotripsy, laser-induced shock-wave lithotripsy, or extracorporeal shock-wave lithotripsy. We concluded that endoscopic techniques can resolve the vast majority of retained stones and that less than 1% of all patients with bile duct stones still require surgical intervention.16 In summary, ERCP is an effective technique for diagnosis and treatment of retained post-LC stones. Its morbidity is acceptably low, and should be considered as an alternative to surgical CBD exploration even in cases in which choledocholithiasis is diagnosed intraoperatively.

BILIARY COMPLICATIONS ASSOCIATED WITH KEHR’S TUBE Historically, postoperative T-tube drainage has been used by biliary surgeons to prevent stasis, to decompress the biliary tree, to minimize the risk of leakage through a choledochotomy, and to prevent strictures with cicatrisation of a sutured choledochus. T-tubes also offer easy percutaneous access for cholangiography and extraction of retained stones, but this resource is only useful 4 or more weeks following surgery, when a fistulous track has been established. Despite these advantages, T-tube morbidity rates as high as 16% have been reported.17 Accidental T-tube displacement leading to CBD obstruction, bile leakage, duodenal erosion, persistent biliary fistula and excoriation of the skin, dehydration, saline depletion, cholangitis and CBD stenosis have been reported as postoperative complications secondary to T-tube use (Fig. 31.8). Such complications and the demonstrated benefit of minimally invasive methods have been associated with a tendency among laparoscopic surgeons to avoid T-tube usage. Both laparoscopic endobiliary stent placement under direct or fluoroscopic guidance with primary closure of the common bile duct (CBD), and primary closure of the CBD without drainage, have been proposed as safe and effective alternatives to Ttube placement. Isla prospectively collected 53 consecutive patients who underwent laparoscopic CBD exploration through a choledochotomy and compared the results of a group treated with T-tube placement versus a group treated with biliary stent placement and primary CBD closure. His results suggest that the use of a biliary 340

Fig. 31.8

Displaced T-tube.

endoprosthesis leads to lower morbidity, shorter hospital stay, less postoperative discomfort and earlier return to full activities.13 If a T-tube is placed, a postoperative cholangiogram will show the presence of residual retained stones, but it is always necessary to wait at least four weeks before percutaneous extraction or tube withdrawal. If accidental tube dislodgement occurs, we recommend attempting guidewire passage through the early fistulous track in order to reach the CBD and place a new tube. If this is not possible, an ES with stent placement will be necessary for treatment of the remnant bile leak. Otherwise, if an endoprosthesis has been placed as an alternative to a T-tube, early ERCP is possible, and with the use of a small catheter passed through the stent, a cholangiogram is readily obtained. If stones are not found the prosthesis can be removed. In the case of retained stones, a precut ES is performed over the prosthesis which minimizes pancreatic duct injury and leads to an inherently safer stone extraction. Even though prosthesis insertion during surgery mandates a postoperative ERCP, we prefer this alternative because of our ability to remove retained stones more safely and the poor quality of life related to the T-tube. Wani studied the use of an endonasobiliary drainage tube as an alternative to the T-tube for postoperative, intraductal drainage. His paper reviewed 20 patients who underwent closure of the common duct over an endonasobiliary tube without any difficulty.18 None of the patients experienced biliary complications such as bile leak, biliary peritonitis, biliary fistula, pancreatitis or cholangitis. The tubes were removed between days 6 and 8 and the length of the postoperative hospital stay varied from 7 to 15 days. We do not use this alternative because of possible patient discomfort and need for prolonged hospitalization.

SUMP SYNDROME Even though side-to-side choledochoduodenostomy is a commonly performed operation, postoperative biliary “sump syndrome” is an unusual complication. Caroli-Bosc analyzed 30 cases of sump

Chapter 31 Biliary Surgery Complications including Transplantation

Fig. 31.10 Dilatation of anastomotic stricture through a subcutaneously placed afferent limb in a patient with choledochojejunostomy.

Fig. 31.9 Sump syndrome. Food debris and calculi in the distal choledochus; (arrow) note Dormia’s basket passed through a choledochoduodenostomy.

syndrome and described the clinical presentation and the outcome of endoscopic sphincterotomy.19 The median clinical latency was five years and the median delay between surgery and diagnosis six years. Abdominal pain with fever was the main symptom and hepatic abscesses, and acute pancreatitis were also noted. Liver function tests were abnormal in 79% of cases. Endoscopic sphincterotomy appeared to be a safe, reliable treatment and symptom recurrence post-ES has not been reported. Following an ES, food debris and calculi can be removed from the biliary sump (Fig. 31.9). As a consequence of debris and stones impacted within the sump, catheterization of the papilla is sometimes difficult. In those instances, a wire should be advanced through the choledochoduodenostomy to reach the sump and cross the papilla in an antegrade way. Once the wire is placed in the duodenal lumen, the duodenoscope is withdrawn and the wire is pushed at the same time to release it from the endoscope’s channel. With the wire entering through the patient’s mouth and crossing the choledochocholedostomy and the papilla, the duodenoscope is introduced again with a snare in order to grip the guidewire and pull it out through the accessory channel of the duodenoscope. Finally, the papillotome is inserted endoscopically over the guidewire allowing ES in almost all cases. Alternatively, the wire can be grasped with a polyp snare and pulled through the endoscope channel, a so-called “internal rendezvous” procedure.

POST-CHOLECYSTECTOMY SYNDROME Endoscopy plays an important role in diagnosis and treatment of the post-cholecystectomy syndrome (PCS). In our experience, the vast majority of PCS can be attributed to organic causes and can be effectively treated. This experience is mirrored in a retrospective

study, in which Zhou described ERCP in the management of 371 patients with PCS.20 ERCP is a useful tool for both diagnosis and treatment of PCS. Patients found to have choledocholithiasis can be subjected to endoscopic stone extraction, those with papillary inflammatory stricture or sphincter of Oddi dysfunction to ES, and those with papillary or hepatobiliary tumor to endoscopic biliary endoprosthesis placement.

DILATATION OF BILIARY STRICTURES THROUGH A SUBCUTANEOUSLY PLACED AFFERENT LIMB IN PATIENTS WITH A CHOLEDOCHOJEJUNOSTOMY Until the development of minimally invasive procedures to access hepaticojejunostomy anastomoses, reoperation was needed for anastomotic strictures or retained stones. Endoscopic techniques have been described which can replace the radiological approach using a combined technique that includes endoscopy to reach the stricture both to guide balloon dilatations but also to allow directed stricture biopsy, strictureplasty, and injection of depot corticosteroids such as triamcinolone. Using local anesthesia, a small incision is performed over the subcutaneous limb and a minimally invasive access to the lumen is established. With a front-viewing endoscope, the hepaticojejunostomy is easily reached through a subcutaneously placed afferent limb. If malignancy is suspected, biopsies can be taken to confirm the diagnosis or in case of a benign stricture, different sized balloons can be used to effect dilatation. By means of a precut ES, several radial cuts can facilitate dilatation (Fig. 31.10). Local injection of depot corticosteroids into benign esophageal strictures has been proven to maintain the effects of bougienage or balloon dilatation. This resource has not been proven for biliary strictures and a single pilot trial which included eight patients with CBD strictures has been published.21 Given the absence of strong evidence demonstrating efficacy, we do not use corticosteroids for the treatment of CBD strictures as an adjuvant to multiple stent therapy. However, we have used injection of two 10 mg doses of triamcinolone into the stricture site with a 341

SECTION 3 APPROACH TO CLINICAL PROBLEMS

sclerotherapy needle to improve late results of balloon dilatation and strictureplasty when treating selected benign anastomotic stenoses managed endoscopically through a subcutaneous limb.

SPECIAL CONSIDERATIONS FOR LIVER TRANSPLANTATION

LATE COMPLICATIONS

EARLY COMPLICATIONS

Biliary complications are important causes of early and late postoperative morbidity and mortality following orthotopic liver transplantation (OLT) and are present in up to 20% of the patients.22 The most common complications in OLT are strictures, bile leaks, stones and sphincter of Oddi dysfunction (Table 31.3). Reconstruction following OLT has an important relationship to the treatment of biliary complications. The continuity of donor bile ducts with the intestinal tract is performed as either an end-to-end choledochocholedochostomy or as a Roux-en-Y reconstruction with an end-to-side choledochojejunostomy. Choledochocholedochostomy anastomosis is the technique of choice because it is simpler, has a lower complication rate, preserves sphincter of Oddi function and allows retrograde evaluation by means of an ERCP. Roux-en-Y reconstruction with an end-to-side choledochojejunostomy is the reconstruction of choice in children, and in adults with biliary duct conditions such as sclerosing cholangitis, or in cases of different bile duct diameters between the donor and recipient. As previously described, a subcutaneously placed afferent limb of a choledochojejunostomy can be used to perform a minimally invasive access to the transplanted biliary ducts and recent data suggest that doubleballoon enteroscopes or Shape-LockTM overtubes facilitate ERCP in patients with Roux anatomy. The clinical presentation of post-liver transplant bile duct complications is often subtle. The classical right upper quadrant abdominal pain is absent due to hepatic denervation and the only clue for

Bile leaksa

Anastomotic siteb Cystic duct Accessory bile ducts “T” tube tract Incidental intrahepatic injury Cut surface of the liverc Migrated T-tube

Early strictures

Mismatched bile duct diameters Technical errors

Late strictures

Anastomotic Nonanastomotic

Cholangitis Filling defects

Choledocholithiasis Sludge Biliary cast syndrome

Ampullary obstruction

Spinchter of Oddi dysfunction Stenosis

Recurrent biliary disease

Recurrent sclerosing cholangitis Recurrent malignant neoplasms

Table 31.3 Biliary complications after liver transplantation a

Septic related collections must be appropriately managed. Thrombosis of the hepatic artery should be ruled out. c Only in live-donor liver transplantation. b

342

the diagnosis is commonly an asymptomatic increase in the baseline serum transaminases or bilirubin levels. Even in the presence of severe obstruction, bile duct dilatation may not be present early in the transplanted liver. Moreover, common, non-invasive examinations often lack the sensitivity to detect mild but clinically significant sources of biliary obstruction. If there is a clinical suspicion of biliary obstruction or leak following OLT, an early cholangiogram is needed for definitive diagnosis. The use of T-tube splinting of the anastomosis allows a prompt evaluation of the biliary anatomy during the early postoperative period, but has been associated to a higher rate of complications related to biliary sludge, migration of the tube, and a higher incidence of bile leak.23 Moreover, there is an increased tendency to avoid T-tubes, not only because of complications, but also because it doesn’t help in the treatment of identified abnormalities, found in up to 80% of suspicious cases. ERCPs have been reported to be normal in only 15% of symptomatic liver transplant patients.24 The early recognition and prompt treatment of most biliary complications after OLT, has resulted in a clear recognition that endotherapy is an effective tool to prevent unnecessary surgical re interventions and improve long-term graft and patient survival. The use of endoscopy for biliary complications after OLT is influenced by the type of biliary reconstruction, the use of “T” tubes and the availability of subcutaneously placed limbs (Fig. 31.11).

Bile leaks and fistulas associated with liver transplantation OTL has been associated with numerous leakage sites, including the anastomosis, cystic duct, the “T” tube tract, and accessory conduits. Endoscopic management of bile leaks after transplantation follows the same principles described for the treatment of bile leaks secondary to LC or biliary surgery. As a general rule, drainage of a related fluid collection, ES, and stenting must be used for all cases. It is important to note that an early nonanastomotic leak usually means vascular insufficiency, and therefore thrombosis of the hepatic artery must be ruled out. Furthermore, in live-donor transplantation, leaks from the cut surface of the liver are common, but most cases close spontaneously and rarely need endoscopic treatment. If a “T” Tube cholangiogram identifies a minor leak, it can be conservatively managed leaving the tube in place. Only refractory cases need endoscopic treatment (Fig. 31.11).

Strictures associated with liver transplantation Strictures are the most common complication associated with OTL. They can be divided into early (within 60 days of transplantation), subacute (between 60 days and 1 year of transplantation) and late. Early strictures are mainly associated with technical errors at the anastomosis, while subacute and late strictures are often the consequence of vascular insufficiency. This classification is significant because if transient narrowing in a duct-to-duct connection appears within the first 30–60 days after transplantation, it is likely a consequence of postoperative edema and inflammation. These patients respond very well to balloon dilatation and temporary stent placement (3 months). Repeated procedures are required uncommonly.22 Anastomotic strictures identified during the first postoperative year

Chapter 31 Biliary Surgery Complications including Transplantation

Biliary complication after OLT

Choledochocholedochostomy

Normal

Choledochojejunostomy

“T” tube in situ

No “T” tube in situ

Subcutaneous limb

No subcutaneous limb*

“T” tube cholangiogram

ERCP

Endoscopic treatment

Percutaneous procedure

Abnormal**

Failure

Success

Open surgery

Success

Failure

Success

Open surgery

Failure

Open surgery

Follow up

Fig. 31.11 Role of endoscopy in the treatment of biliary complications after orthotopic liver transplant (OLT). * Endoscopic therapy can be attempted when trans-oral access to hepaticojejunostomy is feasible. **Abnormal “T” tube cholangiogram usually leads to ERCP. Minor leaks can be conservatively managed by leaving the tube in place.

show excellent response to short-term stent placement (3–6 months), but these patients require long-term and repeated endoscopic treatment as strictures may recur years after the treatment. Late strictures usually respond well to initial balloon dilatation and temporary stent placement (3 months), but relapse rates can reach 40% leading to a more complex treatment which includes repetitive balloon dilatation and long-term (12–24 months) therapy using multiple (up to three) large diameter stents. Except when the stricture compromises the hilum, nonanastomotic strictures are difficult to distinguish on the basis of cholangiography. A more difficult endoscopic treatment should be expected as nonanastomotic strictures are multiple and ischemic in nature. In fact, up to 50% of patients with nonanastomotic strictures require a new transplant or die despite multiple attempts using balloon dilatation, debris removal, and stenting. It is important to note that any ischemic injury that involves a large portion of intrahepatic bile ducts is associated with poor graft survival and is best managed by repeated transplantation.22

Filling defects and biliary cast syndrome The differential diagnosis of filling defects after OLT includes stones, blood clots, debris, sludge, and casts. Filling defects can appear as

an isolated finding, but frequently stones, sludge and casts management is complementary to stricture therapy. An unusual form of massive cast filling of the proximal bile ducts is the biliary cast syndrome. This incompletely explained disease has been associated with ischemic events and is often accompanied by strictures which can include diffuse stricturing of the hilum. ERCP plays an important role in the treatment of this entity. Baron et al. reported a severe case which was endoscopically treated, suggesting that even when massive compromise is present, combined therapy of stricture treatment and biliary toilette can yield good results.25 (Fig. 31.12)

Endoscopic management of recurrent biliary disease after liver transplantation Sclerosing cholangitis is a benign disease that can recur in a transplanted liver. In fact, there is a high risk of anastomotic stricture after OLT for this entity. As Roux-en-Y reconstruction with an endto-side choledochojejunostomy is the reconstruction of choice in case of sclerosing cholangitis, for the most part, an endoscopic approach can be done only if an afferent limb has been placed subcutaneously. With this anatomy, balloon dilatation, strictureplasty, 343

SECTION 3 APPROACH TO CLINICAL PROBLEMS

A

C

B

D

Fig. 31.13 Strictureplasty of an hepaticojejunostomy undertaken through a subcutaneously placed limb. Note “mucosectomy” cap on tip of the endoscope.

Fig. 31.12 Biliary cast syndrome: Successful endoscopic treatment. A A large filling defect was found in the common hepatic duct proximal to the anastomosis with extension into the intrahepatic system. B Endoscopic biliary sphincterotomy was performed followed by balloon retrieval of a large biliary cast. C Immediate post extraction cholangiogram was markedly improved. D The cholangitis resolved, but the patient developed recurrent biliary obstruction 3 months later. ERCP demonstrated nonanastomotic narrowing at the bifurcation requiring repeated endoscopic and percutaneous therapy. (Reproduced with permission from Baron TH, Yates RM, III, Morgan DE, et al. Biliary cast syndrome: successful endoscopic treatment. Gastrointest Endosc 2000 Jul; 52(1):78–79.)

stenting and even injection of depot glucocorticoids can be undertaken as described previously (Fig. 31.13). Liver transplantation for malignancies is still a controversial issue. Many centers worldwide perform OLT for hepatocellular carcinoma associated with liver cirrhosis, liver metastases from neuroendocrine tumors and epithelioid hemangio-endothelioma. This setting is potentially associated with bile duct obstruction due to local recurrence. Endotherapy is a well-recognized entity for the palliation of malignancies that obstruct bile flow and these techniques, to include

self-expandable metal stent (SEMS) placement, can be expeditiously applied in the treatment of malignant obstruction after OLT. In view of the minimal morbidity and the proven efficacy, we believe that for biliary complications after OLT, endoscopic management should be considered as initial management before either percutaneous or surgical treatment. If endoscopic therapy fails, if patients have multiple intrahepatic strictures, or if a Roux-en-Y hepaticojejunostomy has been done without a subcutaneously placed afferent limb, re-operation should be considered.

SUMMARY The morbidity of endoscopic treatment of biliary surgery complications is well documented. However, these have approximated 1.5% in one large series, an incidence lower than operative morbidity. Complications are mainly composed of post-ERCP pancreatitis and duodenal perforations which can generally be managed by conservative therapy; surgery is rarely required. Mortality has not been reported, in the largest series to date.12 As mentioned throughout the chapter, the safety and effectiveness of endoscopy in treating the complications of biliary surgery and liver transplantation have become firmly established. These minimally invasive techniques have complemented and supplemented classic surgery, but with lower morbidity, mortality and metabolic impact.

REFERENCES 1.

Ginsberg G, Cope C, Shah J, et al. In vivo evaluation of a new bioabsorbable self-expanding biliary stent. Gastrointest Endosc 2003 Nov; 58(5):777–784. 2. Elmi F, Silverman WB. Nasobiliary tube management of postcholecystectomy bile leaks. J Clin Gastroenterol 2005 May; 39(5):441–444. 344

3. Seewald S, Groth S, Sriram PV, et al. Endoscopic treatment of biliary leakage with n-butyl-2 cyanoacrylate. Gastrointest Endosc 2002 Dec; 56(6):916–919. 4. Seewald S, Brand B, Groth S, et al. Endoscopic sealing of pancreatic fistula by using N-butyl-2-cyanoacrylate. Gastrointest Endosc 2004 Apr; 59(4):463–470.

Chapter 31 Biliary Surgery Complications including Transplantation

5. Fogel EL, Sherman S, Park SH, et al. Therapeutic biliary endoscopy. Endoscopy 2003 Feb; 35(2):156–163. 6. van Berkel AM, Cahen DL, van Westerloo DJ, et al. Self-expanding metal stents in benign biliary strictures due to chronic pancreatitis. Endoscopy 2004 May; 36(5):381–384. 7. Strasberg SM, Hertl M, Soper NJ. An analysis of the problem of biliary injury during laparoscopic cholecystectomy. J Am Coll Surg 1995 Jan; 180(1):101–125. 8. Csendes A, Navarrete C, Burdiles P, et al. Treatment of common bile duct injuries during laparoscopic cholecystectomy: endoscopic and surgical management. World J Surg 2001 Oct; 25(10):1346–1351. 9. Parlak E, Cicek B, Disibeyaz S, et al. Treatment of biliary leakages after cholecystectomy and importance of stricture development in the main bile duct injury. Turk J Gastroenterol 2005 Mar; 16(1):21–28. 10. Kaffes AJ, Hourigan L, De LN, Impact of endoscopic intervention in 100 patients with suspected postcholecystectomy bile leak. Gastrointest Endosc 2005 Feb; 61(2):269–275. 11. Baron TH, Feitoza AB, Nagorney DM. Successful endoscopic treatment of a complete transection of the bile duct complicating laparoscopic cholecystectomy. Gastrointest Endosc 2003 May; 57(6):765–769. 12. Sandha GS, Bourke MJ, Haber GB, et al. Endoscopic therapy for bile leak based on a new classification: results in 207 patients. Gastrointest Endosc 2004 Oct; 60(4):567–574. 13. Isla AM, Griniatsos J, Karvounis E, et al. Advantages of laparoscopic stented choledochorrhaphy over T-tube placement. Br J Surg 2004 Jul; 91(7):862–866. 14. Kiltz U, Baier J, Adamek RJ. [Selective embolization of a bile leak after operative resection of an echinococcal cyst]. Dtsch Med Wochenschr 1999 May 28; 124(21):650–652. 15. Anwar S, Rahim R, Agwunobi A, et al. The role of ERCP in management of retained bile duct stones after

16.

17.

18.

19.

20.

21.

22.

23.

24.

25.

laparoscopic cholecystectomy. N Z Med J 2004 Oct 8; 117(1203): U1102. Seitz U, Bapaye A, Bohnacker S, et al. Advances in therapeutic endoscopic treatment of common bile duct stones. World J Surg 1998 Nov; 22(11):1133–1144. Martin IJ, Bailey IS, Rhodes M, et al. Towards T-tube free laparoscopic bile duct exploration: a methodologic evolution during 300 consecutive procedures. Ann Surg 1998 Jul; 228(1):29–34. Wani MA, Chowdri NA, Naqash SH, et al. Primary closure of the common duct over endonasobiliary drainage tubes. World J Surg 2005 Jul; 29(7):865–868. Caroli-Bosc FX, Demarquay JF, Peten EP, et al. Endoscopic management of sump syndrome after choledochoduodenostomy: retrospective analysis of 30 cases. Gastrointest Endosc 2000 Feb; 51(2):180–183. Zhou PH, Liu FL, Yao LQ, et al. Endoscopic diagnosis and treatment of post-cholecystectomy syndrome. Hepatobiliary Pancreat Dis Int 2003 Feb; 2(1):117–120. Wehrmann T, Schmitt T, Caspary WF, et al. [Local injection of depot corticosteroids in endoscopic therapy of benign bile duct strictures]. Z Gastroenterol 2000 Mar; 38(3):235–241. Thuluvath PJ, Pfau PR, Kimmey MB, et al. Biliary complications after liver transplantation: the role of endoscopy. Endoscopy 2005 Sep; 37(9):857–863. Qian YB, Liu CL, Lo CM, et al. Risk factors for biliary complications after liver transplantation. Arch Surg 2004 Oct; 139(10):1101–1105. Thuluvath PJ, Atassi T, Lee J. An endoscopic approach to biliary complications following orthotopic liver transplantation. Liver Int 2003 June; 23(3):156–162. Baron TH, Yates RM, III, Morgan DE, et al. Biliary cast syndrome: successful endoscopic treatment. Gastrointest Endosc 2000 Jul; 52(1):78–79.

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32

APPROACH TO CLINICAL PROBLEMS

ERCP for the Acute and Chronic Complications of Pancreatic Surgery James J. Farrell and David L. Carr-Locke

Types of pancreatic surgery performed for benign and malignant pancreatic diseases include pancreaticoduodenectomy (Whipple, classic and pylorus preserving), distal pancreatectomy (tail resection), lateral pancreaticojejunostomy (Puestow and related procedures), and duodenum preserving local resection of the pancreatic head (Beger and Frey procedures).1–6 This review will focus predominantly on the role of ERCP in patients who have undergone pancreaticoduodenectomy. The role of ERCP following other types of surgery are discussed in detail in Chapter 24. Although most often performed for malignant disease (including pancreatic cancer, ampullary cancer and duodenal cancer), pancreaticoduodenectomy is increasingly being performed for management of benign disease (e.g. chronic pancreatitis, premalignant pancreatic cystic neoplasms) (Table 32.1).7 For example, in one study, there was an increasing proportion of patients undergoing pancreaticoduodenectomy for intraductal papillary mucinous neoplasia (IPMN) compared with pancreatic ductal adenocarcinoma over a 10 year period.8 Due to this shift in indications and the improved postoperative survival of patients with cancer undergoing this operation, a greater proportion of these patients are surviving longer. Consequently, there has been an increase in both short-term and long-term postoperative complications requiring intervention. Distal pancreatectomy is performed for resection of both malignant and premalignant pancreatic diseases. It can be complicated by the development of pancreatic duct leak, which is most often treated conservatively by external management of the leak. However, pancreatic duct stenting may help in healing pancreatic duct leaks that fail medical treatment. Prophylatic placement of pancreatic duct stent to prevent development of a postoperative pancreatic duct leak after a distal pancreatectomy has also been suggested, but is not practiced widely (Fig. 32.1).9 Lateral pancreaticojejunostomy (Puestow procedure) is performed for management of symptomatic chronic pancreatitis in setting a dilated main pancreatic duct. Endoscopists are frequently asked to perform ERCP to assess patency of the pancreaticojejunal anastomosis when symptoms recur after surgery. If the pancreaticojejunal anastomosis is found to be stenosed, endoscopic dilatation and stent placement can be performed (Fig. 32.2).

ROLE OF ERCP IN PREVENTING POST PANCREATIC SURGERY COMPLICATIONS Specific avoidance of preoperative ERCP may be instrumental in preventing postoperative pancreatic surgical complications. Because obstructive jaundice can cause defects in hepatic, renal, and immune function, it was long believed that preoperative relief of biliary obstruction would correct these defects and decrease post-

operative morbidity and mortality rates. However, several randomized, controlled studies have proven that routine preoperative bile duct stent placement does not improve postoperative outcomes and, in fact, may increase postoperative infectious complications (Table 32.2).10–19 Though it is recommended that when operative intervention is delayed by several weeks (including in the setting of neoadjuvant therapy), or if cholangitis or pruritus occurs, a biliary stent (at least 10 French diameter) should be placed endoscopically, recent data suggests that placement of short-length expandable metal biliary stents does not interfere with pancreaticoduodenectomy and decreases the rate of cholangitis as compared to plastic biliary stents in patients receiving preoperative neoadjuvant therapy.20,21 In addition, patients found to be unresectable at the time of surgery do not require biliary bypass.22 Preoperative pancreatic duct stent placement prior to distal pancreatectomy has been shown in a small study to reduce the incidence of postoperative pancreatic duct leaks.9

SHORT-TERM COMPLICATIONS ASSOCIATED WITH PANCREATIC SURGERY Short-term complications following pancreaticoduodenectomy include anastomotic leakage (either a bile leak or a pancreatic fistula), hemorrhage, fluid or abscess collection, afferent limb obstruction, and delayed gastric emptying. Magnetic resonance cholangiopancreatography (MRCP) is becoming increasingly important in the diagnostic evaluation of patients with suspected bile or pancreatic duct leaks. Anastomotic pancreaticobiliary leaks may require intervention, including ERCP therapy. However, the potential risks associated with endoscopy in the acute post surgical setting have led to the use of interventional radiologic techniques for the management of these post surgical complications. This applies especially to biliary complications including abscess formation, bilomas, bile leaks and biliary obstruction.23,24 In a recent study, up to 44% of patient who had undergone a pancreaticoduodenectomy required interventional radiologic procedures.23 Post pancreatic surgery pancreatic duct leaks occur in 3–30% of cases. Patients present with pancreatico-cutaneous fistula, intraabdominal fluid collection, ileus or delayed gastric emptying. Expectant management may be undertaken by placement of operative drains to monitor output. Conservative management involves nutritional support with nil per os and administration of octreotide. Occasionally, re-operation or placement of percutaneous drains is required. ERCP plays a very limited role in the management of post pancreatic surgery pancreatic leaks in the early postoperative period. Before contemplating endoscopic evaluation and management of post pancreatic surgery pancreatic duct leaks, the risk of infecting a 347

SECTION 3 APPROACH TO CLINICAL PROBLEMS

Pathology Pancreatic adenocarcinoma Ampullary cancer Bile duct cancer Duodenal cancer Ampullary adenoma Pancreatic cystic neoplasm Islet cell tumor Chronic pancreatitis

UCLA (1990–2004)

JHH (1990–1999)

38 21 6 7

43 11 10 4 3 6 5 11

11 3 8

Table 32.1 Pathologies associated with panceaticoduodenectomy (%) UCLA, University of California, Los Angeles, Los Angeles, CA JHH, Johns Hopkins Hospital, Baltimore, MD

A

LONG-TERM COMPLICATIONS OF PANCREATIC SURGERY

B

Fig. 32.1 A ERCP showing a pancreatic duct leak with cyst formation after a distal pancreatectomy for chronic pancreatitis. (Image courtesy of Todd Barron, MD.) B Pancreatic duct stenting with a 7 fr pancreatic duct stent for management of pancreatic duct leak after distal pancreatectomy. (Image courtesy of Todd Barron, MD.)

A

B

Fig. 32.2 A ERCP showing an anastomotic stricturing of a lateral pancreaticojejunostomy (Peustow Procedure). (Image courtesy of Todd Barron, MD.) B Pancreatic duct stenting of the anastomotic structuring of a lateral pancreaticojejunostomy (Puestow Procedure). (Image courtesy of Todd Barron, MD.)

Study

n

Stented

Unstented

Povoski Sohn Hochwald Heslin Pisters Hodul

240 567 71 74 265 212

41 32 66 46 37 28

25 22 38 11 11 20

Table 32.2 Studies of preoperative biliary stenting in pancreatic cancer: infectious complications (%) 348

pancreatic fluid collection should be addressed. A secretin—MRCP prior to consideration of endoscopic treatment may assist in planning endoscopic treatment of the pancreatic duct leak25 and may allow determination of fistula location, degree of pancreatic ductal disruption (incomplete or complete) and the cause of obstruction (stone, main pancreatic duct stricture, anastomotic stricture), if present. Endoscopic pancreatic duct stent placement has been reported for the management of pancreatic duct leaks following pancreatic surgery.26–31 It may be used to bypass a distal obstruction of the MPD as well as for bridging a MPD leakage. Telford et al. suggest that bridging a leak is a associated with a better long-term outcome (92% vs 50%).31 The endoscopic application of N-butyl-2-cyanoacrylate glue has been successfully used in the management of distal pancreatectomy associated leaks.32

Long-term complications associated with pancreatic surgery include the development of diabetes mellitus and obstruction at either the choledochojejunostomy or the pancreaticojejunostomy. Complications of either the choledochojejunostomy or pancreaticojejunostomy may be related to either persistence or recurrence of the original disease including adenocarcinoma, IPMN and chronic pancreatitis. Occasionally, ERCP may be required for the evaluation and management of these complications. Patients with problems related to the choledochojejunostomy typically present with obstructive jaundice or recurrent cholangitis. Possible causes include benign anastomotic strictures, tumor recurrence or biliary stones. Complications of the pancreaticojejunostomy also include development of benign or malignant strictures. These may present with abdominal pain or recurrent pancreatitis. Retained, surgically placed anastomotic pancreatic stents may cause steatorrhoea or recurrent pancreatitis. Endoscopic retrieval is feasible and can result in resolution of symptoms.33 A decision to pursue ERCP in the post pancreatic surgery patient should be based on the decision to provide therapy (e.g. stent placement, removal of stones). This is best achieved by preprocedure evaluation with laboratory studies and non-invasive imaging including CT and MRCP. Although there is an increasing role for MRCP in the evaluation of such patients, therapeutic intervention is often necessary.7

UNDERSTANDING THE ANATOMY Prior to performing endoscopy in a patient who has undergone pancreaticoduodenectomy it is important to understand the exact anatomy and reconstruction in the individual patient. There are two main types of pancreaticoduodenectomy: classic and pylorus preserving.

Classic pancreaticoduodenectomy (Fig. 32.3) In the classic pancreaticoduodenectomy, the gastric antrum, head of pancreas, distal bile duct and duodenum are resected. Although there are several different techniques described, one well-accepted reconstruction creates all necessary anastomoses with a single limb of bowel. A side-to-side gastroenteroanastomosis is usually encountered endoscopically with a relatively large gastric remnant. The opening to the afferent limb which should lead to the biliary and

Chapter 32 ERCP for the Acute and Chronic Complications of Pancreatic Surgery

Fig. 32.3 Diagram of a classic pancreaticoduodenectomy. (Reproduced with permission: Feitoza AB, Baron TH. Gastrointest Endosc 2002; 55(1):75–79.)

pancreatic anastomoses is often found along the lesser curvature of the stomach. The length of the afferent limb varies according to the position of the jejunal loop relative to the mesocolon and surgeon preference. Shorter limbs (about 40 cm) may be found within antecolic anastomoses, whereas longer limbs (60 cm or more) may be found with retrocolic/antecolic combinations. Several sharp angulations are found along the afferent limb due to fixation of the limb to adjacent organs. The afferent limb ends blindly, where a pancreatic duct anastomosis may be found if an end-to-end pancreaticojejunostomy has been created. The choledochojejunostomy tends to be located approximately 10 cm proximal (endoscopically) to the pancreaticojejunostomy, along the antimesenteric border of the afferent limb. It is an end-toside anastomosis that may be difficult to find, often hidden behind a fold. The pancreaticojejunostomy may be an end-to-end or an end-toside anastomosis. The anastomosis may be performed by suturing the pancreatic ductal mucosa to the jejunal mucosa (mucosal to mucosal anastomosis), thereby creating a small opening; or by invaginating the pancreatic stump into the jejunum, with either an end-to-end or end-to-side pancreaticojejunostomy.34,35 This is known as the “dunking” anastomosis. Due to the various locations and type of anastomoses (flat with mucosa-to-mucosa; protuberant with lateral dunking) the identification and subsequent cannulation of the pancreatic duct is sometimes difficult, and may be facilitated by administration of intravenous secretin.

The pylorus-preserving pancreaticoduodenectomy (Fig. 32.4) In this variation of the Whipple procedure the antrum of the stomach, is not resected. A short proximal duodenal stump remains and is anastomosed to the jejunum as a duodenojejunostomy. After

Fig. 32.4 Diagram of pylorus-preserving pancreaticoduodenectomy. (Reproduced with permission: Feitoza AB, Baron TH. Gastrointest Endosc 2002; 55(1):75–79.)

traversing the pylorus endoscopically, a short segment of duodenal bulb is present and two openings are identified which correspond to the end-side duodenojejunostomy. Typically the opening visualized to the right in the endoscopic field leads to the afferent limb with its biliary and pancreatico anastomoses. Issues relating to length of afferent limb and the locations of the anastomoses are the same as with the classic Whipple procedure. 349

SECTION 3 APPROACH TO CLINICAL PROBLEMS

ENDOSCOPES AND ACCESSORIES Following pancreaticoduodenectomy the pancreatic and biliary anastomoses may be reached using a standard forward-viewing or sideviewing endoscope. In some patients it may be necessary to use a longer length endoscope such as a colonoscope, or even a pushenteroscope. The use of variable stiffness colonoscopes is useful in avoiding loop formation during passage of the colonoscope to the distal aspect of the limb after initial intubation. There have been reports of using oblique viewing endoscopes with elevators in the post pancreatic surgery setting.36 There is limited data on the role of double-balloon enteroscopy in accessing the afferent jejunal limb in patients with pancreaticoduodenectomy. The use of a colonoscope does not limit the range of endoscopic accessories that may be used for ERCP therapy, including standard catheters and sphincterotomes. However, most balloon catheters and stent introducing systems are not long enough. When the standard ERCP balloon catheter is not of sufficient length, using nonERCP wire-guided balloons may be an alternative. Similarly the use of a nasobiliary tube as a pusher tube may be required for stent placement. However, the absence of an elevator makes diagnostic and therapeutic manipulation more difficult. The number of available accessories for use with an enteroscope is limited.

NEGOTIATING THE ANATOMY Several technical, often time-consuming challenges are involved in performing ERCP in patients with post pancreatic surgery anatomy, especially in patients who have undergone pancreaticoduodenectomy. These include accessing and traversing the afferent jejunal limb, and the identification of the choledochojejunostomy and pancreaticojejunostomy.

Accessing and traversing the afferent limb Having detailed operative information about the surgical procedure is helpful. In addition to differentiating between a non-pylorus sparing versus a pylorus sparing operation, critical information about the length of the afferent limb and the relative location of the choledochojejunostomy and the pancreaticojejunostomy is helpful. For most patients with a pancreaticoduodenectomy, the initial endoscope of choice is a duodenoscope, as this allows the greater flexibility for the use of therapeutic instruments. Should there be failure to access the afferent limb or advance the appropriate length of the limb, a standard therapeutic channel gastroscope or colonoscope can be used. Both of these instruments allow passage of therapeutic diameter accessories. The primary goal is to identify and access the afferent limb. For patients with a standard pancreaticoduodenectomy, the afferent limb is typically off the lesser curve of the stomach. For patients with a pylorus preserving pancreaticoduodenectomy, the afferent limb is typically distal to the pylorus and in the right of the endoscopic field. Unfortunately however, the distinction between afferent and efferent limb is not always possible using these guidelines. Invariably, the more easily accessed limb is the efferent limb. Using a combination of endoscopic and fluoroscopic guidance, the chosen limb is traversed for up to 20 to 40 cm before a decision can be made about whether the correct limb has been intubated. Using fluoroscopy and demonstrating the endoscope moving in the

350

direction of the liver and the possible surgical clips associated with the choledochojejunostomy anastomosis can be enough evidence to continue forward. Often due to the acute angulation at the site of the afferent jejunal limb anastomosis initial intubation of the limb can be difficult. This is due to the need for 180 degree flexion of the endoscope to enter the limb. This tends to put excessive pressure on bowel wall by the bend of the endoscope and increases the risk of perforation. This can be corrected by “backing into” the afferent limb, whereby the endoscope is guided almost blindly into the afferent limb without excessive flexion of the endoscope, similar to the maneuver required to enter the ileum during colonoscopy. The length of the afferent limb is variable and is often surgeondependent. Typically it ranges from 20 cm up to 80 cm. Therefore a considerable length of jejunal limb needs to be traversed before deciding whether one is in the correct limb. If the efferent limb has been intubated, careful and slow withdrawal of the endoscope should be performed in order to identify and intubate the afferent limb at the level of the jejunal anastomosis. An alternative strategy to prevent repeated intubation of the efferent limb includes taking endoscopic biopsies at 10 cm and 20 cm distal to the jejunal anastomosis. The limited bleeding associated with these biopsies serves as an indicator of limb status. When the afferent limb is finally identified and intubated, care should be taken to carefully advance the endoscope. In the post surgical patient the presence of adhesions and extraluminal recurrence of malignancy increase the risk for perforation. Intermittent endoscope reduction should be performed to avoid excessive looping. Often abdominal pressure and changing the position of the patient (including to a left lateral or supine position) may facilitate passage of the endoscope to the end of the afferent limb where the hepaticojejunostomy and pancreaticojejunostomy are located. As these are post operative patients with a high risk of endoscope induced perforation, it is important to know when to stop advancing the endoscope. Occasionally information about the hepaticojejunostomy and pancreaticojejunostomy can be obtained without reaching the end of the afferent limb. The presence of a non-dilated appearing air cholangiogram on fluoroscopy, although not positive proof, favors against complete biliary obstruction (Fig. 32.5). It may also be possible to perform an occlusion contrast study by inflating an extraction balloon in the afferent jejunal limb, and allowing contrast to flow into the bile duct and pancreatic duct outlining the anatomy.

Identification of the hepaticojejunostomy The hepaticojejunostomy is typically an end-to-side anastomosis located within the last 5 to 10 cm of the afferent limb, proximal to the pancreaticojejunostomy site. When not strictured, it should be widely patent (Figs 32.6, 32.7). If not clearly visible, the endoscopist should search carefully behind jejunal folds on the antimesenteric side of the jejunum for a possible opening, and insure that the end of the afferent limb has truly been identified. The use of fluoroscopy can sometimes help locate where the anastomosis should be, either by tracing an air cholangiogram or recognizing the presence of surgical clips at the site of the hepaticojejunostomy. Often the only endoscopic evidence of a hepaticojejunostomy is a small dimple. When faced with a strictured hepaticojejunostomy anastomosis, probing the anastomosis with a wire-guided system is preferred.

Chapter 32 ERCP for the Acute and Chronic Complications of Pancreatic Surgery

A

Fig. 32.5 Fluoroscopic pancreatogram in a patient with a pancreaticoduodenectomy for chronic pancreatitis. Note the air cholangiogram (arrow).

B

Blind injection of a presumed anastomosis can lead to submucosal injection of contrast and even perforation. After access to the biliary tree has been confirmed by contrast injection, standard ERCP accessories may be used including stents, balloons and sphincterotomes (for orientation).

Identification of the pancreaticojejunostomy The pancreaticojejunostomy is more difficult to identify than the hepaticojejunostomy (Figs 32.8, 32.9). Knowledge of the operation, including the type and location of the anastomosis is important. All that may be present is a focal dimple in the region of the end of the afferent limb. The use of methylene blue spray (0.5%) may enhance the endoscopic image to locate the pancreaticojejunostomy as the pancreatic secretions create a halo of clearing of the dye. Alternatively, the use of secretin to stimulate pancreatic juice flow may help locate the opening. As with stenotic biliary orifices, wire-guided probing of the presumed pancreatic duct is preferred to blind contrast injection.

ENDOTHERAPY FOR THE POST-PANCREATIC SURGERY PATIENT The reason for obstruction at the hepaticojejunostomy or pancreaticojejunostomy anastomoses needs to be defined prior to attempted therapeutic intervention. If there is evidence of tumor recurrence, then endoscopic stent placement is adequate. If there is evidence of benign stricturing, then short-term stenting or balloon dilatation may be adequate. In all patients requiring anastomotic dilatation (e.g. hepaticojejunostomy anastomosis, pancreaticojejunostomy anastomosis), endoscopic balloon dilatation with standard biliary dilating catheters is preferable. If stenting of a biliary anastomotic stricture is required, single 10 Fr plastic biliary stents are employed and the

Fig. 32.6 A Endoscopic image of a widely patent hepaticojejunostomy. B Endoscopic image of biliary tree through the heapticojejunostomy orifice.

stricture re-evaluated after 2–5 months. If stenting of a pancreatic anastomotic stricture is required, a single 5 Fr plastic pancreatic stent is often inserted and the stricture re-evaluated after 2–4 weeks.

NOVEL APPROACHES TO ERCP IN THE POST PANCREATICODUODENECTOMY PATIENTS The use of combined interventional radiology ERCP rendezvous procedures has been described, when the endoscopist is able to

351

SECTION 3 APPROACH TO CLINICAL PROBLEMS

Fig. 32.7 Balloon occlusion cholangiogram of the biliary tree in a patient with a hepaticojejunostomy after pancreaticoduodenectomy.

Fig. 32.9 Fluoroscopic normal pancreatogram in patient with pancreaticoduodenectomy for pancreatic neoplasia. Evidence of stenotic choledochojejunostomy requiring endoscopic stenting.

duct.37 Although it provides the potential for improved access, there is limited experience with the use of double-balloon enteroscopy on post pancreaticoduodenectomy afferent jejunal limbs. The development of this technology for the management of patients after pancreatic surgery will require the development of compatible ERCP accessories.

BRIGHAM AND WOMEN’S HOSPITAL EXPERIENCE

Fig. 32.8 Endoscopic pancreaticojejunostomy stenting for pancreatic duct obstruction secondary to pancreaticojejunostomy stenosis.

reach the end of the afferent limb, but cannot obtain access to the biliary system. The percutaneous transhepatic placement of an internal-external biliary catheter can serve as a guide for the endoscopist to access the biliary tree. A combined EUS-ERCP rendezvous procedure has been described whereby EUS guided transgastric access to the pancreatic duct with placement of a wire antegrade through the pancreaticojejunostomy is followed by ERCP access to the pancreatic 352

Because of the difficulties encountered in negotiating the proximal portion of the afferent limb with an endoscope, as well as identification of the pancreatic duct opening and sometimes the bile duct opening, the overall success rate of cannulation is variable. There are limited specific data available from either the endoscopic or interventional radiology literature about the indications and outcomes (either technical or clinical) of non-operative intervention in patients undergoing biliary or pancreatic therapy after pancreatic surgery.35 One hundred and thirty-five ERCPs were performed on 61 patients after pancreatic surgery at the Brigham and Women’s Hospital between 1990 and 2000. Four endoscopists performed all the procedures, although one (DCL) was involved in the majority of cases. Surgical operations included pancreaticoduodenectomy,32 distal pancreatectomy (tail resection)11 and lateral pancreaticojejunostomy.21 Indications for surgery included neoplasia (pancreatic ductal adenocarcinoma, intraductal papillary mucinous neoplasia (IPMN), neuroendocrine tumors), chronic pancreatitis and trauma. No procedure-related limb perforations occurred. Twenty-nine patients with a pancreaticoduodenectomy underwent 56 ERCPs. Ten of these patients had a classic

Chapter 32 ERCP for the Acute and Chronic Complications of Pancreatic Surgery

29 Patients ERCP indication

Jaundice (16)

Pain (13)

Afferent limb access

15/16 (94%)

12/13 (92%)

Cholangiogram

11/15 (73%)

Pancreatogram

N/A

7/12 (58%)a 5/10 (50%)b

Table 32.3 ERCP in pancreaticoduodenectomy patients: Brigham and Women’s experience a

Choledochojejunostomy seen in all 12, but cholangiogram performed in only 7 Two of these patients had a satisfactory biliary explanation for their symptoms, hence not necessitating a pancreatic evaluation

b

pancreaticoduodenectomy, while 19 had a pylorus-preserving pancreaticoduodenectomy. Indications for surgery included neoplasia,17 chronic pancreatitis11 and trauma.1 The mean time from surgery to ERCP was 15 months (range: 1– 120 months). The mean number of ERCPs performed per patient was 1.9 (range: 1–11). Only three patients had more than three ERCP procedures performed. These were all due to recurrent stricturing of the pancreaticojejunostomy anastomosis, requiring repeated dilatation and stenting, in patients with a history of chronic pancreatitis. The indications for ERCP in patients with pancreaticoduodenectomy were jaundice16 and pain.13 Patients undergoing ERCP for evaluation of jaundice were more likely to have undergone surgery for neoplasia (14/16, 88%), compared with patients undergoing ERCP for evaluation of pain who were more likely to have undergone surgery for chronic pancreatitis (10/13, 77%) (p < 0.05). Pain in the immediate postoperative period in one patient was attributed to a bile leak (Table 32.3). Of the 16 patients undergoing ERCP for jaundice, 14 had had surgery for neoplasia, and one each had surgery for trauma or chronic pancreatitis. The afferent limb was accessed in 15/16 (94%). The reason for failure in one patient was the presence of a metal enteral stent traversing the gastrojejunostomy into the efferent limb (previously placed for malignant gastric outlet obstruction). The choledochojejunostomy was identified in 11/15 patients (73%) whose afferent limb was accessed for evaluation of jaundice. Inability to identify the choledochojejunostomy was related to an excessively long afferent limb (n = 2) or poor visualization even when the end of the afferent limb was reached (n = 2). Inability to identify the choledochojejunostomy was equally distributed amongst both types of surgical procedures (pylorus-preserving pancreaticoduodenectomy (n = 2) and classic pancreaticoduodenectomy (n = 2)). For patients being evaluated for jaundice and in whom the choledochojejunostomy was identified, all had successful cholangiography (often balloon occlusion cholangiography). Only four cholangiograms provided an explanation for the jaundice (bile duct stricture2 and choledochojejunostomy anastomotic stricture2) and all required endoscopic therapy. Patients with the choledochojejunostomy strictures were treated by dilatation and temporary stenting. All four patients had long-term resolution of their jaundice. The remaining seven cholangiograms performed in this subgroup were normal. Thus, of the 16 patients undergoing ERCP for jaundice,

cholangiography was successful in 11/16 (69%), excluding a biliary structural issue in 7/11. An air cholangiogram was identified in two patients, suggesting the absence of a significant high-grade obstruction and the remaining three underwent a subsequent percutaneous cholangiogram. Thirteen patients underwent ERCP for evaluation of pain. Three had surgery for neoplasia, and 10 had surgery for chronic pancreatitis. The afferent limb was accessed in 12/13 (92%). The choledochojejunostomy was identified in all 12 patients whose afferent limbs were accessed. A cholangiogram was performed in seven of these 12 patients, of which only one was abnormal, showing a choledochojejunostomy anastomotic stricture which was dilated and stented successfully. The remaining five patients did not have a cholangiogram performed in the evaluation of their pain, because a pancreatic etiology was suspected based on the nature of the pain, laboratory tests, or a non-invasive imaging study. Of the 12 patients undergoing ERCP for evaluation of pain whose afferent limbs were accessed, the pancreaticojejunostomy was identified in five, aided by the use of secretin or dye-spraying in three, and no pancreaticojejunostomy was identified in the remaining seven. Three of these five patients had a pancreaticojejunostomy stricture which required dilatation and stenting, with long-term improvement in their pain symptoms. The remaining two had no evidence of a pancreaticojejunostomy stricture. In the remaining seven patients who were undergoing ERCP evaluation for pain and in whom the afferent limb was accessed, reasons for not visualizing the pancreaticojejunostomy included: very long afferent limbs,3 inability to identify the pancreaticojejunostomy despite the use of dye-spraying or secretin,2 and an alternative satisfactory non-pancreatic explanation (e.g. choledochojejunostomy anastomotic stricture1 or exclusion of a bile duct leak1). Overall, patients with a previous history of cancer were more likely to undergo ERCP for the evaluation of jaundice (14/17, 82%), and those with a previous history of chronic pancreatitis were more likely to undergo an ERCP for evaluation of pain (10/11, 91%), although technical success was slightly better in patients being evaluated for jaundice than for pain (69% vs 54%). This experience with ERCP in the post pancreaticoduodenectomy setting has several limitations. Its retrospective nature affects the ability to clearly define the indications for the procedures and longterm clinical outcome. Indications for the procedure were obtained from medical records and procedure reports. Long-term clinical outcome (including resolution of symptoms) was not sought and limits the value of this data. The use of other non-invasive imaging studies such as MRCP in the evaluation of these patients was not evaluated. The evolution of non-invasive imaging technology during the study period has altered the diagnostic role of ERCP in this patient population. There are two main benefits of MRCP imaging in this patient population, The first is to identify patients who would benefit from either biliary or pancreatic endotherapy, and those who could be spared an endoscopic procedure. The second main benefit of MRCP is the evaluation of the anatomy in cases where endoscopy has not been successful due to inability to access the relevant limb or inability to identify the choledochojejunostomy or pancreaticojejunostomy. With respect to the first benefit, we estimate that for indications relating to jaundice in our study population, it is likely that an adequate MRCP would have precluded need for an ERCP in 9 of 16 patients. For indications of pain, it is likely that adequate MRCP would have resulted in endoscopic cholangiograms not being performed in at least 6 of 7 353

SECTION 3 APPROACH TO CLINICAL PROBLEMS

cases and endoscopic pancreatograms not being performed in 2 of 5 cases. This is based on the assumptions that MRCP could easily diagnose or rule out pancreatic lesions requiring endotherapy such as pancreaticojejunostomy anastomotic stricturing, and that all biliary duct abnormalities on MRCP would result in an ERCP. For the second benefit, it is much more speculative to determine how MRCP might have impacted on the diagnosis and management of patients in whom minimal endoscopic evaluation was possible in our study. Based on these data it seems prudent to undertake an initial non-invasive MRCP rather than an ERCP, except perhaps in cases where there is a very high suspicion of the need for a therapeutic intervention, e.g. recurrent anastomotic stricture, occlusion of a biliary stent.

CONCLUSION ERCP in the post pancreatic surgery setting is useful for both biliary and pancreatic indications. With the hope of improved survival with adjuvant therapy for pancreatic neoplasia, increased surgical rates for preneoplastic conditions of the pancreas (e.g. intraductal papillary mucinous tumor, benign cysts of the pancreas), and continued surgical management of patients with chronic pancreatitis, the need for therapeutic ERCP in these patient populations will continue. Improved cooperation between the pancreatic surgeon and endoscopist (especially in patients with benign disease) and the development of more specialized endoscopes will improve the success of ERCP in these patients.

REFERENCES 1. 2.

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Bolman RM, 3rd. Surgical management of chronic relapsing pancreatitis. Ann Surg 1981; 193(2):125–131. Traverso LW, Tompkins RK, Urrea PT, Longmire WP, Jr. Surgical treatment of chronic pancreatitis. Twenty-two years’ experience. Ann Surg 1979; 190(3):312–319. Whipple A. Treatment of carcinoma of the ampulla of Vater. Ann Surg 1935; 102:763–769. Puestow C. Retrograde surgical drainage of pancreas for chronic relapsing pancreatitis. Arch Surg 1958; 76:698–707. DuVall M. Caudal pancreatico-jejunostomy for chronic relapsing pancreatitis. Ann Surg 1954; 140:775–785. Feitoza AB, Baron TH. Endoscopy and ERCP in the setting of previous upper GI tract surgery. Part II: postsurgical anatomy with alteration of the pancreaticobiliary tree. Gastrointest Endosc 2002; 55(1):75–79. Yeo CJ, Cameron JL, Sohn TA, et al. Six hundred fifty consecutive pancreaticoduodenectomies in the 1990s: pathology, complications, and outcomes. Ann Surg 1997; 226(3):248–257; discussion 257–260. Sohn TA, Yeo CJ, Cameron JL, et al. Intraductal papillary mucinous neoplasms of the pancreas: an increasingly recognized clinicopathologic entity. Ann Surg 2001; 234(3):313–321; discussion 321–322. Abe N, Sugiyama M, Suzuki Y, et al. Preoperative endoscopic pancreatic stenting for prophylaxis of pancreatic fistula development after distal pancreatectomy. Am J Surg 2005; 191(2):198–200. Hatfield AR, Tobias R, Terblanche J, et al. Preoperative external biliary drainage in obstructive jaundice. A prospective controlled clinical trial. Lancet 1982; 2(8304):896–899. McPherson GA, Benjamin IS, Hodgson HJ, et al. Pre-operative percutaneous transhepatic biliary drainage: the results of a controlled trial. Br J Surg 1984; 71(5):371–375. Pitt HA, Gomes AS, Lois JF, et al. Does preoperative percutaneous biliary drainage reduce operative risk or increase hospital cost? Ann Surg 1985; 201(5):545–553. Lai EC, Mok FP, Fan ST, et al. Preoperative endoscopic drainage for malignant obstructive jaundice. Br J Surg 1994; 81(8):1195–1198. Povoski SP, Karpeh MS, Jr., Conlon KC, et al. Association of preoperative biliary drainage with postoperative outcome following pancreaticoduodenectomy. Ann Surg 1999; 230(2):131–142. Sohn TA, Yeo CJ, Cameron JL, et al. Do preoperative biliary stents increase postpancreaticoduodenectomy complications? J Gastrointest Surg 2000; 4(3):258–267; discussion 267–268.

16. Pisters PW, Hudec WA, Hess KR, et al. Effect of preoperative biliary decompression on pancreaticoduodenectomy-associated morbidity in 300 consecutive patients. Ann Surg 2001; 234(1):47–55. 17. Hochwald SN, Burke EC, Jarnagin WR, et al. Association of preoperative biliary stenting with increased postoperative infectious complications in proximal cholangiocarcinoma. Arch Surg 1999; 134(3):261–266. 18. Heslin MJ, Brooks AD, Hochwald SN, et al. A preoperative biliary stent is associated with increased complications after pancreatoduodenectomy. Arch Surg 1998; 133(2):149–154. 19. Hodul P, Creech S, Pickleman J, et al. The effect of preoperative biliary stenting on postoperative complications after pancreaticoduodenectomy. Am J Surg 2003; 186(5):420–425. 20. Mullen JT, Lee JH, Gomez HF, et al. Pancreaticoduodenectomy after placement of endobiliary metal stents. J Gastrointest Surg. 2005 Nov; 9(8):1094–1104; discussion 1104–1105. 21. Wasan SM, Ross WA, Staerkel GA, et al. Use of expandable metallic biliary stents in resectable pancreatic cancer. Am J Gastroenterol. 2005 Sep; 100(9):2056–2061. 22. Lawrence C, Howell DA, Conklin DE, et al. Delayed pancreaticoduodenectomy for cancer patients with prior ERCP-placed, nonforeshortening, self-expanding metal stents: a positive outcome. Gastrointest Endosc 2006 May; 63(6):804–807. 23. Sohn TA, Yeo CJ, Cameron JL, et al. Pancreaticoduodenectomy: role of interventional radiologists in managing patients and complications. J Gastrointest Surg 2003; 7(2):209–219. 24. Gervais DA, Fernandez-del Castillo C, O’Neill MJ, et al. Complications after pancreatoduodenectomy: imaging and imaging-guided interventional procedures. Radiographics 2001; 21(3):673–690. 25. Gillams AR, Kurzawinski T, Lees WR. Diagnosis of duct disruption and assessment of pancreatic leak with dynamic secretinstimulated MR cholangiopancreatography.AJR Am J Roentgenol. 2006 Feb; 186(2):499–506. 26. Kozarek RA, Ball TJ, Patterson DJ, et al. Endoscopic transpapillary therapy for disrupted pancreatic duct and peripancreatic fluid collections. Gastroenterology 1991; 100(5 Pt 1):1362–1370. 27. Saeed ZA, Ramirez FC, Hepps KS. Endoscopic stent placement for internal and external pancreatic fistulas. Gastroenterology 1993; 105(4):1213–1217. 28. Bracher GA, Manocha AP, DeBanto JR, et al. Endoscopic pancreatic duct stenting to treat pancreatic ascites. Gastrointest Endosc 1999; 49(6):710–715.

Chapter 32 ERCP for the Acute and Chronic Complications of Pancreatic Surgery

29. Boerma D, Rauws EA, van Gulik TM, et al. Endoscopic stent placement for pancreaticocutaneous fistula after surgical drainage of the pancreas. Br J Surg 2000; 87(11):1506–1509. 30. Costamagna G, Mutignani M, Ingrosso M, et al. Endoscopic treatment of postsurgical external pancreatic fistulas. Endoscopy 2001; 33(4):317–322. 31. Telford JJ, Farrell JJ, Saltzman JR, et al. Pancreatic stent placement for duct disruption. Gastrointest Endosc 2002; 56(1):18–24. 32. Seewald S, Brand B, Groth S, et al. Endoscopic sealing of pancreatic fistula by using N-butyl-2-cyanoacrylate. Gastrointest Endosc 2004; 59(4):463–470. 33. Levy MJ, Chari S, Adler DG, et al. Complications of temporary pancreatic stent insertion for pancreaticojejunal anastomosis during pancreaticoduodenectomy. Gastrointest Endosc 2004 May; 59(6):719–724.

34. Toledo-Pereyra L. The pancreas—principals of medical and surgical practice. New York: John Wiley & Sons; 1985. 35. Braasch JG, Ganger M. Pylorus-preserving pancreaticoduodenctomy. Langenbecks Arch Chirg 1991; 376:50–58. 36. Law NM, Freeman ML. ERCP by using a prototype oblique-viewing endoscope in patients with surgically altered anatomy. Gastrointest Endosc 2004; 59(6):724–728. 37. Mallery S, Matlock J, Freeman ML. EUS-guided rendezvous drainage of obstructed biliary and pancreatic ducts: Report of 6 cases. Gastrointest Endosc 2004; 59(1):100–107. 38. Kugelberg C, Wehlin L, Arnesjo B, et al. Endoscopic pancreatography in evaluating results of pancreatico-jejunostomy. Gut 1976; 17(4):267–272.

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33

APPROACH TO CLINICAL PROBLEMS

Choledocholithiasis Yuk Tong Lee and Joseph Sung

INTRODUCTION

DIAGNOSIS OF CHOLEDOCHOLITHIASIS

Choledocholithiasis, defined as the presence of stone inside the common bile duct (CBD), is a common condition. At least 15% of patients with cholelithiasis have choledocholithiasis. Conversely, 95% of patients with CBD stones also have gallstones.1 It is estimated that over 20 million Americans have gallstone disease and up to 25% of elderly patients have calculi in the CBD at the time of cholecystectomy.2 In the West, the majority of CBD stones are composed of cholesterol stones that originated from the gallbladder. Less than 10% of CBD stones are formed de novo within the CBD. On the other hand, in the East, because of a higher incidence of chronic biliary tree infection and infestation, the occurrence of pigment stones is much more common. This condition, which begins with inflammation in the bile ducts, is referred to as recurrent pyogenic cholangitis (RPC). It is characterized by recurrent cholangitis due to the presence of multiple pigment stones formed inside the intrahepatic ducts. This chapter focuses on the current management of choledocholithiasis, and the related problem of cholelithiasis. Readers should refer to other chapters for the technique of bile duct cannulation (Chapter 8), sphincterotomy (Chapter 12), CBD stone extraction (Chapter 13), management of RPC (Chapter 38) and acute biliary pancreatitis (Chapter 39).

Trans-abdominal ultrasound (US) is commonly used for diagnosis of choledocholithiasis. However, limited by various technical factors and compounded by variable experience of operators, the sensitivity of US in detecting choledocholithiasis ranges from 22% to 80%.1 As extrahepatic biliary dilation is present in 70–94% of patients with choledocholithiasis, it serves as a useful surrogate marker for the diagnosis. However, it is important to note that a normal US study does not exclude the possibility of choledocholithiasis. Although ERCP is a time-honored gold standard for the diagnosis of choledocholithiasis, its accuracy for the detection of small stones and biliary sludge is being questioned.5,6 Both under-filling and overfilling of the bile duct during contrast injection may cause CBD and intrahepatic ductal stones to be missed. Occasionally, stones cannot be differentiated from air bubbles. A recent study in which ERCP alone was compared to ERCP combined with miniprobe intraductal ultrasound (IDUS) showed the latter approach had a higher accuracy (87% versus 97%) in diagnosing bile duct stones and sludge.5 Furthermore, because of its invasive nature and the possible complications associated with cannulation of the CBD, the use of diagnostic ERCP has been gradually replaced with other modalities for the detection of choledocholithiasis. Helical CT has a sensitivity of detecting choledocholithiasis of 65% to 88%. With the use of contrast-enhanced CT cholangiography, the sensitivity increases to 90%.7 However, the use of CT cholangiography is limited in patients with significant hyperbilirubinemia or advanced liver disease. Up to 10% of patients have adverse events after administration of contrast. Magnetic resonance cholangiopancreatography (MRCP) is proven to be an accurate non-invasive imaging for choledocholithiasis. In a recent meta-analysis of 67 studies, the pooled sensitivity and specificity for MRCP in diagnosing biliary obstruction were 95% and 97%, respectively.8 The sensitivity for detecting choledocholithiasis is slightly lower (92%) as detection of small CBD stones can still be a challenge. For CBD stones less than 5 mm in size, the sensitivity of detection by MRCP drops to below 65%. MRCP is also poor in detecting biliary sludge. Despite these limitations, using MRCP to select patients for ERCP is shown to be substantially cost-saving and improves the quality of life in patients with low to intermediate risk of choledocholithiasis.9 If available, MRCP should replace diagnostic ERCP. In the last decade, the advent of EUS has changed the management of CBD stones. The sensitivity of EUS in detecting choledocholithiasis reported in various studies ranges from 93 to 100%. Unlike the other imaging modalities, performance of EUS is less affected by the size of CBD stones and the diameter of the bile duct (Figs 33.1–33.3). Most studies comparing MRCP against EUS

CLINICAL MANIFESTATION The natural history of choledocholithiasis is not fully recognized. The clinical manifestation largely depends on the location of the stones and the presence of bacterial invasion. Stones formed in the intrahepatic ducts could be asymptomatic and remain in the bile ducts for a long period of time without being recognized. Small CBD stones may pass through the papilla spontaneously causing few symptoms.3 From a recent study up to one-fifth of CBD stones less than 5 mm in diameter pass into the duodenum spontaneously without causing significant symptoms.4 On the other hand, spontaneous passage of small calculi through the papilla may be complicated by biliary pancreatitis. In patients with mild biliary pancreatitis, spontaneous stone passage may occur in 70–80% of patients. Stones impacted in the distal bile duct often lead to biliary colic, jaundice, cholangitis or pancreatitis. When bacterial infection develops, stone impaction will be complicated by suppurative cholangitis. If the bile duct obstruction is gradual and insidious, patients may present with progressive obstructive jaundice and rarely, secondary biliary cirrhosis. If the stone is impacted in the cystic duct causing obstruction of bile flow in the gallbladder and/or the biliary tract, acute cholecystitis or Mirizzi syndrome may arise.

357

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Fig. 33.1 EUS examination demonstrating a small stone (arrow) in a non-dilated bile duct. Acoustic shadowing is seen behind the stone.

showed superiority of the latter in accuracy. In a recent study comparing MRCP with EUS in detecting choledocholithiasis, MRCP (sensitivity 87.5%, specificity 96.6%) was outperformed by EUS (sensitivity 93.8%, specificity 96.6%).10 The high negative predictive value of EUS helps to reduce unnecessary diagnostic ERCP. Based on a decision analysis model, using EUS to triage patients for therapeutic ERCP was shown to be safe and cost-effective in patients with biliary pancreatitis.11 The finding is in accord with a prospective study in which 485 patients who were suspected (based on clinical, biochemical and US parameters) to have choledocholithiasis were triaged by EUS to receive ERCP and stone extraction.12 EUS showed a superb result of sensitivity, specificity, positive and negative predictive value of 98%, 99%, 99% and 98% respectively. In 214 (46%) patients, invasive ERCP was avoided. The mean cost for patients managed by the EUS-based strategy was significantly lower than the theoretical mean cost for patients managed by the ERCP-based strategy. However, EUS causes more discomfort than MRCP and patient preference may aid in the choice of one modality over another. Depending on clinical suspicion and serum laboratory tests, patients can be divided into low risk (e.g. atypical pain with normal liver function test), intermediate risk (pain and biochemical evidence of biliary obstruction) and high risk (fever, jaundice and pain) of having choledocholithiasis. The following algorithm is suggested to investigate these patients according to the risk stratification (Fig. 33.4). For low-risk patients, a normal US examination is adequate to exclude the presence of choledocholithiasis and no further testing is needed. If a CBD stone is detected the patient is referred for ERCP. If a dilated bile duct without a stone is detected, the patient should undergo an additional non-invasive study such as CT or MRCP, or less invasive study (EUS) to look for underlying causes before con358

Fig. 33.2 EUS examination demonstrates sludge (arrow) in the distal CBD. The sludge appears as homogeneous amorphous material without casting any acoustic shadowing.

Fig. 33.3 Endoscopic appearance of biliary sludge extraction using an occlusion balloon after a sphincterotomy was performed. sidering invasive ERCP examination. There may be a small benefit by adding EUS to a patient who has a dilated duct but otherwise normal MRCP examination. For the intermediate risk patient, if US detects any CBD stone, the patient should be referred for ERCP. However, if the US

Chapter 33 Choledocholithiasis

Fig. 33.4 Algorithm in investigating patients with suspected choledocholithiasis. More than one option can be followed in each clinical situation (solid arrow). The dotted line represents an alternative EUS-based approach.

Suspected choledocholithiasis

High risk

Low risk

Intermediate risk

US

CBD stone

Normal

Dilated duct with no stone

CBD stone

Normal

Dilated duct with no stone

CBD stone

Normal

MRCP (contrast CT) ERCP ERCP (+ IDUS) + sphincterotomy

Observe

Normal

EUS

CBD stone

examination is normal, additional testing such as CT, MRCP or EUS is still needed. If US examination shows a dilated duct with no stone, MRCP or EUS would be needed to rule out underlying pathology. The patient may also be considered for ERCP. For the high-risk patient, especially in a patient with features of acute cholangitis, the patient may go directly for ERCP without US examination. If the patient’s condition is stable, an US can be performed to exclude other intra-abdominal pathology before an ERCP is performed. Whether a normal EUS examination spares the patient from invasive ERCP deserves further study.

MANAGEMENT OF CHOLANGITIS SECONDARY TO CHOLEDOCHOLITHIASIS When stones become impacted in the distal CBD, biliary stasis ensues. The normal pressure in the ductal system is 10–15 cm H2O. When the pressure exceeds 30 cm H2O, bile flow stops. Due to the raised intraductal pressure, secretion of IgA, the predominant immunoglobulin in bile, is suppressed and hence antibacterial function of bile weakened. Bacteria ascending through the transpapillary route or translocating through the portal venous circulation may invade into the biliary system resulting in cholangitis.13 The most commonly found bacteria are Escherichia coli, enterococci, Klebsiella, Proteus species and Pseudomonas (after surgical or endoscopic manipulations). Anaerobic organisms such as Bacteroides fragilis or Clostridium perfringens are found in about 15% of cases. With the raised intraductal pressure in the setting of choledocholithiasis, bacteria in the bile ducts may reflux back into the hepatic venous system leading to the development of septicemia. The elevated intraductal pressure also suppresses active and passive secretion of antibiotics into the biliary system thus hampering their antimicrobial activity. Among commonly used antibiotics, only ciprofloxacin is excreted in detectable levels in the presence of biliary obstruction.14 As elevated intrabiliary pressure is the main pathophysiological mechanism of biliary sepsis, decompression of the obstructed system is a critical step in reversing these processes and controlling endotoxaemia,15 and is the mainstay of treatment for cholangitis.

The symptoms of cholangitis include right upper quadrant pain, fever and jaundice which represent the classical Charcot’s triad. However, these classical symptoms may occur in only 70% of cases. When more severe septicemia occurs, the patient may present with hypotension, mental confusion and sign of peritonitis (when occurring with Charcot’s triad is known as Reynold’s pentad). Laboratory examination in patients with cholangitis demonstrates an obstructive liver enzyme pattern and leukocytosis. Acute cholangitis carries a high morbidity and mortality, especially in elderly patients. Conservative treatment with antibiotics for patients with cholangitis is effective in only 80% of cases. Before the development of ERCP and endoscopic drainage, the surgical mortality rate of acute suppurative cholangitis was around 40%. ERCP has established its role in the treatment of cholangitis in the 1980s. In patients suffering from suppurative cholangitis, emergency endoscopic drainage through the insertion of a nasobiliary catheter was shown to be effective in controlling sepsis.16 A randomized controlled trial showed endoscopic decompression of the bile duct reduces morbidity and mortality rates when compared with emergency open surgery and CBD exploration.17 With successful drainage of the biliary system, abdominal pain and fever subside, and the patient’s hemodynamic status stabilizes. The mortality rate of cholangitis has been brought down to 5–8% in recent years. When performing ERCP for patients with acute suppurative cholangitis, one should exercise extra caution when introducing radiological contrast into the obstructed biliary system since this will further increase the intraductal pressure precipitating septicemia. The use of a guidewire instead of contrast during the cannulation is recommended. After deep cannulation is achieved, the CBD should be decompressed by aspiration of the infected bile prior to contrast injection. Only a minimal amount of contrast should be used to outline the bile ducts. There are several potential strategies in the treatment of choledocholithiasis after successful cannulation and decompression of the bile duct is achieved. A one-step approach with endoscopic sphincterotomy and stone extraction is the treatment of choice for patients 359

SECTION 3 APPROACH TO CLINICAL PROBLEMS

Fig. 33.5 Endoscopic view of basket extraction of a large mixed stone through a biliary sphincterotomy.

with stable clinical conditions (Fig. 33.5). In patients who are critically ill or with coagulopathy due to prolonged cholestasis, the complication rate of biliary sphincterotomy is substantial. Complete ductal clearance at first ERCP may only be achieved in 57–85%.18 Prolongation of the procedure and increasing sedation poses unnecessary challenges to the cardiopulmonary function of these patients.

