Volume I ABCD — Delta-9-tetrahydrocannabinol
Editor
Jeffrey A. Knight, Ph.D. Mount Holyoke College
Medical Consultan...
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Volume I ABCD — Delta-9-tetrahydrocannabinol
Editor
Jeffrey A. Knight, Ph.D. Mount Holyoke College
Medical Consultants
Laurie Jackson-Grusby, Ph.D. Children’s Hospital Boston, Harvard Medical School
Wendy White-Ryan, M.D., FAAP Golisano Children’s Hospital at Strong Memorial Hospital
SALEM PRESS, INC. Pasadena, California Hackensack, New Jersey
Editor in Chief: Dawn P. Dawson Editorial Director: Christina J. Moose Project Editors: Tracy Irons-Georges, Rowena Wildin Dehanke Editorial Assistant: Dana Garey
Production Editor: Joyce I. Buchea Acquisitions Editor: Mark Rehn Photo Editor: Cynthia Breslin Beres Design and Graphics: James Hutson Layout: William Zimmerman
Copyright © 2009, by Salem Press, Inc. All rights in this book are reserved. No part of this work may be used or reproduced in any manner whatsoever or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without written permission from the copyright owner except in the case of brief quotations embodied in critical articles and reviews or in the copying of images deemed to be freely licensed or in the public domain. For information address the publisher, Salem Press, Inc., P.O. Box 50062, Pasadena, California 91115. ∞ The paper used in these volumes conforms to the American National Standard for Permanence of Paper for Printed Library Materials, Z39.48-1992 (R1997). Note to Readers The material presented in Salem Health: Cancer is intended for broad informational and educational purposes. Readers who suspect that they or someone whom they know or provide caregiving for suffers from cancer or any other physical or psychological disorder, disease, or condition described in this set should contact a physician without delay; this work should not be used as a substitute for professional medical diagnosis or staging. Readers who are undergoing or about to undergo any treatment or procedure described in this set should refer to their physicians and other health care team members for guidance concerning preparation and possible effects. This set is not to be considered definitive on the covered topics, and readers should remember that the field of health care is characterized by a diversity of medical opinions and constant expansion in knowledge and understanding. Library of Congress Cataloging-in-Publication Data Salem health : cancer / Jeffrey A. Knight, Laurie Jackson-Grusby, Wendy White-Ryan. p. cm. Includes bibliographical references and index. ISBN 978-1-58765-505-0 (set : alk. paper) — ISBN 978-1-58765-506-7 (vol. 1 : alk. paper) — ISBN 978-1-58765-507-4 (vol. 2 : alk. paper) — ISBN 978-1-58765-508-1 (vol. 3 : alk. paper) — ISBN 978-1-58765-509-8 (vol. 4 : alk. paper) 1. Cancer. I. Knight, Jeffrey A., 1948- II. Jackson-Grusby, Laurie. III. White-Ryan, Wendy. RC265.S32 2008 616.99′4—dc22 2008030861
First Printing
printed in the united states of america
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Contents Alopecia . . . . . . . . . . . . . . . . . . . . . . . . 47 ALP. See Alkaline phosphatase test Alpha-fetoprotein (AFP) levels . . . . . . . . . . . . 48 Alternative therapies. See Complementary and alternative therapies Alveolar soft-part sarcomas . . . . . . . . . . . . . . 49 Amenorrhea . . . . . . . . . . . . . . . . . . . . . . 50 American Association for Cancer Research (AACR) . . . . . . . . . . . . . . . . . . . . . . . 52 American Cancer Society (ACS) . . . . . . . . . . . 53 American Institute for Cancer Research (AICR) . . . 54 4-Aminobiphenyl . . . . . . . . . . . . . . . . . . . 56 AML. See Acute myelocytic leukemia Amputation . . . . . . . . . . . . . . . . . . . . . . 56 Amyloidosis . . . . . . . . . . . . . . . . . . . . . . 58 Anal cancer . . . . . . . . . . . . . . . . . . . . . . 59 Androgen drugs . . . . . . . . . . . . . . . . . . . . 61 Anemia . . . . . . . . . . . . . . . . . . . . . . . . 62 Anemia, aplastic. See Aplastic anemia Anemia, hemolytic. See Hemolytic anemia Angiogenesis . . . . . . . . . . . . . . . . . . . . . 64 Angiogenesis inhibitors . . . . . . . . . . . . . . . . 66 Angiography. . . . . . . . . . . . . . . . . . . . . . 68 Angiosarcomas . . . . . . . . . . . . . . . . . . . . 69 Anoscopy . . . . . . . . . . . . . . . . . . . . . . . 70 Anthraquinones . . . . . . . . . . . . . . . . . . . . 71 Anthrax . . . . . . . . . . . . . . . . . . . . . . . . 71 Antiandrogens . . . . . . . . . . . . . . . . . . . . . 72 Antidiarrheal agents . . . . . . . . . . . . . . . . . . 73 Antiestrogens . . . . . . . . . . . . . . . . . . . . . 75 Antifungal therapies . . . . . . . . . . . . . . . . . . 76 Antimetabolites in chemotherapy . . . . . . . . . . . 78 Antinausea medications . . . . . . . . . . . . . . . . 81 Antineoplastics in chemotherapy . . . . . . . . . . . 83 Antioxidants . . . . . . . . . . . . . . . . . . . . . . 86 Antiperspirants and breast cancer . . . . . . . . . . . 88 Antiviral therapies. . . . . . . . . . . . . . . . . . . 90 Anxiety . . . . . . . . . . . . . . . . . . . . . . . . 93 APBI. See Accelerated partial breast irradiation APC gene testing . . . . . . . . . . . . . . . . . . . 94 Aplastic anemia . . . . . . . . . . . . . . . . . . . . 95 Appendix cancer . . . . . . . . . . . . . . . . . . . 97 Appetite loss. . . . . . . . . . . . . . . . . . . . . . 98 APR. See Abdominoperineal resection Arsenic compounds . . . . . . . . . . . . . . . . . 100 Arterial embolization . . . . . . . . . . . . . . . . 101 Artificial sweeteners . . . . . . . . . . . . . . . . . 102 Asbestos . . . . . . . . . . . . . . . . . . . . . . . 103
Publisher’s Note . . . . . . . . . . . . . . . . . . . . ix About the Editors . . . . . . . . . . . . . . . . . . . xi Contributors . . . . . . . . . . . . . . . . . . . . . xiii Complete List of Contents . . . . . . . . . . . . . . xv AACR. See American Association for Cancer Research ABCD. . . . . . . . . . . . . . . . . . . . . . . . . . 1 ACC. See Adenoid cystic carcinoma Abdominoperineal resection (APR) . . . . . . . . . . 1 Accelerated partial breast irradiation (APBI). . . . . . 3 Achlorhydria . . . . . . . . . . . . . . . . . . . . . . 4 Acoustic neuromas . . . . . . . . . . . . . . . . . . . 4 Acquired immunodeficiency disease-related cancers. See HIV/AIDS-related cancers Acrylamides . . . . . . . . . . . . . . . . . . . . . . 6 ACS. See American Cancer Society Acupuncture and acupressure for cancer patients . . . 8 Acute lymphocytic leukemia (ALL) . . . . . . . . . 11 Acute myelocytic leukemia (AML) . . . . . . . . . . 13 Adenocarcinomas . . . . . . . . . . . . . . . . . . . 16 Adenoid cystic carcinoma (ACC) . . . . . . . . . . . 17 Adenomatoid tumors . . . . . . . . . . . . . . . . . 18 Adenomatous polyps . . . . . . . . . . . . . . . . . 18 Adenoviruses . . . . . . . . . . . . . . . . . . . . . 19 Adjuvant therapy . . . . . . . . . . . . . . . . . . . 20 Adrenal gland cancers . . . . . . . . . . . . . . . . . 21 Adrenocortical cancer . . . . . . . . . . . . . . . . . 23 Advance directives . . . . . . . . . . . . . . . . . . 24 Aflatoxins . . . . . . . . . . . . . . . . . . . . . . . 26 AFP levels. See Alpha-fetoprotein levels African Americans and cancer . . . . . . . . . . . . 28 Africans and cancer . . . . . . . . . . . . . . . . . . 31 Afterloading radiation therapy . . . . . . . . . . . . 32 Agent Orange . . . . . . . . . . . . . . . . . . . . . 34 Aging and cancer . . . . . . . . . . . . . . . . . . . 34 AICR. See American Institute for Cancer Research Aids and devices for cancer patients . . . . . . . . . 38 AIDS-related cancers. See HIV/AIDS-related cancers Air pollution . . . . . . . . . . . . . . . . . . . . . . 39 Alcohol, alcoholism, and cancer . . . . . . . . . . . 42 Aleukemia . . . . . . . . . . . . . . . . . . . . . . . 43 Alkaline phosphatase test (ALP) . . . . . . . . . . . 44 Alkylating agents in chemotherapy . . . . . . . . . . 45 ALL. See Acute lymphocytic leukemia Allicin, garlic and. See Garlic and allicin v
Salem Health: Cancer Ascites . . . . . . . . . . . . Ashkenazi Jews and cancer . Asian Americans and cancer. Astrocytomas. . . . . . . . . Ataxia telangiectasia (AT) . . Autologous blood transfusion Axillary dissection . . . . . . Azathioprine . . . . . . . . .
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105 107 109 112 114 115 116 117
Bacillus Calmette Guérin (BCG) . . . . . . . . Bacteria as causes of cancer . . . . . . . . . . . Barium enema . . . . . . . . . . . . . . . . . . Barium swallow . . . . . . . . . . . . . . . . . Barrett esophagus . . . . . . . . . . . . . . . . Basal cell carcinomas . . . . . . . . . . . . . . BCG. See Bacillus Calmette Guérin Beckwith-Wiedemann syndrome (BWS) . . . . Benign prostatic hyperplasia (BPH) . . . . . . . Benign tumors . . . . . . . . . . . . . . . . . . Benzene . . . . . . . . . . . . . . . . . . . . . Benzidine and dyes metabolized to benzidine . . Benzodiazepines . . . . . . . . . . . . . . . . . Bereavement, grief and. See Grief and bereavement Beryllium and beryllium compounds . . . . . . Beta-carotene . . . . . . . . . . . . . . . . . . Bethesda criteria . . . . . . . . . . . . . . . . . BHDS. See Birt-Hogg-Dubé syndrome Bile duct cancer . . . . . . . . . . . . . . . . . Bilobectomy . . . . . . . . . . . . . . . . . . . Bioflavonoids . . . . . . . . . . . . . . . . . . Biological therapy . . . . . . . . . . . . . . . . Biopsy. See also Computed tomography-guided biopsy; Core needle biopsy; Liver biopsy; Needle biopsies; Pleural biopsy; Stereotactic needle biopsy; Surgical biopsies . . . . . . . Birt-Hogg-Dubé syndrome (BHDS) . . . . . . . Birth control pills and cancer . . . . . . . . . . Bis(chloromethyl) ether and technical-grade chloromethyl methyl ether . . . . . . . . . . Bisphenol A (BPA) . . . . . . . . . . . . . . . Bisphosphonates . . . . . . . . . . . . . . . . . Bladder cancer . . . . . . . . . . . . . . . . . . Blood cancers . . . . . . . . . . . . . . . . . . BMT. See Bone marrow transplantation BNCT. See Boron neutron capture therapy Body image. See Self-image and body image Bone cancers . . . . . . . . . . . . . . . . . . . Bone marrow aspiration and biopsy . . . . . . . Bone marrow transplantation (BMT) . . . . . . Bone pain . . . . . . . . . . . . . . . . . . . .
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118 118 120 121 123 124
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126 128 128 130 131 132
Bone scan . . . . . . . . . . . . . . . . . . . . Boron neutron capture therapy (BNCT) . . . . . Bowen disease . . . . . . . . . . . . . . . . . . BPA. See Bisphenol A BPH. See Benign prostatic hyperplasia BPI. See Brief Pain Inventory Brachytherapy . . . . . . . . . . . . . . . . . . BRAF gene . . . . . . . . . . . . . . . . . . . . Brain and central nervous system cancers . . . . Brain scan . . . . . . . . . . . . . . . . . . . . BRCA1 and BRCA2 genes . . . . . . . . . . . . Breakthrough pain . . . . . . . . . . . . . . . . Breast, calcifications of. See Calcifications of the breast Breast, medullary carcinoma of. See Medullary carcinoma of the breast Breast cancer, cutaneous. See Cutaneous breast cancer Breast cancer, estrogen-receptor-sensitive. See Estrogen-receptor-sensitive breast cancer Breast cancer in children and adolescents . . . . Breast cancer in men . . . . . . . . . . . . . . . Breast cancer in pregnant women . . . . . . . . Breast cancers . . . . . . . . . . . . . . . . . . Breast implants. . . . . . . . . . . . . . . . . . Breast reconstruction. . . . . . . . . . . . . . . Breast self-examination (BSE). . . . . . . . . . Breast ultrasound. . . . . . . . . . . . . . . . . Breslow’s staging . . . . . . . . . . . . . . . . Brief Pain Inventory (BPI) . . . . . . . . . . . . Brompton cocktail . . . . . . . . . . . . . . . . Bronchial adenomas . . . . . . . . . . . . . . . Bronchoalveolar lung cancer . . . . . . . . . . Bronchography. . . . . . . . . . . . . . . . . . Bronchoscopy . . . . . . . . . . . . . . . . . . BSE. See Breast self-examination Burkitt lymphoma . . . . . . . . . . . . . . . . 1,3-Butadiene . . . . . . . . . . . . . . . . . . 1,4-Butanediol dimethanesulfonate . . . . . . . BWS. See Beckwith-Wiedemann syndrome
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CA 15-3 test . . . . . . . . . . . . . CA 19-9 test . . . . . . . . . . . . . CA 27-29 test . . . . . . . . . . . . CA 125 test. . . . . . . . . . . . . . Cachexia . . . . . . . . . . . . . . . Cadmium and cadmium compounds. Caffeine . . . . . . . . . . . . . . . Calcifications of the breast. . . . . . Calcium . . . . . . . . . . . . . . . Cancell . . . . . . . . . . . . . . . . vi
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Contents Cancer biology . . . . . . . . . . . . . . . . . . . Cancer care team . . . . . . . . . . . . . . . . . . Cancer clusters . . . . . . . . . . . . . . . . . . . Cancer education. . . . . . . . . . . . . . . . . . Candidiasis . . . . . . . . . . . . . . . . . . . . . Carcinoembryonic antigen antibody (CEA) test . . . . . . . . . . . . . . . . . . . . . . . . Carcinogens, known . . . . . . . . . . . . . . . . Carcinogens, reasonably anticipated. . . . . . . . Carcinoid tumors and carcinoid syndrome . . . . Carcinoma of unknown primary origin (CUP) . . . . . . . . . . . . . . . . . . . . . . Carcinomas. . . . . . . . . . . . . . . . . . . . . Carcinomas, invasive ductal. See Invasive ductal carcinomas Carcinomas, invasive lobular. See Invasive lobular carcinomas Carcinomas, leptomeningeal. See Leptomeningeal carcinomas Carcinomatosis. . . . . . . . . . . . . . . . . . . Carcinomatous meningitis . . . . . . . . . . . . . Carcinosarcomas . . . . . . . . . . . . . . . . . . Cardiomyopathy in cancer patients . . . . . . . . Cardiopulmonary resuscitation (CPR) . . . . . . . Caregivers and caregiving . . . . . . . . . . . . . Caregiving, long-distance. See Long-distance caregiving Carney complex . . . . . . . . . . . . . . . . . . Carotenoids . . . . . . . . . . . . . . . . . . . . Cartilage supplements . . . . . . . . . . . . . . . Case management . . . . . . . . . . . . . . . . . Castleman disease . . . . . . . . . . . . . . . . . CBC. See Complete blood count CBE. See Clinical breast exam CDKN2A. See Cyclin-dependent kinase inhibitor-2A CEA test. See Carcinoembryonic antigen antibody test Cell phones. . . . . . . . . . . . . . . . . . . . . Cervical cancer. . . . . . . . . . . . . . . . . . . Chemoembolization . . . . . . . . . . . . . . . . Chemoprevention . . . . . . . . . . . . . . . . . Chemotherapy . . . . . . . . . . . . . . . . . . . Chemotherapy, cognitive effects of. See Cognitive effects of cancer and chemotherapy Chewing tobacco. . . . . . . . . . . . . . . . . . Childbirth and cancer . . . . . . . . . . . . . . . Childhood cancers . . . . . . . . . . . . . . . . . Chlorambucil. . . . . . . . . . . . . . . . . . . . 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)1-nitrosourea (MeCCNU) . . . . . . . . . . . .
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213 216 218 220 221
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223 224 227 230
Cholecystectomy . . . . . . . . . . . . . . . . . Chordomas . . . . . . . . . . . . . . . . . . . . Choriocarcinomas . . . . . . . . . . . . . . . . CHPP. See Continuous hyperthermic peritoneal perfusion Chromium hexavalent compounds. . . . . . . . Chromosomes and cancer . . . . . . . . . . . . Chronic lymphocytic leukemia (CLL) . . . . . . Chronic myeloid leukemia (CML). . . . . . . . Cigarettes and cigars . . . . . . . . . . . . . . . Clinical breast exam (CBE) . . . . . . . . . . . Clinical trials . . . . . . . . . . . . . . . . . . . CLL. See Chronic lymphocytic leukemia CML. See Chronic myeloid leukemia Coal tars and coal tar pitches . . . . . . . . . . Cobalt 60 radiation. . . . . . . . . . . . . . . . Coenzyme Q10. . . . . . . . . . . . . . . . . . Cognitive effects of cancer and chemotherapy . Coke oven emissions. . . . . . . . . . . . . . . Cold nodule . . . . . . . . . . . . . . . . . . . Colectomy . . . . . . . . . . . . . . . . . . . . Coloanal anastomosis . . . . . . . . . . . . . . Colon polyps . . . . . . . . . . . . . . . . . . . Colonoscopy and virtual colonoscopy . . . . . . Colony-stimulating factors (CSFs) . . . . . . . Colorectal cancer. . . . . . . . . . . . . . . . . Colorectal cancer screening . . . . . . . . . . . Colostomy . . . . . . . . . . . . . . . . . . . . Colposcopy. . . . . . . . . . . . . . . . . . . . Comedo carcinomas . . . . . . . . . . . . . . . Complementary and alternative therapies . . . . Complete blood count (CBC) . . . . . . . . . . Computed tomography (CT)-guided biopsy . . . . . . . . . . . . . . . . . . . . . Computed tomography (CT) scan . . . . . . . . Conization . . . . . . . . . . . . . . . . . . . . Continuous hyperthermic peritoneal perfusion (CHPP) . . . . . . . . . . . . . . . . . . . . Cordectomy . . . . . . . . . . . . . . . . . . . Cordotomy . . . . . . . . . . . . . . . . . . . . Core needle biopsy. . . . . . . . . . . . . . . . Corticosteroids . . . . . . . . . . . . . . . . . . Coughing . . . . . . . . . . . . . . . . . . . . . Counseling for cancer patients and survivors . . Cowden syndrome . . . . . . . . . . . . . . . . COX-2 inhibitors. See Cyclooxygenase 2 inhibitors CPR. See Cardiopulmonary resuscitation Craniopharyngiomas . . . . . . . . . . . . . . . Craniosynostosis . . . . . . . . . . . . . . . . . Craniotomy. . . . . . . . . . . . . . . . . . . .
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288 289 289 290 292 292 293 294 296 297 299 300 304 306 308 309 309 312
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Salem Health: Cancer Crohn disease . . . . . . . . . . . . . . . Cruciferous vegetables . . . . . . . . . . . Cryoablation . . . . . . . . . . . . . . . . Cryptorchidism. . . . . . . . . . . . . . . CSFs. See Colony-stimulating factors CT scan. See Computed tomography scan CTCL. See Cutaneous T-cell lymphoma Culdoscopy. . . . . . . . . . . . . . . . . CUP. See Carcinoma of unknown primary origin Curcumin. . . . . . . . . . . . . . . . . . Cushing syndrome and cancer . . . . . . . Cutaneous breast cancer . . . . . . . . . . Cutaneous T-cell lymphoma (CTCL) . . . Cyclin-dependent kinase inhibitor-2A (CDKN2A). . . . . . . . . . . . . . . .
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332 335 336 338
Cyclooxygenase 2 (COX-2) inhibitors . Cyclophosphamide. . . . . . . . . . . . Cyclosporin A . . . . . . . . . . . . . . Cystography . . . . . . . . . . . . . . . Cystoscopy . . . . . . . . . . . . . . . . Cytogenetics . . . . . . . . . . . . . . . Cytokines . . . . . . . . . . . . . . . . Cytology . . . . . . . . . . . . . . . . . Cytology, sputum. See Sputum cytology
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339 340 341 342
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344 345 346 347 347 348 350 350
D&C. See Dilation and curettage Dana-Farber Cancer Institute . . . . . . . . . . . . 354 DCIS. See Ductal carcinoma in situ DEA. See Diethanolamine DEHP. See Di(2-ethylhexyl) phthalate Delta-9-tetrahydrocannabinol . . . . . . . . . . . . 355
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Publisher’s Note not only the names of the specializations but also related subspecialists, the cancers they treat, how they are trained and certified, and the range of services and procedures they perform. Finally, a group of topics addressing social and personal issues, lifestyle choices, nutritional supplements, and complementary or alternative therapies are similarly formatted into subsections that call out key areas of interest for readers. Special features of the set include tables throughout identifying the most important chemotherapeutic and other drugs and the symptoms and conditions they address, population statistics, survival rates, and other core information. Every essay includes a section of “See also” cross-references to other essays in the set that will be of interest to those consulting the topic at hand. A fully crossreferenced “Complete List of Contents” at the beginning of every volume also assists readers in locating related topics of interest. Photographs display for readers typical instances of lesions, tumors, procedures, and anatomical cross-sections to locate areas of the body affected. In addition, 8 appendixes at the end of volume 4 provide information on the following:
Salem Health: Cancer alphabetically arranges 835 essays on all aspects of cancer for all nonspecialist interest groups—from those who have been diagnosed to caregivers, family members, students, and readers with a general interest in health. The essays in this 4-volume set address diseases, conditions, symptoms, cancer-related syndromes, chemotherapy and other drugs, cancer centers, genetics, the biology of cancer, medical specialties, tests, procedures, complementary and alternative therapies, lifestyles, healthy and preventive strategies, and the many social and personal issues surrounding cancer, from cancer’s impact on minority populations to finances, insurance, relationships, and emotional coping. Written by physicians, nurses, and professional medical writers whose credentials and degrees are clearly listed in the byline to every essay, this comprehensive reference publication will be of interest not only to public library patrons but also to premedical students and those building collections for the patient population. Essays vary in length from 400 to 2,000 words, ranging from one to five pages. The information is presented in one of six standard essay formats by type of topic covered: carcinogen, disease or condition, drug or drug class, medical specialty, procedure, or “overview” (of an aspect of cancer biology, a personal or lifestyle issue, or an area of social concern). All essays present a capsule definition of the topic, and all but the briefest essays list sources of further information from both print and online resources. The essay formats are designed for the reader for whom the information is compelling or urgent, fostering quick identification and retrieval of essential facts: Essays on diseases and conditions, for example, list “also known as” names and describe related conditions, risk factors, the disease process, incidence, symptoms, screening and diagnosis, treatment, and prognosis. Essays on carcinogens list “also known as” names for the chemical or substance, cancers related to the carcinogen, exposure routes, principal places where the substance is found, populations at risk, symptoms to watch for, and a brief history of how we came to identify the substance as a carcinogen. Essays on drugs list the Anatomical Therapeutic Chemical (ATC) classification system code if one exists; the types of cancer, side effect, or other condition for which the drug is indicated; the delivery routes (such as pill form or injection); the way the drug works; and side effects. Essays on procedures apprise patients and their caregivers of why the procedure is performed, how to prepare, aftercare, risks, and the range of results. Essays on medical specialties identify
• • • • • • • •
Drugs by Generic Name Drugs by Trade Name Associations and Agencies Cancer Centers and Hospitals Cancer Support Groups Carcinogens Glossary Bibliography
A Category List and a complete subject index round out the set. Salem Health: Cancer has been the beneficiary of many expert contributors—physicians, nurses, pharmacists, and professional medical writers—whose names and academic or professional affiliations appear in the list of contributors that follows. Finally, this publication was made possible above all by our three consulting editors: Jeffrey A. Knight, Chair of the Department of Biological Sciences at Mount Holyoke College; Laurie JacksonGrusby, Ph.D., Assistant Professor in Pathology at Harvard Medical School, Children’s Hospital Boston; and Wendy White-Ryan, M.D., FAAP, is a board-certified pediatrician and member of the American Academy of Pediatrics. ix
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About the Editors from the Sontag Foundation for her work on pediatric brain tumors.
Jeffrey A. Knight, Ph.D., is Chair of the Department of Biological Sciences at Mount Holyoke College, where he teaches courses in genetics, molecular biology, and microbiology. He has held Visiting Professor appointments at the medical schools of the Universities of Massachusetts, Florida, and Vermont. Author of several research papers on the mitochondrial genetics of baker’s yeast, he has also been a frequent contributor to Salem Press publications. He edited the first edition of the Encyclopedia of Genetics (Salem Press, 1999), winner of the American Library Association, Reference and User Services Association’s “Outstanding Reference Source,” 2000.
Wendy White-Ryan, M.D., FAAP, is a board-certified pediatrician and member of the American Academy of Pediatrics as well as Alpha Omega Alpha. She completed her B.A. at Mount Holyoke College, her M.D. at New York Medical College, and her residency training in pediatrics at Strong Memorial Hospital in Rochester, New York. She worked in toxicology research at the University of Rochester for two years between earning her bachelor’s degree and entering medical school. She practiced pediatrics full-time for nine years in the inner city of Rochester until being diagnosed with Stage IV breast cancer in 2005. She became medically stable after undergoing both conventional and integrative treatments, including changes in diet and exercise, while remaining affiliated with Golisano Children’s Hospital at Strong Memorial Hospital in Rochester. She supports mind-body work, nutritional support through nutriceuticals, and other health-promoting lifestyle changes in the prevention or treatment of cancer.
Laurie Jackson-Grusby, Ph.D., is an Assistant Professor in Pathology at Harvard Medical School, Children’s Hospital Boston, and a faculty member of the Harvard Stem Cell Institute and Kirby Center for Neuroscience. She is a visiting instructor at the Harvard Extension school, where she teaches genetics. Her laboratory investigates the role of epigenetics in development of disease. She was awarded the Distinguished Scientist Award
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Contributors
Abbie L. Abboud, M.S., C.G.C.
Kerry L. Cheesman, Ph.D.
H. Bradford Hawley, M.D.
Richard Adler, Ph.D.
Wanda E. Clark, M.T. (ASCP)
Peter B. Heller, Ph.D.
Jane Adrian, M.P.H., Ed.M., M.T. (ASCP)
Lisa M. Cockrell, B.S.
Collette Bishop Hendler, R.N., M.S.
Pam Conboy, B.S.
Michelle L. Herdman, Ph.D.
Pamela S. Cooper, Ph.D.
Jennifer M. Hickin, B.S.
Angela M. Costello, B.S.
Carl W. Hoagstrom, Ph.D.
Charlotte Crowder, M.P.H., ELS
Christine G. Holzmueller, B.L.A.
Reyniel Cruz-Aguado, Ph.D.
Mary Hurd, M.A.
D. Scott Cunningham, M.D., Ph.D.
Bernard Jacobson, Ph.D.
Arun S. Dabholkar, Ph.D.
Clair Kaplan, R.N., M.S.N., A.P.R.N. (WHNP), M.H.S., M.T. (ASCP)
Robert J. Amato, D.O. Cathy Anderson, R.N., B.A. Terry A. Anderson, B.S. Wendell Anderson, B.A. Michele Arduengo, Ph.D., ELS Bryan C. Auday, Ph.D. Tanja Bekhuis, Ph.D. Paul F. Bell, Ph.D. Alvin K. Benson, Ph.D. Anna Binda, Ph.D. Robert Bockstiegel, B.S. Scott A. Boerner, M.S. Patricia Boone, Ph.D. Andrea Bradford, M.A. Wanda Todd Bradshaw, R.N.C., M.S.N. Thomas L. Brown, Ph.D. Suzette Buhr, R.T.R., C.D.A. Amy Bull, D.S.N., A.P.N. Michael A. Buratovich, Ph.D. Bharat Burman, B.A. Jaime Stockslager Buss, M.S.P.H., ELS Alex B. Cantrell, B.A. Richard P. Capriccioso, M.D. Mary Car-Blanchard, O.T.D., B.S.O.T. Christine M. Carroll, R.N., B.S.N., M.B.A.
Helen Davidson, B.A. Martiscia Davidson, A.M. Cynthia L. De Vine, B.A. Jackie Dial, Ph.D. Jeremy W. Dugosh, Ph.D. Aldo C. Dumlao, M.D Patricia Stanfill Edens, R.N., Ph.D., FACHE Renée Euchner, R.N. Jill Ferguson, Ph.D.
Susan J. Karcher, Ph.D. Sarah Kasprowicz, M.D. Michelle Kasprzak, R.N., B.S.N., O.C.N. Keller Kaufman-Fox, B.A. Debra B. Kessler, M.D., Ph.D. A. K. Khan, M.D., M.R.C.P. M. A. Q. Khan, M.D., Ph.D. Samreen F. Khan, M.A. Ing-Wei Khor, Ph.D.
Adi Ferrara, B.S. Amber L. Fields, M.S. K. Thomas Finley, Ph.D. MaryAnn Foote, M.S., Ph.D. Jo Gambosi, M.A., B.S.N. James S. Godde, Ph.D. Janet R. Green, M.S.P.H. Katrina Green, R.N., B.S.N., O.C.N. Silke Haidekker, Ph.D. Linda Hart, M.S., M.A. Melanie Hawkins, B.S.N., R.N., O.C.N. xiii
Michael R. King, Ph.D. Samuel V. A. Kisseadoo, Ph.D. Jeffrey A. Knight, Ph.D. Marylane Wade Koch, M.S.N., R.N. Robert W. Koch, D.N.S., R.N. Lalitha Krishnan, Ph.D. Anita P. Kuan, Ph.D. Steven A. Kuhl, Ph.D. Jeffrey P. Larson, P.T., B.S., A.T.C. Lindsay Lewellyn, B.S. Lisa M. Lines, M.P.H.
Salem Health: Cancer Martha O. Loustaunau, Ph.D.
Marcia Pinneau, R.N.
Amanda McQuade, Ph.D.
Nancy A. Piotrowski, Ph.D.
Kyle J. McQuade, Ph.D.
Victoria Price, Ph.D.
Marianne M. Madsen, M.S.
Christopher Pung, B.S., C.L.Sp. (CG)
Judy Majewski, M.S.
Cynthia Racer, M.A., M.P.H.
Elizabeth A. Manning, Ph.D.
Bagirathy Ravishankar, Ph.D.
Vicki Miskovsky, B.S., R.D.
Pamela Richardson, M.S.
Paul Moglia, Ph.D.
Alice C. Richer, R.D., M.B.A., L.D.
Christina J. Moose, M.A.
Elizabeth D. Schafer, Ph.D.
Linda August Vrooman, R.N., B.S.N., O.C.N.
Karen M. Nagel, Ph.D.
Jason J. Schwartz, Ph.D., J.D.
C. J. Walsh, Ph.D.
Anita Nagypál, Ph.D.
Miriam E. Schwartz, M.D., M.A., Ph.D.
Stephanie Watson, B.S.
Amy J. Neil, M.S., M.A.P. David A. Olle, M.S. Colm A. Ó’Moráin, M.A., M.D., M.Sc., D.Sc.
Banalata Sen, Ph.D. Terry J. Shackleford, Ph.D. Lisa J. Shientag, V.M.D.
Carol Ann Suda, B.S., M.T. (ASCP), S.M. Rena C. Tabata, M.Sc. Dorothy P. Terry, R.N. Susan E. Ullmann, M.T. (ASCP), M.A. Nicole M. Van Hoey, Pharm.D. Charles L. Vigue, Ph.D.
Marcia J. Weiss, J.D. John B. Welsh, M.D., Ph.D. Bradley R. A. Wilson, Ph.D.
Ophelia Panganiban, B.S.
R. Baird Shuman, Ph.D.
Nicola E. Wittekindt, Dr.Sc. (ETH Zürich)
Jeannie V. Pasacreta, Ph.D., A.P.R.N.
Vonne Sieve, M.A.
Geetha Yadav, Ph.D.
Anna Perez, M.Sc.
Dwight G. Smith, Ph.D.
John L. Zeller, M.D., Ph.D.
Susan H. Peterman, M.P.H.
Richard S. Spira, D.V.M.
Diego Pineda, M.S.
Kelli Miller Stacy, ELS
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Complete List of Contents Volume 1 Alkylating agents in chemotherapy . . . . . . . ALL. See Acute lymphocytic leukemia Allicin, garlic and. See Garlic and allicin Alopecia . . . . . . . . . . . . . . . . . . . . . ALP. See Alkaline phosphatase test Alpha-fetoprotein (AFP) levels . . . . . . . . . Alternative therapies. See Complementary and alternative therapies Alveolar soft-part sarcomas . . . . . . . . . . . Amenorrhea . . . . . . . . . . . . . . . . . . . American Association for Cancer Research (AACR) . . . . . . . . . . . . . . . . . . . . American Cancer Society (ACS) . . . . . . . . American Institute for Cancer Research (AICR) 4-Aminobiphenyl . . . . . . . . . . . . . . . . AML. See Acute myelocytic leukemia Amputation . . . . . . . . . . . . . . . . . . . Amyloidosis . . . . . . . . . . . . . . . . . . . Anal cancer . . . . . . . . . . . . . . . . . . . Androgen drugs . . . . . . . . . . . . . . . . . Anemia . . . . . . . . . . . . . . . . . . . . . Anemia, aplastic. See Aplastic anemia Anemia, hemolytic. See Hemolytic anemia Angiogenesis . . . . . . . . . . . . . . . . . . Angiogenesis inhibitors . . . . . . . . . . . . . Angiography. . . . . . . . . . . . . . . . . . . Angiosarcomas . . . . . . . . . . . . . . . . . Anoscopy . . . . . . . . . . . . . . . . . . . . Anthraquinones . . . . . . . . . . . . . . . . . Anthrax . . . . . . . . . . . . . . . . . . . . . Antiandrogens . . . . . . . . . . . . . . . . . . Antidiarrheal agents . . . . . . . . . . . . . . . Antiestrogens . . . . . . . . . . . . . . . . . . Antifungal therapies . . . . . . . . . . . . . . . Antimetabolites in chemotherapy . . . . . . . . Antinausea medications . . . . . . . . . . . . . Antineoplastics in chemotherapy . . . . . . . . Antioxidants . . . . . . . . . . . . . . . . . . . Antiperspirants and breast cancer . . . . . . . . Antiviral therapies. . . . . . . . . . . . . . . . Anxiety . . . . . . . . . . . . . . . . . . . . . APBI. See Accelerated partial breast irradiation APC gene testing . . . . . . . . . . . . . . . . Aplastic anemia . . . . . . . . . . . . . . . . . Appendix cancer . . . . . . . . . . . . . . . . Appetite loss. . . . . . . . . . . . . . . . . . .