A

B

For patients that are not suitable for prolonged endoscopic intervention, urgent decompression followed by elective ERCP to remove the stone is recommended. After sphincterotomy and stone extraction, it is sometimes useful to leave a nasobiliary drain (NBD) or biliary stent for temporary drainage. This procedure is particularly useful after edema develops due to manipulation of the papilla. Incomplete clearance of the CBD after basket mechanical lithotripsy (BML) may leave small stone fragments behind blocking bile flow. A NBD will secure drainage of the CBD. After the sepsis subsides a follow-up cholangiogram can be obtained by injecting contrast through the NBD without need for passage of the endoscope. If a stone is not detected, the drain can safely be removed. NBD is widely used for the initial decompression in patients with acute cholangitis (Fig. 33.6). The insertion of a NBD is an easy procedure once deep cannulation of bile duct is achieved. Bile sample can be obtained through NBD for bacteriological culture; bile output can be continuously monitored. In case of clogging of the NBD, the drain can be gently flushed with water. However, the insertion and re-routing of the drain through the nose may be difficult in septic patients with confusion. The drain may be pulled out inadvertently by the patients. In patients that require prolonged drainage, it is uncomfortable to the patients and the fluid and electrolyte loss through the external drainage could be significant. The alternative to NBD is the insertion of a biliary stent. Unlike NBD, stent placement does not require re-routing through the nose so that it can be done even in uncooperative or confused patients. An indwelling biliary stent cannot be removed by the patient, does not cause discomfort, and does not disturb fluid and electrolyte balance. The benefit of combining sphincterotomy to NBD or stent placement to improve biliary drainage has been debated. In a retrospec-

C

Fig. 33.6 A Cholangitis due to impacted distal CBD stone. B A typical nasobiliary drain (NBD). C Radiographic image after successful NBD insertion in same patient. 360

Chapter 33 Choledocholithiasis

tive study, 166 patients who underwent ERCP and NBD insertion with and without concomitant sphincterotomy for treatment of cholangitis were compared.19 The success rates of NBD insertion were 95% and 96% and efficient drainage was achieved in 92% and 94% in patients with and without sphincterotomy, respectively. Eleven percent of the patients who underwent sphincterotomy developed complications (including hemorrhage, cholecystitis and pancreatitis) as compared to 2% in the non-sphincterotomy group. In another retrospective study, 74 patients received ERCP and biliary stent placement for decompression in the setting of acute cholangitis.20 Half of the patients had a concomitant sphincterotomy. Three patients in the sphincterotomy group had bleeding that required endoscopic treatment and one had acute pancreatitis. One patient who received stent placement alone developed pancreatitis. Clinical outcomes of the two groups were similar but procedure time was significantly shorter in those without a sphincterotomy. Both studies suggest that endoscopic sphincterotomy may not be necessary in acute cholangitis when biliary decompression can be achieved by either NBD or biliary stenting. Two randomized, controlled studies compared initial NBD insertion to biliary stent placement in the treatment of acute cholangitis. Lee et al. recruited 79 patients presenting with severe acute cholangitis to receive either a 6.5 Fr NBD or insertion of a 10-Fr stent.21 Endoscopic sphincterotomy was not performed in either group. NBD were successfully inserted in all cases whereas there was one failed stent insertion. Four patients pulled out their NBD inadvertently and in one patient the NBD kinked. There was one early occlusion in the stent group. Patients in the stent group experienced less discomfort than patients in the NBD group. The overall mortality rate was 6.8% (2.5% NBD group; 12% stent group). The higher mortality rate in the stent group was attributed to more severe cholangitis in this group. Sharma et al. randomized 150 patients with severe cholangitis to receive either a 7 Fr NBD or a 7 Fr biliary stent insertion for biliary drainage.22 Biliary drainage was achieved in 74/75 (99%) patients in the NBD group and in 73/75 (98%) patients in the stent group. There were no episodes of displacement, kinking, or occlusion of the NBD, and no episodes of stent occlusion or migration. Two patients died in each group. Based on these two randomized trials, biliary drainage can be achieved equally well by NBD or stenting in the treatment of severe cholangitis. In patients who are debilitated by chronic illness and those with limited life expectancy, endoscopic stenting can be used as a definitive treatment for cholangitis. However, for patients treated with biliary stents alone the rate of recurrent cholangitis is expected to be higher than those who have achieved complete stone clearance in long-term follow-up.23 In one non-randomized study, 36 patients with difficult CBD stones were treated with either electrohydraulic lithotripsy (EHL) for ductal clearance or stent placement only. Patients treated with stents experienced a significantly higher rate of recurrent cholangitis (63.2% versus 7.7%) and mortality (73.7% versus 41.2%) compared to patients treated with EHL for duct clearance.24 Therefore in patients who are medically fit, one should aim for complete ductal clearance of the common bile duct. Age alone should not be a determining factor limiting patients to receive endoscopic treatment of choledocholithiasis. From a retrospective study, 126 elderly patients (median age 92.2 years) underwent a total of 159 ERCPs.25 Most of the patients (92.4%) tolerated the procedures well. In the 68 patients with choledocholithiasis, 59 (86.8%) achieved bile duct stone clearance. There were 3 mild complications (2 cholangitis, 1 hemorrhage) and one fatal complication

(post-sphincterotomy bleeding). The mean survival for patients with non-malignant disease after ERCP was 22.5 months. Occasionally in patients with suspected cholangitis, no stone is found at ERCP. It is because a small stone or sludge can be missed by the cholangiogram, which was reported in 25.5% of the patients in one study.6 It raises the question of performing empirical endoscopic sphincterotomy to ensure biliary drainage, realizing the potential complications. In a prospective randomized study of 111 patients with cholangitis but without a stone found at cholangiography, they were randomized to undergo endoscopic biliary sphincterotomy or no endoscopic therapy. In the sphincterotomy group both duration of fever and length of hospital stay were significantly shorter than patients who did not receive sphincterotomy. However, during follow-up no difference in occurrence of recurrent cholangitis was seen.26 Therefore, routine sphincterotomy does not appear to be justified in these patients because of potential complications.6 Alternatively, NBD insertion is effective in providing temporary drainage.19 If follow-up NBD cholangiography confirms absence of a stone, the patient is then referred for cholecystectomy. Box 33.1 summarizes the endoscopic management of cholangitis due to choledocholithiasis.

BOX 33.1 PRACTICAL TIPS IN MANAGING PATIENTS WITH CHOLANGITIS CAUSED BY CHOLEDOCHOLITHIASIS • Adequate resuscitation before performing ERCP • Avoid over-sedation of the patient • Avoid over-injection of contrast during bile duct cannulation • Aspirate infected bile once deep cannulation is achieved to reduce biliary pressure before contrast injection • Avoid performing biliary sphincterotomy and stone extraction in an unstable patient • Insert a nasobiliary drain or a biliary stent for decompression in unstable patients • Avoid unnecessary sphincterotomy when NBD or biliary stent is placed • Delay second stage ERCP to remove stones until stabilization of the patient • In the stable patient always attempt to achieve complete stone clearance • Consider surveillance for recurrent choledocholithiasis after endoscopic clearance in high-risk patients or those who would poorly tolerate recurrence • Recommend cholecystectomy in healthy patients with residual gallstones after endoscopic clearance of bile duct stones

361

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MANAGEMENT OF DIFFICULT CBD STONES The standard endoscopic technique for stone removal consists of biliary sphincterotomy followed by stone extraction with Dormia basket or balloon. Ductal clearance is achieved in 95% of cases. However, there are situations where ductal clearance is difficult. These include stones larger than 2 cm in size, stones impacted in relatively small or non-dilated common bile duct, and small sphincterotomy because of difficult anatomic position. For large CBD stone (>2 cm), biliary mechanical lithotripsy (BML) allows successful ductal clearance in 80–90% of cases. Stone impaction in the bile duct is a significant predictive factor of endoscopic failure.27 Electrohydraulic lithotripsy (EHL) via peroral endoscopic choledochoscopy is a safe technique that allows successful management of difficult CBD and intrahepatic ductal stones in a high percentage of patients (Figs 33.7–33.8). The fragmentation rate is as high as 96% and complete stone clearance as high as 90%.28 In a cohort of 313 patients with difficult CBD stones, 90% achieved ductal clearance with the use of high-energy extracorporeal shock wave lithotripsy (ESWL). The success of ESWL was not influenced by stone location, size, or presence of bile duct stricture.29 The selection of specific treatment methods depends on the availability of the equipment and local expertise. If this equipment is not available the temporary insertion of a biliary stent may fragment the stone and aid in future endoscopic treatment (Fig. 33.9).30

SURVEILLANCE AFTER TREATMENT OF CHOLEDOCHOLITHIASIS Recurrence of biliary complications after endoscopic and surgical treatment of choledocholithiasis ranges from 3.7% to 32%. Higher rates of recurrent choledocholithiasis are seen in patients with an

A

362

B

intact gallbladder, dilated CBD, periampullary diverticula, history of primary bile duct stone, and use of T-tube drainage at the time of cholecystectomy.31 Patients with a history of recurrent cholangitis may have a shortened period of remission.32 Therefore, in high-risk patients it is logical to perform surveillance. In one study of patients who underwent a follow-up program of serum liver enzymes testing and US examination every 3–6 months, recurrent stones were detected when asymptomatic.33 Therefore, in patients with risk factors of recurrent choledocholithiasis, multiple episodes of cholangitis, and presence of major systemic diseases, a regular surveillance program should be considered. Repeat ERCP and endoscopic sphincterotomy in patients with prior sphincterotomy may be safe in expert hands but does not eliminate the risk of recurrent choledocholithiasis.32

PERI-OPERATIVE MANAGEMENT OF CHOLEDOCHOLITHIASIS The management of bile duct stone in the era of laparoscopic cholecystectomy (LC) has been a subject of much debate. The current options available include preoperative ERCP, intraoperative ERCP, postoperative ERCP, laparoscopic exploration of the CBD (LECBD) through a transcystic route or laparoscopic choledochotomy, and open CBD exploration. In patients who are at high risk of choledocholithiasis (history of cholangitis, pancreatitis, deranged liver function, dilated CBD) preoperative ERCP should be performed prior to LC. From a retrospective audit of 1139 patients, 227 (20%) patients were selected for ERCP examinations based on the above criteria. 53% of the patients had choledocholithiasis; among them, 97% had successful endoscopic stone extraction.34 In a prospective study, 427 patients were assessed for ERCP before surgery based on the same criteria. Forty-

Fig. 33.7 A Multiple intrahepatic CBD stones. B Photograph of a mother and “baby scope” (choledochoscope) seen passing through the duodenoscope. A forceps is pictured exiting the baby scope working channel which allows extraction of stone fragments after intraductal lithotripsy.

Chapter 33 Choledocholithiasis

A

Fig. 33.8 A Endoscopic view from the baby scope shows the detail of the bile duct and the presence of pigment stones. B The extracted pigment stone.

B

one patients (9.6%) met the criteria and among them 22 patients (53.7%) were found to have choledocholithiasis. The strongest predictive factor for CBD stones on ERCP was a dilated CBD in association with abnormal serum liver chemistries. During follow-up, 28 patients (6.6%) were found to have recurrent or residual CBD stones.35 These studies demonstrated that selective use of ERCP before LC reduces the routine use of time-consuming laparoscopic cholangiography or LCBDE. However, there are drawbacks in employing these selection criteria since only half of the patients selected were confirmed to have choledocholithiasis and hence up to 50% of patients were subjected to an unnecessary invasive procedure. Thus better methods of selecting patients for ERCP are needed. Studies have shown that MRCP36 and EUS37 are both useful in selecting patients for ERCP before LC. Recently, a decision analysis model suggested that when the risk of bile duct stones is less than 10% (low risk), expectant management with postoperative ERCP for recurrent symptoms is less costly. When the risk of stones is greater than approximately 55% (high risk), preoperative ERCP is most costeffective. When the risk is intermediate (10–55%), preoperative testing with either EUS or MRCP, or intraoperative cholangiography is the best approach.38

Occasionally bile duct stones are discovered during LC. A recent study shows that by using intraoperative ERCP, one can avoid LCBDE which is technically more demanding. In a two-year prospective study of 674 patients, 34 (5.7%) patients were found to have a CBD stone detected during laparoscopic cholangiography and required intraoperative ERCP.39 Cannulation of the CBD was aided by surgical passage of a guidewire through the cystic duct and across the papilla. Successful cannulation was reported in 100% and no pancreatitis occurred. CBD stones were successfully extracted in 93.5% of patients. The operating time was prolonged but the length of hospitalization was not increased. This combined procedure may actually reduce the cost and hospital stay for patients by preventing two separate procedures. If the stones cannot be cleared during the intraoperative ERCP the operation can be converted to LECBD or even open bile duct exploration.40 Postoperative ERCP and stone removal allows successful clearance in 93–100% of patients.3,41 Should the stone be removed during the operation or postoperatively at ERCP? In a prospective randomized trial, 471 patents underwent LC and 80 (17%) patients were found to have CBD stones by cholangiogram.41 Half of the patients were randomized to receive LECBD and the other half randomized to postoperative ERCP and stone 363

SECTION 3 APPROACH TO CLINICAL PROBLEMS

A

B

C

D

Fig. 33.9 The use of biliary stent in the treatment of difficult CBD stone. A Fluoroscopic image of large CBD stone impacted in the CBD; there was no room in which to open the biliary mechanical lithotripter (BML). B A biliary stent was inserted. C Three months later the stone had reduced in size to allow entrapment and crushing using the BML. D Only small fragments remained in the CBD which were subsequently removed using standard retrieval techniques.

extraction. The ductal clearance after first intervention was 75% in both groups. There was no difference in clinical outcome but the postoperative hospital stay was significantly shorter in the laparoscopic group than the ERCP group (median 1 day versus 3–5 days). The advantage of one-stage laparoscopic approach is also supported

364

by a decision analysis model.42 It showed LCBDE is a cost-effective method of managing CBD stones found on LC. If expertise in LECBD is unavailable, then postoperative ERCP should be offered. These conclusions from the above studies should be considered with caution. Despite the reported high success rate of postoperative ERCP, there are still about 5% of cases in whom complete stone clearance is not achieved. The patient may then need to undergo another operation for stone removal. Therefore, patient selection for preoperative stone extraction is very important. If endoscopic stone extraction fails, CBD exploration is deemed inevitable. Findings of large stone size (>25 mm diameter), presence of intrahepatic stones or multiple tightly packed CBD stones, CBD stricture, duodenal diverticulum, and history of Bilroth II or Roux-en-Y operation during LC predicts failure of postoperative ERCP.3 In these situations, open or laparoscopic CBDE for stone removal seems to be a better choice. An algorithm for the management of choledocholithiasis incorporating endoscopic and laparoscopic treatment had been proposed.43

CHOLECYSTECTOMY AFTER ENDOSCOPIC SPHINCTEROTOMY Endoscopic sphincterotomy and stone extraction have gained wide acceptance in the management of choledocholithiasis. However, following the endoscopic removal of bile duct stones, the need for cholecystectomy in patients with concomitant gallstone is less clear. Various studies had shown that further biliary complications occur in 4–24% of patients after varying periods of follow-up and the rate of subsequent cholecystectomy ranges from 6% to 18%.44,45 The age and presence of comorbidity of the patients also factors into the equation. A randomized, prospective study of 120 patients (mean age 62 years) who underwent ERCP with CBD stone removal followed by either LC or expectant management showed that recurrent biliary symptoms, mainly biliary pain and acute cholecystitis, occurred in 2% of patients in the LC group as compared with 47% of patients in the expectant group.46 In the expectant group, 37% of the patients subsequently required cholecystectomy and in over half of them conversion to open surgery was required. In contrast, in an Oriental non-randomized study of 140 patients (mean age 67 years) there were no significant differences in the incidence of recurrent bile duct stones, biliary symptoms and complications between those who received elective LC or were managed expectantly.47 The discrepancy in outcome arises from the origin of choledocholithiasis which is gallstone predominantly from the gallbladder in the West and pigment stone from the bile ducts in the East. In a recent study from Hong Kong 178 patients (mean age 71 years) were randomized to LC or expectant management after endoscopic sphincterotomy and stone extraction.48 During 5 years of follow-up, 6 patients in the cholecystectomy group returned with biliary events (cholangitis 5, epigastric pain 1); whereas in those with gallbladders in situ, 21 patients developed further biliary events including recurrent choledocholithiasis with cholangitis in 13, epigastric pain in 2, obstructive jaundice in 1, and acute cholecystitis in 5. The cumulative probability of recurrent biliary events in the cholecystectomy group and gallbladders in situ group was

Chapter 33 Choledocholithiasis

5.8% and 25.4%. It is concluded that after endoscopic sphincterotomy and removal of bile duct stones, even in Asian patients, cholecystectomy should be performed to reduce the risk of recurrent biliary events.

CONCLUSION

treatment of choledocholithiasis. Advances in therapeutic ERCP have resulted in successful clearance rates of choledocholithiasis and improved patient outcome. Endoscopic and laparoscopic treatments of bile duct stones should be considered complementary approaches to the management of choledocholithiasis.

Advances in recent imaging techniques have replaced diagnostic ERCP for choledocholithiasis. ERCP remains the mainstay for

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30. Chan AC, Ng EK, Chung SC, et al. Common bile duct stones become smaller after endoscopic biliary stenting. Endoscopy 1998; 30(4):356–359. 31. Uchiyama K, Onishi H, Tani M, et al. Long-term prognosis after treatment of patients with choledocholithiasis. Ann Surg 2003; 238(1):97–102. 32. Sugiyama M, Suzuki Y, Abe N, et al. Endoscopic retreatment of recurrent choledocholithiasis after sphincterotomy. Gut 2004; 53(12):1856–1859. 33. Lai KH, Lo GH, Lin CK, et al. Do patients with recurrent choledocholithiasis after endoscopic sphincterotomy benefit from regular follow-up? Gastrointest Endosc 2002; 55(4):523–526. 34. Coppola R, Riccioni ME, Ciletti S, et al. Selective use of endoscopic retrograde cholangiopancreatography to facilitate laparoscopic cholecystectomy without cholangiography. A review of 1139 consecutive cases. Surg Endosc 2001; 15(10):1213–1216. 35. Katz D, Nikfarjam M, Sfakiotaki A, et al. Selective endoscopic cholangiography for the detection of common bile duct stones in patients with cholelithiasis. Endoscopy 2004; 36(12):1045–1049. 36. Laokpessi A, Bouillet P, Sautereau D, et al. Value of magnetic resonance cholangiography in the preoperative diagnosis of common bile duct stones. Am J Gastroenterol 2001; 96(8):2354–2359. 37. Palazzo L, O’Toole D. EUS in common bile duct stones. Gastrointest Endosc 2002; 56(4 Suppl):S49–S57. 38. Sahai AV, Mauldin PD, Marsi V, et al. Bile duct stones and laparoscopic cholecystectomy: a decision analysis to assess the roles of intraoperative cholangiography, EUS, and ERCP. Gastrointest Endosc 1999; 49(3 Pt 1):334–343. 39. Enochsson L, Lindberg B, Swahn F, et al. Intraoperative endoscopic retrograde cholangiopancreatography (ERCP) to remove common bile duct stones during routine laparoscopic

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SECTION 3

Chapter

34

APPROACH TO CLINICAL PROBLEMS

Pancreaticobiliary Pain and Suspected SOD Paul R. Tarnasky and Robert H. Hawes

INTRODUCTION The diagnosis and treatment of suspected sphincter of Oddi dysfunction (SOD) presents a significant challenge for physicians who care for patients with digestive diseases. This chapter is intended to provide readers with a practical guide to the evaluation and management of patients with pancreaticobiliary type pain and suspected SOD. The overall goals of this chapter include identifying the challenges which these patients present and offering a pragmatic approach to the clinical evaluation and decisions regarding treatment. The specific goals are: (1) describe pain patterns that are consistent and not consistent with SOD; (2) define SOD and the clinical scenarios where SOD might be considered; (3) describe a rational initial evaluation for patients with suspected SOD; (4) provide guidance for patient and physician decisions regarding management of SOD; (5) describe techniques of sphincter of Oddi manometry (SOM) and endoscopic treatment of SOD; and (6) reinforce the risks inherent to the endoscopic evaluation of SOD and how they can be minimized. It should be emphasized that there is a paucity of good data to guide clinicians in this arena. When data is available, recommendations will be evidence based but much of the following information is derived from anecdotal experience of which the authors have a considerable amount. Clinical syndromes which may be attributed to SOD range from functional disorders with purely subjective symptomatology to structural disorders having objective pathologic features. Functional and structural SOD diagnoses are widely divergent with regard to their presentation and management. Unexplained upper abdominal pain and acute pancreatitis represent the two most important examples at each end of this spectrum and will be the focus of this review. Other clinical scenarios that may be associated with SOD include chronic acalculous cholecystitis, early chronic pancreatitis, biliary pancreatitis, postoperative bile leak, and pancreatic fistula.

DEFINITIONS Confusing terminology and varied clinical presentations explain part of the complexity regarding SOD. Biliary dyskinesia is the encompassing term for a group of disorders with acalculous biliary-type pain. Subgroup diagnoses include chronic acalculous cholecystitis, gallbladder dyskinesia, cystic duct syndrome, and SOD. Sphincter of Oddi dysfunction may occur in patients with or without a gallbladder but is most commonly diagnosed in patients with postcholecystectomy symptoms. Attempts have been made to develop consensus on defining the signs and symptoms of SOD culminating in what are called the

“Rome criteria.”1 Definitions established for post cholecystectomy patients and those with gallbladder in situ are listed in Tables 34.1 and 34.2. Revisions in the Rome criteria for SOD were recently published.2 The Rome criteria are meant to provide a general framework for clinicians but obviously do not describe all patients. A unifying symptom, present in all patients with SOD, is pain. There may be associated symptoms such as nausea with or without vomiting but the hallmark symptom is pain—located in the epigastrium and/ or right upper quadrant (RUQ). When evaluating a patient with possible SOD, the most important aspect of the evaluation is the history. It is imperative that the clinician gain a clear understanding of the nature, location and timing of pain. The Rome criteria specify that the pain should be intermittent with pain-free intervals. This is a very controversial point. While biliary pain is typically intermittent, in some cases, patients will have a constant, low-grade discomfort with exacerbations. This can be seen particularly in those with pancreatic sphincter hypertension who typically have exacerbations after eating. These patients should undergo careful review and extensive evaluation for other causes of pain (Table 34.3) but should not be excluded from evaluation for SOD based solely on there being a constant component to their pain. However, if associated symptoms such as nausea, vomiting, abdominal distention or bowel dysfunction are dominant, then the patient likely does not have SOD as the predominant explanation for their symptoms. Based on observations and after developing correlations between patients’ presentation and outcomes after endoscopic sphincterotomy, Joseph Geenen, Walter Hogan, and Wylie Dodds published what have become to be known as “The Geenen-Hogan Criteria” (Table 34.4).3 These have been modified over the years but still serve as a very good “compass” to clinicians to direct them in their evaluation and therapeutic decision making. The original criteria were applied to patients who had previously undergone cholecystectomy and were based on three factors which could be assessed without ERCP-presence of “typical” pancreatic or biliary type pain, the presence or absence of elevated liver or pancreatic tests during or shortly following an episode of pain, and the presence or absence of bile and/or pancreatic duct dilation. The original criteria also included measurement of pancreatic and biliary drainage times. Drainage times are very imprecise, require instillation of contrast into the respective duct and in the case of biliary drainage times, the endoscope must be withdrawn, the patient placed in the supine position and an abdominal film obtained at 45 minutes. Studies have shown that drainage times do not correlate with SOM4 and delayed drainage is common in asymptomatic postcholecystectomy volunteers.5 As a result, drainage times are no longer performed and are not part of the current Geenen-Hogan (G-H) criteria. 367

SECTION 3 APPROACH TO CLINICAL PROBLEMS

Post cholecystectomy Episodes of severe steady pain located in the epigastrium and right upper quadrant and all of the following: 1. Episodes lasting 30 minutes or longer 2. Recurrent symptoms occurring at different intervals and not daily 3. The pain is steady, interrupts daily activity and/or leads to medical encounter 4. The pain is not relieved by bowel movements, postural change, or antacids 5. Structural diseases that could explain symptoms are excluded

Table 34.1 Rome criteria for sphincter of Oddi dysfunction Gallbladder in situ Episodes of severe steady pain located in the epigastrium and right upper quadrant and all of above criteria plus: Normal liver and pancreas chemistries Absence of gallbladder stones, sludge, or microlithiasis Abnormal gallbladder emptying

Table 34.2 Rome criteria for sphincter of Oddi dysfunction Esophageal Spasm or other motility disorder Esophagitis Gastric Gastroparesis Ulcer Hiatal hernia Volvulus Pyloric stenosis Duodenal Stricture Ulcer Diverticulitis Ampullary neoplasm Biliary Stone Benign stricture Sump syndrome Neoplasm Pancreatic Chronic pancreatitis Neoplasm Abdominal Wall Neuroma Myopathy/myositis Irritable bowel syndrome

LFT > 2X Normal × 2

BD diam > 10 mm

+ + +

+ + −

+ + −

or

Table 34.4 Geenen-Hogan classification for SOD

368

The first step is a detailed review of prior health care encounters pertinent to the clinical presentation with a focus on questions of when, where, and what (Table 34.5). A complete history and thorough review of records will define the clinical symptoms, reveal what tests have been done, what treatments (surgical, endoscopic, medical) have been tried, and what the impact has been on the patient. Patients with unexplained symptoms that may be attributed to SOD often end up undergoing a massive assault with both diagnostic and therapeutic fronts. It can be helpful to organize objective data with regards to prior laboratory testing, imaging and treatments (Table 34.6).

Table 34.5 Important history questions for suspected SOD

Typical pain

LFT = Liver function tests. BD = Bile duct.

CLINICAL EVALUATION

When did the attacks begin? When do the attacks occur? Where is the pain? Where does the pain radiate? What is associated with the attacks? What has been done to investigate the cause? What has been done to treat the attacks? What are the consequences of the attacks?

Table 34.3 Diagnoses to consider (other than SOD) for unexplained upper abdominal pain

Type I Type II Type III

The G-H criteria are important because they represent a framework around which a clinician can plan patient evaluation. If one obtains an appropriate history of pain, bile duct imaging should be obtained and the patient should be given a prescription directing health care providers (in an emergency room, hospital lab or clinic) to obtain liver and pancreatic tests (amylase and lipase) during or shortly after a pain episode. These data then can be used to stratify patients as to their likelihood of having SOD.

Laboratory and pathology Serum liver and pancreas chemistries Serum fasting triglyceride Gallbladder pathology Imaging Transabdominal ultrasound Computed tomography Magnetic resonance with MRCP Biliary scintigraphy Endoscopic ultrasound Intraoperative cholangiography Previous Treatment Surgical Cholecystectomy Biliary bypass Pseudocyst drainage Pancreatic bypass or resection Partial gastrectomy Gastric bypass Endoscopic Biliary sphincterotomy Pancreatic sphincterotomy Stenting

Table 34.6 Clinical details pertinent to sphincter of Oddi dysfunction

Chapter 34 Pancreaticobiliary Pain and Suspected SOD

Type

I

II

III

Definition Baseline pressure >40 mmHg Benefit from sphincterotomy

Pain + 3 criteria* 70–100% 55–91%

Pain + 1 or 2 criteria* 40–86% p > 40 mmHg: 80–90% p < 40 mmHg: 30–35%

Pain only 20–55% p > 40 mmHg: 8–56%

Table 34.7 Correlation between Geenen/Hogan Criteria, results of SOM and outcome with sphincterotomy The criteria used were the following: 1. ALT and alkaline phosphatase over twice upper limit of normal. 2. Dilated bile duct on sonography. 3. Delayed drainage of contrast material at ERCP.

Some historical details may indicate that SOD is likely. It is not uncommon for SOD patients to have undergone cholecystectomy because of a “diseased” or dysfunctional gallbladder. Patients with a history of chronic narcotic analgesic use who then develop pancreaticobiliary pain often have SOD. Symptomatic patients who have a history of common bile duct exploration, postoperative bile leak and/or post-ERCP pancreatitis are often discovered to have SOD. Pain is a subjective complaint. Nevertheless, considerable information can be obtained. There are a number of “classic” descriptors that can help guide whether or not SOD is a likely cause for pain. Typical pancreatic/biliary pain occurs intermittently, begins after meals, and lasts minutes to hours. It is located in the epigastric or right upper quadrant areas and may radiate to the back, chest or right shoulder. Occasionally, the pain is perceived first in the back or chest. Daily pain that is constant is not typical for SOD unless associated with chronic pancreatitis. Patients may be awakened from sleep because of pain. It is not uncommon for patients to describe their symptoms as “my gallbladder pain” and even describe symptoms that are “worse than my gallbladder attack.” Transient elevations of serum liver and/or pancreas enzymes drawn hours after pain onset may suggest SOD. The possibility of more common and potentially more treatable diagnoses should be considered before proceeding with an evaluation for possible SOD. Symptom history and diagnostic testing should be directed at evaluation for the potential diagnoses listed in Table 34.3. For example, bile duct dilation should raise a suspicion for neoplasia or bile duct stones if associated with abnormal liver tests. Alternatively, a dilated bile duct with normal liver tests in a patient with intermittent pain should raise suspicion for SOD. Evaluation for possible common bile duct stones deserves careful consideration. Bile duct stones are very rarely found when routine imaging tests such as transabdominal ultrasound and laboratory testing are normal. Therefore, unless there are objective indicators to suggest bile duct pathology, ERCP should be avoided when purely used to “rule out bile duct stones.” Additional imaging such as MRCP or EUS can be helpful in this setting. It is most reasonable to consider ERCP when SOM and/or definitive endoscopic therapy is planned. Ideally, patients with unexplained upper abdominal pain can be categorized as to the likelihood for SOD and a favorable response to endoscopic treatment. The Geenen-Hogan classification (Table 34.4) is the standard in this regard. Type I SOD patients have objective evidence of impaired drainage and are more likely to have structural obstruction (papillary stenosis). In addition to characteristic pain, they have dilated duct(s) and abnormal liver tests during episodes of pain. Patients with Type II SOD will have characteristic pain and either a dilated duct or abnormal laboratory tests with pain. Type III SOD

patients have typical biliary or pancreatic pain but no objective evidence of impaired drainage. Such patients likely have a purely functional disorder. The reason that this categorization of patients is important is that it predicts, to a certain extent, the chance of finding an abnormal SOM and having a favorable outcome following sphincterotomy (Table 34.7).6 Remarkably, disease and/or interventions of such a small structure may lead to a tremendous burden on behalf of the patient and their physician. From the patient standpoint, SOD may present a wide spectrum of physical and emotional symptoms ranging from nuisance to total disability. Much of the emotional burden is derived from uncertainty. Patients become desperate when not knowing the cause of their symptoms; whether and when they will have future attacks, and if there are safe and effective treatments. Diverse challenges which face physicians include substantial time-requirements, potential legal ramifications, and the broad range of necessary skills such as history taking, record-keeping, radiology interpretation, and psychological assessment. Moreover, physicians who decide on doing ERCP in this setting need to possess appropriate technical skills such as sphincter manometry, selective cannulation, sphincterotomy (perhaps precut), and pancreatic therapy. Compassion and judgment are the intangible physician qualities that are more important than knowing how to cut a sphincter or place a stent. These qualities are tested when faced with the often asked question: “What would you do if I was your mother or daughter or . . .?” Once a clinical impression of SOD is established, ideally a noninvasive test would be available to confirm one’s clinical impression before proceeding to ERCP. Several tests have been studied and individual centers have reported good correlation with SOM and/or sphincterotomy. The problem is that when these tests are evaluated on a broader scale, their accuracy does not match previous, single center reports. The Hopkins group first reported on the accuracy of dynamic (quantitative) biliary scintigraphy.7–8 The test was designed to measure delayed bile flow through the ampulla by assessing the time it takes for the radionuclide to reach the duodenum. These authors found a good correlation with SOM. Their results were supported by Corazziari, et al.9 This prompted the Hopkins group to suggest that this test could substitute for SOM.10 However, when this test was evaluated in normal volunteers, we found it had very poor specificity and it had little value in excluding SOD in patients suspected to suffer from this disorder.11 Another test hypothesized to detect SOD is fatty meal ultrasound (FMS). An abnormal test is defined by a >2 mm dilation of the bile duct 45 minutes after ingestion of a standardized “fatty meal.” Rosenblatt et al. compared SOM, FMS and hepatobiliary scintigraphy (HBS) in a retrospective comparative study.12 Poor correlation was observed between FMS and HBS with SOM. However, of the patients with abnormal SOM who had a good long-term response to 369

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sphincterotomy, 85% (11/13) had an abnormal FMS and HBS. This raises an interesting point; perhaps non-invasive tests should be evaluated as to whether they predict response to sphincterotomy rather than whether they correlate with SOM. What a clinician really wants to know from a non-invasive test is whether or not the patient will respond to endoscopic sphincterotomy.

UPPER ABDOMINAL PAIN WITH GALLBLADDER IN SITU Management of patients with biliary-type pain without evidence of gallstones on standard imaging represents a challenge. Physicians (including surgeons) and patients usually prefer to identify some proof of gallbladder pathology before considering cholecystectomy. Biliary crystal analysis can be performed on bile collected from the duodenum or bile duct after cholecystokinin (CCK) stimulation. Endoscopic ultrasound is more sensitive for discovering biliary sludge13–14 and can also be used to assess for evidence of pancreatitis. If EUS and CCK stimulated biliary drainage are performed and biliary crystals or gallbladder sludge are found, >90% of patients will have resolution of pain with cholecystectomy.15 Biliary scintigraphy may reveal evidence of chronic acalculous cholecystitis (gallbladder ejection fraction <35%).16 Empiric cholecystectomy, however, will benefit about three-fourths of those patients with classic biliary pain, independent of other testing.17–21 The exact role for SOM in this setting is not established. There has been limited study of the prevalence of sphincter of Oddi dysfunction (SOD) in patients with gallbladder in situ. Guelrud reported on 121 patients with biliary pain and a finding of gallstones but a normal caliber bile duct by ultrasound.22 ERCP and sphincter of Oddi manometry was performed and he found elevated basal sphincter pressures in 14 patients (11.6%). Interestingly, 4% of patients in this group with a normal alkaline phosphatase had elevated basal sphincter pressures while 40% with an elevated alkaline phosphatase were found to have SOD. Ruffolo et al. investigated 81 patients with typical biliary-type pain and a normal gallbladder ultrasound.23 When ERCP and sphincter of Oddi manometry was performed, 53% of these patients had sphincter of Oddi dysfunction as diagnosed by elevated basal sphincter pressures. For the whole group, 49% had an abnormal ejection fraction on gallbladder scintigraphy but the finding of sphincter of Oddi dysfunction did not correlate with ejection fraction. All patients in this group with elevated sphincter pressures underwent biliary sphincterotomy and the short-term results of pain relief (one year) were quite good. However, with longer-term follow-up, most patients ultimately required cholecystectomy.24 Our approach is to avoid SOM in patients with gallbladder in situ because laparoscopic cholecystectomy is safer than ERCP. Also, SOM testing may be misleading in this setting. While sphincter of Oddi dyskinesia (tachyoddia) may be detected, basal sphincter pressure may still be normal in patients without prior upper abdominal surgery because inhibitory neurons to the sphincter remain intact. However, ERCP with SOM may be reasonable where typical biliary pain is accompanied by transient elevations of liver enzymes.

UNEXPLAINED ACUTE PANCREATITIS The diagnosis of acute pancreatitis is usually straightforward. Pancreatic pain is most often epigastric and radiates through to the back. Serum amylase and/or lipase should be three times normal before 370

making a diagnosis of acute pancreatitis. In situations where there are equivocal laboratory results or when labs were drawn many hours after the onset of pain, a diagnosis can be made if there is radiographic evidence of pancreatitis. A thorough review on the approach to acute pancreatitis is covered elsewhere is this book. Sphincter of Oddi dysfunction is considered along with other structural causes (microlithiasis, neoplasia, pancreas divisum, duodenal diverticulum, choledochocele) when more common causes (alcohol, gallstones, medications) have been excluded. Evaluation with ERCP and SOM should be considered when a patient has had either recurrent attacks or at least one attack that was considered to be severe. Patients of 50 years and older should also undergo endoscopic evaluation in order to exclude neoplasia.

INFORMED CONSENT FOR ERCP FOR SUSPECTED SOD Most important to any discussion on suspected SOD is informed consent. Proper informed consent before ERCP in a patient with suspected SOD is in itself a complex venture. “Informed” means that both the physician and patient have a thorough understanding of the clinical situation before determining the potential for risk and benefit. The physician’s role is largely limited to acquiring and sharing information. Information that is relayed to the patient includes review of relevant data (if any) regarding efficacy and safety of endoscopic treatment. It may be just as important to disclose the fact that there is very little efficacy data. Fortunately, we do have reasonable data regarding complications of ERCP in suspected SOD (see below). A physician should share their own complication data that is specific for that situation. For example it is inappropriate to either state complication data from other endoscopists or that from other clinical situations e.g. bile duct stones. At the present time, it remains particularly important that patients with purely functional symptoms who have no objective evidence of digestive duct obstruction understand that they are making a benefit/risk decision that pertains to a quality of life problem. Patients should understand that they are ultimately responsible for giving their consent and that they should not solely depend on “physician advice.”

SPHINCTER OF ODDI MANOMETRY Equipment Traditionally, sphincter of Oddi manometry has been performed using a water perfused, low-compliance pneumohydraulic system. This is the same system that was originally used for esophageal manometry. However, unlike esophageal manometry, which is now undertaken primarily with electronic systems, almost all centers performing sphincter of Oddi manometry, continue to use the water perfused system because: 1. All of the “normal” data has been generated with a water perfused system. 2. The electronic manometry catheters are expensive and fragile. Advances have been made in water perfused systems, particularly in the software, which makes set-up, recording and interpreting the manometry much easier. These systems are available through Sandhill (Sandhill Scientific, Inc., Highlands Ranch, Colorado) and Medtronic (Minneapolis, Minnesota), as well as other manufac-

Chapter 34 Pancreaticobiliary Pain and Suspected SOD

perfused systems are readily available as are the catheters used to perform SOM. The equipment can be contained on a small mobile cart which can be wheeled into and out of the ERCP suite easily. It takes a matter of only a few minutes to set up the system and thus is not an onerous addition to an ERCP case.

Technique

Fig. 34.1 Distal tip of SOM catheter. Top arrow points to guidewire. Bottom arrow points to distal side hole.

turers. The entire system consisting of the computer and the water perfusion system, can be placed on a small cart and is readily mobile. The original catheter used for sphincter of Oddi manometry was manufactured by Arndorfer (Arndorfer Inc., Greendale, Wisconsin) and some practitioners still use these catheters. However, the majority of catheters used in sphincter of Oddi manometry are manufactured by Cook GI Endoscopy (Winston-Salem, NC). The catheter consists of three lumens, two of which terminate in a side hole of the catheter while the third lumen has both a side port as well as an end port (Fig. 34.1). The lumen with the end port does accommodate a 0.018” guidewire. All three channels can be used for the manometry recording but a randomized study showed that sacrificing the third lumen with the side and end port, and using that for aspiration during a pancreatic manometry, significantly reduced the postmanometry pancreatitis rate.25 It was found that aspiration during manometry of the biliary sphincter was not necessary.26 Water is perfused at 0.25 ml per minute through each port. The triple lumen manometry catheter made by Cook GI Endoscopy consists of Teflon and is tapered at the end. In the distal end of the catheter, there are black rings spaced 1 mm apart. Moving proximally to distally, there are seven black rings followed by a red ring, a black ring and another red ring in sequence. The rings allow communication between the endoscopists and the manometry assistant to record the position of the catheter relative to the papilla orifice. The proximal end of the catheter (that portion that is outside the scope channel) is bolstered by an additional plastic coating that helps stiffen the catheter and prevents kinking as the catheter is inserted and withdrawn. The catheter is supplied in two types—the so-called “short nose” and “long nose.” The short-nose catheter has 5 mm between the last black ring and the tip of the catheter. The length of the distal tip on the long nose catheter is 20 mm. The main advantage of the long nose catheter is that the manometry can be completed (withdrawn to the last ring) while maintaining the cannulation. The downside of this catheter, in the opinion of these authors, is that the long nose catheter is harder to cannulate with. In summary, the equipment to perform sphincter of Oddi manometry is reasonably uncomplicated. The computer and water

The technique of sphincter of Oddi manometry is relatively straightforward. It consists of deep cannulation followed by a slow “stationed” withdrawal. There are two basic cannulation techniques employed when performing sphincter of Oddi manometry. The first is called the “kissing” technique (video). Here, the manometry catheter is advanced a short distance into the visual field and the elevator is moved maximally “up.” The endoscopist’s left thumb is positioned on the up/down knob with the right hand grasping the shaft of the scope. Using the right hand, the scope is inserted or withdrawn as necessary to allow the manometry catheter to be inserted into the papillary orifice using the “up” dial of the endoscope. Once the tip of the catheter is seated in the papillary orifice, the manometry catheter is slowly advanced until slight resistance is met. Now, with a greater amount of catheter beyond the elevator, the shaft of the endoscope is then regrasped with the right hand and then deep cannulation is accomplished by varying the trajectory of the catheter using the up/down dial and driving it forward into the duct by withdrawing the scope. The second method of cannulation relies on the more standard approach of advancing the catheter into the papillary orifice using the elevator (video). However, once the tip of the catheter is “seated” into the ampullary orifice (a step that we call insinuation), the most effective way to advance the catheter deeply is to withdraw the scope. The most common mistake in trying to achieve deep cannulation is to simply advance the catheter. The natural curve of the catheter will cause the tip to be driven into the roof of the papilla with this technique and one usually fails to get deep cannulation. One must remember that whatever technique is used to advance the catheter, it must be advanced directly in line with the trajectory of the duct. As mentioned earlier, this is usually best achieved by withdrawing the scope and adjusting the up/down of the scope tip. Another common problem is the natural mucosal folds that are usually present within the intraduodenal segment of the ampulla. The catheter tip is commonly driven into these folds and trying to forcibly advance the catheter against these folds usually fails and can result in trauma and even tearing of the ampullary mucosa. The most effective way to get around these folds is to advance the scope very slightly which results in backing the catheter out of the papilla. Once the catheter has been withdrawn, the tip should be redirected and then the scope withdrawn which will drive the catheter into the papilla hopefully this time avoiding the folds. One should remember that the ampulla is never so tight that brute force is needed to cannulate. It is virtually always an issue of achieving the proper tip trajectory. There are two general approaches to cannulation when one is planning to perform sphincter of Oddi manometry. One first achieves cannulation using a standard accessory such as a diagnostic cannula or a sphincterotome. Once cannulation is achieved, a cholangiogram or pancreatogram is performed and if no pathology is seen (stone or stricture) a 0.018 inch guidewire is passed and then the manometry catheter is advanced over the guidewire. This is usually employed at centers that do not do a lot of sphincter of Oddi 371

SECTION 3 APPROACH TO CLINICAL PROBLEMS

manometry and who wish to perform manometry of the biliary sphincter only. The technique that we advocate is to perform free cannulation as the initial step in the ERCP with the manometry catheter alone. Our reasoning for this approach is: 1. With good technique and experience, free cannulation with a manometry catheter in one or both ducts can be achieved in over 90% of the time. Attempted free cannulation of course does not prohibit the use of a standard catheter if this technique fails. 2. Cannulation with a standard catheter is no easier than with a manometry catheter and adds additional steps to the procedure. A guidewire exchange then must be performed. The best guidewire to use in conjunction with sphincter of Oddi manometry is the Nitinol based 0.018” wire. This particular wire does not aid in cannulation as its very thin, soft and floppy tip easily gets caught on the mucosal fold within the ampullary segment. 3. The manometry catheter can be used to obtain a cholangiogram by infusing contrast through the aspiration port. Before recording the sphincter pressures, one must obtain a “duodenal baseline” pressure. This can be achieved two ways. The technique that we utilize (and is utilized in most centers) is to advance the entire tip of the manometry catheter into the duodenal lumen. The catheter is then perfused and a baseline pressure is established. During this “baseline,” the catheter should not come in contact with the duodenal wall. A second method for obtaining duodenal baseline achieves a continuous recording of the duodenum. With this technique, a separate manometry catheter is taped to the side of the duodenoscope and the duodenal baseline is recorded continuously throughout the manometry. We do not make any attempt to select a particular duct as we begin sphincter of Oddi manometry. We perfuse only two of the three channels and use the third channel for aspiration. Once the manometry catheter is deeply in the duct, gentle aspiration is applied to the “auxiliary” channel (video). If a clear fluid is withdrawn, then it is known that we are in the pancreatic duct. If yellow fluid is seen, then this identifies the bile duct. We then perform a standard stationed pull-back. In a stationed pull-back, we withdraw the catheter until the first black ring is identified and at this point, we notify the manometry assistant that we are “at one black.” The manometry assistant then informs the endoscopists as to whether or not any phasic contractions are seen. If not, then the endoscopist withdraws the catheter to “two black.” Again, this position is held to determine if any phasic waves are identified. This process of withdrawal of one black ring at a time continues until typical phasic contractions are identified. Once phasic contractions are identified, it is determined whether the nadir of the phasic contractions dips below 40 mm Hg or not. If so, then the catheter is withdrawn to the next station. If however, a station is achieved in which the nadir of the phasic contractions remains above 40 mm Hg, then the manometry assistant informs the endoscopists of this and instructs the endoscopists to hold that position for at least 30 seconds. If the nadir of the phasic contractions remains above 40 mm Hg throughout that 30 second time period, then this would be interpreted as an abnormal recording for that lead. Once the 30 second span has been achieved, then the manometry assistant instructs the endoscopists to withdraw another station. Again, the nadir of the phasic waves is viewed to determine if it remains above 40 mm Hg. An abnormal sphincter of Oddi manometry is determined when the nadir of the phasic waves remains above 40 mm Hg for a 30 second span in both leads. As the catheter is withdrawn, the more proximal of the two side ports 372

should come into the sphincter zone and one should obtain abnormal 30 second recording. Then as the catheter is withdrawn, the more proximal port will eventually come back to normal while the distal port then enters the abnormal sphincter zone. With further withdrawal, both leads are withdrawn out of the sphincter zone and the nadir of the contractions returns to baseline. One “weakness” in sphincter of Oddi manometry is that interpretation of the recordings is not standardized. Most people accept 40 mm or greater as being abnormal, yet the largest study looking at normals suggests that 35 mm Hg is a better figure.27 Various systems are used to obtain an actual value for the basal sphincter pressure. The Indiana group advocates taking the nadir value for the four lowest nadirs over a 30 second run and then averaging those three values.28 The most important factor however is that most agree that there should be a sustained time (most agree on 30 seconds) where the nadir of the phasic waves does not dip below 40 mm Hg. During this time, it can be extremely important to keep the position of the catheter steady. This can be challenging if there is active duodenal motility or respiratory movements are transmitted to the abdominal cavity. During the critical zone of recording, it is extremely important that there be immediate communication between the endoscopists, and the manometry nurse to indicate the exact position of the manometry catheter relative to the ampullary orifice. If the basal pressure is changed, it is important to know that the catheter is in the same position. A very controversial part of sphincter of Oddi manometry has been the type of sedation and adjunctive medications which are acceptable while performing sphincter of Oddi manometry. Traditionally, conscious sedation for endoscopy has been accomplished with the combination of narcotic and benzodiazepine. It is known that narcotics do affect intestinal motility and sphincter recordings. Thus for many years, conscious sedation for ERCP and sphincter of Oddi manometry was accomplished with a benzodiazepine alone. However, benzodiazepines alone frequently provide inadequate sedation for patients and many patients develop “paradoxical agitation” when high doses of benzodiazepines are used. Credit should be given to Grace Elta and her colleagues at the University of Michigan who were the first to question the validity of avoiding narcotics for conscious sedation for sphincter of Oddi manometry.29 In a small limited study, they found that basal sphincter pressures (the values used to determine if a manometry is normal or abnormal) were not affected by Demerol in a dose of 1 mg/kg. This finding was confirmed by a larger, better designed study done at Indiana University.30 This initiated an era where meperidine was routinely used in conjunction with benzodiazepines for sphincter of Oddi manometry. More recently, propofol has been advocated for use during ERCP to achieve even better sedation. Several animal studies have demonstrated that it does not affect SOM in dogs and sheep.31– 32 However, only one human study has been reported and involves only 11 patients. This study concluded that propofol did not alter basal sphincter of Oddi pressures.33 Today, propofol is routinely used in many centers to achieve deep sedation for the performance of sphincter of Oddi manometry. In some cases, duodenal motility can make cannulation very difficult. While glucagon (Eli Lilly, Indianapolis, Indiana) is used routinely in standard ERCP to control duodenal movement, it cannot be used during sphincter of Oddi manometry as it does affect sphincter pressures. If it is impossible to cannulate without the aid of glucagon, it is recommended that 5 minutes pass between a dose of glucagon and manometry recording.

Chapter 34 Pancreaticobiliary Pain and Suspected SOD

TREATMENT Medical Medical therapy has not been widely studied as a treatment for sphincter of Oddi dysfunction. Because the sphincter of Oddi is a smooth muscle structure, it makes some sense that pharmacologic therapy might be of benefit. If the theory is correct that sphincter of Oddi dysfunction falls into functional or structural categories, medications would then be of benefit only for those with functional disease. Empiric pharmacologic trials are most reasonable in Geenen-Hogan Type III patients with relatively mild and infrequent episodes of pain. The drugs most studied in sphincter of Oddi dysfunction are calcium channel blockers and nitrates. Khuroo et al. investigated nifedipine in a placebo-controlled crossover trial in 28 patients.34 End points for the study included reduction in pain scores, emergency room visits and use of oral pain medication. Seventy-five percent of 28 patients responded to nifedipine. Sand et al. looked at the effects of three calcium channel blockers with differing smooth muscle selectivity (verapamil, nifedipine and felodipine) on human sphincter of Oddi contractions.35 Results showed that all 3 calcium channel blockers are potent inhibitors of contraction and it was concluded that this category of drugs might be helpful in SOD. Sand et al. performed a 16-week double-blind crossover study using nifedipine in Geenen-Hogan type II patients and showed that it decreased the number of days in which patients experienced pain.36 A slowrelease form of nifedipine was tested in a small pilot study in patients with SOD with encouraging early results.37 Nitrates have been studied experimentally but there has not been a large literature using this class of medications in humans. Gocer et al. found that isosorbide dinitrate decreased rhythmic and tonic contraction in guinea pig-isolated sphincter of Oddi muscle.38 Bar-Meir described the disappearance of pain as well as a decrease in both basal and phasic sphincter activity on repeat manometry after nitrate therapy in a woman with manometry-proven papillary dysfunction.39 Finally, Wehrmann et al. looked at topical application of nitrates onto the papilla of Vater and found that topically applied nitrates had a profound inhibition of sphincter of Oddi motility.40 The new “drug” on the block may be nitric oxide (NO). Nitric oxide plays an important role in the regulation of intestinal and pancreaticobiliary motility. Inhibition of nitric oxide synthetase (NOS) increases intraluminal pressure within the GI tract. We looked at the effect of an inhibitor of NOS, NG-Nitro-L-arginine methyl ester (L-NAME) on the mean basal pressure of the sphincter of Oddi in the anesthetized pig. We found that L-NAME significantly increases mean sphincter of Oddi pressure in this animal model and the physiologic affect was sustained for the duration of the experiment (3 hours).41 Noting that topical administration of a NO donor induces SO relaxation in humans, Niiyama et al. looked at the effect of intrasphincteric injection of sodium nitroprusside (SNP) on the pig SO. They found that intrasphincteric injection of SNP significantly reduced the mean basal pressures which lasted up to 45 minutes without inducing side effects or significantly lowering blood pressure.42 Research is ongoing to develop pharmaceutical agents that will generate nitric oxide and these may serve as potential treatment for sphincter of Oddi dysfunction.43 Despite some promising developments, medical therapy for sphincter of Oddi is still problematic for a number of reasons: 1. Current therapy, particularly nitrates, have a significant side effect profile (especially headache).

2. There is lack of long-term data. 3. The variability of response may be due to our inability to differentiate between fixed stenosis and functional spasm. To move forward with medical therapy, well-conducted, placebocontrolled, randomized trials with long-term follow-up need to be performed. The main drawbacks of medical therapy at this point are the lack of specificity for the sphincter of Oddi and the lack of a long-acting medication with a low side effect profile.44

Endoscopic Endoscopic therapy has been the most widely employed treatment for sphincter of Oddi dysfunction. When assessing outcomes after endoscopic sphincterotomy, specifics of the patient population (G-H Type I, II or III) and the exact nature of the intervention (biliary or dual sphincterotomy) must be taken into account. There is only one study that focuses on sphincterotomy solely in G-H type I patients.45 This was a relatively small study population of 17 patients with biliary type pain, dilated bile duct and abnormal liver tests during episodes of pain. At ERCP, only 65% had abnormal basal sphincter pressures with SOM but all benefited from biliary sphincterotomy with a mean of 2.3 years follow-up. The strongest data supporting the efficacy of endoscopic intervention is contained in three randomized trials,46–48 two of which46,48 included only G-H type II patients who underwent either sham therapy or biliary sphincterotomy alone. In the landmark study by Geenen et al. all patients underwent ERCP with SOM and all patients were then randomized to either sham therapy or biliary sphincterotomy (the endoscopist was blinded to the results of the manometry).46 The results helped validate both the predictive capability of SOM as well as the benefit of sphincterotomy. The patients with normal SOM did not benefit from sphincterotomy but those with abnormal basal sphincter pressures did. The important “take home” points of this trial are: 1. Only Type II patients were included 2. Patients underwent biliary sphincterotomy alone 3. Those patients with abnormal basal sphincter pressures treated with sphincterotomy benefited significantly more than those with normal SO pressures treated by sham or sphincterotomy. The Toouli et al. study48 was designed somewhat similar to the Geenen study. It included only G-H type II patients and involved randomization of all patients to sham therapy or biliary sphincterotomy. In this trial, however, if the manometry was initially normal, the patients were provoked with cholecystokinin in an effort to detect a subset of patients with “functional SOD.” The outcomes were similar to the Geenen study, 85% (11/13) patients with elevated basal sphincter pressures benefited from sphincterotomy whereas only 38% (5/13) patients benefited from sham therapy (P = 0.041). The outcomes were similar for both the sphincterotomy and the sham group who had normal SOM. The Indiana trial, however, was distinctive for several reasons: it had a 3 group randomization—sham, endoscopic biliary sphincterotomy, surgical (dual) sphincteroplasty, and the trial involved G-H Type II and III patients.47 The latter characteristic of the Indiana trial is particularly important because most centers that have expertise in SOD see a predominance of G-H type III patients. However, this trial did not randomize all patients; only those with abnormal SOM. The results with 3-year follow-up revealed that 69% of patients in the endoscopic sphincterotomy and surgical sphincteroplasty groups benefited compared to only 24% of the sham group (P = 0.009). 373

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The most serious void in our data is the lack of well-designed trials that address whether SOM predicts outcome and whether sphincterotomy is beneficial in G-H type III patients. The Indiana data did contain type II patients but did not address the predictability of SOM. Such a trial is currently being designed and will be undertaken as part of a multi-center protocol. The other issue regarding endoscopic intervention that has not been adequately addressed in properly designed studies is the efficacy of biliary sphincterotomy alone versus combined biliary and pancreatic sphincterotomy. There is, however, a growing body of evidence that suggests that some patients may benefit from dual sphincterotomy. It is known from reports in which dual manometry has been performed that there is generally a concordance between the pancreatic and biliary sphincter pressures. In the majority of cases, they are either both normal or both abnormal. There is however, some discordance which suggests that about 10% of the time there is isolated biliary sphincter hypertension and about 20% of the time there is isolated pancreatic sphincter hypertension.49–50 In a previous report by Guelrud51 biliary sphincterotomy alone versus biliary and pancreatic sphincterotomy was evaluated in a group of patients with Type II pancreatic sphincter of Oddi dysfunction and recurrent pancreatitis. Twenty-eight percent of patients undergoing biliary sphincterotomy alone showed improvement whereas 86% (12/14) showed improvement if dual sphincterotomy was performed. There was also a subset of 13 patients who underwent biliary sphincterotomy followed by pancreatic sphincterotomy in a later session, and ultimately 77% of those patients improved. In both cases (biliary and pancreatic sphincterotomy at the same session or pancreatic sphincterotomy at a later session), results were significantly improved over patients with biliary sphincterotomy alone. Another study from the University of Iowa52 looked at a group of 26 patients who had not responded to biliary sphincterotomy despite abnormal sphincter of Oddi motility. 25/26 underwent a repeat ERCP and pancreatic sphincterotomy and 16 of them (64%) responded. A further study by Kaw et al.53 looked at biliary versus dual sphincterotomy and related it to which sphincter had abnormal manometry. For those with an abnormal biliary manometry alone, 80% responded to biliary sphincterotomy. However, if isolated pancreatic sphincter hypertension or combined biliary and pancreatic sphincter hypertension were found, only 7/23 (30%) responded if patients underwent a biliary sphincterotomy alone. Alternatively, if patients had isolated pancreatic sphincter hypertension or combined biliary and pancreatic sphincter abnormalities, 11/16 (69%) responded to dual sphincterotomy. Although there is increasing enthusiasm for performing a dual sphincterotomy in those patients in which the pancreatic sphincter has been shown to be abnormal, a definitive recommendation must await a properly designed, randomized clinical trial. Some investigators have tried botulinum toxin (BoTox, Allergan Inc., Irving, California) injections directly into the sphincter as a substitute for sphincter of Oddi manometry,54 as a permanent treatment for sphincter of Oddi dysfunction,55–56 or to prevent post-ERCP pancreatitis.57 The presumption with BoTox is that the pain of sphincter of Oddi dysfunction comes from the sphincter itself and by preventing tonic contraction, symptoms can be relieved. Sand et al.58 demonstrated that botulinum toxin inhibits pig sphincter of Oddi smooth muscle contractions and Wang et al.59 showed that in dogs, it reduced contractile activity for a prolonged time. The first clinical report of its use in SOD was by Wehrmann.55 They injected 100 international units of botulinum toxin in 22 patients with 374

manometrically documented SOD (all were Geenen-Hogan type III patients). Six weeks later, 55% (12 patients) were symptom-free and 45% (10 patients) were not. The 10 non-responders underwent ERCP and biliary sphincterotomy. Five of ten patients had normalized their sphincter pressure and did not respond to biliary sphincterotomy with longer-term follow-up. Eleven of twelve initial responders relapsed at a median of six months. Repeat manometry revealed sphincter hypertension in 11/23 and 11 responded to endoscopic sphincterotomy. This initial report has not been followed by a prospective randomized study. Goerlick et al.57 found it to be effective in decreasing the risk of post-ERCP pancreatitis in manometrically positive SOD patients; however, the incidence of pancreatitis was 25%, which in the era of pancreatic stenting, is unacceptable.60 There are several drawbacks to this approach. 1. Botulinum toxin has not been subjected to a randomized study in the way that manometry has—at least in Geenen-Hogan type II patients. 2. When botulinum toxin is used as a treatment of sphincter of Oddi dysfunction, it is logical that its effect will be transient as we have seen in botulinum toxin in achalasia patients. 3. When used as a predictor of response to sphincterotomy, it requires a second procedure, which exposes patients with suspected SOD to yet another procedure that could cause pancreatitis. In summary, there are inherent drawbacks to botulinum toxin use in sphincter of Oddi dysfunction. The most important factors are that overall experience is very small and botulinum toxin has not been subjected to well-designed, randomized studies with sufficient follow-up to determine efficacy. Though data is scant, BoTox does not appear to be as effective as short-term pancreatic stenting in preventing post-ERCP pancreatitis.

PREVENTION OF POST ERCP PANCREATITIS It was originally thought that it was the actual performance of SOM that caused post ERCP pancreatitis (PEP). We have come to learn however that the risk is in fact inherent in the patients themselves. This was outlined in a study published by Freeman et al. This landmark paper clearly outlines risk factors for post ERCP pancreatitis and most are related to the patients themselves (Table 34.8).61 Performance of ERCP, with or without manometry, in a young female with suspected SOD carries a very high risk of post ERCP pancreatitis. To date, the best study done which has looked at the role of manometry itself as a causative factor in PEP reviewed 76 patients with suspected SOD undergoing SOM.25 The group was randomized to manometry in the standard fashion with all three ports perfused with 0.25 cc of water per minute versus perfusion through two

Multivariate analysis Suspected SOD Younger age

p. value <0.001 <0.001

Univariate analysis History of ERCP induced pancreatitis Female sex History of pancreatitis Distal bile duct diameter

<0.001 <0.001 <0.001 0.02

Table 34.8 Patient factors correlated with increased risk of pancreatitis From Freeman et al., NEJM 1996 [61].

Chapter 34 Pancreaticobiliary Pain and Suspected SOD

leads with simultaneous aspiration through the third channel. A previous study proved that aspiration during SOM did not affect the manometry results.62 This study was important because the procedure consisted only of SOM and the patients did not undergo ERCP after the manometry was complete. Thus, the study isolated SOM and recorded the incidence of PEP. The results showed that in the group being perfused, the pancreatitis rate was 23.5% whereas in the group undergoing aspiration, the pancreatitis rate was 3% (p = 0.01). The recorded rate of pancreatitis in the aspiration group is an acceptable rate for PEP, in general, and well below the rate generally quoted for patients with suspected SOD. The most important factor in reducing the risk of PEP in patients with suspected SOD reported to date is stenting of the pancreatic duct. The hypothesis is that manipulation of the ampulla in the course of performing ERCP (with or without sphincterotomy) may cause swelling and compromise pancreatic fluid drainage leading to pancreatitis. In a landmark study, patients with manometrically documented SOD were randomized to short-term pancreatic stenting versus no stent following biliary sphincterotomy.63 The results showed that the stented group had a PEP rate of 7% compared to a rate of 26% in the non-stented group (p = 0.03). A number of other studies have also suggested that there was benefit to pancreatic stenting to prevent PEP.64–67 Subsequently, Singh et al. performed a meta-analysis of published studies and concluded that pancreatic stenting was effective in reducing the incidence of post ERCP pancreatitis in patients with suspected or proven SOD.68 Pancreatic stenting is not without potential problems. The original prospective trials used short 5 Fr stents that required endoscopic removal. In an effort to avoid a second procedure to remove stents, we began utilizing stents that did not have a flap on the pancreatic side. The latter typically migrate within 1–2 weeks and are equally effective in preventing PEP.69 Many experts favor the use of smaller caliber (3 Fr), longer (8, 10 or 12 cm) pancreatic stents for this indication for the same reason (video). These stents have a pigtail on the duodenal side and no retention flap on the pancreatic side (Lehman pancreatic stent, Cook GI Endoscopy, Winston-Salem, NC). They must be placed over a 0.018” guidewire and because of the length of the stent, the guidewire must be passed into the tail of the pancreas. These stents typically fall out within 2 weeks and can be checked by obtaining a “plain film of the abdomen to include the diaphragms” 2–3 weeks after the procedure. If the stent is still in place, it will be seen as a radio-opaque thread crossing the spine in the upper abdomen underneath the diaphragm. If the stent is present at 3 weeks, one can wait an additional week and repeat the x-ray. If the stent remains after 4 weeks, then it is probably best to remove it with a side-viewing endoscope and a mini-snare. The main reason for using this stent is that it is very soft and flexible, and when left in place for 3–4 weeks, is associated with less iatrogenic ductal damage than that seen with larger stents.70–71 Three French stents also predictably stay in place for at least 72 hours which is probably the timeframe necessary to prevent PEP. The only drawback to this stent is that it requires passing the 0.018” guidewire to the tail of the pancreas. This can be difficult if there are multiple acute turns as the duct courses through the head of the pancreas. Occasionally we also encounter patients with an “ansa pancreaticus” in which the main pancreatic duct makes a 360° turn as it courses through the head of the pancreas. In cases with severe “sigmoid” bends or ansa pancreaticus, we favor placement of a short 5 Fr stent with the internal (pancreatic side) flap removed.

Though controversial and not yet subjected to a randomized trial, current retrospective data suggests that pancreatic stenting is helpful in preventing PEP in those patients found to have a normal SOM.72 The reason for this is unknown but the risk of PEP is inherent in patients with suspected SOD not just those proven to have it with abnormal manometry. Also, our data shows that 42% of patients with suspected SOD who have a normal manometry at their index ERCP, have an abnormal manometry if they return for a repeat examination suggesting that the initial manometry was falsely negative.73 Though current evidence is not as strong as it could be, our recommendation is that a short-term pancreatic stent be placed even if SOM is found to be normal.

EVALUATION OF PATIENTS WITH RECURRENT PAIN AFTER ENDOSCOPIC INTERVENTION FOR SPHINCTER OF ODDI DYSFUNCTION Despite an abnormal manometry, patients may not respond to endoscopic intervention or may demonstrate a transient response followed by a relapse. The results of a reinvestigation can lead to several potential findings: 1. incomplete prior biliary sphincterotomy 2. residual pancreatic sphincter hypertension 3. restenosis of the pancreatic sphincter 4. completely normal examination 5. evidence of early chronic pancreatitis If patients re-present with typical pancreaticobiliary pain after endoscopic therapy for sphincter of Oddi dysfunction and the recurrent symptoms warrant the risks of ERCP, this examination should be repeated. There are no comprehensive reports that systematically detail the findings at a second examination. In most centers that see a significant number of sphincter of Oddi patients, as complete a biliary sphincterotomy as possible is usually performed if biliary sphincterotomy is indicated. The exact source of pain in sphincter of Oddi patients is still not known but it is likely that in those with functional stenosis (as opposed to structural obstruction), the pain emanates from the sphincter itself. This is the reason to perform a complete biliary sphincterotomy. Under these circumstances, it is unusual to find recurrent stenosis of the biliary sphincter on followup examination, but rather residual pancreatic sphincter hypertension. In this setting, available data suggests that patients symptomatically improve following pancreatic sphincterotomy. In a study by Elton,74 pancreatic manometry was performed following biliary sphincterotomy in patients with sphincter of Oddi dysfunction. If pancreatic sphincter hypertension was found, pancreatic sphincterotomy was performed. The results showed that 73% of patients had complete resolution of symptoms after the index ERCP and an additional 18% showed partial or transient change. Only 8% of these Type I and Type II SOD patients had no change in symptoms. These results are somewhat better than other reports in the literature. Additionally, Eversman et al.75 looked at long-term follow-up after biliary sphincterotomy and correlated it with the sphincter of Oddi manometry results. In this study, 37 patients had isolated biliary sphincter hypertension and only 16% required reintervention. In a group of 62 patients who had elevated biliary and pancreatic basal pressures, 29% required reintervention. For the 33 patients who had isolated pancreatic sphincter hypertension (and underwent a biliary sphincterotomy alone), 39% required reintervention. 375

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This concept of improved outcomes with dual sphincterotomy when pancreatic sphincter hypertension is present was further investigated by Park et al.76 In this report, there was no significant difference in outcome when comparing dual sphincterotomy versus biliary sphincterotomy alone in patients with isolated biliary sphincter hypertension. Interestingly, there was also no difference between dual and biliary sphincterotomy alone in patients who had both abnormal biliary as well as abnormal pancreatic sphincter pressures. However, there was a significant difference in the rate of reintervention in patients with isolated abnormal pancreatic sphincter pressures (21% vs 39%, p value < .05). In summary, it does appear that outcomes can be improved if pancreatic sphincterotomy is performed in patients with documented pancreatic sphincter hypertension. However, definitive recommendations await appropriate randomized trials.

CONCLUDING REMARKS The evaluation and treatment of patients with suspected sphincter of Oddi dysfunction remains a challenge for gastroenterologists. Obtaining a detailed history is a critical step and the evaluation for other causes of upper abdominal pain should be undertaken and empiric medical trials for endoscopically and radiologically negative diseases (GERD, IBS) should be tried. However, with an appropriate history and a failure to respond to empiric interventions, one should consider sphincter of Oddi dysfunction. In these cases, evaluation for ductal dilation and hepatic and pancreatic chemistry panels

during or shortly after an episode of significant pain should be obtained. With this information, the patient can be categorized into Geenen-Hogan criteria (I, II or III). Because of a 90% response to sphincterotomy and the fact that they appear to have a lower incidence of post-ERCP pancreatitis, those patients who fall into category I can undergo ERCP and sphincterotomy without the need for manometry. Geenen-Hogan category II and III patients, should be referred to a gastroenterologist or pancreaticobiliary center with expertise in sphincter of Oddi manometry. Category II patients should undergo a manometry because randomized trails have proven that manometry is an accurate discriminator of those who will respond to sphincterotomy. We clearly need randomized trials in category III patients. In the absence of those trials, current data suggests that manometry is helpful in selecting those who will respond to sphincterotomy. Moreover, emerging data suggests that both sphincters should be studied, and in selected patients with pancreatic sphincter hypertension, one should consider dual sphincterotomy. Additionally, category III patients are at high risk for post-ERCP pancreatitis and should undergo short-term pancreatic stenting, even if their manometry is normal. The need for dual manometry combined with a potential need for pancreatic sphincterotomy and the mandatory requirement for pancreatic stenting all dictate that type III patients be managed by endoscopists who have significant experience and interest in patients with sphincter of Oddi dysfunction. Finally, patients with sphincter of Oddi dysfunction who relapse after initial endoscopic intervention should be reevaluated if the severity of their recurrent symptoms warrants either endoscopical or surgical intervention.

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62. Sherman S, Troiano FP, Hawes RH, et al. Does continuous aspiration from an end and side port in a sphincter of Oddi manometry catheter alter recorded pressures? Gastrointest Endosc 1990; 36(5):500–503. 63. Tarnasky PR, Palesch YY, Cunningham JT, et al. Pancreatic stenting prevents pancreatitis after biliary sphincterotomy in patients with sphincter of Oddi dysfunction. Gastroenterology 1998; 115(6):1518–1524. 64. Aizawa T, Ueno N. Stent placement in the pancreatic duct prevents pancreatitis after endoscopic sphincter dilation for removal of bile duct stones. Gastrointest Endosc 2001; 54(2):209–213. 65. Fazel A, Quadri A, Catalano MF, et al. Does a pancreatic duct stent prevent post-ERCP pancreatitis? A prospective randomized study. Gastrointest Endosc 2003; 57(3):291–294. 66. Smithline A, Silverman W, Rogers D, et al. Effect of prophylactic main pancreatic duct stenting on the incidence of biliary endoscopic sphincterotomy-induced pancreatitis in high-risk patients. Gastrointest Endosc 1993; 39(5):652–657. 67. Sherman S, Bucksot EL, Esber E, et al. Does leaving a main pancreatic duct stent in place reduce the incidence of precut biliary sphincterotomy-induced pancreatitis? Randomized prospective study. Am J Gastroenterol 1995; 90:241 (Abstr). 68. Singh P, Das A, Isenberg G, et al. Does prophylactic pancreatic stent placement reduce the risk of post-ERCP acute pancreatitis? A meta-analysis of controlled trials. Gastrointest Endosc 2004; 60(4):544–550.

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69. Rashdan A, Fogel EL, McHenry L Jr, et al. Improved stent characteristics for prophylaxis of post-ERCP pancreatitis. Clin Gastroenterol Hepatol 2004; 2(4):322–329. 70. Sherman S, Hawes RH, Savides TJ, et al. Stent-induced pancreatic ductal and parenchymal changes: correlation of endoscopic ultrasound with ERCP. Gastrointest Endosc 1996; 44(3):276–282. 71. Smith MT, Sherman S, Ikenberry SO, et al. Alterations in pancreatic ductal morphology following polyethylene pancreatic stent therapy. Gastrointest Endosc 1996; 44(3):268–275. 72. Fogel EL, Varadarajulu S, Sherman S, et al. Prophylactic pancreatic duct stenting in patients with suspected sphincter of Oddi dysfunction but normal sphincter of Oddi manometry. Gastrointest Endosc 2003; 57(5):AB88. 73. Varadarajulu S, Hawes RH, Cotton PB. Determination of sphincter of Oddi dysfunction in patients with prior normal manometry. Gastrointest Endosc 2003; 58(3):341–344. 74. Elton E, Howell DA, Parsons WG, et al. Endoscopic pancreatic sphincterotomy: indications, outcome and a safe stentless technique. Gastrointest Endosc 1998; 47(3):240–249. 75. Eversman D, Fogel E, Phillips S, et al. Sphincter of Oddi dysfunction (SOD): long-term outcome of biliary sphincterotomy (BES) correlated with abnormal biliary and pancreatic sphincters. Gastrointest Endosc 1999; 49(4):AB78. 76. Park S-H, Watkins JL, Fogel EL, et al. Long-term outcome of the endoscopic dual pancreatobiliary sphincterotomy in patients with manometry-documented sphincter of Oddi dysfunction and normal pancreatogram. Gastrointest Endosc 2003; 57(4):483–491.