Contents . . . . . . . . . . . . . . . . . . . . . . . . v Publisher’s Note . . . . . . . . . . . . . . . . . . . . ix About the Editors . . . . . . . . . . . . . . . . . . . xi Contributors . . . . . . . . . . . . . . . . . . . . . xiii Complete List of Contents . . . . . . . . . . . . . . xv AACR. See American Association for Cancer Research ABCD. . . . . . . . . . . . . . . . . . . . . . . . . . 1 ACC. See Adenoid cystic carcinoma Abdominoperineal resection (APR) . . . . . . . . . . 1 Accelerated partial breast irradiation (APBI). . . . . . 3 Achlorhydria . . . . . . . . . . . . . . . . . . . . . . 4 Acoustic neuromas . . . . . . . . . . . . . . . . . . . 4 Acquired immunodeficiency disease-related cancers. See HIV/AIDS-related cancers Acrylamides . . . . . . . . . . . . . . . . . . . . . . 6 ACS. See American Cancer Society Acupuncture and acupressure for cancer patients . . . 8 Acute lymphocytic leukemia (ALL) . . . . . . . . . 11 Acute myelocytic leukemia (AML) . . . . . . . . . . 13 Adenocarcinomas . . . . . . . . . . . . . . . . . . . 16 Adenoid cystic carcinoma (ACC) . . . . . . . . . . . 17 Adenomatoid tumors . . . . . . . . . . . . . . . . . 18 Adenomatous polyps . . . . . . . . . . . . . . . . . 18 Adenoviruses . . . . . . . . . . . . . . . . . . . . . 19 Adjuvant therapy . . . . . . . . . . . . . . . . . . . 20 Adrenal gland cancers . . . . . . . . . . . . . . . . . 21 Adrenocortical cancer . . . . . . . . . . . . . . . . . 23 Advance directives . . . . . . . . . . . . . . . . . . 24 Aflatoxins . . . . . . . . . . . . . . . . . . . . . . . 26 AFP levels. See Alpha-fetoprotein levels African Americans and cancer . . . . . . . . . . . . 28 Africans and cancer . . . . . . . . . . . . . . . . . . 31 Afterloading radiation therapy . . . . . . . . . . . . 32 Agent Orange . . . . . . . . . . . . . . . . . . . . . 34 Aging and cancer . . . . . . . . . . . . . . . . . . . 34 AICR. See American Institute for Cancer Research Aids and devices for cancer patients . . . . . . . . . 38 AIDS-related cancers. See HIV/AIDS-related cancers Air pollution . . . . . . . . . . . . . . . . . . . . . . 39 Alcohol, alcoholism, and cancer . . . . . . . . . . . 42 Aleukemia . . . . . . . . . . . . . . . . . . . . . . . 43 Alkaline phosphatase test (ALP) . . . . . . . . . . . 44 xv
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Salem Health: Cancer APR. See Abdominoperineal resection Arsenic compounds . . . . . . . . . . Arterial embolization . . . . . . . . . Artificial sweeteners . . . . . . . . . . Asbestos . . . . . . . . . . . . . . . . Ascites . . . . . . . . . . . . . . . . . Ashkenazi Jews and cancer . . . . . . Asian Americans and cancer. . . . . . Astrocytomas. . . . . . . . . . . . . . Ataxia telangiectasia (AT) . . . . . . . Autologous blood transfusion . . . . . Axillary dissection . . . . . . . . . . . Azathioprine . . . . . . . . . . . . . .
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Bacillus Calmette Guérin (BCG) . . . . . . . . Bacteria as causes of cancer . . . . . . . . . . . Barium enema . . . . . . . . . . . . . . . . . . Barium swallow . . . . . . . . . . . . . . . . . Barrett esophagus . . . . . . . . . . . . . . . . Basal cell carcinomas . . . . . . . . . . . . . . BCG. See Bacillus Calmette Guérin Beckwith-Wiedemann syndrome (BWS) . . . . Benign prostatic hyperplasia (BPH) . . . . . . . Benign tumors . . . . . . . . . . . . . . . . . . Benzene . . . . . . . . . . . . . . . . . . . . . Benzidine and dyes metabolized to benzidine . . Benzodiazepines . . . . . . . . . . . . . . . . . Bereavement, grief and. See Grief and bereavement Beryllium and beryllium compounds . . . . . . Beta-carotene . . . . . . . . . . . . . . . . . . Bethesda criteria . . . . . . . . . . . . . . . . . BHDS. See Birt-Hogg-Dubé syndrome Bile duct cancer . . . . . . . . . . . . . . . . . Bilobectomy . . . . . . . . . . . . . . . . . . . Bioflavonoids . . . . . . . . . . . . . . . . . . Biological therapy . . . . . . . . . . . . . . . . Biopsy. See also Computed tomography-guided biopsy; Core needle biopsy; Liver biopsy; Needle biopsies; Pleural biopsy; Stereotactic needle biopsy; Surgical biopsies . . . . . . . Birt-Hogg-Dubé syndrome (BHDS) . . . . . . . Birth control pills and cancer . . . . . . . . . . Bis(chloromethyl) ether and technical-grade chloromethyl methyl ether . . . . . . . . . . Bisphenol A (BPA) . . . . . . . . . . . . . . . Bisphosphonates . . . . . . . . . . . . . . . . . Bladder cancer . . . . . . . . . . . . . . . . . . Blood cancers . . . . . . . . . . . . . . . . . . BMT. See Bone marrow transplantation BNCT. See Boron neutron capture therapy
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Body image. See Self-image and body image Bone cancers . . . . . . . . . . . . . . . . . . . Bone marrow aspiration and biopsy . . . . . . . Bone marrow transplantation (BMT) . . . . . . Bone pain . . . . . . . . . . . . . . . . . . . . Bone scan . . . . . . . . . . . . . . . . . . . . Boron neutron capture therapy (BNCT) . . . . . Bowen disease . . . . . . . . . . . . . . . . . . BPA. See Bisphenol A BPH. See Benign prostatic hyperplasia BPI. See Brief Pain Inventory Brachytherapy . . . . . . . . . . . . . . . . . . BRAF gene . . . . . . . . . . . . . . . . . . . . Brain and central nervous system cancers . . . . Brain scan . . . . . . . . . . . . . . . . . . . . BRCA1 and BRCA2 genes . . . . . . . . . . . . Breakthrough pain . . . . . . . . . . . . . . . . Breast, calcifications of. See Calcifications of the breast Breast, medullary carcinoma of. See Medullary carcinoma of the breast Breast cancer, cutaneous. See Cutaneous breast cancer Breast cancer, estrogen-receptor-sensitive. See Estrogen-receptor-sensitive breast cancer Breast cancer in children and adolescents . . . . Breast cancer in men . . . . . . . . . . . . . . . Breast cancer in pregnant women . . . . . . . . Breast cancers . . . . . . . . . . . . . . . . . . Breast implants. . . . . . . . . . . . . . . . . . Breast reconstruction. . . . . . . . . . . . . . . Breast self-examination (BSE). . . . . . . . . . Breast ultrasound. . . . . . . . . . . . . . . . . Breslow’s staging . . . . . . . . . . . . . . . . Brief Pain Inventory (BPI) . . . . . . . . . . . . Brompton cocktail . . . . . . . . . . . . . . . . Bronchial adenomas . . . . . . . . . . . . . . . Bronchoalveolar lung cancer . . . . . . . . . . Bronchography. . . . . . . . . . . . . . . . . . Bronchoscopy . . . . . . . . . . . . . . . . . . BSE. See Breast self-examination Burkitt lymphoma . . . . . . . . . . . . . . . . 1,3-Butadiene . . . . . . . . . . . . . . . . . . 1,4-Butanediol dimethanesulfonate . . . . . . . BWS. See Beckwith-Wiedemann syndrome
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CA 15-3 test . CA 19-9 test . CA 27-29 test CA 125 test. . Cachexia . . . xvi
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Complete List of Contents Cadmium and cadmium compounds. . . . . . . . Caffeine . . . . . . . . . . . . . . . . . . . . . . Calcifications of the breast. . . . . . . . . . . . . Calcium . . . . . . . . . . . . . . . . . . . . . . Cancell . . . . . . . . . . . . . . . . . . . . . . . Cancer biology . . . . . . . . . . . . . . . . . . . Cancer care team . . . . . . . . . . . . . . . . . . Cancer clusters . . . . . . . . . . . . . . . . . . . Cancer education. . . . . . . . . . . . . . . . . . Candidiasis . . . . . . . . . . . . . . . . . . . . . Carcinoembryonic antigen antibody (CEA) test . . . . . . . . . . . . . . . . . . . . . . . . Carcinogens, known . . . . . . . . . . . . . . . . Carcinogens, reasonably anticipated. . . . . . . . Carcinoid tumors and carcinoid syndrome . . . . Carcinoma of unknown primary origin (CUP) . . Carcinomas. . . . . . . . . . . . . . . . . . . . . Carcinomas, invasive ductal. See Invasive ductal carcinomas Carcinomas, invasive lobular. See Invasive lobular carcinomas Carcinomas, leptomeningeal. See Leptomeningeal carcinomas Carcinomatosis. . . . . . . . . . . . . . . . . . . Carcinomatous meningitis . . . . . . . . . . . . . Carcinosarcomas . . . . . . . . . . . . . . . . . . Cardiomyopathy in cancer patients . . . . . . . . Cardiopulmonary resuscitation (CPR) . . . . . . . Caregivers and caregiving . . . . . . . . . . . . . Caregiving, long-distance. See Long-distance caregiving Carney complex . . . . . . . . . . . . . . . . . . Carotenoids . . . . . . . . . . . . . . . . . . . . Cartilage supplements . . . . . . . . . . . . . . . Case management . . . . . . . . . . . . . . . . . Castleman disease . . . . . . . . . . . . . . . . . CBC. See Complete blood count CBE. See Clinical breast exam CDKN2A. See Cyclin-dependent kinase inhibitor-2A CEA test. See Carcinoembryonic antigen antibody test Cell phones. . . . . . . . . . . . . . . . . . . . . Cervical cancer. . . . . . . . . . . . . . . . . . . Chemoembolization . . . . . . . . . . . . . . . . Chemoprevention . . . . . . . . . . . . . . . . . Chemotherapy . . . . . . . . . . . . . . . . . . . Chemotherapy, cognitive effects of. See Cognitive effects of cancer and chemotherapy Chewing tobacco. . . . . . . . . . . . . . . . . . Childbirth and cancer . . . . . . . . . . . . . . .
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Childhood cancers . . . . . . . . . . . . . . . . Chlorambucil. . . . . . . . . . . . . . . . . . . 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)1-nitrosourea (MeCCNU) . . . . . . . . . . . Cholecystectomy . . . . . . . . . . . . . . . . . Chordomas . . . . . . . . . . . . . . . . . . . . Choriocarcinomas . . . . . . . . . . . . . . . . CHPP. See Continuous hyperthermic peritoneal perfusion Chromium hexavalent compounds. . . . . . . . Chromosomes and cancer . . . . . . . . . . . . Chronic lymphocytic leukemia (CLL) . . . . . . Chronic myeloid leukemia (CML). . . . . . . . Cigarettes and cigars . . . . . . . . . . . . . . . Clinical breast exam (CBE) . . . . . . . . . . . Clinical trials . . . . . . . . . . . . . . . . . . . CLL. See Chronic lymphocytic leukemia CML. See Chronic myeloid leukemia Coal tars and coal tar pitches . . . . . . . . . . Cobalt 60 radiation. . . . . . . . . . . . . . . . Coenzyme Q10. . . . . . . . . . . . . . . . . . Cognitive effects of cancer and chemotherapy . Coke oven emissions. . . . . . . . . . . . . . . Cold nodule . . . . . . . . . . . . . . . . . . . Colectomy . . . . . . . . . . . . . . . . . . . . Coloanal anastomosis . . . . . . . . . . . . . . Colon polyps . . . . . . . . . . . . . . . . . . . Colonoscopy and virtual colonoscopy . . . . . . Colony-stimulating factors (CSFs) . . . . . . . Colorectal cancer. . . . . . . . . . . . . . . . . Colorectal cancer screening . . . . . . . . . . . Colostomy . . . . . . . . . . . . . . . . . . . . Colposcopy. . . . . . . . . . . . . . . . . . . . Comedo carcinomas . . . . . . . . . . . . . . . Complementary and alternative therapies . . . . Complete blood count (CBC) . . . . . . . . . . Computed tomography (CT)-guided biopsy . . . . . . . . . . . . . . . . . . . . . Computed tomography (CT) scan . . . . . . . . Conization . . . . . . . . . . . . . . . . . . . . Continuous hyperthermic peritoneal perfusion (CHPP) . . . . . . . . . . . . . . . . . . . . Cordectomy . . . . . . . . . . . . . . . . . . . Cordotomy . . . . . . . . . . . . . . . . . . . . Core needle biopsy. . . . . . . . . . . . . . . . Corticosteroids . . . . . . . . . . . . . . . . . . Coughing . . . . . . . . . . . . . . . . . . . . . Counseling for cancer patients and survivors . . Cowden syndrome . . . . . . . . . . . . . . . . COX-2 inhibitors. See Cyclooxygenase 2 inhibitors
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269 269 271 272
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274 274 276 279 281 283 285
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288 289 289 290 292 292 293 294 296 297 299 300 304 306 308 309 309 312
. . 313 . . 315 . . 317 . . . . . . . .
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318 318 319 321 321 322 324 326
Salem Health: Cancer CPR. See Cardiopulmonary resuscitation Craniopharyngiomas . . . . . . . . . . . . Craniosynostosis . . . . . . . . . . . . . . Craniotomy. . . . . . . . . . . . . . . . . Crohn disease . . . . . . . . . . . . . . . Cruciferous vegetables . . . . . . . . . . . Cryoablation . . . . . . . . . . . . . . . . Cryptorchidism. . . . . . . . . . . . . . . CSFs. See Colony-stimulating factors CT scan. See Computed tomography scan CTCL. See Cutaneous T-cell lymphoma Culdoscopy. . . . . . . . . . . . . . . . . CUP. See Carcinoma of unknown primary origin Curcumin. . . . . . . . . . . . . . . . . . Cushing syndrome and cancer . . . . . . . Cutaneous breast cancer . . . . . . . . . . Cutaneous T-cell lymphoma (CTCL) . . .
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Cyclin-dependent kinase inhibitor-2A (CDKN2A). . . . . . . . . . . . . . . Cyclooxygenase 2 (COX-2) inhibitors . Cyclophosphamide. . . . . . . . . . . . Cyclosporin A . . . . . . . . . . . . . . Cystography . . . . . . . . . . . . . . . Cystoscopy . . . . . . . . . . . . . . . . Cytogenetics . . . . . . . . . . . . . . . Cytokines . . . . . . . . . . . . . . . . Cytology . . . . . . . . . . . . . . . . . Cytology, sputum. See Sputum cytology
327 329 331 332 335 336 338
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344 344 345 346 347 347 348 350 350
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D&C. See Dilation and curettage Dana-Farber Cancer Institute . . . . . . . . . . . . 354 DCIS. See Ductal carcinoma in situ DEA. See Diethanolamine DEHP. See Di(2-ethylhexyl) phthalate Delta-9-tetrahydrocannabinol . . . . . . . . . . . . 355
339 340 341 342
Volume 2 Down syndrome and leukemia. . . . . . . . DPC4 gene testing . . . . . . . . . . . . . . DRE. See Digital rectal exam Drug resistance and multidrug resistance (MDR) . . . . . . . . . . . . . . . . . . . Dry mouth . . . . . . . . . . . . . . . . . . DSRCT. See Desmoplastic small round cell tumor Duct ectasia . . . . . . . . . . . . . . . . . Ductal carcinoma in situ (DCIS). . . . . . . Ductal lavage. . . . . . . . . . . . . . . . . Ductogram . . . . . . . . . . . . . . . . . . Duke Comprehensive Cancer Center . . . . Dukes’ classification . . . . . . . . . . . . . Duodenal carcinomas . . . . . . . . . . . . Dye, hair. See Hair dye Dysplastic nevus syndrome . . . . . . . . .
Contents . . . . . . . . . . . . . . . . . . . . . . xxxiii Complete List of Contents . . . . . . . . . . . . xxxvii Denys-Drash syndrome and cancer . . . . . . Depression . . . . . . . . . . . . . . . . . . . Dermatofibrosarcoma protuberans (DFSP) . . Dermatology oncology. . . . . . . . . . . . . DES. See Diethylstilbestrol Desmoid tumors . . . . . . . . . . . . . . . . Desmoplastic small round cell tumor (DSRCT) . . . . . . . . . . . . . . . . . . Developing nations and cancer . . . . . . . . DFSP. See Dermatofibrosarcoma protuberans Di(2-ethylhexyl) phthalate (DEHP) . . . . . . Diarrhea . . . . . . . . . . . . . . . . . . . . DIC. See Disseminated intravascular coagulation Dietary supplements . . . . . . . . . . . . . . Diethanolamine (DEA) . . . . . . . . . . . . Diethylstilbestrol (DES) . . . . . . . . . . . . Digital rectal exam (DRE) . . . . . . . . . . . Dilation and curettage (D&C) . . . . . . . . . Dioxins . . . . . . . . . . . . . . . . . . . . . Disseminated intravascular coagulation (DIC) . . . . . . . . . . . . . . . . . . . . Diverticulosis and diverticulitis . . . . . . . . DNR. See Do-not-resuscitate order Do-not-resuscitate (DNR) order . . . . . . . .