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35

APPROACH TO CLINICAL PROBLEMS

Sclerosing Cholangitis Jawad Ahmad and Adam Slivka

BACKGROUND Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the biliary tree. It is characterized by stricturing and dilation of the intra- and/or extrahepatic bile ducts, with concentric obliterative fibrosis of intrahepatic biliary radicles. PSC is closely associated with inflammatory bowel disease (IBD), particularly ulcerative colitis (UC), which is found in approximately two-thirds of northern European PSC patients.1,2 The disease leads to chronic cholestasis but patients can be asymptomatic at presentation, diagnosed by abnormal liver enzymes, particularly elevation of the alkaline phosphatase, or they can present with pruritus, fatigue, right upper quadrant pain, and jaundice. As the disease progresses, symptoms of cirrhosis can be manifested. PSC is associated with an unpredictable risk of developing cholangiocarcinoma in up to 30% of patients.3 The etiology and pathogenesis of PSC are unclear but it is likely an immune-mediated disease involving an exaggerated cell-mediated immune response leading to chronic inflammation of the biliary epithelium. PSC is diagnosed by radiographic imaging of the biliary tree (Fig. 35.1).4 This has traditionally been performed using endoscopic retrograde cholangiopancreatography (ERCP) but more recently magnetic resonance cholangiopancreatography (MRCP) is thought to be as sensitive as ERCP in the diagnosis of PSC if the best equipment and operator are available (Fig. 35.2). Liver biopsy has a limited role in diagnosis but is a useful adjunct to determine the stage of the disease. Histology can range from normal to frank biliary cirrhosis with the typical appearances being of portal inflammation, concentric “onion skin” periductal fibrosis and periportal fibrosis developing into septal and bridging necrosis. The endoscopist’s role in PSC involves diagnostic cholangiography, therapeutic intervention of strictures in the bile duct including dilation and stenting, and differentiating between benign and malignant strictures.

DIAGNOSIS AND NATURAL HISTORY Introduction and scientific basis The role of ERCP in the diagnosis of PSC has become more controversial with the availability of high-quality MRCP. The latter has the benefit of being non-invasive but is operator and machine dependent and does not allow therapeutic intervention or cytological sampling. ERCP is still considered to be the gold standard and allows sampling and intervention, although it is still operator dependent. In addition, ERCP provides endoscopic staging of portal hypertension. Several studies have compared ERCP and MRCP in patients with clinical or biochemical evidence of cholestasis and MRCP appears to have a comparable diagnostic accuracy. Textor et al. examined 150

patients with cholestatic liver enzymes and obtained a diagnostic MRCP in 146 of these patients (97%). PSC was found in 34 of the 150 patients (23%) at ERCP and MRCP was able to correctly identify 88% (29 of 33) and had a specificity of 99% (108 of 109).5 A similar study by Angulo and colleagues determined that MRCP had a diagnostic accuracy of 90% compared to 97% with invasive cholangiography in 73 patients with a variety of cholestatic diseases, including 23 patients with PSC. However, three-quarters of the PSC patients required a therapeutic intervention.6

Description of technique The technique for ERCP in PSC does not differ from the standard approach to biliary cannulation and is described elsewhere (see Chapter 8). In certain cases an occlusion cholangiogram is required using a stone-extraction balloon to prevent drainage of contrast from the biliary tree or filling of the gallbladder. However, care should be taken to avoid filling of segments of the intrahepatic ducts that subsequently cannot be drained thus increasing the risk of infection. We treat all PSC patients with antibiotics immediately before and for several days after ERCP.

Indications/contraindications Any patient with a clinical picture consistent with cholestasis is a candidate for imaging of the biliary tree. This is especially true in patients with underlying inflammatory bowel disease. The use of ERCP or MRCP will be affected by several factors as described above. If therapy is potentially indicated, then ERCP has the advantage of treating a stricture without the need for an additional test, although MRCP may help to plan a therapeutic intervention. Secondary causes of biliary sclerosis need to be excluded before a diagnosis of PSC can be confidently made. Biliary surgery, calculi and neoplasms, hepatic artery injury, hepatic arterial chemotherapy and AIDS can lead to strictures in the biliary tree. Figure 35.3 illustrates the cholangiogram of a patient several months following intraarterial chemotherapy with floxuridine (FUDR) with resultant toxic cholangiopathy. Several processes can mimic PSC on a cholangiogram. Hepatic malignancies polycystic liver disease, infiltrative liver disease and inflammatory pseudotumors need to be considered. Abdominal CAT scan or ultrasound can differentiate many of these disease entities from PSC. Another potential role for ERCP in PSC patients may be in predicting prognosis. A recent study suggests that using a scoring system for severity of disease based on the initial cholangiogram has prognostic value, and in combination with the age at first ERCP, is strongly predictive of survival.7

Complications The complications of ERCP in the setting of PSC are typical of those for any other indication and are described in Chapter 6. There may 379

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BOX 35.1 KEY POINTS—DIAGNOSIS OF PSC ERCP Invasive Operator dependent Gold standard Therapeutic Tissue sampling Stage portal hypertension

MRCP Non-invasive Operator dependent Accuracy < 100% Non-therapeutic No sampling Less expensive No complications

Fig. 35.1 Typical endoscopic retrograde cholangiogram of a patient with PSC. The disease is in an early stage with areas of stricturing and beading of the intrahepatic biliary tree but little attenuation. Note that an occlusion cholangiogram has been performed with the balloon inflated proximal to the take off of the cystic duct, so that contrast fills the intrahepatic bile ducts and not the gallbladder. This technique is useful to minimize possible post-procedure cholecystitis.

Fig. 35.3 Cholangiogram demonstrating the effects of intraarterial chemotherapy using FUDR. Note the discrete area of narrowing in the extrahepatic duct which otherwise looks normal, and the areas of diffuse structuring in the intrahepatics.

380

ity of these patients received prophylactic antibiotics. A similar study in 104 patients with PSC who underwent diagnostic and therapeutic ERCP found an 18% complication rate in those with a diagnostic procedure but these were all mild and not life-threatening.9

Fig. 35.2 Magnetic resonance cholangiogram of a patient with PSC. The disease is relatively early without much attenuation of the intrahepatic biliary tree. The biliary radicles appear to be greater in diameter more peripherally and several discrete strictures are seen centrally. Both the left and right systems are involved but the extrahepatic duct is not well seen. The gallbladder is seen in the center of the image.

Relative cost

be an increased risk of cholangitis but the use of prophylactic antibiotics has become standard care in these patients. A prospective study from Europe assessed the complications occurring within a week after ERCP on 83 patients with PSC who underwent 103 procedures.8 Of the 47 diagnostic procedures the only complication that occurred was worsening of symptoms in one patient. The vast major-

A recent study examined the cost of MRCP versus ERCP in the diagnosis of PSC.10 The average cost per correct diagnosis by MRCP or ERCP, as the initial testing strategy in 73 patients with clinically suspected biliary disease, was $724 and $793, respectively. MRCP had a sensitivity of 82% and a specificity of 98%. MRCP thus resulted in cost savings when used as the initial test strategy for diagnosing PSC, particularly as there are essentially no procedure-related complications. However, this was in a cohort of patients with a 32%

Chapter 35 Sclerosing Cholangitis

BOX 35.2 KEY POINTS—ENDOSCOPIC THERAPY IN PSC • Dominant strictures in PSC can be treated at ERC. • More important than the stricture is the state of the pre-stenotic biliary tree. • Tissue sampling and liberal antibiotics are mandatory. • Reserve treatment for patients with symptomatic jaundice. • Concomitant dilation with stenting may improve results. • Balloon dilation and short-term (10–14 day) stenting preferable. • Avoid sphincterotomy if possible. • More complications compared to diagnostic ERCP. • No convincing data we are altering long-term natural history.

prevalence of PSC and with a very high specificity of MRCP. With a lower MRCP specificity (<85%) and a higher prevalence of PSC (>45%), ERCP becomes more cost-effective, suggesting that ERCP should be used when the suspicion of PSC is high or if local MRCP facilities are sub-optimal. The same study illustrated the high cost of dealing with complications of PSC. The average cost of managing post-ERCP-related complications was $2902 with a range of $1915–$5032.

ENDOSCOPIC TREATMENT Introduction and scientific basis Interpreting the results of endoscopic therapy trials for PSC is limited by the small numbers of cases tested and the variety of endoscopic techniques used. In addition, most series reporting therapy involve dilation or stenting of a dominant stricture—a term for which there is no consensus, although a stenosis of less than 1.5 mm in the extrahepatic bile duct, or less than 1 mm in the right or left common hepatic duct is commonly used. The status of the upstream bile duct is not considered in this definition and is critically important in determining the impact of an intervention. Repeated endoscopy to maintain biliary patency may improve the survival of patients with PSC.11 By comparing the survival of 63 patients with PSC who underwent therapeutic ERCP (primarily repeated balloon dilation of dominant biliary strictures) over a 6-year period with the predicted survival using the Mayo Clinic survival model for PSC, Baluyut and colleagues demonstrated an 83% 5-year survival compared to an expected survival of 65% (p = 0.027). However, it should be remembered that the Mayo risk score uses bilirubin in its formula and therefore will be profoundly affected by stenting of a stricture with resultant rapid decrease in serum biliru-

bin. This raises the question whether studies looking at outcome of therapy in PSC can use this model, which was designed to assess slow longitudinal decompensation, as a comparison for a control group following acute endoscopic interventions in highly selected patients. A recent study by Bjornsson et al. suggested that cholestasis in PSC patients did not appear to be related to the presence of dominant strictures.12 They found no difference in the change in cholestatic laboratory values in patients with and without dominant strictures after therapeutic ERCP and hence concluded that endoscopic therapy of dominant strictures should not be undertaken routinely. However, there was very little difference between serum bilirubin and alkaline phosphatase levels between patients with and without dominant strictures prior to therapeutic ERCP casting doubt as to the validity of their assessment of what constituted a dominant stricture. The paucity of controlled data indicates that it is unclear whether endoscopic therapy alters the long-term natural history of PSC.

Description of technique Once biliary cannulation has been achieved there are a variety of instruments that can be used to perform stricture dilation (see Chapter 30). Wire access across strictures is the first step in therapy and soft tip wires with diameters of 0.018–0.035” must be used to avoid perforation of the biliary tree. Push catheters have a tapered tip and the dilating part is typically 7–10 Fr in diameter. They are wireguided but their limited diameter and limited radial force mean that they are seldom used in PSC. More commonly inflatable balloons are employed. These are also wire-guided but come in a variety of diameters (up to 12 mm) and have a greater radial force. They are difficult to use if the stricture is tortuous. A temporary plastic stent can be placed after dilation or in some cases can be placed without dilation. Any dominant stricture should undergo sampling for cholangiocarcinoma. We perform brush cytology and/or intraductal forceps biopsy. In cases of refractory strictures, a screw catheter can be used over a wire although there is no controlled data on its efficacy. Several studies have performed biliary sphincterotomy prior to dilation or stent insertion but we do not advocate this as there is no reliable data that this is required and the complication rate is undoubtedly higher. Initial studies in PSC patients with dominant strictures did not use a standardized technique. Van Milligen de Wit and colleagues demonstrated technical success in 21 of 25 PSC patients with a dominant stricture who underwent endoscopic stent therapy.13 Of these 25 patients, 18 had a biliary sphincterotomy and 9 underwent dilation prior to stent insertion with either a balloon or dilating catheter. Stents were exchanged electively every 2–3 months or if they became occluded. After a median follow-up of 29 months, 16 of the 21 patients had improved or stable liver tests. More recent data indicates that short-term stenting may be effective with the benefit extending for several years.14 A European study described 32 PSC patients with dominant strictures treated with plastic stent placement for a mean of only 11 days. Again the technique was heterogeneous with some patients undergoing biliary sphincterotomy and push dilation, and both 7 Fr and 10 Fr stents were used. Improvements in symptoms and cholestasis were seen in all patients and these improvements were maintained for several years, with 80% of patients intervention free at 1 year, and 60% at 3 years. There were 7 transient procedure-related complications out of 45 procedures but all but one was managed conservatively. 381

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The addition of ursodeoxycholic acid (UDCA) to endoscopic therapy has been examined in a prospective trial by Stiehl et al., in 106 PSC patients followed for up to 13 years.15 All patients received UDCA along with balloon dilation of dominant strictures or placement of short-term biliary stents whenever necessary. Ten patients had dominant strictures at the beginning of the trial and a further 43 patients developed dominant strictures during the follow-up period. This combined approach appeared to improve overall survival rates compared with the Mayo PSC survival model but as the study was not controlled it was unclear whether the UDCA, the endoscopic therapy or the combination of the two improved outcome. Our approach in PSC patients is to use therapeutic ERCP in patients with a dominant stricture with pre-stenotic dilation who have an elevated serum bilirubin or severe symptomatic cholestasis. All our PSC patients are on UDCA at a dose of 20–25 mg/kg. We use balloon dilation over a guidewire ensuring that the diameter of the balloon is no greater than the smallest diameter of the duct either proximal or distal to the stricture. The balloon is inflated until there is no waist to the balloon or to a pressure of 12 atmospheres. We then leave a 10 Fr plastic stent across the stricture for 2–3 weeks and then repeat an ERCP and provide further therapy if indicated. All procedures are covered with prophylactic antibiotics and we will use several days of oral antibiotics after the procedure to minimize the risk of cholangitis. Figures 35.4 and 35.5 illustrate dilation and stent therapy in patients with a dominant stricture.

Indications/contraindications Endoscopic therapy is indicated in PSC patients if there is clinical or biochemical evidence of cholangitis or if a dominant stricture is suspected. However, due to lack of controlled data it is unclear if treatment alters the natural history of the disease. Occasionally bile duct calculi are encountered in patients with PSC and can be removed using standard techniques (see Chapter 13), although stones proximal to a stricture can be challenging. We typically do not perform therapy in patients who are not clinically jaundiced as the complication rate is higher and the potential benefit is questionable.

A

B

Fig. 35.4 A Balloon dilation of a dominant stricture in a patient with PSC. The cholangiogram on the left demonstrates intrahepatic and extrahepatic PSC. The extrahepatic duct has a dominant stricture (just below the scope) with pre-stenotic dilation. Retained contrast in the pancreatic duct is seen. The cholangiogram on the right shows a deflated balloon introduced into the extrahepatic duct over a wire. Note the radiopaque markers on the proximal and distal ends of the balloon. B Balloon dilation of a dominant stricture in a patient with PSC. The cholangiogram on the left demonstrates the balloon inflated across the stricture. There is no waist to the balloon. Typically the balloon is inflated to 12 atmospheres for 30–45 seconds. This can lead to pain and additional sedation may need to be given. The post-dilation appearance is shown on the right. Note the marked improvement.

Complications and their management Complications after therapeutic procedures in PSC patients are more frequent than after diagnostic ERCP. Of the 10 complications after 106 procedures studied by van den Hazel et al., all but one was in therapeutic cases.8 These included two episodes of cholangitis, three episodes of pancreatitis, a post-sphincterotomy bleed, a perforation, an upper extremity venous thrombosis, and a single patient with worsening of symptoms. Of the two patients with cholangitis, one had not received preprocedure antibiotics, but both responded to treatment. The pancreatitis patients were treated conservatively and all recovered. The postsphincterotomy bleed occurred three days after a needle-knife sphincterotomy and was mild. It was treated endoscopically. The perforation was asymptomatic but resulted from a guidewire making a false route in the cystic duct. The patient with worsening symptoms had had a stent placed and this needed a second ERCP to remove the stent. Factors that appeared to increase the risk of complications included a therapeutic indication such as jaundice or recurrent cholangitis, and also if the patient had undergone ERCP previously. These patients had a 14% complication rate. A similar number of 382

early complications have been noted by other investigators with cholangitis usually the most common.9–13 These are usually easily treated with antibiotics but liver abscesses and septic shock have been reported. Prolonged stent therapy is associated with cholangitis or jaundice due to stent occlusion that can be successfully treated by stent exchange or removal. Studies using short-term stent therapy indicate a similar early complication rate but cholangitis is less frequent.14

Relative cost There is no cost-effectiveness data available in studies of therapeutic endoscopy in PSC patients. Although the equipment used in balloon dilation is more expensive than push dilators the likely increased efficacy of the former may translate into fewer follow-up procedures and hence reduce the cost. We typically always deploy a stent after dilation and this necessitates a repeat procedure in a few weeks that adds to the cost of treatment. Due to the lack of controlled trials in PSC patients undergoing therapeutic ERCP, it is unclear if dilation therapy alone is sufficient. Reducing the number of subsequent

Chapter 35 Sclerosing Cholangitis

A

B

C

D

E

F

G

H

I

Fig. 35.5 Diffusely irregular distal bile and common hepatic ducts in deeply jaundiced patient with PSC, pigment stones in the biliary tree A. Note intrahepatic duct changes. Following biliary sphincterotomy and stone extraction B,C,D the strictures are balloon dilated E, brushed for cytology F, and stented with a 10 Fr biliary stent G. Note persistent but improved stenosis at time of stent retrieval 4 weeks later H,I.

procedures without affecting long-term outcome would improve the cost-effectiveness of endoscopic treatment.

CHOLANGIOCARCINOMA Introduction and scientific basis Cholangiocarcinoma (CCA) will develop in up to 10–30% of patients with PSC, with a lifetime risk of 10–15%. A recent study determined the incidence and risk factors for CCA in 161 patients with PSC, monitored for a median of 11.5 years. CCA developed in 11 patients (6.8%) at a rate of approximately 0.6% per year.16 This equated to a relative risk of CCA compared with that in the general population of 1560. No association was found between the duration of PSC and the incidence of CCA. Similarly, in a Swedish cohort of 604 PSC patients followed for many years, the frequency of CCA was 13% and the incidence rate of CCA after the first year of diagnosis was 1.5% per year.17 Early diagnosis of CCA may improve patient survival as it may permit curative surgical resection, but it is hampered by the absence of sufficiently accurate and non-invasive diagnostic tests. Diagnosing CCA in PSC patients is even more challenging because of the presence of multiple non-neoplastic strictures.

Description of technique Diagnosis

Several endoscopic methods have been employed to try and diagnose CCA in PSC patients. Brush cytology, fine needle aspiration and forceps biopsy have been used but all have low sensitivity and high specificity. In addition, the tumor markers carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) have been examined alone or in various combinations. Brush cytology involves gaining access to the biliary tree and then inserting a wire into the intrahepatic ducts. The closed cytology brush is then advanced over the wire into the area of the stricture to be brushed and then opened and vigorously pushed in and out of the stricture to try and increase the cellular yield. Occasionally, push or balloon dilation of the stricture is required to enable passage of the cytology brush. The brush is then closed while still inside the duct and removed through the endoscope and the cellular specimen sent to cytology on preprepared slides. It is important for the nurse or endoscopy technician to prepare the cytology slides quickly to prevent excessive drying which can cause artifacts that affect interpretation. The overall sensitivity of cytology in the diagnosis of CCA in PSC is around 50%. Adding K-ras or p53 mutational analysis of brush samples does not 383

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Treatment and palliation

Fig. 35.6 Intraductal biopsy in a patient with PSC and a dominant stricture. The scope is in a short position and the forceps have been placed into the bile duct. The bile duct proximal to the stricture is irregular and dilated. This technique enables a biopsy of the stricture such that tissue can be obtained for pathology rather than cytology, improving the diagnostic yield.

appear to increase the sensitivity although repeated brushing on two or three occasions appears to increase the sensitivity significantly.18,19 The increased cellular load obtained by an intraductal biopsy also appears to increase the sensitivity. The technique involves cannulating directly with the biopsy forceps. Figure 35.6 illustrates a biopsy being taken in a patient with a suspicious stricture. Using a formula with the sum of the CA19-9 and 40 times the CEA, Ramage et al. concluded that a diagnostic accuracy of 86% could be achieved in making a diagnosis of CCA in a small cohort of PSC patients.20 We have shown that a CEA level of >5.2 ng/ml or a CA19-9 of >180 U/ml leads to 70% sensitivity and combined with brush cytology a sensitivity of close to 90% can be achieved.21 Similarly, combining brush cytology, DNA analysis by flow cytometry, CA19-9 and CEA, a diagnostic sensitivity of 88% and specificity of 80% can be expected. Interestingly, measurement of CA19-9 or CEA in bile has no diagnostic significance.22 Recently, several newer techniques have shown some promise in differentiating benign from malignant disease in PSC. Quantifying nuclear DNA content from a stricture using digital image analysis (DIA) provides a diagnostic accuracy equivalent to brush cytology.23 Analysis of tumor suppressor gene linked microsatellite marker loss of heterozygosity and detection of k-ras mutation in brush cytology samples also yielded excellent sensitivity and specificity in a small group of patients with biliary strictures.24 Screening patients with PSC for CCA with CA19-9 and CEA would appear to be reasonable, but the ideal interval at which to obtain these tests and the cost-effectiveness remain to be determined. 384

Until the emergence of ERCP, patients who presented with jaundice in the setting of malignant biliary obstruction required surgical biliary bypass if fit enough for surgery, or percutaneous drainage. Smith and colleagues demonstrated the efficacy of endoscopic stent insertion compared to surgical biliary bypass in a randomized prospective controlled trial of 204 patients with malignant low bile duct obstruction.25 Technical success was achieved in 94 surgical and 95 stented patients, with functional biliary decompression obtained in 92 patients in both groups. The overall survival between the two groups did not differ (median survival: surgical 26 weeks; stented 21 weeks). The authors concluded that endoscopic stenting and surgery were both effective palliative treatments with the former having fewer early treatment-related complications and the latter fewer late complications. For patients with unresectable disease an expandable metal stent can be deployed for palliation using a standard technique (see Chapter 17). In a prospective randomized trial, Davids et al. demonstrated that metal stents resulted in significantly prolonged patency compared to polyethylene stents in 105 patients with unresectable distal bile-duct malignancy.26 Median patency of the metal stent was 273 days compared to 126 days with a plastic stent. Tumor ingrowth typically led to occlusion in metal stents whereas sludge deposition caused occlusion with plastic stents. However, the overall median survival was 149 days and did not differ significantly between patients with metal or plastic stents. The addition of chemotherapy to stenting has been tried without much success but a recent study demonstrated the benefit of photodynamic therapy (PDT) and stenting in non-resectable proximal CCA (involving the hilum) compared to stenting alone.(27) The technique requires initial placement of plastic stents (see Chapter 16) into both the left and right intrahepatics so that biliary drainage is achieved. Patients receiving PDT then are treated with Photofrin at a dose of 2 mg/kg intravenously 48 hours before laser activation. The plastic stents are then removed during a repeat ERCP and intraluminal photoactivation is performed, following which the plastic stents are redeployed. Patients are kept in a darkened room for 3–4 days following the procedure. In this randomized study, PDT and stenting resulted in a median survival of 493 days compared to 98 days with stenting alone. In addition, jaundice and quality of life were also significantly improved. The only complication seen in the PDT group was photosensitivity in 10% of the patients. This procedure should only be performed by experienced endoscopists and in facilities with PDT capability. The costs may also be prohibitive.

Indications/contraindications Any patient with PSC who has an unexpected rise in cholestatic enzymes or bilirubin should be investigated for the development of CCA. In addition, a sudden rise in CA19-9 or CEA should prompt a cholangiogram. We do not advocate routine surveillance ERCP in asymptomatic patients with PSC. Diagnosing cholangiocarcinoma at an early stage is not usually helpful in PSC patients as resection is usually contraindicated because of the presence of cirrhosis, and the results of liver transplant for early CCA are not encouraging. The diagnosis should ideally be made in a premalignant stage but as yet this is not possible. The timing of liver transplant in patients with PSC is therefore difficult as many patients will have preserved liver synthetic function and are early for transplant but are still at risk of developing a tumor that will then likely preclude transplant.

Chapter 35 Sclerosing Cholangitis

Complications and their management The complications and management of metal or plastic stent insertion for patients with CCA in the setting of PSC are as described elsewhere (see Chapters 16 and 17). Comparing stent insertion to surgical bypass in CCA, Smith et al. demonstrated a lower procedure-related mortality (3% vs 14%), major complication rate (11% vs 29%), and median total hospital stay (20 vs 26 days) in stented patients compared to surgery. However, late complications including recurrent jaundice and late gastric outlet obstruction were more frequent in stented patients.25

Relative cost For diagnostic purposes, CEA and CA19-9 measurement are relatively inexpensive but their low sensitivity means cytology is required. The cost-effectiveness of these tumor markers and the newer DNAbased tests remains to be seen. In terms of providing palliation, metal stents are more costeffective than plastic stents because the longer patency compared to plastic stents translates into fewer follow-up procedures. Although there are no formal studies looking at risks and benefits of plastic versus metal stents in PSC patients who develop CCA, Davids et al. using incremental cost-effectiveness analysis, showed that intial placement of a metal stent resulted in a 28% decrease in subsequent endoscopic procedures in patients with distal malignant obstructive jaundice.26 However, in patients with a life expectancy of less than 3 months a plastic stent may be adequate palliation as a follow-up procedure is unlikely to be required.

The high initial cost of surgical palliation compared to endoscopic therapy means that the former has very limited application (Box 35.3).

BOX 35.3 KEY POINTS—DIAGNOSING CHOLANGIOCARCINOMA IN PSC • Cholangiocarcinoma may develop in 10–30% patients with PSC. • No proven screening method. • Brush cytology has only 50% sensitivity. • Combining tumor markers with cytology may increase sensitivity. • Newer DNA and molecular techniques may increase sensitivity. • Pre-malignant diagnosis would allow liver transplant prior to development of cholangiocarcinoma—not currently possible.

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cholangiopancreatography. Canadian Journal of Gastroenterology 2003; 17:243–248. Talwakar JA, Angulo P, Johnson CD, et al. Cost-minimization analysis of MRC versus ERCP for the diagnosis of primary sclerosing cholangitis. Hepatology 2004; 40:39–45. Baluyut AR, Sherman S, Lehman GA, et al. Impact of endoscopic therapy on the survival of patients with primary sclerosing cholangitis. Gastrointest Endosc 2001; 53:308–312. Bjornsson E, Lindqvist-Ottosson J, Asztely M, et al. Dominant strictures in patients with primary sclerosing cholangitis. Am J Gastroenterol 2004; 99:502–508. Van Milligen de Wit AWM, van Bracht J, Rauws EAJ, et al. Endoscopic stent therapy for dominant extrahepatic bile duct strictures in primary sclerosing cholangitis. Gastrointest Endosc 1996; 44:293–299. Ponsioen CY, Lam K, van Milligen de Wit AWM, et al. Four years experience with short term stenting in primary sclerosing cholangitis. Am J Gastroenterol 1999; 94:2403–2407. Stiehl A, Rudolph G, Kloters-Plachky P, et al. Development of dominant bile duct stenoses in patients with primary sclerosing cholangitis treated with ursodeoxycholic acid: outcome after endoscopic treatment. J Hepatol 2002; 36:151–156. Burak K, Angulo P, Pasha TM, et al. Incidence and risk factors for cholangiocarcinoma in primary sclerosing cholangitis. Am J Gastroenterol 2004; 99:523–526. Bergquist A, Ekbom A, Olsson R, et al. Hepatic and extrahepatic malignancies in primary sclerosing cholangitis. J Hepatol 2002; 36:321–327. Ponsioen CY, Vrouenraets SME, van Milligen de Wit AWM, et al. Value of brush cytology for dominant strictures in primary sclerosing cholangitis. Endoscopy 1999; 31:305–309. 385

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19. de Bellis M, Fogel EL, Sherman S, et al. Influence of stricture dilation and repeat brushing on the cancer detection rate of brush cytology in the evaluation of malignant biliary obstruction. Gastrointest Endosc 2003; 58(2):176–182. 20. Ramage JK, Donaghy A, Farrant JM, et al. Serum tumor markers for the diagnosis of cholangiocarcinoma in primary sclerosing cholangitis. Gastroenterol 1995; 108:865–869. 21. Siqueira E, Schoen RE, Silverman W, et al. Detecting cholangiocarcinoma in patients with primary sclerosing cholangitis. Gastrointest Endosc. 2002; 56:40–47. 22. Lindberg B, Arnelo U, Bergquist A, et al. Diagnosis of biliary strictures in conjunction with endoscopic retrograde cholangiopancreaticography, with special reference to patients with primary sclerosing cholangitis. Endoscopy 2002; 34:909–916. 23. Baron TH, Harewood GC, Rumalla A, et al. A prospective comparison of digital image analysis and routine cytology for the

386

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27.

identification of malignancy in biliary tract strictures. Clin Gastroenterol Hepatology. 2004; 2:214–219. Khalid A, Pal R, Sasatomi E, et al. Use of microsatellite marker loss of heterozygosity in accurate diagnosis of pancreaticobiliary malignancy from brush cytology samples. Gut 2004; 53:1860–1865. Smith AC, Dowse JF, Russell RC, et al. Randomized trial of endoscopic stenting versus surgical bypass in malignant low bile duct obstruction. Lancet 1994; 344:1655–1660. Davids PH, Groen AK, Rauws EA, et al. Randomized trial of self-expanding metal stents versus polyethylene stents for distal malignant biliary obstruction. Lancet 1992; 34: 1488–1492. Ortner MEJ, Caca K, Berr F, et al. Successful photodynamic therapy for nonresectable cholangiocarcinoma: A randomized prospective study. Gastroenterol 2003; 125:1355–1363.

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Choledochal Cysts Annie On On Chan, Chi Leung Liu and Benjamin Chun-Yu Wong

INTRODUCTION AND SCIENTIFIC BASIS Choledochal cysts are congenital anomalies characterized by cystic dilatation of the biliary tree, extrahepatic or intrahepatic, or both extrahepatic and intrahepatic. Choledochal cysts are classified into five subtypes under the Todani classification, based on the anatomical site of the cystic dilatation1 (Fig. 36.1). They are more common in women than in men, and their prevalence is higher in Asian and Japanese descendants than in Caucasians. For additional images and discussion see Chapters 22 and 42.

BOX 36.1 INDICATIONS/CONTRAINDICATIONS OF ERCP FOR CHOLEDOCHAL CYST Indications Diagnosis Preoperative assessment Therapeutics Management of complications Contraindications: Coagulopathy Unfit to undergo sedation Clinical perforation “Usual contraindications” to ERCP

Choledochal cysts are thought to be the result of an anomalous junction of the common bile duct with the pancreatic duct (anomalous pancreatobiliary junction (APBJ)) (Figs. 36.2A, 36.2B). An APBJ is characterized when the pancreatic duct enters the common bile duct 1 cm or more proximal to where the common bile duct reaches the ampulla of Vater. Miyano and Yamataka2 have demonstrated such APBJs in more than 90% of their patients with choledochal cysts. The APBJ allows pancreatic secretions and enzymes to reflux into the common bile duct. In the relatively alkaline conditions found in the common bile duct, pancreatic proenzymes can be activated, resulting in inflammation and weakening of the bile duct wall. Severe damage leads to complete denuding of the common bile duct mucosa. Another proposed theory for the formation of choledochal cysts is the presence of defects in epithelialization and recanalization

of the developing bile ducts during organogenesis resulting in congenital weakness of the duct wall.

DESCRIPTION OF TECHNIQUE Choledochal cysts can present at any age. With the increasing use of imaging studies in clinical management, more cases are diagnosed incidentally. Presenting symptoms are age-dependent with jaundice prevailing in children and abdominal pain in adults. In view of the high risk of cholangiocarcinoma, early resection and not internal drainage is the appropriate treatment of extrahepatic cysts. Patients who underwent internal drainage in the past still should undergo resection of the cyst. Neonates and children usually present with abdominal pain and/or abdominal mass3 and jaundice.4 Initial presentation in adults is rare, but, when present, may cause nonspecific right upper quadrant abdominal pain, jaundice, acute cholangitis, or acute pancreatitis.4,5 Hence, prior to the advent of MRCP, endoscopic retrograde cholangiopancreatography (ERCP) was one of the most commonly used methods for the diagnosis of choledochal cyst, especially in the initial management of acute cholangitis, acute pancreatitis and biliary malignancies. ERCP can be performed with a standard diagnostic or therapeutic channel duodenoscope. After identification of the papilla, cannulation of the common bile duct (CBD) should be performed using 30% water-soluble contrast solution. Immediate and delayed spot film radiographs should be obtained (Figs 36.3A, 36.3B). Sphincterotomy and biliary stent placement are performed as needed. Bile duct stones, if present, are extracted with a Dormia basket and/or balloon catheters as in patients with non-variant anatomy as described in Chapters 13 and 33. Biopsy specimens are obtained if a tumor mass is suspected with conventional or specially designed biopsy forceps (Fig. 36.4). Choledochal cyst is mainly a disease seen in children (see Chapter 22). The technique of ERCP is no more difficult in children than in adults, and there is no need for a special pediatric endoscope, except in infants younger than 12 months of age. The rate of successful cannulation of the desired duct in children is as good as in adults, and is reported to be in the range of 92–96%.6 Occasionally, ERCP via the accessory papilla is an effective method for visualization of the detailed structure of the entire pancreatic ductal system and junction of the pancreatic and biliary ducts when ERCP via the major duodenal papilla is unsuccessful.7 Most endoscopists use general anesthesia with an endotracheal tube in situ in children, particularly in infants, to prevent airway obstruction and dyspnea caused by abdominal distension. There are also reports of conducting ERCP under ketamine sedation. It has been shown to be safe and effective and does not require an extensive monitoring system.8 The complication rate of performing ERCP in children is reported to be less than that in adults.9 387

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I

II

III

IVa

V

A B

Fig. 36.2 A Initial injection during ERCP showing a long common channel in a patient with type IVA choledochal cyst and long bile duct stricture. B Same patient. The long stricture is seen with cystic dilatation above the stricture.

Fig. 36.3 A Initial injection into a massive type I choledochal cyst (arrow). B Late filling clearly demonstrates cyst.

A

B

388

Fig. 36.1 Todani classification of choledochal cysts. (Redrawn with permission from de Vries JS et al. J Pediatr Surg. 2002:37(11);1568– 1573.)

Chapter 36 Choledochal Cysts

does not overlap with the second duodenal portion or the endoscope in order to identify the dilated end of the distal CBD in the intramural portion (Fig. 36.5C). A radiolucent halo can be seen between the contrast-filled dilated sac and the contrast-filled duodenal lumen. Cholangiography should be done in profile. When adequate cholangiographic images are combined with a careful ERCP examination, it is possible to diagnose small choledochoceles that may otherwise be overlooked by inspection during ERCP alone. Optimal radiographic technique during ERCP is necessary and it has been proposed that a cannulating catheter should be withdrawn from the duodenum after contrast material has been instilled into the bile duct. This is necessary to avoid masking the dilated sac by the balloon and the catheter. In patients with a choledochocele sphincterotomy is performed by cannulating both the cyst and the common bile duct with a papillotome (Fig. 36.5D). The latter allows simultaneous unroofing of the cyst and sphincterotomy. In cases where a case of a large choledochocele is suspected needle knife sphincterotomy appears to be safe.13

DIAGNOSIS As mentioned above, the presentation of choledochal cyst in adults is usually atypical, and individuals seldom present with an abdominal mass. Instead, they usually present with biliary complications. Historically, the final diagnosis of choledochal cyst has been established by ERCP as it was considered the only method to precisely define the extent of the cyst as well as confirm the presence or absence of an anomalous pancreaticobiliary junction. Fig. 36.4

Biopsy of stricture depicted in Figure 36.2B.

Cystic dilatation is known to occur in all parts of the biliary system (see Chapter 42). Todani’s classification (Fig. 36.1) comprises five types of cysts: Type I Common type: (a) choledochal cyst in a narrow sense; (b) segmental choledochal dilatation; and (c) diffuse or cylindrical dilatation. Type II Diverticulum type in the extrahepatic duct Type III Choledochocele Type IVa Multiple cysts in the intra- and extrahepatic ducts Type IVb Multiple cysts in the extrahepatic duct only Type V Intrahepatic bile duct cyst only (single or multiple) For the technique on diagnosing choledochocele (type III choledochal cyst), it has been recommended that patients fulfill these criteria: (a) a radiolucent halo around the distal end of the CBD, (b) bulbous end of the distal CBD, and (c) dynamic sequential morphologic changes of the distal CBD. Patients who meet two or more of these criteria are diagnosed as having choledochocele on cholangiography. In addition, the presence of a waist, a pseudoweb, and wrinkling of the distal CBD may also be observed.10 Characteristic duodenoscopic features of choledochocele include a hemispherical or pear-shaped bulge protruding into the duodenal lumen, soft and smooth overlying mucosa, easy compressibility with a cannulating catheter, and visible ballooning of the ampulla during injection of contrast (Figs 36.5A, 36.5B).11 Park et al.12 recommended that the duodenal lumen should be filled with an optimal amount of contrast material. The patient should be positioned so that the dilated sac

PREOPERATIVE ASSESSMENT ERCP not only provides an accurate diagnosis, but also provides useful anatomical details that help to plan appropriate surgical intervention and obviates an intraoperative cholangiogram. Traditionally, preoperative ERCP is used to determine the upper and lower margin of a cyst and provide detailed anatomy of the biliary tract and pancreaticobiliary junction before is contemplated. More recently, MRCP has been shown to be an effective imaging modality for diagnosis and preoperative evaluation of choledochal cysts (Figs 36.6A, 36.6B).14,15

THERAPEUTIC MEASURES Due to cystic formation, stones and strictures may form within the biliary tree. Therapeutic ERCP should be carried out for biliary decompression, stone removal, stricture dilatation, stent insertion, and sphincterotomy. In children with choledochal cysts, surgery has traditionally been performed soon after ERCP because of the risk of cholangitis. Malignancy may arise in long-standing choledochal cysts. Hence brush cytology or biopsy from a suspected tumor mass should be undertaken during ERCP. The current treatment of choledochal cysts is essentially surgical, irrespective of the age of the patient. Endoscopic treatment is the method of choice for uncomplicated choledochocele (type III) (Fig. 36.5),16,17 after which long-term follow-up is unnecessary.18 Choledochoceles are difficult to distinguish from duplication cysts of the duodenum unless the mucosal lining is examined histologically. Endoscopic sphincterotomy or unroofing the cyst to permit adequate drainage are common methods of treatment.19 However, carcinoma may rarely co-exist with choledochocele, and ERCP with biopsies may be needed to exclude malignancy. 389

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A

B

C

D

Fig. 36.5 Choledochocele. A The choledochocele (arrow) can be seen above the papilla (arrowhead). B The choledochocele is seen to enlarge as contrast is injected into the bile duct. C Characteristic cholangiographic appearance of choledochocele. D Endoscopic appearance immediately after biliary sphincterotomy.

MANAGEMENT OF COMPLICATIONS FROM CHOLECHODAL CYSTS Usually, total choledochal cyst resection followed by Roux-en-Y hepaticojejunostomy is the preferred treatment in most types of choledochal cysts (Fig. 36.7). Internal cyst drainage is associated with an increased risk of cholangitis,20 pancreatitis,21 and biliary tract cancer.22,23 Patients with choledochal cysts who have undergone surgery remain at increased risk for recurrent cholangitis, pancreatitis, intrahepatic strictures, stones, and malignancy. ERCP will be indicated if these complications arise, assuming the hepaticojejunostomy can be reached (Fig. 36.8). Long-term management of 390

patients with Caroli’s disease, however, remains controversial. Usually this involves treatment of recurrent cholangitis with eventual surgical intervention, including external abscess drainage, partial resection, and even orthotopic liver transplantation.24,25 The time interval between diagnosis and surgery is, however, highly variable. Alternatively, bile stasis can be prevented by internal drainage via ERCP with endoscopic sphincterotomy, biliary stent placement, and stone extraction. Gold et al.25 described placement of an endobiliary stent in the right liver lobe alone for two years in a patient with type V choledochal cyst, with a good clinical response. Ciambotti et al.26 treated a patient with monolobar Caroli’s disease and multiple intrahepatic stones by stent placement for one year,

Chapter 36 Choledochal Cysts

A

B

A

Fig. 36.6 MRCP of choledochal cyst. A Long common channel corresponds to Figure 36.2a. B Intrahepatic cystic dilatation and extrahepatic stricture corresponds to Figure 36.2b.

B

Fig. 36.7 A Roux-en-Y hepaticojejunostomy after resection of extrahepatic cyst. B Temporary percutaneous transhepatic stents may be placed across the hepaticojejunostomy.

together with administration of ursodeoxycholic acid (UDCA), until the stone burden was eliminated.

COMPLICATIONS AND THEIR MANAGEMENT Choledochal cysts should be completely resected if possible because of the long-term consequences of cholangitis, liver cirrhosis, pancreatitis, and cancer.27 These problems can be exacerbated if internal drainage procedures rather than cyst resection are performed. Pancreatitis is a common presentation of choledochal cysts which may be due to the activation of pancreatic enzymes by bile reflux. In addition, an APBD not only predisposes to biliary tract anomalies but also causes pancreatic duct abnormalities such as dilatation, protein plugs and stones.28 The association between pancreatic calculi and choledochal cysts has been recognized. Pancreatic calculi can cause recurrent or chronic pancreatitis after cyst excision.29 Guelrud et al.30 showed that sphincter of Oddi dysfunction may be associated with APBD and choledochal cysts and could be a cause of acute recurrent pancreatitis. In addition, patients with choledochal cysts may be more prone to developing post-ERCP pancreatitis because of the presence of the long common channel (Fig. 36.2A). Similarly, some have postulated that endoscopic placement of a stent

Fig. 36.8 PTC from patient illustrated in Figure 36.2b after hepaticojejunostomy for management of cholangitis. ERCP failed to reach the hepaticojejunostomy.

through the long common channel may increase the high risk of pancreatitis, though there are no data to support this observation. Cholangitis is a common complication of choledochal cysts and may be the presenting feature, as mentioned earlier. It is also a commonly reported complication after surgical management. Strictures of the hepatic ducts have been attributed to recurrent infection, especially in patients with type V cysts, a group in which strictures occur in up to 50% of patients.31 Matsumoto et al.32 and 391

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Ando et al.33 suggest that concomitant congenital strictures contribute to dilatation of the intrahepatic bile ducts. These investigators recommend more extensive evaluation using choledochoscopy, as the strictures may be characteristic of choledochal cyst disease.

The incidence of malignancy in choledochal cysts is reported at between 10% and 30%.34,35 Anomalous pancreaticobiliary ductal junction is strongly associated with gallbladder cancer among Chinese patients.36

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Todani T, Urushihara N, Morotomi Y, et al: Characteristics of choledochal cysts in neonates and early infants. Eur J Pediatr Surg 1995; 5:143–145. Miyano T, Yamataka A. Choledochal cysts. Curr Opin Pediatr 1997; 9:283–288. Stringer MD, Dhawan A, Davenport M, et al. Choledochal cysts: lessons from a 20 year experience. Arch Dis Child. 1995; 73:528–531. de Vries JS, de Vries S, Aronson DC, et al. Choledochal cysts: age of presentation, symptoms, and late complications related to Todani’s classification. J Pediatr Surg. 2002 Nov; 37(11):1568–1573. Lipsett PA, Pitt HA, Colombani PM, et al. Choledochal cyst disease. A changing pattern of presentation. Ann Surg. 1994; 220:644–652. Hsu RK, Draganov P, Leung JW, et al. Therapeutic ERCP in the management of pancreatitis in children. Gastrointest Endosc. 2000 Apr; 51(4 Pt 1):396–400. Kouchi K, Yoshida H, Matsunaga T, et al. Efficacy of ERCP via the accessory papilla in children with choledochal cysts. Gastrointest Endosc. 2004; 59:119–123. Aggarwal A, Ganguly S, Anand VK, et al. Efficacy and safety of intravenous ketamine for sedation and analgesia during pediatric endoscopic procedures. Indian Pediatr. 1998 Dec; 35(12):1211–1214. Shirai Z, Toriya H, Maeshiro K, et al. The usefulness of endoscopic retrograde cholangiopancreatography in infants and small children. Am. J. Gastroenterol. 1993; 88:536–541. Park KB, Auh YH, Kim JH, et al. Diagnostic pitfalls in the cholangiographic diagnosis of choledochoceles: cholangiographic quality and its effect on visualization. Abdom Imaging 2001 Jan–Feb; 26(1):48–54. Kim MH, Myung SJ, Lee SK, et al. Ballooning of the papilla during contrast injection: the semaphore of a choledochocele. Gastrointest Endosc 1998; 48:258–262. Park KB, Auh YH, Kim JH, et al. Diagnostic pitfalls in the cholangiographic diagnosis of choledochoceles: cholangiographic quality and its effect on visualization. Abdom Imaging 2001; 26:48–54. Katsinelos P, Dimiropoulos S, Galanis I, et al. Needle-knife sphincterotomy. Surg Endosc 2003 Jan; 17(1):158. Shaffer E. Can MRCP replace ERCP in the diagnosis of congenital bile-duct cysts? Nat Clin Pract Gastroenterol Hepatol. 2006 Feb; 3(2):76–77. Park DH, Kim MH, Lee SK, et al. Can MRCP replace the diagnostic role of ERCP for patients with choledochal cysts? Gastrointest Endosc 2005 Sep; 62(3):360–366. Geenen JE. Choledochocele: endoscopic diagnosis and treatment. In: GNJ Tytgat and K Huibregtse (eds), Bile and bile duct abnormalities, Thieme, New York (1989):72–78. Martin RF, Biber BP, Bosco JJ, et al. Symptomatic choledochoceles in adults: endoscopic retrograde cholangiopancreatography recognition and management. Arch Surg 1992; 127:536–539. Ladas SD, Katsogridakis I, Tassios P, et al. Choledochocele, an overlooked diagnosis: report of 15 cases and review of 56

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published reports from 1984 to 1992. Endoscopy 1995; 27:233–239. Chatila R, Anderson DK, Topazean M. Endoscopic resection of a choledochocele. Gastrointest Endosc 1999; 50:578. Scudamore CH, Himming AW, Teare JP, et al. Surgical management of choledochal cysts. Am J Surg 1994; 167:497–500. Sugivama M, Atomi Y. Anomalous pancreaticobiliary junction without choledochal cyst. Br J Surg 1998; 85:911–916. Ishibashi T, Kasakara K, Yasuda Y, et al. Malignant change in the biliary tract after excision of choledochal cyst. Br J Surg 1997; 84:1687–1691. Watanabe Y, Toki A, Todani T. Bile duct cancer developed after cyst excision for choledochal cyst. J Hepatobil Pancreat Surg 1999; 6:207–212. Gold DM, Stark B, Pettei MJ, et al. Successful use of an internal biliary stent in Caroli’s disease. Gastrointest Endosc 1995; 42:589–592. Nagasue N. Successful treatment of Caroli’s disease by hepatic resection: report of six patients. Ann Surg 1984; 200:718–734. Ciambotti GF, Ravi J, Abrol RP, et al. Right-sided monolobar Caroli’s disease with intrahepatic stones: Nonsurgical management with ERCP. Gastrointest Endosc 1994; 40:761–764. Kobayashi S, Asano T, Yamasaki M, et al., Risk of bile duct carcinogenesis after excision of extrahepatic bile ducts in pancreaticobiliary maljunction. Surgery 1999; 126:939–944. Kato O, Hattori K, Suzuta T, et al. Clinical significance of anomalous pancreaticobiliary union. Gastrointest Endosc 1983; 29:94–98. Yamataka A, Ohshiro K, Okada K, et al. Complication after cyst excision with hepatico enterostomy for choledochal cysts and their surgical management in children versus adults. J Pediatr Surg 1997; 32:1097–1102. Guelrud M, Morera C, Rodriguez M, et al. Sphincter of Oddi dysfunction in children with recurrent pancreatitis and anomalous pancreatiocobiliary union: an etiological concept. Gastrointest Endosc 1999; 50:194–199. Benhamou JP, Congenital hepatic fibrosis and Caroli’s syndrome. In: ER Schiff, L Schiff (eds), Diseases of the liver (7th edn), Lippincott, Philadelphia (1993): 1204–1209. Matsumoto Y, Fujii H, Yoshioka M, et al. Biliary strictures as a cause of primary bile duct stones. World J Surg 1986; 10:867–875. Ando H, Ito T, Kaneko K, et al. Congenital stenosis of the intrahepatic bile duct associated with choledochal cysts. J Am Coll Surg 1995; 181:426–430. Stain SC, Guthrie CR, Yellin AE, et al. Choledochal cyst in the adult. Ann Surg. 1995; 222:128–133. Ohtsuka T, Inoue K, Ohuchida J, et al. Carcinoma arising in choledochocele. Endoscopy 2001; 33:614–619. Hu B, Gong B, Zhou DY. Association of anomalous pancreaticobiliary ductal junction with gallbladder carcinoma in Chinese patients: an ERCP study. Gastrointest Endosc 2003; 57:541–545.

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Parasitic Disease: Endoscopic Diagnosis and Management of Tropical Parasitic Infestations Nageshwar Reddy, G. Venkat Rao, Wai Choung Ong and Banerjee Rupa

INTRODUCTION Parasitic infestation of the biliary tract is a common cause of hepatobiliary disease in developing countries and in rural areas of developed countries. In developing countries biliary parasitoses often mimic biliary stone disease. With the advent of international travel and immigration, clinicians in developed countries will encounter these conditions with increasing frequency. Ascariasis, hydatid liver disease, clonorchiasis, opisthorchiasis and fascioliasis are the commonly encountered parasitic infestations of the biliary tract. They may present with cholestasis, obstructive jaundice, biliary colic, acute cholangitis and less commonly pancreatitis. An abdominal ultrasound facilitates the diagnosis in most cases. Although medical therapy remains the mainstay of treatment, endoscopic retrograde cholangiopancreatography (ERCP), and endoscopic sphincterotomy with bile duct clearance is essential when biliary complications occur.1 In contrast to ascariasis and hydatid disease in which the radiological assessment may suggest the diagnosis clonorchiasis, opisthorchiasis and fascioliasis require astute clinical suspicion in non-endemic areas.

ASCARIS LUMBRICOIDES The roundworm, Ascaris lumbricoides, is the most common helminthic infestation the world over, infecting an estimated one billion people. Cases have been reported from non-endemic areas in both developing and developed countries.2–5 Often the infestation is asymptomatic. When present, symptoms can vary from a nonspecific abdominal pain to intestinal obstruction. Symptomatic patients present with a variety of hepatobiliary and pancreatic complications due to migration of worms into the common bile duct. Biliary-pancreatic ascariasis is commonly reported from high endemic regions such as the Kashmir valley in India. In a study of 500 patients with hepatobiliary and pancreatic ascariasis, Khuroo et al. reported biliary colic in 56%, acute cholangitis in 24%, acute cholecystitis in 13%, acute pancreatitis in 6% and hepatic abscess in less than 1%.6 Biliary-pancreatic ascariasis should be suspected in patients from an endemic area presenting with biliary symptoms.6 In this setting, identification of eggs, larva or the adult worm from bile or feces is strongly suggestive of the disease. Diagnosis is confirmed by ultrasound, abdominal CT, or ERCP.

Abdominal ultrasonographic features highly suggestive of biliary ascariasis include the presence of long, linear, parallel echogenic structures without acoustic shadowing and the “four lines sign” of non-shadowing echogenic strips with a central anechoic tube representing the digestive tract of the parasite.7

Endotherapy During endosocpy, worms can be seen in the duodenum and are often seen protruding from the ampulla of Vater. During ERCP, radiographic features of the Ascaris worm include the presence of long, smooth, linear filling defects with tapering ends (Fig. 37.1); smooth, parallel filling defects; curves, and loops crossing the hepatic ducts transversely; and dilatation of bile ducts (usually the common bile duct). Endoscopy is the mainstay of treatment for biliary ascariasis.1,8–11 Worm extraction is easy when it protrudes out of the ampulla of Vater (Fig. 37.2). Held with a grasping forceps, the worm can be brought out by withdrawing the endoscope out of the patient. A Dormia basket can also be used: the outer end of the worm should be maneuvered into the strings of the basket and gently held before extraction.9 It is best to avoid using a polypectomy snare as it tends to cut the worm. As remnant worms lead to stone formation, worms in the biliary tree should be extracted completely.1 Worms within the common bile duct occasionally protrude out of the papilla after contrast injection. Alternatively, they can be extracted using a Dormia basket or a biliary occlusion balloon.1 Endoscopic sphincterotomy should be avoided in endemic areas in view of the high reinfestation rates and easy entry of worms into post-sphincterotomy bile ducts. Ascariasis may co-exist with biliary calculi or strictures. In these situations, endoscopic balloon dilatation of the biliary sphincter (sphincteroplasty) is an alternative to sphincterotomy to retrieve the parasite and associated calculi.12 In endemic areas, pregnant women are prone to develop biliary ascariasis. Endoscopic intervention in such cases requires special precautions including lead shielding of the foetus and limitation of total fluoroscopic exposure. Failure of endoscopic extraction may require surgical extraction which has increased risks of fetal wastage and premature labor.13 Extraction of the culprit worm is usually associated with rapid symptom relief. Following endoscopic therapy, all patients should receive antihelminthic therapy to eradicate remaining worms. A single dose of albendazole (400 mg) is highly effective against 393

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Fig. 37.2 Ascaris protruding from the ampulla of Vater. Held with a grasping forceps, the worm can be brought out by withdrawing the endoscope out of the patient. Fig. 37.1 Linear filling defect within the opacified common bile duct in a case of biliary ascariasis. The worm was eventually removed with a Dormia basket following endoscopic biliary sphincterotomy.

ascariasis.14 In endemic areas periodic deworming may have a significant role in preventing recurrences.

ECHINOCOCCUS GRANULOSUS The “domestic strain” of Echinococcus granulosus is the main cause of human hydatid disease. Infections are found worldwide and remain endemic in sheep raising areas. The life cycle involves two hosts; the adult tapeworm is usually found in dogs (definitive host) whereas sheep (intermediate host) are the usual host for the larval stages. Human exposure is via the oral-fecal route with food or water contaminated by the feces of the infected definitive host, usually dogs.15 Embryonated eggs hatch in the small intestines and liberate oncospheres that migrate to distant sites. The right lobe of the liver is the most common site for hydatid cyst formation. The majority of patients remain asymptomatic. In symptomatic patients, abdominal ultrasound and serologic studies usually establish the diagnosis. In approximately one-fourth of cases, hydatid cysts rupture into the biliary tree causing obstructive jaundice.16 Contents of the cyst (the scolices and daughter cysts) draining into the biliary ducts cause intermittent or complete obstruction of bile duct, resulting in obstructive jaundice, cholangitis, and sometimes cholangiolytic abscesses. Rarely, acute pancreatitis complicates intrabiliary rupture of hydatid cyst.17 Cysto-biliary communication is common, occurring in 10–42% of patients. Cysto-biliary communications are often recognized at surgery when cysts are stained with bile.18,19 Unrecognized cysto-biliary communications may present in the postoperative period as a persistent biliary fistula resulting in prolonged hospitalization and increased morbidity. Hydatid cyst involving the pancreatic head has been rarely reported.20 These cysts enlarge manifesting as acute pancreatitis, 394

chronic pancreatitis or obstructive jaundice and are easily confused with pancreatic pseudocyst, tumor or other congenital pancreatic cyst. Surgical intervention is generally required for management.

Endotherapy Treatment of hydatid disease involves antihelminthic therapy (Albendazole) combined with surgical resection of the cyst. Endoscopic intervention plays an important role (1) when intrabiliary rupture of the hydatid cyst occurs and (2) in the management of biliary complications following surgery.21–35

1. Intrabiliary rupture of a hydatid cyst Intrabiliary rupture is a common and serious complication of hepatic hydatid cyst. The incidence varies from 1% to 25%.36 ERCP is indicated when intrabiliary rupture is suspected clinically (jaundice), biochemically (cholestasis) or sonographically (a dilated biliary ductal system in association with hydatid cysts in the liver).23,25 Duodenoscopy sometimes shows whitish, glistening membranes lying in the duodenum, or protruding from the papilla of Vater. On cholangiography, the hydatid cyst remnants appear as: (a) filiform, linear wavy material in the common bile duct representing the laminated hydatid membranes; (b) round or oval lucent filling defects representing daughter cysts floating in the common bile duct; or (c) brown, thick, amorphous debris.25,35 Cholangiography often reveals minor communications, particularly with peripheral ducts. The significance of these communications remains unclear. In patients presenting with obstructive jaundice or cholangitis, endoscopic biliary sphincterotomy facilitates extraction of the cysts and membranes with use of a Dormia basket (Fig. 37.3) or a biliary occlusion balloon.27,28 Saline irrigation of the bile duct may be necessary to flush out the hydatid sand and small daughter cysts. Lifethreatening episodes of acute cholangitis can be managed by initial nasobiliary drainage as a temporizing method, followed by extraction of hydatid cysts and membranes with or without sphincterotomy. The nasobiliary drain output can be examined for hydatid hooklets or membranes. Endoscopic management of acute biliary

Chapter 37 Parasitic Disease: Endoscopic Diagnosis and Management of Tropical Parasitic Infestations

Obstructive jaundice occurs in up to 2% of patients following surgical resection of a hydatid cyst. This typically presents within two to four weeks of surgery.23–27 Obstructive jaundice results from common bile duct obstruction by echinococcal remnants in the presence of cysto-biliary communications. As such, endoscopic biliary sphincterotomy and ductal clearance followed by internal stenting may be required for approximately four to eight weeks to achieve fistula closure. Sclerosing cholangitis and Sphincter of Oddi stenosis are seen in patients in whom formalin is used to sterilize the cysts during surgery. Seepage of formalin into bile ducts through minor communications may result in inflammatory changes and stricture formation in the long term. Almost all scolicidal agents are associated clinically or experimentally with this complication. Amongst the various scolicidal agents currently available, the use of hypertonic saline (20%) may be preferable.41,42 These complications can be treated endoscopically by sphincterotomy and stenting with or without dilatation of the stricture using biliary balloons. Fig. 37.3 Hydatid membranes protruding from the ampulla of Vater in a case of hydatid disease of the liver with intrabiliary rupture. Endoscopic biliary sphincterotomy facilitates extraction of the cysts and membranes using a Dormia basket.

complications allows for definitive surgery to be performed electively. Rarely, rupture with complete drainage may be treated endoscopically alone.37 In the presence of a hydatid cyst communicating with the biliary ductal system, a hydrophilic guidewire can usually be negotiated into the cyst followed by a placement of a nasobiliary catheter to facilitate cyst evacuation. Irrigating the cyst with hypertonic saline solution through the nasobiliary catheter ensures sterilization of the germinal layers plus the remaining daughter cysts.22 In the presence of extensive disease with multiple cysto-biliary communications, this method should not be used because of the potential to elicit biliary strictures from seepage of the hypertonic saline solution into the biliary tree.38,39

2. Biliary complications following surgery Biliary complications occur in up to 14–16% of patients following surgery for Echinococcus complications.18,40 Early postoperative complications include persistent biliary fistula and obstructive jaundice. Sclerosing cholangitis and sphincter of Oddi stenosis are late postoperative complications. Persistent biliary fistula is the most common postoperative complication and occurs in 50–63% of patients following surgery.19,40 Unrecognized cysto-biliary communications manifest as persistent biliary drainage through a T-tube or development of an external biliary fistula in the postoperative period. Low output fistulas (less than 300 mL/day) usually close spontaneously after a mean duration of four weeks. Patients with high output fistulae require endoscopic intervention.18 Endoscopic biliary sphincterotomy and ductal clearance, followed by internal biliary stenting for approximately 4–8 weeks, is usually sufficient to achieve fistula closure. Sphincterotomy alone may also be effective.24 Occasionally, fistulous communication may develop between the hepatic hydatid cyst and the bronchi, leading to the development of a broncho-biliary fistula either de novo or following surgery. Endoscopic biliary sphincterotomy and nasobiliary drainage or stenting is effective in closing these fistulae non-operatively.33

CLONORCHIS SINENSIS Clonorchis sinensis, also known as the Chinese liver fluke, is a trematode commonly found in South East and Far East Asian countries, mainly China, Japan, Korea, Taiwan, and Vietnam. It is estimated that about 35 million people are infected globally, of whom approximately 15 million are in China.43 It is harbored in the biliary tract of man and other fish-eating animals. Liver flukes have a lifespan of 10–30 yrs; this creates a problem for Asian immigrants who develop clinical symptoms many years after leaving the endemic area.44 Opisthorchis felineus and Opisthorchis viverrini also cause similar clinical manifestations. Clonorchiasis is acquired from eating infested raw fresh water fish (carp and salmon group). The infective metacercariae adhere to the common bile duct and migrate along the epithelial lining of the duct into the intrahepatic ducts, where they mature into flat, elongated, 10–23 mm long adult worms. The smaller branches of the left lobe of liver are commonly involved where the adult form attains maturity at about one month and begins to lay eggs. The migration of the immature flukes causes trauma, ulceration and desquamation of the bile duct epithelium. Adenomatous hyperplasia and goblet cell metaplasia develop as a result of epithelial injury and may lead to encapsulating fibrosis of the bile duct. While a single exposure to the parasite is of little significance, repeated exposures provoke diffuse involvement of the biliary tree, including the large bile ducts and gallbladder. The average infection leads to harboring of about 20–200 adult flukes, which which can increase to 20 000 flukes during a heavy infection. Dilated sub-capsular bile ducts, adenomatous ductal hyperplasia with or without peri-ductal fibrosis, and eosinophilic infiltration are seen in early infections. Cirrhosis may develop in patients with repeated infections in later phases. The endemic areas of Clonorchiasis and Opisthorchiasis coincide with the geographical distribution of liver tumors in Southeast Asia, particularly cholangiocarcinoma.45 The clinical presentation of biliary clonorchiasis is protean. Most patients with low parasite loads remain asymptomatic. Patients with large parasite loads present with cholangitis, cholangiohepatitis or intrahepatic calculi. The liver fluke causes mechanical obstruction of bile flow; subsequent bile stasis predisposes to cholangitis that results in the death of the fluke. Paroxysms of colicky upper abdominal pain due to cholangitis may be confused with gallstone disease. 395

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Biliary calculi may coexist as the eggs can act as a nidus for stone formation. Chronic infection is associated with the development of cholangiocarcinoma. Clonorchiasis should be suspected in any patient who has lived in or has traveled to an endemic region, consumed raw fresh water fish and subsequently developed clinical signs consistent with a biliary or hepatic disease.

Endotherapy In patients presenting with acute cholangitis, emergency biliary decompression following sphincterotomy is the treatment of choice.46 Aspirated bile may show adult worms and ova. On cholangiography, characteristic features include mulberry-like appearance due to multiple saccular or cystic dilatations of the intrahepatic bile ducts; the “arrow head sign” due to rapid tapering of the intrahepatic bile ducts towards the periphery; and decrease in the number of intrahepatic radicles due to portal and periportal fibrosis. Ductal irregularities are due to adenomatous hyperplasia, which vary from small indentations to hemispherical filling defects. A scalloped appearance is seen, sometimes visualized as filamentous, wavy, and elliptical shaped filling defects. Endoscopic biopsy or brush cytology is indicated whenever cholangiocarcinoma is suspected. Surgical intervention is indicated in patients with hepatolithiasis complicated by multiple biliary strictures. All patients with biliary clonorchiasis should receive praziquantel (75 mg/kg per day in three divided doses for 2 days) to eradicate the infection. Biliary ductal abnormalities usually persist even after successful drug therapy.47

FASCIOLA HEPATICA Fascioliasis is caused by Fasciola hepatica, the sheep liver fluke. The most important definitive hosts are sheep and fasciola infestation remains an important veterinary disease. A wide variety of mammalian ruminants, particularly goats, cattle, horses, camels, hogs, rabbits, and deer, are commonly infected. Intermediate hosts include numerous species of snail, both amphibious and aquatic. Because of the wide range of definitive and intermediate hosts, the disease is geographically widespread and occurs worldwide. Physicians should therefore be aware of the possibility of infection in all geographical areas. Peru and Bolivia (La Paz, Lake Titicaca) are areas of highest endemicity.48 Fascioliasis occurs where watercress (water plants) is eaten; its epidemiology is related to the distribution of the intermediate snail host populations in freshwater areas. Human infection occurs following ingestion of watercress that is infested with metacercariae, the infective form of the fluke. These larvae pass through the duodenal wall into the abdominal cavity and migrate toward the liver. The disease occurs in two stages. The “acute or hepatic” phase of the illness occurs when the organism penetrates the liver capsule and migrates through the liver parenchyma toward the biliary system. Patients in the acute phase usually present with dyspepsia, followed by an acute onset of fever and abdominal pain, especially in the right hypochondrium or in the right upper quadrant. Urticaria and eosinophilia may be present. These symptoms result from the destruction and inflammatory response caused by the migrating larvae. In approximately 50% of such cases, the infection remains subclinical. The acute phase usually lasts for 3 months following ingestion of the metacercariae. 396

The second “chronic” or “biliary” phase occurs when the parasite enters the bile canaliculi 3 to 4 months after the contaminated meal is ingested. Typical manifestations are jaundice, fever, right upper quadrant pain, and rarely acalculus cholecystitis, severe hemobilia, and acute pancreatitis.49 During the chronic stage, motile flukes may be visualized in the gallbladder.50 Liver function tests reflect a cholestatic picture. Serological tests (FAST-ELISA/Falcon assay screening test or dot blot ELISA) are highly sensitive (95–100%) and specific (97%), thus aiding in diagnosis.51 Inflammation due to toxic metabolites and mechanical effects of the larvae in the bile ducts leads to epithelial necrosis and adenomatous changes, eventually leading to biliary fibrosis. These changes further evolve into cystic dilatation, total or partial obstruction of bile ducts, and periportal fibrosis and cirrhosis. Although the fibrotic changes are likely to persist despite successful therapy, some of the ductal changes are reversible.49 The adult form has a life span of approximately 9–13 years. Eggs or the dead parasites can form a nidus for calculus formation, potentially leading to intra or extra hepatic biliary calculi.

Endotherapy Oral drug therapy is the standard treatment for hepatic fascioliasis. Triclabendazole (10 mg/kg as a single dose) is the drug of choice. In severe or persistent infections, two doses of 10 mg/kg administered 12–24 hours apart are recommended.51 An alternative includes Bithionol (30–50 mg/kg on alternate days for 10–15 doses). Chloroquine, mebendazole, albendazole, and praziquantel have also been used with variable success. Patients should be advised regarding expected biliay colic caused by expulsion of parasites or parasite fragments which usually occurs 2–7 days after commencing drug therapy. Endoscopic therapy is required (1) when biliary complications occur or medical therapy fails and (2) in management of severe infection with multiple worms. During ERCP, Fasciola appear as small, radiolucent linear or crescent-like shadows, with jagged, irregular margins in the gallbladder or in dilated bile ducts. The worms can be extracted by using a balloon catheter or Dormia basket following biliary sphincterotomy (Fig. 37.4). Patients usually harbor a single Fasciola worm in the bile duct with an occasional one in the

Fig. 37.4 Fasciola hepatica extracted using a balloon catheter following biliary sphincterotomy.

Chapter 37 Parasitic Disease: Endoscopic Diagnosis and Management of Tropical Parasitic Infestations

gallbladder. When worms are present in the gallbladder or in the intrahepatic biliary radicles where they are not amenable to mechanical extraction, irrigating the biliary system with 20 ml of 2.5% povidone iodine solution (5 ml of 10% povidone iodine plus 15 ml of contrast material) during ERCP is helpful.52 Aspirated bile may be examined for parasite eggs. The management of “massive forms “of biliary fascioliasis where dozens or hundreds of mature parasites reside in the intrahepatic and extrahepatic ducts has been successfully described.53 Initial extraction of parasites with a basket or balloon catheter is performed. This is followed by a 10 minute instillation of 20 ml of 2.5% povidone iodine solution (5 ml of 10% povidone iodine plus 15 ml of contrast material) with balloon occlusion of the common hepatic duct. The ducts are then washed with saline solution and the dead parasites are removed instrumentally. Repeat treatment sessions

may be required for complete parasite clearance. In cases with cholangitis and liver abscesses, nasobiliary drainage with iodine treatment repeated three times under direct fluoroscopic control may be used.

SUMMARY Biliary parasitosis will remain a problem infrequently encountered by the practicing endoscopist in non-endemic areas. Ascariasis and hydatid disease are clinically and radiologically evident: fasciola, clonorchis and opisthorchis infections require astute clinical suspicion and awareness for early diagnosis and appropriate management.

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17. A1 Toma AA, Vermeijden RJ, Van De WA. Acute pancreatitis complicating intrabiliary rupture of liver hydatid cyst. Eur J Intern Med 2004; 15:65–67. 18. Agarwal S, Sikora SS, Kumar A, et al. Bile leaks following surgery for hepatic hydatid disease. Indian J Gastreenterol 2005; 24:55–58. 19. Simsek H, OZaslan E, Sayek I, et al. Diagnostic and therapeutic ERCP in hepatic hypatic hydatid disease. Gastrointest Endosc 2003; 58:384–389. 20. Lemmer ER, Krige JE, Price SK, et al. Hydatid cyst in the head of the pancreas with obstructive jaundice. J Clin Gastroenterol 1995; 20:136–138. 21. A1 Karawi MA, Mohamed AR, Yasawy I, et al. Non-surgical endoscopic trans-papillary treatment of ruptured echinococcus liver cyst obstructing the biliary tree. Endoscopy 1987; 19:81–83. 22. A1 Karawi MA, Yasawy MI, Shiek Mohamed AR. Endoscopic management of biliary hydatid disease: report on six cases. Endoscopy 1991; 23:278–281. 23. Magistrelli P, Masetti R, Coppola R, et al. Value of ERCP in the diagnosis and management of pre- and postoperative biliary complications in hydatid desease of the liver. Gastrointest Radiol 1989; 14:315–320. 24. Iscan M, Duren M. Endoscopic sphincterotomy in the management of postoperative complications of hepatic hydatid disease. Endoscopy 1991; 23:282–283. 25. Aargar SA, Khuroo MS, Khan BA, et al. Intrabiliary rupture of hepatic hydatid cyst: sonographic and cholangiographic appearances. Gastrointest Radiol 1992; 17:41–45. 26. Spiliadis C, Georgopoulos S, Dailianas A, et al. The use of ERCP in the study of patients with hepatic echinococcosis before and after surgical intervention. Gastrointest Endosc 1996; 43:575–579. 27. Tekant Y, Bile O, Acarli K, et al. Endoscopic sphincterotomy in the treatment of postoperative biliary fistulas of hepatic hydatid disease. Surg Endosc 1996; 10:909–911. 28. Rodriguez AN, Sanchez del Rio AL, Alguacil LV, et al. Effectiveness of endoscopic sphincterotomy in complicated hepatic hydatid disease. Gastrointest Endosc 1998; 48:593–597. 29. Yilmaz U, Sakin B, Boyaxioglu S, et al. Management of postoperative biliary strictures secondary to hepatic hydatid disease by endoscopic stenting. Hepatogastroenterology 1998; 45:65–69. 30. De A, X, Perez OL. The use of endoprostheses in biliary fistula of hydatid cyst. Gastrointest Endosc 1999; 49:797–799. 397

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31. Dumas R, Le Gall P, Hastier P, et al. The role of endoscopic retrograde cholangiopancreatography in the management of hepatic hydatid disease. Endoscopy 1999; 31:242–247. 32. Giouleme O, Nikolaidis N, Zezos P, et al. Treatment of complications of hepatic hydatid disease by ERCP. Gastrointest Endosc 2001; 54:508–510. 33. Partrinou V, Dougenis D, Kritikos N, et al. Treatment of postoperative bronchobiliary fistula by nasobiliary drainage. Surg Endosc 2001; 15:758. 34. Saritas U, Parlak E, Akoglu M, et al. Effectiveness of endoscopic treatment modalities in complicated hepatic hydatid disease after surgical intervention. Endoscopy 2001; 33:858–863. 35. Busic Z, Amic E, Servis D, et al. Common bile duct obstruction caused by the hydatid daughter cysts. Coll Antropol 2004; 28:325–329. 36. Erzurumlu K, Dervisoglu A, Polat C, et al. Intrabiliary rupture: an algorithm in the treatment of controversial complication if hepatic hydatidosis. World J Gastroenterol 2005; 11:2472–2476. 37. Hilmioglu F, Karincaoglu M, Yilmaz S, et al. Complete treatment of ruptured hepatic cyst into biliary tree by ERCP. Dig Dis Sci 2001; 46:463–467. 38. Belghiti J, Benhamou JP, Houry S, et al. Caustic sclerosing cholangitis. A complication of the surgical treatment of hydatid disease of the liver. Arch Surg 1986; 121:1162–1165. 39. Belghiti J, Perniceni T, Kabbej M, et al. Complication of preoperative sterilization of hydatid cysts of the liver. Apropos of 6 cases. Chirurgie 1991; 117:343–346. 40. Bilse Y, Bulut T, Yamaner S, et al. ERCP in the diagnosis and management of complications after surgery for hepatic echinococcosis. Gastrointest Endosc 2003; 57:210–213. 41. Sahin M, Eryilmaz R, Bulbuloglu E. The effect of scolicidal agents on liver and biliary tree (experimental study). J Invest Surg 2004; 17:323–326.