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357 357 360 362
. . . 365 . . . 365 . . . 366 . . . 368 . . . 369
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370 373 373 374 375 376
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. . . 380 xviii
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386 387 389 389 390 392 393
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Eaton-Lambert syndrome. See Lambert-Eaton myasthenic syndrome EBRT. See External beam radiation therapy Edema . . . . . . . . . . . . . . . . . . . . . Education, cancer. See Cancer education Elderly and cancer . . . . . . . . . . . . . . . Electrolarynx . . . . . . . . . . . . . . . . . . Electromagnetic radiation . . . . . . . . . . . Electroporation therapy . . . . . . . . . . . . Electrosurgery . . . . . . . . . . . . . . . . .
. . . 378 . . . 378
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396 399 399 400 401
Complete List of Contents Embolization . . . . . . . . . . . . . . . . . . . . Embryonal cell cancer . . . . . . . . . . . . . . . End-of-life care . . . . . . . . . . . . . . . . . . Endocrine cancers . . . . . . . . . . . . . . . . . Endocrinology oncology . . . . . . . . . . . . . . Endometrial cancer . . . . . . . . . . . . . . . . Endometrial hyperplasia . . . . . . . . . . . . . . Endorectal ultrasound . . . . . . . . . . . . . . . Endoscopic retrograde cholangiopancreatography (ERCP) . . . . . . . . . . . . . . . . . . . . . Endoscopy . . . . . . . . . . . . . . . . . . . . . Endoscopy, upper gastrointestinal. See Upper gastrointestinal endoscopy Endotheliomas . . . . . . . . . . . . . . . . . . . Enteritis . . . . . . . . . . . . . . . . . . . . . . Enterostomal therapy . . . . . . . . . . . . . . . Eosinophilic leukemia . . . . . . . . . . . . . . . Ependymomas . . . . . . . . . . . . . . . . . . . Epidemiology of cancer . . . . . . . . . . . . . . Epidermoid cancers of mucous membranes . . . . Epstein-Barr virus . . . . . . . . . . . . . . . . . ERCP. See Endoscopic retrograde cholangiopancreatography ERD. See Estrogen receptor downregulator Erionite. . . . . . . . . . . . . . . . . . . . . . . Erythroplakia. . . . . . . . . . . . . . . . . . . . Esophageal cancer . . . . . . . . . . . . . . . . . Esophageal speech . . . . . . . . . . . . . . . . . Esophagectomy . . . . . . . . . . . . . . . . . . Esophagitis . . . . . . . . . . . . . . . . . . . . . Essiac . . . . . . . . . . . . . . . . . . . . . . . Estrogen receptor downregulator (ERD) . . . . . Estrogen-receptor-sensitive breast cancer . . . . . Ethnicity and cancer . . . . . . . . . . . . . . . . Ethylene oxide . . . . . . . . . . . . . . . . . . . Ewing sarcoma . . . . . . . . . . . . . . . . . . . Exenteration . . . . . . . . . . . . . . . . . . . . Exercise and cancer . . . . . . . . . . . . . . . . External beam radiation therapy (EBRT) . . . . . Eye cancers . . . . . . . . . . . . . . . . . . . . Eyelid cancer. . . . . . . . . . . . . . . . . . . .
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Fallopian tube cancer . . . . . . . Family history and risk assessment Fanconi anemia . . . . . . . . . . Fatigue . . . . . . . . . . . . . . . Fecal occult blood test (FOBT) . . Fertility drugs and cancer . . . . . Fertility issues . . . . . . . . . . . Fever . . . . . . . . . . . . . . . . Fiber . . . . . . . . . . . . . . . .
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402 403 404 406 409 412 414 416
. 417 . 417
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420 421 422 424 425 426 429 431
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433 433 434 436 438 439 441 441 442 444 447 447 450 451 454 455 458
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460 461 464 466 467 469 471 472 474 xix
Fibroadenomas . . . . . . . . . . . . . . . . Fibrocystic breast changes . . . . . . . . . . Fibrosarcomas, soft-tissue . . . . . . . . . . Financial issues . . . . . . . . . . . . . . . 5HIAA test. See 5-Hydroxyindoleacetic acid test 5Q minus syndrome . . . . . . . . . . . . . Flow cytometry . . . . . . . . . . . . . . . FOBT. See Fecal occult blood test Folic acid. . . . . . . . . . . . . . . . . . . Formaldehyde . . . . . . . . . . . . . . . . Fox Chase Cancer Center . . . . . . . . . . Fred Hutchinson Cancer Research Center . . Free radicals . . . . . . . . . . . . . . . . . Fruits . . . . . . . . . . . . . . . . . . . . .
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475 476 478 481
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486 486 487 488 490 491
Gallbladder cancer . . . . . . . . . . . . . . Gallium scan . . . . . . . . . . . . . . . . . Gamma Knife . . . . . . . . . . . . . . . . Gardner syndrome . . . . . . . . . . . . . . Garlic and allicin . . . . . . . . . . . . . . . Gastric polyps . . . . . . . . . . . . . . . . Gastrinomas . . . . . . . . . . . . . . . . . Gastrointestinal cancers . . . . . . . . . . . Gastrointestinal complications of cancer treatment. . . . . . . . . . . . . . . . . . Gastrointestinal oncology . . . . . . . . . . Gastrointestinal stromal tumors (GISTs) . . GCTs. See Giant cell tumors Gene therapy . . . . . . . . . . . . . . . . . Genetic counseling . . . . . . . . . . . . . . Genetic testing . . . . . . . . . . . . . . . . Genetics of cancer . . . . . . . . . . . . . . Geography and cancer . . . . . . . . . . . . Germ-cell tumors . . . . . . . . . . . . . . Gerson therapy . . . . . . . . . . . . . . . . Gestational trophoblastic tumors (GTTs) . . Giant cell tumors (GCTs) . . . . . . . . . . Ginseng, panax. . . . . . . . . . . . . . . . GISTs. See Gastrointestinal stromal tumors Gleason grading system . . . . . . . . . . . Gliomas . . . . . . . . . . . . . . . . . . . Glomus tumors . . . . . . . . . . . . . . . . Glossectomy . . . . . . . . . . . . . . . . . Glutamine . . . . . . . . . . . . . . . . . . Gonioscopy . . . . . . . . . . . . . . . . . Grading of tumors . . . . . . . . . . . . . . Graft-versus-host disease (GVHD) . . . . . Granulosa cell tumors . . . . . . . . . . . . Green tea . . . . . . . . . . . . . . . . . . . Grief and bereavement . . . . . . . . . . . .
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493 495 497 498 499 500 501 502
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512 515 517 519 522 525 527 527 530 531
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532 533 534 535 536 536 537 538 540 540 541
Salem Health: Cancer GTTs. See Gestational trophoblastic tumors GVHD. See Graft-versus-host disease Gynecologic cancers . . . . . . . . . . . . . . . . . 543 Gynecologic oncology . . . . . . . . . . . . . . . . 547 H. pylori. See Helicobacter pylori HAI. See Hepatic arterial infusion Hair dye . . . . . . . . . . . . . . . . . . . . . . Hairy cell leukemia . . . . . . . . . . . . . . . . Hand-foot syndrome (HFS) . . . . . . . . . . . . HBV. See Hepatitis B virus HCG. See Human chorionic gonadotropin HCV. See Hepatitis C virus Head and neck cancers . . . . . . . . . . . . . . . Health maintenance organizations (HMOs) . . . . Helicobacter pylori. . . . . . . . . . . . . . . . . Hemangioblastomas . . . . . . . . . . . . . . . . Hemangiopericytomas . . . . . . . . . . . . . . . Hemangiosarcomas . . . . . . . . . . . . . . . . Hematemesis . . . . . . . . . . . . . . . . . . . . Hematologic oncology . . . . . . . . . . . . . . . Hematuria . . . . . . . . . . . . . . . . . . . . . Hemochromatosis . . . . . . . . . . . . . . . . . Hemolytic anemia . . . . . . . . . . . . . . . . . Hemoptysis. . . . . . . . . . . . . . . . . . . . . Hemorrhoids . . . . . . . . . . . . . . . . . . . . Hepatic arterial infusion (HAI) . . . . . . . . . . Hepatitis B virus (HBV) . . . . . . . . . . . . . . Hepatitis C virus (HCV) . . . . . . . . . . . . . . Hepatomegaly . . . . . . . . . . . . . . . . . . . HER2/neu protein . . . . . . . . . . . . . . . . . Herbs as antioxidants . . . . . . . . . . . . . . . Hereditary cancer syndromes . . . . . . . . . . . Hereditary diffuse gastric cancer . . . . . . . . . Hereditary leiomyomatosis and renal cell cancer (HLRCC) . . . . . . . . . . . . . . . . Hereditary mixed polyposis syndrome . . . . . . Hereditary non-VHL clear cell renal cell carcinomas . . . . . . . . . . . . . . . . . . . Hereditary pancreatitis . . . . . . . . . . . . . . . Hereditary papillary renal cell carcinomas . . . . Hereditary polyposis syndromes . . . . . . . . . . Herpes simplex virus. . . . . . . . . . . . . . . . Herpes zoster virus. . . . . . . . . . . . . . . . . HFS. See Hand-foot syndrome Hispanics and cancer. See Latinos/Hispanics and cancer Histamine 2 antagonists . . . . . . . . . . . . . . Histiocytosis X . . . . . . . . . . . . . . . . . . . HIV/AIDS-related cancers . . . . . . . . . . . . .
HLRCC. See Hereditary leiomyomatosis and renal cell cancer HMOs. See Health maintenance organizations Hodgkin disease . . . . . . . . . . . . . . . . . Home health services . . . . . . . . . . . . . . Hormonal therapies . . . . . . . . . . . . . . . Hormone receptor tests . . . . . . . . . . . . . Hormone replacement therapy (HRT) . . . . . . Horner syndrome. . . . . . . . . . . . . . . . . Hospice care . . . . . . . . . . . . . . . . . . . Hot flashes . . . . . . . . . . . . . . . . . . . . HPV. See Human papillomavirus HRAS gene testing . . . . . . . . . . . . . . . . HRT. See Hormone replacement therapy HTLV. See Human T-cell leukemia virus Human chorionic gonadotropin (HCG) . . . . . Human growth factors and tumor growth . . . . Human immunodeficiency virus-related cancers. See HIV/AIDS-related cancers Human papillomavirus (HPV) . . . . . . . . . . Human T-cell leukemia virus (HTLV) . . . . . Hydatidiform mole . . . . . . . . . . . . . . . . 5-Hydroxyindoleacetic acid (5HIAA) test . . . . Hypercalcemia . . . . . . . . . . . . . . . . . . Hypercoagulation disorders . . . . . . . . . . . Hyperthermia therapy . . . . . . . . . . . . . . Hyperthermic perfusion . . . . . . . . . . . . . Hypopharyngeal cancer . . . . . . . . . . . . . Hysterectomy . . . . . . . . . . . . . . . . . . Hysterography . . . . . . . . . . . . . . . . . . Hystero-oophorectomy. . . . . . . . . . . . . . Hysteroscopy. . . . . . . . . . . . . . . . . . .
. 550 . 550 . 552
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554 557 558 559 559 560 561 562 564 565 566 566 567 568 569 570 571 573 573 574 576
IEP. See Immunoelectrophoresis iFOBT. See Immunochemical fecal occult blood test Ileostomy. . . . . . . . . . . . . . . . . . . . . Imaging tests . . . . . . . . . . . . . . . . . . . Immune response to cancer . . . . . . . . . . . Immunochemical fecal occult blood test (iFOBT) . . . . . . . . . . . . . . . . . . . . Immunocytochemistry and immunohistochemistry . . . . . . . . . . . . Immunoelectrophoresis (IEP) . . . . . . . . . . Immunotherapy . . . . . . . . . . . . . . . . . IMRT. See Intensity-modulated radiation therapy Indoles . . . . . . . . . . . . . . . . . . . . . . Infection and sepsis . . . . . . . . . . . . . . . Infectious cancers . . . . . . . . . . . . . . . . Infertility and cancer . . . . . . . . . . . . . . .
. 577 . 579 . . . . . .
580 580 581 582 584 586
. 587 . 588 . 590 xx
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593 597 599 601 603 605 606 608
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611 612 612 613 614 615 617 618 619 620 621 622 623
. . 625 . . 626 . . 629 . . 632 . . 633 . . 634 . . 635
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638 638 641 643
Complete List of Contents Inflammatory bowel disease . . . . . . . . . . Informed consent. . . . . . . . . . . . . . . . Infusion therapies . . . . . . . . . . . . . . . Insurance . . . . . . . . . . . . . . . . . . . . Integrative oncology . . . . . . . . . . . . . . Intensity-modulated radiation therapy (IMRT) Interferon. . . . . . . . . . . . . . . . . . . . Interleukins. . . . . . . . . . . . . . . . . . . Invasive cancer. . . . . . . . . . . . . . . . . Invasive ductal carcinomas . . . . . . . . . . Invasive lobular carcinomas . . . . . . . . . . Ionizing radiation . . . . . . . . . . . . . . . Iridium seeds . . . . . . . . . . . . . . . . . . Islet cell tumors . . . . . . . . . . . . . . . . Isoflavones . . . . . . . . . . . . . . . . . . . Itching . . . . . . . . . . . . . . . . . . . . .
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645 646 647 648 651 652 653 654 655 656 657 657 658 659 661 661
Lambert-Eaton myasthenic syndrome (LEMS) Laparoscopy and laparoscopic surgery . . . . Laryngeal cancer . . . . . . . . . . . . . . . . Laryngeal nerve palsy . . . . . . . . . . . . . Laryngectomy . . . . . . . . . . . . . . . . . Laryngoscopy . . . . . . . . . . . . . . . . . Laser therapies . . . . . . . . . . . . . . . . . Latinos/Hispanics and cancer . . . . . . . . . Laxatives . . . . . . . . . . . . . . . . . . . . LCIS. See Lobular carcinoma in situ LDH test. See Lactate dehydrogenase test Leiomyomas . . . . . . . . . . . . . . . . . . Leiomyosarcomas . . . . . . . . . . . . . . . LEMS. See Lambert-Eaton myasthenic syndrome Leptomeningeal carcinomas . . . . . . . . . . Leukapharesis . . . . . . . . . . . . . . . . . Leukemia, Down syndrome and. See Down syndrome and leukemia Leukemia, eosinophilic. See Eosinophilic leukemia Leukemia, hairy cell. See Hairy cell leukemia Leukemias . . . . . . . . . . . . . . . . . . . Leukoencephalopathy . . . . . . . . . . . . . Leukopenia. . . . . . . . . . . . . . . . . . . Leukoplakia . . . . . . . . . . . . . . . . . . Leydig cell tumors . . . . . . . . . . . . . . . Li-Fraumeni syndrome (LFS) . . . . . . . . . Limb salvage . . . . . . . . . . . . . . . . . . Linear accelerator . . . . . . . . . . . . . . . Lip cancers . . . . . . . . . . . . . . . . . . . Liposarcomas . . . . . . . . . . . . . . . . . Liver biopsy . . . . . . . . . . . . . . . . . . Liver cancers . . . . . . . . . . . . . . . . . .
Jonsson Comprehensive Cancer Center (JCCC) . . . . . . . . . . . . . . . . . . . . . . 664 Journaling . . . . . . . . . . . . . . . . . . . . . . 665 Juvenile polyposis syndrome . . . . . . . . . . . . 665 Kaposi sarcoma . . . . . . . . . . . . . Karnofsky performance status (KPS) . . Keratosis . . . . . . . . . . . . . . . . . Ki67 test . . . . . . . . . . . . . . . . . Kidney cancer . . . . . . . . . . . . . . Klinefelter syndrome and cancer . . . . KPS. See Karnofsky performance status Krukenberg tumors . . . . . . . . . . .
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667 669 670 670 671 674
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Lacrimal gland tumors . . . . . . . . . . . . . . . . 677 Lactate dehydrogenase (LDH) test . . . . . . . . . 678 Laetrile . . . . . . . . . . . . . . . . . . . . . . . . 679
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679 681 682 685 686 687 688 690 692
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. . . 696 . . . 698
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698 702 704 704 706 706 708 709 710 712 714 715
Volume 3 Lumps . . . . . . . . . . . . . . Lung cancer, brochoalveolar. See Bronchoalveolar lung cancer Lung cancers . . . . . . . . . . . Lutein . . . . . . . . . . . . . . Lycopene . . . . . . . . . . . . . Lymphadenectomy. . . . . . . . Lymphangiography . . . . . . . Lymphangiosarcomas . . . . . . Lymphedema. . . . . . . . . . . Lymphocytosis . . . . . . . . . . Lymphomas . . . . . . . . . . .
Contents . . . . . . . . . . . . . . . . . . . . . . . . lv Complete List of Contents . . . . . . . . . . . . . . lix Living will . . . . . . . . . . . . . . . . . Living with cancer . . . . . . . . . . . . . Lobectomy . . . . . . . . . . . . . . . . . Lobular carcinoma in situ (LCIS) . . . . . Long-distance caregiving . . . . . . . . . Loop electrosurgical excisional procedure (LEEP) . . . . . . . . . . . . . . . . . Lumbar puncture . . . . . . . . . . . . . . Lumpectomy . . . . . . . . . . . . . . . .
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719 720 723 725 726
. . . . . 727 . . . . . 728 . . . . . 730 xxi
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733 737 737 738 740 741 742 743 744
Salem Health: Cancer M. D. Anderson Cancer Center . . . . . . . . . Macrobiotic diet . . . . . . . . . . . . . . . . . Magnetic resonance imaging (MRI) . . . . . . . Malignant fibrous histiocytoma (MFH) . . . . . Malignant rhabdoid tumor of the kidney . . . . Malignant tumors . . . . . . . . . . . . . . . . MALT lymphomas. See Mucosa-associated lymphoid tissue lymphomas Mammography . . . . . . . . . . . . . . . . . . Managed care . . . . . . . . . . . . . . . . . . Mantle cell lymphoma (MCL) . . . . . . . . . . Mastectomy . . . . . . . . . . . . . . . . . . . Mastocytomas . . . . . . . . . . . . . . . . . . Matrix metalloproteinase inhibitors . . . . . . . Mayo Clinic Cancer Center . . . . . . . . . . . MCC. See Merkel cell carcinomas MCL. See Mantle cell lymphoma MDR. See Drug resistance and multidrug resistance Mediastinal tumors. . . . . . . . . . . . . . . . Mediastinoscopy . . . . . . . . . . . . . . . . . Medical marijuana . . . . . . . . . . . . . . . . Medical oncology . . . . . . . . . . . . . . . . Medicare and cancer . . . . . . . . . . . . . . . Medullary carcinoma of the breast. . . . . . . . Medulloblastomas . . . . . . . . . . . . . . . . Melanomas . . . . . . . . . . . . . . . . . . . . Melphalan . . . . . . . . . . . . . . . . . . . . Memorial Sloan-Kettering Cancer Center . . . . MEN 1. See Multiple endocrine neoplasia type 1 MEN 2. See Multiple endocrine neoplasia type 2 Meningeal carcinomatosis . . . . . . . . . . . . Meningiomas. . . . . . . . . . . . . . . . . . . Merkel cell carcinomas (MCC) . . . . . . . . . Mesenchymomas, malignant. . . . . . . . . . . Mesothelioma . . . . . . . . . . . . . . . . . . Metastasis . . . . . . . . . . . . . . . . . . . . Metastatic squamous neck cancer with occult primary . . . . . . . . . . . . . . . . . . . . MFH. See Malignant fibrous histiocytoma Microcalcifications. . . . . . . . . . . . . . . . Microwave hyperthermia therapy . . . . . . . . Mineral oils . . . . . . . . . . . . . . . . . . . Mistletoe . . . . . . . . . . . . . . . . . . . . . Mitochondrial DNA mutations. . . . . . . . . . MLH1 gene. . . . . . . . . . . . . . . . . . . . Mohs surgery. . . . . . . . . . . . . . . . . . . Molecular oncology . . . . . . . . . . . . . . . Moles. . . . . . . . . . . . . . . . . . . . . . . Monoclonal antibodies . . . . . . . . . . . . . . Motion sickness devices . . . . . . . . . . . . .
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748 750 750 752 753 754
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754 757 759 761 763 764 765
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766 768 768 770 772 774 775 776 779 780
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MRI. See Magnetic resonance imaging MSH genes . . . . . . . . . . . . . . . . . . . . Mucinous carcinomas . . . . . . . . . . . . . . Mucosa-associated lymphoid tissue (MALT) lymphomas . . . . . . . . . . . . . . . . . . Mucositis . . . . . . . . . . . . . . . . . . . . . Mucous membranes, epidermoid cancers of. See Epidermoid cancers of mucous membranes Multiple endocrine neoplasia type 1 (MEN 1). . Multiple endocrine neoplasia type 2 (MEN 2). . Multiple myeloma . . . . . . . . . . . . . . . . Mustard gas . . . . . . . . . . . . . . . . . . . Mutagenesis and cancer . . . . . . . . . . . . . Myasthenia gravis . . . . . . . . . . . . . . . . MYC oncogene . . . . . . . . . . . . . . . . . . Mycosis fungoides . . . . . . . . . . . . . . . . Myelodysplastic syndromes . . . . . . . . . . . Myelofibrosis . . . . . . . . . . . . . . . . . . Myeloma . . . . . . . . . . . . . . . . . . . . . Myeloproliferative disorders. . . . . . . . . . . Myelosuppression . . . . . . . . . . . . . . . . 2-Naphthylamine. . . . . . . . . . . . . . . . Nasal cavity and paranasal sinus cancers . . . National Cancer Institute (NCI) . . . . . . . . National Science Foundation (NSF) . . . . . . Native North Americans and cancer . . . . . . Nausea and vomiting. . . . . . . . . . . . . . NCI. See National Cancer Institute Needle biopsies . . . . . . . . . . . . . . . . Needle localization. . . . . . . . . . . . . . . Nephroblastomas. . . . . . . . . . . . . . . . Nephrostomy . . . . . . . . . . . . . . . . . . Neuroblastomas . . . . . . . . . . . . . . . . Neuroectodermal tumors. . . . . . . . . . . . Neuroendocrine tumors . . . . . . . . . . . . Neurofibromatosis type 1 (NF1) . . . . . . . . Neurologic oncology. . . . . . . . . . . . . . Neutropenia . . . . . . . . . . . . . . . . . . NF1. See Neurofibromatosis type 1 Nickel compounds and metallic nickel . . . . Night sweats . . . . . . . . . . . . . . . . . . Nijmegen breakage syndrome . . . . . . . . . Nipple discharge . . . . . . . . . . . . . . . . Non-Hodgkin lymphoma . . . . . . . . . . . Nonsteroidal anti-inflammatory drugs (NSAIDs) . . . . . . . . . . . . . . . . . . NSAIDs. See Nonsteroidal anti-inflammatory drugs NSF. See National Science Foundation Nuclear medicine scan . . . . . . . . . . . . .
781 782 783 785 786 788
. . 790 . . . . . . . . . . .
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790 791 792 793 794 795 796 796 798 800 802 xxii
. . 803 . . 803 . . 804 . . 806
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807 808 809 812 813 815 817 817 819 820 822 823 825
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826 826 829 830 832 834
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836 838 839 839 841 842 844 845 847 849
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851 852 853 854 855
. . . 858
. . . 859
Complete List of Contents Pediatric oncology and hematology . . . . . . . . . 938 Pelvic examination . . . . . . . . . . . . . . . . . . 940 Penile cancer . . . . . . . . . . . . . . . . . . . . . 941 Percutaneous transhepatic cholangiography (PTHC) . . . . . . . . . . . . . . . . . . . . . . 943 Pericardial effusion . . . . . . . . . . . . . . . . . 944 Pericardiocentesis . . . . . . . . . . . . . . . . . . 946 Peritoneovenous shunts . . . . . . . . . . . . . . . 946 Personality and cancer . . . . . . . . . . . . . . . . 947 Pesticides and the food chain . . . . . . . . . . . . 948 PET. See Positron emission tomography Peutz-Jeghers syndrome (PJS) . . . . . . . . . . . . 951 Pharmacy oncology . . . . . . . . . . . . . . . . . 952 Phenacetin . . . . . . . . . . . . . . . . . . . . . . 955 Phenolics . . . . . . . . . . . . . . . . . . . . . . . 955 Pheochromocytomas . . . . . . . . . . . . . . . . . 956 Pheresis . . . . . . . . . . . . . . . . . . . . . . . 958 Photodynamic therapy (PDT) . . . . . . . . . . . . 959 Phyllodes tumors. . . . . . . . . . . . . . . . . . . 960 Phytoestrogens . . . . . . . . . . . . . . . . . . . . 962 Pineoblastomas. . . . . . . . . . . . . . . . . . . . 963 Pituitary tumors . . . . . . . . . . . . . . . . . . . 965 PJS. See Peutz-Jeghers syndrome Placental alkaline phosphatase (PALP) . . . . . . . 968 Plant alkaloids and terpenoids in chemotherapy . . . . . . . . . . . . . . . . . . . 968 Plasticizers . . . . . . . . . . . . . . . . . . . . . . 971 Pleural biopsy . . . . . . . . . . . . . . . . . . . . 972 Pleural effusion . . . . . . . . . . . . . . . . . . . 973 Pleurodesis . . . . . . . . . . . . . . . . . . . . . . 975 Pleuropulmonary blastomas . . . . . . . . . . . . . 975 PMS genes . . . . . . . . . . . . . . . . . . . . . . 976 Pneumonectomy . . . . . . . . . . . . . . . . . . . 977 Pneumonia . . . . . . . . . . . . . . . . . . . . . . 979 Polycyclic aromatic hydrocarbons . . . . . . . . . . 981 Polycythemia vera . . . . . . . . . . . . . . . . . . 981 Polypectomy . . . . . . . . . . . . . . . . . . . . . 982 Polyps . . . . . . . . . . . . . . . . . . . . . . . . 983 Polyps, colon. See Colon polyps Polyps, gastric. See Gastric polyps Positron emission tomography (PET) . . . . . . . . 984 Poverty and cancer . . . . . . . . . . . . . . . . . . 987 PPOs. See Preferred provider organizations Prayer and cancer support . . . . . . . . . . . . . . 989 Preferred provider organizations (PPOs) . . . . . . 990 Pregnancy and cancer . . . . . . . . . . . . . . . . 992 Premalignancies . . . . . . . . . . . . . . . . . . . 994 Prevent Cancer Foundation . . . . . . . . . . . . . 997 Prevention . . . . . . . . . . . . . . . . . . . . . . 999 Primary care physician . . . . . . . . . . . . . . . 1001
Nutrition and cancer prevention . . . . . . . . . . . 861 Nutrition and cancer treatment. . . . . . . . . . . . 864 Obesity-associated cancers . . . . . Occupational exposures and cancer . Occupational therapy . . . . . . . . OCs. See Organochlorines Oligodendrogliomas . . . . . . . . . Omega-3 fatty acids . . . . . . . . . Ommaya reservoir . . . . . . . . . . Oncogenes . . . . . . . . . . . . . . Oncogenic viruses . . . . . . . . . . Oncology . . . . . . . . . . . . . . . Oncology clinical nurse specialist . . Oncology social worker . . . . . . . Oophorectomy . . . . . . . . . . . . Ophthalmic oncology . . . . . . . . Opioids . . . . . . . . . . . . . . . . Oral and maxillofacial surgery. . . . Oral and oropharyngeal cancers . . . Orbit tumors . . . . . . . . . . . . . Orchiectomy . . . . . . . . . . . . . Organ transplantation and cancer . . Organochlorines (OCs) . . . . . . . Oropharyngeal cancers. See Oral and oropharyngeal cancers Orthopedic surgery. . . . . . . . . . Otolaryngology . . . . . . . . . . . Ovarian cancers . . . . . . . . . . . Ovarian cysts. . . . . . . . . . . . . Ovarian epithelial cancer . . . . . . Overtreatment . . . . . . . . . . . .
. . . . . . . . 868 . . . . . . . . 871 . . . . . . . . 873 . . . . . . . . . . . . . . . . .
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875 877 878 878 881 882 885 887 888 889 892 893 894 897 898 899 901
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902 903 905 908 909 911
Paget disease of bone . . . . . . . . . . . . . Pain management medications. . . . . . . . . Palliative treatment . . . . . . . . . . . . . . PALP. See Placental alkaline phosphatase Palpation . . . . . . . . . . . . . . . . . . . . Pancolitis . . . . . . . . . . . . . . . . . . . . Pancreatectomy . . . . . . . . . . . . . . . . Pancreatic cancers . . . . . . . . . . . . . . . Pancreatitis . . . . . . . . . . . . . . . . . . . Pap test . . . . . . . . . . . . . . . . . . . . . Paracentesis . . . . . . . . . . . . . . . . . . Paranasal sinus cancers. See Nasal cavity and paranasal sinus cancers Paraneoplastic syndromes . . . . . . . . . . . Parathyroid cancer . . . . . . . . . . . . . . . Pathology . . . . . . . . . . . . . . . . . . . PC-SPES . . . . . . . . . . . . . . . . . . . . PDT. See Photodynamic therapy
. . . 912 . . . 914 . . . 917 . . . . . . .
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920 920 921 923 927 928 929
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931 932 934 937 xxiii
Salem Health: Cancer Primary central nervous system lymphomas . . . . . . . . . . . . . . . . Progesterone receptor assay . . . . . . . . Prostate cancer . . . . . . . . . . . . . . . Prostate-specific antigen (PSA) test . . . . Prostatectomy. . . . . . . . . . . . . . . . Prostatitis . . . . . . . . . . . . . . . . . . Proteasome inhibitors. . . . . . . . . . . . Protein electrophoresis . . . . . . . . . . . Proteomics and cancer research . . . . . . Proton beam therapy . . . . . . . . . . . . Proto-oncogenes and carcinogenesis . . . . PSA test. See Prostate-specific antigen test Psycho-oncology . . . . . . . . . . . . . . Psychosocial aspects of cancer . . . . . . . PTHC. See Percutaneous transhepatic cholangiography Radiation, ionizing. See Ionizing radiation Radiation oncology . . . . . . . . . . . . . Radiation therapies . . . . . . . . . . . . . Radiation therapy, afterloading. See Afterloading radiation therapy Radical neck dissection . . . . . . . . . . . Radiofrequency ablation . . . . . . . . . . Radionuclide scan . . . . . . . . . . . . . Radiopharmaceuticals . . . . . . . . . . . Radon . . . . . . . . . . . . . . . . . . . . RB1 gene . . . . . . . . . . . . . . . . . . Receptor analysis . . . . . . . . . . . . . .
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1003 1003 1004 1006 1008 1009 1010 1010 1012 1014 1015
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. . . . 1021 . . . . 1023
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1027 1027 1030 1030 1032 1032 1033
Reconstructive surgery . . . . . . . . . . . . . . Rectal cancer . . . . . . . . . . . . . . . . . . . Recurrence . . . . . . . . . . . . . . . . . . . . Rehabilitation . . . . . . . . . . . . . . . . . . . Relationships . . . . . . . . . . . . . . . . . . . Renal pelvis tumors. . . . . . . . . . . . . . . . Report on Carcinogens (RoC) . . . . . . . . . . Resveratrol . . . . . . . . . . . . . . . . . . . . Retinoblastomas . . . . . . . . . . . . . . . . . Rhabdomyosarcomas . . . . . . . . . . . . . . . RhoGD12 gene . . . . . . . . . . . . . . . . . . Richter syndrome . . . . . . . . . . . . . . . . . Risk assessment, family history and. See Family history and risk assessment Risks for cancer. . . . . . . . . . . . . . . . . . Robert H. Lurie Cancer Center . . . . . . . . . . RoC. See Report on Carcinogens Rothmund-Thomson syndrome . . . . . . . . . .
. . . . . . . . . . . .
Salivary gland cancer . . . . . . . . . . . . . Salpingectomy and salpingo-oophorectomy . Sarcomas, soft-tissue . . . . . . . . . . . . . Saw palmetto . . . . . . . . . . . . . . . . . Schwannoma tumors . . . . . . . . . . . . . SCLC1 gene. . . . . . . . . . . . . . . . . . Screening, colorectal cancer. See Colorectal cancer screening Screening for cancer . . . . . . . . . . . . . Second opinions . . . . . . . . . . . . . . . Self-image and body image. . . . . . . . . .
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1034 1036 1038 1038 1041 1043 1044 1045 1046 1048 1050 1050
. 1052 . 1054 . 1056 1058 1060 1062 1065 1066 1067
. . . 1067 . . . 1070 . . . 1071
Volume 4 Sjögren syndrome. . . . . . . . . . . . . . . . Skin cancers . . . . . . . . . . . . . . . . . . SLN biopsy and mapping. See Sentinel lymph node biopsy and mapping Small intestine cancer . . . . . . . . . . . . . Smoking cessation . . . . . . . . . . . . . . . Social Security Disability Insurance (SSDI) . . Soft-tissue fibrosarcomas. See Fibrosarcomas, soft-tissue Soots . . . . . . . . . . . . . . . . . . . . . . Soy foods . . . . . . . . . . . . . . . . . . . . Spermatocytomas . . . . . . . . . . . . . . . . Spinal axis tumors . . . . . . . . . . . . . . . Spinal cord compression . . . . . . . . . . . . Splenectomy . . . . . . . . . . . . . . . . . . Sputum cytology . . . . . . . . . . . . . . . .
Contents . . . . . . . . . . . . . . . . . . . . . . lxxvii Complete List of Contents . . . . . . . . . . . . . lxxix Sentinel lymph node (SLN) biopsy and mapping . . . . . . . . . . . . . . . Sepsis. See Infection and sepsis Sertoli cell tumors . . . . . . . . . . . Sexuality and cancer . . . . . . . . . . Sézary syndrome . . . . . . . . . . . . SIADH. See Syndrome of inappropriate antidiuretic hormone production Side effects . . . . . . . . . . . . . . . Sigmoidoscopy . . . . . . . . . . . . . Silica, crystalline . . . . . . . . . . . . Simian virus 40 . . . . . . . . . . . . . Singlehood and cancer . . . . . . . . .