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42. Tozar E, Topeu O, Karayalcin K, et al. The effects of cetrimidechlorhexidine combination on the hepato-pancreatico-biliary system. World J Surg 2005; 29:754–758. 43. Lun ZR, Gasser RB, Lai DH, et al. Clonorchiasis: a key foodborne zoonosis in China. Lancet Infect Dis 2005; 5:31–41. 44. Stauffer WM, Sellman JS, Walker PR. Biliary liver flukes (Opisthorchiasis and Clonorchiasis) in immigrants in the United States: often subtle and diagnosed years after arrival. J Travel Med 2004; 11:157–159. 45. Srivatanakul P, Sriplung H, Deerasamee S. Epidemiology of liver cancer: an overview. Asian Pac J Cancer Prev 2004; 5:118–125. 46. Navab F, Diner WC, Westbrook KC, et al. Endoscopic biliary lavage in a case of Clonorchis sinensis. Gastrointest Endosc 1984; 30:292–294. 47. Leung JW, Sung JY, Banez VP, et al. Endoscopic cholangiopancreatography in hepatic clonorchiasis: a follow-up study. Gastrointest Endosc 1990; 36:360–363. 48. Mas-Coma MS, Esteban JG, Bargues MD. Epidemiology of human fascioliasis: a review and proposed new classification. Bull World Health Organ 1999; 77:340–346. 49. Dias LM, Silva R, Viana HL, et al. Biliary fascioliasis: diagnosis, treatment and follow-up by ERCP. Gastrointest Endosc 1996; 43:616–620. 50. Bassily S, Iskander M, Youssef FG, et al. Sonography in diagnosis of fascioliasis. Lancet 1989; 1:1270–1271. 51. Saba R, Korkmaz M. Human fascioliasis. Clinical Microbiology Newsletter 2005; 27:27–34. 52. Dowidar B, EI Sayad M, Osman M, et al. Endoscopic therapy of fascioliasis resistant to oral therapy. Gastrointest Endosc 1999; 50:345–351. 53. Roig GV. Hepatic fascioliasis in the Americas: a new challenge for therapeutic endoscopy. Gastrointest Endosc 2002; 56:315–317.

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38

APPROACH TO CLINICAL PROBLEMS

Recurrent Pyogenic Cholangitis Khean-Lee Goh and Dong Wan Seo

INTRODUCTION AND SCIENTIFIC BASIS Recurrent pyogenic cholangitis (RPC) is a condition that is characterized by repeated attacks of bacterial infection of the biliary tract. It is believed that the initiating event is the entry of enteric flora into the biliary tree causing infection and inflammation and through bacterial deconjugation of bilirubin diglucoronide, the formation of primary biliary stones.1 Persistent inflammation results in biliary strictures and stasis of bile in the biliary tree which encourages further formation of stones leading to a vicious cycle of repeated or persistent inflammation and infection. There have been reports linking helminthiasis to RPC—Ascaris lumbricoides and Clonorchis sinensis worms have been identified in the biliary tract of patients with RPC.2 RPC has been most commonly reported in countries in the Asian Pacific region including China, Taiwan, Japan, Korea and the South East Asian countries and is distinctly uncommon in the western world.3

BOX 38.1 KEY POINTS • Recurrent pyogenic cholangitis (RPC) is characterized by repeated attacks of cholangitis and presence of intrahepatic strictures and stones. • Modalities of treatment include: endoscopic retrograde cholangiography techniques, percutaneous transhepatic cholangioscopy (PTCS) and surgery. • PTCS requires skill and patience and involves the passage of a cholangioscope through a percutaneous transhepatic tract. Repeated procedures are usually needed. • Dilation of strictures with catheters and balloons and fragmentation of stones with electrohydraulic lithotripsy and laser may be necessary. The hallmark of RPC is the presence of stones and strictures, which can be located in both intrahepatic and extrahepatic ducts (Fig 38.1). The treatment of RPC is difficult and requires a multimodality approach encompassing endoscopy, radiological techniques and surgery. Successful treatment of RPC depends on the success in clearing stones, dilating strictures and maintaining the patency of the stenosed ducts. Specific management aims at accurate localization of the pathology, application of specific techniques to removing stones and dilating strictures. It serves to eliminate bile stasis and achieve control of cholangitis. Amongst the endoscopic techniques used are standard endoscopic retrograde cholangiopancreato-graphy

(ERCP) with or without cholangioscopy, percutaneous transhepatic cholangioscopy (PTCS) and postoperative cholangioscopy (POCS) though a T-tube tract. Surgery is an important treatment modality in RPC and will be discussed briefly at the end of the chapter to place it in the overall scheme of management.

INITIAL MANAGEMENT OF THE PATIENT WITH CHOLANGITIS Patients with RPC often present with acute ascending cholangitis. Acute cholangitis may be the first attack or a recurrent episode. These patients may develop septic shock quite rapidly. Initial management includes intravenous fluid replacement and the institution of intravenous potent, broad-spectrum antibiotics. Emergency surgical decompression may be necessary in some patients but carries with it a high postoperative morbidity and mortality rate.4 Non-surgical biliary drainage procedures provide an important alternative treatment option in these patients, especially in those with concomitant common bile duct stones. Urgent ERCP with placement of an indwelling stent or a nasobiliary catheter has significantly reduced the mortality rate5 (Fig, 38.2). Percutaneous transhepatic biliary drainage (PTBD) may be necessary in patients with cholangitis associated with intrahepatic stones.6

SPECIFIC TREATMENT OF INTRAHEPATIC STONES Description of techniques

Standard ERCP and peroral cholangioscopy Stones that are found in the extrahepatic bile duct and the main intrahepatic ducts can often be dealt with using conventional ERCP techniques of sphincterotomy and passing a basket and balloon into the appropriate ducts and extracting the stones. Strictures in the CBD or in the main intrahepatic ducts can be dilated with biliary dilating balloons of inflated diameters of 4–10 mm (Quantum TTC balloon, Cook Endoscopy Inc, Winston Salem, USA, MaxForce Hurricane Boston Scientific, Natrick, USA) to facilitate passage of a retrieval basket for stone extraction. The use of a “through the scope” mechanical lithotripter (Olympus Optical Company, Tokyo, Japan or MTW, Wessel, Germany) is helpful in crushing large stones. The usefulness of this approach is limited by the difficult access into the intrahepatic ducts. This is often due to angulated bile ducts, tight strictures and impacted stones making it difficult to pass and open a Dormia retrieval basket and sometimes even to pass a guidewire.7 Lithotripsy using an electrohydraulic lithotripsy (EHL) or a laser probe through a mother-baby scope set-up can be attempted to break-up main intrahepatic duct stones and allow further passage 399

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Fig. 38.1 Endoscopic retrograde cholangiogram from a patient presenting with acute ascending cholangitis showing intra- and extrahepatic strictures with stones.

Fig. 38.3 Acute angulation caused by inappropriate selection of PTBD site.

Fig. 38.2 Intra- and extrahepatic stones and strictures. A long plastic stent has been placed via ERCP to relieve the cholangitis. of Dormia basket and balloons. Eventual success is limited by location and severity of strictures and duct angulation.

Fig. 38.4 PTBD kit. A complete kit includes Chiba needles for puncture, guidewires, a dilator, and pigtail drainage catheters.

Percutaneous transhepatic cholangioscopy (PTCS) This technique requires a percutaneous transhepatic tract and three steps are required for PTCS; percutaneous transhepatic biliary drainage, dilation of the tract, and cholangioscopic examination.

1. Percutaneous Transhepatic Biliary Drainage (PTBD) The technique, PTBD, has been used to relieve obstructive jaundice, to drain infected bile, and to prevent or control cholangitis and sepsis.8 It is an initial step for creating a percutaneous tract and can be performed under fluoroscopic or ultrasonographic guidance.9 For PTCS, the site of PTBD is very important. If the puncture site is misplaced, there can be an acute angulation during the course to the target lesion (Fig. 38.3). Acute angulation is an important factor causing PTCS failure. Before selection of a PTBD site, the cholangioscopist or interventional radiologist should be familiar with the anatomy of the biliary tree. The ideal PTBD site is selected after meticulous review 400

of several imaging studies such as ultrasonography, CT scan, endoscopic retrograde cholangiography or magnetic resonance cholangiography (MRCP). A PTBD kit is composed of puncture needles, a guidewire, dilators and pigtail drainage tubes (Fig. 38.4). The usual diameter of an initial PTBD tube is around 6–8.5 Fr. For the initial puncture, the selection of a peripheral duct is important because the direct insertion of a PTBD tube into the central duct carries a significant risk of bleeding. Ultrasonography-guided puncture or fluoroscopy-guided puncture technique is commonly adopted for initial peripheral duct selection. After selective puncture of a peripheral duct, a guidewire is inserted and a bougienage dilator is pushed over the guidewire. After dilation of the tract, a pigtail catheter is introduced into the biliary tree (Fig. 38.5). In cases with a nondilated intrahepatic duct, PTBD carries a high risk of bleeding and biliary leakage. To prevent these complications, the insertion of

Chapter 38 Recurrent Pyogenic Cholangitis

an endoscopic nasobiliary drainage tube before PTBD and simultaneous cholangiography using this tube during PTBD is helpful in the accurate targeting of the desired intrahepatic duct.10

2. Tract dilation For cholangioscopic examination of the biliary tree, the diameter of the percutaneous transhepatic tract should be larger than that of the cholangioscope (e.g. CHF P 20, Olympus Optical Company, Tokyo, Japan). The cholangioscope diameter varies from 3.0 mm to 5.2 mm. Therefore the diameter of the percutaneous tract should be dilated to at least 11–12 Fr when an 11 Fr cholangioscope is to be used. In most centers, the tract is dilated to 16–18 Fr because a cholangioscope with an outer diameter of 16 Fr is commonly used for therapeutic purposes. This dilation procedure can be performed by the aid of a specialized dilation Kit (Nipro, Tokyo, Japan) (Fig. 38.6). The dilation process can be accomplished by “multi-stage” dilation or by “onestage” dilation.11 Multi-stage dilation means reaching the fully dilated diameter of percutaneous tract through several repeated dilations. The diameter of PTBD tube is around 6–8.5 Fr at the first attempt. The tract can be dilated in stages every two to four days; to 10–12 Fr, then up to 14–16 Fr, and, finally, up to more than 18 Fr. In the “one-

A

B

C

D

Fig. 38.5 Fluoroscopic images of PTBD procedures. A A guidewire is inserted into the left intrahepatic duct after selection of S3 segmental duct by puncture needle. B The tract is dilated by a dilator up to 8 Fr. C A 7.5 Fr pigtail drainage catheter is inserted into the dilated tract. D Previously injected contrast material is well drained through the pigtail catheter.

A

B

stage” dilation protocol, however, the PTBD tract is dilated up to 16 or 18 Fr in a single session 2–4 days after the initial PTBD. There are advantages and disadvantages of each method. The main advantage of “multi-stage” dilation is that the dilation process is less painful and less traumatic to the patient. Gradual dilation with repeated procedures can reduce the risk of severe pain or the chance of significant bleeding after dilation. However, “multi-stage” dilation is time consuming, requires several procedures until satisfactory dilation is achieved, and is costlier. The one-stage dilation protocol saves time and money compared to the “multi-stage” dilation protocol but can cause significant pain and bleeding during the procedure. For the “one-stage” dilation protocol, it is mandatory to provide adequate analgesia in addition to antibiotics.

3. Percutaneous transhepatic cholangioscopic examination Following full dilation of the percutaneous transhepatic tract, 10–14 days are usually required for maturation of the sinus tract at which time the cholangioscopic examination can be safely performed (Fig. 38.7). The patient is positioned in the supine position on the fluoroscopy table. The position of the cholangioscopist can be changed according to the site of PTBD. For example, when PTBD is performed on a right intrahepatic duct, the right side of the patient is the preferred position and when PTBD is done on a left intrahepatic duct, the left side of the patient is the preferred position. The video monitor and fluoroscopic monitor should be located at a favorable

Fig. 38.6 Nipro set for tract dilation. A complete set for tract dilation is composed of a guidewire, a tapered tip catheter, variable sized bougienage tubes, and a PTCS catheter.

C

D

Fig. 38.7 Percutaneous transhepatic cholangioscopic examination. A Dressing set for PTCS. B Draping was done before cholangioscopic examination. An 18 Fr PTCS catheter is visible and the tube is tied to the skin to prevent migration. C Checking of light source and saline flow before insertion of the cholangioscope into the body. D Insertion of cholangioscope. After insertion of the tip of the cholangioscope into the tract, the cholangioscopist monitors the videoscopic view and guides the cholangioscope tip to maintain the view of the bile duct lumen. 401

SECTION 3 APPROACH TO CLINICAL PROBLEMS

angle for the cholangioscopist. Premedication is required to relieve pain and anxiety using a combination of meperidine and midazolam or diazepam. The insertion of a cholangioscope into a fully dilated tract is not difficult. However, if the waiting period between the tract dilation and cholangioscopic examination is short, the insertion of the cholangioscope can be difficult and sometimes traumatic. The tract may collapse after removal of the dilation tube, especially during the first cholangioscopic examination. A guidewire, which is inserted before removal of the dilation tube, is used to smoothly guide the cholangioscope into the biliary tree. PTCS offers several advantages. The percutaneous approach allows evaluation of both the intrahepatic ducts and common bile duct and it is the shortest distance to the biliary tree. The handling and angulation maneuvers of the tip of the percutaneous cholangioscope are easier compared to those of peroral cholangioscopy. The application of various techniques such as biopsy, suction, and dye spraying during cholangioscopic examination is also not difficult. Insertion of a balloon or a catheter under cholangioscopic guidance and application of biopsy forceps or electrohydraulic lithotripsy are much easier than the peroral approach. The only drawback compared to the peroral route is the necessity of creating a percutaneous tract, which is an invasive process. During cholangioscopic evaluation of the biliary tree, irrigation is required to obtain an optimal view of the bile duct. In the biliary tree, pus, sludge and blood can cause blurring of the view. Thick bile may also “coat” the bile duct wall. To obtain a clear view of the bile duct continuous saline irrigation is recommended and is usually achieved by suspending a bottle of normal saline and letting the saline flow continuously into the instrumental channel of the cholangioscope to “wash” the bile duct (Fig. 38.8).

When compared to a percutaneous transhepatic tract, the T-tube tract is a relatively long tract and traverses a longer length of free peritoneal space before reaching the common bile duct. When percutaneous transhepatic cholangioscopy is employed, the distance of free space between parietal peritoneum and liver capsule is usually less than 1 cm whereas the T-tube tract has a free space between parietal peritoneum and common bile duct which is usually longer than 4–5 cm. Because of this difference, maturation of the T-tube tract usually takes a longer period of time, normally at least 4 weeks after T-tube insertion. An ideal T-tube tract should run a straight course from the skin to the insertion point in the bile duct. If this tract meets the common bile duct at a right angle, cholangioscopic examination of the common bile duct and the intrahepatic ducts is not difficult (Fig. 38.9). The technique of bile duct examination is basically similar to that of percutaneous transhepatic cholangioscopy. However, there are also some limitations of postoperative cholangioscopy. In addi-

A

B

Postoperative Cholangioscopy (POCS) Although the practice of performing ERCP and laparoscopic cholecystectomy is commonly carried out in patients with gallbladder and common bile duct stones, many patients still undergo open cholecystectomy with common bile duct exploration and with a T-tube left in situ in the common bile duct. POCS can be performed in these patients following maturation of the T-tube tract, when there are concomitant common bile duct and/or intrahepatic stones.12

A

B

Fig. 38.8 Normal saline irrigation by gravity. A A bottle of normal saline is connected to the cholangioscope. Gravity provides a continuous flow of normal saline into the bile duct during cholangioscopic examination. B The flow can be controlled by the on and off switching of a two-way stopcock.

C

Fig. 38.9 Ideal course of T-tube tract. A A successful cholangioscopic examination is dependent on the straightness of the tract. The ideal T-tube tract for POCS should be straight and the insertion angle into CBD is a right angle. B,C In the setting of a right angle, the insertion of the cholangioscope into intrahepatic duct or distal CBD is possible with the aid of flexion or extension movement of tip of cholangioscope. 402

Chapter 38 Recurrent Pyogenic Cholangitis

tion to having to wait for a longer period until full maturation of the tract, insertion of the cholangioscope may not be easy because the T-tube tract may contain angulations (Fig. 38.10). An acute angulation makes cholangioscopic examination very difficult and perforation of T-tube tract during insertion of a cholangioscope can occur.

Techniques for cholangioscopic stone removal 1. Removal with a basket

Biliary stones can be found in a straight duct and/or in an angulated duct. Cholangioscopic removal of stones requires an experienced operator in order to make an otherwise laborious procedure less time-consuming and safer. The basic steps for cholangioscopic removal of stones are as follows: first, the basket is inserted into the biliary tract; second, the basket is opened just beyond the stones; third, the stone is engaged by withdrawing the opened basket; fourth, stones are grasped firmly by withdrawing the basket further; finally removal of the stone by removal of the cholangioscope and basket simultaneously (Fig. 38.11).

A

B

Fig. 38.10 Various angulations of a T-tube tract. A,B During operative insertion of T-tube into the bile duct, various angulations can be made at the sinus tract and are important factors that limit successful cholangioscopy. The surgeon should be cautious to prevent these types of angulations.

A

B

For removal of stones, a Dormia-type basket is used. The ideal position of the basket tip before opening is just beyond the stones and they can be captured only by gentle withdrawal of the opened basket (Fig. 38.12). If a basket is opened in front of a stone, there is a possibility of pushing the stone into a peripheral duct. The basket may be opened just before the stone or at the exact site of the stone; the stones can be captured by pushing the opened basket or by the back and forth movement of the basket. However, this pushing maneuver or back and forth movement is not recommended because these movements can cause deformity of the basket. Gentle with-

A

B

C

D

Fig. 38.11 Illustration of the four basic steps of cholangioscopic stone removal. A A basket is inserted through the cholangioscope and the basket tip is positioned beyond the stone. B The basket is opened just beyond the stone to grasp the stone easily. C Gentle withdrawing of the opened basket is usually enough to engage intraluminal stones. To facilitate this step, the basket should keep its original shape when it is opened within the lumen. D Further closure of the basket in which the stone is engaged allows the stone to be grasped tightly; removal of stone is usually achieved by gentle, simultaneous withdrawal of the cholangioscope and stone basket.

C

Fig. 38.12 Cholangiography during basket stone removal. A The cholangioscope is just in front of an intrahepatic stone (arrow) and a basket tip is located just beyond the stone before opening. B The basket is opened beyond the stone. C By withdrawing the opened basket, a small stone is engaged within the basket. 403

SECTION 3 APPROACH TO CLINICAL PROBLEMS

drawal of the basket and closure of the basket to engage the stones during this withdrawal movement is recommended.

2. Stone fragmentation Large stones cannot be extracted directly from the biliary tree, and need to be broken into smaller fragments. The easiest way to fragment large stones is to crush them by tightening or closing the basket. Some of the softer brown pigment stones can be broken into several pieces by this simple maneuver. Electrohydraulic lithotripsy (EHL) or laser lithotripsy are needed to fragment harder stones. The mechanism of EHL fragmentation is compression waves (shock waves). The shock waves are generated at the tip of the probe directly in front of the stones by an explosive spark discharge in a liquid medium (Fig. 38.13). The different power adjustment and different frequency modes permit adaptation to various fields of application and sites. Higher energy with high frequency is very effective to fragment hard stones, but it can easily damage the bile duct wall. To avoid tissue damage, lower energy levels are preferable. For the best results, the probe must be placed directly on the stone. The EHL shock wave can only be generated in an aqueous media and there-

A

B

fore an electrolyte solution such as physiologic saline (0.9% NaCl) is used to irrigate the area. This technique can be applied not only to the fragmentation of large and hard stones, but also to the fragmentation of smaller stones that are impacted in the peripheral duct or in a strictured segment.13 It may not be possible to remove impacted stones using only a basket because there is no space to open the basket and grasp the stones. When EHL lithotripsy is used, only a small aperture is needed and the tip of probe can then come into contact with the stone. Once the tip of the electrohydraulic lithotripsy probe is directed at the stones, the electrohydraulic shock wave can be generated in an aqueous media and the force applied to the stone (Fig. 38.14). After fragmentation of large stones into small pieces, a basket can be introduced past the strictured segment and small fragmented stones can then be extracted or washed away by forceful saline irrigation.

3. Stricture dilation Intrahepatic stones frequently occur upstream to a strictured segment of the bile duct. For cholangioscopic removal of these

C

Fig. 38.13 Stone fragmentation using EHL. A The tip of the EHL probe is placed on the surface of a pigmented stone. B During EHL firing, an electric spark and accompanying shock wave is generated in the area of the probe tip. C Exposed inner core. Layered structure of inner core is visible after destruction of outer shell.

A

B C

Fig. 38.14 Application of EHL to an impacted stone. A This cholangiogram shows a large stone impacted in the left intrahepatic duct. There is no space to permit the introduction of a stone basket. B Cholangioscopic view reveals only small anterior surface of the impacted large stone. The tip of the EHL probe is positioned at the surface of the stone. C Shockwave is generated to the impacted stone. 404

Chapter 38 Recurrent Pyogenic Cholangitis

stones, stricture dilation is required. A balloon dilator or a dilating catheter can be used for this purpose.14 When balloon dilation is performed, a balloon and pressure gauge are required. There are several types of balloons which can be used for dilation of strictures (Cook, Bloomington, USA). The ideal balloon should have a small shaft diameter and the balloon should be strong enough to endure the pressure applied during dilation. The balloon must be long enough to cover the stricture segment. For balloon dilation, a guidewire is inserted across the strictured segment under cholangioscopic and fluoroscopic guidance. After insertion of a guidewire, the balloon is advanced though the strictured segment over a guidewire and positioned under fluoroscopy. It is important to keep the guidewire straight during the advancement of the balloon catheter. The optimal location of the balloon is usually obtained when the mid-portion of the balloon (where the expansile force is greatest) is located at the stricture. If the balloon is not placed centrally over the stricture as described, there is a tendency for the balloon to slip in or out of the stricture during inflation of the balloon. Contrast media or distilled water mixed with radioopaque contrast material is used to inflate the balloon and allow visualization of the dilating balloon under fluoroscopy. Radio-opaque

A

B

contrast material acts as an indicator of the degree of dilation (Fig. 38.15) by showing up waisting of the balloon at the site of the stricture and obliteration of the waisting with successful dilation (Fig 38.16). The dilation pressure should be monitored to achieve and maintain the optimum inflation pressure of 6–10 atmospheres. Dilation of the bile duct can also be achieved with catheters.13 There are two types of catheters according to the shape of the tips; a tapered tip catheter (Akita Sumitomo, Bakelite Company, Akita, Japan) and a straight tip catheter (Cook, Bloomington, USA) (Fig 38.17). The main advantage of the tapered tip catheter is that it is easier to pass into and across the strictured segment. However, a catheter with tapered tip has a tendency to slip away from the lesion when the strictured segment is tight, while a straight tip catheter does not. The main disadvantage of a straight tip catheter is that the insertion of this catheter can be traumatic and may cause severe pain or bleeding because of its blunt end. For the insertion of a catheter into the strictured segment, a guidewire is passed through the strictured portion. The catheter is pushed though the strictured segment over the guidewire. If there is an acute angulation during the course of passage, catheter insertion frequently fails. To overcome difficult angulations, two or more

C

Fig. 38.15 Balloon dilation of left main duct. A A tight stricture in the left main duct with upstream duct dilation is seen. Under cholangioscopic and fluoroscopic guidance, a guidewire is passed into the stricture segment. B A balloon is inserted over the guidewire and centered across the strictured segment (the two radio-opaque markers of the balloon are seen). The balloon is inflated with contrast material. C After successful dilation, the cholangioscope is able to pass the stricture segment.

A

B

Fig. 38.16 Waist formation and disappearance during balloon dilation. A The tight stricture causes a waist of the balloon during pressure exertion. B When the pressure exceeds the strength of stricture, the waist disappears. Once this occurs the inflation pressure should not be increased.

405

SECTION 3 APPROACH TO CLINICAL PROBLEMS

INDICATIONS AND CONTRAINDICATIONS

Fig. 38.17 Two types of catheters. According to the shape of the tip, catheters are classified into two types; tapered (lower two catheters) and straight (uppermost catheter).

guidewires can be used simultaneously to guide the tip of the dilating catheter (Fig. 38.18). Balloon dilation and catheter dilation can be used in combination. In case of tight strictures, balloon dilation followed by catheter placement into the stricture segment allows for an effective dilation. To allow efficient bile drainage from other intrahepatic ducts at the same time, the catheters should have side-holes. The side-holes can be fashioned just before catheter insertion (Fig. 38.19). The number, location, and size of side-holes are important to ensure adequate drainage through the catheter and to prevent bile leakage. Before making side-holes, the cholangioscopist should measure the length of catheter which will be inserted into the bile duct. This measurement can be done by measuring the length of the cholangioscope inserted into the target lesion or the length of a guidewire after insertion into the stricture segment. Side-holes should not be located at the portion of the catheter at the sinus tract because this can cause bile leakage.

Results of cholangioscopic stone removal The cholangioscopic approach is a good therapeutic option for treatment of intrahepatic stones, especially for multiple and bilateral intrahepatic stones. Complete stone removal can usually be achieved after several cholangioscopic sessions (Fig. 38.20). However, there are some difficult cases with multiple strictures and angulations. From studies of long-term results and risk factors for stone recurrence, complete stone clearance can be achieved in 80% of patients.15 The rate of complete stone clearance by the cholangioscopic approach is significantly lower in patients with severe intrahepatic strictures than those without strictures. Patients with severe intrahepatic strictures also show a higher recurrence rate than those with mild strictures or no strictures. In addition, the stone recurrence rate is different according to the hepatic functional reserve. The recurrence rate is significantly higher in patients with advanced biliary cirrhosis such as Child class B or C than those with mild cirrhosis such as Child class A or no cirrhotic change.16 406

Standard ERCP is important and indicated in the initial evaluation of a patient presenting with acute cholangitis. A good quality cholangiogram can be obtained with ERCP. However, with tight strictures and impacted stones the biliary anatomy upstream to the pathology may not be seen. Extrahepatic stones and stones with strictures in the main intrahepatic ducts can be treated using conventional ERCP techniques with retrieval basket and balloons and dilating balloons. This is indicated in providing acute, albeit temporary, relief of biliary obstruction and cholangitis with the placement of plastic stents or nasobiliary drain. PTCS is indicated in patients with peripheral intrahepatic stones, multiple bilateral intrahepatic stones, or stones located upstream to tight intrahepatic strictures. It allows better access to the affected intrahepatic ducts with a cholangioscope. It is also indicated in providing biliary drainage with a PTBD. Apart from the general contraindications to ERCP there are no specific contraindications in the setting of RPC. PTCS is contraindicated in patients with bleeding diathesis. The risk of bleeding is high in patients with concomitant advanced cirrhosis. Ascites makes establishment of a mature percutaneous tract difficult and special precautions are needed, including the use of sheaths. For patients with a history of allergy to contrast media, prophylactic steroids should be given or, alternatively, non-ionic contrast media is given. Patients must be cooperative and well sedated for both ERCP and PTCS. These procedures are relatively high risk and sophisticated and the full concentration of endoscopists and assistants is needed.

COMPLICATIONS AND THEIR MANAGEMENT Complications of ERCP are as for other indications. Cholangitis may be a particularly difficult problem especially when contrast is injected into intrahepatic ducts that cannot be drained and/or following the insertion of catheters and manipulation in the biliary tree.17 In these instances percutaneous drainage of the appropriate duct should be carried out. Intravenous antibiotics are administered prior to and continued post-procedurally. The main complications from PTCS are related to transhepatic catheter placement and dilation of the cutaneous hepatic fistula. Hemobilia due to biliovenous fistula is a commonly encountered problem. Bleeding may not be apparent when the percutaneous catheter is in place as the catheter provides a tamponading effect and occurs when the catheters are removed. Complications with the use of the cholangioscope are usually minor. Bleeding is reported in about 10% of cases but major bleeding requiring transfusion or therapeutic intervention occurs in 1– 2%. Perforation of the intrahepatic bile ducts is reported in 1.7%.18 Cholangitis is a problem with PTCS and occurs following vigorous manipulation of the biliary tree and the inability to completely drain the bile ducts where “lakes” of contrast-filled intrahepatic ducts may be present. If a sinus or T-tube tract is not mature enough, partial or complete migration of the catheter may cause bile leakage and bile peritonitis, which is a serious complication. The risk of a percutaneous tube dislocation is reduced if the distal end of the tube is place in the common bile duct or through the papilla into the duodenum. When dislocation of the tube occurs, immediate replacement of the

Chapter 38 Recurrent Pyogenic Cholangitis

A

B

D

E

C

Fig. 38.18 Catheter insertion using double guidewires. A Two guidewires are inserted into the distal common bile duct. B The cholangioscope was removed while two guidewires are kept in the bile duct. C Insertion of a 16 Fr PTCS catheter is tried and would not pass the angulated area. D After several negotiations, it was possible for the catheter to pass the angulated area. E Catheter cholangiogram shows the tip of PTCS catheter located in the distal common bile duct.

tube along the same tract is required, although this may not be possible.

LONG-TERM MANAGEMENT OF RPC As complete dilation of intrahepatic strictures is rarely successful, one of the biggest problems in RPC is persistent infection and recurrent stone formation. When a percutaneous access has already been created for cholangioscopy, access can be maintained with the placement of a Yamakawa-type transhepatic tube, which can be occluded at the skin-level. Repeat cholangioscopy with extraction of newly formed stones or further dilation of strictures can then be carried out.

SURGERY Fig. 38.19 PTCS catheters before (above) and after making sideholes (below).

Non-surgical approaches to treatment of RPC have often proven to be difficult with persisting or recurrent problems. Another concern 407

SECTION 3 APPROACH TO CLINICAL PROBLEMS

A C

B

Fig. 38.20 Sequential dilations of multiple strictures and stone removal. A Upon catheter cholangiogram, many branches of right intrahepatic ducts are missing. Several right intrahepatic stones are faintly delineated. B After several sessions of stricture dilation using balloons and PTCS catheters, this cholangiogram reveals multiple stones in the right superior and inferior branch ducts. C After full dilation of multiple segmental ducts and cholangioscopic stone removal, many right intrahepatic ducts are visualized.

in RPC is the development of cholangiocarcinoma. Hepatectomy, where feasible, can provide definitive treatment for hepatolithiasis as it removes not only the stones, but the strictured bile ducts and abolishes the possibility of recurrent stone formation and risks of cholangiocarcinoma. Intrahepatic stones that are confined to one lobe allow removal of the affected lobe with cure of the disease. In most cases there is predilection for stones to be confined to the left lobe of the liver. Bilobar stone disease poses a therapeutic dilemma. At aggressive surgical centers the more severely affected lobe is removed and a hepaticocutaneous jejunostomy is fashioned in the

remaining lobe for access to allow further percutaneous cholangioscopic treatment.19

RELATIVE COST Surgery, although the highest initial cost, offers the best definitive treatment when feasible and is probably the most cost-effective treatment. PTCS requires repeated procedures and uses both endoscopy and radiology time. Cost of treatment will therefore escalate over time.

REFERENCES 1.

2. 3. 4. 5. 6.

7.

8.

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Maki T. Pathogenesis of calcium bilirubinate gallstone: role of E. coli, b-glucuronidase and coagulation by inorganic ions, polyelectrolytes and agitation. Ann. Surg 1966; 164:90–100. Leung JW, Yu AS. Hepatolithiasis and biliary parasites. Ballière’s Clinical Gastroenterology 1997; 11:681–706. Cheung KL, Lai EC. The management of intrahepatic stones. Advances in Surgery 1996; 29:111–129. Fan ST, Lai EC, Mok FP, et al. Acute cholangitis secondary to hepatolithiasis. Arch Surg 1991; 126:1027–1031. Lai EC, Mok FP, Tan ES, et al. Endoscopic biliary drainage for severe acute cholangitis. N Engl J Med 1992; 326:1582–1586. Huang MH, Ker CG. Ultrasonic guided percutaneous transhepatic bile drainage for cholangitis due to intrahepatic stones. Arch Surg 1988; 123:106–109. Mahadeva S, Prabakharan R, Goh KL. Endoscopic intervention for hepatolithiasis associated with sharp angulation of right intrahepatic ducts. Gastrointest Endosc 2003; 58:279–282. Lukes P, Ceder S, Wihed A, et al. Evaluation of percutaneous cholangiography and percutaneous biliary drainage in obstructive jaundice. Eur J Radiol 1985; 5:267–270.

9. Makuuchi M, Yamazaki S, Hasegawa H, et al. Ultrasonically guided cholangiography and bile drainage. Ultrasound Med Biol 1984; 10:617–623. 10. Seo DW, Kim MH, Lee SK, et al. Usefulness of cholangioscopy in patients with focal stricture of the intrahepatic duct unrelated to intrahepatic stones. Gastrointest Endosc 1999; 49:204–209. 11. Nimura Y, Shionoya S, Hayakawa N, et al. Value of percutaneous transhepatic cholangioscopy (PTCS). Surg Endosc 1988; 2:213–219. 12. Cheng YF, Chen TY, Ko SF, et al. Treatment of postoperative residual hepatolithiasis after progressive stenting of associated bile duct strictures through the T-tube tract. Cardiovasc Intervent Radiol 1995; 18:77–81. 13. Sheen-Chen SM, Cheng YF, Chen FC, et al. Ductal dilatation and stenting for residual hepatolithiasis: a promising treatment strategy. Gut 1998; 42:708–710. 14. Yoshida J, Chijiiwa K, Shimizu S, et al. Hepatolithiasis: outcome of cholangioscopic lithotomy and dilation of bile duct stricture. Surgery 1998; 123:421–426. 15. Cheng YF, Lee TY, Sheen-Chen SM, et al. Treatment of complicated hepatolithiasis with intrahepatic biliary stricture by

Chapter 38 Recurrent Pyogenic Cholangitis

ductal dilatation and stenting: long-term results. World J Surg 2000; 24:712–716. 16. Lee SK, Seo DW, Myung SJ, et al. Percutaneous transhepatic cholangioscopic treatment for hepatolithiasis: an evaluation of long-term results and risk factors for recurrence. Gastrointest Endosc 2001; 53:318–323. 17. Audisio RA, Bozzetti F, Severini A, et al. The occurrence of cholangitis after percutaneous biliary drainage:

evaluation of some risk factors. Surgery 1988; 103: 507–512. 18. Seo DW. Complications of cholangioscopy. In: Seo DW, Lee SK, Kim MH, et al. (eds) Cholangioscopy. Seoul: Koonja/Lippincott Williams & Wilkins; 2002:160–167. 19. Chen DW, Poon RTP, Liu CL, et al. Immediate and long-term outcomes of hepatectomy for hepatolithiasis. Surgery 1993; 135:386–393.

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39

APPROACH TO CLINICAL PROBLEMS

Biliary Intervention in Acute Gallstone Pancreatitis Kanul Jajoo and David L. Carr-Locke

BACKGROUND Gallstones are the most common cause of pancreatitis, accounting for approximately 35% of cases of acute pancreatitis (AP) in the United States and Europe1,2 and up to 65% of cases in Asia.3 The majority of patients with acute gallstone pancreatitis (AGP) will follow a benign clinical course. However, up to 25% will progress to severe acute pancreatitis (SAP), which confers a significant increase in morbidity and mortality.4 Although the exact mechanism by which gallstones cause AP remains elusive, the correlation between gallstones and AP is well documented. Gallstones were found in the stool of approximately 90% of patients with recent ABP, whereas they are found in only 10% of patients with cholelithiasis without AP.5 In addition, persistent obstruction of the ampulla by a common bile duct (CBD) stone is believed to result in more severe pancreatic injury. Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy (ES) are effective tools for removal of such an obstructing stone and re-establishment of biliary drainage,3,6,7 with success rates exceeding 90%.

BOX 39.1 • Four controlled studies, one in abstract form only, have addressed the role of ERCP in acute gallstone pancreatitis (AGP) • Three studies demonstrated a benefit in morbidity for those patients who underwent early ERCP and one also demonstrated a mortality benefit • Systematic review of these studies confirmed that the morbidity benefit of early ERCP is seen in those patients with severe AGP

DIAGNOSIS OF ACUTE GALLSTONE PANCREATITIS The effective utilization of ERCP intervention for the management of AGP necessitates differentiating AGP from other causes of AP. As with all examples of diagnostic investigation, this requires a combination of keen history taking, physical examination and interpretation of laboratory values and imaging. A history of cholelithiasis

or symptoms consistent with biliary colic is suggestive, but not diagnostic, of a biliary etiology. The physical examination is not specific for distinguishing AGP from other causes. However, concurrent cholecystitis producing Murphy’s sign or signs of cholangitis are findings that can increase the likelihood that gallstones are the etiology of a patient’s pancreatitis. Much of the published literature involves the use of biochemical values and imaging studies for predicting a biliary etiology of AP. Serum amylase levels have been shown to be higher in patients with AGP in comparison to those with alcohol-related AP and authors have postulated that a serum amylase level of greater than 1000 indicates a biliary cause of AP.8,9 The presence of elevated liver chemistries has been evaluated and meta-analysis of these studies demonstrated that elevations of alanine aminotransferase (ALT) levels greater than threefold are suggestive of AGP.10 This study also found that total bilirubin level and alkaline phosphatase level were not useful and aspartate aminotransferase (AST) was no more useful than ALT in diagnosing AGP. In addition, once AGP is established, patients with rising serum pancreatic enzymes or liver tests carry a fourfold risk of persistent CBD stones and approximately threefold risk of complications when compared to patients with stable or declining laboratory values.11 Demonstration of cholelithiasis by imaging can further support the diagnosis of AGP. Abdominal ultrasound is the preferred initial imaging study given its high sensitivity and specificity (>95%) for gallstones.12 In the setting of AP, however, this sensitivity can be reduced.13 A more recent study found that abdominal ultrasound in the setting of AP remains a very sensitive test (86%) and, when combined with an elevation of ALT greater than 80 IU/L, is 98% sensitive and 100% specific for a biliary etiology.14 The clinician should be aware that the lack of biliary dilatation on ultrasound does not exclude choledocholithiasis as the cause of AP, especially in the first 48 hours of an attack. The attendant risks of ERCP, the gold standard for detecting choledocholithiasis, have prompted the study of magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS) as alternative diagnostic modalities. MRCP has been shown to have high sensitivity (84–95%) and high specificity (96–100%) for the diagnosis of common duct stones.15–17 The most common cause of a false negative MRCP was gallstone size of less than 5 mm.16 EUS demonstrates equivalent accuracy to MRCP for the detection of choledocholithiasis.17 EUS can detect choledocholithiasis at a sensitivity of 98% with 99% specificity,18 and may safely replace diagnostic ERCP.19 The exact role of each of these modalities in the diagnosis of AGP and the patient group to which they should be individually applied must be clarified in future studies and is inevitably dependent on local availability and logistics. 411

SECTION 3 APPROACH TO CLINICAL PROBLEMS

System

Complication

Pulmonary

Mechanical ventilation; pneumonia with hypoxemia (PaO2 ≤ 60 mm Hg); and hypoxemia (PaO2 ≤ 60 mm Hg) or dyspnea requiring frequent assessment of need for intubation Hypotension requiring pressor support; ischemia or acute myocardial infarction noted on electrocardiogram or cardiac enzymes; and new onset arrhythmia other than sinus tachycardia Sepsis of any origin New onset oliguric or nonoliguric renal failure or new onset dialysis Disseminated intravascular coagulation and platelet counts <50 × 109/L Glasgow Coma Scale score ≤9 and diminished responsiveness or agitation (requiring significant sedation) with need for frequent airway monitoring Stress ulcer with hematemesis or melena (requiring >2 U of blood per 24 hours)

Cardiovasoular

Infectious Renal Hematologic Neurologic

Gastrointestinal tract

Table 39.1 Definition of severe complications requiring intensive care unit monitoring and treatment (Reproduced with permission from Meek K et al. Arch Surg 2000;135(9):1048–1052.) Physiological variable

Reference range

Rectal temperature, °C Mean arterial pressure, mm Hg Heart rate (ventricular response), beats/min Respiratory rate, breaths/min Oxygenation, mm Hg

36–38.4 70–109 70–109

Arterial pH Serum sodium level, mmol/L Serum potassium level, mmol/L Serum creatinine level, μmol/L (mg/dL) (double point score for acute renal failure) Hematocrit Leukocyte count, ×109/L Glasgow Coma Scale score (GCS)

12–24 PAO2 − PaO2 < 200 or PO2 > 70 7.33–7.49 130–149 3.5–5.4 0.6–1.4 (53–123)

0.30–0.46 0.003–0.015 15—actual GCS score

Table 39.2 The APACHE II scoring systema (Reproduced with permission from Meek K et al Arch Surg 2000;135(9):1048–52.) a To calculate the Acute Physiology and Chronic Health Evaluation (APACHE) II score, the 12 physiological variables are assigned points between 0 and 4, with 0 being normal and 4 being the most abnormal. The sum of these values is added to a point weighting for patient age (≤44 years = 0; 45–54 years = 2; 55–64 years = 3; 65–74 years = 5; ≥75 years = 6) and a point weighting for chronic health problems. PAO2 − PaO2 indicates alveolar-arterial difference in partial pressure of oxygen.

ASSESSMENT OF SEVERITY OF ACUTE PANCREATITIS Early recognition of patients with severe acute pancreatitis (SAP) is crucial, as those patients will require intensive care management and will likely benefit from endoscopic intervention.3,7,20 Several clinical and radiographic parameters have been used to evaluate the severity of AP: the presence of organ failure; prognostic indices; and 412

At admission a Age > 70 years a WBC > 18,000/mm3 Serum glucose > 200 mg/dl (11.1 mmol/L) a Serum LDH > 400 IU/L Serum AST > 250 IU/L Within 48 hours of hospital admission Hematocrit fall > 10 percentage points a BUN rise > 2 mg/dl (0.7 mmol/L) a Base deficit > 5 meq/L (5 mol/L) a Fluid sequestration > 4 L Serum calcium < 8 mg/dl (2 mmol/L) Arterial PaO2 < 60 mm Hg

Table 39.3 Ranson’s criteria of pancreatitis severity for biliary pancreatitis Modified from Table 4, Reference 24. a Denotes changes from original Ranson criteria for all other causes of acute pancreatitis.

the presence of local complications such as pancreatic necrosis, abscess or fluid collection by cross-sectional imaging. With these parameters, the Atlanta Classification of 1992 standardized the definition of SAP as the presence of local complications and/or organ failure (Table 39.1), or an Acute Physiology and Chronic Health Evaluation II (APACHE II) (Table 39.2) score greater than 8 or greater than three Ranson’s criteria.21 It is important to note that a modification of Ranson’s original criteria is used for biliary pancreatitis (Table 39.3).22 Organ failure, particularly persistent or worsening organ failure, is a strong determinant of mortality in patients with SAP.23,24 Though many definitions of organ failure have been used, more recent studies utilize the multiple organ dysfunction syndrome (MODS) score or the systemic inflammatory response syndrome (SIRS) score to ensure that findings can be generalized. Mortality in the setting of AP with organ failure can range from 20% to as high as 50% and is dependent upon the duration, severity and number of organ systems in failure.20,21,25 Prognostic indices have been formulated to predict which patients are more likely to develop severe AGP and to direct appropriate care toward that group. These include Ranson’s criteria (biliary version), modified Glasgow criteria and APACHE II score. Radiologic scores such as the Balthazar score and the modified CT severity index which are based on the extent of pancreatic necrosis and fluid collections, have been shown to correlate with mortality.26,27 Several biochemical markers of inflammation have been studied to predict SAP, but serum C-reactive protein level of greater than 150 mg/L at 48–72 hours after symptom onset remains the standard.28 Recent data suggest that a genetic polymorphism that confers an enhanced chemokine response to an inflammatory stimulus is a risk factor for progression to SAP.29 The search continues for a biochemical marker that can be easily measured in the first 24 hours of AP and reliably predicts progression to severe disease.

ENDOSCOPIC THERAPY FOR ACUTE GALLSTONE PANCREATITIS The mainstay of therapy for all forms of SAP remains supportive care including aggressive hydration, adequate nutritional support, pain control and often an intensive care unit (ICU).30 With regard to severe AGP in particular, early endoscopic therapy has become

Chapter 39 Biliary Intervention in Acute Gallstone Pancreatitis

an integral management strategy, supported by anecdotal reports31 and evidence from randomized clinical trials (RCTs).3,7,20 An additional RCT from Germany brought into question the benefit of early ERCP with ES in a subgroup of patients without signs of biliary obstruction.6 These studies differ on the assessment of pancreatitis severity, timing to ERCP, exclusion criteria and possibly endoscopic expertise. The four RCTs designed to assess the safety and benefit of early ERCP in AGP are described below and summarized in Table 39.4.

Neoptolemos et al. 1988 This landmark study comparing ERCP and ES against conservative management of AGP was performed by Neoptolemos and colleagues from 1983 through 1987 and published in 1998.7 The investigators randomized 121 of 146 consecutive patients who presented to a single institution with suspected AGP to receive either conservative management or ERCP within 72 hours of admission. The diagnosis of AGP was established by ultrasound and laboratory data. The severity of pancreatitis was predicted within 48 hours of admission using the modified Glasgow criteria.32 If choledocholithiasis was found on ERCP, an ES with stone extraction was performed. Outcome measures included mortality, length of stay, local complications and organ failure. Predicted severe AP was present in 44% of all patients enrolled (25 of 59 in the ERCP group and 28 of 62 in the conservative management group). ERCP was successful in 94% of mild disease and 80% of severe disease. One ERCP-related complication was cited, a case of vertebral osteomyelitis. There were no cases of ERCP-related hemorrhage, cholangitis or perforation. The overall mortality was not significantly different in the two patient groups (ERCP group: 2% vs conservative management group: 8%; p = 0.23). However, the overall morbidity was significantly lower in the group that underwent ERCP within 72 hours of admission (17% vs 34%; p = 0.03). Sub-group analysis demonstrated that the morbidity difference was limited to the group of patients with predicted SAP. In patients with predicted SAP who were randomized to urgent ERCP, the complication rate was 24%, in comparison to 61% in patients with predicted SAP managed conservatively (p < 0.01). Accordingly, the length of hospitalization was shorter in

Study

No. treated patients

No. control patients

the patients with SAP who underwent urgent ERCP (9.5 days vs 17 days; p < 0.035). The investigators acknowledged the concern that the benefit of early ERCP +/− ES might be a result of treating cholangitis and not pancreatitis. They controlled for this possible confounding factor by excluding the patients who presented with cholangitis and analyzing the remaining patients separately. The complication rate remained significantly lower in the group of patients without cholangitis who underwent urgent ERCP (11% vs 33%; p = 0.02). Again, the majority of this difference occurred in the sub-group of patients with predicted SAP. In summary, this study by Neoptolemos and colleagues demonstrated that it is safe to perform ERCP in patients with AGP admitted to an expert center and early ERCP is associated with significantly decreased morbidity and hospital stay in patients with predicted severe AGP in comparison to conservative management.

Fan et al. 1993 The investigators of this trial from Hong Kong randomized 195 patients with acute pancreatitis of all etiologies to undergo urgent ERCP within 24 hours of hospital admission or conservative management followed by selective ERCP for clinical deterioration. The authors utilized this approach of selecting all patients with pancreatitis in order to minimize selection bias. Analysis of the subgroup of patients with AGP, revealed that 127 of the 195 randomized patients (65%) had biliary stones. Sixty-four of the 97 patients randomized to early ERCP were found to have biliary stones and 38 of these required ES for CBD or ampullary stones. Of the 98 patients in the conservative therapy group, 63 had biliary stones and 27 of these patients required ERCP for clinical deterioration. Ten of these patients were found to have CBD or ampullary stones. The severity of pancreatitis was graded by serum urea concentration and plasma glucose concentration and Ranson’s score. Patients were categorized as having SAP if serum urea concentration was greater than 45 mg/dL or if plasma glucose concentration was greater than 198 mg/dL at admission. Predicted SAP was diagnosed in 41.5% of the patient population, distributed evenly between the treatment groups. The overall morbidity (urgent ERCP group: 18%

Study design

Outcomes

Neoptolemos

59

62

Single center Consecutive patients with suspected AGP

Significant morbidity reduction in severe AGP Significant length of stay reduction in severe AGP

Fan

97

98

Single center Consecutive patients with AP, regardless of etiology AGP analyzed separately

Significant morbidity reduction in AGP Significant reduction in biliary sepsis in severe AGP

Fölsch

126

112

Multi-center Patients with suspected AGP, excluded those with bilirubin > 5 mg/dL

Similar morbidity rates between study groups Significantly higher incidence of respiratory insufficiency in ERCP group

Nowak

178

102

Single center Consecutive patients with suspected AGP All underwent duodenoscopy, immediate ES if obstructed, randomized if not

Significant reduction in both morbidity and mortality in the early ERCP + ES group

Table 39.4 Summary of randomized controlled trials 413

SECTION 3 APPROACH TO CLINICAL PROBLEMS

vs conservative management group: 29%; p = 0.07) and mortality (5% vs 9%; p = 0.4) were not significantly different in the two patient groups. When considering only those patients with biliary stones, the morbidity rate in the urgent ERCP group was significantly lower than in the conservative management group (16% vs 33%, p = 0.03) and there was a trend toward lower mortality (2% vs 8%; p = 0.09). These findings were driven by the significant morbidity advantage of urgent ERCP in the sub-group of patients with predicted SAP. In particular, the incidence of biliary sepsis among those patients predicted to have SAP was significantly lower in the urgent ERCP group than in the conservative management group (0% vs 20%; p = 0.008). In contrast, among patients with mild pancreatitis, there was no difference in the incidence of biliary sepsis between the two study groups. In summary, this trial demonstrated a morbidity benefit in patients with predicted severe AGP who underwent urgent ERCP +/− ES as compared to those managed conservatively. Despite the high prevalence of cholelithiasis in the study population, this trial corroborates the findings of the earlier study from the UK.

Fölsch et al. 1997 In this German multi-center study, 126 patients with AGP were randomly assigned to early ERCP within 72 hours of the onset of symptoms and 112 patients with AGP were assigned to conservative management. The inclusion criteria in this study were distinct from the previous studies in that patients with obstructive jaundice (total bilirubin >5 mg/dL) were excluded. In doing so, the investigators sought to determine the effect of early ERCP upon AGP independent of its known benefit in patients with cholangitis.33 In these patients with acute pancreatitis, the diagnosis of AGP was made if gallstones were seen on imaging or if two of three serum liver chemistry values (ALT, alkaline phosphatase and/or total bilirubin) were abnormal. The severity of pancreatitis was predicted by the modified Glasgow criteria. Early ERCP was successful in 96% of the treatment group and 46% of patients in this group were found to have choledocholithiasis. Elective ERCP was required in 20% of the conservative treatment group and 59% of those patients were found to have bile duct stones. Predicted SAP was seen in 19.3% of patients overall and similarly distributed between the treatment groups. Complications directly attributable to ERCP were minimal, with post-sphincterotomy hemorrhage seen in 2.8% and no duodenal wall perforations reported. Overall complications were similar in the early ERCP and control groups (46% vs 51%) and mortality rates were also similar (11% vs 6%; p = 0.10). Stratification of patients by predicted severity of pancreatitis did not alter these findings. Though systemic complications overall were not significantly different, the patients in the early ERCP group had a higher rate of respiratory insufficiency, as defined by pO2 <60 mm Hg despite use of an oxygen mask (12% vs 4%; p = 0.03). Several critiques of this study have been put forth in the literature. In this multi-center trial involving 22 institutions, the majority of patients were enrolled by three centers. This brings into question the level of experience and frequency of patients with AGP at a number of the study centers. Also, the excessive rate of respiratory insufficiency in the treatment group was not seen in any of the other trials addressing this subject. The investigators concluded that early ERCP in patients with AGP, without biliary obstruction or sepsis, does not confer a mortality or morbidity benefit and may result in a higher rate of respiratory insufficiency as compared to conservative management. 414

Nowak et al. 1998 The fourth and largest prospective study to assess the role of early ERCP in acute gallstone pancreatitis included 280 patients and was conducted at a single center in Poland. The predicted severity of AGP was assessed using Ranson’s criteria. All patients underwent an ERCP within 24 hours of admission and 75 patients underwent an endoscopic sphincterotomy due to evidence of an impacted stone at the papilla. Patients with a normal appearing papilla were randomized to immediate ES (n = 103) or conservative management (n = 102). The investigators found a significant reduction in morbidity (17% vs 36%; p < 0.001) and mortality (2% vs 13%; p < 0.001) in the group of patients randomized to ERCP + ES. After stratifying for severity of pancreatitis, the morbidity and mortality benefit of early ERCP + ES remained significant in the group with predicted mild pancreatitis. This study is discussed in brief, as it has only been published in abstract form. Particulars of the study design, patient groups and criteria for enrollment are not provided. Comprehensive critical analysis is not possible until a complete manuscript is made available.

SYSTEMATIC REVIEWS Any attempt to create a unified recommendation for the care of patients with AGP based on these trials is hindered by their distinct study methods. A meta-analysis by Sharma and Howden34 sought to estimate the overall effect of ERCP for AGP. They performed a pooled analysis of all four trials, assessing 460 treated patients and 374 controls. In analyzing complications and mortality, they found that the number of patients with AGP needed to treat (NNT) with ERCP + ES for avoidance of complications was 7.6 and the NNT for avoidance of death was 25.6. Sub-group analysis by severity of AGP was not possible due to unavailable data. The authors concluded that ERCP + ES reduces mortality and morbidity in patients with AGP. These results must be viewed with caution as this was pooled data and the largest contribution to the pool of patients came from the Nowak study, which is only available in abstract form. The Cochrane Database systematic review of this subject by Ayub and colleagues only included the studies by Neoptolemos, Fan and Fölsch. The authors sought to assess the value of ERCP +/− ES versus conservative therapy in patients with AGP. In particular, this review sought to address the effect of confounding by indication by controlling for associated acute cholangitis and by stratifying according to disease severity. To this end, the investigators of the Fölsch trial provided additional data regarding the severity of pancreatitis in each patient group. The authors concluded that ERCP +/− ES was associated with a significant reduction in morbidity in predicted severe AGP (OR = 0.27, 95% CI = 0.14 to 0.53). However, there was no significant difference in morbidity in patients with predicted mild AGP. In addition, no significant difference in mortality was found, regardless of predicted disease severity. Figure 39.1 demonstrates their findings, comparing ERCP +/− ES versus conservative management and stratified by severity of AGP.

Acute gallstone pancreatitis with biliary obstruction Acosta et al. 2006

The four studies above and their inherent differences in patient inclusion, interval time to ERCP and classification of severe acute pancreatitis prompted Acosta and colleagues to perform a random-

Chapter 39 Biliary Intervention in Acute Gallstone Pancreatitis

Review: Endoscopic retrograde cholangiopancreatography in gallstone-associated acute pancreatitis Comparison: 01 Early ERCP+/–ES versus Conservative Mx Outcome: 02 Complications stratified by severity of GAP Study

Weight (%)

Odds ratio (fixed) 95% CI

7.7 33.5 5.6

1.44 [0.47, 4.47] 0.79 [0.42, 1.48] 0.70 [0.14, 3.41]

46.8

0.89 [0.53, 1.49]

27.6 8.3 17.2

0.21 [0.08, 0.55] 0.81 [0.23, 2.83] 0.12 [0.03, 0.51]

Subtotal (95% CI) 29/87 52/85 Test for heterogeneity chi-square = 4.47 df = 2 p = 0.1071 Test for overall effect = 3.86 p = 0.0001

53.2

0.27 [0.14, 0.53]

Total (95% CI) 75/260 98/251 Test for heterogeneity chi-square = 12.68 df = 5 p = 0.0266 Test for overall effect = 2.86 p = 0.004

100.0

0.56 [0.38, 0.83]

01 Mild GAP Fan 1993 Fölsch 1997 Neoptolemos 1988

Early Conservative ERCP+/–ES Mx n/N n/N 8/56 35/84 3/33

Odds ratio (fixed) 95% CI

6/58 36/76 4/32

Subtotal (95% CI) 46/173 46/166 Test for heterogeneity chi-square = 0.92 df = 0.6299 Test for overall effect = 0.45 p = 0.7 02 Severe GAP Fan 1993 Fölsch 1997 Neoptolemos 1988

9/41 17/26 3/20

23/40 14/20 15/25

.1

.2

Favors ERCP +/– ES

1

5

Fig. 39.1 Cochrane Database systematic review, K Ayub et al.

10

Favors cons Mx

ized trial of early ERCP + ES in a more narrowly defined group of patients. The investigators randomized 61 consecutive patients with AGP and persistent ampullary obstruction to undergo ERCP +/− ES between 24 and 48 hours of the onset of symptoms (study group, n = 30) or conservative management followed by selective ERCP +/− ES if jaundice or cholangitis were present 48 hours after the onset of symptoms (control group, n = 31). Persistent ampullary obstruction was defined by a previously validated method.35 This method utilized three clinical findings to detect ampullary obstruction: severe and continuous epigastric pain, bile-free gastric aspirate and elevated serum bilirubin (followed serially every 6 hours). Ranson or Acosta criteria were utilized to predict severity of pancreatitis. The majority of patients experienced spontaneous relief of biliary obstruction within 48 hours of the onset of symptoms (71% of control group and 53% of study group). Fourteen patients in the study group underwent ERCP within 48 hours of symptom onset; impacted stones were found in 11 (79%) of these patients. There were no deaths in either group and no complications attributable to ERCP or ES. The study group had a significantly lower incidence of immediate complications (3% vs 26%; p = 0.026) and overall complications (7% vs 29%; p = 0.043). The incidence of severe AGP (10%) was relatively low in this study. The two groups did not differ in length of hospitalization or time to cholecystectomy. Collective analysis of both the study and control groups demonstrated that ampullary obstruction of less than 48 hours duration was associated with fewer complications (p < 0.001), shorter time interval to cholecystectomy (p = 0.018), and shorter hospitalization (p = 0.003).

Biliary microlithiasis Small diameter biliary stones, measuring less than 5 mm and known as microlithiasis, biliary sludge or biliary sand, have been implicated

as a cause of recurrent acute pancreatitis and other biliary complications.36 In practice, microlithiasis can be diagnosed by transabdominal ultrasound and is seen as mobile, echogenic material that layers with gravity and does not produce shadows.37 EUS has also been shown to be effective in detecting microlithiasis, particularly in the setting of typical biliary pain and normal abdominal ultrasound.38 The gold standard for the detection of biliary microlithiasis is microscopic analysis, which documents cholesterol monohydrate crystals or calcium bilirubinate granules in up to 80% of patients with AP of presumed biliary origin in whom gallstones could not be documented on imaging.39 Though no prospective, randomized controlled trials have been performed to establish the role of ERCP in patients with AGP due to microlithiasis, uncontrolled studies have suggested that these patients benefit from intervention.40,41

Cholecystectomy after AGP Once a patient stabilizes from an episode of mild AGP, laparoscopic cholecystectomy should be performed prior to discharge from the hospital.42 Delay in cholecystectomy is associated with a 20% risk of recurrent biliary complications including AGP, cholangitis and cholecystitis43 and a near 50% recurrence rate of any biliary symptoms.44 A recent prospective study of 178 Chinese patients over the age of 60 demonstrated that those patients randomized to early cholecystectomy after ES and bile duct clearance had a significantly lower rate of biliary events compared to those randomized to conservative management after ES (7% vs 24%; p = .001). In patients who are unable to undergo surgery, ES does confer some degree of protection from subsequent biliary events. In the case of severe AGP, cholecystectomy should be delayed until the systemic inflammatory response has subsided. In cases with significant pancreatic necrosis or pancreatic fluid collection, 415

SECTION 3 APPROACH TO CLINICAL PROBLEMS

Fig. 39.2 Algorithm for the management of acute gallstone pancreatitis.

Acute gallstone pancreatitis (AGP)

Severe AGP

ERCP +/– ES

Cholecystectomy (after recovery)

Mild AGP

Deterioration, jaundice, cholangitis

ERCP + ES (non-surgical candidate)

cholecystectomy should be delayed 3–6 weeks due to an increased risk of infection and surgical complications.45,46 If necessary and indicated, cholecystectomy can be combined with drainage procedures for pancreatic fluid collection or debridement of pancreatic necrosis.

ALGORITHM FOR THE MANAGEMENT OF ACUTE GALLSTONE PANCREATITIS The studies presented above provide a framework within which to manage patients with AGP (Fig. 39.2). We advocate ERCP +/− ES in

Recovery

Cholecystectomy (same admission)

patients with severe AGP, defined by Ranson’s criteria or the modified CT severity index when available, as soon as that diagnosis is made. Additional indications for ERCP include concurrent cholangitis or jaundice, persistent ampullary obstruction or clinical deterioration in a patient who initially presented with mild disease. Once selection criteria are met for ERCP, ES should be performed in those patients with confirmed choledocholithiasis or ampullary edema causing obstruction. In patients who cannot undergo cholecystectomy due to medical co-morbidities, ES is protective against further bouts of AGP, but may not protect against other biliary complications. The fear that ERCP with or without ES can exacerbate existing AP is not borne out by the literature nor our clinical experience.

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9. Frakes JT. Biliary pancreatitis: a review. Emphasizing appropriate endoscopic intervention. Journal of Clinical Gastroenterology 1999; 28:97–109. 10. Tenner S, Dubner H, Steinberg W. Predicting gallstone pancreatitis with laboratory parameters: a meta-analysis. American Journal of Gastroenterology 1994; 89:1863–1866. 11. Cohen ME, Slezak L, Wells CK, et al. Prediction of bile duct stones and complications in gallstone pancreatitis using early laboratory trends. American Journal of Gastroenterology 2001; 96:3305–3311. 12. Cooperberg PL, Burhenne HJ. Real-time ultrasonography: diagnostic technique of choice in calculous gallbladder disease. New England Journal of Medicine 1980; 302:1277–1279. 13. Neoptolemos JP, Hall AW, Finlay DF, et al. The urgent diagnosis of gallstones in acute pancreatitis: a prospective study of three methods. British Journal of Surgery 1984; 71:230–233. 14. Ammori BJ, Boreham B, Lewis P, et al. The biochemical detection of biliary etiology of acute pancreatitis on admission: a revisit in the modern era of biliary imaging. Pancreas 2003; 26:e32–e35. 15. Topal B, Van de Moortel M, Fieuws S, et al. The value of magnetic resonance cholangiopancreatography in predicting common bile duct stones in patients with gallstone disease. British Journal of Surgery 2003; 90:42–47. 16. Griffin N, Wastle ML, Dunn WK, et al. Magnetic resonance cholangiopancreatography versus endoscopic retrograde

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cholangiopancreatography in the diagnosis of choledocholithiasis. European Journal of Gastroenterology & Hepatology 2003; 15:809–813. Aube C, Delorme B, Yzet T, et al. MR cholangiopancreatography versus endoscopic sonography in suspected common bile duct lithiasis: a prospective, comparative study. American Journal of Roentgenology 2005; 184:55–62. Buscarini E, Tansini P, Vallisa D, et al. EUS for suspected choledocholithiasis: do benefits outweigh costs? A prospective, controlled study. Gastrointestinal Endoscopy 2003; 57:510–518. Liu CL, Fan ST, Lo CM, et al. Comparison of early endoscopic ultrasonography and endoscopic retrograde cholangiopancreatography in the management of acute biliary pancreatitis: a prospective randomized study. Clinical Gastroenterology and Hepatology 2005; 3(12):1238–1244. Nowak A, Marek TA, Nowakowska-Dulawa E, et al. Biliary pancreatitis needs endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy for cure. Endoscopy 1998; 30:A256–A259. Bradley EL, 3rd. A clinically based classification system for acute pancreatitis. Summary of the International Symposium on Acute Pancreatitis. Archives of Surgery 1993; 128:586–590. Meek K, Toosie K, Stabile BE, et al. Simplified admission criterion for predicting severe complications of gallstone pancreatitis. Arch Surg 2000; 135(9):1048–1052. Buter A, Imrie CW, Carter CR, et al. Dynamic nature of early organ dysfunction determines outcome in acute pancreatitis. British Journal of Surgery 2002; 89:298–302. Johnson CD, Abu-Hilal M. Persistent organ failure during the first week as a marker of fatal outcome in acute pancreatitis. Gut 2004; 53:1340–1344. Perez A, Whang EE, Brooks DC, et al. Is severity of necrotizing pancreatitis increased in extended necrosis and infected necrosis? Pancreas 2002; 25:229–233. Balthazar EJ. Acute pancreatitis: assessment of severity with clinical and CT evaluation. Radiology 2002; 223:603–613. Mortele KJ, Wiesner W, Intriere L, et al. A modified CT severity index for evaluating acute pancreatitis: improved correlation with patient outcome. American Journal of Roentgenology 2004; 183:1261–1265. Papachristou GI, Whitcomb DC. Predictors of severity and necrosis in acute pancreatitis. Gastroenterology Clinics of North America. 2004; 33:871–890. Papachristou GI, Sass DA, Avula H, et al. Is the monocyte chemotactic protein-1—2518 G allele a risk factor for severe acute pancreatitis? Clinical Gastroenterology and Hepatology 2005; 3:475–481. Nathens AB, Curtis JR, Beale RJ, et al. Management of the critically ill patient with severe acute pancreatitis. Critical Care Medicine 2004; 32:2524–2536.

31. van der Spuy S. Endoscopic sphincterotomy in the management of gallstone pancreatitis. Endoscopy 1981; 13:25–26. 32. Blamey SL, Imrie CW, O’Neill J, et al. Prognostic factors in acute pancreatitis. Gut 1984; 25:1340–1346. 33. Leese T, Neoptolemos JP, Baker AR, et al. Management of acute cholangitis and the impact of endoscopic sphincterotomy. British Journal of Surgery 1986; 73:988–992. 34. Sharma VK, Howden CW. Metaanalysis of randomized controlled trials of endoscopic retrograde cholangiography and endoscopic sphincterotomy for the treatment of acute biliary pancreatitis. American Journal of Gastroenterology 1999; 94:3211–3214. 35. Acosta JM, Ronzano GD, Pellegrini CA. Ampullary obstruction monitoring in acute gallstone pancreatitis: a safe, accurate, and reliable method to detect pancreatic ductal obstruction. American Journal of Gastroenterology 2000; 95:122–127. 36. Ko CW, Sekijima JH, Lee SP. Biliary sludge. Annals of Internal Medicine 1999; 130:301–311. 37. Chen EY, Nguyen TD. Images in clinical medicine. Gallbladder sludge. New England Journal of Medicine 2001; 345:e2. 38. Thorboll J, Vilmann P, Jacobsen B, Hassan H. Endoscopic ultrasonography in detection of cholelithiasis in patients with biliary pain and negative transabdominal ultrasonography. Scandanavian Journal of Gastroenterology 2004; 39:267–269. 39. Kohut M, Nowak A, Nowakowska-Dulawa E, et al. The frequency of bile duct crystals in patients with presumed biliary pancreatitis. Gastrointestinal Endoscopy 2001; 54:37–41. 40. Lee SP, Nicholls JF, Park HZ. Biliary sludge as a cause of acute pancreatitis. New England Journal of Medicine 1992; 326:589–593. 41. Ros E, Navarro S, Bru C, et al. Occult microlithiasis in “idiopathic” acute pancreatitis: prevention of relapses by cholecystectomy or ursodeoxycholic acid therapy. Gastroenterology 1991; 101:1701–1709. 42. Uhl W, Warshaw A, Imrie C, et al. IAP Guidelines for the surgical management of acute pancreatitis. Pancreatology. 2002; 2:565–573. 43. Hernandez V, Pascual I, Almela P, et al. Recurrence of acute gallstone pancreatitis and relationship with cholecystectomy or endoscopic sphincterotomy. American Journal of Gastroenterology 2004; 99:2417–2423. 44. Boerma D, Rauws EA, Keulemans YC, et al. Wait-and-see policy or laparoscopic cholecystectomy after endoscopic sphincterotomy for bile-duct stones: a randomised trial. Lancet 2002; 360:761–765. 45. Uhl W, Muller CA, Krahenbuhl L, et al. Acute gallstone pancreatitis: timing of laparoscopic cholecystectomy in mild and severe disease. Surgical Endoscopy 1999; 13:1070–1076. 46. Nealon WH, Bawduniak J, Walser EM. Appropriate timing of cholecystectomy in patients who present with moderate to severe gallstone-associated acute pancreatitis with peripancreatic fluid collections. Annals of Surgery 2004; 239:741–749.

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40

APPROACH TO CLINICAL PROBLEMS

Pancreatic Interventions in Acute Pancreatitis: Ascites, Fistulae, Leaks and Other Disruptions Richard A. Kozarek

INTRODUCTION BOX 40.1 1. With the exception of sphincter of Oddi dysfunction, the use of ERCP to diagnose the etiology of relapsing attacks of pancreatitis has been supplanted by pancreas protocol CT, MRI/MRCP, and endoscopic ultrasound. 2. The most common therapeutic interaction between ERCP and acute pancreatitis is in the setting of biliary pancreatitis. 3. Biliary intervention in pancreatitis may be related not only to biliary calculi but also biliary obstruction from pancreatic edema and fluid collections. 4. Therapeutic pancreatography in acute pancreatitis includes bypass of obstruction and treatment of leaks and their consequences and should be undertaken as one aspect of a multidisciplinary approach.

Background

The role of ERCP in acute pancreatitis has primarily been twofold.1 On the one hand, it has been used after resolution of an acute attack, or more commonly, multiple attacks, in an attempt to define etiology. As such, congenital variants to include duodenal duplication, anomalous pancreaticobiliary union, annular pancreas, or pancreas divisum can be diagnosed as can other anatomic causes of pancreatitis to include ampullary adenoma or surreptitious stone disease. For the most part, endoscopic ultrasound (EUS) and magnetic resonance imaging (MRI/MRCP) have supplanted the need for an invasive study that can actually cause the disease for which it is being applied.2 There remains, however, a major role for ERCP in conjunction with sphincter of Oddi manometry and most series actually suggest that sphincter of Oddi dysfunction (SOD) is the most common cause of “idiopathic” pancreatitis when other diagnostic studies have been exhausted. The second role that ERCP has played is in the treatment of acute biliary pancreatitis.3,4 This subject is covered, in detail, in the preceding chapter. Suffice it to say, however, most endoscopists use ERCP selectively, as opposed to universally, in patients with presumptive

biliary pancreatitis, particularly in patients with an intact gallbladder or those with mild disease. In addition to its application in conjunction with SOM in patients with ARP and its selective application in biliary pancreatitis, ERCP is being evaluated as a means to provide pancreatic endotherapy in the setting of severe or smoldering pancreatitis related to ductal disruption, or spasm or edema of the sphincter of Oddi.5–7 This chapter will focus on these latter indications, although admittedly, many of these ductal disruptions can also occur in a background of chronic as well as acute pancreatitis. Moreover, in contrast to controlled observations about the timing and appropriateness of ERCP in acute relapsing or severe biliary pancreatitis, respectively, most publications related to pancreatic endotherapy during an attack of pancreatitis have been uncontrolled, anecdotal, but also, often dramatic.