. . . . . . 1073 . . . . . . 1073 . . . . . . 1074 . . . . . . 1076
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1078 1082 1083 1084 1084 xxiv
. . 1086 . . 1088
. . 1091 . . 1093 . . 1096
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1097 1098 1099 1100 1102 1103 1105
Complete List of Contents Squamous cell carcinomas . . . . . . . . . . . SRS. See Stereotactic radiosurgery SSDI. See Social Security Disability Insurance Staging of cancer . . . . . . . . . . . . . . . . Statistics of cancer . . . . . . . . . . . . . . . Stem cell transplantation . . . . . . . . . . . . Stent therapy . . . . . . . . . . . . . . . . . . Stereotactic needle biopsy . . . . . . . . . . . Stereotactic radiosurgery (SRS) . . . . . . . . Sterility . . . . . . . . . . . . . . . . . . . . . Stomach cancers . . . . . . . . . . . . . . . . Stomatitis . . . . . . . . . . . . . . . . . . . . Stress management . . . . . . . . . . . . . . . Sunlamps . . . . . . . . . . . . . . . . . . . . Sun’s soup . . . . . . . . . . . . . . . . . . . Sunscreens . . . . . . . . . . . . . . . . . . . Superior vena cava syndrome . . . . . . . . . Support groups . . . . . . . . . . . . . . . . . Surgical biopsies . . . . . . . . . . . . . . . . Surgical oncology. . . . . . . . . . . . . . . . Survival rates . . . . . . . . . . . . . . . . . . Survivorship issues . . . . . . . . . . . . . . . Symptoms and cancer. . . . . . . . . . . . . . Syndrome of inappropriate antidiuretic hormone production (SIADH) . . . . . . . . Synovial sarcomas . . . . . . . . . . . . . . . Taste alteration . . . . . . . . . . . . . . Teratocarcinomas . . . . . . . . . . . . . Teratomas . . . . . . . . . . . . . . . . . Testicular cancer . . . . . . . . . . . . . Testicular self-examination (TSE) . . . . Thermal imaging . . . . . . . . . . . . . Thiotepa. . . . . . . . . . . . . . . . . . Thoracentesis . . . . . . . . . . . . . . . Thoracoscopy . . . . . . . . . . . . . . . Thoracotomy . . . . . . . . . . . . . . . Throat cancer . . . . . . . . . . . . . . . Thrombocytopenia . . . . . . . . . . . . Thymomas . . . . . . . . . . . . . . . . Thymus cancer . . . . . . . . . . . . . . Thyroid cancer . . . . . . . . . . . . . . Thyroid nuclear medicine scan . . . . . . TNF. See Tumor necrosis factor TNM staging . . . . . . . . . . . . . . . Tobacco, chewing. See Chewing tobacco Tobacco-related cancers . . . . . . . . . Topoisomerase inhibitors . . . . . . . . . TP53 protein . . . . . . . . . . . . . . . Tracheostomy . . . . . . . . . . . . . . . Transfusion therapy. . . . . . . . . . . .
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Transitional care . . . . . . . . . . . Transitional cell carcinomas . . . . . Transrectal ultrasound . . . . . . . . Transvaginal ultrasound . . . . . . . Trichilemmal carcinomas. . . . . . . TSE. See Testicular self-examination Tuberous sclerosis . . . . . . . . . . Tubular carcinomas . . . . . . . . . . Tumor flare . . . . . . . . . . . . . . Tumor lysis syndrome . . . . . . . . Tumor markers . . . . . . . . . . . . Tumor necrosis factor (TNF) . . . . . Tumor-suppressor genes . . . . . . . Turcot syndrome . . . . . . . . . . . Tyrosine kinase inhibitors . . . . . .
. . 1106
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1108 1111 1114 1116 1118 1119 1120 1121 1124 1125 1127 1128 1129 1130 1132 1135 1138 1140 1143 1144
. . 1147 . . 1149 . . . . . . . . . . . . . . . .
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1151 1152 1153 1154 1156 1157 1158 1158 1160 1161 1162 1164 1166 1167 1169 1172
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1182 1183 1185 1186 1187
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1187 1188 1189 1189 1191 1193 1194 1195 1196
Ultrasound, breast. See Breast ultrasound Ultrasound, endorectal. See Endorectal ultrasound Ultrasound, transrectal. See Transrectal ultrasound Ultrasound, transvaginal. See Transvaginal ultrasound Ultrasound tests . . . . . . . . . . . . . . . Ultraviolet radiation and related exposures Umbilical cord blood transplantation. . . . Upper gastrointestinal (GI) endoscopy . . . Upper gastrointestinal (GI) series . . . . . Urethral cancer . . . . . . . . . . . . . . . Urinalysis . . . . . . . . . . . . . . . . . . Urinary system cancers . . . . . . . . . . . Urography . . . . . . . . . . . . . . . . . Urologic oncology . . . . . . . . . . . . . Urostomy . . . . . . . . . . . . . . . . . . Uterine cancer . . . . . . . . . . . . . . .
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1199 1200 1201 1202 1203 1205 1207 1209 1213 1214 1216 1217
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1220 1221 1223 1225 1226
Vaccines, preventive . . . . . . . . . . . Vaccines, therapeutic . . . . . . . . . . . Vaginal cancer . . . . . . . . . . . . . . Vascular access tubes. . . . . . . . . . . Vasectomy and cancer . . . . . . . . . . Vegetables, cruciferous. See Cruciferous vegetables Veterinary oncology . . . . . . . . . . . VHL disease. See Von Hippel-Lindau disease Vinyl chloride . . . . . . . . . . . . . . Viral oncology . . . . . . . . . . . . . . Virus-related cancers . . . . . . . . . . . Von Hippel-Lindau (VHL) disease. . . . Vulvar cancer . . . . . . . . . . . . . . .
. . . . . 1173 . . . . .
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1174 1175 1177 1179 1180 xxv
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1230 1230 1232 1235 1237
Salem Health: Cancer WAGR syndrome. See Wilms’ tumor aniridiagenitourinary anomalies-mental retardation syndrome and cancer Waldenström macroglobulinemia (WM) . . . . . . 1240 Watchful waiting . . . . . . . . . . . . . . . . . . 1242 Weight loss . . . . . . . . . . . . . . . . . . . . . 1243 Wilms’ tumor . . . . . . . . . . . . . . . . . . . . 1245 Wilms’ tumor aniridia-genitourinary anomaliesmental retardation (WAGR) syndrome and cancer . . . . . . . . . . . . . . . . . . . . . . 1248 Wine and cancer . . . . . . . . . . . . . . . . . . 1250 Wire localization . . . . . . . . . . . . . . . . . . 1250 WM. See Waldenström macroglobulinemia Wood dust . . . . . . . . . . . . . . . . . . . . . 1251
Yolk sac carcinomas . . . . . . . . . . . . . . . . 1256 Young adult cancers . . . . . . . . . . . . . . . . 1256 Zollinger-Ellison syndrome . . . . . . . . . . . . 1260 Drugs by Generic Name . . . Drugs by Trade Name . . . . Associations and Agencies . . Cancer Centers and Hospitals Cancer Support Groups . . . . Carcinogens. . . . . . . . . . Glossary . . . . . . . . . . . Bibliography . . . . . . . . .
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1265 1309 1348 1352 1357 1362 1383 1400
Category List . . . . . . . . . . . . . . . . . . . . 1409 Index . . . . . . . . . . . . . . . . . . . . . . . . 1419
X-ray tests . . . . . . . . . . . . . . . . . . . . . 1252 Xeroderma pigmentosa . . . . . . . . . . . . . . . 1254
xxvi
Volume II Denys-Drash syndrome and cancer — Liver cancers
Editor
Jeffrey A. Knight, Ph.D. Mount Holyoke College
Medical Consultants
Laurie Jackson-Grusby, Ph.D. Children’s Hospital Boston, Harvard Medical School
Wendy White-Ryan, M.D., FAAP Golisano Children’s Hospital at Strong Memorial Hospital
SALEM PRESS, INC. Pasadena, California Hackensack, New Jersey
Editor in Chief: Dawn P. Dawson Editorial Director: Christina J. Moose Project Editors: Tracy Irons-Georges, Rowena Wildin Dehanke Editorial Assistant: Dana Garey
Production Editor: Joyce I. Buchea Acquisitions Editor: Mark Rehn Photo Editor: Cynthia Breslin Beres Design and Graphics: James Hutson Layout: William Zimmerman
Copyright © 2009, by Salem Press, Inc. All rights in this book are reserved. No part of this work may be used or reproduced in any manner whatsoever or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without written permission from the copyright owner except in the case of brief quotations embodied in critical articles and reviews or in the copying of images deemed to be freely licensed or in the public domain. For information address the publisher, Salem Press, Inc., P.O. Box 50062, Pasadena, California 91115. ∞ The paper used in these volumes conforms to the American National Standard for Permanence of Paper for Printed Library Materials, Z39.48-1992 (R1997). Note to Readers The material presented in Salem Health: Cancer is intended for broad informational and educational purposes. Readers who suspect that they or someone whom they know or provide caregiving for suffers from cancer or any other physical or psychological disorder, disease, or condition described in this set should contact a physician without delay; this work should not be used as a substitute for professional medical diagnosis or staging. Readers who are undergoing or about to undergo any treatment or procedure described in this set should refer to their physicians and other health care team members for guidance concerning preparation and possible effects. This set is not to be considered definitive on the covered topics, and readers should remember that the field of health care is characterized by a diversity of medical opinions and constant expansion in knowledge and understanding. Library of Congress Cataloging-in-Publication Data Salem health : cancer / Jeffrey A. Knight, Laurie Jackson-Grusby, Wendy White-Ryan. p. cm. Includes bibliographical references and index. ISBN 978-1-58765-505-0 (set : alk. paper) — ISBN 978-1-58765-506-7 (vol. 1 : alk. paper) — ISBN 978-1-58765-507-4 (vol. 2 : alk. paper) — ISBN 978-1-58765-508-1 (vol. 3 : alk. paper) — ISBN 978-1-58765-509-8 (vol. 4 : alk. paper) 1. Cancer. I. Knight, Jeffrey A., 1948- II. Jackson-Grusby, Laurie. III. White-Ryan, Wendy. RC265.S32 2008 616.99′4—dc22 2008030861
First Printing
printed in the united states of america
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Contents
Complete List of Contents . . . . . . . . . . . . xxxvii Denys-Drash syndrome and cancer . . . . . . Depression . . . . . . . . . . . . . . . . . . . Dermatofibrosarcoma protuberans (DFSP) . . Dermatology oncology. . . . . . . . . . . . . DES. See Diethylstilbestrol Desmoid tumors . . . . . . . . . . . . . . . . Desmoplastic small round cell tumor (DSRCT) . . . . . . . . . . . . . . . . . . Developing nations and cancer . . . . . . . . DFSP. See Dermatofibrosarcoma protuberans Di(2-ethylhexyl) phthalate (DEHP) . . . . . . Diarrhea . . . . . . . . . . . . . . . . . . . . DIC. See Disseminated intravascular coagulation Dietary supplements . . . . . . . . . . . . . . Diethanolamine (DEA) . . . . . . . . . . . . Diethylstilbestrol (DES) . . . . . . . . . . . . Digital rectal exam (DRE) . . . . . . . . . . . Dilation and curettage (D&C) . . . . . . . . . Dioxins . . . . . . . . . . . . . . . . . . . . . Disseminated intravascular coagulation (DIC) . . . . . . . . . . . . . . . . . . . . Diverticulosis and diverticulitis . . . . . . . . DNR. See Do-not-resuscitate order Do-not-resuscitate (DNR) order . . . . . . . . Down syndrome and leukemia. . . . . . . . . DPC4 gene testing . . . . . . . . . . . . . . . DRE. See Digital rectal exam Drug resistance and multidrug resistance (MDR) . . . . . . . . . . . . . . . . . . . . Dry mouth . . . . . . . . . . . . . . . . . . . DSRCT. See Desmoplastic small round cell tumor Duct ectasia . . . . . . . . . . . . . . . . . . Ductal carcinoma in situ (DCIS). . . . . . . . Ductal lavage. . . . . . . . . . . . . . . . . . Ductogram . . . . . . . . . . . . . . . . . . . Duke Comprehensive Cancer Center . . . . . Dukes’ classification . . . . . . . . . . . . . . Duodenal carcinomas . . . . . . . . . . . . . Dye, hair. See Hair dye Dysplastic nevus syndrome . . . . . . . . . .
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Edema . . . . . . . . . . . . . . . . . . . . . . . Education, cancer. See Cancer education Elderly and cancer . . . . . . . . . . . . . . . . . Electrolarynx . . . . . . . . . . . . . . . . . . . . Electromagnetic radiation . . . . . . . . . . . . . Electroporation therapy . . . . . . . . . . . . . . Electrosurgery . . . . . . . . . . . . . . . . . . . Embolization . . . . . . . . . . . . . . . . . . . . Embryonal cell cancer . . . . . . . . . . . . . . . End-of-life care . . . . . . . . . . . . . . . . . . Endocrine cancers . . . . . . . . . . . . . . . . . Endocrinology oncology . . . . . . . . . . . . . . Endometrial cancer . . . . . . . . . . . . . . . . Endometrial hyperplasia . . . . . . . . . . . . . . Endorectal ultrasound . . . . . . . . . . . . . . . Endoscopic retrograde cholangiopancreatography (ERCP) . . . . . . . . . . . . . . . . . . . . . Endoscopy . . . . . . . . . . . . . . . . . . . . . Endoscopy, upper gastrointestinal. See Upper gastrointestinal endoscopy Endotheliomas . . . . . . . . . . . . . . . . . . . Enteritis . . . . . . . . . . . . . . . . . . . . . . Enterostomal therapy . . . . . . . . . . . . . . . Eosinophilic leukemia . . . . . . . . . . . . . . . Ependymomas . . . . . . . . . . . . . . . . . . . Epidemiology of cancer . . . . . . . . . . . . . . Epidermoid cancers of mucous membranes . . . . Epstein-Barr virus . . . . . . . . . . . . . . . . . ERCP. See Endoscopic retrograde cholangiopancreatography ERD. See Estrogen receptor downregulator Erionite. . . . . . . . . . . . . . . . . . . . . . . Erythroplakia. . . . . . . . . . . . . . . . . . . . Esophageal cancer . . . . . . . . . . . . . . . . . Esophageal speech . . . . . . . . . . . . . . . . . Esophagectomy . . . . . . . . . . . . . . . . . . Esophagitis . . . . . . . . . . . . . . . . . . . . . Essiac . . . . . . . . . . . . . . . . . . . . . . . Estrogen receptor downregulator (ERD) . . . . . Estrogen-receptor-sensitive breast cancer . . . . . Ethnicity and cancer . . . . . . . . . . . . . . . . Ethylene oxide . . . . . . . . . . . . . . . . . . . Ewing sarcoma . . . . . . . . . . . . . . . . . . . Exenteration . . . . . . . . . . . . . . . . . . . . Exercise and cancer . . . . . . . . . . . . . . . . External beam radiation therapy (EBRT) . . . . . Eye cancers . . . . . . . . . . . . . . . . . . . . Eyelid cancer. . . . . . . . . . . . . . . . . . . .
357 357 360 362
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370 373 373 374 375 376
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386 387 389 389 390 392 393
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Eaton-Lambert syndrome. See Lambert-Eaton myasthenic syndrome EBRT. See External beam radiation therapy xxxiii
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396 399 399 400 401 402 403 404 406 409 412 414 416
. 417 . 417
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420 421 422 424 425 426 429 431
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433 433 434 436 438 439 441 441 442 444 447 447 450 451 454 455 458
Salem Health: Cancer Fallopian tube cancer . . . . . . . . . . . . Family history and risk assessment . . . . . Fanconi anemia . . . . . . . . . . . . . . . Fatigue . . . . . . . . . . . . . . . . . . . . Fecal occult blood test (FOBT) . . . . . . . Fertility drugs and cancer . . . . . . . . . . Fertility issues . . . . . . . . . . . . . . . . Fever . . . . . . . . . . . . . . . . . . . . . Fiber . . . . . . . . . . . . . . . . . . . . . Fibroadenomas . . . . . . . . . . . . . . . . Fibrocystic breast changes . . . . . . . . . . Fibrosarcomas, soft-tissue . . . . . . . . . . Financial issues . . . . . . . . . . . . . . . 5HIAA test. See 5-Hydroxyindoleacetic acid test 5Q minus syndrome . . . . . . . . . . . . . Flow cytometry . . . . . . . . . . . . . . . FOBT. See Fecal occult blood test Folic acid. . . . . . . . . . . . . . . . . . . Formaldehyde . . . . . . . . . . . . . . . . Fox Chase Cancer Center . . . . . . . . . . Fred Hutchinson Cancer Research Center . . Free radicals . . . . . . . . . . . . . . . . . Fruits . . . . . . . . . . . . . . . . . . . . .
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486 486 487 488 490 491
Gallbladder cancer . . . . . . . . . . . . . . Gallium scan . . . . . . . . . . . . . . . . . Gamma Knife . . . . . . . . . . . . . . . . Gardner syndrome . . . . . . . . . . . . . . Garlic and allicin . . . . . . . . . . . . . . . Gastric polyps . . . . . . . . . . . . . . . . Gastrinomas . . . . . . . . . . . . . . . . . Gastrointestinal cancers . . . . . . . . . . . Gastrointestinal complications of cancer treatment. . . . . . . . . . . . . . . . . . Gastrointestinal oncology . . . . . . . . . . Gastrointestinal stromal tumors (GISTs) . . GCTs. See Giant cell tumors Gene therapy . . . . . . . . . . . . . . . . . Genetic counseling . . . . . . . . . . . . . . Genetic testing . . . . . . . . . . . . . . . . Genetics of cancer . . . . . . . . . . . . . . Geography and cancer . . . . . . . . . . . . Germ-cell tumors . . . . . . . . . . . . . . Gerson therapy . . . . . . . . . . . . . . . . Gestational trophoblastic tumors (GTTs) . . Giant cell tumors (GCTs) . . . . . . . . . . Ginseng, panax. . . . . . . . . . . . . . . . GISTs. See Gastrointestinal stromal tumors Gleason grading system . . . . . . . . . . . Gliomas . . . . . . . . . . . . . . . . . . .
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493 495 497 498 499 500 501 502
Glomus tumors . . . . . . . . . . . . . . . . Glossectomy . . . . . . . . . . . . . . . . . Glutamine . . . . . . . . . . . . . . . . . . Gonioscopy . . . . . . . . . . . . . . . . . Grading of tumors . . . . . . . . . . . . . . Graft-versus-host disease (GVHD) . . . . . Granulosa cell tumors . . . . . . . . . . . . Green tea . . . . . . . . . . . . . . . . . . . Grief and bereavement . . . . . . . . . . . . GTTs. See Gestational trophoblastic tumors GVHD. See Graft-versus-host disease Gynecologic cancers . . . . . . . . . . . . . Gynecologic oncology . . . . . . . . . . . .
460 461 464 466 467 469 471 472 474 475 476 478 481
H. pylori. See Helicobacter pylori HAI. See Hepatic arterial infusion Hair dye . . . . . . . . . . . . . . . . . . Hairy cell leukemia . . . . . . . . . . . . Hand-foot syndrome (HFS) . . . . . . . . HBV. See Hepatitis B virus HCG. See Human chorionic gonadotropin HCV. See Hepatitis C virus Head and neck cancers . . . . . . . . . . . Health maintenance organizations (HMOs) Helicobacter pylori. . . . . . . . . . . . . Hemangioblastomas . . . . . . . . . . . . Hemangiopericytomas . . . . . . . . . . . Hemangiosarcomas . . . . . . . . . . . . Hematemesis . . . . . . . . . . . . . . . . Hematologic oncology . . . . . . . . . . . Hematuria . . . . . . . . . . . . . . . . . Hemochromatosis . . . . . . . . . . . . . Hemolytic anemia . . . . . . . . . . . . . Hemoptysis. . . . . . . . . . . . . . . . . Hemorrhoids . . . . . . . . . . . . . . . . Hepatic arterial infusion (HAI) . . . . . . Hepatitis B virus (HBV) . . . . . . . . . . Hepatitis C virus (HCV) . . . . . . . . . . Hepatomegaly . . . . . . . . . . . . . . . HER2/neu protein . . . . . . . . . . . . . Herbs as antioxidants . . . . . . . . . . . Hereditary cancer syndromes . . . . . . . Hereditary diffuse gastric cancer . . . . . Hereditary leiomyomatosis and renal cell cancer (HLRCC) . . . . . . . . . . . . Hereditary mixed polyposis syndrome . . Hereditary non-VHL clear cell renal cell carcinomas . . . . . . . . . . . . . . . Hereditary pancreatitis . . . . . . . . . . . Hereditary papillary renal cell carcinomas Hereditary polyposis syndromes . . . . . .
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512 515 517 519 522 525 527 527 530 531
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534 535 536 536 537 538 540 540 541
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554 557 558 559 559 560 561 562 564 565 566 566 567 568 569 570 571 573 573 574 576
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580 580 581 582
Contents Herpes simplex virus. . . . . . . . . . . . . . . . Herpes zoster virus. . . . . . . . . . . . . . . . . HFS. See Hand-foot syndrome Hispanics and cancer. See Latinos/Hispanics and cancer Histamine 2 antagonists . . . . . . . . . . . . . . Histiocytosis X . . . . . . . . . . . . . . . . . . . HIV/AIDS-related cancers . . . . . . . . . . . . . HLRCC. See Hereditary leiomyomatosis and renal cell cancer HMOs. See Health maintenance organizations Hodgkin disease . . . . . . . . . . . . . . . . . . Home health services . . . . . . . . . . . . . . . Hormonal therapies . . . . . . . . . . . . . . . . Hormone receptor tests . . . . . . . . . . . . . . Hormone replacement therapy (HRT) . . . . . . . Horner syndrome. . . . . . . . . . . . . . . . . . Hospice care . . . . . . . . . . . . . . . . . . . . Hot flashes . . . . . . . . . . . . . . . . . . . . . HPV. See Human papillomavirus HRAS gene testing . . . . . . . . . . . . . . . . . HRT. See Hormone replacement therapy HTLV. See Human T-cell leukemia virus Human chorionic gonadotropin (HCG) . . . . . . Human growth factors and tumor growth . . . . . Human immunodeficiency virus-related cancers. See HIV/AIDS-related cancers Human papillomavirus (HPV) . . . . . . . . . . . Human T-cell leukemia virus (HTLV) . . . . . . Hydatidiform mole . . . . . . . . . . . . . . . . . 5-Hydroxyindoleacetic acid (5HIAA) test . . . . . Hypercalcemia . . . . . . . . . . . . . . . . . . . Hypercoagulation disorders . . . . . . . . . . . . Hyperthermia therapy . . . . . . . . . . . . . . . Hyperthermic perfusion . . . . . . . . . . . . . . Hypopharyngeal cancer . . . . . . . . . . . . . . Hysterectomy . . . . . . . . . . . . . . . . . . . Hysterography . . . . . . . . . . . . . . . . . . . Hystero-oophorectomy. . . . . . . . . . . . . . . Hysteroscopy. . . . . . . . . . . . . . . . . . . . IEP. See Immunoelectrophoresis iFOBT. See Immunochemical fecal occult blood test Ileostomy. . . . . . . . . . . . . . . . . . . . . Imaging tests . . . . . . . . . . . . . . . . . . . Immune response to cancer . . . . . . . . . . . Immunochemical fecal occult blood test (iFOBT) . . . . . . . . . . . . . . . . . . . . Immunocytochemistry and immunohistochemistry . . . . . . . . . . . .
Immunoelectrophoresis (IEP) . . . . . . Immunotherapy . . . . . . . . . . . . . IMRT. See Intensity-modulated radiation therapy Indoles . . . . . . . . . . . . . . . . . . Infection and sepsis . . . . . . . . . . . Infectious cancers . . . . . . . . . . . . Infertility and cancer . . . . . . . . . . . Inflammatory bowel disease . . . . . . . Informed consent. . . . . . . . . . . . . Infusion therapies . . . . . . . . . . . . Insurance . . . . . . . . . . . . . . . . . Integrative oncology . . . . . . . . . . . Intensity-modulated radiation therapy (IMRT) . . . . . . . . . . . . . . . . Interferon. . . . . . . . . . . . . . . . . Interleukins. . . . . . . . . . . . . . . . Invasive cancer. . . . . . . . . . . . . . Invasive ductal carcinomas . . . . . . . Invasive lobular carcinomas . . . . . . . Ionizing radiation . . . . . . . . . . . . Iridium seeds . . . . . . . . . . . . . . . Islet cell tumors . . . . . . . . . . . . . Isoflavones . . . . . . . . . . . . . . . . Itching . . . . . . . . . . . . . . . . . .
. 584 . 586
. 587 . 588 . 590
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593 597 599 601 603 605 606 608
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. 609 . 610
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638 638 641 643 645 646 647 648 651
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652 653 654 655 656 657 657 658 659 661 661
Jonsson Comprehensive Cancer Center (JCCC) . . . . . . . . . . . . . . . . . . . . . . 664 Journaling . . . . . . . . . . . . . . . . . . . . . . 665 Juvenile polyposis syndrome . . . . . . . . . . . . 665
611 612 612 613 614 615 617 618 619 620 621 622 623
Kaposi sarcoma . . . . . . . . . . . . . Karnofsky performance status (KPS) . . Keratosis . . . . . . . . . . . . . . . . . Ki67 test . . . . . . . . . . . . . . . . . Kidney cancer . . . . . . . . . . . . . . Klinefelter syndrome and cancer . . . . KPS. See Karnofsky performance status Krukenberg tumors . . . . . . . . . . . Lacrimal gland tumors . . . . . . . . . Lactate dehydrogenase (LDH) test . . Laetrile . . . . . . . . . . . . . . . . . Lambert-Eaton myasthenic syndrome (LEMS) . . . . . . . . . . . . . . . Laparoscopy and laparoscopic surgery Laryngeal cancer . . . . . . . . . . . . Laryngeal nerve palsy . . . . . . . . . Laryngectomy . . . . . . . . . . . . . Laryngoscopy . . . . . . . . . . . . . Laser therapies . . . . . . . . . . . . .
. . 625 . . 626 . . 629 . . 632 . . 633 xxxv
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667 669 670 670 671 674
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679 681 682 685 686 687 688
Salem Health: Cancer Latinos/Hispanics and cancer . . . . . . . . . . . Laxatives . . . . . . . . . . . . . . . . . . . . . . LCIS. See Lobular carcinoma in situ LDH test. See Lactate dehydrogenase test Leiomyomas . . . . . . . . . . . . . . . . . . . . Leiomyosarcomas . . . . . . . . . . . . . . . . . LEMS. See Lambert-Eaton myasthenic syndrome Leptomeningeal carcinomas . . . . . . . . . . . . Leukapharesis . . . . . . . . . . . . . . . . . . . Leukemia, Down syndrome and. See Down syndrome and leukemia Leukemia, eosinophilic. See Eosinophilic leukemia
. 690 . 692
Leukemia, hairy cell. See Hairy cell leukemia Leukemias . . . . . . . . . . . . . . . . . . . Leukoencephalopathy . . . . . . . . . . . . . Leukopenia. . . . . . . . . . . . . . . . . . . Leukoplakia . . . . . . . . . . . . . . . . . . Leydig cell tumors . . . . . . . . . . . . . . . Li-Fraumeni syndrome (LFS) . . . . . . . . . Limb salvage . . . . . . . . . . . . . . . . . . Linear accelerator . . . . . . . . . . . . . . . Lip cancers . . . . . . . . . . . . . . . . . . . Liposarcomas . . . . . . . . . . . . . . . . . Liver biopsy . . . . . . . . . . . . . . . . . . Liver cancers . . . . . . . . . . . . . . . . . .
. 693 . 694 . 696 . 698
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698 702 704 704 706 706 708 709 710 712 714 715
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Complete List of Contents Volume 1
Contents . . . . . . . . . . . . . . . . . . . . . . . . v Publisher’s Note . . . . . . . . . . . . . . . . . . . . ix About the Editors . . . . . . . . . . . . . . . . . . . xi Contributors . . . . . . . . . . . . . . . . . . . . . xiii Complete List of Contents . . . . . . . . . . . . . . xv AACR. See American Association for Cancer Research ABCD. . . . . . . . . . . . . . . . . . . . . . . . . . 1 ACC. See Adenoid cystic carcinoma Abdominoperineal resection (APR) . . . . . . . . . . 1 Accelerated partial breast irradiation (APBI). . . . . . 3 Achlorhydria . . . . . . . . . . . . . . . . . . . . . . 4 Acoustic neuromas . . . . . . . . . . . . . . . . . . . 4 Acquired immunodeficiency disease-related cancers. See HIV/AIDS-related cancers Acrylamides . . . . . . . . . . . . . . . . . . . . . . 6 ACS. See American Cancer Society Acupuncture and acupressure for cancer patients . . . 8 Acute lymphocytic leukemia (ALL) . . . . . . . . . 11 Acute myelocytic leukemia (AML) . . . . . . . . . . 13 Adenocarcinomas . . . . . . . . . . . . . . . . . . . 16 Adenoid cystic carcinoma (ACC) . . . . . . . . . . . 17 Adenomatoid tumors . . . . . . . . . . . . . . . . . 18 Adenomatous polyps . . . . . . . . . . . . . . . . . 18 Adenoviruses . . . . . . . . . . . . . . . . . . . . . 19 Adjuvant therapy . . . . . . . . . . . . . . . . . . . 20 Adrenal gland cancers . . . . . . . . . . . . . . . . . 21 Adrenocortical cancer . . . . . . . . . . . . . . . . . 23 Advance directives . . . . . . . . . . . . . . . . . . 24 Aflatoxins . . . . . . . . . . . . . . . . . . . . . . . 26 AFP levels. See Alpha-fetoprotein levels African Americans and cancer . . . . . . . . . . . . 28 Africans and cancer . . . . . . . . . . . . . . . . . . 31 Afterloading radiation therapy . . . . . . . . . . . . 32 Agent Orange . . . . . . . . . . . . . . . . . . . . . 34 Aging and cancer . . . . . . . . . . . . . . . . . . . 34 AICR. See American Institute for Cancer Research Aids and devices for cancer patients . . . . . . . . . 38 AIDS-related cancers. See HIV/AIDS-related cancers Air pollution . . . . . . . . . . . . . . . . . . . . . . 39 Alcohol, alcoholism, and cancer . . . . . . . . . . . 42 Aleukemia . . . . . . . . . . . . . . . . . . . . . . . 43 Alkaline phosphatase test (ALP) . . . . . . . . . . . 44
Alkylating agents in chemotherapy . . . . . . . ALL. See Acute lymphocytic leukemia Allicin, garlic and. See Garlic and allicin Alopecia . . . . . . . . . . . . . . . . . . . . . ALP. See Alkaline phosphatase test Alpha-fetoprotein (AFP) levels . . . . . . . . . Alternative therapies. See Complementary and alternative therapies Alveolar soft-part sarcomas . . . . . . . . . . . Amenorrhea . . . . . . . . . . . . . . . . . . . American Association for Cancer Research (AACR) . . . . . . . . . . . . . . . . . . . . American Cancer Society (ACS) . . . . . . . . American Institute for Cancer Research (AICR) 4-Aminobiphenyl . . . . . . . . . . . . . . . . AML. See Acute myelocytic leukemia Amputation . . . . . . . . . . . . . . . . . . . Amyloidosis . . . . . . . . . . . . . . . . . . . Anal cancer . . . . . . . . . . . . . . . . . . . Androgen drugs . . . . . . . . . . . . . . . . . Anemia . . . . . . . . . . . . . . . . . . . . . Anemia, aplastic. See Aplastic anemia Anemia, hemolytic. See Hemolytic anemia Angiogenesis . . . . . . . . . . . . . . . . . . Angiogenesis inhibitors . . . . . . . . . . . . . Angiography. . . . . . . . . . . . . . . . . . . Angiosarcomas . . . . . . . . . . . . . . . . . Anoscopy . . . . . . . . . . . . . . . . . . . . Anthraquinones . . . . . . . . . . . . . . . . . Anthrax . . . . . . . . . . . . . . . . . . . . . Antiandrogens . . . . . . . . . . . . . . . . . . Antidiarrheal agents . . . . . . . . . . . . . . . Antiestrogens . . . . . . . . . . . . . . . . . . Antifungal therapies . . . . . . . . . . . . . . . Antimetabolites in chemotherapy . . . . . . . . Antinausea medications . . . . . . . . . . . . . Antineoplastics in chemotherapy . . . . . . . . Antioxidants . . . . . . . . . . . . . . . . . . . Antiperspirants and breast cancer . . . . . . . . Antiviral therapies. . . . . . . . . . . . . . . . Anxiety . . . . . . . . . . . . . . . . . . . . . APBI. See Accelerated partial breast irradiation APC gene testing . . . . . . . . . . . . . . . . Aplastic anemia . . . . . . . . . . . . . . . . . Appendix cancer . . . . . . . . . . . . . . . . Appetite loss. . . . . . . . . . . . . . . . . . .
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64 66 68 69 70 71 71 72 73 75 76 78 81 83 86 88 90 93
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Salem Health: Cancer APR. See Abdominoperineal resection Arsenic compounds . . . . . . . . . . Arterial embolization . . . . . . . . . Artificial sweeteners . . . . . . . . . . Asbestos . . . . . . . . . . . . . . . . Ascites . . . . . . . . . . . . . . . . . Ashkenazi Jews and cancer . . . . . . Asian Americans and cancer. . . . . . Astrocytomas. . . . . . . . . . . . . . Ataxia telangiectasia (AT) . . . . . . . Autologous blood transfusion . . . . . Axillary dissection . . . . . . . . . . . Azathioprine . . . . . . . . . . . . . .