Epidemiology of ductal disruption If the underlying pathophysiology of acute pancreatitis is colocalization of zymogen granules with cell membranes, setting off an inflammatory cascade with local effects related to cytokine release and recruitment of inflammatory cells, it seems reasonable that this sequence antedates disruption of ductular epithelial cells and subsequent pancreatic juice leak in most cases of acute pancreatitis.5,8 However, acute sphincter obstruction in the setting of a common bile duct stone may increase intraductal pressure leading to sidebranch or acinar leak with resultant pancreatitis. Likewise, any other downstream obstruction may increase upstream duct pressure leading to PD blowout and perpetuation or exacerbation of pancreatitis.9,10 In acute pancreatitis, this is most commonly seen with severe edema, whereas in chronic pancreatitis, disruptions are usually the consequence of a downstream stricture or stone. In the setting of severe pancreatic necrosis, ductal disruption is almost invariable, although whether the ductal disruption is the cause or the consequence of the necrosis remains ill-defined.10,11 Nor does the presence of a peripancreatic fluid collection imply a significant ongoing leak in all instances. In fact, up to 40% of patients with acute pancreatitis develop a fluid collection, yet less than 5% of these patients go on to develop a pseudocyst.12

Anatomic classification Although this chapter will focus on pancreatic duct leaks and their endoscopic treatment, Table 40.1 summarizes some of the other endoscopically amenable lesions that endoscopists see not infrequently in a busy ERCP practice. They include bile duct obstruction from stones, edema within the head of the pancreas, and neoplasms 419

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that occasionally present with pancreatitis. From a pancreatic standpoint, they include neoplastic obstruction of the papilla or duct, edema or spasm of the sphincter mechanism, and an inflammatory PD stenosis. Pancreatic duct leaks can be defined anatomically by site of disruption, which in conjunction with the size of the leak, and presence

Biliary obstruction: jaundice, cholangitis • Common bile duct stones • Biliary stenosis from edema, head of pancreas • Extrinsic obstruction from pseudocyst Pancreatic duct obstruction: exacerbation/perpetuation of pancreatitis • Sphincter spasm/stenosis/edema • Stenosis – Acute, inflammatory – Fixed, fibrotica – Neoplastic • PD stonea Pancreatic duct leak: see Table 40.2

Table 40.1 Endoscopically amenable anatomic lesions seen in acute pancreatitis a

Implies concomitant chronic pancreatitis.

or absence of concomitant necrosis, often determines the manifestations8,12,13 (Fig. 40.1). As such, a major blowout of the PD tail may cause an acute perisplenic fluid collection with or without a high amylase, left pleural effusion. Alternatively, pancreatic juice may follow anatomic pathways around the left kidney and even into the pelvis with resultant scrotal or labial edema. Blowouts in the head of the pancreas may be associated with C Loop edema and gastric outlet obstruction, biliary compression or even pancreaticobiliary fistulization, right perinephric fluid accumulation, and dissection into the pelvis or perihilar area. A central disruption may result in fluid collection within the lesser sac, dissection into the mediastinum or pericardium, and, when associated with significant central pancreatic necrosis, result in a permanently disconnected duct/ gland syndrome.13 Anatomic classifications based upon the presence of an acute or chronic pancreatic duct leak are outlined in Table 40.2. Classically, pancreatic duct leaks (fistulas) are classified as internal or external, the latter almost always a consequence of trauma, surgery, or interventional radiologic drainage procedures.14–18 Internal fistulas, in turn, classically have included pseudocysts, pancreatic ascites, high amylase pleural effusions, and erosion of pancreatic fluid collections into contiguous organs, resulting in pancreaticoenteric, gastric, colic or biliary fistulae.19–23 They also include evolving pancreatic necrosis in which variable amounts of high amylase fluid collect, usually in the context of central pancreatic necrosis.

2 Pancreaticoenteric/biliary fistula 5 Pancreatic pleural effusion

6 Pancreatic necrosis

Surgical or percutaneous drain

7 External pancreatic fistula

3 Pseudocyst 1 Bile duct compression by fluid collection/edema

4 Pancreatic ascites

Fig. 40.1 Consequences of pancreatic duct leak. (1) Bile duct compression by fluid collection/edema. (2) Pancreaticoenteric/biliary fistula. (3) Pseudocyst. (4) Pancreatic ascites. (5) Pancreatic pleural effusion. (6) Pancreatic necrosis. (7) External pancreatic fistula. 420

Chapter 40 Pancreatic Interventions in Acute Pancreatitis: Ascites, Fistulae, Leaks and Other Disruptions

Internal Fistula • Peripancreatic fluid collection • Pseudocyst • Pancreatic ascites • High amylase pleural effusion • Pancreaticoenteric/biliary/bronchial fistula • Evolving pancreatic necrosis • ± smoldering pancreatitis External fistula • Pancreaticocutaneous fistula

Table 40.2 Manifestations of pancreatic duct leak

MANAGEMENT STRATEGIES BOX 40.2 KEY POINTS 1. The diagnosis of external pancreatic fistulas is usually self-evident. 2. Pancreas protocol CT scan is most often the best way to define the consequences (fluid collection, necrosis) of an internal pancreatic fistula. 3. Unless endotherapy can be done at the time of an ERCP, Secretin-MRCP (S-MRCP) may be a better test to define the location or persistence of an internal pancreatic fistula.

Diagnosis The management of pancreatic fistulas presupposes their diagnosis. The diagnosis of external fistulas is usually self-evident and consists of variable output of clear pancreatic juice following percutaneous drainage of a pseudocyst or peripancreatic fluid collection (Table 40.3).1 Alternatively, persistent output from a JP drain following pancreatic resection, decompression, or peripancreatic surgery (e.g. splenectomy, left nephrectomy or gastrectomy) is not usually a subtle manifestation of an external leak. More troublesome, however, may be the patient who sustains a penetrating abdominal surgery such as a knife or gunshot wound in whom the external fistula is overlooked because of concerns of more significant injury. The diagnosis of internal fistulas is outlined in Table 40.3. In essence, non-invasive imaging, particularly pancreas protocol CT, remains the best initial diagnostic test in patients with smoldering or severe pancreatitis or those patients with underlying chronic pancreatitis and an acute exacerbation of symptoms.13 Not only will CT define the consequences of pancreatitis (fluid collections, necrosis, effusions, ascites . . .)24 but can also be used to define the potential etiology (e.g. stones or strictures) as well as following the subsequent evolution of pancreatitis. CT remains an imperfect tool, however, in that biliary stone disease is underestimated, the fluid component associated with evolving pancreatic necrosis is overestimated, and leaks are implied rather than defined.25 Further confirmation of a ductal disruption may require sequential scans demonstrating an

External Fistulas • High amylase output through a surgically or percutaneously placed drain • ± demonstrable pancreatogram through JP drain Internal Fistula • Pseudocyst/evolving pancreatic necrosis – CT – MRI/MRCP – US/ – EUS – ERCP • Pancreatic Ascites – High amylase fluid with aspiration – Flat film (ground glass appearance) – CT/MRCP Concomitant pseudocyst 1/3–1/2 – ERCP – Ductal disruption vs obstruction/upstream leak • High Amylase Pleural Effusion – ERCP – S-MRCP

}

Table 40.3 Diagnostic studies in pancreatic duct leaks

JP = Jackson-Pratt; CT = computerized tomography; MRI = magnetic resonance imaging; S-MRCP = secretin magnetic resonance cholangiopancreatography; US = ultrasound; EUS = endoscopic ultrasound; ERCP = endoscopic retrograde cholangiopancreatography.

enlarging fluid collection, aspiration of that fluid collection with measurement of amylase or lipase, an ERCP demonstrating presence and location of the leak, or S-MRCP. The latter study has been shown by Deviere and his colleagues to be predictive of ongoing ductal disruption and clearly minimizes potential ERCP complications such as exacerbation of pancreatitis and iatrogenic infection of an undrained fluid collection.26 It may also demonstrate patients with a complete ductal disruption and a disconnected gland syndrome who may be better managed with non-endoscopic forms of therapy. Finally, use of S-MRCP prior to ERCP may help in defining subsequent endoscopic management comparable to its utilization in hilar neoplasms of the liver. ERCP, in turn, is usually definitive in showing not only the site of the ductal disruption (if persistent) but also the proximate cause or reason for persistence (PD stones, inflammatory or fibrotic structure).13,27 For the most part, however, ERCP adds an unnecessary risk to the care of acutely or chronically ill patients with presumptive leak, unless endoscopic percutaneous, or surgical therapy is contemplated.28

MANAGEMENT

BOX 40.3 KEY POINTS 1. The appropriate management of pancreatic fistulas should include a multidisciplinary team. 2. Transpapillary stent placement has a markedly higher success rate in treating internal fistulas if the disruption is bridged.

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The presence of a presumptive pancreatic fistula is not, per se, a demand to undertake endotherapy. Important considerations include whether the patient has acute or underlying chronic pancreatitis, whether pancreatic necrosis is present or absent, whether there is superinfection of a fluid collection, and whether the leak is controlled or uncontrolled. For instance, the vast majority of low-volume leaks following pancreatic resection are low grade, controlled by a surgically placed JP drain, and spontaneously close with or without concomitant octreotide over days or several weeks.29,30 On the other hand, a patient may have rapidly increasing ascites or pleural effusion or concomitant jaundice or cholestasis that demand urgent attention. From a personal perspective, I use the following indications to define the necessity of approaching a patient with pancreatic duct leak endoscopically: 1. an enlarging pancreatic fluid collection (pseudocyst, pancreatic ascites, high amylase pleural effusion) despite conservative management; 2. a symptomatic fluid collection; 3. persistence of an external fistula; and 4. inability to refeed a patient without developing recurring pain or pancreatitis.13 A fifth indication may be the question of concomitant biliary tract disease. While the latter may occasionally be a concern for a retained stone in the setting of biliary pancreatitis, it is more commonly seen in patients with jaundice or cholangitis from pancreatic head edema or pseudocyst. Perhaps as important as indications for study are contraindications. The foremost is inability to render therapy if a ductal disruption is demonstrated. As such, diagnosis of a leak may result in iatrogenic infection of necrosis or pseudocyst as the consequences of internal fistulization. The latter may require endoscopic, percutaneous, or even surgical drainage. The endoscopic and non-endoscopic management of pancreatic pseudocysts31–35 and evolving pancreatic necrosis36–41 are covered by Dr Baron in Chapter 45. Suffice it to say that therapy usually requires treatment of the underlying ductal disruption, if anatomically feasible, as well as the consequences of that disruption. Thus, surgical, percutaneous, and endoscopic decompression of fluid collections have all been variously described. Likewise, treatment of other types of internal and external pancreatic fistulas does not occur in a vacuum and a multidisciplinary approach between an endoscopist, pancreaticobiliary surgeon, and interventional radiologist is often required to diagnose and properly treat these complex and acutely ill patients.

Pancreatic ascites and high amylase pleural effusions Historically, pancreatic ascites and pleural effusions were treated with gut rest and total parenteral nutrition (TPN) to minimize pancreatic juice stimulation. Diuretics, large volume thoracentesis and paracentesis, and octreotide have all been used for weeks or months in an attempt to preclude need for surgical resection or bypass. Successful in <50% of these patients, “salvage” type surgery, usually defined by ERCP preoperatively, consisted of partial pancreatectomy or Roux-en-Y cyst-jejunostomy in the subset of patients with concomitant pancreatic pseudocysts. These attempts were associated with high morbidity, an 8–15% peri procedural mortality, and recurrence of 15–20%.13 422

Our group initially published a small series in which transpapillary stent placement beyond the site of ductal disruption, in conjunction with large volume paracentesis, was successful in treating patients with pancreatic ascites42 (Fig. 40.2.) This therapy was derivative and a consequence of previous experience using transpapillary stents with or without concomitant cyst-gastrostomy or cyst-duodenostomy in patients with pseudocysts. Since our initial publication, a number of other authors including Bracher et al. have confirmed our findings.43 Combining the two series, over 90% of the patients resolved their ascites without complication, and there were no recurrences in the two series at 5 years and 14 months, respectively. Transpapillary stenting appears to work by changing the ductal drainage gradient and making the duodenum the area with the least resistance to flow. Potential areas of downstream obstruction that are bypassed include the sphincter, possible stones, and the inflammatory or fibrotic stricture frequently associated with a leak (Fig. 40.3). Transpapillary stenting will not work in the setting of a disconnected gland syndrome in which the bulk of the pancreatic juice that enters the thoracic or abdominal cavity comes from a disconnected pancreatic duct tail. This situation is also noted in other forms of internal as well as external pancreatic fistulas, all of which are better handled with resective surgery unless there is concomitant portal vein thrombosis and prohibitive surgical risk (Figs 40.4, 40.5).13 A nice review of the endoscopic and surgical treatments of pancreatic ascites has recently been published by GomezCerezo et al.44 An additional retrospective series by Telford et al. reported 43 patients with pancreatic duct disruption and a variety of clinical manifestations.45 The etiology was acute pancreatitis in 24, chronic pancreatitis in 9, operative injury in 7, and trauma in 3 patients. Stent placement was successful in resolution of the disruption in 25, unsuccessful in 16, and indeterminate in 2 patients. On univariate analyses, bridging of the ductal disruption and duration of stenting were associated with a statistically significant successful outcome whereas female gender and acute pancreatitis were negative predictive factors of success. With multivariant analysis, only bridging of the disruption remained statistically significant as a definer of success (Figs 40.6, 40.7, 40.8).

Pancreaticoenteric fistulae and acute pancreatic trauma To date, our group has treated over 30 patients with pancreaticoenteric or biliary fistulae. Although these patients may present with spontaneous and rapid resolution of a fluid collection for which no treatment is required, a stenosis at the site of ductal disruption may result in relapsing attacks of pancreatitis. Alternatively, fistulization into the bile duct or splenic flexure (Fig. 40.5) of the colon may result in cholestasis or cholangitis, or recurrent sepsis, respectively. In our initial series of 8 patients with pancreaticoenteric fistulae, 3 healed their fistulas after downsizing or removal of an external drain that had eroded into a contiguous loop of bowel, 3 healed with transpapillary stent placement, and 2 patients ultimately required surgical resection.46 Fistulization into the bile duct, in turn, is almost invariably treated successfully by concomitant biliary and pancreatic duct stenting assuming that the fistula is not from the upstream disconnected portion of the pancreas47 (Figs 40.9 and 40.10). In addition to pancreaticoenteric or biliary fistulae that usually occur in the setting of pancreatic necrosis or chronic pancreatitis,

Chapter 40 Pancreatic Interventions in Acute Pancreatitis: Ascites, Fistulae, Leaks and Other Disruptions

A

C

B

D

E

Fig. 40.2 Abdominal CT demonstrates bilateral pleural effusions A and ascites B,C in patient with pancreatic ascites. ERCP demonstrates site of disruption D treated with PD stent E. Ascites was tapped and did not reaccumulate. Stent was retrieved after 6 weeks.

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A

B

D

C

F

E

Fig. 40.3 ERCP demonstrates ductal disruption in pancreatic head A in patient with huge, high amylase effusion of right lung B. Patient treated with transpapillary pigtail stent into fluid collection C as well as stenting of minor papilla D,E to decompress upstream pancreatic duct.

ERCP has also been used to treat internal fistulae as a consequence of acute pancreatic trauma. By way of example, Kim et al. diagnosed normal pancreatograms in 14 of 23 patients with acute abdominal trauma.18 Eight of these patients had a leak from the main PD into the parenchyma and resolved spontaneously where 3 had an MPD leak that could be bridged and responded to transpapillary stenting. Although early ERCP was felt to be advantageous to project the need for medical, surgical, or endoscopic therapy, it is possible that SMRCP may evolve to play a diagnostic role, selecting patients who have the greatest potential for benefit from therapeutic ERCP.17

External fistulas As previously discussed, with the exception of penetrating abdominal trauma, the vast majority of external fistulas are iatrogenic. They may occasionally follow partial pancreatic resection or bypass in the setting of a downstream stricture. Most, however, are a consequence of disconnected gland following percutaneous or surgical drainage of a pancreatic fluid collection.13 Our group initially reported a series of patients undergoing transpapillary stenting for amenable external

424

fistulas almost a decade ago.48 Since that time, multiple additional series have been published or abstracted.13,49,50 By way of summary of the available series, 86% of patients (50/58) could be successfully stented and 46 of the latter (92%) had resolution of their fistulas. Procedural complications were limited to mild flare of pancreatitis in several series although there were two deaths in the series by Costamagna et al., neither related to the fistula or its endoscopic treatment. No recurrences were reported in patients undergoing successful fistula closure at follow-up ranging from 12 to 36 months. In our practice, endotherapy was initially reserved for postoperative or percutaneously drained patients whose external fistula did not respond to several weeks of clear liquids, total parenteral nutrition, and octreotide. Currently, we have become considerably more aggressive, studying patients with high-volume fistulas with SMRCP if they have marginal change in fistula volume after several days of somatostatin analogue, and undertake ERCP and transpapillary stent placement unless imaging documents a disconnected gland syndrome (Figs 40.4, 40.5). Historically, the latter patients

Chapter 40 Pancreatic Interventions in Acute Pancreatitis: Ascites, Fistulae, Leaks and Other Disruptions

A

B

E

F

C

D

H

G

I

J

K

Fig. 40.4 JP drain demonstrates disconnected pancreatic duct A in patient with a history of pancreatic necrosis, portal hypertension. ERCP demonstrates cut off main pancreatic duct below the genu B. Transduodenal contrast injection fills residual pancreatic duct through small upstream pseudocyst C,D,E. Following needle-knife fistulization through the bulb F,G,H, parallel 7 Fr pigtail and straight stents were placed I,J,K. Fistula closed within 24 hours, allowing JP drain removal 3 years after original placement.

have usually required distal pancreatectomy,13 although our interventional radiologists have treated a subset of these patients with cyanoacrylate injection. The latter therapy requires guidewire placement to the pancreatic duct tail through the fistulous tract, placement of a microcatheter over the wire, and injection of the entire disconnected portion of the duct to include side branches. Mild postprocedural pancreatitis has been noted in approximately 50% of patients and recurrent fistulas may occur unless the entire duct and its side branches are sealed. This procedure works best with 3–4 cm of disconnected gland and is less likely to be successful when the glandular disconnection is at the genu requiring the major portion of the gland to be glued shut.

In addition to the percutaneous approach to the disconnected gland, as well as the surgical approach using glue injection to minimize post-pancreatectomy leak,51 Soehendra’s group has utilized this technique in internal fistulas by transpapillary injection of methyl-butyl cyanoacrylate into the distal duct at the site of glandular disruption.52 Eight of 11 patients in their series healed their disruption without recurrence although all had concomitant pancreatic duct stents or drains as well as endoscopic drainage of associated fluid collections. This group has also used glue injection as an adjunct in patients with severe pancreatic necrosis who are undergoing aggressive endoscopic drainage using EUS-directed lavage or debridement.53

425

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A

B

C

D

Fig. 40.5 ERCP demonstrates transgastric pigtail stent (arrows) A,B, in patient with severe necrotizing pancreatitis, portal vein thrombosis, and disconnected pancreatic duct (arrow) C. Note embolized coils for previous splenic artery aneurysm C (arrows), JP drain for persistent colonic fistula into pancreatic head D.

426

Chapter 40 Pancreatic Interventions in Acute Pancreatitis: Ascites, Fistulae, Leaks and Other Disruptions

A

B

C

D

E

F

G

Fig. 40.6 CT demonstrates perisplenic fluid collection A and markedly thickened gastric wall (arrow) in patient with hereditary pancreatitis. ERCP demonstrates severe chronic pancreatitis B with dilated tail and ductal disruption C requiring percutaneous drainage. Stricture is “dilated” with Soehendra stent extractor D followed by balloon dilation E and 7 Fr stent placement beyond ductal disruption F. Note improvement in CT scan, persistent dilation of the pancreatic duct tail G.

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A

B

C

D

Fig. 40.7 ERCP demonstrates PD disruption at junction of body and tail A,B in patient with severe LUQ/flank pain, splenic vein thrombosis. Pain, ductal disruption resolved with prosthesis placement C,D. Disruption recurred 1 year later, requiring distal pancreatectomy/splenectomy.

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Chapter 40 Pancreatic Interventions in Acute Pancreatitis: Ascites, Fistulae, Leaks and Other Disruptions

A

B

C

D

E

F

G

H

Fig. 40.8 Patient with chronic pancreatitis, pancreas divisum, and ductal disruption in pancreatic head who presented with jaundice, intractable pain, and 50 lb weight loss. Note pseudocyst in head A, leak from VPD B, which was stented C, dorsal papillary sphincterotomy and, 2 dorsal pancreatic duct stents into fluid collection in the head D,E. Note stent retrieval progressive pseudocyst resolution and reconstitution of the DPD following stent exchange after 6 weeks F,G,H.

It is the author’s opinion that endoscopic glue injection into the pancreatic duct needs further critical evaluation before widespread adoption and its application must be weighed against the risks of long-term, indwelling drain placement or surgical resection.

COMPLICATIONS

BOX 40.4 KEY POINTS 1. The risk of procedural or post-procedural complications in treating PD fistulas endoscopically should be weighed against the risk of persistent fistula or alternative treatments. 2. Procedural pancreatitis and iatrogenic infection of a concomitant fluid collection are the major risks in endoscopically treating internal PD fistulae. Fig. 40.9 Arrow demonstrates fistula between CBD (stented) and PD. Fistula resolved at 4 weeks following pancreaticobiliary stent placement.

3. Iatrogenic ductitis to include irreversible stricture formation can follow PD stenting.

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A B

D

E

C

F

Fig. 40.10 High grade bile duct stricture in patient with pancreatic necrosis, intramural pancreatic ductal disruption. Note contrast in colon A, deformed edematous papilla B, biliary stent placement C. Small arrows demonstrate intraduodenal abscess and large arrow, dilated pancreatic duct D. Note dual stent placement E,F which resolved jaundice, concomitant PD disruption and obstruction.

Immediate complications The immediate complications of transpapillary stent placement are those of diagnostic ERCP and include drug reaction, aspiration, cardiopulmonary events, pancreatitis from contrast injection or sphincter manipulation, and cholangitis if there is a concomitant biliary stenosis that is not endoscopically treated. Bleeding and iatrogenic perforation can occasionally be seen if sphincterotomy is done to facilitate stent placement.54 Pancreatitis flare, in my experience, approximates 10% in normal ducts and is uncommon in patients who already have ductal changes of chronic pancreatitis. It may approach 50% in the setting of unsuccessful stenting when multiple accessories and guidewires have been placed into the PD to facilitate bridging the area of leak. This pancreatitis is usually attenuated, however, if a short transpapillary stent is left to preclude ductal obstruction by an edematous papilla or traumatized 430

sphincter.55 Pancreatitis is more common in the setting of a poorly chosen prosthesis even if the disruption can be bridged. As such, placement of a 7 Fr stent into a 5 Fr diameter duct should be discouraged. Likewise, placement of a 12 cm prosthesis to bridge a ductal leak 3 cm from the papilla is inappropriate.

Subacute complications Subacute complications are usually infectious and result from iatrogenic introduction of bacteria into a fluid collection or necrotic debris at the time of ERCP. As such, all patients with a presumptive internal fistula deserve antibiotic coverage with a broad spectrum antibiotic prior to a diagnostic ERCP and may require more prolonged treatment afterwards, particularly in the setting of necrosis. Moreover, clearly contaminated fluid collections should be considered for concomitant endoscopic or percutaneous drainage of necro-

Chapter 40 Pancreatic Interventions in Acute Pancreatitis: Ascites, Fistulae, Leaks and Other Disruptions

sis as described by Dr. Baron later in this text. Note that our group has previously demonstrated that bacterial contamination within the pancreatic duct is invariable in patients with indwelling stents and that stent occlusion is a necessary, but not sufficient, cause of pancreatic sepsis.56 Stent occlusion may also be associated with obstructive pancreatitis and it is for this reason as well as fear of iatrogenic duct injury,57 that indwelling stents should be retrieved within 1 week of external fistula closure and after 4–6 weeks of treating an internal PD fistula.13

Chronic complications Although iatrogenic ductal injury is listed under chronic complications, prostheses never belong in the pancreas, particularly in those with otherwise normal pancreatic ducts. A number of procedural and stent modifications have decreased trauma to the major pancreatic duct and minimized side branch occlusion over the past several years. These modifications include utilization of 3–4 Fr diameter stents, elimination of internal stent flanges, and recognition that stents which apply significant pressure proximally may cause duct ulceration and subsequent fibrosis.57,58 Despite this, 3 Fr, unflanged, pigtail stents almost always spontaneously migrate within a week or two and are probably appropriate only in the patient in whom bridging of the disruption was unsuccessful, and then only to prevent or ameliorate post-ERCP pancreatitis. Iatrogenic ductitis should be anticipated and minimized by selecting a prosthesis with a smaller diameter than the PD downstream from the leak, one that is the appropriate length to bridge the disruption without an inordinate stent length beyond the site of leak, and one that avoids upstream impaction or angulation on the ductal wall.

SUMMARY 1. Pancreatic duct leaks are the consequence of acute inflammation with duct disruption, downstream obstruction, or both. 2. Minor leaks in the setting of acute pancreatitis/necrosis are probably common and respond to conservative therapy. 3. The consequences of major ductal disruptions include internal fistulas (pseudocysts, necrosis, pancreatic ascites, pancreatic pleural effusions, pancreaticoenteric or biliary communication), and external fistulas. 4. Treatment of internal fistulas requires treatment of the leak and/or the sequelae/consequences of the leak. 5. Bridging the site of ductal disruption with a transpapillary prosthesis is more likely to result in resolution of the disruption unless there is a disconnected gland syndrome. 6. External pancreatic fistulas that are the consequence of a disconnected pancreatic duct may ultimately close if low volume but are traditionally treated with resection of the disconnected gland.

REFERENCES 1. 2.

3. 4. 5.

6.

7.

Kozarek R. Role of ERCP in acute pancreatitis. Gastrointest Endosc. 2002; 56:S231–S236. Mariani A. Is secretin magnetic resonance cholangiopancreatography an effective guide for a diagnostic and/or therapeutic flow-chart in acute recurrent pancreatitis? JOP. 2001; 2:414–421. Enns R, Baillie J. Review article: the treatment of acute biliary pancreatitis. Aliment Pharmacol Ther. 1999; 1:1379–1389. Frakes JT. Biliary pancreatitis: a review. Emphasizing appropriate endoscopic intervention. J Clin Gastroenterol. 1999; 28:97–109. Kozarek RA, Attia FM, Traverso LW, et al. Pancreatic duct leak in necrotizing pancreatitis. Role of diagnostic and therapeutic ERCP as part of a multi-disciplinary approach. J Gastrointest Endosc. 2000; 51:AB138. Delhaye M, Matos C, Deviere J. Endoscopic technique for the management of pancreatitis and its complications. Best Pract Res Clin Gastroenterol. 2004; 18:155–181. Varadarajulu S, Noone T, Hawes RH, et al. Pancreatic duct stent insertion for functional smoldering pancreatitis. Gastrointest Endosc. 2003; 58:438–441.

8. Kozarek RA, Traverso LW. Pancreatic fistulas and ascites. In: Brandt JL (ed.) Textbook of clinical gastroenterology. Philadelphia: Current Medicine 1998:1175–1181. 9. Chebli JM, Gaburri PD, de Souza AF, et al. Internal pancreatic fistulas: proposal of a management algorithm based on a case series analysis. J Clin Gastroenterol. 2004; 38:795–800. 10. Lau ST, Simchuk EJ, Kozarek RA, et al. A pancreatic ductal leak should be sought to direct treatment in patients with acute pancreatitis. Am J Surg. 2001; 181:411–415. 11. Uomo G, Molino D, Visconti M, et al. The incidence of main pancreatic duct disruption in severe biliary pancreatitis. Am J Surg. 1998; 176:49–52. 12. Andrén-Sandberg Å, Dervenis C. Pancreatic pseudocysts in the 21st century. Part I: classification, pathophysiology, anatomic considerations and treatment. JOP. 2004; 5:8–24. 13. Kozarek RA. Pancreatic duct leaks and pseudocysts. In: Ginsberg G, Kochman M, Norton I, et al. (eds) Clinical gastrointestinal endoscopy; Textbook with DVD. Philadelphia: Saunders, 2005:807–820. 431

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14. Poon RT, Lo SH, Fong D, et al. Prevention of pancreatic anastomotic leakage after pancreaticoduodenectomy. Am J Surg. 2002; 183:42–52. 15. Sheehan MK, Beck K, Creech S, et al. Distal pancreatectomy: does the method of closure influence fistula formation? Am Surg. 2002; 68:264–267. 16. Freeny PC, Hauptmann E, Althaus SJ, et al. Percutaneous CTguided catheter drainage of infected acute necrotizing pancreatitis: techniques and results. AJR Am J Roentgenol. 1998; 170:969–975. 17. Memis A, Parildar M. Interventional radiological treatment in complications of pancreatitis. Eur J Radiol. 2002; 43: 219–228. 18. Kim HS, Lee DK, Kim IW, et al. The role of endoscopic retrograde pancreatography in the treatment of traumatic pancreatic duct injury. Gastrointest Endosc. 2001; 54:49–55. 19. Oksuz MO, Altehoefer C, Winterer JT, et al. Pancreaticomediastinal fistula with a mediastinal mass lesion demonstrated by MR imaging. J Magn Reson Imaging. 2002; 16:746–750. 20. Sakorafas GH, Sarr MG, Farnell MB. Pancreaticobiliary fistula: an unusual complication of necrotising pancreatitis. Eur J Surg. 2001; 167:151–153. 21. De Backer AI, Mortele KJ, Vaneerdeweg W, et al. Pancreatocolonic fistula due to severe acute pancreatitis: imaging findings. JBR-BTR. 2001; 84:45–47. 22. Salih A. Massive pleural effusion. Postgrad Med J. 2001; 77:536, 546–536, 547. 23. Ito H, Matsubara N, Sakai T, et al. Two cases of thoracopancreatic fistula in alcoholic pancreatitis: clinical and CT findings. Radiat Med. 2002; 20:207–211. 24. Balthazar EJ, Robinson DL, Megibow AJ, et al. Acute pancreatitis: value of CT in establishing prognosis. Radiology. 1990; 174:331–336. 25. Baron TH, Morgan DE. Acute necrotizing pancreatitis. N Engl J Med. 1999; 340:1412–1417. 26. Matos C, Bali MA, Delhaye M, et al. Magnetic resonance imaging in the detection of pancreatitis and pancreatic neoplasms. Best Pract Res Clin Gastroenterol. 2006; 20:157–178. 27. Kozarek RA. Endoscopic therapy of complete and partial pancreatic duct disruptions. Gastrointest Endosc Clin N Am. 1998; 8:39–53. 28. Szentes MJ, Traverso LW, Kozarek RA, et al. Invasive treatment of pancreatic fluid collections with surgical and nonsurgical methods. Am J Surg. 1991; 161:600–605. 29. Kaman L, Behera A, Singh R, et al. Internal pancreatic fistulas with pancreatic ascites and pancreatic pleural effusions: recognition and management. ANZ J Surg. 2001; 71:221–225. 30. Li-Ling J, Irving M. Somatostatin and octreotide in the prevention of postoperative pancreatic complications and the treatment of enterocutaneous pancreatic fistulas: a systematic review of randomized controlled trials. Br J Surg. 2001; 88:190–199. 31. Pitchumoni CS, Agarwal N. Pancreatic pseudocysts. When and how should drainage be performed? Gastroenterol Clin North Am. 1999; 28:615–639. 32. Kozarek RA, Brayko CM, Harlan J, et al. Endoscopic drainage of pancreatic pseudocysts. Gastrointest Endosc. 1985; 31:322–327. 33. De Palma GD, Galloro G, Puzziello A, et al. Endoscopic drainage of pancreatic pseudocysts: a long-term follow-up study of 49 patients. Hepatogastroenterology. 2002; 49:1113–1115. 34. Sanchez Cortes E, Maalak A, Le Moine O, et al. Endoscopic cystenterostomy of nonbulging pancreatic fluid collections. Gastrointest Endosc. 2002; 56:380–386.

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35. Kozarek RA, Ball TJ, Patterson DJ, et al. Endoscopic transpapillary therapy for disrupted pancreatic duct and peripancreatic fluid collections. Gastroenterology. 1991; 100:1362–1370. 36. Seifert H, Wehrmann T, Schmitt T, et al. Retroperitoneal endoscopic debridement for infected peripancreatic necrosis. Lancet. 2000; 356:653–655. 37. Takeda K, Matsuno S, Sunamura M, et al. Surgical aspects and management of acute necrotizing pancreatitis: recent results of a cooperative national survey in Japan. Pancreas. 1998; 16:316–322. 38. Büchler P, Reber HA. Surgical approach in patients with acute pancreatitis. Is infected or sterile necrosis an indication–in whom should this be done, when, and why? Gastroenterol Clin North Am. 1999; 28:661–671. 39. Büchler MW, Gloor B, Muller CA, et al. Acute necrotizing pancreatitis: treatment strategy according to the status of infection. Ann Surg. 2000; 232:619–626. 40. Baron TH, Thaggard WG, Morgan DE, et al. Endoscopic therapy for organized pancreatic necrosis. Gastroenterology. 1996; 111:755–764. 41. Baron TH, Harewood GC, Morgan DE, et al. Outcome differences after endoscopic drainage of pancreatic necrosis, acute pancreatic pseudocysts, and chronic pancreatic pseudocysts. Gastrointest Endosc. 2002; 56:7–17. 42. Kozarek RA, Jiranek GC, Traverso LW. Endoscopic treatment of pancreatic ascites. Am J Surg. 1994; 168:223–226. 43. Bracher GA, Manocha AP, DeBanto JR, et al. Endoscopic pancreatic duct stenting to treat pancreatic ascites. Gastrointest Endosc. 1999; 49:710–715. 44. Gomez-Cerezo J, Barbado CA, Suarez I, et al. Pancreatic ascites: study of therapeutic options by analysis of case reports and case series between the years 1975 and 2000. Am J Gastroenterol. 2003; 98:568–577. 45. Telford JJ, Farrell JJ, Saltzman JR, et al. Pancreatic stent placement for duct disruption. Gastrointest Endosc. 2002; 56:18–24. 46. Wolfsen HC, Kozarek RA, Ball TJ, et al. Pancreaticoenteric fistula: no longer a surgical disease? J Clin Gastroenterol. 1992; 14:117–121. 47. Carrere C, Heyries L, Barthet M, et al. Biliopancreatic fistulas complicating pancreatic pseudocysts: a report of three cases demonstrated by endoscopic retrograde cholangiopancreatography. Endoscopy. 2001; 33:91–94. 48. Kozarek RA, Ball TJ, Patterson DJ, et al. Transpapillary Stenting for Pancreaticocutaneous Fistulas. J Gastrointest Surg. 1997; 1:357–361. 49. Costamagna G, Mutignani M, Ingrosso M, et al. Endoscopic treatment of postsurgical external pancreatic fistulas. Endoscopy. 2001; 33:317–322. 50. Saeed ZA, Ramirez FC, Hepps KS. Endoscopic stent placement for internal and external pancreatic fistulas. Gastroenterology. 1993; 105:1213–1217. 51. Suc B, Msika S, Fingerhut A, et al. Temporary fibrin glue occlusion of the main pancreatic duct in the prevention of intra-abdominal complications after pancreatic resection: prospective randomized trial. Ann Surg. 2003; 237:57–65. 52. Seewald S, Brand B, Groth S, et al. Endoscopic sealing of pancreatic fistula by using N-butyl-2-cyanoacrylate. Gastrointest Endosc. 2004; 59:463–470. 53. Seewald S, Groth S, Omar S, et al. Aggressive endoscopic therapy for pancreatic necrosis and pancreatic abscess: a new safe and effective treatment algorithm. Gastrointest Endosc. 2005; 62:92–100. 54. Kozarek RA, Ball TJ, Patterson DJ, et al. Endoscopic pancreatic duct sphincterotomy: indications, technique, and analysis of results. Gastrointest Endosc. 1994; 40:592–598.

Chapter 40 Pancreatic Interventions in Acute Pancreatitis: Ascites, Fistulae, Leaks and Other Disruptions

55. Fazel A, Quadri A, Catalano MF, et al. Does a pancreatic duct stent prevent post-ERCP pancreatitis? A prospective randomized study. Gastrointest Endosc. 2003; 57:291–294. 56. Kozarek R, Hovde O, Attia F, et al. Do pancreatic duct stents cause or prevent pancreatic sepsis? Gastrointest Endosc. 2003; 58:505–509.

57. Smith MT, Sherman S, Ikenberry SO, et al. Alterations in pancreatic ductal morphology following polyethylene pancreatic stent therapy. Gastrointest Endosc. 1996; 44: 268–275. 58. Raijman I. Biliary and pancreatic stents. Gastrointest Endosc Clin N Am. 2003; 13:561–592.

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41

APPROACH TO CLINICAL PROBLEMS

Idiopathic Acute Pancreatitis: Role of ERCP in Diagnosis and Therapy Stuart Sherman

Determining the cause of acute pancreatitis is not usually difficult. Alcohol and gallstones are the two most common etiologies and account for 60–90% of the cases (Table 41.1). Alcoholism is diagnosed by history, and gallstones, by a combination of demographic characteristics, laboratory findings, and radiographic imaging studies. In patients in whom acute pancreatitis is due to hypertriglyceridemia, hypercalcemia, drug reactions, trauma, surgery, ERCP, etc, the relationship of the episode of pancreatitis to the cause is usually clear. Nevertheless, a cause for acute pancreatitis will not be identified in 10–30% of patients after a careful history, physical examination, laboratory testing, and radiological evaluation.1 These patients are conventionally classified as having idiopathic acute pancreatitis (IAP).2,3 Patients with recurrent episodes of IAP are diagnosed with idiopathic acute recurrent pancreatitis (IARP). This chapter will review the role of ERCP and ancillary endoscopic techniques in the evaluation and therapy of patients with IAP and IARP. The reader should be aware that significant controversy exists as to the appropriate use of ERCP in IAP because the available evidence is often sparse and largely uncontrolled.4

RATIONALE FOR AN ENDOSCOPIC APPROACH The literature is now replete with evidence to suggest that pancreatic duct obstruction can lead to acute pancreatitis. The pathophysiologic mechanisms are based on two key points: (1) pancreatic ductal obstruction leads to ductal hypertension that is exacerbated by pancreatic secretion and (2) Ductal hypertension causes inhibition of enzyme secretion resulting in colocalization of inactive pancreatic enzymes and lysosomal hydrolases with subsequent acinar cell injury and the clinical sequelae of acute pancreatitis.5 Advanced endoscopic evaluation of IAP and IARP focuses on identifying causes of pancreatic ductal obstruction with the therapeutic goal of alleviating the obstruction. It is assumed that relief of the obstruction will prevent further episodes of pancreatitis. The obstructive theory of acute pancreatitis assumes that ductal obstruction is intermittent or that a second risk factor predisposes patients with impaired ductal drainage.6

DIAGNOSTIC FINDINGS AND TIMING OF ERCP There are two major concerns that prompt the physician to do a more intensive evaluation of the patient with acute pancreatitis in whom no obvious cause is determined. The first is that the patient may have an underlying disease which will predispose to further attacks of acute pancreatitis unless the cause is identified and adequately treated. Acute pancreatitis is likely to recur in 33–67% of patients with biliary tract disease when not diagnosed and treated.7

Similarly, other anatomical or functional disorders of the pancreaticobiliary tree may predispose patients to recurrent episodes of acute pancreatitis. The second concern is that the pancreatitis may be related to a tumor. As a result, ERCP now plays a central role in the evaluation and therapy of patients with IAP. There are a number of potential causes of IAP that can be diagnosed by ERCP and ancillary techniques. These include occult gallstones, abnormalities and anomalies of the pancreatic duct and bile duct, sphincter of Oddi dysfunction, and ampullary and pancreatic neoplasms. The techniques applied at ERCP to diagnose the cause of IAP are shown on Table 41.2. Although there are potential gains by performing ERCP (identifying and treating the cause and preventing another episode of acute pancreatitis), there are potential downsides for the patient and the health care system as a whole (the inappropriate performance of the procedure and its complications).8 The timing of ERCP in patients with IAP is controversial. Ballinger and colleagues2 reported only one of 27 patients with one unexplained episode of acute pancreatitis and the gallbladder in situ had a second episode of pancreatitis during a 3-year follow-up period. They felt that the risks of ERCP were greater than the risks of a second episode of acute pancreatitis and advised against its use. On the other hand, Trapnell and Duncan reported that 35 of 148 patients (24%) with IAP suffered a recurrence, but that if gallstones were present, the rate increased to 38%.9 Using an actuarial method, the authors found that 10% of patients with IAP were likely to have a first recurrence within one year of the initial attack, 17% within two years and 25% within six years. Patients who had one recurrence were likely to have a second. In a cost-utility analysis, Gregor and colleagues found that performing an ERCP on all patients after a first episode of idiopathic pancreatitis was neither of great benefit nor particularly costly.8 However, it is of substantial benefit and cost-effective in a subgroup of patients with greater probability of having an occult gallstone. Our approach is (usually) to evaluate patients 40 years and older by ERCP (usually with sphincter of Oddi manometry and bile microscopy) after their first episode. This is based on the findings of Choudari et al.10 In this study, 21% of patients aged 40–60 years and 25% of patients older than 60 years had a neoplastic process as the cause for their pancreatitis in contrast to only 3% younger than 40 years (Table 41.3). Because of the low incidence of a neoplastic process, patients younger than 40 years undergo ERCP after their second episode unless the first episode was considered severe. In a series of 1108 patients with idiopathic pancreatitis, Fischer and colleagues reported a progressive increase in the incidence of mucinous tumors (as a cause for the pancreatitis) with age ranging from 1.3% in patients <25 years to 11.4% in patients older than 70 years.11 435

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Alcohol Autoimmune pancreatitis Biliary calculous disease Macrolithiasis (bile duct stone) Microlithiasis (biliary crystals) Biliary cystic disease Choledochal cyst Choledochocele/duplication cyst Congenital anomaly Annular pancreas Anomalous pancreaticobiliary junction Pancreas divisum Chronic pancreatitis Duodenal obstruction Afferent limb obstructed (Billroth II) Atresia Crohn’s disease Diverticulum Drugs Genetic Alpha 1-antitrypsin deficiency Cystic fibrosis Hereditary pancreatitis Iatrogenic ERCP Abdominal surgery

Idiopathic Infection Bacterial Parasites/worms Viral Metbolic Hypercalcemia Hyperlipidemia Inborn errors of metabolism Neoplasm Duodenal Ampullary Pancreatic Biliary Renal disease Chronic renal failure Dialysis related Sphincter of Oddi dysfunction Toxin Organophosphate insecticides Scorpion bite Trauma Tropical Vasculitis Polyarteritis nodosa Systemic lupus erythematosus

Table 41.1 Etiologies of acute pancreatitis

• Screening endoscopy – Ampullary and mucinous tumor • Ductography – Bile duct stones – Anomalies/abnormalities of the pancreatic duct and bile duct – Chronic pancreatitis – Tumors • Sphincter of Oddi manometry – Sphincter of Oddi dysfunction • Aspiration of bile for crystals – Microlithiasis

Table 41.2 Techniques applied at ERCP to diagnose cause of idiopathic acute pancreatitis

The findings of ERCP and the outcomes of therapy for each disease identified will be discussed individually.

OCCULT GALLSTONE DISEASE Although microlithiasis and biliary sludge are technically different, the terms are often used interchangeably. Microlithiasis most commonly refers to stones <3 mm in diameter and biliary sludge is considered to be a suspension of crystals, mucin, glycoproteins, cellular debris, and proteinaceous material within bile.12 The crystals are made up of cholesterol monohydrate, calcium bilirubinate, or calcium carbonate. Microlithiasis and biliary sludge may not be detected by standard gallbladder imaging techniques. Endoscopic 436

Diagnosis

<20 yr n = 15

20–40 yr n = 53

40–60 yr n = 95

>60 yr n = 62

Pancreatic cancer Ampullary Ca/Adenoma Mucinous tumor SOD Pancreas divisum Chronic pancreatitis Miscellaneous Normal

0% 0% 0% 47% 13% 27% 7% 7%

0% 2% 2% 43% 15% 11% 9% 21%

2% 2% 17% 35% 19% 9% 9% 6%

2% 0% 23% 26% 23% 13% 3% 11%

Table 41.3 Idiopathic acute pancreatitis: yield of ERCP ± sphincter of Oddi manometry ± bile microscopy correlated with age (n = 225) SOD = Sphincter of Oddi dysfunction; Ca = cancer. From reference 10.

ultrasound may help identify patients with underlying microlithiasis when conventional transcutaneous ultrasound is normal.13–15 Microlithiasis has been implicated as a common cause of IAP. Two prospective studies found that approximately two-thirds to three-fourths of patients with IAP harbored occult gallstones in the gallbladder.16,17 The diagnosis was based on microscopic examination of bile for crystals and usually confirmed on evaluation of the resected gallbladder or follow-up gallbladder ultrasound showing gallstones and/or sludge. On multivariate analysis, the finding of biliary crystals in bile is a strong predictor of small stones or sludge in the gallbladder (p < 0.001).17 Moreover, the finding of crystals in bile had a sensitivity of 86%, specificity of 86% and a positive predictive value of 92% for the diagnosis of gallstone disease as the missed cause of IAP. In contrast to the results of Lee and colleagues, and Ros and colleagues, some investigators have detected microlithiasis in fewer than 10% of patients with IAP.16–19 Bile may be collected at the time of ERCP from the duodenum or bile duct after gallbladder stimulation with cholecystokinin or by direct cannulation of the gallbladder. Treatment of microlithiasis can significantly reduce the incidence of recurrent pancreatitis.16,17 There are several therapeutic options for managing patients with pancreatitis due to microlithiasis. Laparoscopic cholecystectomy should be considered the procedure of choice as it is almost always curative. Ros and colleagues reported no further episodes of pancreatitis in 17 of 18 patients followed for 3 years after cholecystectomy.17 Endoscopic biliary sphincterotomy is an excellent alternative for the elderly and high-risk surgical patient.7 Dissolution therapy with ursodeoxycholic acid has also been shown to prevent recurrent pancreatitis.17 However, maintenance therapy appears necessary to prevent recurrent stone formation. Given the high prevalence of occult microlithiasis in some series, some authorities advocate empiric cholecystectomy as a first line of therapy, particularly in patients with recurrent attacks.20,21

SPHINCTER OF ODDI DYSFUNCTION The sphincter of Oddi (SO) is a small complex of smooth muscles surrounding the terminal common bile duct, main pancreatic duct, and the common channel. It is important to appreciate that there are separate biliary and pancreatic sphincters and that treatment aimed at the biliary sphincter may leave a diseased pancreatic sphincter intact (see below). The main function of the SO is to

Chapter 41 Idiopathic Acute Pancreatitis: Role of ERCP in Diagnosis and Therapy

regulate bile and pancreatic exocrine juice flow and prevent reflux of duodenal contents into the ducts. SO dysfunction (SOD) refers to an abnormality of SO contractility that is manifested clinically by pancreaticobiliary pain, pancreatitis, or deranged liver function tests. Sphincter of Oddi manometry (SOM) is considered by most authorities to be the gold standard test for diagnosing SOD.22–26 SOM can be performed percutaneously or intraoperatively, but is most commonly performed at the time of ERCP. SOM utilizes a water-perfused catheter which is inserted into the common bile duct, pancreatic duct, or both to measure sphincter pressures. The diagnosis of SOD is established when the basal sphincter pressure is equal to or greater than 40 mm Hg.24 Because SOM is difficult to perform, invasive, not widely available, and associated with a high complication rate, several non-invasive and provocative tests have been designed in an attempt to identify patients with SOD. The currently available data suggest that these tests lack the sensitivity and specificity to replace SOM.23,27 However, Mariani and colleagues recently reported that secretin-stimulated magnetic resonance cholangiopancreatography (s-MRCP) and SOM were concordant in 13 of 15 patients (86.7%).28 SOD is a frequent cause of recurrent pancreatitis previously labeled as IARP. It has been manometrically documented in 15–72% of such patients (Table 41.4).10,11,18,29–33 Pancreatic sphincter manometry should be done in patients with IARP, particularly those with normal biliary manometry and in those who have recurrent attacks after a biliary sphincterotomy. It is not surprising that isolated pancreatic sphincter hypertension is common among patients with IARP found to have SOD.6,34 Also pancreatic sphincter dysfunction may explain recurrent pancreatitis despite biliary sphincterotomy or surgical biliary sphincteroplasty.6 Sphincter ablation is the recommended therapy for patients with recurrent pancreatitis due to SOD. Historically, this has been done surgically.35,36 However, with increasing experience, endoscopic sphincterotomy has become the treatment of choice. The value of ERCP, SOM and sphincter ablation therapy was studied in 51 patients with idiopathic pancreatitis.37 Twenty-four patients (47.1%) had an elevated basal sphincter pressure. Thirty were treated by biliary sphincterotomy (n = 20), or surgical sphincteroplasty with septoplasty (n = 10). Fifteen of 18 patents (83%) with an elevated basal sphincter pressure had long-term benefit (mean follow-up, 38 months) from sphincter ablation therapy (including 10 of 11 treated by biliary sphincterotomy) in contrast to only 4 of 12 (33.3%, p < 0.05) with a normal basal sphincter pressure (including

Author (yr)

Frequency

Toouli (1985) Guelrud (1986) Gregg (1989) Venu (1989) Sherman (1993) Choudari (1998) Kaw (2002) Fischer (2005)

16/26 (57%) 17/42 (40%) 38/125 (30%) 17/116 (15%) 18/55 (33%) 79/225 (35%) 67/126 (53%) 445/1108 (40%)

Total

697/1823 (38%)

Table 41.4 Manometrically documented sphincter of Oddi dysfunction causing idiopathic acute recurrent pancreatitis From references 10, 11, 18, 29–33.

4 of 9 treated by biliary sphincterotomy). However, Guelrud and colleagues found that severance of the pancreatic sphincter was necessary to resolve the pancreatitis (Fig. 41.1).38 In this series, 69 patients with idiopathic pancreatitis due to SOD underwent treatment by standard biliary sphincterotomy (n = 18), biliary sphincterotomy with pancreatic sphincter balloon dilation (n = 24), biliary sphincterotomy followed by pancreatic sphincterotomy in separate sessions (n = 13), or combined pancreatic and biliary sphincterotomy in the same session (n = 14). Eighty-one percent of patients undergoing pancreatic and biliary sphincterotomy had resolution of their pancreatitis compared to 28% of patients undergoing biliary sphincterotomy alone (p < 0.005). Sherman and colleagues reported that only 44% of SOD patients with IARP had no further attacks during a 5-year follow-up interval after biliary sphincterotomy alone.32 These data are consistent with the theory that many such patients who benefit from biliary sphincterotomy alone may have subtle gallstone pancreatitis or perhaps the follow-up has not been long enough to detect another attack of pancreatitis. The results of Guelrud and colleagues also support the anatomic findings of separate biliary and pancreatic sphincters, and the manometry findings of residual pancreatic sphincter hypertension in more than 50% of persistently symptomatic patients who undergo biliary sphincterotomy alone.38 Kaw and Brodmerkel reported that among patients with idiopathic pancreatitis secondary to SOD, 78% had persistent manometric evidence of pancreatic sphincter hypertension despite a biliary sphincterotomy.33 Toouli et al. also demonstrated the importance of pancreatic and biliary sphincter ablation in patients with idiopathic pancreatitis.39 In this series, 23 of 26 patients (88%) undergoing surgical ablation of both the biliary and pancreatic sphincter were either

Fig. 41.1 Patient with idiopathic acute recurrent pancreatitis that reoccurred after biliary sphincterotomy. Top left shows pancreatic manometry being performed. Top right, bottom left and bottom right show pancreatic sphincterotomy being performed. 437

SECTION 3 APPROACH TO CLINICAL PROBLEMS

asymptomatic or had minimal symptoms at a median follow-up of 24 months (range 9–105 months). Okolo and colleagues retrospectively evaluated the long-term results of endoscopic pancreatic sphincterotomy in 55 patients with manometrically documented or presumed pancreatic sphincter hypertension (presumption based on recurrent pancreatitis with pancreatic duct dilation and contrast medium drainage time from the pancreatic duct greater than 10 minutes).40 During a median follow-up of 16 months (range 3–52 months), 34 patients (62%) reported significant pain improvement. Patients with normal pancreatograms were more likely to respond to therapy than those with pancreatographic evidence of chronic pancreatitis (73% vs 58%). Jacob et al. postulated that SOD might cause recurrent episodes of pancreatitis even though SOM was normal, and pancreatic stent placement might prevent further attacks.41 In a randomized study, 34 patients with IARP, normal pancreatic duct SOM, ERCP, secretin testing, and no biliary crystals (probably best considered “true IARP”) were treated with pancreatic stents (n = 19, 5–7 Fr, with stents exchanged 3 times over a 1-year period) or conservative therapy (n = 15). During a three-year followup, pancreatitis recurred in 53% of the patients in the control group and only 11% of the stented patients (p < .02). This study suggests that SOM may be an imperfect test, as patients may have SOD but not be detected at the time of SOM. However, long-term studies are needed to evaluate the outcome after removal of stents, and concern remains regarding stent-induced ductal and parenchymal changes.42,43 Because of the concern of stent-induced injury to the pancreas, trial pancreatic duct stenting to predict outcome from pancreatic sphincterotomy is not recommended.44 Wehrmann and colleagues evaluated the feasibility and effectiveness of botulinum toxin injection in patients with recurrent pancreatitis due to pancreatic sphincter hypertension.45 No side effects of the injection were noted in any of the 15 treated patients. Twelve patients (80%) remained asymptomatic at 3-month follow-up, but 11 developed a relapse at a follow-up period of 6 ± 2 months. These 11 patients underwent pancreatic or combined pancreatobiliary sphincterotomy with subsequent remission after a median follow-up of 15 months. This study showed that injection of botulinum toxin is safe, may be effective short term, and predict the outcome from pancreatic sphincter ablation in patients having frequent episodes of pancreatitis, but the need for definitive sphincter ablation in the majority of patients limits its clinical use. In summary, these data show that SOD is the most common cause of IARP when detailed endoscopic evaluation is performed. SOM should be considered the gold standard for diagnosing SOD. Complete sphincter evaluation requires manometric assessment of both the biliary and pancreatic sphincters. Although the best endoscopic therapy of SOD warrants further investigation, there is mounting evidence that pancreatic sphincter ablation will be necessary in the majority of patients to achieve the best long-term results. However, at present, controversy persists as to the appropriateness of performing SOM in patients with IAP.46 In the absence of a well-conducted randomized controlled trial and long-term patient follow-up, many authorities consider sphincter ablation therapy experimental and should not be performed in routine clinical practice.47,48

PANCREAS DIVISUM Pancreas divisum, the most common congenital variant of pancreatic duct anatomy, occurs when the dorsal and ventral ducts fail to fuse during the second month of gestation.49 With non-union of the 438

ducts, the major portion of the pancreatic exocrine juice drains into the duodenum via the dorsal duct and minor papilla. It has been proposed that a relative obstruction to pancreatic exocrine juice flow through the minor papilla with resultant pancreatic duct hypertension could precipitate recurrent pancreatitis in a subpopulation of pancreas divisum patients.50–52 Whereas a few epidemiological studies dispute the relation of pancreas divisum and pancreatitis, three lines of evidence favor this association: (1) histological studies and pancreatograms have demonstrated features of chronic pancreatitis isolated to the dorsal pancreas; (2) numerous studies have shown a statistically significant higher prevalence of pancreas divisum in this patient population; and (3) numerous studies indicated symptom resolution by facilitating dorsal duct decompression endoscopically or surgically.49,53,54 The diagnosis of pancreas divisum is suspected at ERCP when only a small ventral ductal system is visualized following contrast injection of the major papilla. It is confirmed when the remainder of the pancreatic ductal system (dorsal duct) is visualized by injecting contrast into the minor papilla and there is no communication between the two ductal systems. The clinical presentation and response to therapy for incomplete pancreas divisum where there is a small filamentous communication between the ventral and dorsal ducts appears to be similar to complete pancreas divisum.3,55 The aim of endoscopic therapy in symptomatic pancreas divisum patients is to alleviate the outflow obstruction at the level of the minor papilla. The available endoscopic options include dilation, long-term dorsal duct stenting, minor papilla sphincterotomy, or a combination of therapies. Table 41.5 shows the outcome of endoscopic therapy in 8 selected series in the literature.56–63 Overall, 81% of 127 patients had no further episodes of pancreatitis during a mean follow-up interval of 27 months. It must be appreciated that acute pancreatitis is an episodic illness. A follow-up duration as short as 20 months after intervention would not be long enough to conclude that a patient is “cured.”46 Moreover we lack the necessary randomized trials proving the efficacy of endoscopic intervention. There is only one randomized study evaluating the role of endoscopic therapy of pancreas divisum in the setting of IARP. Lans and colleagues reported the results of a randomized controlled trial of long-term (12 months) stenting of the minor papilla in patients with at least 2 prior episodes of unexplained pancreatitis (n = 19).59 The mean follow-up interval was 2.5 years and all stented patients were

Author, yr Liguory ‘86 McCarthy ‘88 Lans ‘92 Lehman ‘93 Coleman ‘94 Kozarek ‘95 Ertan ‘00 Heyries ‘02 Total

N 8 19 10 17 9 15 25 24

Endoscopic Therapy

Follow-up (mos)

% Improved

MiES Stent Stent MiES MiES/Stent MiES/Stent Stent MiES/Stent

24 21 30 20 23 26 24 39

63 89 90 76 78 73 76 92

27

81

127

Table 41.5 Endoscopic therapy of acute recurrent pancreatitis due to pancreas divisum MiES = Minor papilla sphincterotomy. From references 56–63.

Chapter 41 Idiopathic Acute Pancreatitis: Role of ERCP in Diagnosis and Therapy

followed for at least 12 months after stent removal. Stented patients had statistically significant fewer hospitalizations and episodes of pancreatitis (p < 0.05) and were more frequently judged to be improved (90% vs 11% for controls, p < 0.05). These promising results certainly support the role of endoscopic therapy in patients with pancreas divisum presenting with IARP. However, long-term stenting requires repeated procedures for stent change, each with an associated risk. Moreover pancreatic stenting is associated with pancreatic ductal and parenchymal changes which may be permanent.42,43 Finally, an unanswered question is whether stenting for 1 year permanently alleviates the obstruction at the level of the minor papilla. We prefer performing a minor papilla sphincterotomy which results in a “more permanent” enlargement of the minor papilla orifice (Fig. 41.2).49 In summary, patients with IARP found to have pancreas divisum are good candidates for minor papilla therapy. However long-term outcome studies (at least 5- to 10-year follow-up), preferably as randomized trials, are necessary to prove the safety and efficacy of endoscopic therapy not only in the setting of pancreas divisum but in other settings where a cause for the IARP has been uncovered.

CHOLEDOCHOCELE Choledochal cysts are uncommon anomalies of the biliary tree manifested by cystic dilation of the intrahepatic or extrahepatic ducts. A choledochocele, or Type III choledochal cyst using the Todani et al. classification system, most commonly refers to a cystic dilation of

the terminal common bile duct usually involving the intramural segment.64 Although pancreatitis has been reported to occur in association with all types of extrahepatic choledochal cysts, it occurs most commonly with the choledochocele. Moreover, choledochoceles are rarely identified by standard radiologic imaging (and therefore meet the definition of IAP) while other extrahepatic choledochal cysts are typically suspected or recognized by abdominal ultrasound or CT scan. IAP has been reported in 30–70% of patients found to have a choledochocele.65 Although choledochoceles commonly present with pancreatitis they are an uncommon cause of IAP because of their low prevalence. Choledochoceles are most commonly diagnosed at the time of ERCP. Endoscopically, the papilla has a “bulging” appearance but is soft (pillow sign) when probed with a catheter tip. A rounded cystic structure can be demonstrated at the terminal end of the common bile duct following contrast injection into the biliary tree with associated progressive enlargement or “ballooning” of the papilla.66,67 Surgical therapy, either by excision or sphincteroplasty, has been the traditional approach to choledochoceles.65 There is limited data to suggest that endoscopic therapy is a safe and effective alternative to surgery. The endoscopic approach is to unroof the cyst and perform a biliary sphincterotomy (Fig. 41.3). Table 41.6 presents the results of three selected series reporting the outcome of endoscopic therapy. Ten of 11 patients treated had no further episodes of pancreatitis during the follow-up period.66,68,69 In summary, choledochoceles are an uncommon cause of IARP but commonly present with pancreatitis. The diagnosis is made on endoscopic views of the papilla and contrast injection of the biliary tree. Endoscopic therapy appears to be an effective treatment in the large majority of patients.

Fig. 41.3 Left: Endoscopic view of a choledochocele. Right: Six weeks after endoscopic unroofing of the choledochocele and biliary sphincterotomy.

Fig. 41.2 Minor papilla sphincterotomy. Top left: A normal minor papilla. A highly tapered catheter and guidewire used to cannulate the dorsal duct are in view. Top right: A sphincterotome is in the minor papilla. Bottom left: Completed minor papilla sphincterotomy. Bottom right: A dorsal pancreatic duct stent was placed for pancreatitis prophylaxis.

Author (yr)

N

Venu (1984) Martin (1992) Ladas (1995)

8 10 15

Total

33

# Pancreatitis 5 7 1 13 (39%)

# Improved/# with IARP Treated at ERCP 2/3 7/7 1/1 10/11 (91%)

Table 41.6 Endoscopic therapy of choledochoceles in patients presenting with idiopathic acute recurrent pancreatitis IARP = idiopathic acute recurrent pancreatitis. From references 66, 68, 69.

439

SECTION 3 APPROACH TO CLINICAL PROBLEMS

TUMORS Five to seven percent of patients with benign or malignant pancreaticobiliary and ampullary tumors present with IAP.3 These tumors should be considered in patients 40 years or older who present with their first episode of acute pancreatitis.10,11 Patients with hereditary conditions such as Familial Adenomatous Polyposis (FAP) may have ampullary involvement and present with IAP at a youger age. The most common tumors reported in IARP series are: intraductal papillary mucinous tumors (IPMT) and cystic tumors, ampullary (papillary) tumors, pancreatic adenocarcinoma, and islet cell tumors. Ampullary tumors and IPMT deserve special mention since they are commonly missed on standard abdominal imaging tests and identified at the time of ERCP.6 There are a wide array of benign tumors that arise at the major papilla including adenoma, lipoma, fibroma, lymphangioma, leiomyoma and hamartoma.70 All have the potential to cause pancreatitis by obstructing pancreatic juice flow. Adenoma is the most common benign tumor of the major papilla. Endoscopy is the most sensitive and specific method for diagnosis of papillary tumors, as it accurately localizes the lesion and provides biopsy confirmation. Although there is uniform agreement that papillary adenomas should be resected, there is controversy as to the optimal method of excision. Regardless of the method of resection, complete removal is mandatory.70 The trend in management of papillary adenomas has been toward an increased use of endoscopic therapy perhaps because of more widespread use and experience with endoscopic mucosal resection in other parts of the GI tract. Evidence is accumulating to indicate that endoscopic resection (“snare papillectomy”), thermal ablation or a combination of the two are the treatment of choice for most papillary adenomas (Fig. 41.4).71–75 The techniques of endoscopic management and surveillance are discussed in detail by Kim and colleagues.70 There are a variety of primary malignant tumors of the major papilla including carcinoma, lymphoma, and neuroendocrine tumors. Metastatic tumors include malignant melanoma, hypernephroma, and lymphoma.70 Although most patients with malignant tumors of the papilla present with obstructive jaundice, there are occasional patients who develop pancreatitis as their first sign of the disease. ERCP is used to confirm the diagnosis and offer palliative stenting in non-resectable patients. IPMTs are clearly premalignant lesions, with up to 50% of patients having invasive carcinoma at operation.76 It is not uncommon to find patients with IPMT present with recurrent pancreatitis for many years before the diagnosis is made.77 Endoscopy and ERCP are essential to the diagnosis. ERCP was previously considered the standard for evaluation and diagnosis.76,78 Pancreatography typically reveals a dilated main pancreatic duct with intraductal cast-like filling defects representing mucin (Fig. 41.6).76 A patulous pancreatic orifice exuding mucin is seen in up to 80% of patients (Fig. 41.7).76 However, pancreatographic findings may be much more subtle and be misinterpreted as normal when a small cast-like filling defect is missed or a filling defect is labeled a pancreatic stone or air bubble. A missed diagnosis often comes in the setting of a normal diameter pancreatic duct (Fig. 41.7). Finally, IPMT may be misinterpreted as chronic pancreatitis. A high index of suspicion of the endoscopist is therefore critical particularly in patients older than 40 years. During pancreatography, early x-ray films should be obtained and the fluoroscopic image should be carefully observed so that small filling defects are not missed. At ERCP, it is also possible to 440

A

B

C

D

Fig. 41.4 A Endoscopic view of a tubulovillous adenoma involving the papilla and extending caudually down the duodenal wall. B The papilla was snared and electrocautery applied. C Appearance of the ampullary segment following snare resection of the papilla. D The tumor involving the duodenal wall was resected and a biliary sphincterotomy was done (patient has pancreas divisum, so a pancreatic stent was not placed in the ventral pancreatic duct). This endoscopic picture shows the area of the resected tumor.

Fig. 41.5 Intraductal papillary mucinous tumor (IPMT). Endoscopic retrograde pancreatogram showing a markedly dilated pancreatic duct containing filling defects in the body and tail consistent with mucus.

obtain cytologic specimens by aspiration or brushing, guided forceps biopsy specimens for histology and tissue and pancreatic juice for tumor markers. Pancreatoscopy and intraductal ultrasound are ancillary techniques utilized at the time of ERCP to help localize the tumor, differentiate benign from malignant disease and aid in the differential diagnosis of amorphous filling defects in the pancreatic duct.79

Chapter 41 Idiopathic Acute Pancreatitis: Role of ERCP in Diagnosis and Therapy

Fig. 41.6 Endoscopic views of an intraductal papillary mucinous tumor (IPMT). The patulous pancreatic orifice is exuding mucin.

Such unions may occur in isolation or be associated with choledochal cyst disease. Pancreatitis may be a complication of this anomaly. Samavedy and colleagues suggested that endoscopic therapy eliminates or reduces the frequency of recurrent pancreatitis and would be a logical first step in the management of most symptomatic patients.84 Annular pancreas is another congenital anomaly associated with pancreatitis that manifests as a band of pancreatic tissue partially or completely encircling the duodenum. ERCP typically identifies the duct of the annulus. Pancreas divisum is present in about one-third of patients.49,85 Duodenal duplication cyst, also a distinctly rare congenital anomaly, may present with pancreatitis. A potential role of endoscopic therapy in the treatment of such cysts has been described.86 Finally, chronic pancreatitis can be diagnosed at ERCP when main duct and/or side branch changes are present. In a series of 90 patients with IAP and IARP, 44% of patients had chronic pancreatitis by EUS and ERCP criteria.87 An obvious structural cause for the clinical episodes of acute pancreatitis may not be apparent after detailed endoscopic evaluation has been done.

OTHER INVESTIGATIONS

Fig. 41.7 Intraductal papillary mucinous tumor (IPMT). In this case, the cast-like filling defect (arrows) is present in a normal diameter pancreatic duct.

There appears to be no role or very little role of endoscopic therapy in IPMT (except when biliary obstruction occurs). However, the value of pancreatic sphincterotomy to assist in passage of mucin in high-risk surgical patients has not been evaluated. Given the fact that many of these patients already have gaping pancreatic orifices, it is unlikely to be of significant long-term benefit. EUS is assuming an increasingly important role in the assessment of patients with IAP and IARP (see below).80 Many studies have found EUS to have the highest sensitivity for identifying pancreatic neoplasms relative to other imaging modalities, especially for tumors smaller than 2–3 cm in diameter.3,81,82 This seems to be a reasonable test to perform particularly in patients older than 40, when other radiological imaging tests are negative, and perhaps should be considered prior to ERCP.

OTHER ANATOMICAL CAUSES There are a number of other non-neoplastic structural lesions that can cause acute pancreatitis. Pancreatic ductal strictures, which result in upstream ductal hypertension, are usually the result of prior trauma, or develop after healing of a pseudocyst or necrosis.6 Duodenal diverticula are rarely associated with pancreatitis.83 Anomalous pancreaticobiliary duct junction is a rare congenital malformation in which the union of the pancreatic duct and bile duct occurs outside the duodenal wall. As a result, the sphincter of Oddi is unable to prevent the reciprocal regurgitation of pancreatic enzymes and bile into the alternate biliary and pancreatic ducts.

The literature is now replete with evidence showing that patients with IAP and IARP may have mutations in the genes encoding cationic trypsinogen (PRSS1), pancreatic secretory trypsin inhibitor (Serine Protease Inhibitor Kazal Type I or SPINK-1), and cystic fibrosis transmembrane conductance regulator (CFTR).20,88–92 Testing for these genetic mutations is commercially available although many of the mutations causing pancreatitis cannot be detected by the currently available techniques. The role of genetic testing in IAP is controversial.20,88 However, detection of a genetic cause for the pancreatitis may obviate further testing, assist with family planning, and identify the patient for surveillance for complications of their pancreatitis including pancreatic cancer.93 In most situations, endoscopic therapy does not differ in patients with acute pancreatitis, chronic pancreatitis or pancreaititis complications regardless of whether a genetic mutation is present. Autoimmune pancreatitis is a relatively newly described entity characterized radiographically by diffuse or segmental irregular narrowing of the main pancreatic duct and diffuse enlargement of the pancreas, laboratory evidence of elevated levels of serum IgG (particularly the IgG 4 subtype) and the presence of autoantibodies, and histopathologically by fibrotic changes with lymphoplasmacytic infiltration of the pancreas.94 In contrast to other forms of chronic pancreatitis, it responds dramatically to steroids. Thus, laboratory screening with antinuclear antibody and serum immunoglobulins with IgG subtypes can be considered in selected patients with IAP.20 Endoscopic Ultrasound (EUS) has assumed a central role in the evaluation of patients with IAP and IARP.3,4 The findings on EUS may direct an alternative therapy (e.g. cholecstectomy for microlithiasis) and obviate a more invasive ERCP. Clearly EUS can identify small tumors of the pancreas not seen on other radiologic imaging studies and that may also be missed at ERCP.82 Frossard and colleagues reported that EUS identified a cause for IAP in 131 of 168 patients (78%) including 103 (61%) with biliary tract disease, 16 (10%) with chronic pancreatitis, 4 (2%) with IPMT, 4 (2%) with pancreatic cancer, 3 (2%) with amullary tumors, and 1 (1%) with a choledochal cyst.80 The definitive diagnosis was made at surgery in 101 patients (60%), at ERCP in 49 (29%) and by bile crystal analysis 441

SECTION 3 APPROACH TO CLINICAL PROBLEMS

Diagnosis

Number abnormal

Sphincter of Oddi Dysfunction Pancreas Divisum Pancreatic or papillary tumor Gallbladder or duct stones Pancreatic duct stricture/chronic pancreatitis Choledochocele

179 (34%) 70 (13%) 46 (9%) 37 (7%) 37 (7%) 12 (2%)

Total abnormal

381/522 (73%)

Table 41.7 Idiopathic acute recurrent pancreatitis—diagnostic yield of ERCP, sphincter of Oddi manometry and bile microscopy (4 selected series of 522 patients) From references 10, 18, 32, 33.

Diagnosis

Fig. 41.8 Secretin-stimulated MRCP demonstrating pancreas divisum. Note the normal dorsal duct.

Sphincter of Oddi Dysfunction Gallbladder or duct stones Pancreas Divisum Tumor Choledochocele Pancreatic duct stricture Total

or clinical follow-up in 18 (11%). Canadian researchers compared the diagnostic yield of EUS in 201 patients with a single episode of IAP with 169 patients with recurrent episodes.95 When chronic pancreatitis was not considered a positive finding, 29.2% of patients were found to have a cause for their pancreatitis. Biliary tract disease (18.7%) was the most common positive finding in the patients with the gallbladder in situ, whereas pancreas divisum (11.3%) was the most common finding in the post-cholecystectomy group. The frequency of positive findings did not differ between those with a single attack vs those with recurrent attacks. EUS identified an unsuspected cystic or solid neoplasm in 3.5% of patients. Chronic pancreatitis, the most common abnormality found (29.5%), was identified in about twice as many patients with recurrent episodes as in those with single episodes. MRI/MRCP has also assumed a vital role in the evaluation of patients with IAP and IARP because of its high-quality imaging of parenchymal and ductal structures. Secretin stimulaton can add to the diagnostic accuracy of this test (Fig. 41.8).96–99 Like EUS, MRI/ MRCP has a 90–100% sensitivity and specificity for detecting bile duct stones. Both EUS and MRI/MRCP are operator-dependent and their sensitivity and specificity in identifying a cause for the pancreatitis will depend on local expertise and availability.

YIELD OF ERCP FOR IAP AND IARP Table 41.7 summarizes the results of 4 selected series that utilized ERCP, SOM and bile microscopy in the assessment of 522 patients with IAP and IARP.10,18,32,33 Overall, 73% of patients were found to have a cause for their pancreatitis with SOD being the most common diagnosis. 442

No. patients

No. treated Followat ERCP up (mos) Asymptomatic

67

67

33

79%

18

16a

31

89%

9 2 2 2

8b 0c 2 2

24 28 18 31

89% 50% 100% 50%

30

81%

100

95

Table 41.8 Outcome of endoscopic therapy in 100 patients found to have a cause for idiopathic acute recurrent pancreatitis From reference 33. a Two treated with cholecystectomy. b One had unsuccessful minor papilla sphincterotomy. c One treated with Whipple; 1 with unresectable adenocarcinoma.

OUTCOMES OF ENDOSCOPIC THERAPY IN IARP Unfortunately there is a paucity of controlled data regarding outcomes in patients undergoing endoscopic therapy for previously diagnosed IARP. In fact, only two randomized controlled trials have been reported.41,59 It is also difficult to interpret what data are available due to loosely defined outcome measures, inhomogeneous clinical characteristics, generally short-term follow-up, and varied treatment techniques.6 Also, as emphasized above, since recurrent pancreatitis is an episodic illness, long-term follow-up (at least 5–10 years) after therapy is necessary before concluding that the therapy was effective.46,100 The outcomes of endoscopic therapy are detailed in the sections above. One recent study should be highlighted.33 One hundred and twenty-six patients with IARP underwent ERCP, SOM, and biliary crystal analysis. Patients had a mean of 3.2 episodes of pancreatitis (mean interval between recurrent attacks was 3.8 months). A cause for the pancreatitis was identified in 100 patients (79%) and included sphincter of Oddi dysfunction or papillary stenosis with or without crystals in 67 (53%), microcrystals alone in 12 (9.5%), pancreas divisum in 9 (7.1%), common duct stones in 6 (4.8%), malignancy in 2 (1.6%), chronic pancreatitis with a pancreatic stricture in 2 (1.6%) and choledochocele in 2 (1.6%). Endoscopic therapy was performed in 95 patients and 3 patients underwent surgery. The outcome of therapy is shown on Table 41.8. During a mean follow-

Chapter 41 Idiopathic Acute Pancreatitis: Role of ERCP in Diagnosis and Therapy

up of 30 months, 81% of patients were asymptomatic. Twenty-four patients had procedure-related complications; 20 had pancreatitis.

CONCLUSIONS IAP and IARP are a challenging clinical problem for the physician and often a frustrating one for the patient. ERCP with ancillary techniques can identify a probable cause for the pancreatitis in about 75% of patients. The majority of the diseases uncovered appear to be treatable by endoscopic or surgical techniques. EUS and MRI/MRCP are assuming a more central role in the evaluation

of patients with IAP and IARP. When these studies identify the cause of the pancreatitis, appropriate targeted treatment should be recommended. In this setting, ERCP should be utilized for therapy when appropriate. ERCP with ancillary endoscopic techniques is clearly indicated when EUS and/or MRI/MRCP fail to identify a cause for the recurrent pancreatitis. Further investigation is necessary to develop an algorithm which will provide the most cost-effective approach for these patients. Patients with IAP and IARP are best evaluated in centers where specialized expertise and equipment are available when advanced endoscopic methods are required.

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Chapter 41 Idiopathic Acute Pancreatitis: Role of ERCP in Diagnosis and Therapy

75.

Cheng CL, Sherman S, Fogel EL, et al. Endoscopic snare papillectomy for tumors of the duodenal papillae. Gastrointest Endosc 2004; 60:757–764. 76. Farrell JJ, Brugge WR. Intraductal papillary mucinous tumor of the pancreas. Gastrointest Endosc 2002; 55:701–714. 77. Enner S, Carr-Locke DL, Banks PA, et al. Intraductal mucinhypersecreting neoplasm “mucinous duct ectasia”: endoscopic recognition and management. Am J Gastroenterol 1996; 91:2548–2553. 78. Loftus EV, Olivares-Pakzad BA, Batts KP, et al. Intraductal papillary mucinous tumors of the pancreas: clinicopathologic features, outcome, and nomenclature. Gastroenterol 1996; 110:1909–1918. 79. Hara T, Yamaguchi T, Ishihara T, et al. Diagnosis and patient management of intraductal papillary mucinous tumor of the pancreas by using peroral pancreatoscopy and intraductal ultrasonography. Gastroenterology 2002; 122:34–43. 80. Frossard JL, Sosa-Valencia L, Amouyal G, et al. Usefulness of endoscopic ultrasonography in patients with “idiopathic” acute pancreatitis. Am J Med 2000; 109:196–200. 81. Rosch T. Staging of pancreatic cancer: Analysis of literature results. Gastrointest Endosc Clin North Am 1995; 5:735–739. 82. DeWitt J, Devereaux B, Chriswell M, et al. Comparison of endoscopic ultrasonography and multidetector computed tomography for detecting and staging pancreatic cancer. Ann Intern Med 2004; 141:753–763. 83. Uomo G, Manes G, Ragozzino A, et al. Periampullary extraluminal duodenal diverticula and acute pancreatitis: An underestimated etiological association. Am J Gastroenterol 1996; 91:1186–1190. 84. Samavedy R, Sherman S, Lehman GA. Endoscopic therapy in anomalous pancreatobiliary duct junction. Gastrointest Endosc 1999; 50:623–627. 85. Tagge EP, Smith SD, Raschbaum GR, et al. Pancreatic ductal abnormalities in children. Surgery 1991; 110:709–717. 86. Johanson JF, Geenen JE, Hogan WJ, et al. Endoscopic therapy of a duodenal duplication cyst. Gastrointest Endosc 1992; 38:60–64. 87. Coyle WJ, Pineau BC, Tarnasky PR, et al. Evaluation of unexplained acute and acute recurrent pancreatitis using endoscopic retrograde cholangiopancreatography, spincter of Oddi manometry and endoscopic ultrasound. Endoscopy 2002; 34:617–623.

88. Gorry MC, Gabbaizedeh D, Furey W, et al. Mutations in the cationic trypsinogen gene are associated with recurrent acute and chronic pancreatitis. Gastroenterol 1997; 113:1063–1068. 89. Cohn JA, Friedman KJ, Noone PG, et al. Relation between mutations of the cystic fibrosis gene and idiopathic pancreatitis. N Engl J Med 1998; 339:653–658. 90. Choudari CP, Imperiale TF, Sherman S, et al. Risk of pancreatitis with mutation of the cystic fibrosis gene. Am J Gastroenterol 2004; 99:1358–1363. 91. Cohn JA, Neoptolemos JP, Feng J, et al. Increased risk of idiopathic chronic pancreatitis in cystic fibrosis carriers. Hum Mutat 2005; 26:303–307. 92. Morinville V, Whitcomb D. Recurrent acute and chronic pancreatitis: Complex disorders with a genetic basis. Gastroenterol & Hepatol 2005; 1:195–205. 93. Ellis I. Genetic counseling for hereditary pancreatitis-the role of molecular genetics testing for the cationic trypsinogen gene, cystic fibrosis and serine protease inhibitor Kazal type 1. Gastroenterol Clin NAm 2004; 33:839–854. 94. Kim KP, Kim MH, Song MH, et al. Automimmune chronic pancreatitis. Am J Gastroenterol 2004; 99:1605–1616. 95. Yusoff IF, Raymond G, Sahai AV. A prospective comparison of the yield of EUS in primary vs. recurrent idiopathic acute pancreatitis. Gastrointest Endosc 2004; 60:673–678. 96. Moon JH, Cho YD, Cha SW, et al. The detection of bile duct stones in suspected biliary pancreatitis: comparison of MRCP, ERCP, and intraductal US. Am J Gastroenterol 2005; 100:1051–1057. 97. Arvanitakis M, Delhaye M, De Maertelaere V, et al. Computed tomography and magnetic resonance imaging in the assessment of acute pancreatitis. Gastroenterology 2004; 126:715–723. 98. Matos C, Metens T, Deviere J, et al. Pancreatic duct: morphologic and functional evaluation with dynamic MR pancreatography after secretin stimulation. Radiology 1997; 203:435–441. 99. Hellerhoff KJ, Helmberger, H, 3rd, Rosch T, et al. Dynamic MR pancreatography after secretin administration: image quality and diagnostic accuracy. AJR 2002; 179:121–129. 100. Steinberg WM, Chari ST, Forsmark CE, et al. Controversies in clinical pancreatology: management of acute idiopathic recurrent pancreatitis. Pancreas. 2003; 27:103–117.

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Pancreas Divisum and Other Pancreaticobiliary Anomalies Mark Topazian

INTRODUCTION Anomalies of the biliary and pancreatic ducts are commonly encountered during ERCP, and are important to both surgeons and gastroenterologists. This chapter reviews the diagnosis, clinical relevance, and therapy of these variants.

AMPULLARY ANOMALIES Ectopic major papilla The major papilla, which is typically located in the mid or distal second duodenum, is occasionally located in the third duodenum.1 Ectopic distal location of the ampulla is associated with anomalous pancreaticobiliary junction, congenital biliary dilatation, and biliary cysts.2 The distal displacement of the papilla may correspond to the length of an abnormally long common channel,3 and may reflect failure of the ducts to migrate normally into the duodenum during embryologic development. Rarely the major papilla may be located in the duodenal bulb.4 Double papilla of Vater has been described.5 When the papilla is in an anomalous location, the oblique intramural course of the bile duct is often absent,6 leaving less room for endoscopic biliary sphincterotomy.

Anomalous pancreaticobiliary junction The bile duct and pancreatic duct typically form a short common channel in the papilla of Vater. In about 1% of persons there is no common channel, and separate orifices of the bile duct and pancreatic duct are found on the major papilla. Less commonly the ducts join each other proximal to the sphincter apparatus, and a long common channel (>10 mm, and often >2 cm) is present (Fig. 42.1). A long common channel is often referred to as an anomalous pancreaticobiliary junction (APBJ); synonyms include pancreaticobiliary malunion. APBJ can be sub-classified according to the presence or absence of pancreas divisum, a dilated common channel, and an acute angle between the bile duct and pancreatic duct.7 These findings may influence choice of management and surgical strategy in symptomatic patients. For instance, symptomatic obstruction of the common channel is often treated endoscopically. APBJ is present in the majority of patients with biliary cysts, and appears to be a risk factor for the development of malignancy in a biliary cyst as discussed below. Patients with APBJ and no biliary cyst have increased risk of gallbladder cancer, and develop gallbladder cancer at an earlier age (Fig. 42.2).8,9 The finding of an isolated

APBJ should prompt consideration of elective cholecystectomy, even when asymptomatic.

BILIARY ANOMALIES Bile duct anatomy

Coiunaud10 described the liver as being composed of 4 sectors, defined by the 3 hepatic veins.11 The 4 sectors can be further subdivided into 8 segments, which are drained by segmental bile ducts (Fig. 42.3). Ducts from segments II, III, and IV form the left hepatic duct, and ducts from segments V, VI, VII, and VIII form the right hepatic duct. The right and left hepatic ducts drain into the common duct at the biliary confluence. The caudate lobe (segment 1) is typically drained by several short, small ducts into both the right and left hepatic ducts, and the caudate branches are generally not well seen during ERCP. The right hepatic duct is typically formed by a right anterior sectoral duct (draining segments V and VIII) and a right posterior sectoral duct (draining segments VI and VII). The right anterior duct has a relatively vertical and medial course, and the right posterior duct has a more horizontal and lateral course (Fig. 42.4, see also Figures 42.6, 42.7).11 Moving away from the confluence along the left hepatic duct, the first visualized branches generally drain segment IV, which may be drained by I to III segmental ducts. Moving further to the left, the left hepatic duct bifurcates into the segment II and III ducts (Fig. 42.4).11 Variants of confluence anatomy are common, and the normal confluence anatomy described above is seen in only 57% of persons. The commonest variations involve the right anterior and posterior ducts, and are shown in Figure 42.5. These include low drainage of one of the right sectoral ducts into the common duct (seen in 20%) (Fig. 42.6), a “triple confluence” in which the two right sectoral ducts drain separately into the confluence (12%), and drainage of a right sectoral duct into the left duct (6%). In about 2% a right sectoral duct drains into the cystic duct as shown in Figure 42.7. These variants of right duct anatomy may increase the risk of a bile duct injury during cholecystectomy, and if identified on a preoperative ERCP, should be conveyed to the operating surgeon. They are also important to the endoscopist when managing hilar malignant obstruction and evaluating postoperative biliary strictures and leaks. When a right sectoral duct draining into the cystic duct is divided and clipped during laparoscopic cholecystectomy, resulting in a Bismuth V ductal injury, cholangiographic diagnosis is difficult and requires a

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Fig. 42.1 Anomalous pancreaticobiliary junction (APBJ) (arrows) and pancreas divisum in a 14-year-old with recurrent pancreatitis. A A long, dilated common channel is present, which contains a stone. B The common bile duct is dilated, suggestive of a Type I choledochal cyst.

A B

The cystic duct may drain into the ampulla separately from the common bile duct.12

Biliary cysts

Fig. 42.2 Anomalous pancreaticobiliary junction (APBJ) (arrow) with a bile duct stricture (arrowhead) caused by gallbladder cancer in a 32-year-old with obstructive jaundice. APBJ is a risk factor for development of gallbladder cancer. Note the absence of a bile duct cyst.

high degree of suspicion to recognize that a right sectoral duct is not visualized. Variants of segmental duct anatomy also commonly occur (particularly segments IV, V, VI, and VIII) and are shown in Figure 42.8. In one common variant, a segment IV duct drains into one of the right sectoral ducts rather than the left duct. Ectopic drainage of the gallbladder and cystic duct may occur, and is discussed elsewhere.11 448

Biliary cysts, also called choledochal cysts, are cystic dilatations of the biliary tree. One widely adopted classification of biliary cysts was described by Alonso-Lej and modified by Todani, and is shown in Figure 42.9.13,14 Type I cysts, which are commonest, are dilatations of the common bile duct, as illustrated in Figure 42.10. They can be subdivided into Types 1a, 1b, and 1c based on the presence or absence of an APBJ and fusiform or segmental dilatation, as shown in Figure 42.9. Type II cysts are diverticula of the common duct. Type III cysts involve the major papilla and may also be termed choledochoceles or duodenal duplications (as they are often lined by duodenal rather than biliary mucosa). Type III cysts may be further subdivided into Type IIIA (in which the bile duct and pancreatic duct enter the cyst proximally, and the cyst drains through a separate distal opening into the duodenum) and Type IIIB (a diverticulum of the intra-ampullary common channel). Endoscopically Type IIIA cysts present as an enlargement of the ampulla and intramural ducts, although this may not be apparent until they bulge during contrast injection (Fig. 42.11). Type IV cysts are multiple cysts located in both the intra- and extrahepatic ducts (IVA) or in the extrahepatic biliary tree (IVB). Type V cysts, also called Caroli’s disease, are located in the intrahepatic ducts. Various mechanisms probably lead to formation of biliary cysts, as reviewed elsewhere.15 In the majority of patients with extrahepatic cysts an anomalous pancreaticobiliary junction (APBJ) is present, and it is likely that chronic reflux of pancreatic juice into the bile duct leads to ductal dilatation and biliary mucosal inflammation. Sequelae may include pancreatitis, ductal stones, biliary dysplasia, and cholangiocarcinoma. The risk of cholangiocarcinoma increases with age, and may be as high as 14% in young adults16 and 50% in older adults17 presenting with symptomatic complications of their cysts. In one report, the increased risk of cholangiocarcinoma in extrahepatic biliary cysts appeared to be confined to those patients with APBJ.18 The possibility of cholangiocarcinoma should always

Chapter 42 Pancreas Divisum and Other Pancreaticobiliary Anomalies

Fig. 42.3 Functional division of the liver into segments, according to Couinaud’s nomenclature. From LH Blumgart and Y Fong (eds) Surgery of the liver and biliary tract, Saunders, 2002, Philadelphia, PA, Fig 1.7B, p. 7. Reproduced with permission.11

II

VIII VII

III

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IV V

VI

Fig. 42.4 Normal intrahepatic ductal anatomy. RA = right anterior duct, RP = right posterior duct, L = left duct, numbers indicate drained hepatic segments. Note that the right anterior duct has a relatively vertical and medial course, and the right posterior duct has a more horizontal and lateral course. See also Figures 42.6 and 42.7.

Type I cysts with associated dilatation of central intrahepatic ducts can be distinguished from Type IVA (combined intrahepatic and extrahepatic cysts) by the presence of a distinct change in ductal caliber at the distal end of a true intrahepatic cyst.13 Diagnosis of early cholangiocarcinoma in a dilated segment of bile duct is difficult, and it is likely that intraductal ultrasound is more sensitive than cholangiography for detection of early cholangiocarcinoma in this setting. Extrahepatic biliary cysts are best treated with surgical resection, which manages local complications of the disease and decreases the risk of subsequent malignancy. Exceptions include Type III cysts or choledochoceles, which can be treated with endoscopic sphincterotomy19 (Type IIIA) or endoscopic resection20 (Type IIIB). It appears that cancer is uncommon in choledochoceles, but has been reported.19 In some patients with Type I cysts, obstruction of a long common channel may be best treated endoscopically.

PANCREATIC ANOMALIES Pancreas divisum

Embryology and terminology be considered in an adult patient with a newly diagnosed biliary cyst, especially when an APBJ is also present. Diagnosis of a biliary cyst requires a high degree of clinical suspicion, particularly for Type I cysts, which may have a similar cholangiographic appearance to a chronically obstructed bile duct. The absence of obstruction distal to the dilated segment is a key diagnostic finding, although patients with biliary cysts may become symptomatic only when an obstruction (due to stone or malignancy) occurs. An APBJ, when present, is an important clue to diagnosis.

The embryological development of the pancreatic ductal system is shown in Figure 42.12. The pancreas develops from dorsal and ventral pancreatic buds that appear in the dorsal mesentery during the fifth week of embryologic development. The dorsal bud is larger, and eventually forms the pancreatic tail, body, neck, and portions of head including the uncinate process. The ventral bud arises together with the bile duct, and eventually forms part of the periampullary pancreatic head. Growth and rotation of the duodenum brings the ventral bud around the posterior aspect of the duodenum towards the dorsal bud. The two buds fuse as shown in Figure 42.12. Typically the ducts 449

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A

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rp 57%

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Fig. 42.5 Common variations of biliary confluence anatomy. (a) typical anatomy, (b) triple confluence, (c) ectopic drainage of a right sectoral duct into common hepatic duct, (d) ectopic drainage of a right sectoral duct into left hepatic duct, (e) absence of a confluence, (f) ectopic drainage of the right posterior sectoral duct into the cystic duct. rp = right posterior, ra = right anterior, lh = left hepatic duct. From LH Blumgart and Y Fong (eds) Surgery of the liver and biliary tract, Saunders, 2002, Philadelphia, PA, Fig 1.25, p. 19. Reproduced with permission.11

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Fig. 42.6 Ectopic drainage of the right posterior duct into the common hepatic duct. RA = right anterior duct, RP = right posterior duct, L = left duct, CD = cystic duct.

450

2% F1

Fig. 42.7 Ectopic drainage of the right anterior duct into the cystic duct. RA = right anterior duct, RP = right posterior duct, L = left duct, CD = cystic duct.

Chapter 42 Pancreas Divisum and Other Pancreaticobiliary Anomalies

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Fig. 42.8 Common variations of the segmental intrahepatic ducts. A segment V, B segment VI, C segment VIII, D segment IV. From LH Blumgart and Y Fong (eds) Surgery of the liver and biliary tract, Saunders, 2002, Philadelphia, PA, Fig 1.26, p. 19. Reproduced with permission.11

I

IV-A

II

IV-B

III

Fig. 42.9 Classification of biliary cysts. From Todani, Watanabe, Toki, et al. Classification of congenital biliary cystic disease: special reference to type Ic and IVA cysts with primary ductal stricture. J Hepatobiliary Pancreat Surg. 2003; 10(5):340–344, Figure 1. Reproduced with kind permission of Springer Science and Business Media.13

V

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Fig. 42.10 Type I biliary cyst. An anomalous pancreaticobiliary junction was also present.

A

B

C

Fig. 42.11 Choledochocele, or Type IIIA biliary cyst. A The major papilla appears normal prior to cannulation. B The intramural duct balloons outward after cholangiography. C Cholangiography demonstrates a cystic dilatation of the intra-ampullary common channel.

452

Chapter 42 Pancreas Divisum and Other Pancreaticobiliary Anomalies

A Stomach

Dorsal mesentery

Ventral mesentery Dorsal pancreatic bud Liver Gall bladder Foregut part of duodenum Ventral pancreatic bud

Midgut part of duodenum

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Dorsal pancreatic bud

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Spleen Duodenum Level of section G Tail of pancreas Head of pancreas

Tail of pancreas

Opening of bile and main pancreatic ducts

Accessory pancreatic duct

Body of pancreas

Fig. 42.12 Embryological development of the pancreas and pancreatic ductal system. From KL Moore and TVN Persaud, The developing human: clinically oriented embryology, 7th edn, Saunders, 2003, Philadelphia, PA. Fig. 12.10, p. 267. Reproduced with permission.47 453

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A

A

B B

Fig. 42.13 Complete pancreas divisum. A Cannulation of the major papilla demonstrates an arborizing ventral pancreatic duct that does not cross the midline or give rise to an uncinate branch. B Cannulation of the minor papilla demonstrates a dominant dorsal pancreatic duct, with no communication to the ventral pancreas. The uncinate branch arises from the dorsal pancreatic duct.

within the buds also fuse, and the main pancreatic duct drains both dorsal and ventral pancreas into the duodenum via the major papilla. In pancreas divisum the ducts do not fuse or fuse incompletely, and the dorsal pancreas duct drains the bulk of pancreatic exocrine secretions into the duodenum via the minor papilla. Pancreas divisum can be subdivided into cases in which there is no communication between ventral and dorsal pancreas (“complete pancreas divisum”) (Fig. 42.13), and cases in which there is a communication between dorsal and ventral pancreatic ducts (“incomplete pancreas divisum”) (Fig. 42.14). Patients with complete divisum usually have a small ventral pancreatic duct communicating with the major papilla, but this cannot always be demonstrated. Incomplete pancreas divisum can be further subdivided into cases in which a narrow connecting duct joins ventral and dorsal pancreas, but most pancreatic exocrine secretion must drain through the minor papilla (“dominant dorsal duct drainage”), and cases in which the connecting duct is large and most pancreatic drainage is likely to occur via the major papilla. 454

Fig. 42.14 Incomplete pancreas divisum. A Cannulation of the major papilla demonstrates a small ventral pancreatic duct without filling of the dorsal duct. B Cannulation of the minor papilla demonstrates a dominant dorsal pancreatic duct, with communication to the ventral pancreatic duct and major papilla. The uncinate branch arises from the dorsal pancreatic duct.

Diagnosis Diagnosis of pancreas divisum can typically be made by CT, MR, or EUS, although this may require review of diagnostic images with attention to the possibility of divisum. EUS demonstrates the main pancreatic duct coursing through the dorsal pancreas to the expected location of the minor papilla, entering the duodenum separately from the bile duct, with or without visualization of a diminutive ventral pancreatic duct.21 When viewed from the duodenal bulb, the bile duct and pancreatic duct may appear to cross each other rather than converging at the duodenal wall.22 While the accuracy of EUS is as high as 97% using a linear echoendoscope,21 CT, MR, or EUS do not fully exclude a diminutive or collapsed duct connecting ventral and dorsal pancreas, and they do not prove patency of the minor papilla. ERCP thus remains the gold standard for diagnosis.

Chapter 42 Pancreas Divisum and Other Pancreaticobiliary Anomalies

A

B

Major papilla injections in complete divisum usually demonstrate a diminutive, arborizing ventral pancreatic duct, which does not cross the midline (Fig. 42.13). The uncinate branch is not visualized because the uncinate process is part of the dorsal pancreas; this is another clue to diagnosis.23 When divisum is diagnosed on the basis of a ventral pancreatogram alone, the possibility of pseudodivisum (in which an obstruction of the main pancreatic duct in the head simulates divisum) should be considered (Fig. 42.15). Pseudodivisum typically causes an eccentric, rapidly tapering, or abrupt terminus of the ventral pancreatic duct, while in true divisum the ventral duct arborizes. In some clinical situations, cannulation of the minor papilla to confirm the diagnosis of divisum may be necessary to exclude pseudodivisum. Techniques of minor papilla cannulation are discussed in Chapter 8.

Association with pancreatitis and role of endoscopic treatment The relationship of pancreas divisum to pancreatic disease is controversial. An early study found pancreas divisum in up to 25% of patients with idiopathic pancreatitis presenting for ERCP,24 but in a subsequent larger study divisum was not seen more commonly in ERCP patients with a history of acute, chronic, or idiopathic pancreatitis compared to those with no history of pancreatic disease.25 Referral bias may explanation the high incidence of divisum seen at some centers. Pancreas divisum is a common anomaly, with a prevalence of 5% to 10% at autopsy.26,27 Since, in the United States, less than 0.1% of the population is admitted to hospital yearly with pancreatitis of any cause,28 the vast majority of persons with divisum must be asymptomatic. If pancreas divisum causes pancreatic disease it does so only in a very small percentage of persons with this anomaly. Factors proposed to trigger pancreatitis in persons with divisum include obstruction to outthe minor papilla, and the presence of genetic abnormalities linked to pancreatitis. A stenotic minor papilla orifice or spasm of a minor papilla sphincter29 might result in divisum-related pancreatitis due to relative obstruction of dorsal duct drainage. Several lines of evi-

Fig. 42.15 Pseudodivisum. A Cannulation of the major papilla demonstrates an arborizing ventral pancreatic duct, suggestive of pancreas divisum, but with some filling of an irregular duct superiorly. B With deep cannulation of the ventral pancreatic duct and further injection a stricture of the main pancreatic duct is demonstrated. Biopsies showed adenocarcinoma.

dence lend some support to this hypothesis. In a surgical series, minor papilla sphincteroplasty was of most benefit in divisum patients whose minor papilla was stenotic by intra-operative assessment with lacrimal probes.30 In a small randomized, prospective study, endoscopic stenting of the minor papilla resulted in significantly better outcomes than sham therapy in patients with pancreas divisum and at least 2 attacks of unexplained acute pancreatitis.31 The occasional finding of a Santorinicele, or a dilated terminus of the dorsal pancreatic duct in the duodenal wall, may also be taken as evidence of pancreatic outflow obstruction in some patients with pancreas divisum. Secretin-stimulated MRI in patients with Santorinicele demonstrates larger pancreatic duct diameters and delayed drainage into the duodenum compared to divisum patients without a Santorinicele.32 Manometry of the minor papilla and dorsal pancreatic duct has been performed, showing high dorsal duct pressures, although normal control data is not available.29 Botulinum toxin injections into the minor papilla predicted subsequent response to minor papilla sphincterotomy in one small series, presumably by treating sphincter or duodenal wall spasm.33 The obstruction theory has led to widespread adoption of endoscopic therapy for idiopathic pancreatitis associated with pancreas divisum. In addition to the randomized, controlled series described above, uncontrolled surgical and endoscopic reports indicate that about 70% of persons with divisum and idiopathic recurrent acute pancreatitis will improve following sphincterotomy or stenting of the minor papilla. These relatively good outcomes are reported in patients with recurrent acute pancreatitis who have no evidence of chronic pancreatitis; patients with chronic pancreatitis and divisum are less likely to respond, and patients with chronic upper abdominal pain and no history of pancreatitis will improve about 30% of the time.34 A randomized trial of minor papilla sphincterotomy versus sham therapy in divisum patients with pain alone, reported only in abstract form, did not show a significant benefit to endoscopic treatment.35 Difficulties with the obstruction theory persist. Those patients who respond best to endoscopic therapy do not have pancreato455

SECTION 3 APPROACH TO CLINICAL PROBLEMS

graphic evidence of chronic ductal obstruction. Endoscopists have not developed a reliable method of assessing the minor papilla for stenosis or spasm at the time of ERCP: normal values for minor papilla manometry are not known, and delayed drainage has not been studied as a predictor of outcome following endoscopic treatment. The secretin ultrasound test has not proven to reliably demonstrate pancreatic duct obstruction in divisum patients with recurrent acute pancreatitis. In addition, a recent series reports poorer response to minor papilla treatment than previously seen, with immediate improvement in the majority but later recurrence in most patients.36 These difficulties have led investigators to look for other physiologic or genetic factors responsible for pancreatitis in divisum patients. Two groups of investigators have studied cystic fibrosis transmembrane receptor (CFTR) abnormalities in patients with divisum and recurrent pancreatitis. One group assayed for 13 common CFTR mutations, and found a mutated allele significantly more often in divisum patients with pancreatitis (22%) than in divisum patients without pancreatitis (0%).37 Since about 1000 CFTR mutations have been described, the authors pointed out that the true prevalence of mutations in their subjects may well be higher. A second group assayed CFTR function by nasal transepithelial potential difference testing. They found that patients with divisum and recurrent pancreatitis had intermediate results between normal controls and patients with classic cystic fibrosis, a result that parallels findings in other adult onset single organ diseases linked to CFTR dysfunction.38 These findings suggest that an underlying physiologic abnormality likely contributes to the development of pancreatitis in some divisum patients. In the case of CFTR, diminished function may result in more viscous pancreatic secretions, potentially contributing to ductal obstruction. Only 2 of 12 divisum patients with diminished CFTR function improved after endoscopic or surgical therapy.38 A non-invasive test that reliably identifies obstruction to pancreatic duct outflow and predicts response to minor papilla therapy is needed. The secretin ultrasound test has been used for this purpose. In this test intravenous secretin is administered and changes in pancreatic duct diameter are measured using either transabdominal ultrasound or endoscopic ultrasound. While transient dilatation of the pancreatic duct occurs after secretin administration in normal subjects, ductal dilatation of more than 1 mm, persisting for at least 15 minutes after secretin administration, may indicate ductal obstruction. In some series this technique has been a strong predictor of clinical response to minor papilla therapy in pancreas divisum.30,39 Other investigators, however, have not reproduced these findings.40 In one study, abnormal secretin ultrasound results were seen after episodes of acute pancreatitis due to a variety of causes.41 The major concern with this test is the potential for false positive results; false negative results are likely to be seen only in patients with chronic pancreatitis and some exocrine insufficiency. Secretin MRI has theoretical advantages over secretin ultrasound, since the entire pancreatic duct is visualized, and the timing and volume of pancreatic juice secretion into the duodenum can be estimated.42,43 The value of secretin MRI for predicting response to endoscopic therapy in pancreas divisum has not been reported. In summary, while endoscopic minor papilla therapy probably helps a minority of patients with pancreas divisum, its role is limited, and optimal patient selection requires further clarification.

456

A practical approach to divisum patients based on current evidence is to discourage endoscopic therapy in patients with pain alone or one episode of pancreatitis, and to consider endoscopic therapy in those who have had at least two episodes of otherwise unexplained acute pancreatitis. Even these patients face a substantial chance of persistent or recurrent disease after endoscopic treatment. Prior to endoscopic treatment, both secretin-stimulated MR and tests of CFTR status may be useful, although more data is needed regarding the predictive value of these tests. If testing is performed for CFTR mutations it should include mutations associated with adult onset, single organ disease. If the patient is having frequent episodes of pancreatitis, botulinum toxin injection of the minor papilla may also be considered as a therapeutic trial, again based on limited data. Patients considering minor papilla sphincterotomy or stenting should be told about the variable outcomes reported with these interventions, the chance of recurrent symptoms, and the possibility of complications such as post-sphincterotomy stenosis. Endoscopic techniques of minor papilla therapy are discussed in detail in Chapter 15.

Incomplete pancreas divisum As discussed earlier in this chapter, incomplete pancreas divisum is characterized by communicating ventral and dorsal pancreatic ducts, with a patent minor papilla and pancreatic duct drainage at both the major papilla and the minor papilla. Despite having two routes of pancreatic drainage, some patients with incomplete divisum may nevertheless have symptoms related to pancreatic outflow obstruction. Some have dominant dorsal duct drainage, in which the duct connecting ventral and dorsal pancreas is diminutive, and most pancreatic exocrine secretion must drain through the minor papilla (Fig. 42.14). Others may have stenosis at both the major and minor papillae. As with complete pancreas divisum, incomplete divisum is a common anatomic variant, and most persons with incomplete divisum are asymptomatic. It seems likely that incomplete divisum occasionally causes or contributes to disease, as in the reported case of an adult with acute relapsing pancreatitis, incomplete divisum, and a carcinoid tumor of the minor papilla causing partial obstruction.44 However the caveats discussed above regarding pancreas divisum are germane to incomplete divisum as well. There is no randomized, controlled trial of endoscopic therapy for incomplete divisum, and convincing evidence of benefit from endoscopic treatment is lacking. Two series of endoscopic treatment for incomplete divisum report short-term improvement in 50–60%, without longterm follow-up.45,46 Therapy was most successful in patients with otherwise unexplained recurrent acute pancreatitis. The decision to direct endoscopic treatment at the minor papilla, major papilla, or both is affected by the presence or absence of dominant dorsal duct drainage.

Annular pancreas

Annulus is the Latin word for ring, and an annular pancreas is a ringed pancreas partially or completely encircling the duodenum. As shown in Figure 42.16, the likely embryologic basis of annular pancreas is encirclement of the duodenum by the ventral pancreas during duodenal rotation in the 5th to 8th week of fetal development. The encircling ring of pancreas typically involves the second duode-

Chapter 42 Pancreas Divisum and Other Pancreaticobiliary Anomalies

C B

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Bile duct (passing dorsal to duodenum and pancreas)

Stomach

Duodenum Bile duct

Annular pancreas

Bile duct Bifid ventral pancreatic bud

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Site of duodenal obstruction

Fig. 42.16 Embryological basis of annular pancreas. From KL Moore and TVN Persaud, The developing human: clinically oriented embryology, 7th edn, Saunders, 2003, Philadelphia, PA. Fig. 12.11, p. 268. Reproduced with permission.47

num or apex of duodenal bulb. The commonest clinical presentation of annular pancreas is duodenal obstruction, most often diagnosed in infancy but occasionally presenting later in life. Cases of annular pancreas associated with pancreatitis and pancreatic cancer have been reported, but it is unclear if annular pancreas predisposes to these diseases. In adults annular pancreas is typically diagnosed by CT. EUS is also useful for diagnosis, showing a ring of ventral pancreatic tissue encircling the duodenum proximal to the papilla. At pancreatography a ventral pancreatic duct is seen encircling the duodenum, as shown in Figure 42.17.

Fig. 42.17 Annular pancreas. The ventral pancreatic duct encircles the second duodenum (arrow). This patient also has a stricture of the main pancreatic duct, caused by pancreatic adenocarcinoma.

REFERENCES 1.

2.

3.

4.

5.

6.

Schwartz A, Birnbaum D. Roentgenologic study of the topography of the choledocho-duodenal junction. Am J Roentgenol Radium Ther Nucl Med 1962; 87:772–776. Li L, Yamataka A, Wang Y, et al. Anomalous pancreatic duct anatomy, ectopic distal location of the papilla of Vater and congenital biliary dilatation: a new developmental triad? Pediatr Surg Int 2003; 19:180–185. Li L, Yamataka A, Yian-Xia W, et al. Ectopic distal location of the papilla of vater in congenital biliary dilatation: Implications for pathogenesis. J Pediatr Surg 2001; 36: 1617–1622. Kubota T, Fujioka T, Honda S, et al. The papilla of Vater emptying into the duodenal bulb. Report of two cases. Jpn J Med 1988; 27:79–82. Rajnakova A, Tan W, Goh P. Double papilla of Vater: a rare anatomic anomaly observed in endoscopic retrograde cholangiopancreatography. Surg Laparosc Endosc 1998; 8:345–348. Pereira-Lima J, Pereira-Lima L, Nestrowski M, et al. Anomalous location of the papilla of Vater. Am J Surg 1974; 128:71–74.

7. Komi N, Takehara H, Kunitomo K, et al. Does the type of anomalous arrangement of pancreaticobiliary ducts influence the surgery and prognosis of choledochal cyst? J Pediatr Surg 1992; 27:728–731. 8. Elnemr A, Ohta T, Kayahara M, et al. Anomalous pancreaticobiliary ductal junction without bile duct dilatation in gallbladder cancer. Hepatogastroenterology 2001; 48:382–386. 9. Hu B, Gong B, Zhou D. Association of anomalous pancreaticobiliary ductal junction with gallbladder carcinoma in Chinese patients: an ERCP study. Gastrointest Endosc 2003; 57:541–545. 10. Couinaud C, Le Foi. Etudes anatomogiques et chirurgicales. Masson, 1957. 11. Blumgart L, Fong Y. Surgery of the liver and biliary tract. 3rd ed. New York: WB Saunders, 2000. 12. Watanabe A, Ohashi Y, Nagashima H. Anomalies of the bile ducts: a case report of direct drain of the cystic duct into the papilla of Vater. Acta Med Okayama 1983; 37:409–415. 13. Todani T, Watanabe Y, Toki A, et al. Classification of congenital biliary cystic disease: special reference to type Ic and IVA cysts with primary ductal stricture. J Hepatobiliary Pancreat Surg 2003; 10:340–344. 457

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14. Alonso-Lej F, Rever WJ, Pessagno D. Congenital choledochal cyst, with a report of 2, and an analysis of 94, cases. Int Abstr Surg 1959; 108:1. 15. Corso M, Topazian M. Biliary cysts. UpToDate 2005. [http:// patients.uptodate.com] 16. Voyles C, Smadja C, Shands W, et al. Carcinoma in choledochal cysts. Age-related incidence. Arch Surg 1983; 118:986–988. 17. Todani T, Watanabe Y, Toki A, et al. Carcinoma related to choledochal cysts with internal drainage operations. Surg Gynecol Obstet 1987; 164:61–64. 18. Song H, Kim M, Myung S, et al. Choledochal cyst associated the with anomalous union of pancreaticobiliary duct (AUPBD) has a more grave clinical course than choledochal cyst alone. Korean J Intern Med 1999; 14:1–8. 19. Ladas S, Katsogridakis I, Tassios P, et al. Choledochocele, an overlooked diagnosis: report of 15 cases and review of 56 published reports from 1984 to 1992. Endoscopy 1995; 27: 233–239. 20. Chatila R, Andersen D, Topazian M. Endoscopic resection of a choledochocele. Gastrointest Endosc 1999; 50:578–580. 21. Lai R, Freeman M, Cass O, Mallery S. Accurate diagnosis of pancreas divisum by linear-array endoscopic ultrasonography. Endoscopy 2004; 36:705–709. 22. Bhutani MS, Hoffman BJ, Hawes RH. Diagnosis of pancreas divisum by endoscopic ultrasonography. Endoscopy 1999; 31:167–169. 23. Morgan D, Logan K, Baron T, et al. Pancreas divisum: implications for diagnostic and therapeutic pancreatography. AJR Am J Roentgenol 1999; 173:193–198. 24. Cotton P. Congenital anomaly of pancreas divisum as cause of obstructive pain and pancreatitis. Gut 1980; 21:105–114. 25. Burtin P, Person B, Charneau J, et al. Pancreas divisum and pancreatitis: a coincidental association? Endoscopy 1991; 23:55–58. 26. Dawson W, Langman J. An anatomical-radiological study on pancreatic duct pattern in man. Anat Rec 1961; 139:59–68. 27. Berman L, Prior J, Abramow S, et al. A study of the pancreatic duct system in man by the use of vinyl acetate casts of postmortem preparations. Surg Gynecol Obstet 1960; 110:391–403. 28. Russo M, Wei J, Thiny M, et al. Digestive and liver diseases statistics, 2004. Gastroenterology 2004; 126:1448–1453. 29. Satterfield S, McCarthy J, Geenen J, et al. Clinical experience in 82 patients with pancreas divisum: preliminary results of manometry and endoscopic therapy. Pancreas 1988; 3:248–253. 30. Warshaw A, Simeone J, Schapiro R, et al. Evaluation and treatment of the dominant dorsal duct syndrome (pancreas divisum redefined). Am J Surg 1990; 159:59–64. 31. Lans J, Geenen J, Johanson J, et al. Endoscopic therapy in patients with pancreas divisum and acute pancreatitis: a prospective, randomized, controlled clinical trial. Gastrointest Endosc 1992; 38:430–434.

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32. Manfredi R, Brizi M, Costamagna G, et al. Pancreas divisum and santorinicele: assessment by dynamic magnetic resonance cholangiopancreatography during secretin stimulation. Radiol Med (Torino) 2002; 103:55–64. 33. Wehrmann T, Schmitt T, Seifert H. Endoscopic botulinum toxin injection into the minor papilla for treatment of idiopathic recurrent pancreatitis in patients with pancreas divisum. Gastrointest Endosc 1999; 50:545–548. 34. Lehman G, Sherman S, Nisi R, et al. Pancreas divisum: results of minor papilla sphincterotomy. Gastrointest Endosc 1993; 39:1–8. 35. Sherman S, Hawes R, Nisi R, et al. Randomized controlled trial of minor papilla sphincterotomy in patients with pancreas divisum and pain only. Gastrointestinal Endoscopy 1994; 40:P125. 36. Gerke H, Byrne M, Stiffler H, et al. Outcome of endoscopic minor papillotomy in patients with symptomatic pancreas divisum. JOP 2004; 5:122–131. 37. Choudari C, Imperiale T, Sherman S, et al. Risk of pancreatitis with mutation of the cystic fibrosis gene. Am J Gastroenterol 2004; 99:1358–1363. 38. Gelrud A, Sheth S, Banerjee S, et al. Analysis of cystic fibrosis gener product (CFTR) function in patients with pancreas divisum and recurrent acute pancreatitis. Am J Gastroenterol 2004; 99:1557–1562. 39. Catalano M, Lahoti S, Alcocer E, et al. Dynamic imaging of the pancreas using real-time endoscopic ultrasonography with secretin stimulation. Gastrointest Endosc 1998; 48:580–587. 40. Lowes J, Lees W, Cotton P. Pancreatic duct dilatation after secretin stimulation in patients with pancreas divisum. Pancreas 1989; 4:1–4. 41. Cavallini G, Rigo L, Bovo P, et al. Abnormal US response of main pancreatic duct after secretin stimulation in patients with acute pancreatitis of different etiology. J Clin Gastroenterol 1994; 18:298–303. 42. Khalid A, Peterson M, Slivka A. Secretin-stimulated magnetic resonance pancreaticogram to assess pancreatic duct outflow obstruction in evaluation of idiopathic acute recurrent pancreatitis: a pilot study. Dig Dis Sci 2003; 48:1475–1481. 43. Punwani S, Gillams A, Lees W. Non-invasive quantification of pancreatic exocrine function using secretin-stimulated MRCP. Eur Radiol 2002; 13:273–276. 44. Singh V, Bhutani M, Draganov P. Carcinoid of the minor papilla in incomplete pancreas divisum presenting as acute relapsing pancreatitis. Pancreas 2003; 27:96–97. 45. Kim M, Lee S, Kim C, et al. Incomplete pancreas divisum: is it merely a normal anatomic variant without clinical implications? Endoscopy 2001; 33:778–785. 46. Jacob L, Geenen JE, Catalano M, et al. Clinical presentation and short-term outcome of endoscopic therapy of patients with symptomatic incomplete pancreas divisum. Gastrointestinal Endoscopy 1999; 49:53–57. 47. Moore KL, Persaud TVN. The developing human: clinically oriented embryology, 7th edn. Saunders, Philadelphia, PA, 2003.

SECTION 3

Chapter

43

APPROACH TO CLINICAL PROBLEMS

Chronic Pancreatitis: Stones and Strictures Jacques Deviere

INTRODUCTION Chronic pancreatitis (CP) is a rare disease in Western countries (incidence 2–10/100000/ year). It ultimately leads to irreversible damage of the pancreas with exocrine and endocrine insufficiency. Pain is the major clinical symptom and is present early in the course of the disease, in the majority of the cases.1,2 With the exception of the rare hereditary chronic pancreatitis, the etiology of CP has not yet been demonstrated. Chronic alcoholism is a precipitating factor and dramatically increases the probability of CP development but the disease can also develop in non-alcoholic subjects without any obvious genetic background and is then defined as “idiopathic” CP. The pathophysiology of CP is still debated. Adherents of the “stone theory”‘ believe that the initiating event is protein plug formation due to a congenital lack of lithostatin.3 Proponents of the “necrosis fibrosis” theory, in turn, ascribe fibrosis and ductal stricture as the consequence of focal inflammation and necrosis.4 Pain associated with chronic pancreatitis is obviously multifactorial and includes increased interstitial and intraductal pressures, closed compartment syndrome, neural infiltration, ongoing acute pancreatitis, pseudocyst(s) and/or biliary obstruction. Elevated intraductal pressure due to the presence of stones and/or stricture is one of the major phenomena leading to pain in CP.5–8 Due to the lack of compliance of the pancreatic gland, which is already present in the early stages of CP, elevated intraductal pressure is quickly associated with increased parenchymal pressure that impairs blood flow, leading to hypoxia, release of oxygen-derived free radicals and further stimulation of inflammation with subsequent fibrosis development.8 Surgical decompression of the main pancreatic duct has been shown to be associated with pain relief in many patients and is associated with a decrease in intraductal and interstitial pressures.9 Another characteristic of pain in CP is its heterogeneous pattern, from relapsing episode to persistent pain of varying intensity which cannot be predicted by pancreatic morphology. The initial episodes of acute recurrent abdominal pain or acute pancreatitis often increase and may evolve into a continuous pain syndrome requiring narcotics. During the natural history of chronic pancreatitis, pain may disappear after several years, often associated with the development of endocrine and/or exocrine insufficiency.10 This heterogeneous pain pattern is one of the difficulties we have in interpreting the clinical results of studies reporting on the effectiveness of surgical or endoscopic drainage for pain relief in CP.

ENDOSCOPIC TREATMENT: DUCTAL DECOMPRESSION BY MANAGING STONES AND STRICTURES The goal of endotherapy in severe CP is to decompress the main pancreatic duct (MPD) by removing stones and bypassing strictures. Another clinical goal for MPD drainage might be to reduce the incidence, or delay the development, of steatorrhea as a consequence of increased flow of pancreatic juice to the duodenum. This remains controversial.11,12 Therapeutic endoscopy offers several modalities for pancreatic duct drainage including endoscopic pancreatic sphincterotomy, stone removal, extracorporeal shock wave lithotripsy (ESWL), stricture dilation and insertion of pancreatic stents.

Pretherapeutic planning In addition to standard laboratory testing and plain films of the pancreatic area or a non-contrast CT scan for detection of pancreatic calcifications, magnetic resonance imaging is currently the best modality for the selection of patients who may benefit from endoscopic treatment and for pretherapeutic planning of the sequence of interventions which may be required (Fig. 43.1). Where preformed in conjunction with secretin stimulation, it adequately depicts the pancreatic ductal anatomy, the presence of peripancreatic fluid collections, and possible obstruction of the bile duct. Moreover, it can be used to quantify pancreatic exocrine function and to evaluate the short- and long-term effect of a pancreatic ductal drainage procedure (Fig. 43.2).13,14

MPD cannulation and endoscopic pancreatic sphincterotomy This is the first step of pancreatic endoscopy and provides improved access to the MPD. Minor papilla sphincterotomy may be needed in up to 20% of patients in cases of dominant dorsal duct anatomy (complete or incomplete pancreas divisum, ansa pancreatica). In a small subset of patients, pancreatic sphincterotomy (EPS) itself may resolve papillary stenosis and allow the removal of small floating stones. However, especially in Western countries, when a calcification in the head of the pancreas is visible on routine radiographs or unenhanced CT scan, and when MPD dilation is recognized at MRCP, the stones are most often deeply impacted in the ductal wall and very difficult to remove. In this case, ESWL should be performed prior to attempted endoscopic intervention. 459

SECTION 3 APPROACH TO CLINICAL PROBLEMS

B

A

C

Fig. 43.1 Example of pretherapeutic planning in a patient with CP and severe pain. The plain film A shows a dense calcification, which is even more clearly visible on an unenhanced CT Scan B, while the dynamic MRCP after secretin injection shows an impacted stone at the level of the genu of the pancreas, with upstream dilation, while the distal MPD is normal size C. This patient will first undergo ESWL before any endoscopic intervention.

B

A

D

Position 1

A

C

B

Position 2 Fig. 43.2 Patient with a residual prepapillary stricture after extraction of stone fragments A, treated by placement of two 8.5 Fr stents side by side B. The comparison of S-MRCP performed before C and after D drainage shows the decrease in MPD diameter and earlier duodenal filling of pancreatic secretions (arrow).

Biliary sphincterotomy may be performed before endoscopic pancreatic sphincterotomy in case of cholangitis or obstructive jaundice, associated cholestasis, or when it is technically necessary to facilitate access to the pancreatic duct. If such a biliary sphincterotomy is performed, the orifice of the pancreas is always located between 3 and 6 o’clock on the right margin of the sphincterotomy. After pancreatic opacification, a hydrophilic guidewire (Terumo Inc, Japan) can be maneuvered through the stricture or alongside the stones, using a torque device under precise radiological control (Fig. 43.3). Pancreatic sphincterotomy is performed over the guidewire after deep cannulation. Section of the pancreatic sphincter is performed under direct vision with a standard or tapered pull-type sphincterotome, using, in our experience, only pure cutting current, extending the incision to the duodenal wall. The same technique can be used for minor papilla sphincterotomy. 460

Fig. 43.3 The use of a minitome (Cook, Winston Salem, NC) with a 0.018 J tip Terumo guidewire manipulated by the assistant using a torque device offers the best performance for cannulating difficult and tortuous strictures under fluoroscopic control.

Alternatively, when feasible, a small stent can be inserted into the pancreatic duct and sphincterotomy performed with a needle knife over the stent.

Extracorporeal shock wave lithotripsy In multidisciplinary referral centers which use endoscopic management to treat severe chronic pancreatitis, ESWL is performed as the initial procedure before any endoscopic access to the pancreas. Good-quality plain films of the pancreatic area are taken in left and right oblique positions to help improve fluoroscopic control during lithotripsy. Technically, it is of major importance to use a lithotriptor with a bidimensional x-ray focusing system and a high-power generator. Ultrasonic localization of pancreatic stones lacks precision and efficacy. When performed under general anesthesia or deep sedation,

Chapter 43 Chronic Pancreatitis: Stones and Strictures

3 to 6000 shock waves can be applied at an intensity of 0.33 to 0.54 mJ/mm2, which provides a complete fragmentation of the stones after a median of 1 session (with a maximum of 5 sessions in our experience).15,16 The patient is in a prone position and the shock waves generator is placed to his right when stones are in the head of the pancreas and to his left for stones located in the body or tail of the pancreas. The effectiveness of ESWL on calcium carbonate pancreatic stones is much better than that obtained for biliary stones and provides fragmentation into millimeter fragments which can usually be easily removed by ERCP (Fig. 43.4). When the lithotriptor is available within or close to the endoscopy unit, ESWL and therapeutic ERCP may be performed consecutively, even during the same general anesthesia.

Intraductal lithotripsy Intraductal mechanical lithotripsy has been claimed to facilitate pancreatic stone fragmentation before extraction.17 However, mechanical lithotripsy requires encircling the stone with a Dormia basket, which is most often impossible for impacted calcified stones and much less successful than when utilized for stones in the bile duct. A pulsed dye-laser lithotriptor has also been used to fragment pancreatic stones, the laser fiber inserted under visual control with a pancreatoscope or directly applied under fluoroscopic control.18,19 Laser lithotripsy has proven useful in a minority of patients. However, intraductal fragmentation remains anecdotal and does not really challenge ESWL which, because of efficacy, simplicity, and lack of complications, make it the gold standard for pancreatic stone fragmentation.

A

B

D

Stones extraction and dilation After ESWL, minute stone fragments are visible within the pancreatic duct. If located above a stricture, dilation of this stricture using a 4 to maximum 6 mm dilating balloon (Maxforce, Boston Scientific, Boston, MA) should be performed before stone removal. Most commonly, we initially use a small Dormia basket to remove the fragments (Fig. 43.4). When these are visible on fluoroscopy, a good trick is to first introduce a guidewire into the main pancreatic duct and then the Dormia basket with either no or minimal contrast injection. The localization of residual fragments is easier and the basket can be manipulated at their level to trap them. Most often, the basket is left opened in the duct, turning on its axis while gently perfusing the duct with saline. A slightly inflated balloon catheter may be used in some cases but is of limited use in the pancreas because sharp stone fragments frequently break the balloons. Tight strictures may be present. Although balloon dilation is used most frequently, bougies may be necessary and, in case of strictures in which any catheter passage proves impossible, a Soehendra stent retriever (8.5 Fr) can usually be rotated through the stricture to create the necessary passage for placement of a dilation balloon (Fig. 43.5). If multiple sessions of endoscopy are necessary for stone fragment removal or fragmentation of multiple stones, a nasopancreatic catheter (NPC) is left in place for drainage between the sessions. This may decrease the risk of acute pancreatitis due to fragment impaction.20 In addition, placement of a NPC can also be used as a clinical predictor for the requirement of pancreatic stenting when the presence of a stricture is not obvious. Indeed, if a patient toler-

C

F E

Fig. 43.4 Same patient as Figure 43.1. Successful fragmentation (A versus B) after ESWL is illustrated by a decrease in radiological density, an increase of the stone surface area and a heterogeneity of the stones (powder-like material). After fragmentation, a pancreatic sphincterotomy is performed C, a guidewire is inserted in the pancreatic duct D and a small Dormia basket E is maneuvered alongside the guidewire to remove the stone fragments. At the end of the procedure, a nasopancreatic catheter is left in place F. 461

SECTION 3 APPROACH TO CLINICAL PROBLEMS

A

B

C

Fig. 43.5 Usual techniques of dilation: A 4 cm × 6 mm Maxforce balloon is inflated through the stricture of which the imprint is visible at the beginning of inflation. B A biliary bougie is passed over a guidewire. C In extremely tight strictures, an 8.5 F Soehendra stent retriever is rotated through the stricture in order to create the room necessary for insertion of a balloon. In this case, after dilation, the stent retriever should be removed while turning it counterclockwise in order to avoid the risk of displacing the guidewire.

ates perfusion of a NPC without pain, the absence of a significant stricture of the pancreatic duct is likely and further stenting may be avoided or postponed. In contrast, if perfusion of NPC is painful, the catheter should be placed to gravity drainage and further stone extraction or stenting considered.

A

B

Stenting When a stricture is present, adequate outflow from the pancreas to the duodenum must be achieved by placement of a stent. In contrast to stenting to prevent acute pancreatitis in high-risk patients, in severe chronic pancreatitis only large (8.5 or 10 Fr) stents are used. Stent lengths are adapted to the morphology of the pancreas and are placed through the stricture after complete removal of stone fragments. Stents are usually replaced every 6 months for a period of 2 years, or on demand in case of relapsing symptoms. The tendency now is to place multiple stents side by side. Two 8.5 Fr stents can usually be easily placed after a dilation to 6 mm. The number of stents can be further increased over successive exchanges if the morphology of the pancreas allows it (Fig. 43.2). This policy has been recently recommended as a means to reduce the duration of stenting needed to provide effective calibration and prolonged symptom relief.21 The technique of multiple stent placement is easier when two guidewires are placed initially through the stricture and the two stents are implanted successively over the two guidewires. This technique avoids the need to recannulate the pancreas and bypass a tight stricture with a guidewire when the first stent is already in place. The use of the new Fusion systemTM (Cook Endoscopy, Winston Salem, NC) allows intraductal exchange and placement of multiple stents side by side without losing access with a single guidewire. This system has become our preferred technique for placement of multiple plastic stents in the pancreas (Fig. 43.6).

Technical results The majority of patients with severe painful chronic pancreatitis have stones which require shock wave lithotripsy. In our experience, ESWL is required in 2/3 of the patients who are referred for treatment, whereas in a multicentric study of more than 1000 patients pancreatic obstruction was due to the presence of obstructive stones alone in 17%, stricture of the main pancreatic duct in 47% of the 462

C

D

Fig. 43.6 Patient with CP and daily pain. Left (A,C): plain film and MRCP at admission, showing a single impacted stone in the head of pancreas with upstream dilation of the MPD. Right (B,D): after a single session of ESWL, without any endoscopic therapy, the major part of the stone has disappeared B, the size of the MPD has decreased D and duodenal filling, at the same time-point after secretin injection, is much more obvious.

cases, and both stones and stricture in 32%.11 Numerous reports have shown that ESWL is a low-risk and technically successful method with fragmentation rate of up to 100%. Nevertheless, complete clearance of the main pancreatic duct is only achieved in 44 to 75% of the cases (Table 43.1). A recent meta-analysis showed that the use of ESWL was clearly associated with ductal clearance and pain relief.22 Technical success of endoscopic ductal drainage, however, is generally defined as a decrease in the diameter of main pancreatic duct with or without complete ductal stone clearance.12 Using this definition, technical successes have been noted in 54– 99% of the cases in the largest series published to date.11,15,16,23–31

Chapter 43 Chronic Pancreatitis: Stones and Strictures

Fragmentation (%)

Complete clearance (%)

Complete or partial pain relief (%)

Need for surgery (%)

Mean follow-up (months)

Study (ref)

Year

No. of patients

ESWL and endotherapy Delhaye (15) Schneider (23) Costamagna, et al. (27) Adamek, et al. (28) Brand, et al. (29) Farnbacher, et al. (26) Kozarek, et al. (30) Inui, et al. (16)

1992 1994 1997 1999 2000 2002 2002 2005

123 50 35 80 48 125 40 470

99 86 100 54 60 85 100 92

59 60 74 ND 44 64 ND 73

85 62 72 76 82 48a 80 69a

8 12 3 10 4 13 20 4

14 20 27 40 7 29 30 44

ESWL alone Ohara (31)

1996

32

100

75

86

3

44

Table 43.1 Results of extracorporeal shock wave lithotripsy (ESWL) and endotherapy for chronic calcific pancreatitis a

Patients with complete pain relief during follow-up.

Series (ref)

Number of patients

Technical success (%)

Associated factor

Clinical success (%)

Associated factor (ref)

Short-term follow-up <2 y (15)

123

90

None

85

Decrease in MPD diameter

Medium-term follow-up 2y–5y (11,24–26,28,33–35)

53–996

54–99

Availability of ESWL (24) Single stone (28)

48–84

Short duration of disease (24,33) Low frequency of pain (24) Absence of MPD stricture (24)

Total

1557

86

56

86

Long-term follow-up >5 y (12)

65 None

66

Short duration of disease No current smoking

Table 43.2 Predictive factors of technical and clinical success in published series of more than 50 chronic pancreatitis patients treated by ESWL and endoscopic pancreatic ductal drainage

Dumonceau et al. identified ESWL as the only independent factor associated with technical success. In most reports, successful fragmentation and stone clearance have not been correlated with the initial size or the number of main pancreatic duct stones.24 In one recent study, stone clearance was negatively correlated with the presence of a stricture.32

Clinical results Early pain relief after endoscopic pancreatic duct drainage is experienced by 82–94% of patients and can be expected when drainage of the main pancreatic duct is adequate.23,24,26 Medium-term clinical improvement has been observed in 48–84% of the patients after a mean follow-up period of 2–5 years and an independent predictor for pain relapse during follow-up has been reported as a high frequency of pain attacks.24,36 Other factors include a long duration of disease before treatment and the presence of a stenosis of the main pancreatic duct (Table 43.2).24,32,33 In our series, reporting the longest follow-up to date (14,4 years), a good clinical outcome was recorded in 2/3 of the patients and was associated with a short duration of disease before treatment and cessation of smoking.12 This suggests that ESWL and/or endoscopic therapy should be initiated as early as possible in the course of CP since it increases the probability of long-term benefit. In most series, recurrent pain attacks during the follow-up period were related to stone fragment migration or recurrent, progressive

stricture of the main pancreatic duct, or pancreatic stent obstruction or dislodgement. Interestingly, re-treatments are usually easier than initial treatment and remain very effective in controlling pain.26 The latter is dramatically different from surgery which is associated with increased morbidity when it has to be repeated. Dominant strictures of the main pancreatic duct are often the indication for insertion of a pancreatic stent, required in 50–60% of the patients with severe chronic pancreatitis.11,26,27,33,34 The problem with stenting is that even large stents may become occluded and result in relapsing symptoms and even infectious pancreatitis. They can be exchanged on a regular basis or on demand (in patients with recurrence of pain and recurrent dilation of the main pancreatic duct). This latter strategy results in stent replacement at a mean period of 8–12 months, likely because even an occluded stent may serve as a wick to allow pancreatic juice to flow into the duodenum.33,36 Stenting for a short period of time (6 months) is not enough to provide adequate calibration of a stricture and long-term pain relief.37 However, since the presence of a stent may be associated with the need for repeated endoscopy, two large studies have assessed longterm outcomes in patients following pancreatic stent removal. In one study, stents could be removed from 49 of 93 patients after a mean stenting period of 16 months and 73% of these patients remained pain-free without a stent during a mean follow-up of 3.8 years.33 In the second study, following a median stenting duration 463

SECTION 3 APPROACH TO CLINICAL PROBLEMS

of 23 months, 62% of the patients maintained satisfactory pain control without pancreatic stent replacement during a median follow-up of 27 months.36 The only significant predictive factor of the need of pancreatic restenting within one year of stent removal was the presence of pancreas divisum. Interestingly, the majority of patients with pain recurrence requiring restenting relapsed during the first year after removal of the stent and almost all of them relapsed within two years. Therefore, if a patient remains stable during the first year after stent removal, subsequent relapse and need for restenting is unlikely. It is interesting to note that if a patient has frequent pain relapses due to stent clogging but good control of pain when a patent stent is in place, the decision for elective pancreaticojejunostomy can be considered as there is a high chance for good outcome after surgical pancreatic decompression. This further reinforces the idea that endotherapy should be performed within multidisciplinary teams. From the latter perspective, data are clear that pancreatic stenting does not complicate subsequent surgical procedures when they are indicated.38 In an attempt to decrease the duration of stenting, Costamagna’s group was the first to propose placement of multiple stents into the pancreas for a period of 6–12 months before removal.21 These endoscopists inserted as many stents as possible, contingent upon the tightness of the stricture and the pancreatic duct diameter (a median of 3). After removal of the stents, 84% of 19 patients remained asymptomatic for a mean follow-up of 38 months. Additional information gleaned from these latter patients is that the majority of them have all stents occluded at time of removal, yet no pain relapse. This suggests that pancreatic juice can still flow through the space located between the plastic tubes and that a more aggressive approach of dominant pancreatic strictures might decrease the duration of stenting required to provide long-term pain relief. Another area needing further investigation in patients with distal strictures, is the long-term efficacy of an iatrogenic pancreaticoduodenal fistula. The latter can then be maintained by placement of one or two stents.39 This technique, can be also applied to patients with a complete obstruction of the main pancreatic duct and has the potential advantage of creating a true pancreaticoduodenal fistula that might not be dependent on stent patency. The fistula would act more as a wick comparable to the communication created after drainage of a pancreatic pseudocyst associated with a disconnected main pancreatic duct.

Impact of pancreatic duct drainage on pancreatic endocrine and exocrine functions In contrast to the multicentric study published by Rösch et al., our long-term outcome study suggests that endoscopic ductal drainage including ESWL can delay the development of clinical steatorrhea by about 10 years when compared to the natural history of chronic pancreatitis patients.10–12 The risk of new onset steatorrhea was higher in alcoholic patients and also significantly associated with long duration of symptomatic ductal obstruction before treatment, suggesting that early ductal decompression in the course of the disease may be beneficial. However, in the setting of painless steatorrhea endotherapy does not appear warranted at this time. Moreover, previous studies have confirmed that the development of diabetes mellitus was not prevented by pancreatic duct drainage. Rather it appeared to be a consequence of ongoing alcohol abuse suggesting that only the exocrine pancreatic function may be dependent on early relief of ductal obstruction.11,28,40 464

DISCUSSION There are now multiple large series with long follow-up which demonstrate that pancreatic endotherapy for painful chronic pancreatitis is effective and should be first-line interventional management. There are still criticisms, however, and papers which suggest that this treatment is experimental and should be conducted only in the setting of clinical trials.41 One of the criticisms is the absence of sham-controlled trial, something very difficult to undertake in a referral center where patients with severe pain are referred for treatment. Over a 3-year period, we were able to include only 8 patients in such a trial currently ongoing in our institution. This number represents only 5% of the new patients treated. A recent publication has reported the results of pancreatic duct drainage in a subgroup of patients with continuous pain and a dilated duct.42 Authors observed 100% complete pain relief and analgesic discontinuation after endotherapy, suggesting that in this particular group, MPD drainage is at least better than a placebo. Another discussion centers around whether endotherapy challenges surgery in the treatment of pain. The first published, randomized trial comparing endotherapy with surgery disclosed a similar efficacy for short-term pain relief while surgery was better for mid-term pain control.43 However, surgery included resection in 80% of patients, a procedure difficult to compare with ductal drainage. Moreover, ESWL was not available for endoscopic treatment (which, in our experience, would render treatment not feasible in 44% of cases) and repeated endotherapy was not available in case of symptom recurrence.15 Multiple previous studies have demonstrated the need for such retreatment during the early period following initially directed endoscopic decompression.15,26 Another trial, recently published,44 reported better efficacy at 2 years following surgery (75% vs 32%) for pain relief. However, in this study, stenting in case of stricture was only maintained for a median of 6 months, a policy previously shown to be ineffective for long-term pain relief 37 and the vast majority of patients had tight strictures. Randomized studies will be helpful to better establish the efficacy of this therapy.45 Moreover, standardization of the endoscopic approach (ESWL, duration of stenting in case of strictures, multidisciplinary units with the ability to perform additional interventions in the early phase of endotherapy) is required. Measurement of outcomes is also important as most pain relapses following endotherapy occur within one year after initial treatment.12 After surgery, in turn, relapse commonly occurs after a median of 6–7 years.10 A final issue is to define whether or not we are doing too many procedures in these patients. We have learned from Japanese series that ESWL alone, without any endoscopic therapy, is able to relieve pain in many patients.16,31 This is a likely consequence of minute fragmentation of calcium carbonate stones, especially in patients with a single stone located in the head of the pancreas. We have recently conducted a RCT in this particular group of patients, comparing ESWL alone as an initial treatment vs ESWL plus endotherapy.46 We observed similar clinical benefits and only 31% of the patients from the ESWL alone required endotherapy over a median 4 years follow-up (Fig. 43.6). This is another argument to support the proposition that ESWL remains the cornerstone technology to manage these patients and it has proven to be an incentive to critically look at even less invasive procedures.

Chapter 43 Chronic Pancreatitis: Stones and Strictures

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21. Costamagna G, Bulajic M, Tringali A, et al. Multiple stenting of refractory pancreatic duct strictures in severe chronic pancreatitis: long-term results. Endoscopy 2006; 38:254–259. 22. Guda NM, Partington S, Freeman ML. Extracorporeal shock wave lithotripsy in the management of chronic calcific pancreatitis: a meta-analysis. JOP 2005; 6:6–12. 23. Schneider HT, May A, Benninger J, et al. Piezoelectric shock wave lithotripsy of pancreatic duct stones. Am J Gastroenterol 1994; 89: 2042–2048. 24. Dumonceau JM, Devière J, Le Moine O, et al. Endoscopic pancreatic drainage in chronic pancreatitis associated with ductal stones: long-term results. Gastrointest Endosc 1996; 43:547–555. 25. Smits ME, Rauws EAJ, Tytgat GNJ, et al. Endoscopic treatment of pancreatic stones in patients with chronic pancreatitis. Gastrointest Endosc 1996; 43:556–560. 26. Farnbacher MJ, Schoen C, Rabenstein T, et al. Pancreatic duct stones in chronic pancreatitis: criteria for treatment intensity and success. Gastrointest Endosc 2002; 56:501–506. 27. Costamagna G, Gabbrielli A, Multignani M, et al. Extracorporeal shock wave lithotripsy of pancreatic stones in chronic pancreatitis: immediate and medium-term results. Gastrointest Endosc 1997; 46:231–236. 28. Adamek HE, Jakobs R, Buttmann A, et al. Long-term follow-up of patients with chronic pancreatitis and pancreatic stones treated with extracorporeal shock wave lithotripsy. Gut 1999; 45:402–405. 29. Brand B, Kahl M, Sidhu S, et al. Prospective evaluation of morphology, function and quality of life after extracorporeal shockwave lithotripsy and endoscopic treatment of chronic calcific pancreatitis. Am J Gastroenterol 2000; 95:3428–3438. 30. Kozarek RA, Brandabur JJ, Ball TJ, et al. Clinical outcomes in patients who undergo extracorporeal shock wave lithotripsy for chronic calcific pancreatitis. Gastrointest Endosc 2002; 56: 496–500. 31. Ohara H, Hoshino M, Hayakawa T, et al. Single application extracorporeal shock wave lithotripsy is the first choice for patients with pancreatic duct stones. Am J Gastroenterol 1996; 91:1388–1394. 32. Tadenuma H, Ishihara T, Yamaguchi T, et al. Long-term results of extracorporeal shock wave lithotripsy and endoscopic therapy for pancreatic stones. Clin Gastroenterol Hepatol 2005; 3:1128–1135. 33. Binmoeller KF, Jue P, Seifert H, et al. Endoscopic pancreatic stent drainage in chronic pancreatitis and a dominant stricture: longterm results. Endoscopy 1995; 27:638–644. 34. Cremer M, Devière J, Delhaye M, et al. Stenting in severe chronic pancreatitis: results of medium-term follow-up in 76 patients. Endoscopy 1991; 23:171–176. 35. Sherman S, Lehman GA, Hawes RH, et al. Pancreatic ductal stones: frequency of successful endoscopic removal and improvement in symptoms. Gastrointest Endosc 1991; 37:511–517. 36. Eleftheriadis N, Dinu F, Delhaye M, et al. Long-term outcome after pancreatic stenting in severe chronic pancreatitis. Endoscopy 2005; 37:223–230. 37. Ponchon T, Bory RM, Hedelius F, et al. Endoscopic stenting for pain relief in chronic pancreatitis: results of a standardized protocol. Gastrointest Endosc 1995; 42:452–456. 38. Boerma D, van Gulik TM, Rauws EAJ, et al. Outcome of pancreaticojejunostomy after previous endoscopic stenting in patients with chronic pancreatitis. Eur J Surg 2002; 168:223–228. 39. Tessier G, Bories E, Arvanitakis M, et al. EUS guided pancreaticogastrostomy and pancreaticobulbostomy for the treatment of pain in patients with pancreatic ductal dilatation 465

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inaccessible for transpapillary endoscopic therapy. Gastrointest Endosc 2007; 65:233–241. 40. Malka D, Hammel P, Sauvanet A, et al. Risk factors for diabetes mellitus in chroinc pancreatitis. Gastroenterology 2000; 119: 1324–1332. 41. Mel Wilcox C. Endoscopic therapy for pain in chronic pancreatitis: is it time for the naysayers to throw in the towel? Gastrointest Endosc 2005; 61:582–586. 42. Gabbrielli A, Pandolfi M, Mutignani M, et al. Efficacy of main pancreatic-duct endoscopic drainage in patients with chronic pancreatitis, continuous pain, and dilated duct. Gastrointest Endosc 2005; 61:576–581.

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43. Dite P, Ruzicka M, Zboril V, et al. A prospective, randomized trial comparing endoscopic and surgical therapy for chronic pancreatitis. Endoscopy 2003; 35:553–558. 44. Cahen D, Gouma DJ, Nio Y, et al. Endoscopic versus surgical drainage of the pancreatic duct in chronic pancreatitis. N Engl J Med 2007; 356:676–684. 45. Elta GH. Is there a role for the endoscopic treatment of pain in chronic pancreatitis? N Engl J Med 2007; 356:727–729. 46. Dumonceau JM, Costamagna G, Tringali A, et al. Treatment for painful calcified chronic pancreatitis: extracorporeal shock wave lithotripsy versus endoscopic treatment: a randomized controlled trial. Gut 2007; 56:545–552.

SECTION 3

Chapter

44

APPROACH TO CLINICAL PROBLEMS

Suspected IPMN and Cystic Lesions of the Pancreas William R. Brugge

INTRODUCTION Cystic lesions of the pancreas consist of a spectrum of benign, premalignant, and variably invasive malignancies. In the past, cystic neoplasms of the pancreas were thought to be relatively rare, but the widespread use of cross-sectional imaging has dramatically increased the frequency of diagnosis. Although the vast majority of the lesions are discovered incidentally, large or invasive lesions may produce sufficient symptoms to cause the patient to seek medical attention. Cystic neoplasms are often confused or misdiagnosed as pseudocysts. Alternatively, peripancreatic collections of inflammatory fluid may morphologically mimic cystic neoplasms. Furthermore, the presenting symptoms of pseudocysts may be identical to the symptoms associated with cystic neoplasms. Cystic neoplasms of the pancreas are traditionally organized by the type of lining epithelium since this feature dominates the risk of malignancy and management (Table 44.1).1 There are three types of mucinous lesions, benign mucinous cystadenomas, malignant mucinous cystic lesions, and intraductal papillary mucinous neoplasms (IPMNs). The non-mucinous lesions include serous cystadenomas, cystic endocrine tumors and other rare lesions.

PREVALENCE The prevalence of pancreatic cysts has been examined with autopsy examinations of the pancreas in adults without known pancreatic disease. The prevalence of pancreatic cysts found at autopsies in Japan was approximately 73 of 300 (24.3%) cases.2 The prevalence of cysts increased with increasing age of the patient. The cysts were located throughout the pancreatic parenchyma and were not related to chronic pancreatitis. The epithelium of the cysts displayed a spectrum of neoplastic change, including atypical hyperplasia (16.4%) to carcinoma in situ (3.4%). The malignancy simulated pancreatic adenocarcinoma and arose from the epithelium lining the cyst. The prevalence of pancreatic cysts in the United States has been estimated in patients undergoing MRI for a variety of medical problems.3 This study revealed that approximately 15–20% of 1444 patients had at least one pancreatic cyst. Older patients are more likely to have a cyst than younger patients. Screening abdominal ultrasound in a younger population revealed that (0.21%) of 130,951 adults had a pancreatic cystic lesion.4

CLINICAL EPIDEMIOLOGY Mucinous cystic neoplasms account for approximately 2–5% of all exocrine pancreatic tumors and are the more common type of

cystadenoma. Women are affected far more commonly than men (9 : 1 ratio), with a mean age at diagnosis in the fifth decade. Intraductal papillary mucinous neoplasms share many of the features of mucinous cystic neoplasms. Their true incidence is uncertain, but estimates range from 1% to 8% of all pancreatic tumors. IPMNs affect men and women equally or men predominantly, depending on the reported series, and they tend to occur in an older age group than MCNs. Serous cystadenomas have been estimated to account for about 25% of all cystic neoplasms of the pancreas.5 Estimates of the incidence and prevalence vary. Using surgical pathology studies, it has been estimated that serous cystadenomas account for about 1–2% of all exocrine pancreatic neoplasms. Serous cystadenomas occur only in adults with a median age in the sixth or seventh decade. The vast majority of patients with serous cystadenomas are female.6 Traditionally about 1/2 of tumors are discovered as incidental findings during abdominal imaging or surgery or at autopsy.

RISK FACTORS FOR CYSTIC LESIONS In the vast majority of patients with a cystic lesion, no risk factor is apparent. Von Hippel–Lindau (VHL) syndrome is the best-described inherited disorder associated with cystic lesions.7 In the largest series to date, pancreatic involvement was observed in 122/158 patients (77.2%) and included true cysts (91.1%), serous cystadenomas (12.3%), neuroendocrine tumors (12.3%), or combined lesions (11.5%).

PATHOGENESIS The pathogenesis of cystic neoplasms of the pancreas is poorly understood. Serous cystadenomas are strongly associated with mutations of the VHL gene, located on chromosome 3p25.8 The VHL gene is likely to play an important role in the pathogenesis of sporadic serous cystadenomas. In one study, 70% of the sporadic serous cystadenomas studied demonstrated loss of heterozygosity (LOH) at 3p25 with a VHL gene mutation in the remaining allele.9 The mutations in the VHL gene probably affect most commonly the centroacinar cell and result in hamartomatous proliferation of these small cuboidal cells. The expression of keratin in clear epithelial cells resembles that in ductal and/or centroacinar cells and is most likely responsible for the fibro-collagenous stroma.10 The pathogenesis of mucinous cystic neoplasms and intraductal papillary mucinous neoplasms (IPMN) is likely very different compared to serous cystadenomas. K-ras mutations are present only in mucinous cystic neoplasms but not in serous microcystic adenomas. 467

SECTION 3 APPROACH TO CLINICAL PROBLEMS

Tumor type

Gender

Age

Morphology

Type of epithelium

Risk of malignancy

Mucinous cystadenoma Mucinous cystic neoplasm Intraductal papillary mucinous tumor Serous cystadenoma

Female Female Mixed

Middle-aged Middle-aged Elderly

Mucinous Malignant mucinous Papillary mucinous

Moderate High Moderate

Female

Middle-aged

Unilocular Associated mass Unilocular, septated, associated dilated ducts Microcystic

Low

Cystic endocrine tumor Solid cystic pseudopapillary tumor

Mixed Female

Middle-aged Young

Associated mass Mixed solid and cystic

Serous (PAS positive for glycogen) Endocrine Endocrine-like

Low Low

Table 44.1

In addition, LOH at 3p25, the chromosomal location of VHL gene, was present in 57% (8/14) of serous microcystic adenomas compared with 17% (2/12) of mucinous cystic neoplasms in one study.11 Mucinous cystic neoplasms frequently contain mutations of the Kras oncogene and p53 tumor suppressor gene, and the frequency of these mutations increases with increasing degrees of dysplasia in the neoplasm.12 The frequency of k-ras mutation in mucinous cystic neoplasms is linearly related to the grades of atypia.13 However, the degree of atypia in IPMT does not seem to correlate with the presence of k-ras mutations. LOH of the p16 gene was observed with increasing degrees of histological atypia in IPMN, whereas LOH of the p53 gene was seen only in invasive carcinomas. The distribution of loss of heterozygosity in 9p21(p16) and 17p13(p53) of IPMT lesions is mostly clonal, without the presence of genetic alterations. The identical genetic statuses in the precursor lesions are consistent with the presence of clonal progression during the development of this tumor.14

PATHOLOGY Serous cystadenomas (Fig. 44.1) Serous cystadenomas are benign, solitary, cystic tumors that arise from centroacinar cells. Although the majority of serous cystadenomas are microcystic, there are two other variants based on growth pattern: macrocystic and solid. Microcystic serous cystadenomas are composed of multiple small thin-walled cysts with a honeycomb-like appearance on cross section. Microcystic serous cystadenomas may grow to a large diameter over the long term and the large lesions often have a fibrotic or calcified central scar. Macrocystic serous cystadenomas are composed of far fewer cysts, and the diameter of each cyst varies from microcystic to large cavities.15 The presence of discrete, large cystic cavities mimics the appearance of mucinous lesions. However, the cyst fluid from serous cystadenomas is nonviscous and may contain blood as a result of the vascular nature of the lesions. All serous lesions contain a prominent fibrous stroma, glycogenrich epithelial cells, endothelial and smooth muscle cells.16 Ultrastructurally, fibrocollagenous stroma is composed of myofibroblasts and endothelial cells embedded in thick collagen bundles.10 Estrogen and progesterone receptors are not present. Mucinous cystic neoplasms Mucinous cystic neoplasms (MCNs) are composed of discrete individual locules that vary in diameter. MCNs are lined by mucinproducing cells in a columnar epithelium. The World Health Organization classification catalogues MCNs into three types, based 468

Fig. 44.1

Gross photograph of a serous cystadenoma.

on the degree of epithelial dysplasia: benign, borderline, and malignant. The degree of atypia of the tumor is classified according to the most advanced degree of dysplasia/carcinoma present. Mucinous cystic neoplasms of the pancreas often contain a unique, highly cellular (so-called “ovarian”) stroma that often contains estrogen and progesterone receptors. It occurs almost exclusively in female patients, although rare cases of MCNs with ovarian stroma in male patients have been encountered. Many authorities have restricted the very definition of MCNs to include only those cystic mucinous tumors that contain ovarian stroma. The cyst fluid from MCNs is often viscous and clear. IPMNs are similar to MCNs in that they are cystic tumors that secrete mucin. However, IPMNs are characterized by a unique papillary epithelium and arise from ductal epithelium. The presence of a papillary neoplasm and obstructing mucus causes the pancreatic duct to dilate. The degree of ductal ectasia produced varies with the degree of mucin production, but duct dilation great enough to be seen on imaging studies or gross pathologic examination is a diagnostic feature of the diagnosis. Mucin production may be so excessive that mucin will be spontaneously secreted out of the ampulla. The degree of dysplasia exhibited by the epithelium may range from

Chapter 44 Suspected IPMN and Cystic Lesions of the Pancreas

mild to moderate to severe (carcinoma in situ), and the foci of early malignancy may be evident by the presence of mural nodules.17 The solid malignancies that arise from IPMN are more likely to have papillary features, as compared to typical pancreatic malignancies that arise from the main pancreatic duct.18

Cystic endocrine neoplasms Cystic neoplasms are composed of neuroendocrine tissue. The cystic lesions are not true cysts since they are composed of centralized tumor necrosis. The lesions are rare and comprise 0.5–4% of all primary pancreatic neoplasms. The classic neuroendocrine cystic tumor is populated with a characteristic small, granular population of cells that are stainable for immunoreactive hormones, chromogranin and synaptophysin.19 It is rare for the cystic endocrine tumors to produce sufficient hormones to be clinically active. Cystic endocrine tumors are seen in association with Von Hippel–Lindau syndrome.20 A related cystic lesion, the solid pseudopapillary tumor, contains cells with neuroendocrine characteristics.21 The tumor often contains areas of hemorrhage and necrosis as well as cystic components. These neoplasms exhibit low-grade malignant behavior and have an excellent prognosis when resected, but a small percent metastasize.

CLINICAL PRESENTATION Most patients with a pancreatic cystic lesion have non-specific symptoms.22 The cystic lesion is usually found with CT or US imaging

Fig. 44.2

Gross photograph of a mucinous cystic neoplasm.

performed for the evaluation of another condition. When symptoms are present, the most common presentation is recurrent abdominal pain, nausea, and vomiting as result of mild pancreatitis.22 Cystic lesions that cause duct compression or involvement of the main pancreatic duct are prone to cause pancreatitis. Chronic abdominal pain and jaundice are rare presentations of a cystic lesion and suggest a malignancy or a pseudocyst. Patients with a cystic malignancy will present with symptoms and signs similar to pancreatic cancer, i.e. pain, weight loss, and jaundice.23 Pseudocysts may arise after an episode of acute pancreatitis or insidiously in the setting of chronic pancreatitis and are associated with chronic abdominal pain. It is common for cystic lesions associated with pancreatitis to be diagnosed as pseudocysts and be confused with cystic neoplasms that also cause pancreatitis.24

DIFFERENTIAL DIAGNOSIS The differential diagnosis of a cystic lesion of the pancreas is very wide and often causes confusion. Since the treatment of a pseudocyst and cystic neoplasm are so different, it is incumbent on the clinician to first differentiate between these major categories of lesions. Although it is unusual for a patient with a pseudocyst to present without preceding symptoms, it may occur in mild chronic pancreatitis. Evidence of inflammatory changes or calcifications in the pancreas is suggestive of a pancreatic pseudocyst. However, in the initial setting of mild pancreatitis it may be difficult to differentiate between a cystic neoplasm that has caused pancreatitis and a small pseudocyst that has formed as a result of pancreatitis. If a cystic lesion has been present for many years, it is highly likely that the lesion represents a cystic neoplasm. Congenital cysts of the pancreas are rare.25 Once a pancreatic pseudocyst has been excluded, attention should be focused on the differential between the types of cystic neoplasms. The principal differentiation is between mucinous and serous lesions because the fundamental difference in management is based on the neoplastic potential of mucinous lesions. The non-neoplastic serous cystadenomas may be diagnosed on the initial imaging test because of their typical microcystic morphology. Once a serous lesion has been confidently diagnosed, the lesion may be followed by serial imaging, looking for evidence of growth of organ impingement. In contrast, the approach to mucinous lesions is quite different. The underlying risk of malignancy or the development of malignancy often results in resection of the lesion. Under some clinical circumstances, such as patients who are at high risk for complications of pancreatectomy, differentiation between benign and grossly malignant mucinous lesions is important. The risk of surgery must be weighed against the risk of malignancy in the decision-making process. The risk of surgery must also take into account the variation in risk that is inherent in the location of the lesion.

Type of lesion

Morphology

Location

Cytology

CEA (ng/ml)

Serous Mucinous IPMT Pseudocyst

Microcystic Macrocystic Mixed Unilocular

Evenly distributed Tail Head Evenly distributed

Bland PAS+ Mucinous Mucinous Pigmented histiocytes

<0.5 >200 >200 <200

Table 44.2 469

SECTION 3 APPROACH TO CLINICAL PROBLEMS

DIAGNOSTIC METHODS CT is an excellent test for cystic lesions of the pancreas because of its widespread availability and ability to detect cysts (Fig. 44.3).26 MR imaging is used increasingly because of its ability to determine if there is involvement of the main pancreatic duct.27 Ultrasonography whether performed transabdominally or intraoperatively is generally not helpful.28 Recently PET scanning has been shown to be positive in a high percentage of malignant cystic lesions.29 Although seen in less than 20 percent of lesions, demonstration of a central scar by CT or MR is a highly diagnostic feature of a serous cystadenoma.30 The honey-combed or microcystic appearance of the lesion is commonly used to provide a diagnosis. However, macrocystic serous cystadenomas are difficult to diagnose with cross-sectional imaging because of the morphologic similarities with mucinous lesions.15,31 The presence of multiple small thin-walled cysts is suggestive of Von Hippel–Lindau syndrome.32 Mucinous cystic neoplasms, in contrast, are commonly diagnosed with CT based on the unilocular or macrocystic characteristics.33 Although not frequently seen, the finding of peripheral calcification by CT is specific for a mucinous cystic neoplasm. Intraductal papillary mucinous neoplasms (IPMN) may involve the main pancreatic duct exclusively, a side branch or both. MRCP can demonstrate the diagnostic findings of pancreatic duct dilation, mural nodules, and ductal connection better than ERCP.34 However, ERCP can demonstrate the intraductal filling defects, mucin extrusion, and cystic side branches that are associated with IPMN in 70–90% of patients.35,36 Despite these imaging features, the ability to accurately diagnose a specific cystic lesion and to determine whether malignancy is present by CT and MR remains uncertain (Fig. 44.4). The diagnosis of a pancreatic pseudocyst is more dependent upon the clinical history and the associated findings of chronic pancreatitis. Pancreatic pseudocysts appear as unilocular fluid-filled cavities associated with parenchymal changes such as calcifications and atrophy. Recently endoscopic ultrasound (EUS) has been used to diagnose cystic lesions of the pancreas and guide fine needle aspiration (FNA).37 The detailed imaging features of cystic neoplasms by EUS do not appear to be sufficiently accurate to differentiate between benign and malignant cystadenomas unless there is evidence of a

Fig. 44.3 CT scan of a mucinous cystic neoplasm in the tail of the pancreas. 470

solid mass or invasive tumor (Fig. 44.5).38 EUS is also very sensitive for detecting IPMN lesions, but imaging alone may not be sufficient for differentiating between benign and malignant lesions.39,40 The strength of EUS is its ability to detect and aspirate small cystic lesions with a high level of safety.41 EUS is more accurate in the evaluation of lesions less than 3 cm in diameter.42 The macrocystic variant of serous cystadenomas can be diagnosed with EUS using a combination of a thick cyst wall, the presence of microcysts, and a low cyst fluid CEA.43 The fluid contents of cystadenomas are often analyzed for cytology.44 However, the low cellular content of cyst fluid has hampered the use of the cytologic analysis of cyst fluid. Small, cuboidal cells in cytologic specimens are diagnostic of serous cystadenomas.

Fig. 44.4

CT scan of a mucinous cystadenocarcinoma.

Fig. 44.5 EUS image of a mucinous cystadenocarcinoma: note the mass in the wall of the cyst.

Chapter 44 Suspected IPMN and Cystic Lesions of the Pancreas

In contrast, mucinous cystadenoma may have large secretory epithelial cells with evidence of mucin secretion or atypia.45 Only inflammatory cells should be present in the fluid aspirated from pseudocysts. A variety of cyst fluid tumor markers have been studied to help differentiate between the major types of cystic neoplasms. Serum 19-9 is elevated in frank cystic malignancies.46 A number of glycoproteins are present in the epithelium of mucinous neoplasms and are secreted into the cyst fluid.47 The presence of extracellular mucin in aspirated cyst fluid is moderately predictive of a mucinous neoplasm.48 Several studies suggest that carcinoembryonic antigen (CEA) or CA 72-4 are useful for identifying mucinous lesions.49,50 These carbohydrate antigens are secreted by the epithelium lining mucinous lesions and may be present in high concentrations. Cyst fluid concentrations of CEA and CA 72-4 are very low in serous cystadenomas.51 Despite considerable overlap between mucinous and non-mucinous cysts, cyst fluid CEA is the most accurate marker.50,52 Cyst fluid CEA of less than 5 ng/ml is highly diagnostic of serous cystadenomas and values greater than 800 are predictive of mucinous lesions.52 Recently molecular studies of cyst fluid DNA have revealed k-ras, tumor suppressor gene mutations, and altered telomerase activity in mucinous cystic lesions.12,53 Intraductal papillary mucinous neoplasms can be evaluated with endoscopic retrograde cholangiopancreatography (ERCP) or EUS (Fig. 44.6).54 Prior to ERCP or EUS, the endoscopic finding of a patulent ampulla filled with mucin is diagnostic of an intraductal papillary mucinous neoplasm. Contrast retrograde pancreatography will demonstrate the characteristic findings of mucinous filling

defects within the duct, diffuse ductal dilation, and cystic dilation of side branches.55 MRCP may be more sensitive for detecting the side branch lesions of IPMN.56 EUS may assist in the detection of malignancy arising from intraductal papillary mucinous neoplasms by demonstrating focal nodules, invasive lesions and guiding fine needle aspiration of suspicious lesions.57 EUS can also be used to monitor IPMN lesions, looking for increases in the size of cysts and the diameter of the main pancreatic duct.58

DIAGNOSTIC EVALUATION Patients suspected of having a cystic neoplasm of the pancreas should undergo a CT scan with contrast as the initial test. If no lesion is seen in the pancreas, it is very unlikely that a clinically significant neoplasm is present. MR imaging, particularly MRCP, may be substituted for CT scanning (Fig. 44.7). If the CT scan demonstrates a diagnostic finding, such as a classic microcystic serous cystadenoma, a malignant cystic mass, or pancreatitis with a fluid collection, no further evaluation is necessary. If the patient is a young woman and there is a solitary, unilocular cystic lesion in the tail of the pancreas, the patient should undergo surgical resection. Indeterminate lesions should undergo EUS with FNA. Aspirated cyst fluid should be analyzed for CEA, cytology, and amylase (Table 44.3). Preference should be given to sending the fluid for CEA as opposed to cytology in small mucinous lesions. Cytology should be used preferentially in malignant-appearing cystic lesions. IPMN lesions should have FNA of cystic lesions, an enlarged pancreatic duct, and focal mass lesions. Cytology should be used preferentially.

Fig. 44.7 MRCP of side branch IPMT of the head of the pancreas.

Fig. 44.6 ERCP of IPMT: note the dilated and tortuous main pancreatic duct.

Type of lesion

First priority

Second priority

Serous

CEA

Mucinous

Malignant

Third priority

Experimental

Imaging

Fluid cytology

VHL gene testing

CEA

Cytology

Subjective assessment of viscosity

k-ras LOH analysis

Tissue cytology

Fluid cytology

CEA

k-ras LOH analysis

Table 44.3 Use of FNA samples: prioritizing the use of samples 471

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TREATMENT Surgical resection is the treatment of choice for pre-malignant cystic neoplasms. The decision to resect a lesion, however, is based on the presence or absence of symptoms, the risk of malignancy, and the surgical risk of the patient. High-risk patients with low-grade cystic neoplasms may be monitored with periodic CT/MRI scanning or EUS-FNA.59 Experimentally, high-risk patients have been treated with EUS-guided ethanol lavage which safely produces variable ablation of the cyst epithelium.60 Small cystic lesions in the elderly can be safely monitored.61 The increasing safety of surgical resection has prompted the use of surgery for a wider range of lesions.62 However, serous cystadenomas do not require resection except for relief of symptoms.63 Since most mucinous cystic neoplasms are located in the tail of the pancreas, a distal pancreatectomy is sufficient for these pre-malignant lesions. Since intraductal papillary mucinous neoplasms invade the pancreas along ductal structures, it is important that

frozen section histology be used during surgery to assure negative margins.64,65

PROGNOSIS Cystic neoplasms are slow growing and 19% will demonstrate an increase in diameter at 16 months.66 Surgical resection has been associated with a morbidity of 27.9%, with a reoperation rate of 7.3% and a very low mortality rate.6 The overall 5-year survival for patients having IPMNs without invasive cancer was 77%, compared with 43% in those patients with an invasive component.67 The overall postoperative recurrence rate varies from 7% to 43%.68 Approximately 50% of patients will have evidence of malignancy in the resected specimen.69 Similar survival rates are seen in patients with mucinous cystic neoplasms.70 Side branch lesions arising from IPMN have a better prognosis than main duct IPMN.71 The worst prognosis is for advanced, transmural adenocarcinomas arising from mucinous lesions; the 5-year survival is only 30% for resected lesions.

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Brugge WR, Lauwers GY, Sahani D, et al. Cystic neoplasms of the pancreas. N Engl J Med 2004; 351:1218–1226. Kimura W, Nagai H, Kuroda A, et al. Analysis of small cystic lesions of the pancreas. Int J Pancreatol 1995; 18:197–206. Zhang XM, Mitchell DG, Dohke M, et al. Pancreatic cysts: depiction on single-shot fast spin-echo MR images. Radiology 2002; 223:547–553. Ikeda M, Sato T, Morozumi A, et al. Morphologic changes in the pancreas detected by screening ultrasonography in a mass survey, with special reference to main duct dilatation, cyst formation, and calcification. Pancreas 1994; 9:508–512. Compton CC. Serous cystic tumors of the pancreas. Semin Diagn Pathol 2000; 17:43–55. Bassi C, Salvia R, Molinari E, et al. Management of 100 consecutive cases of pancreatic serous cystadenoma: wait for symptoms and see at imaging or vice versa? World J Surg 2003; 27:319–323. Hammel P. Diagnostic value of cyst fluid analysis in cystic lesions of the pancreas: current data, limitations, and perspectives. J Radiol 2000; 81:487–490. Moore PS, Zamboni G, Brighenti A, et al. Molecular characterization of pancreatic serous microcystic adenomas: evidence for a tumor suppressor gene on chromosome 10q. Am J Pathol 2001; 158:317–321. Vortmeyer AO, Lubensky IA, Fogt F, et al. Allelic deletion and mutation of the von Hippel-Lindau (VHL) tumor suppressor gene in pancreatic microcystic adenomas. Am J Pathol 1997; 151: 951–956. Yasuhara Y, Sakaida N, Uemura Y, et al. Serous microcystic adenoma (glycogen-rich cystadenoma) of the pancreas: Study of 11 cases showing clinicopathological and immunohistochemical correlations. Pathol Int 2002; 52:307–312. Ahmad NA, Kochman ML, Brensinger C, et al. Interobserver agreement among endosonographers for the diagnosis of neoplastic versus non-neoplastic pancreatic cystic lesions. Gastrointest Endosc 2003; 58:59–64. Khalid A, McGrath KM, Zahid M, et al. The role of pancreatic cyst fluid molecular analysis in predicting cyst pathology. Clin Gastroenterol Hepatol 2005; 3:967–973.

13. Yoshizawa K, Nagai H, Sakurai S, et al. Clonality and K-ras mutation analyses of epithelia in intraductal papillary mucinous tumor and mucinous cystic tumor of the pancreas. Virchows Arch 2002; 441:437–443. 14. Wada K, Takada T, Yasuda H, et al. Does “clonal progression” relate to the development of intraductal papillary mucinous tumors of the pancreas? J Gastrointest Surg 2004; 8:289–296. 15. Khurana B, Mortele KJ, Glickman J, et al. Macrocystic serous adenoma of the pancreas: radiologic-pathologic correlation. AJR Am J Roentgenol 2003; 181:119–123. 16. Mohr VH, Vortmeyer AO, Zhuang Z, et al. Histopathology and molecular genetics of multiple cysts and microcystic (serous) adenomas of the pancreas in von Hippel-Lindau patients. Am J Pathol 2000; 157:1615–1621. 17. Tanaka M. Intraductal papillary mucinous neoplasm of the pancreas: diagnosis and treatment. Pancreas 2004; 28:282–288. 18. Furuta K, Watanabe H, Ikeda S. Differences between solid and duct-ectatic types of pancreatic ductal carcinomas. Cancer 1992; 69:1327–1333. 19. Kann P, Bittinger F, Engelbach M, et al. Endosonography of insulin-secreting and clinically non-functioning neuroendocrine tumors of the pancreas: criteria for benignancy and malignancy. Eur J Med Res 2001; 6:385–390. 20. Marcos HB, Libutti SK, Alexander HR, et al. Neuroendocrine tumors of the pancreas in von Hippel-Lindau disease: spectrum of appearances at CT and MR imaging with histopathologic comparison. Radiology 2002; 225:751–758. 21. Notohara K, Hamazaki S, Tsukayama C, et al. Solidpseudopapillary tumor of the pancreas: immunohistochemical localization of neuroendocrine markers and CD10. Am J Surg Pathol 2000; 24:1361–1371. 22. Wiesenauer CA, Schmidt CM, Cummings OW, et al. Preoperative predictors of malignancy in pancreatic intraductal papillary mucinous neoplasms. Arch Surg 2003; 138:610–617; discussion 617–618. 23. Holly EA, Chaliha I, Bracci PM, et al. Signs and symptoms of pancreatic cancer: a population-based case-control study in the

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distinguishing mucinous and serous lesions. Gastrointest Endosc 2004; 59:823–829. 44. Centeno BA, Warshaw AL, Mayo-Smith W, et al. Cytologic diagnosis of pancreatic cystic lesions. A prospective study of 28 percutaneous aspirates. Acta Cytol 1997; 41:972–980. 45. Recine M, Kaw M, Evans DB, et al. Fine-needle aspiration cytology of mucinous tumors of the pancreas. Cancer 2004; 102:92–99. 46. Sperti C, Pasquali C, Guolo P, et al. Serum tumor markers and cyst fluid analysis are useful for the diagnosis of pancreatic cystic tumors. Cancer 1996; 78:237–243. 47. Yamaguchi K, Enjoji M. Cystic neoplasms of the pancreas. Gastroenterology 1987; 92:1934–1943. 48. Walsh RM, Henderson JM, Vogt DP, et al. Prospective preoperative determination of mucinous pancreatic cystic neoplasms. Surgery 2002; 132:628–633; discussion 633–634. 49. Frossard JL, Amouyal P, Amouyal G, et al. Performance of endosonography-guided fine needle aspiration and biopsy in the diagnosis of pancreatic cystic lesions. Am J Gastroenterol 2003; 98:1516–1524. 50. Brugge WR, Lewandrowski K, Lee-Lewandrowski E, et al. Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study. Gastroenterology 2004; 126: 1330–1336. 51. Hammel P, Voitot H, Vilgrain V, et al. Diagnostic value of CA 72-4 and carcinoembryonic antigen determination in the fluid of pancreatic cystic lesions. Eur J Gastroenterol Hepatol 1998; 10: 345–348. 52. van der Waaij LA, van Dullemen HM, Porte RJ. Cyst fluid analysis in the differential diagnosis of pancreatic cystic lesions: a pooled analysis. Gastrointest Endosc 2005; 62:383–389. 53. Zhou GX, Huang JF, Li ZS, et al. Detection of K-ras point mutation and telomerase activity during endoscopic retrograde cholangiopancreatography in diagnosis of pancreatic cancer. World J Gastroenterol 2004; 10:1337–1340. 54. Telford JJ, Carr-Locke DL. The role of ERCP and pancreatoscopy in cystic and intraductal tumors. Gastrointest Endosc Clin N Am 2002; 12:747–757. 55. Dachman AH, Namieno T, Ichimura T, et al. Mucin-producing pancreatic tumors: comparison of MR cholangiopancreatography with endoscopic retrograde cholangiopancreatography. Radiology 1998; 208:231–237. 56. Koito K, Namieno T, Ichimura T, et al. Mucin-producing pancreatic tumors: comparison of MR cholangiopancreatography with endoscopic retrograde cholangiopancreatography. Radiology 1998; 208:231–237. 57. Sugiyama M, Atomi Y, Saito M. Intraductal papillary tumors of the pancreas: evaluation with endoscopic ultrasonography. Gastrointest Endosc 1998; 48:164–171. 58. Kobayashi G, Fujita N, Noda Y, et al. Mode of progression of intraductal papillary-mucinous tumor of the pancreas: analysis of patients with follow-up by EUS. J Gastroenterol 2005; 40:744–751. 59. Irie H, Yoshimitsu K, Aibe H, et al. Natural history of pancreatic intraductal papillary mucinous tumor of branch duct type: followup study by magnetic resonance cholangiopancreatography. J Comput Assist Tomogr 2004; 28:117–122. 60. Gan SI, Thompson CC, Lauwers GY, et al. Ethanol lavage of pancreatic cystic lesions: initial pilot study. Gastrointest Endosc 2005; 61:746–752. 61. Kimura W, Makuuchi M. Operative indications for cystic lesions of the pancreas with malignant potential–our experience. Hepatogastroenterology 1999; 46:483–491. 62. Fernandez del Castillo CF, Targarona J, Thayer SP, et al. Incidental pancreatic cysts: clinicopathologic characteristics and comparison with symptomatic patients. Arch Surg 2003; 138:427–434.

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63. Le Borgne J, de Calan L, Partensky C. Cystadenomas and cystadenocarcinomas of the pancreas: a multiinstitutional retrospective study of 398 cases. French Surgical Association. Ann Surg 1999; 230:152–161. 64. Gigot JF, Deprez P, Sempoux C, et al. Surgical management of intraductal papillary mucinous tumors of the pancreas: the role of routine frozen section of the surgical margin, intraoperative endoscopic staged biopsies of the Wirsung duct, and pancreaticogastric anastomosis. Arch Surg 2001; 136: 1256–1262. 65. Chari ST, Yadav D, Smyrk TC, et al. Study of recurrence after surgical resection of intraductal papillary mucinous neoplasm of the pancreas. Gastroenterology 2002; 123:1500–1507. 66. Spinelli KS, Fromwiller TE, Daniel RA, et al. Cystic pancreatic neoplasms: observe or operate. Ann Surg 2004; 239:651–657; discussion 657–659.

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67. Sohn TA, Yeo CJ, Cameron JL, et al. Intraductal papillary mucinous neoplasms of the pancreas: an updated experience. Ann Surg 2004; 239:788–797; discussion 797–799. 68. Lai EC, Lau WY. Intraductal papillary mucinous neoplasms of the pancreas. Surgeon 2005; 3:317–324. 69. Falconi M, Salvia R, Bassi C, et al. Clinicopathological features and treatment of intraductal papillary mucinous tumour of the pancreas. Br J Surg 2001; 88:376–381. 70. Suzuki Y, Atomi Y, Sugiyama M, et al. Cystic neoplasm of the pancreas: a Japanese multiinstitutional study of intraductal papillary mucinous tumor and mucinous cystic tumor. Pancreas 2004; 28:241–246. 71. Kobari M, Egawa S, Shibuya K, et al. Intraductal papillary mucinous tumors of the pancreas comprise 2 clinical subtypes: differences in clinical characteristics and surgical management. Arch Surg 1999; 134:1131–1136.

SECTION 3

Chapter

45

APPROACH TO CLINICAL PROBLEMS

Endoscopic Drainage of Pancreatic Pseudocysts, Abscesses and Organized (Walled-Off ) Necrosis Todd H. Baron

BOX 45.1 KEY POINTS • Pancreatic fluid collections comprise pancreatic pseudocysts, abscesses, and organized pancreatic necrosis • Pancreatic pseudocysts may be acute or chronic • Endoscopic drainage of pancreatic fluid collections can be achieved using transmural (transgastric or transduodenal) and transpapillary drainage techniques, alone or in combination • The short-term outcome following endoscopic drainage of pancreatic fluid collections depends on the degree of liquid or solid components • The long-term outcome following endoscopic drainage of pancreatic fluid collections depends on the presence or absence of pancreatic ductal damage • Transmural drainage is usually required for drainage of pancreatic fluid collections

INTRODUCTION AND SCIENTIFIC BASIS Pancreatic pseudocysts, abscesses, and pancreatic necrosis are types of pancreatic fluid collections (PFCs) that arise as a consequence of pancreatic injury.1 At the basis of this pancreatic injury is disruption of the pancreatic duct or side branches. Ductal disruption can be due to acute pancreatic injury (acute pancreatitis, trauma, surgical resection or injury to the pancreas during abdominal surgery) or chronic injury (chronic pancreatitis, autoimmune pancreatitis). The sequela to this ductal injury is the formation of a collection of fluid with or without solid debris. Thus the basis of endoscopic therapy is directed at either the drainage of the fluid and solid components using a transmural approach and/or correction of ductal abnormalities using a transpapillary approach. Correction of pancreatic abnormalities may decrease the long-term recurrence rate and improve the outcome following successful resolution of a collection and can be assessed and treated endoscopically. This chapter will discuss the endoscopic approaches to PFCs.

SPECIFIC TYPES OF FLUID COLLECTIONS Classification systems exist for defining types of PFCs1 which are useful for understanding mechanisms of formation and making meaningful comparisons of therapies between or amongst disciplines. At the time of this writing, the classification and nomenclature for PFCs is being revised. When undertaking endoscopic therapy of a PFC, however, it is more important to make two main distinctions: (1) Is the collection composed primarily of liquid or does it contain significant solid debris? and (2) What is the status and etiology of the disruption of the main pancreatic duct? Using these two basic questions, an approach to drainage can be formulated for both the short-term and long-term approach of patients with PFCs. The approach to collections that are composed primarily of fluid is different than that of those containing significant solid debris, since liquefied collections can be managed with either placement of modest sized diameter stents via transpapillary or transmural approaches alone, whereas those with solid debris usually require aggressive transmural dilation to allow egress of solid material and placement of large-bore stents and irrigation catheters, and are associated with higher complication rates.

COLLECTIONS COMPOSED ENTIRELY OR PREDOMINANTLY OF LIQUID 1. Acute fluid collections: Acute fluid collections arise early in the course of acute pancreatitis, are usually peripancreatic in location, and usually resolve without sequelae but may evolve into pancreatic pseudocysts.1 2. Pancreatic pseudocysts (a) Acute pancreatic pseudocysts: Acute pseudocysts arise as a sequela of acute pancreatitis, require at least four weeks to form, and are devoid of significant solid debris. The mechanism of formation of an acute pancreatic pseudocyst is usually as a result of limited pancreatic necrosis that produces a pancreatic ductal leak (Fig. 45.1). Alternatively, areas of pancreatic and peripancreatic fat necrosis may completely liquefy over time and become a pseudocyst.2 Despite the requirement of at least 4 weeks for a pseudocyst to form, it is important to note that this time period in and of itself does not define the collection as a pancreatic pseudocyst. Patients with significant pancreatic necrosis (>30%) may evolve the early acute pancreatic necrosis and peripancreatic necrosis into a collection that 475

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resembles a pseudocyst radiographically, but has been present for more than 4 more weeks (see organized pancreatic necrosis below). By definition, if these collections contain significant solid debris, they are not pseudocysts and endoscopic treatment of these collections by typical pseudocyst drainage methods may result in infectious complications because of inadequate removal of solid debris.1,3,4 (b) Chronic pseudocysts: A chronic pseudocyst arises as a sequela of chronic pancreatitis due to downstream pancreatic obstruction from fibrotic strictures and/or stones.5 This results in a pancreatic ductal blowout (leak) and accumulation of pancreatic fluid. These collections do not contain solid debris and usually do not arise as a result of acute inflammatory processes (Fig. 45.2). 3. Infected pancreatic pseudocysts (in some nomenclatures also known as pancreatic abscesses1) 4. Pancreatic abscesses. True pancreatic abscesses have formerly been considered rare and not synonymous with infected pancreatic pseudocysts.1 However, for the purposes of this chapter and based

upon pending revisions of the existing nomenclature, an abscess will be considered as an infected PFC that contains little to no solid debris (as opposed to infected pancreatic necrosis which will be described later). It is my belief that using this definition, abscesses can be drained through modest sized catheters without need for irrigation or debridement.

INDICATIONS FOR DRAINAGE OF LIQUEFIED COLLECTIONS In general, the indications for drainage of a liquefied PFC are symptom driven and infection driven, not merely the presence of a collection by imaging studies. For many years, a size cut-off of approximately 6 cm or persistence of a collection for more than a certain amount of time was used a criterion for drainage. It has been established, however, that patients may remain asymptomatic with collections of 6 cm or more with little risk of complication such as rupture, infection, or bleeding,6 whereas endoscopic intervention is associated with a finite (and presumably higher) risk of

Fig. 45.1 Illustration of the mechanism of formation of an acute pancreatic pseudocyst. Limited necrosis of the main pancreatic duct produces a ductal leak with accumulation of amylase-rich fluid.

Fig. 45.2 Illustration of the mechanism of formation of a chronic pancreatic pseudocyst. Obstruction of the main pancreatic duct by stones and/or stricture produces a duct blowout with accumulation of amylaserich fluid.

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BOX 45.2 INDICATIONS AND CONTRAINDICATIONS • In general, the indications for drainage of pancreatic fluid collections are the presence of symptoms and/or infection • Pancreatic pseudocysts produce symptoms because of mass compression of surrounding structures, pancreatic leaks, and pancreatic fistulae • Prior to drainage it should be established that the collection is an inflammatory collection and not a true pancreatic cyst or cystic neoplasm • Prior to drainage it should be established whether the collection contains significant solid debris • Contraindication to any type of endoscopic drainage is free luminal perforation. Contraindications to transmural drainage include a distance of “free space” between the gastric or duodenal wall of more than 1 cm from the and presence of underlying coagulopathy.

Cystic pancreatic neoplasm Duplication cyst True pancreatic cyst Pseudoaneurysm Solid necrotic neoplasm (e.g. retroperitoneal sarcoma) Lymphocele Gallbladder

Table 45.1 Masqueraders of pancreatic fluid collections

complications. Progressive enlargement of a collection is one exception to symptoms that is cited as an indication for drainage1, although even then a patient can be followed until symptoms occur. Symptoms related to liquefied pancreatic collections include abdominal pain—often exacerbated by eating, weight loss, gastric outlet obstruction, obstructive jaundice, and leakage. The leakage results in pancreatic ascites and pancreatic fistulae and has been discussed in Chapter 40. Infection is considered an absolute indication for drainage.

PRE-DRAINAGE EVALUATION Prior to undertaking drainage of a liquefied pancreatic collection, a pre-drainage evaluation should be performed. The goals of the predrainage evaluation include the following: 1. Establish whether the collection represents a PFC or a “masquerader” of a PFC such as a cystic neoplasm7 or other entity (Table 45.1, Fig. 45.3). If the patient does not have a well-documented history of acute or chronic pancreatitis, the endoscopist should be wary that something other than a pseudocyst is present.8 With the development of endoscopic ultrasonography (EUS),

Fig. 45.3 Metastatic malignant fibrous histiocytoma detected in a woman with abdominal pain and “pancreatitis” mimicking a pancreatic pseudocyst. She had a previous known primary lesion. The lesion was diagnosed by EUS-FNA and resected for palliation.

cystic neoplasms have been better recognized and defined.9 Cystic neoplasms are discussed in more detail in Chapter 44. 2. Establish whether the collection is predominately liquid or contains significant solid debris. 3. Establish the relationship of the collection to surrounding lumenal and vascular structures. 4. Consider underlying etiologies of true pancreatic pseudocyst which have implications for alternative/adjuvant therapies such as pancreatic cancer,10 autoimmune pancreatitis,11 and intraductal pancreatic mucinous neoplasms. In addition to a complete history and physical examination, the following evaluation should be undertaken: 1. Coagulation profile in patients with a suspicion of coagulopathy and/or liver disease, especially when transmural drainage is considered. 2. Contrast-enhanced abdominal CT. This allows assessment of the precise location of the collection in relation to the stomach and duodenum in anticipation of possible transmural drainage. Additionally, the relationship of the collection to potential intervening vascular structures can be assessed. Surrounding varices from splenic vein or portal vein thrombosis may also be visualized. The finding of inhomogeneity within the collection suggests the presence of underlying solid debris and/or blood (Fig. 45.4). Consideration should be given to additional studies: 1. Endoscopic ultrasonography (EUS). EUS can be used prior to drainage to allow assessment for the presence of significant solid debris that may alter the management strategy. In addition, if there is uncertainty as to whether the collection represents a true pseudocyst or other non-inflammatory cystic lesion, EUS allows one to obtain a definitive diagnosis by using ultrasonographic features, aspiration and analysis of cyst contents, and biopsy of the cyst wall.12 Once the endoscopist is certain that the lesion in question is a PFC and the decision has been made to proceed with 477

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endoscopic drainage, EUS may be used to guide transmural drainage as discussed in the next section under endoscopic drainage methods. 2. MRI with or without MRCP. Magnetic resonance imaging (MRI) allows detection of the presence of solid debris,13 so that plans for removal and/or alternative drainage strategies can be chosen depending on local expertise and necrosis drainage preferences.

DRAINAGE TECHNIQUES Liquefied PFCs as described above may be drained transpapillary, transmurally, or using a combination of the two. The decision to use one approach over the other depends on the size of the collection, its proximity to the stomach or duodenum, and the ability to enter the pancreatic duct and/or reach the area of disruption. For example, although the intended approach to draining a pseudocyst that formed from an obstructing pancreatic duct stone may be transpapillary (Figs 45.5A–B), failure to negotiate a guidewire beyond the obstructing ductal stone may require transmural drainage. Assessment and treatment of the ductal stone at a later date by other techniques such as ESWL can then be performed (Figs 45.5C–E).

Transpapillary drainage

Fig. 45.4 CT scan obtained 4 weeks after clinically severe gallstone pancreatitis. Note large homogenous fluid collection posterior to the stomach with inhomogenous density (arrowheads) suggesting solid debris.

A

D

B

If the collection communicates with the main pancreatic duct, placement of a pancreatic endoprosthesis with or without pancreatic sphincterotomy is an approach that is useful, especially for collections measuring <6 cm that are not otherwise approachable transmurally.1 The proximal end of the stent (toward the pancreatic tail) may directly enter the collection or bridge the area of leak into the pancreatic duct upstream from the leak (Figs 45.6A–D). The latter is the preferred approach (Fig. 45.7), since it restores ductal continuity.14 In patients with chronic pseudocysts, it is important that the stent bridges any obstructive process (stricture or stone) between the duodenum and the leak. The diameter of pancreatic stent used is dependent on the pancreatic ductal diameter, although 7 Fr stents are most frequently used. In patients with chronic pancreatitis, endoscopic therapy of underlying pancreatic duct strictures and pancreatic stones may reduce the recurrence rate of pancreatic pseudocysts.1 The advantage of the transpapillary approach over the transmural approach is the avoidance of bleeding or perforation that may occur

C

E

Fig. 45.5 Patient with pseudocyst due to chronic pancreatitis. A pseudocyst (PC) is seen compressing duodenum; calcifications present near tail (arrows). B Lower cuts same patient. A large stone (arrow) is obstructing the main pancreatic duct. C Follow-up CT after transmural drainage and ESWL. Transduodenal stents can be seen (arrow). The prior stone has been fragmented (arrowhead). D At the time of duodenal stent removal pancreatography shows a stricture in the head (arrow). E Stone fragments were removed, the stricture was balloon dilated, and a pancreatic duct stent placed. 478

Chapter 45 Endoscopic Drainage of Pancreatic Pseudocysts, Abscesses and Organized (Walled-Off) Necrosis

A

C

B

D

Fig. 45.6 Transpapillary drainage of pancreatic pseudocyst. A CT scan. Collections are seen (arrows). B Pancreatogram shows leakage at the tail. C Transpapillary stent placed to tail. D Follow-up pancreatogram shows no leak.

with transmural drainage. The disadvantage of transpapillary drainage is that pancreatic stents may induce scarring of the main pancreatic duct in patients whose pancreatic duct is otherwise normal (i.e., patients with acute pseudocysts and small side branch disruption or those patients with leakage after surgical resection of the pancreatic tail, see Figure 16.22).

TRANSMURAL DRAINAGE Transmural entry devices The type of devices used to puncture through the gastric or duodenal wall into the collection can be divided into cautery and non-cautery devices. Cautery devices include standard diathermy wires (needle knife) and specialized fistulotomy devices (Cystotome, CST-10, Cook Endoscopy, Winston-Salem, NC). Non-cautery devices include EUS fine needle aspiration (FNA) needles and aspiration needles (BaronTM Aspiration Needle, BAN-18, Cook Medical).

Transmural entry techniques There is no standardized approach to this method of drainage and some endoscopists feel that EUS evaluation is mandatory prior to performing endoscopic transmural drainage of PFCs, although the superiority of EUS-guided versus non EUS-guided drainage has not been demonstrated.15 Approximately 50% of all respondents to a recent survey of transmural drainage practices claimed to use EUSguided transmural drainage.16 EUS-guided and non-EUS guided drainage will be discussed separately.

EUS-GUIDED TRANSMURAL DRAINAGE EUS imaging may theoretically reduce complications related to transmural entry of PFCs, although this has not been proven.16,17 There are two ways EUS can be used for transmural drainage. The first way, using either a radial or linear echoendoscope, is to localize the collection in relationship to surrounding structures and 479

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B A

Fig. 45.7 A Schematic of pancreatic duct leak B Illustration of ideal position of pancreatic duct stent placement across a leak site.

endoscopic landmarks. The optimal location of entry into the gastric or duodenal wall may be “marked” with contrast injection or mucosal biopsy; the echoendoscope is then removed and a therapeutic endoscope or duodenoscope is then used to perform transmural drainage by puncturing into the collection as described under non-EUS guided drainage below. The second way EUS may be used is to perform the evaluation and entry into the collection using direct EUS guidance with a linear echoendoscope similar to EUSguided FNA (Figs 45.8A–D). Using this approach either with a standard or Doppler-equipped echoendoscope, successful entry has been reported in up to 94% of patients with low complication rates, including those without an endoscopically visible extrinsic compression.18–20 Therefore, if EUS is readily available, consideration should be given to EUS assistance during transmural drainage. The lack of EUS availability, however, does not preclude transmural drainage except in the following instances: small “window” of entry based upon CT, especially in the absence of an endoscopically defined area of extrinsic compression or unusual location;1 coagulopathy or thrombocytopenia; documented intervening varices;21 and failed transmural entry using non-EUS-guided techniques.

NON-EUS-GUIDED TRANSMURAL DRAINAGE The collection is entered at a point of endoscopically visible extrinsic compression using electrocautery with or without prelocalization using a needle (Fig. 45.9a–c). An alternative is localization and entry into the collection using a needle which accepts an 0.035” guidewire (Fig. 45.10) without the use of electrocautery using the 480

Seldinger technique. Entry is confirmed by aspiration of fluid and/ or injection of radiopaque contrast (Figs 45.11A–C). This method may be safer than a cautery puncture for non-EUS guided entry since if unsuccessful entry occurs, the needle is simply withdrawn without adverse sequelae. Similarly, if bleeding occurs upon needle entry, if gross blood is aspirated, or if a visible hematoma develops, the needle is withdrawn to allow the vessel to tamponade. Another transmural entry site may be chosen during the same endoscopic session. Using this technique, successful non-EUS-guided transmural entry has been reported in 41/43 patients (95%) in lesions as small as 3 cm and without endoscopically visible extrinsic compression.22 Other authors have described successful drainage of non-bulging collections with or without EUS guidance.23

Stent placement Transmural drainage of liquefied pancreatic collections is achieved by placing one or more stents through the gastric or duodenal wall. After entry into the collection, the transmural tract is balloon dilated with a standard ERCP dilating balloon of 8–10 mm diameter (Fig. 45.11d) to allow placement of one or two 10 Fr stents (Fig. 45.11e). It is important to secure an ample length of guidewire into the collection with at least one 360 degree loop of wire (Figs 45.8d and 45.11d). The practice of enlarging the transmural tract using cautery and a sphincterotome has been abandoned because it is associated with an increased risk of bleeding. The type of stents used for transmural drainage may be straight or pigtail. Double pigtail stents are recommended for at least two reasons. First, they are less prone to migrate into or out of the collection. Secondly, recent data suggests that straight stents are associ-

Chapter 45 Endoscopic Drainage of Pancreatic Pseudocysts, Abscesses and Organized (Walled-Off) Necrosis

B

A

C

D

Fig. 45.8 EUS-guided drainage. A Illustration of EUS-guided transmural drainage of pancreatic fluid collection. B Ultrasonographic image taken during EUS-guided drainage of pancreatic pseudocyst showing needle entering the collection (arrowheads). C Illustration of guidewire passed through EUS needle. D Same patient as B, contrast has been injected through the FNA needle and a guidewire coiled into the collection. Subsequent stents were placed with successful drainage.

A

B

C

Fig. 45.9 Transmural drainage without EUS using the Cystotome (Cook Endoscopy). A Extrinsic compression with Cystotome in view. B Initial entry is made with the inner, smaller-sized cautery device. C The outer, larger (10 Fr) cautery portion is passed over the smaller one and through the wall of the collection. 481

SECTION 3 APPROACH TO CLINICAL PROBLEMS

ated with delayed bleeding complications resulting from impaction of the stent against the wall of the collection as it contracts around the stent.24 We routinely place one to two short-length (3–5 cm) 10 Fr double pigtail stents during transmural drainage. Stents are available from several companies. I use “standard” 10 Fr double pigtail stents (Cook Endoscopy, Winston-Salem, NC), although the tapered tip will not allow an inner guiding catheter to pass unless it is trimmed off. One must be careful when placing double pigtail stents to not push the entire stent into the collection. This can be avoided by passing no more than 50% of the stent. An indelible marker can be placed at the midpoint of the stent if radiopaque markers are not already present. When the midpoint of the stricture is at the gastric or duodenal wall, the endoscope is withdrawn away from the collection while simultaneously pushing the stent out of the endoscope channel. Recently, softer stents (Hobbs Medical Inc., Stafford Springs, CT and the SolusTM stent, Cook Endoscopy) have become available. The SolusTM stent has an inner guiding catheter as well as endoscopic and radiopaque markers (Fig. 45.12).

PANCREATIC NECROSIS Fig. 45.10 Baron needle with guidewire in place (Cook Endoscopy).

A

B

D

E

Pancreatic necrosis is defined as non-viable pancreatic parenchyma usually with associated peripancreatic fat necrosis. In the earliest form, this is detected radiographically on contrast enhanced CT by the presence of non-enhancing pancreatic parenchyma (Fig. 45.13). Pancreatic necrosis is frequently accompanied by major pancreatic

C

Fig. 45.11 Transmural drainage using the Seldinger technique (same patient as in Figure 45.5). A A needle is passed transduodenally through the duodenal wall. B Contrast is injected and fills the pseudocyst. C A guidewire is coiled within the collection. D The duodenal wall is balloon dilated using a 10 mm biliary dilating balloon. E Two double pigtail stents are placed. 482

Chapter 45 Endoscopic Drainage of Pancreatic Pseudocysts, Abscesses and Organized (Walled-Off) Necrosis

Fig. 45.14 Same patient as in Figure 45.13, five weeks later. There is now a large collection occupying the area of the pancreatic bed consistent with walled-off necrosis (organized pancreatic necrosis).

Fig. 45.12 SolusTM double pigtail stent. The markers are both endoscopically and radiographically visible (arrows).

Fig. 45.13 Early acute necrotizing pancreatitis. Lack of glandular perfusion of non-viable pancreatic parenchyma (NV) is seen in the neck of the pancreas. The viable parenchyma (V) is seen in the body and tail.

ductal disruptions. Over the course of several weeks, the collection may continue to evolve and expand the initial area of necrosis and contains both liquid and solid debris (Fig. 45.14). The term organized pancreatic necrosis has been used to differentiate this process from the early (acute phase) of pancreatic necrosis, although many investigators now refer to this entity as walled-off necrosis (WON) (Fig. 45.15). The CT appearance of organized pancreatic necrosis may be similar to that of an acute pseudocyst. Because the underlying solid debris is frequently not discernible by CT, its homogeneous appearance may lead one to embark on standard pseudocyst drain-

age methods which do not adequately remove the underlying solid material. This may result in serious infectious complications.1 The distinction between an acute pseudocyst and organized necrosis may be made on clinical, radiologic, or endoscopic findings at the time of drainage. Clinically, if the patient suffered a severe or complicated course of acute pancreatitis, it is likely that pancreatic necrosis occurred and is present within the collection. Radiographically, several features indicate the presence of underlying solid material within the collection. Firstly, if an initial contrastenhanced computerized tomographic scan obtained at the time of—or soon after—the initial bout of pancreatitis demonstrated significant glandular necrosis, the collection likely contains solid debris. Secondly, the evolution of changes on serial CT scans can be traced from the original pancreatic glandular necrosis to the present collection. Thirdly, magnetic resonance imaging (MRI) prior to attempted drainage can delineate the solid debris within the collection. Lastly, a repeat abdominal CT scan after endoscopic drainage will depict solid material once some of liquid has been evacuated (Fig. 45.16). Endoscopic findings at the time of drainage may alert the endoscopist to the presence of necrotic debris within the collection. If the collection is drained transmurally, solid material may be seen to flow from the collection; the presence of chocolate-brown or extremely turbid fluid (in the absence of clinical infection) also suggests underlying necrosis is present. During pancreatography, the finding of complete main pancreatic duct disruption (Figs 45.17a and b) suggests that pancreatic necrosis occurred during the initial course of pancreatitis and may be present in the collection. During contrast injection, either through the main pancreatic duct or transmurally, the finding of large filling defects within the collection denotes the presence of solid material. If any or all of the above are recognized, then appropriate steps must be taken to evacuate the underlying solid debris to prevent secondary infection. Overall, one should consider the evolution of a pancreatic collection from the early phase of acute pancreatic necrosis toward a pseudocyst as a spectrum, with organized pancreatic necrosis as an intermediate stage, realizing that some collections will never become completely liquefied. 483

SECTION 3 APPROACH TO CLINICAL PROBLEMS

Fig. 45.15 Illustration depicting organized pancreatic necrosis (walled-off necrosis). Note viable pancreatic head and tail typically occurs and is the mechanism of pancreatic duct disconnection.

Fig. 45.16 Typical appearance after intervention in necrosis. The collection (arrows) contains non-dependent air and debris. A

484

B

Fig. 45.17 Severe pancreatic ductal disruption identified at the time of endoscopic drainage of necrosis. A,B Initial injection shows short normal pancreatic duct that then disrupts into necrotic cavity.

Chapter 45 Endoscopic Drainage of Pancreatic Pseudocysts, Abscesses and Organized (Walled-Off) Necrosis

Successful resolution Complications Recurrence Hospital days

AP

CP

PN

AP vs. CP

AP vs. PN

CP vs. PN

23/31 (74%) 6/31 (19%) 2/23 (9%) 9

59/64 (92%) 11/64 (17%) 7/59 (12%) 3

31/43 (72%) 16/43 (37%) 9/31 (29%) 20

p = 0.02 NS NS p = 0.0003

NS NS NS NS

p = 0.006 p = 0.02 p = 0.047 p = 0.0001

Table 45.2 Outcomes after attempted endoscopic drainage of patient fluid collections AP, Acute pseudocyst; CP, chronic pseudocyst; PN, pancreatic necrosis. Source: Baron TH, Harewood GC, Morgan DE, Yates MR. Gastrointest Endosc. 2002 Jul;56(1):7–17 (with permission)

The indications for—and the timing of—drainage of sterile pancreatic necrosis are controversial. Pancreatic necrosis is not amenable to endoscopic drainage until the process becomes organized, which usually occurs several weeks after onset of pancreatitis. If the process remains sterile, the general indications for drainage are refractory abdominal pain, gastric outlet obstruction or failure to thrive (continued systemic illness, anorexia, and weight loss) at 4 or more weeks after the onset of acute pancreatitis. The severity of CT scan findings alone is not an indication for drainage. Since endoscopic drainage of these collections is more technically difficult, carries a higher rate of complications, and tends to involve a more severely ill patient group (Table 45.2), the decision to endoscopically intervene in patients with sterile pancreatic necrosis must be carefully considered.25 Alternative management options to endoscopic drainage include nutritional support with parenteral or enteral jejunal feeding and non-endoscopic drainage methods such as percutaneous or surgical drainage. The final management option is usually based upon local expertise and severity of comorbid medical illnesses. Ideally, these patients are best managed by a multidisciplinary approach in tertiary centers. Infected pancreatic necrosis is considered an indication for drainage. Infected necrosis may not be distinguishable clinically from sterile necrosis because of leukocytosis and fever. Percutaneous fine needle aspiration may be required to determine the bacteriologic status of the necrosis, especially when the decision to intervene is predicated on infection. Surgical therapy is still considered the gold standard when a debridement is felt to be necessary in the management of pancreatic necrosis. In some centers, placement of large-bore percutaneous drains is undertaken as an alternative to surgery and in preference to endoscopic therapy as described below.

Endoscopic drainage of organized pancreatic necrosis Because of the need to evacuate solid material, the endoscopic approach to drainage of organized pancreatic necrosis differs from drainage of other PFCs. In general, the transpapillary approach is not adequate to allow removal of solid debris. Therefore, the transmural drainage approach is recommended for these collections. After entry into the collection, the gastric or duodenal wall is balloon dilated to a diameter ≥15 mm (Fig. 45.18a). This allows egress of solid material around the endoprostheses. Several approaches, alone or in combination, can be used to evacuate solid debris. The first is to place an irrigation system to lavage the solid debris. This is achieved by placing a 7 Fr naso-irrigation tube (standard nasobiliary tube) into the collection alongside the transmural stents (Figs 45.18b and c). Up to 200 cc of normal saline is forcefully and rapidly infused via the tube every two to four hours initially. In patients who are

intolerant to nasocystic irrigation tubes and/or it is anticipated that irrigation may be required for many weeks, an alternative to nasocystic lavage is the placement of a percutaneous endoscopic gastrostomy tube (PEG) with placement of a “jejunal” extension tube into the collection26 (Fig. 45.19). The gastric port may then be used for supplementing nutritional needs. More recently, is the description of placing two PEG tubes. One is placed for irrigation, as described above. Over the course of endoscopic therapy, the authors described upsizing the PEG debridement tube to 20 Fr for even greater irrigation. The second PEG was placed to allow for jejunal feeding through an extension tube.27 Another approach for removal of necrotic debris is to perform endoscopic debridement. Indirect endoscopic debridement can be performed under fluoroscopic guidance by passing catheters transmurally into the collection to irrigate and remove debris with stone retrieval baskets, the Roth Basket, and/or balloons. Direct endoscopic debridement can be performed by passing forward-viewing endoscopes through the balloon-dilated transmural tracts into the collection (Fig. 45.20).28 Baskets and/or grasping forceps are then used to remove solid debris (Figs 45.21a–c). Regardless of the approach, repeat procedures are needed to redilate the transmural tract as it closes, exchange transmural catheters, debride the collection, and to treat pancreatic ductal disruptions. These procedures may be scheduled or “on-demand” based upon clinical status and/or CT scan findings. Patients undergoing endoscopic drainage sterile organized pancreatic necrosis should receive preprocedural antibiotics. We recommend intravenous carbapenem agents such as imipenem or meropenem or an extended penicillin agent such as piperacillin. Those with infected necrosis should continue to receive antibiotics, either empirically or based upon culture data. Outpatients should be admitted to the hospital post-procedurally for observation and institution of irrigation. Patients are discharged home after they are able to tolerate oral intake and care for irrigation tubes. Post-procedurally oral antibiotics and antifungal agents (e.g. ciprofloxacin and fluconazole) are administered, and irrigation is continued until the collection has resolved as documented by follow-up CT. CT scans are obtained weekly or every other week to follow the progress of drainage and to guide need for further debridement. The internal drains are endoscopically removed several weeks after complete resolution of the collection. Recently, we have changed our strategy for the management of organized (walled-off) pancreatic necrosis. After successful entry and dilation of the transmural tract to at least 15 mm we now routinely advance a forward-viewing endoscope into the necrotic collection at the time of the first procedure. Schedule debridements are performed on a weekly basis with follow-up CT performed weekly as well. Naso-irrigation tubes are placed into the collection and 485

SECTION 3 APPROACH TO CLINICAL PROBLEMS

A

B

Fig. 45.18 Endoscopic transmural drainage of necrosis. Patient depicted in Figure 45.14. A The transmural tract is dilated with a 16 mm balloon. B Double pigtail stents and a naso-irrigation tube (arrow at tip) are placed. C Illustration of transmural drainage and naso-irrigation catheter.

C

removed when all of the necrotic material has been evacuated endoscopically.

RESULTS OF ENDOSCOPIC THERAPY OF PANCREATIC FLUID COLLECTIONS It must be emphasized that there are no prospective studies comparing endoscopic drainage to conservative (medical) therapy, percutaneous drainage or surgical drainage.

Pancreatic pseudocysts The success rates, recurrence rates and complication rates following endoscopic drainage of pancreatic pseudocysts are variable, likely because the patient populations and interventions in most of these 486

series are heterogeneous, comprised of acute and chronic pseudocysts, pancreatic abscesses, and some patients have undergone transpapillary drainage while others transmural drainage methods. Nonetheless, cumulatively successful drainage is achieved in approximately 75–90% with complication rates of about 5–10% and recurrence rates of 5–20%.1,15,29 The results of endoscopic therapy compare favorably to surgical therapy. Although percutaneous drainage of pancreatic pseudocysts has a high success rate for resolution, it is can create external fistula formation if the pseudocyst communicates with the main pancreatic duct. In a recent study in which a national database was used to compare percutaneous drainage and surgical drainage of pancreatic pseudocysts, there was a significantly lower length of stay and inpatient mortality (5.9% vs 2.8%) in the surgical group.30

Chapter 45 Endoscopic Drainage of Pancreatic Pseudocysts, Abscesses and Organized (Walled-Off) Necrosis

Fig. 45.19 Illustration of PEG with jejunal extension placed through the posterior gastric wall for irrigation.

Fig. 45.20 Illustration of direct endoscopic debridement using a forwardviewing endoscope.

487

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C A

B

Fig. 45.21 Direct endoscopic debridement. A The endoscope is just within the cavity through a large transmural tract. A pelican forceps can be seen grasping the solid material. B The necrotic material is withdrawn and deposited into the antrum. C Large amount of necrotic debris is seen in the stomach at the end of the procedure.

In terms of transmural drainage results, there may be a slightly lower pseudocyst recurrence rate following transduodenal drainage than transgastric drainage due to the sustained patency of a transduodenal fistula that allows long-term drainage of the main pancreatic duct, although this has not been proven. Therefore, in a patient with severe underlying and irreversible pancreatic ductal abnormalities, I recommend transduodenal drainage, whenever possible.

Pancreatic abscesses When a broad definition of pancreatic abscess is taken to include infected pseudocysts and other infected liquefied collections without necrosis, success rates following endoscopic drainage are high, although there are few series and small patient numbers.19,31–33

Organized pancreatic necrosis (walled-off necrosis) There are limited series of endoscopic treatment of pancreatic necrosis. Successful non-surgical resolution of pancreatic necrosis (symptomatic sterile and infected) was published by our group with a non-surgical success rate of 72% of 43 patients.34 At that time smaller-sized transmural dilating balloons of 8–10 mm were used. Outcome after changing the drainage strategy to the use of largediameter balloon dilation of the transmural entry tract to >15 mm at the initial procedure has not yet been published, although in a series of 53 patients who underwent transoral/transmural endoscopic therapy treated from 1998 to 2006, our non-surgical success rate was 81% (in press). Predictors of failure included diabetes mellitus and a collection size = 15 cm. The presence of paracolic gutter involvement was also associated with failure as well as a need for adjuvant percutaneous drain placement. Other authors have reported results of small numbers of patients who underwent endoscopic therapy for necrosis. Success rates of only 4/8 (50%)18 were reported using “standard” irrigation methods. Using aggressive direct debridement, the results have been better with complete resolution in 5/5 patients29 and 2/2 patients,28 although many endoscopic procedures per patient were required to achieve this result in the former group.26 488

OUTCOME DIFFERENCES FOLLOWING ENDOSCOPIC DRAINAGE OF PANCREATIC FLUID COLLECTIONS Based upon published results18,34 significant differences in successful endoscopic drainage have been noted between patients with pseudocysts and pancreatic necrosis (Table 45.2). Complications occur more commonly in patients with pancreatic necrosis than for pseudocysts. Likewise, hospital stay is shorter in patients with pseudocysts, while pancreatic necrosis is predictive of significantly longer hospital stays. The recurrence rates are significantly higher for patients with pancreatic necrosis than chronic pseudocysts. The differences in success rates, complication rates, recurrences and hospital stay may be explained by the differences in pathology, pathophysiology, and severity of illness between the groups. Patients with pancreatic necrosis tend to be more severely ill patients and endoscopic evacuation of solid debris is less efficient than evacuation of liquid. In terms of recurrence rates, acute pancreatic ductal disruptions occurring in patients with necrosis frequently lead to either severe stricturing or a completely disconnected duct whereby the head and tail of the pancreas are not in communication (Fig. 45.22). Recurrent collections may arise from the undrained viable pancreatic tail. Patients with acute pseudocysts tend to have less severe ductal abnormalities and less recurrence, while patients with chronic pancreatitis have underlying ductal abnormalities, such as strictures and stones, that may lead to recurrences, especially if left unrecognized and untreated.34,35 I recommend aggressive endoscopic intervention to correct underlying ductal abnormalities, if possible, in all types of PFCs so that recurrent collections or symptoms may be avoided (Figs 45.5d and e).

ROLE OF ENDOSCOPIC EXPERIENCE Endoscopic therapy of PFCs requires a high skill level. Operator experience may play a role in the outcome of these patients as there appears to be a learning curve associated with drainage of PFCs.36

Chapter 45 Endoscopic Drainage of Pancreatic Pseudocysts, Abscesses and Organized (Walled-Off) Necrosis

Animal training models for learning pseudocyst drainage techniques have been described37 and may be helpful for acquiring these techniques.

COMPLICATIONS OF ENDOSCOPIC THERAPY OF PANCREATIC FLUID COLLECTIONS Life-threatening complications may arise following attempted endoscopic drainage of PFCs and are listed in Table 45.3. It is recommended that endoscopic drainage of PFCs is performed with the

availability of surgical and interventional radiology support. The most feared complications of transmural drainage are bleeding and perforation. Bleeding after transmural drainage may be managed supportively, endoscopically, surgically, or with angiographic embolization. If perforation occurs during attempted transgastric drainage and is limited to the gastric wall (does not involve the collection), it may be successfully managed non-surgically, assuming a stent has not been placed through the perforation; the gastric wall rapidly closes with conservative treatment consisting of nasogastric suction and antibiotics. Some authors feel that transduodenal perforation may be managed conservatively, since the perforation is retroduodenal,38 although this is not proven. Infectious complications usually occur from inadequate drainage of fluid and/or solid debris. If transpapillary drainage was performed on a liquefied collection, stent exchange and/or upsizing of the stent may resolve the infection. If solid material was unrecognized during the initial procedure, placement of irrigation tubes or changing to transmural drainage may resolve the infection. Occasionally, some patients will require adjuvant placement of percutaneous drainage and/or irrigation catheters to manage infectious complications, particularly when the necrosis extends to the paracolic gutters. Stent migration into the collection

BOX 45.3 COMPLICATIONS AND CONTROVERSIES • Complications of endoscopic drainage of pancreatic fluid collections include perforation, bleeding, infection, respiratory complications, pancreatic ductal damage, and stent migration

Fig. 45.22 Indirect endoscopic debridement of patient in Figure 45.14. Stone retrieval balloon was inflated inside the cavity and solid debris swept out of the transmural site.

• Endoscopic drainage of pancreatic necrosis is controversial and associated with a higher complication rate than drainage of pancreatic pseudocysts

Fig. 45.23 Final pancreatogram of patient in Figure 45.14. The necrotic cavity resolved as documented by CT. Extravasation of contrast is seen from the pancreatic duct back into the duodenum at the transmural entry site. There is no communication with the tail.

Successful resolution Complications Recurrence Hospital days

Bleeding Perforation Infection Pancreatitis Sedation complications Aspiration Stent migration/occlusion Pancreatic ductal damage

Table 45.3 Complications of endoscopic therapy of PFCs

AP

CP

PN

AP vs. CP

AP vs. PN

CP vs. PN

23/31 (74%) 6/31 (19%) 2/23 (9%) 9

59/64 (92%) 11/64 (17%) 7/59 (12%) 3

31/43 (72%) 16/43 (37%) 9/31 (29%) 20

p = 0.02 NS NS p = 0.0003

NS NS NS NS

p = 0.006 p = 0.02 p = 0.047 p = 0.0001

Table 45.4 Outcomes after attempted endoscopic drainage of patient fluid collections AP, Acute pseudocyst; CP, chronic pseudocyst; PN, pancreatic necrosis.

489

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through the gastric or duodenal wall may occur during or after endoscopic stent placement. Endoscopic retrieval is possible if the collection has not completely collapsed and the transmural tract is still patent.

Endoscopic therapy may be associated with complications and/or failures that require surgical management. It is possible that the outcome of surgical therapy may be adversely altered when compared to those patients undergoing primary surgical therapy.39

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33.

abscesses using a therapeutic echo endoscope. Endoscopy 2001; 33(6):473–477. Azar RR, Oh YS, Janec EM, et al. Wire-guided pancreatic pseudocyst drainage by using a modified needle knife and therapeutic echoendoscope. Gastrointest Endosc 2006; 63(4): 688–692. Kruger M, Schneider AS, Manns MP, et al. Endoscopic management of pancreatic pseudocysts or abscesses after an EUS-guided 1-step procedure for initial access. Gastrointest Endosc 2006; 63(3):409–416. Sriram PV, Kaffes AJ, Rao GV, et al. Endoscopic ultrasound-guided drainage of pancreatic pseudocysts complicated by portal hypertension or by intervening vessels. Endoscopy 2005; 37(3):231–235. Monkemuller KE, Baron TH, Morgan DE. Transmural drainage of pancreatic fluid collections without electrocautery using the Seldinger technique. Gastrointest Endosc 1998; 48(2):195–200. Sanchez Cortes E, Maalak A, Le Moine O, et al. Endoscopic cystenterostomy of nonbulging pancreatic fluid collections. Gastrointest Endosc 2002; 56(3):380–386. Cahen D, Rauws E, Fockens P, et al. Endoscopic drainage of pancreatic pseudocysts: long-term outcome and procedural factors associated with safe and successful treatment. Endoscopy 2005; 37(10):977–983. Kozarek RA. Endoscopic management of pancreatic necrosis: not for the uncommitted. Gastrointest Endosc 2005; 62(1):101–104. Baron TH, Morgan DE. Endoscopic transgastric irrigation tube placement via PEG for debridement of organized pancreatic necrosis. Gastrointest Endosc 1999; 50(4):574–577. Raczynski S, Teich N, Borte G, et al. Percutaneous transgastric irrigation drainage in combination with endoscopic necrosectomy in necrotizing pancreatitis (with videos). Gastrointest Endosc 2006; 64(3):420–424. Seewald S, Groth S, Omar S, et al. Aggressive endoscopic therapy for pancreatic necrosis and pancreatic abscess: a new safe and effective treatment algorithm (videos). Gastrointest Endosc 2005; 62(1):92–100. Weckman L, Kylanpaa ML, Puolakkainen P, et al. Endoscopic treatment of pancreatic pseudocysts. Surg Endosc 2006; 20(4):603–607. Morton JM, Brown A, Galanko JA, et al. A national comparison of surgical versus percutaneous drainage of pancreatic pseudocysts: 1997–2001. J Gastrointest Surg 2005; 9(1):15–20; discussion 20–21. Park JJ, Kim SS, Koo YS, et al. Definitive treatment of pancreatic abscess by endoscopic transmural drainage. Gastrointest Endosc 2002; 55(2):256–262. Venu RP, Brown RD, Marrero JA, et al. Endoscopic transpapillary drainage of pancreatic abscess: technique and results. Gastrointest Endosc 2000; 51(4 Pt 1):391–395. Baron TH, Harewood GC, Morgan DE, et al. Outcome differences after endoscopic drainage of pancreatic necrosis, acute pancreatic pseudocysts, and chronic pancreatic pseudocysts. Gastrointest Endosc 2002; 56(1):7–17.

Chapter 45 Endoscopic Drainage of Pancreatic Pseudocysts, Abscesses and Organized (Walled-Off) Necrosis

34. Zhang AB, Zheng SS. Treatment of pancreatic pseudocysts in line with D’Egidio’s classification. World J Gastroenterol 2005; 11(5):729–732. 35. Nealon WH, Walser E. Main pancreatic ductal anatomy can direct choice of modality for treating pancreatic pseudocysts (surgery versus percutaneous drainage). Ann Surg 2002; 235(6): 751–758. 36. Harewood GC, Wright CA, Baron TH. Impact on patient outcomes of experience in the performance of endoscopic pancreatic fluid collection drainage. Gastrointest Endosc 2003; 58(2):230–235.

37. Schofl R, Buchmeier B, Hauder G. Adaptation of the Erlangen Active Simulator for Interventional Endoscopy (EASIE) model for transmural pancreatic pseudocyst drainage. Endoscopy 2006; 38(1):100. 38. Beckingham IJ, Krige JE, Bornman PC, et al. Endoscopic management of pancreatic pseudocysts. Br J Surg 1997; 84(12):1638–1645. 39. Nealon WH, Walser E. Surgical management of complications associated with percutaneous and/or endoscopic management of pseudocyst of the pancreas. Ann Surg 2005; 241(6):948–957; discussion 957–960.

491

Index

A

accessories for the ERCP room 17, 31–41 disposable 40 evolution of 41 single use vs reusable 40 storage 16, 40 for use in altered anatomy patients 40 see also individual accessories access (precut) sphincterotomes 32–3 access (precut) sphincterotomy 87–90, 110 techniques 77 see also precut accessotomy AccuTouch computer simulator 63 acinarization 26 Acosta criteria 415 acute gallstone pancreatitis (AGP) background 411 biliary intervention 411–17 with biliary obstruction 414–15 cholecystectomy after 415–16 diagnosis 411–12 endoscopic therapy 412–14 management algorithm 416 randomized controlled trials (RCTs) 413–14 severity assessment 412 systematic reviews 414–16 acute pancreatic trauma 424 acute pancreatitis causes 435, 441 in children 227–8 concomitant 330 endoscopically amenable lesions 419–20 episodic illness 438 ERCP in 419 idiopathic see idiopathic acute pancreatitis unexplained 370 see also acute gallstone pancreatitis adenomas ampullary see ampullary adenomas cystadenomas see cystadenomas; serous cystadenomas; mucinous cystic neoplasms major papilla 440 administrators 5 air, retroperitoneal/intraperitoneal 21 air bubbles after sphincterotomy 26 vs gallstones 26 airway problems, risk factors 45 alanine aminotransferase (ALT) 265, 411 albendazole 393–4, 394, 396 alcoholism causing acute pancreatitis 435 and chronic pancreatitis (CP) 459, 464

alkaline phosphatase (AP) 265 allergies see contrast allergies allopurinol 56 altered anatomy, accessories for use with 40 alveolar hypoventilation 46 American Society for Gastrointestinal Endoscopy (ASGE) guidewire review 35 pregnancy guidelines 231, 234 training guidelines 7, 61, 62 American Society of Anesthesiologists (ASA) patients’ physical classification system 43, 44 practice guidelines 43, 44–8 amoxicillin 305 ampicillin 220 ampulla of Vater 87, 88 evaluation 189–90 lymphomas 278 neoplasms 278–9 ampullary adenomas 273, 277 colonoscopy 276–7 treatment 279–80 ampullary anomalies 447 ampullary carcinoma 288 classification 277 colonoscopy 276–7 survival rates 280–3 symptoms and signs 273 transabdominal ultrasound (TUS) 288 treatment 280–3 ampullary diverticula 79 ampullary neoplasm 273–85 adenomas see ampullary adenomas appearances 273 benign vs malignant 273–4 carcinoma see ampullary carcinoma colonoscopy 276–7 computed tomography (CT) scan 275 diagnosis 275 differential diagnosis 278, 279 endoscopic ultrasonography (EUS) 275–6 endoscopy 273–4 ERCP and 274–5 familial adenomatous polyposis (FAP) 189, 273, 274, 277, 279 forceps biopsy 275 gastrointestinal stromal tumors (GIST) 278 intraductal ultrasound (IDUS) 276 lymphomas 278 magnetic resonance imaging (MRI) 275 pathology 277–9 staging advanced cancer 275–6 staging early lesions 276 symptoms and signs 273

transabdominal ultrasound 275 treatment 279–83 see also carcinoid/neuroendocrine tumors ampullary tumors 189, 440 literature on endoscopic resection of 281–2 surgical treatment 189 see also ampullary carcinoma; ampullary neoplasm/ampullary adinoma ampullectomy 189–97 complications 194, 195 contraindications 194 controversies 194–5 costs 196 en bloc 191 endoscopic evaluations 189–90 indications 194 postampullectomy cholangitis 194 postampullectomy pancreatitis 193–4, 195 postampullectomy sphincterotomy 193–4 postampullectomy surveillance 194 preresection sphincterotomy 192–3 snare excision 191–2 specimen retrieval 192 stent placement 193–4 success rates 195–6 techniques 189–94 thermal ablation 192 see also papillectomy analgesia see sedation and analgesia anastomosis dunking anastomosis 349 with more than one exiting lumen 256 anastomotic strictures, in children 226 anatomy, difficult, EST and 112–13 anesthesia induction agents 47–8 mortality rates 43–4 animals, training using 63–6 annular pancreas 441, 456–7 anomalous pancreaticobiliary junction (APBJ) 387, 441, 447 biliary cysts and 448, 449 gallbladder cancer and 392, 447 anomalous pancreatobiliary union (APBU), in children 223 ansa pancreaticus 92, 375 antegrade sphincterotomy 113 antibiotics in cholangitis 359 in hilar malignant biliary obstruction 304, 309 pancreatic sphincterotomy and 129 in primary sclerosing cholangitis 379, 380, 382 493

INDEX anticoagulants, pancreatic sphincterotomy and 129 antiplatelet drugs 114 Apache II scoring system 412 aprons, lead 16, 19 artificial tissue models 66 ASA see American Society of Anesthesiologists ascariasis biliary 393 biliary-pancreatic 393 complications 393 infestation in children 226 in pregnancy 231, 234, 393 Ascaris 231 Ascaris lumbricoides 228, 393–4, 399 endotherapy 393–4 worm extraction 393 ascites, pancreatic see pancreatic ascites ASGE see American Society for Gastrointestinal Endoscopy aspartate aminotransferase (AST) 265 aspirin 56, 129 atropine 16 autoimmune pancreatitis 441

B

bacteria, in cholangitis 359 Bacteroides fragilis, in cholangitis 359 balloon dilation after biliary sphincterotomy 55 of the biliary sphincter 55 in Billroth II gastrectomy 256–7 endoscopic 98–100, 113 informed consent 97 of the papilla 97–107, 231 see also endoscopic papillary balloon dilation; large balloon dilation after minimal biliary sphincterotomy; balloon sphincteroplasty balloon dilators 38 balloons extraction balloons 119–20, 121, 123 over-the-guidewire type 105 balloon sphincter dilation, Billroth II gastric resection 241–2 balloon sphincteroplasty in children 222 in pregnancy 231 balloon stone extraction 119–21 assessing stone size 119 complications 119, 121–2 contraindications 119, 120 extraction balloons 119–20, 121, 123 indications 119, 120 key points 119 technique 120–1 balloon traction, stent removal 179–80 bariatric surgery 245–9 biliopancreatic diversion 245, 246 duodenal switch 246 gastric banding 246, 247 gastric bypass 247–9 malabsorptive-jejunoileal bypass 246 restrictive surgery 246–7 vertical banded gastroplasty 245, 246–7 basket mechanical lithotripsy (BML) 360 baskets cost 124 flower baskets 122

494

in infants 220 lithotripsy baskets 39, 123–7, 126 spiral 122 wire 39, 121–2 basket stone extraction 121–3, 128 assessing stone size 119 complications 121, 123 contraindications 121, 123 indications 121, 123 key points 121 technique 122–3 battery (criminal charge) 6 B-cell lymphomas 278 benign biliary strictures 327–33 causes 327, 328 chronic pancreatitis and 327, 330 classification 327 clinical features 327 complications 330–2 contraindications 330 controversies 330–2 diagnosis 327 endoscopic technique 328 indications 330 management 327–8 postoperative 327 post-sphincterotomy distal 330 SEMS, uncovered vs covered in 330 stenting 328–32 stricture dilation 328 stricture negotiation 328 surgery 329–30 benzodiazepines 44, 91 in pregnancy 233 in sphincter of Oddi manometry (SOM) 372 bile duct adenocarcinoma 214 anomalous anatomy 447–8 decreasing pressure inside 335 dilated see dilated bile duct extrahepatic 105, 269 extravasation from 26 leaks see biliary leaks lesion evaluation 213–15 lesion therapy 216 opacification 22–4 perforation 116 postoperative injuries 327 stones see bile duct stones tumors 214 bile duct stones 357 common bile duct (CBD) 357, 362, 363 extrahepatic, EST for 105 found during laparoscopic cholecystectomy (LC) 363–4 irretrievable, stents for 157 post-EST/EPBD 103 retained after cholecystectomy 339–40 bile microscopy 442 biliary 38 biliary anomalies 447–9 biliary atresia (BA), diagnosis in children 222, 226 biliary biopsy forceps 38 biliary cannulation 75–6 double-wire technique 77 guidewire-assisted 76 methods 75

pancreatic duct stent placement to facilitate 76–7 with a sphincterotome 75–6 standard techniques 75–6 biliary cast syndrome 343 biliary cirrhosis 313 biliary cysts see choledochal (biliary) cysts biliary decompression, stent placement 323 biliary dilation, definition 263 biliary disorders, in pregnancy 234 biliary dyskinesia, definition 367 biliary filling defects 213–14 biliary infections, in children 226 biliary leaks 23–4, 26, 335–7 after hepatic resection 338–9 after laparoscopic cholecystectomy (LC) 337 associated with liver transplantation 342 bypassing bile flow through leak site 335 in children 226 ERCP treatment techniques 335–6 maintaining intraductal flow 335–6 sealing 335 biliary lymphomas 278 biliary malignancies see cholangiocarcinoma; malignant biliary obstruction, distal; malignant biliary obstruction, hilar biliary mechanical lithotripsy (BML) 362 biliary microlithiasis 415 biliary obstruction 313 benign 160 distal 153–7 hilar 158 malignant 160, 165 causes 165 palliation 165 see also malignant biliary obstruction, distal; malignant biliary obstruction, hilar MRCP and 267 perihilar, detection rates 268 see also indeterminate biliary strictures biliary papillomatosis 214, 216 biliary scintigraphy, dilated bile duct 269 biliary sludge 436 biliary sphincter, balloon dilation 55 biliary sphincterotomy 460 balloon dilation after 55 Billroth II gastric resection 241–2 immediately before pancreatic sphincterotomy 134 as indication of EST 114 precut 77–9 in sphincter of Oddi dysfunction (SOD) 114, 374, 375–6 see also endoscopic biliary sphincterotomy biliary stenting, complications 330–2 biliary stents in acute cholangitis 360 categories 165 complications 162 fixed-diameter plastic (FDPS) see fixeddiameter plastic stents palliative insertion 153 plastic 153–8 with antireflux valve 153, 185 indications 160, 177 technique 153 self-expandable metallic (SEMS) see selfexpandable metallic stents

INDEX biliary strictures benign see benign biliary strictures in children 223–6 evaluation of 213–15 indeterminate see indeterminate biliary strictures biliary surgery 252–5 cholecystojejunostomy 254 choledochoduodenostomy 252 complications see biliary surgery complications hepaticocutaneous jejunostomy 255 liver transplantation 254–5 Roux-en-Y choledochojejunostomy 254 Roux-en-Y hepaticojejunostomy 252–4 biliary surgery complications, management of 335–45 collections 338 diagnosis 337–8 endoscopic vs surgical treatment 338 ERCP treatment techniques 335–6 following laparoscopic cholecystectomy 336 injury, nature and magnitude of 336–7 Kehr’s tube 340 septic complications 338 summary 344 surgical risk 338 see also biliary leaks biliary tract disease 442 biliopancreatic diversion 245, 246 bilirubin 265 Billroth I gastrectomy 237 Billroth II anatomy endoscopic biliary sphincterotomy (EST) and 110, 112 endoscopic papillary balloon dilation (EPBD) and 100 Billroth II gastrectomy 237–42, 256–7 EPBD/EST and 98–100 ERCP accessories 256–7 bilobar stone disease 412 biopsy in children 226 cholangioscopy 214–15 image of 27 malignant biliary obstruction, distal 289 pancreatoscopy and 203–4 see also forceps biopsies bipolar electrocautery, in pregnancy 233 bispectral index (BIS) monitoring 46 Bithionol 396 bleeding see hemorrhage botulinum toxin injection 455, 456 in recurrent pancreatitis 438 in sphincter of Oddi dysfunction (SOD) 374 bougies 38 bowel perforation 57 Braun procedure 240–1, 245, 256 breach of duty of care 4 brush cytology in children 226 cholangioscopy 215 devices 38 indeterminate biliary strictures 320 pancreatoscopy 203–4

C

CA 19-9 see carbohydrate antigen 19-9 (CA 19-9) calcium channel blockers 373

cannulas 31–2 cannulation of common bile duct see biliary cannulation of major papilla 73–81 of minor papilla see minor papilla of pancreatic duct 80–1 parallel 80 patients with periampullary duodenal diverticula 79–80 capnography 46 carbapenem agents 485 carbohydrate antigen 19-9 (CA 19-9), in indeterminate biliary strictures 313 carbon dioxide (CO@2) monitoring 46 carcinoids see neuroendocrine tumors carcinoma ampullary see ampullary carcinoma gallbladder, prognosis and risk factors 287 neuroendocrine 277–8 see also cholangiocarcinoma; pancreatic cancer cardiopulmonary complications of ERCP 51–2 cardiovascular complications of ERCP 9 care duty of 4 standards of 4–5 C-arm fluoroscopy units benefits and disadvantages 19 scatter radiation 19 space in ERCP room for 13 Caroli’s disease 287, 390, 448 catheters manometry 92, 94 with microtransducers 94 needle tip 31, 82 pancreaticobiliary manometry catheters 31 sleeve 95 in sphincter of Oddi manometry (SOM) 95–6, 371 swing-tip 31 tapered-tip 31, 95 types 31–2 cefazolin 220 cephalosporin 129, 220 Charcot’s triad 359 chemotherapy in cholangiocarcinoma (CA) 384 in malignant biliary obstruction 295–6 Child-Pugh cirrhosis 101 children choledochal cysts 387, 389 ERCP in see pediatric ERCP Chinese liver fluke see Clonorchis sinensis chloroquine 396 cholangiocarcinoma (CA) 214, 268, 290, 299, 383–5 biliary cysts and 448–9 complications 385 contraindications 384 cost 385 diagnosis 383–4 extrahepatic 299 hilar see hilar cholangiocarcinoma incidence 287 indications 384 mucin-hypersecreting 214 occurrence rate 299 palliation 384

parasitic disease and 396 risk factors 287, 299 stenting 384 technique 383–4 treatment 384 cholangiograms 119 cholangiography dilated bile duct 268–9 extrahepatic biliary lesions 317 identifying malignant lesions 317 percutaneous transhepatic (PTC) 268, 269, 319 cholangiopancreatoscopy, duodenoscope-assisted 39 cholangiopathy, HIV associated, in children 226 cholangioscopes 39 maneuvering 213 cholangioscopic stone removal basket removal 403–4 results 406 stone fragmentation 404 stricture dilation 404–6 techniques 403–6 cholangioscopy 211–17 accessories used 211 bile duct preparation 213 biopsy and 214–15 brush cytology 215 cannulation 212–13 complications 216–17 contraindications 216 cost 217 diagnostic technique 211–12 with fluoroscopy 213 without fluoroscopy 215–16 indeterminate biliary strictures 322–3 indications 213–16 malignancy criteria 214 nomenclature evolvement 211 peroral 399–400 postoperative (POCS) 402–3 preprocedure room set-up 211 stone fragmentation 215 stone removal see cholangioscopic stone removal techniques 211 transhepatic 216 see also percutaneous transhepatic cholangioscopy cholangitis acute, morbidity and mortality 359 acute suppurative, radiological contrast 359 as complication of choledochal cysts 391 as complication of ERCP 52, 58 due to choledocholithiasis/ductal stenosis 114 endoscopic stenting 361 EST-related 116 postampullectomy 194 post-EST/EPBD 101, 103 recurrent pyogenic (RPC) see recurrent pyogenic cholangitis reducing risk 309 risk factors 58 sclerosing see primary sclerosing cholangitis secondary to choledocholithiasis 359–61 symptoms 359

495

INDEX cholecystectomy after acute gallstone pancreatitis (AGP) 415–16 after endoscopic sphincterotomy 364–5 common bile duct dilation after 267 laparoscopic see laparoscopic cholecystectomy cholecystitis as complication of ERCP 52, 58 post-EST/EPBD 101, 103 risk factors 293 cholecystojejunostomy 254 cholecystokinin 91 choledochal anomalies, in children 223 choledochal (biliary) cysts 287, 387–92 anomalous pancreaticobiliary junction (APBJ) and 448, 449 in children 223, 387, 389 cholangiocarcinoma and 448–9 complications 390–2 contraindications of ERCP for 387 diagnosis 389, 449 extrahepatic 449 indications of ERCP for 387 in pregnancy 234 preoperative assessment 389 technique 387–8 therapeutic measures 389 Todani classification 387, 389, 448 see also choledochoceles choledochoceles 389, 448 cancer in 449 IAP and 439 choledochoduodenostomy 252 choledochojejunostomy 349 complications 348 dilatation of biliary strictures 341–2 choledocholithiasis 357–66 after cannulation and decompression of bile duct 359–60 age of patients 361 in children 222–3 cholangitis secondary to 359–61 clinical manifestation 357 detection rates 268 diagnosis 357–9 endoscopic ultrasound and 267 as indication for biliary sphincterotomy 114 natural history 357 patients high-risk 359, 362, 362–3 intermediate-risk 358–9, 363 low-risk 358, 363 risk stratification 358–9 peri-operative management of 362–4 in pregnancy 231, 234 surveillance after treatment 362 see also common bile duct, stones cholelithiasis in children 222–3 in pregnancy 231 see also gallstones cholestasis markers of 265 neonatal 222 obstructive see obstructive cholestasis chronic pancreatitis (CP) 208, 441, 459–66 biliary strictures and 327, 330 in children 228–9 endotherapy in 459 496

idiopathic 459 pain in 459, 464 pancreatic sphincterotomy as primary treatment 138–40 pathophysiology 459 pretherapeutic planning 459 stenting 463 see also severe chronic pancreatitis ciprofloxacin 220, 292, 304–5, 359, 486 cirrhosis, Child-Pugh 101 cisplatin 295–6 clonorchiasis 395–6 biliary 396 endotherapy 396 Clonorchis 231 Clonorchis sinensis 395–6, 399 clopidogrel 114 Clostridium perfringens, in cholangitis 359 coagulation profile, and pancreatic fluid collection 477 coagulopathy, after hepatic resection 339 colonoscopes 31 colonoscopy, ampullary neoplasm 276–7 common bile duct (CBD) 74 cannulation see biliary cannulation dilation 263 laparoscopic exploration of (LECBD) 362–4 size 263–4 stones 357, 362, 363 common hepatic duct (CHD) dilation 263 size 263 communication of endoscopist’s thoughts 26, 27 with patient and family 10 radiologic reporting 28 CompactEASIE simulator 64, 65–6 competence continued 7 definition 7 number of procedures to achieve/maintain 7, 61–2 of patient, and consent 6, 9 privileging and 8 trainee’s 7 complications of ERCP 51–8, 268 adverse events 51 avoidance strategies 9–10 cardiopulmonary 51–2 cardiovascular 9 definitions 51 endoscopists’ experience and 54, 58 legal issues 8–9 long-term 58 managing 10 rates 51–2 risk factors 8, 51–3 risky clinical situations 10 severity 51 strategies for reduction of 58 unplanned events 51 computed tomography (CT) ampullary carcinoma 288 ampullary tumors 275 in choledocholithiasis diagnosis 357 contrast-enhanced abdominal CT, and pancreatic fluid collection 477 in diagnosis of pancreatic cystic lesions 470, 471

in diagnosis of pancreatic fistulas 421 dilated bile duct 266 hilar cholangiocarcinoma 300–1 indeterminate biliary strictures 314 pancreatic malignancies 289–90 computer simulators 63 conscious sedation 43 consent see informed consent contraindications to ERCP 114 contrast non-ionic 56 strength of 20, 26 contrast allergies, policy 9 contrast-enhanced abdominal CT, and pancreatic fluid collection 477 corticosteroids 55, 313, 341–2 Crohn’s disease, in children 224 Cryptosporidium parvum 226 cyanoacrylate after hepatic resection 339 for external pancreatic fistulas 425 sealing biliary/pancreatic leaks 335, 336, 348 cystadenomas 471 serous see serous cystadenomas cyst fluid tumor markers 471 cystic endocrine neoplasms, pathology 469 cystic fibrosis transmembrane receptor (CFTR) abnormalities 456 cystic lesions of the pancreas see pancreatic cystic lesions risk factors 467 cysts see choledochal (biliary) cysts; hydatid cysts; pancreatic pseudocysts cytology brush systems see brush cytology cytology sampling cholangioscopy 214–15 pancreatoscopy 203–4 cytomegalovirus 226 cytotoxic drugs 295

D

damages 4 punitive 4 diazepam 44, 305 in pregnancy 233 diffuse large B-cell lymphomas 278 digital image analysis (DIA), indeterminate biliary strictures 321 dilated bile duct 263–72 approach to patient 269–70 background 263–4 biliary scintigraphy 269 biochemical evaluation 265 cholangiography 268–9 clinical evaluation 264–5 computed tomography (CT) 266 endoscopic ultrasound (EUS) 267–8 etiology 264 evaluation 264–9, 269–70 imaging 265–9 magnetic resonance imaging (MRI) 266–7 ultrasound (US) 265–6 dilation pancreaticobiliary 38 see also balloon dilation; large balloon dilation after minimal biliary sphincterotomy dilation devices 38

INDEX diverticula ampullary 79 duodenal 113 periampullary 79 periampullary duodenal 79–80 documentation 9–10 of informed consent 9–10 dominant dorsal duct drainage 454 double-duct sign 290 in children 224 drainage dominant dorsal duct drainage 454 drainage times, pancreatic/biliary 367 in hilar malignant biliary obstruction 302–3 pancreatic duct see pancreatic duct drainage transmural 478–81 transpapillary 478–0 see also pancreatic fluid collections drainage devices 36 see also nasobiliary drainage catheters; nasopancreatic drainage catheters; stents drugs, emergency, availability of 16 dual sphincterotomy 376 ductal disruption 475, 483, 488 epidemiology 419 ductal hypertension 435 duct of Wirsung see pancreatic duct duct size, calculation 21–2 dunking anastomosis 349 duodenal bypass 245 duodenal diverticula 79–80, 113 juxtapapillary 112 duodenal duplication cysts 441 see also choledochoceles duodenal obstruction, SEMS placement 172–3 duodenal papilla, dilatation 202 duodenal polyposis, staging system 279 duodenal switch 246 duodenojejunostomy 245 duodenoscopes 31, 39 pediatric 31 in self-expandable metallic stents (SEMS) placement 169–70 therapeutic 105 used in children 220 duty of care 4 breach of 4 Duval procedure 252

E

EASIE (Erlangen Active Training Simulator for Interventional Endoscopy) 64 CompactEASIE simulator 64, 65–6 EBD see endoscopic balloon dilation Echinococcus granulosus 394–5 postoperative complications 395 electrocautery, in pregnancy 233 electrocoagulation 116 electrohydraulic lithotripsy (EHL) 215, 362, 399–400, 402, 404 success rates 215 see also intraductal electrohydraulic lithotripsy; lithotripsy electrosurgical current for EST 111, 115 minor papilla sphincterotomy 143–4, 150 during pancreatic sphincterotomy 129–30

pure-cut electrocautery vs blended current 111 electrosurgical generators 14–15 ENDO CUT mode 111 employer liability 5 endoscope processor, in ERCP room 14 endoscopes 31 forward-viewing 31 oblique-viewing 31 side-viewing 31 storage 16 upper 31 see also pancreatoscopes; cholangioscopes endoscopic balloon dilation (EBD) 113 indications for 98–100 see also endoscopic papillary balloon dilation endoscopic biliary sphincterotomy (EST) 97–107, 109–18 alternatives to 113 complications 101–3, 114–17 contraindications 114 cost 117 electrosurgical current for 111, 115 vs endoscopic papillary balloon dilation (EPBD) 97, 98–103 indications 97, 113–14 instruments 109–10 long-term consequences 116–17 pancreatic stent placement 115 for pancreatitis due to microlithiasis 436 patients with difficult anatomy 112–13 procedure 110–12 success rates 97 technique 109–13 endoscopic mechanical lithotripsy (EML) 105 endoscopic pancreatic ductal drainage impact on endocrine and exocrine functions 464 pain relief after 463 in severe chronic pancreatitis 462 endoscopic pancreatic sphincterotomy (EPS) 459–60 see also pancreatic sphincterotomy endoscopic papillary balloon dilation (EPBD) 97–107 complications 101–3 vs endoscopic biliary sphincterotomy (EST) 97, 98–103 indications for 98–100 informed consent 97 limitations 100–1 success rates 97, 100 endoscopic resection (snare papillectomy) 440 endoscopic retrograde cholangiography, indications 26 endoscopic sphincterotomy, indications 26 endoscopic transpancreatic papillary septotomy 79 endoscopic ultrasound (EUS) in acute gallstone pancreatitis 411 ampullary neoplasm 275–6 in assessment of ampullary tumors 189–90 in choledocholithiasis diagnosis 357–8 complications 268 in diagnosis of pancreas divisum 454 in diagnosis of pancreatic cystic lesions 470 dilated bile duct 267–8 EUS-guided rendezvous techniques 80, 83 hilar cholangiocarcinoma 301

in IAP and IARP 441, 441–2 indeterminate biliary strictures 316–17 limitations 268 for minor papilla cannulation 83 and pancreatic fluid collection 477–8 pancreatic malignancies 289 endoscopists communication of thoughts 26, 27 experience of, and complications of ERCP 51, 54, 58 levels of training 66 number of procedures to achieve/maintain competence 7, 61–2 trainees 7 see also training endotherapy and pain, in chronic pancreatitis 464 palliation of malignancies 344 post-pancreatic surgery 351 EndoTrainer simulator 64, 65 enterococci, in cholangitis 359 Enterococcus spp. 304 enteroscopes 31 EPBD see endoscopic papillary balloon dilation epinephrine 56, 88, 96, 116, 150, 195, 229 equipment for ERCP room radiologic imaging 15–16 see also accessories for the ERCP room; and individual accessories and pieces of equipment ERCP, past, present and future ix-x ERCP room 13–18 configuration 13–15 emergency drugs 16 location 13 size 13 see also accessories; equipment for ERCP room; and individual accessories and pieces of equipment Erlangen Active Training Simulator for Interventional Endoscopy (EASIE) 64 Escherichia coli 304 in cholangitis 359 esophageal intubation 73 esophageal resection 237 EST see endoscopic biliary sphincterotomy ESWL see extracorporeal shock wave lithotripsy EUS see endoscopic ultrasound exchange assistance devices 35 experience see competence; endoscopists expert testimony 4, 4–5 extracorporeal shock wave lithotripsy (ESWL) 119 common bile duct stones 362 in severe chronic pancreatitis 460–1 clinical results 463–4 stone extraction and dilation after 461–2 technical results 462–3 extraction balloons 119–20, 123 cost 121 extrahepatic bile duct size 269 stones, EST for 105

F

familial adenomatous polyposis (FAP) 189, 273, 274, 277, 279, 440 screening programs 279 see also ampullary adenomas; Gardner’s syndrome

497

INDEX Fasciola 231 Fasciola hepatica 396–7 fascioliasis 396–7 acute/hepatic phase 396 chronic/biliary phase 396 endotherapy 396–7 massive forms 397 stages of 396 tests 396 fatty meal ultrasound (FMS), in SOD 369–70 felodipine 373 fentanyl 305 fibrin glue 116 filling defects, liver transplantation 343 fistulas, associated with liver transplantation 342 fistulotomy precut 77 suprapapillary 89 fixed-diameter plastic stents (FDPS) 165 cost 174 patency 165–6 vs self-expandable metallic stents (SEMS) 165–6, 174 stent occlusion 165, 166 flow cytometry, indeterminate biliary strictures 321 flower baskets 122 floxuridine 379 fluconazole 485 flumazenil 16 5-Fluoracil (5-FU) 295 fluorescent in-situ hybridization (FISH), indeterminate biliary strictures 321 fluoroquinolone 220 fluoroscopy during cholangioscopy 213 for pediatric ERCP 219–20 views of images 20 fluoroscopy rooms 19 follicular lymphomas 278 forceps, biliary biopsy forceps 38 forceps biopsies ampullary neoplasm 275 biliary 38 indeterminate biliary strictures 320–1 formalin, in hydatid cyst surgery 395 Frey’s procedure 252 Fusion system 36, 462

G

gabexate 55 gabexate mesylate 103, 115, 209 gallbladder, cholecystitis after sphincterotomy 58 gallbladder cancer, anomalous pancreaticobiliary junction (ABPJ) and 392, 447 gallbladder carcinoma, prognosis and risk factors 287 gallstones 357 vs air bubbles 26 causing acute pancreatitis 435 nonradiopaque 20 occult gallstone disease 435, 436 origin 364 see also acute gallstone pancreatitis Gardner’s syndrome 279, see also familial adenomatous polyposis gastrectomy Roux-en-Y see Roux-en-Y gastrectomy total 243–5

498

gastric banding 246, 247 gastric bypass 247–9 gastric resection 237–45 Billroth I 237 Billroth II 237–42, 256–7 Roux-en-Y gastrectomy 242–3 total gastrectomy 243–5 gastroenteroanastomosis 348 gastroenterology, medicolegal issues 3 gastrointestinal endoscopy, medicolegal issues 3, 9 gastrointestinal stromal tumors (GIST) 278 gastrojejunostomy 245 gastroplasty, vertical banded 245, 246–7 Geenen-Hogan (G-H) criteria, sphincter of Oddi dysfunction (SOD) 367–8, 369, 376 gemcitabine 295 gene analysis, pancreatitis in children 228 generator currents 32 generators 14–15 genetic mutations/abnormalities 441, 455 gentamicin 129 glucagon 40, 143, 192, 220, 372 glue injection, into the pancreatic duct 429 guidelines, professional 4 guidewires 33–5 coated (sheathed) 34 coiled 34 hydrophilic 34–5 monofilament 34 types 34–5 wire safety 35

H

Helicobacter pylori 278 hemorrhage (bleeding) as complication of ERCP 52, 53 as complication of EST/EPBD 101–2 as complication of large balloon dilation after minimal biliary sphincterotomy 105 as complication of sphincterotomy 95–6 EST-related 115–16 prevention 56 risk factors for 8 after sphincterotomy 56 during sphincterotomy 56 treatment 56 heparin 56 hepatectomy 412 hepatic ducts 447 hepaticocutaneous jejunostomy 255 hepaticojejunostomy identification 350–1 hepatobiliary disease, parasitic infestation 393 hepatobiliary scintigraphy (HBS), for SOD 369–70 hepatolithiasis 412 hilar cholangiocarcinoma adjuvant therapy 302 Bismuth classification 299 criteria for unresectability 300 imaging 300–1 orthotopic liver transplantation (OLT) for 301 palliation 301–2 percutaneous approach 302 preoperative histological confirmation 301 radiological studies 300–1 risk of acute cholangitis 309

surgery for localized cancer 301 surgery for unresectable cancer 301–2 see also cholangiocarcinoma hilar obstruction, SEMS placement 172 hilar strictures 300, 302–8 hilar tumors 23 HIV-associated cholangiopathy, in children 226 hospital liability 5 hydatid cysts 394 cysto-biliary communication 394, 395 intrabiliary rupture 394–5 and obstructive jaundice 394, 395 postoperative complications 395 hydatid disease 394–5 endotherapy 394 hyoscyamine 40 hyperamylasemia, post-EPBD 102–3 hypoventilation, alveolar 46

I

idiopathic acute pancreatitis (IAP) causes 435 controversy about SOM 438 diagnosis 435–6 diagnostic yield of ERCP 442 due to SOD 437–8 endoscopic approach 435 ERCP timing 435 genetic testing 441 investigations 441–2 recurrent see idiopathic acute recurrent pancreatitis idiopathic acute recurrent pancreatitis (IARP) 435, 455 choledochoceles causing 439 diagnostic yield of ERCP 442 investigations 441–2 outcomes of endoscopy therapy 442–3 pancreas divisum and 438–9 SOD as a cause of 437–8 stenting 438 idiopathic chronic pancreatitis 459 idiopathic pancreatitis 419 IDL see intraductal lithotripsy IDUS see intraductal ultrasound image intensifier 15 imaging, digital vs conventional 15 imatinib mesylate 278 imipenem 485 immunoglobulin G, in indeterminate biliary strictures 313 see also autoimmune pancreatitis indemnity insurance 10 indemnity payments 3 indeterminate biliary strictures 313–25 ancillary techniques 321–4 brush cytology 320 characterization 313, 317 definition 313 ERCP in 314, 317, 319 historical features 313 imaging invasive 316–19 non-invasive 313–16 principles 317–19 inadequate treatment 313 intraductal forceps biopsies 320–1 intraductal transmucosal fine needle aspiration 320

INDEX laboratory features 313 malignant 317 pathologic investigations 319–21 stent placement 323 stricture dilation 318–19 surgical exploration 324 tissue acquisition 319–21 indications for ERCP 26 marginal 9, 10 in pancreaticoduodenectomy 353 in recurrent pyogenic cholangitis (RPC) 406 indigocarmine staining 191 infection, post-EST/EPBD 101, 103 inflammatory bowel disease, in children 223–4 informed consent 9 disclosure of physician’s experience 6, 9 documentation of 9–10 elements of risk in disclosure 6 endoscopic pancreatic sphincterotomy 129 endoscopic papillary balloon dilation (EPBD) 97 for ERCP for suspected sphincter of Oddi dysfunction (SOD) 370 exceptions 6 failure to obtain, legal consequences 6 informed refusal 6 legal principles 5–6 material risks 6 patient’s competence and 6, 9 risk management and 3, 6 theory of 5–6 informed refusal 6 insurance, indemnity insurance 10 insurance companies information for 10 information from 3 interleukin 10 55 intraductal electrohydraulic lithotripsy 127–8 complications 127–8 contraindications 127 indications 127 key points 127 technique 127–8 intraductal lithotripsy (IDL) for pancreatic stone fragmentation 461 see also intraductal electrohydraulic lithotripsy; laser lithotripsy intraductal papillary mucinous neoplasia (IPMN) 467–74 diagnosis 470, 471 incidence 467 pancreaticoduodenectomy for 347 pathogenesis 467 pathology 468–9 prognosis 472 intraductal papillary mucinous tumors (IPMTs) 199, 440, 440–1 endoscopic therapy 441 as indication for pancreatoscopy 206–7 intraductal transmucosal fine needle aspiration, indeterminate biliary strictures 320 intraductal ultrasound (IDUS) 440 ampullary neoplasm 276 biliary cysts (choledochal) 449 in choledocholithiasis diagnosis 357 hilar cholangiocarcinoma 301 indeterminate biliary strictures 321–2 intrahepatic stones, treatment in RCP, techniques 399–406

IPMN see intraductal papillary mucinous neoplasia IPMTs see intraductal papillary mucinous tumors isosorbide dinitrate 103, 202, 373

J

jaundice in biliary malignancies 287, 288 obstructive see obstructive jaundice post pancreatic surgery Brigham and Women’s Hospital experience 353 choledochojejunostomy and 348 as symptom of ampullary tumors 273 as symptom of neuroendocrine tumors 277 juxtapapillary duodenal diverticula 112

K

Kasai procedure (portoenterostomy) 222 Kehr’s tube, associated biliary complications 340 Klatskin tumors 299, 305, 306, 308 Klebsiella, in cholangitis 359 Klebsiella spp. 304

L

laparoscopic cholecystectomy (LC) 97 bile duct stones found during 363–4 bile duct stones retained after 339–40 biliary leaks after 335, 337 classification of biliary injuries during 336 complications after 336 contraindications for endoscopic treatment following 338 for pancreatitis due to microlithiasis 436 laparoscopic exploration of the common bile duct (LECBD) 362–4 laparotomy 116 large balloon dilation after minimal biliary sphincterotomy 103–5 complications 105 laser lithotripsy 127, 399–400, 404 lasso technique, stent removal 185 lateral pancreaticojejunostomy (Puestow procedure) 347 lawsuits avoidance strategies 9–10 if filed 10–11 limiting costs of 10–11 reasons for 8–9 risky clinical situations 10 lead aprons 16, 19 legal principles in medical practice 4 see also medicolegal issues liability employers’ 5 hospitals’ 5 vicarious 5 lithotripsy basket mechanical lithotripsy (BML) 360 electrohydraulic (EHL) 215, 362, 399–400, 402, 404 endoscopic mechanical lithotripsy (EML) 105 intraductal see intraductal lithotripsy laser lithotripsy 127, 399–400, 404 see also extracorporeal shock wave lithotripsy; intraductal electrohydraulic lithotripsy; mechanical lithotripsy

lithotripsy baskets 39, 123–7, 127 lithotripters 124–5 electrohydraulic 127 mechanical 39 through-the-scope (TTS) 125 liver biopsy, in primary sclerosing cholangitis (PSC) 379 liver enzymes, abnormal 379 liver function tests 265 liver transplantation 254–5 bile leaks associated with 342 biliary cast syndrome 343 biliary complications 342–4 complications 342–4 filling defects 343 fistulas associated with 342 for hilar cholangiocarcinoma 301 for malignancies, controversy 344 primary sclerosing cholangitis (PSC) and 384 recurrent biliary disease after 343 stent removal 185 strictures associated with 342–3 lymphomas biliary 278 diffuse large B-cell lymphomas 278 follicular 278 MALT (mucosa-associated lymphoid tissue) lymphomas 278 T-cell lymphoma 278

M

macrocystic serous cystadenomas 468, 470 magnetic resonance cholangiopancreatography (MRCP) in acute gallstone pancreatitis 411 advantages and limitations 267 benefits in post-pancreatic surgery 353 in biliary obstruction 267 in choledochal cyst diagnosis 389 in choledocholithiasis diagnosis 357 in diagnosis of bile/pancreatic duct leaks 347 dilated bile duct 266–7 disadvantages 315–16 hilar cholangiocarcinoma 300–1 in IAP and IARP 442 indeterminate biliary strictures 314, 314–15, 315 in primary sclerosing cholangitis (PSC) 379 secretin-MRCP (S-MRCP) 421, 424, 437, 442 magnetic resonance imaging (MRI) ampullary neoplasm 275 in chronic pancreatitis (CP) 459 dilated bile duct 266–7 hilar cholangiocarcinoma 300–1 in IAP and IARP 442 indeterminate biliary strictures 314–16 pancreas 289 and pancreatic fluid collection 478 periampullary tumors 275 magnification, calculation of 21 main pancreatic duct (MPD), cannulation 459–60 major papilla cannulation of 73–81 ectopic 447 endoscope positioning 74–5 evaluation 74–5 malignant tumors 440 malabsorptive-jejunoileal bypass 246 malabsorptive operations 246

499

INDEX malignant biliary obstruction, distal 287–98 adjuvant therapy 295–6 ampullary carcinoma 288 biopsies 289 chemotherapy 295–6 cholangiocarcinoma 290 clinical features 287–8 differential diagnosis 288–90 endoscopic stenting 291–4 epidemiology 287 imaging techniques 288–90 metastatic disease 290 natural history 287 palliation 291–5 pancreatic malignancies 287, 288–90 patient management 290–6 percutaneous stenting 294–5 presenting symptoms 287–8 stent choices 293–4 stenting 291–5 surgery, curative 291 surgery, palliative 295 tumors causing 287 malignant biliary obstruction, hilar 299–311 classification 299 costs 303, 307, 309–10 diagnosis 301 endoscopic drainage 302–3 epidemiology 299 management strategies 299–302 patient preparation 304–5 percutaneous stenting 303 preoperative histological confirmation 301 preoperative stenting 303 radiological studies 300–1 risk of acute cholangitis 309 stent implantation technique 303–6 stent insertion complications 308–9 summary 309–10 surgical bypass 301–2, 303 tissue sampling 301 see also hilar cholangiocarcinoma malpractice 4 insurance 10 new technology and 7 MALT (mucosa-associated lymphoid tissue) lymphomas 278 manometry, pancreatobiliary 95; see also sphincter of oddi manometry catheters 92 interpretation of recordings 94 triple lumen 94 mask ventilation, difficulties with 45 MCNs see mucinous cystic neoplasms mebendazole 396 mechanical lithotripsy 124–7, 128 basket (BML) 360 complications 124, 126–7 contraindications 124, 126 endoscopic (EML) 105 indications 124, 126 key points 123–4 technique 124–6 through-the-scope (TTS) 125 medical practice, legal principles 4, 7 medicolegal environment 3 medicolegal issues in gastroenterology 3 in gastrointestinal endoscopy 3, 9 500

in medical practice 4 summary 11 meperidine 91, 372 meropenem 485 metastatic disease 290 methylene blue 143, 191, 193, 351 microcystic serous cystadenomas 468, 470 microlithiasis 436 biliary 415 endoscopic ultrasound and 267, 268 midazolam 44, 91, 305 in pregnancy 233 minor papilla cannulation 81–4 advanced techniques 83–4 indications for 81 standard techniques 81–3 locating 81–2 pancreatitis and 455 sphincterotomy see minor papilla sphincterotomy minor papilla sphincterotomy 143–51, 460 accessories 143 cautery unit 143–4 complications 149–50 contraindications 143 current type 143–4 guidewires 143 indications 143 needle-knife sphincterotomy 143, 145 over pancreatic duct stent 147 outcomes 149–50 precut sphincterotomy technique 147–50 orifice seen 147–8 no orifice seen 148 re-do cases 149 with Santorinicele 148–9 pull-type sphincterotomy 143, 145 technique 145–7 sedation 143 sphincterotomes, choice of 145 stents 144–5, 150 summary 151 supplemental drugs 143 Mirizzi syndrome 357 monitors, placement in ERCP room 13–14 MRCP see magnetic resonance cholangiopancreatography MRI see magnetic resonance imaging mucinous cystic neoplasms (MCNs) clinical epidemiology 467 diagnosis 470 k-ras mutation 468 “ovarian stroma” 468 pathogenesis 467, 468 pathology 468–9 types 468 mucinous ductal ectasia 140 see also IPMN, IPMT mucosa-associated lymphoid tissue (MALT) lymphomas 278 multiple organ dysfunction syndrome (MODS) score 412 Murphy’s sign 411

N

nafamostat mesilate 209 naloxone 16

nasobiliary drain (NBD) in acute cholangitis 360–1 temporary 360 nasobiliary drainage catheters 36, 38, 260 nasobiliary tubes, in treatment of biliary leaks 335 nasopancreatic drainage catheters 36, 38 N-butyl-2-cyanoacrylate 178 needle-knife access sphincterotomy, precautions against complications and lawsuits 9 needle-knife papillotomy 89 needle-knife precut accessotomy 88–90 needle-knife sphincterotomy 77–9 complications 77–9 minor papillary 143, 145 pancreatic 134, 136 needle tip catheters 31, 82 negligence 4, 5, 8 neonatal cholestasis 222 neonates, duodenoscopes for examination in 31 neo-papilla 65 neuroendocrine carcinomas 277–8 neuroendocrine tumors (NET) 277–8 neurofibromatosis (von Recklinghausen disease) and 277 neurofibromatosis, neuroendocrine tumors and 277 new onset steatorrhea 464 nifedipine 373 nitrates 373 nitric oxide (NO) 373 non-steroidal anti-inflammatory drugs (NSAIDs) 55, 56, 129

O

obstructive cholestasis, untreated 313 obstructive jaundice, hydatid cysts and 394, 395 occult gallstone disease 435, 436 octreotide 55, 96 operator experience, and complications of ERCP 54, 58 Opisthorchis felineus 395 Opisthorchis viverrini 395 organ failure 412 organized (walled-off ) pancreatic necrosis 483 antibiotics 485 endoscopic debridement 485 endoscopic drainage 485–6 endoscopic therapy results 488 orthotopic liver transplantation (OLT) see liver transplantation oxygen administration 46

P

PACS (picture archiving and computerized storage) system 16, 19 pain in chronic pancreatitis (CP) 459, 464 diagnoses other than SOD 367, 368, 369 Geenen-Hogan (G-H) criteria 367–8, 369 pancreatic 370 pancreaticobiliary 367, 369 in sphincter of Oddi dysfunction (SOD) 367–8, 370 with gallbladder in situ 370 pain evaluation, post pancreatic surgery, Brigham and Women’s Hospital experience 353 pancreas annular 456–7 imaging techniques 199

INDEX pancreas divisum 27, 438–9, 442, 449–56 association with pancreatitis 455–6 complete 454 diagnosis 82, 438, 454–5 embryology 449–54 endoscopic therapy 438–9, 455–6 idiopathic acute recurrent pancreatitis (IARP) and 438–9 incomplete 82, 454, 456 minor papilla therapy 143 minor papilla ductography and 84 minor papilla therapy 143 pseudodivisum 455 stenting 438–9 terminology 454 pancreatectomy, distal 347 pancreatic abscesses 476 endoscopy therapy results 488 pancreatic anomalies 449–57 pancreatic ascites 422 pancreatic cancer differentiation 207–8 early detection 208 see also pancreatic malignancies pancreatic cystic lesions clinical presentation 469 diagnosis, methods 470–1 differential diagnosis 469 loss of heterozygosity (LOH) and 467, 468 pathogenesis 467 prevalence 467 prognosis 472 treatment 472 types 467 pancreatic duct (PD) 74 cannulation of 80–1 drainage see pancreatic duct drainage extravasation from 26 leaks see pancreatic fistulas obstruction 160–1, 435 opacification 24–6 perforation 116 stents see pancreatic duct stents pancreatic duct drainage 250–2, 463 Duval procedure 252 Frey’s procedure 252 Puestow procedure 250 pancreatic duct stents to facilitate biliary cannulation 76–7 insertion 158–9 in sphincter of Oddi manometry 94, 95 pancreatic fistulas 420–1 classification 420 complications 429–31 chronic 431 immediate 430 subacute 430–1 contraindications for endoscopic approach 422 diagnosis 421 external 420, 424–9 indications for endoscopic approach 422 internal 420 management 421–9 pancreatic fluid collections (PFCs) 475 acute fluid collections 475 drainage 159 endoscopic therapy complications 489–90 controversies 489

operator experience 488–9 results 486–8 liquefied 475–6 contraindications to drainage 477 drainage techniques 478 indications for drainage 476–7 pre-drainage evaluation 477–8 stent placement 480–2 symptoms 477 masqueraders of 477 outcome differences following endoscopic drainage 488 types 475 pancreatic malignancies 287, 288–90 presenting symptoms 287–8 risk factors 287 see also pancreatic cancer pancreatic necrosis 475–6, 482–5 organized see organized (walled-off ) pancreatic necrosis walled-off (WON) see organized (walled-off ) pancreatic necrosis pancreaticobiliary dilation 38 pancreaticobiliary manometry 95 catheters 31 see also sphincter of Oddi manometry pancreaticoduodenal fistula, iatrogenic 464 pancreaticoduodenectomy 347 for ampullary adenomas 279 for ampullary carcinomas 280 Brigham and Women’s Hospital experience 353 classic 348–9 ERCP approaches after 351–2 in familial adenomatous polyposis (FAP) 279 indications for ERCP 353 postoperative complications 290 pylorus-preserving 349 types 348–9 see also Whipple procedure pancreaticoenteric fistulas 422–4 pancreaticogastrostomy 250 pancreaticojejunostomy complications 348 identification of 351 lateral (Puestow procedure) 347 pancreatic pseudocysts 422, 467, 469 acute 475–6, 483 chronic 476 diagnosis 470 endoscopic therapy results 486–8 infected 476 pancreatic abscesses 476, 488 pancreatic resection 249–50 mid-pancreatic 250 pancreaticogastrostomy 250 tail of the pancreas 250 Whipple procedure, conventional 249–50 Whipple procedure, pylorus-preserving 250 see also pancreaticoduodenectomy pancreatic sphincter hypertension 376, 438 pancreatic sphincterotomy 129–42, 459–60 antibiotics and anticoagulants 129 biliary sphincterotomy immediately before 134 complications 140–1 costs 141 current type 129–30 endoscopic technique 130–1 equipment 129–30

indications for 135–40 needle-knife sphincterotomy 134, 136 precut pancreatic sphincterotomy 134 preparation 129 as primary therapy 136–40 pull-type sphincterotomy 131–4 as secondary therapy 140 in sphincter of Oddi dysfunction (SOD) 136–8 pancreatic stenosis, differentiation 207–8 pancreatic stents 37 complications 162 for EST patients 115 plastic 153, 155, 158–9 indications 160–1, 177 precautions against complications and lawsuits 9 reducing risk of post-ERCP pancreatitis 54–5 in treatment of post-ERCP pancreatitis 56 pancreatic surgery, complications 347–55 endotherapy 351 ERCP for 347–55 accessing and traversing the afferent limb 350 Brigham and Women’s Hospital experience 352–4 endoscopes and accessories 350 endotherapy 351 hepaticojejunostomy identification 350–1 negotiating the anatomy 350–1 pancreaticojejunostomy identification 351 long-term 348 prevention of 347 short-term 347–8 pancreatitis acute see acute pancreatitis association of pancreas divisum with 455–6 biliary see acute gallstone pancreatitis (AGP) in children 227–9 acute 227–8 as complication of ERCP 229 gene analysis 228 persistent/recurrent/chronic 228–9 chronic see chronic pancreatitis as complication of ERCP 51, 52–6 in children 229 as complication of EST/EPBD 101, 102–3 as complication of pancreatic sphincterotomy 141 as complication of pancreatobiliary manometry 95 ERCP-related 115 EST-related 114, 115 idiopathic 419 lawsuits involving 8 pharmacologic prophylaxis 115 postampullectomy 193–4, 195 risk factors, EST-related 115–16 pancreatitis, post-ERCP (PEP) patient-related risk factors 53–4 pharmacological agents 55–6 prevention of 56, 374–5 risk factors 8 technique-related 54 risk reduction techniques 54–5 treatment 56 pancreatobiliary malunion see anomalous pancreaticobiliary junction; anomalous pancreatobiliary union 501

INDEX pancreatoscopes 199 baby scopes 199–200, 204 cost 209 fiberoptic 199, 200–2, 204 image converters 200–2 insertion procedure 202–3 mother scopes 199–200 peroral electronic (PEPS) 199, 204, 207; see also pancreatoscopy ultrathin 199, 202–3, 203, 204, 209 video 199, 200 pancreatoscopy 199–210, 440 biopsy 203–4 complications 209 cytology sampling 203–4 endoscopic procedure 202–5 equipment 199–202 findings in pancreatic diseases 205 indications 206–9 procedure timing 202 scope insertion 202–3 success rates 204–5 technique 199–202 visualization 204 papillae balloon dilation 97–107 see also major papilla; minor papilla papilla of Vater, double 447 papillary roof incision 33 papillary spasm see sphincter of Oddi dysfunction papillary stenosis 96, 140 re-stenosis 150 see also sphincter of Oddi dysfunction papillectomy 189 papillitis see sphincter of Oddi dysfunction papillomatosis, biliary 214, 216 papillotomes 54 papillotomy needle-knife 89 precut 87 parallel cannulation 80 parasites 231 parasitic disease 393–8 patients monitoring 46–7 physician–patient relationship 4, 8, 9 positioning during ERCP 19, 23, 25 pregnant 19, 41 radiation exposure 19, 40–1 patient table 13 pediatric duodenoscopes 31 pediatric ERCP 219–30 complications 229 contraindications 222–9 cost 229 endoscopists 219 equipment 220 fluoroscopy 219–20 indications 222–9 procedure setting 219 sedation 219 supplemental medications 220 technique 220–1 peer review, adverse events 8 percutaneous endoscopic gastrostomy (PEG) 248 percutaneous transhepatic biliary drainage (PTBD) 400–1 equipment 400 502

percutaneous transhepatic cholangiography (PTC) 268, 269, 319 percutaneous transhepatic cholangioscopy (PTCS) 400–2, 401–2 advantages 402 complications 411 cost 409 drawback 402 examination 401–2 percutaneous transhepatic biliary drainage (PTBD) 400–1 tract dilation 401 percutaneous transhepatic pneumatic dilation 328 percutaneous transhepatic therapy 328 perforation as complication of ERCP 52, 56–8 ERCP-related rates 116 EST-related 116 post-EST/EPBD 101, 103 risk factors during ERCP 8, 57 periampullary diverticula 79 periampullary duodenal diverticula cannulation in patients with 79–80 terminology 79 periampullary tumors, magnetic resonance imaging (MRI) 275 peroral electronic pancreatoscope (PEPS) 199, 204, 207; see also pancreatoscopy pethidine 305 photodynamic therapy (PDT) 384 Photofrin 384 Physician Insurers Association of America (PIAA) 3 physician–patient relationship 4, 8, 9 physician–physician interaction 19 picture archiving and computerized storage (PACS) system 16, 19 piperacillin 129, 305, 485 plastic stents 36–7 biliary 153–8 configurations/sizes 153 cost 162, 291–2, 293 in distal malignant biliary obstruction 291–2 fixed-diameter see fixed-diameter plastic stents (FDPS) in hilar malignant biliary obstruction 305–8 indications for 160–1 pancreatic 153, 158–9 small-caliber 158–9 stent patency 37, 153, 165–6 stent removal 177, 178–9, 183, 185 platelet-activating factor inhibitors 56 Plavix 56 pleural effusions 422 polyposis syndromes hereditary 189 see also familial adenomatous polyposis; Gardner’s syndrome portoenterostomy (Kasai procedure) 222 positron emission tomography (PET), hilar cholangiocarcinoma 301 post-cholecystectomy syndrome (PCS) 341 see also sphincter of Oddi dysfunction practice parameters 4 praziquantel 396 preceptors 5 precut accessotomy 87 complications 90

indications 87 needle-knife 89 technique 87–8 precut biliary sphincterotomy 77–9 precut fistulotomy 77 precut pancreatic sphincterotomy 134 precut papillotomy 87 precut (access) sphincterotomes 32–3 precut sphincterotomy technique 147–50 pregnancy 19, 41, 231–5 ascariasis in 231, 234, 393 avoidance of fluoroscopic images 232–3 biliary disorders 234 choledocholithiasis 231, 234 cholelithiasis 231 complications, ERCP-related 231 fluoroscopy time 232–3 indication for ERCP 231 outcomes 234 physiologic changes of pregnancy 233 positioning 233 radiation protection 231–3 sedation 233–4 primary sclerosing cholangitis (PSC) 287, 379–86 background 379 biliary strictures 332 cholangiocarcinoma in see cholangiocarcinoma (CA) cost 380–1 diagnosis 379 complications of ERCP 379–80 contraindications 379 indications 379 technique 379 endoscopic treatment 381–3 complications 382 contraindications 382 cost 382–3 indications 382 technique 381–2 natural history 379 symptoms 379 privileging 8 proctors 5 propofol 91 case studies 44 guidelines for administration of 47–8 in pregnancy 233, 233–4 in sphincter of Oddi manometry (SOM) 372 Proteus spp., in cholangitis 359 pseudocysts see pancreatic pseudocysts pseudodivisum 455 Pseudomonas, in cholangitis 359 Puestow procedure (lateral pancreaticojejunostomy) 250, 347 pull-type sphincterotomes 32 pull-type sphincterotomy minor papillary 143, 145, 145–7 pancreatic 131–4 pulse oximetry 46

R

radiation ERCP method to avoid exposure 233 exposure types 231 monitoring 19 patient exposure to 19, 40–1 protection, in pregnancy 231–3 staff exposure to 15, 16, 19, 40–1, 231

INDEX radiation dosimeters 16 radiographic images, white-on-black vs black-onwhite 20 radiologic imaging equipment 15–16 comparison of 15 components 15 controls 15–16 digital vs conventional 15 fixed vs portable 15 image capture and storage 16 imaging components 15 radiographic hardware 16 radiologic issues, in ERCP 19–30 Ranson’s criteria, biliary pancreatitis 412, 416 Rapid Exchange (RX) Biliary System 35 recurrent cholangitis, post pancreatic surgery 348 recurrent pyogenic cholangitis (RPC) 357, 399–410 complications 406–8 contraindications for ERCP/PTCS 406 cost 412 indications for ERCP/PTCS 406 initial management 399 key points 399 long-term management 408 surgery 408–9 see also intrahepatic stones rendezvous procedure/technique 80, 110, 113, 351–2 EUS-guided 80, 83 internal rendezvous procedure 341 malignant biliary obstruction, hilar 305 SEMS placement 172 in surgically altered anatomy 249, 255–6 repeat ERCP 80 reprivileging 8 respondeat superior 5 Reynold’s pentad 359 risk management strategies 6–8 avoiding complications and lawsuits 9–10 informed consent and 3, 6 summary 10 technique-related 9 Robotics Interactive Endoscopy Simulation (RIES) System 63 Rome criteria, sphincter of Oddi dysfunction (SOD) 367 roundworms see Ascaris lumbricoides Roux-en-Y anatomy, EST and 113 Roux-en-Y choledochojejunostomy 254 Roux-en-Y gastrectomy 242–3 Roux-en-Y gastric bypass 245, 247 Roux-en-Y hepaticojejunostomy 252–4, 255 RPC see recurrent pyogenic cholangitis RX see Rapid Exchange

S

Santoriniceles 148–9, 455 scintigraphy biliary, dilated bile duct 269 hepatobiliary (HBS), for SOD 369–70 sclerosing cholangitis 343 pediatric 223 see also primary sclerosing cholangitis secretin 55, 81, 82, 91, 193, 220, 349, 351 injection 40 in minor papilla sphincterotomy 143 in pancreatoscopy 203

sources 82 ultrasound tests 456 secretin-MRCP (s-MRCP) 421, 424, 437, 442 sedation minor papilla sphincterotomy 143 for pediatric ERCP 219 in pregnancy 233–4 in sphincter of Oddi manometry (SOM) 372 summary 48 sedation and analgesia 43–9 adverse effects 44 conscious sedation 43 endoscopists and 44 levels of 43, 44 patient evaluation guidelines 45 patient monitoring 46–7 physiology of 43 practice guidelines 44–5 pre-procedure evaluation 45–6 safety of 43–4 self-expandable metallic stents (SEMS) 37–8, 165, 177 benign biliary strictures 330 complications 173–4 contraindications 166 cost-effectiveness 174, 293, 294 covered 166, 168–9, 174, 177, 186 Diamond Ultraflex stent 167–8 in distal malignant biliary obstruction 291, 292–4 vs fixed-diameter plastic stents (FDPS) 165–6, 174 Flexxus stent 168 in hilar malignant biliary obstruction 305–8 complications 308–9 indications 165–6 patency 37, 165–6, 177 placement techniques 169–73 cholangiogram 170 deployment 171–2 dilation 170 duodenal obstruction 172–3 duodenoscope 169–70 endoscopic guides 171 fluoroscopic guides 171 guidewire use 170 hilar stricture 172 rendezvous technique 172 SEMS positioning 170–1 sphincterotomy 170 stent selection 170 polyurethane-covered 293 removal 177, 178, 185–6 stent occlusion 165, 174 types 167–9 uncovered 177, 186, 187 Viabil 169 Wallstent 165–6, 167, 168, 169 Y stent 169 Zilver stent 168 Z stent 168 septicemia 359 serous cystadenomas 467, 468, 470 macrocystic 468, 470 microcystic 468, 470 pathology 468 solid 468 serum amylase levels 411 serum C-reactive protein level 412

“setting sun” 73 severe acute pancreatitis (SAP) organ failure 412 recognition of 412 scoring systems 412 severe chronic pancreatitis clinical results 463–4 stenting 462 technical results 462–3 see also extracorporeal shock wave lithotripsy sheep liver fluke see Fasciola hepatica shouldered strictures 23 Simbionix GI-Mentor computer simulation models 63, 68 simulators 66–7 skills interpersonal 8 maintaining 68 major vs minor 7 see also competence sleeve catheters 95 small intestine, navigating through 256 s-MRCP (secretin-MRCP) 421, 424, 437, 442 snare papillectomy (endoscopic resection) 440, see also ampullary adenomas; ampullary tumors SO see sphincter of Oddi SOD see sphincter of Oddi dysfunction (SOD) sodium nitroprusside (SNP) 373 solid pseudopapillary tumor 469 SOM see sphincter of Oddi manometry (SOM) somatostatin 55, 115, 424 sphincter ablation therapy 437, 438 sphincter of Oddi (SO) 91 function 91, 436–7 sphincter of Oddi dysfunction (SOD) 91, 436–8 biliary sphincterotomy in 114, 374, 375–6 in children 228 clinical evaluation 368–70 clinical syndromes associated with 367 complication rate 51 definitions 367–8 diagnosis 437, 438 emotional burden on patient 369 Geenen-Hogan (G-H) criteria 367–8, 369, 376 informed consent for ERCP 370 pain with gallbladder in situ 370 pain in 367, 369 pancreatic 136–8 diagnostic criteria 137 post-endoscopic recurrent pain 375–6 as risk factor for pancreatitis 53, 419 Rome criteria 367, 368 symptoms 369 tests for 369–70 tests used for detection of 91 sphincter of Oddi dysmotility, in children 226–7 sphincter of Oddi manometry (SOM) 32, 91–6, 136–7, 370–2 abnormalities in 94 cannulation 371–2 catheters 95–6 complications 95–6 for diagnosing SOD 437, 438, 442 duodenal baseline pressure 372 equipment 95–6, 370–1 equipment preparation 91–5 indications 95 interpretation of recordings 372 503

INDEX sphincter of Oddi manometry (SOM) (cont.) kissing technique 371 pancreatic duct stent 94, 95 patient monitoring 96 patient preparation 91 scientific basis 91 sedation 372 sphincterotomy 91, 94 technique 91–5, 371–2 treatment, endoscopic 373–4 treatment, medical 373 type of current 94 sphincterotomes access (precut) 32–3 biliary cannulation with 75–6 in Billroth II gastrectomy 256 for minor papilla sphincterotomy 143, 145 needle-knife 32 for pancreatic sphincterotomy 130 pull-type 32 “reverse” 40 rotatable 32 single vs reusable 40 types of 32, 109–10 sphincterotomy access techniques 77 antegrade 113 biliary see biliary sphincterotomy; endoscopic biliary sphincterotomy in children 222, 228, 229 complication rates 51–2 dual sphincterotomy 376 indications 26 minor papilla see minor papilla sphincterotomy and nasobiliary drain (NBD) in cholangitis 360 needle-knife 77–9 pancreatic see pancreatic sphincterotomy postampullectomy 193–4 precut, hemorrhage after 56 preresection 192–3 prophylactic 193 as risk factor for pancreatitis 54 sphincter of Oddi manometry 91, 94 thermal injury after 55, 56 trans-pancreatic precut 90 see also endoscopic biliary sphincterotomy sphincterotomy perforation 57 spiral baskets 122 staff experience, and complications of ERCP 54, 58 radiation exposure 15, 16, 19, 40–1, 231 standards of care 4–5 majority vs minority standards 4 steatorrhea, new onset 464 stenosis, papillary 96, 140 re-stenosis 150 stent cannulation, in stent removal 180–3 stenting affecting bile leakage 335 benign biliary strictures 328–32 biliary, complication 330–2 in cholangiocarcinoma (CA) 384 cholangitis 361 chronic pancreatitis (CP) 463 pancreatic 375 severe chronic pancreatitis 462 504

stent patency plastic stents 37, 153, 165–6 self-expandable metal stents (SEMS) 37, 165–6, 177 stent placement EST and 115 to facilitate biliary cannulation 76–7 image of 27 indeterminate biliary strictures 323 PFCs and 480–2 postampullectomy 193–4 self-expandable metallic stents (SEMS) techniques 169–73 stent removal 37, 177–87 accessories used 178–9 balloon traction 179–80 complications 186 contraindications 177–8 controversies 186 costs 187 direct grasping 179 duct access and 177 indications 177–8 “lasso” technique 185 liver transplantation and 185 plastic stents 177, 178–9, 185 self-expandable metallic stents (SEMS) 177, 178, 185–6 stent cannulation 180–3 techniques 177, 178–85 stent retrievers 37 as dilators 38 stents antireflux 153, 185 associated with minor papilla sphincterotomy 144–5 biliary see biliary stents bioabsorbable self-expanding 335 double pigtail 159 endoscope requirements 153 migrated 178 occluded 178 pancreatic see pancreatic stents patency see stent patency pigtail 37, 157 placement see stent placement plastic see fixed-diameter plastic stents (FDPS); plastic stents removal see stent removal self-expandable metallic see self-expandable metallic stents (SEMS) temporary 178 Viaduct 185 steroids, for autoimmune pancreatitis 441 stomach, endoscope passage through 73 stone extraction 119–28 accessories 38–9 assessing stone size 119 balloon stone extraction 119–21 basket stone extraction 121–3, 128 and dilation, after extracorporeal shock wave lithotripsy (ESWL) 461–2 image of 27 stone fragmentation methods 119 using electrohydraulic lithotripsy (EHL) 215 stone removal see cholangioscopic stone removal

stones assessing size 119 see also bile duct stones; gallstones; stone extraction strictures dilation devices 38 shouldered 23 sulbactam 220 sump syndrome 80, 252, 340–1 supine hypotensive syndrome 233 suprapapillary fistulotomy 89 surgery ampullary tumors 189 ERCP and 237 hilar cholangiocarcinoma 313–14 malignant biliary obstruction, distal 291, 295 malignant biliary obstruction, hilar 301–2, 303 see also bariatric surgery; biliary surgery; biliary surgery complications; pancreaticoduodenectomy; Whipple procedure surgically altered anatomy 237–58 bariatric surgery 245–9 biliary surgery 252–5 endoscopic techniques 255–6 ERCP accessories 256–7 esophageal resection 237 gastric resection 237–45 pancreatic duct drainage 250–2 pancreatic resection 249–50 upper GI bypass surgery without resection 245 swing-tip catheters 31

T

tachyoddia see sphincter of Oddi dysfunction tapered-tip catheters 31, 95 tazobactam 129, 305 T-cell lymphoma 278 teaching skills, train-the-trainer sessions 67–8 techniques, risk management strategies 9 technology 7–8 and malpractice 7 and training 7 and vicarious liability 7–8 thyroid collars, storage 16 ticlopidin 114 tissue sampling devices 38 TNM staging system 275–6 Todani classification, choledochal (biliary) cysts 387, 389, 448 tort law 4 tort of negligence 5 torus pylorus 64 traction papillotome techniques 90 training 7, 61–70 artificial tissue models 66 ASGE guidelines 61, 62 clinical training 61–3 guidelines 7 hands-on workshops 67–8 levels of 66 with live animals 63–4 models 63, 66 new technology and 7 porcine tissue models 64–6 simulators 63, 66–7 survey of 68

INDEX transabdominal ultrasound (TUS) advances in 288 ampullary carcinoma 288 ampullary neoplasm 275 in choledocholithiasis diagnosis 357 hilar cholangiocarcinoma 300 indeterminate biliary strictures 314 jaundiced patients 314 pancreatic malignancies 288 transmural drainage contraindications 477, 478 entry devices 479 entry techniques 479 EUS-guided 479–80 non-EUS-guided 480–2 transpancreatic papillary septotomy 79 transpancreatic precut sphincterotomy 90 transpapillary drainage 478–9, 485 triamcinolone 341 triclabendazole 396 T-tubes 340, 342, 362, 402–3, 411 tumors benign, as cause of pancreatitis 440 IAP and 440–1

mucinous 435 see also mucinous cystic neoplasms Turcot syndrome 279 TUS see transabdominal ultrasound

U

ulcerative colitis, in children 223–4 ulinastatin 209 Ulistatin 55 ultrasound (US) dilated bile duct 265–6 endoscopic see endoscopic ultrasound (EUS) intraductal see intraductal ultrasound (IDUS) transabdominal see transabdominal ultrasound (TUS) ultrasound probes 39–40 ursodeoxycholic acid (UDCA) 382, 391, 436 US see ultrasound

V

vancomycin 129 verapamil 373 vertical banded gastroplasty 245, 246–7 vicarious liability 5 new technology and 7–8

vital dye staining 191 Von Hippel–Lindau (VHL) syndrome 467, 469, 470 von Recklinghausen disease, neuroendocrine tumors and 277 V-system 36

W

walled-off necrosis (WON) see organized (walledoff ) pancreatic necrosis warfarin 129 weight-reduction surgery see bariatric surgery Whipple procedure conventional 249–50 pylorus-preserving 250, 349 wire baskets 121–2 lithotripsy 39 for stone extraction 39

X

x-ray imaging units 15, 19

Z

“zipper cutting” 94, 110, 111, 116

505