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Bacillus Calmette Guérin (BCG) . . . . . . . . Bacteria as causes of cancer . . . . . . . . . . . Barium enema . . . . . . . . . . . . . . . . . . Barium swallow . . . . . . . . . . . . . . . . . Barrett esophagus . . . . . . . . . . . . . . . . Basal cell carcinomas . . . . . . . . . . . . . . BCG. See Bacillus Calmette Guérin Beckwith-Wiedemann syndrome (BWS) . . . . Benign prostatic hyperplasia (BPH) . . . . . . . Benign tumors . . . . . . . . . . . . . . . . . . Benzene . . . . . . . . . . . . . . . . . . . . . Benzidine and dyes metabolized to benzidine . . Benzodiazepines . . . . . . . . . . . . . . . . . Bereavement, grief and. See Grief and bereavement Beryllium and beryllium compounds . . . . . . Beta-carotene . . . . . . . . . . . . . . . . . . Bethesda criteria . . . . . . . . . . . . . . . . . BHDS. See Birt-Hogg-Dubé syndrome Bile duct cancer . . . . . . . . . . . . . . . . . Bilobectomy . . . . . . . . . . . . . . . . . . . Bioflavonoids . . . . . . . . . . . . . . . . . . Biological therapy . . . . . . . . . . . . . . . . Biopsy. See also Computed tomography-guided biopsy; Core needle biopsy; Liver biopsy; Needle biopsies; Pleural biopsy; Stereotactic needle biopsy; Surgical biopsies . . . . . . . Birt-Hogg-Dubé syndrome (BHDS) . . . . . . . Birth control pills and cancer . . . . . . . . . . Bis(chloromethyl) ether and technical-grade chloromethyl methyl ether . . . . . . . . . . Bisphenol A (BPA) . . . . . . . . . . . . . . . Bisphosphonates . . . . . . . . . . . . . . . . . Bladder cancer . . . . . . . . . . . . . . . . . . Blood cancers . . . . . . . . . . . . . . . . . . BMT. See Bone marrow transplantation BNCT. See Boron neutron capture therapy
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148 149 151 151 154
Body image. See Self-image and body image Bone cancers . . . . . . . . . . . . . . . . . . . Bone marrow aspiration and biopsy . . . . . . . Bone marrow transplantation (BMT) . . . . . . Bone pain . . . . . . . . . . . . . . . . . . . . Bone scan . . . . . . . . . . . . . . . . . . . . Boron neutron capture therapy (BNCT) . . . . . Bowen disease . . . . . . . . . . . . . . . . . . BPA. See Bisphenol A BPH. See Benign prostatic hyperplasia BPI. See Brief Pain Inventory Brachytherapy . . . . . . . . . . . . . . . . . . BRAF gene . . . . . . . . . . . . . . . . . . . . Brain and central nervous system cancers . . . . Brain scan . . . . . . . . . . . . . . . . . . . . BRCA1 and BRCA2 genes . . . . . . . . . . . . Breakthrough pain . . . . . . . . . . . . . . . . Breast, calcifications of. See Calcifications of the breast Breast, medullary carcinoma of. See Medullary carcinoma of the breast Breast cancer, cutaneous. See Cutaneous breast cancer Breast cancer, estrogen-receptor-sensitive. See Estrogen-receptor-sensitive breast cancer Breast cancer in children and adolescents . . . . Breast cancer in men . . . . . . . . . . . . . . . Breast cancer in pregnant women . . . . . . . . Breast cancers . . . . . . . . . . . . . . . . . . Breast implants. . . . . . . . . . . . . . . . . . Breast reconstruction. . . . . . . . . . . . . . . Breast self-examination (BSE). . . . . . . . . . Breast ultrasound. . . . . . . . . . . . . . . . . Breslow’s staging . . . . . . . . . . . . . . . . Brief Pain Inventory (BPI) . . . . . . . . . . . . Brompton cocktail . . . . . . . . . . . . . . . . Bronchial adenomas . . . . . . . . . . . . . . . Bronchoalveolar lung cancer . . . . . . . . . . Bronchography. . . . . . . . . . . . . . . . . . Bronchoscopy . . . . . . . . . . . . . . . . . . BSE. See Breast self-examination Burkitt lymphoma . . . . . . . . . . . . . . . . 1,3-Butadiene . . . . . . . . . . . . . . . . . . 1,4-Butanediol dimethanesulfonate . . . . . . . BWS. See Beckwith-Wiedemann syndrome CA 15-3 test . CA 19-9 test . CA 27-29 test CA 125 test. . Cachexia . . .
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158 161 163 165 166 167 168
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180 182 184 185 188 190 193 194 195 196 196 197 197 199 199
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205 205 206 206 207
Complete List of Contents Cadmium and cadmium compounds. . . . . . . . Caffeine . . . . . . . . . . . . . . . . . . . . . . Calcifications of the breast. . . . . . . . . . . . . Calcium . . . . . . . . . . . . . . . . . . . . . . Cancell . . . . . . . . . . . . . . . . . . . . . . . Cancer biology . . . . . . . . . . . . . . . . . . . Cancer care team . . . . . . . . . . . . . . . . . . Cancer clusters . . . . . . . . . . . . . . . . . . . Cancer education. . . . . . . . . . . . . . . . . . Candidiasis . . . . . . . . . . . . . . . . . . . . . Carcinoembryonic antigen antibody (CEA) test . . . . . . . . . . . . . . . . . . . . . . . . Carcinogens, known . . . . . . . . . . . . . . . . Carcinogens, reasonably anticipated. . . . . . . . Carcinoid tumors and carcinoid syndrome . . . . Carcinoma of unknown primary origin (CUP) . . Carcinomas. . . . . . . . . . . . . . . . . . . . . Carcinomas, invasive ductal. See Invasive ductal carcinomas Carcinomas, invasive lobular. See Invasive lobular carcinomas Carcinomas, leptomeningeal. See Leptomeningeal carcinomas Carcinomatosis. . . . . . . . . . . . . . . . . . . Carcinomatous meningitis . . . . . . . . . . . . . Carcinosarcomas . . . . . . . . . . . . . . . . . . Cardiomyopathy in cancer patients . . . . . . . . Cardiopulmonary resuscitation (CPR) . . . . . . . Caregivers and caregiving . . . . . . . . . . . . . Caregiving, long-distance. See Long-distance caregiving Carney complex . . . . . . . . . . . . . . . . . . Carotenoids . . . . . . . . . . . . . . . . . . . . Cartilage supplements . . . . . . . . . . . . . . . Case management . . . . . . . . . . . . . . . . . Castleman disease . . . . . . . . . . . . . . . . . CBC. See Complete blood count CBE. See Clinical breast exam CDKN2A. See Cyclin-dependent kinase inhibitor-2A CEA test. See Carcinoembryonic antigen antibody test Cell phones. . . . . . . . . . . . . . . . . . . . . Cervical cancer. . . . . . . . . . . . . . . . . . . Chemoembolization . . . . . . . . . . . . . . . . Chemoprevention . . . . . . . . . . . . . . . . . Chemotherapy . . . . . . . . . . . . . . . . . . . Chemotherapy, cognitive effects of. See Cognitive effects of cancer and chemotherapy Chewing tobacco. . . . . . . . . . . . . . . . . . Childbirth and cancer . . . . . . . . . . . . . . .
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Childhood cancers . . . . . . . . . . . . . . . . Chlorambucil. . . . . . . . . . . . . . . . . . . 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)1-nitrosourea (MeCCNU) . . . . . . . . . . . Cholecystectomy . . . . . . . . . . . . . . . . . Chordomas . . . . . . . . . . . . . . . . . . . . Choriocarcinomas . . . . . . . . . . . . . . . . CHPP. See Continuous hyperthermic peritoneal perfusion Chromium hexavalent compounds. . . . . . . . Chromosomes and cancer . . . . . . . . . . . . Chronic lymphocytic leukemia (CLL) . . . . . . Chronic myeloid leukemia (CML). . . . . . . . Cigarettes and cigars . . . . . . . . . . . . . . . Clinical breast exam (CBE) . . . . . . . . . . . Clinical trials . . . . . . . . . . . . . . . . . . . CLL. See Chronic lymphocytic leukemia CML. See Chronic myeloid leukemia Coal tars and coal tar pitches . . . . . . . . . . Cobalt 60 radiation. . . . . . . . . . . . . . . . Coenzyme Q10. . . . . . . . . . . . . . . . . . Cognitive effects of cancer and chemotherapy . Coke oven emissions. . . . . . . . . . . . . . . Cold nodule . . . . . . . . . . . . . . . . . . . Colectomy . . . . . . . . . . . . . . . . . . . . Coloanal anastomosis . . . . . . . . . . . . . . Colon polyps . . . . . . . . . . . . . . . . . . . Colonoscopy and virtual colonoscopy . . . . . . Colony-stimulating factors (CSFs) . . . . . . . Colorectal cancer. . . . . . . . . . . . . . . . . Colorectal cancer screening . . . . . . . . . . . Colostomy . . . . . . . . . . . . . . . . . . . . Colposcopy. . . . . . . . . . . . . . . . . . . . Comedo carcinomas . . . . . . . . . . . . . . . Complementary and alternative therapies . . . . Complete blood count (CBC) . . . . . . . . . . Computed tomography (CT)-guided biopsy . . . . . . . . . . . . . . . . . . . . . Computed tomography (CT) scan . . . . . . . . Conization . . . . . . . . . . . . . . . . . . . . Continuous hyperthermic peritoneal perfusion (CHPP) . . . . . . . . . . . . . . . . . . . . Cordectomy . . . . . . . . . . . . . . . . . . . Cordotomy . . . . . . . . . . . . . . . . . . . . Core needle biopsy. . . . . . . . . . . . . . . . Corticosteroids . . . . . . . . . . . . . . . . . . Coughing . . . . . . . . . . . . . . . . . . . . . Counseling for cancer patients and survivors . . Cowden syndrome . . . . . . . . . . . . . . . . COX-2 inhibitors. See Cyclooxygenase 2 inhibitors
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288 289 289 290 292 292 293 294 296 297 299 300 304 306 308 309 309 312
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318 318 319 321 321 322 324 326
Salem Health: Cancer CPR. See Cardiopulmonary resuscitation Craniopharyngiomas . . . . . . . . . . . . Craniosynostosis . . . . . . . . . . . . . . Craniotomy. . . . . . . . . . . . . . . . . Crohn disease . . . . . . . . . . . . . . . Cruciferous vegetables . . . . . . . . . . . Cryoablation . . . . . . . . . . . . . . . . Cryptorchidism. . . . . . . . . . . . . . . CSFs. See Colony-stimulating factors CT scan. See Computed tomography scan CTCL. See Cutaneous T-cell lymphoma Culdoscopy. . . . . . . . . . . . . . . . . CUP. See Carcinoma of unknown primary origin Curcumin. . . . . . . . . . . . . . . . . . Cushing syndrome and cancer . . . . . . . Cutaneous breast cancer . . . . . . . . . . Cutaneous T-cell lymphoma (CTCL) . . .
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Cyclin-dependent kinase inhibitor-2A (CDKN2A). . . . . . . . . . . . . . . Cyclooxygenase 2 (COX-2) inhibitors . Cyclophosphamide. . . . . . . . . . . . Cyclosporin A . . . . . . . . . . . . . . Cystography . . . . . . . . . . . . . . . Cystoscopy . . . . . . . . . . . . . . . . Cytogenetics . . . . . . . . . . . . . . . Cytokines . . . . . . . . . . . . . . . . Cytology . . . . . . . . . . . . . . . . . Cytology, sputum. See Sputum cytology
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344 344 345 346 347 347 348 350 350
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D&C. See Dilation and curettage Dana-Farber Cancer Institute . . . . . . . . . . . . 354 DCIS. See Ductal carcinoma in situ DEA. See Diethanolamine DEHP. See Di(2-ethylhexyl) phthalate Delta-9-tetrahydrocannabinol . . . . . . . . . . . . 355
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Volume 2 Down syndrome and leukemia. . . . . . . . DPC4 gene testing . . . . . . . . . . . . . . DRE. See Digital rectal exam Drug resistance and multidrug resistance (MDR) . . . . . . . . . . . . . . . . . . . Dry mouth . . . . . . . . . . . . . . . . . . DSRCT. See Desmoplastic small round cell tumor Duct ectasia . . . . . . . . . . . . . . . . . Ductal carcinoma in situ (DCIS). . . . . . . Ductal lavage. . . . . . . . . . . . . . . . . Ductogram . . . . . . . . . . . . . . . . . . Duke Comprehensive Cancer Center . . . . Dukes’ classification . . . . . . . . . . . . . Duodenal carcinomas . . . . . . . . . . . . Dye, hair. See Hair dye Dysplastic nevus syndrome . . . . . . . . .
Contents . . . . . . . . . . . . . . . . . . . . . . xxxiii Complete List of Contents . . . . . . . . . . . . xxxvii Denys-Drash syndrome and cancer . . . . . . Depression . . . . . . . . . . . . . . . . . . . Dermatofibrosarcoma protuberans (DFSP) . . Dermatology oncology. . . . . . . . . . . . . DES. See Diethylstilbestrol Desmoid tumors . . . . . . . . . . . . . . . . Desmoplastic small round cell tumor (DSRCT) . . . . . . . . . . . . . . . . . . Developing nations and cancer . . . . . . . . DFSP. See Dermatofibrosarcoma protuberans Di(2-ethylhexyl) phthalate (DEHP) . . . . . . Diarrhea . . . . . . . . . . . . . . . . . . . . DIC. See Disseminated intravascular coagulation Dietary supplements . . . . . . . . . . . . . . Diethanolamine (DEA) . . . . . . . . . . . . Diethylstilbestrol (DES) . . . . . . . . . . . . Digital rectal exam (DRE) . . . . . . . . . . . Dilation and curettage (D&C) . . . . . . . . . Dioxins . . . . . . . . . . . . . . . . . . . . . Disseminated intravascular coagulation (DIC) . . . . . . . . . . . . . . . . . . . . Diverticulosis and diverticulitis . . . . . . . . DNR. See Do-not-resuscitate order Do-not-resuscitate (DNR) order . . . . . . . .
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Eaton-Lambert syndrome. See Lambert-Eaton myasthenic syndrome EBRT. See External beam radiation therapy Edema . . . . . . . . . . . . . . . . . . . . . Education, cancer. See Cancer education Elderly and cancer . . . . . . . . . . . . . . . Electrolarynx . . . . . . . . . . . . . . . . . . Electromagnetic radiation . . . . . . . . . . . Electroporation therapy . . . . . . . . . . . . Electrosurgery . . . . . . . . . . . . . . . . .
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396 399 399 400 401
Complete List of Contents Embolization . . . . . . . . . . . . . . . . . . . . Embryonal cell cancer . . . . . . . . . . . . . . . End-of-life care . . . . . . . . . . . . . . . . . . Endocrine cancers . . . . . . . . . . . . . . . . . Endocrinology oncology . . . . . . . . . . . . . . Endometrial cancer . . . . . . . . . . . . . . . . Endometrial hyperplasia . . . . . . . . . . . . . . Endorectal ultrasound . . . . . . . . . . . . . . . Endoscopic retrograde cholangiopancreatography (ERCP) . . . . . . . . . . . . . . . . . . . . . Endoscopy . . . . . . . . . . . . . . . . . . . . . Endoscopy, upper gastrointestinal. See Upper gastrointestinal endoscopy Endotheliomas . . . . . . . . . . . . . . . . . . . Enteritis . . . . . . . . . . . . . . . . . . . . . . Enterostomal therapy . . . . . . . . . . . . . . . Eosinophilic leukemia . . . . . . . . . . . . . . . Ependymomas . . . . . . . . . . . . . . . . . . . Epidemiology of cancer . . . . . . . . . . . . . . Epidermoid cancers of mucous membranes . . . . Epstein-Barr virus . . . . . . . . . . . . . . . . . ERCP. See Endoscopic retrograde cholangiopancreatography ERD. See Estrogen receptor downregulator Erionite. . . . . . . . . . . . . . . . . . . . . . . Erythroplakia. . . . . . . . . . . . . . . . . . . . Esophageal cancer . . . . . . . . . . . . . . . . . Esophageal speech . . . . . . . . . . . . . . . . . Esophagectomy . . . . . . . . . . . . . . . . . . Esophagitis . . . . . . . . . . . . . . . . . . . . . Essiac . . . . . . . . . . . . . . . . . . . . . . . Estrogen receptor downregulator (ERD) . . . . . Estrogen-receptor-sensitive breast cancer . . . . . Ethnicity and cancer . . . . . . . . . . . . . . . . Ethylene oxide . . . . . . . . . . . . . . . . . . . Ewing sarcoma . . . . . . . . . . . . . . . . . . . Exenteration . . . . . . . . . . . . . . . . . . . . Exercise and cancer . . . . . . . . . . . . . . . . External beam radiation therapy (EBRT) . . . . . Eye cancers . . . . . . . . . . . . . . . . . . . . Eyelid cancer. . . . . . . . . . . . . . . . . . . .
. . . . . . . .
Fallopian tube cancer . . . . . . . Family history and risk assessment Fanconi anemia . . . . . . . . . . Fatigue . . . . . . . . . . . . . . . Fecal occult blood test (FOBT) . . Fertility drugs and cancer . . . . . Fertility issues . . . . . . . . . . . Fever . . . . . . . . . . . . . . . . Fiber . . . . . . . . . . . . . . . .
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402 403 404 406 409 412 414 416
. 417 . 417
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420 421 422 424 425 426 429 431
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433 433 434 436 438 439 441 441 442 444 447 447 450 451 454 455 458
. . . . . . . . .
460 461 464 466 467 469 471 472 474 xli
Fibroadenomas . . . . . . . . . . . . . . . . Fibrocystic breast changes . . . . . . . . . . Fibrosarcomas, soft-tissue . . . . . . . . . . Financial issues . . . . . . . . . . . . . . . 5HIAA test. See 5-Hydroxyindoleacetic acid test 5Q minus syndrome . . . . . . . . . . . . . Flow cytometry . . . . . . . . . . . . . . . FOBT. See Fecal occult blood test Folic acid. . . . . . . . . . . . . . . . . . . Formaldehyde . . . . . . . . . . . . . . . . Fox Chase Cancer Center . . . . . . . . . . Fred Hutchinson Cancer Research Center . . Free radicals . . . . . . . . . . . . . . . . . Fruits . . . . . . . . . . . . . . . . . . . . .
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475 476 478 481
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486 486 487 488 490 491
Gallbladder cancer . . . . . . . . . . . . . . Gallium scan . . . . . . . . . . . . . . . . . Gamma Knife . . . . . . . . . . . . . . . . Gardner syndrome . . . . . . . . . . . . . . Garlic and allicin . . . . . . . . . . . . . . . Gastric polyps . . . . . . . . . . . . . . . . Gastrinomas . . . . . . . . . . . . . . . . . Gastrointestinal cancers . . . . . . . . . . . Gastrointestinal complications of cancer treatment. . . . . . . . . . . . . . . . . . Gastrointestinal oncology . . . . . . . . . . Gastrointestinal stromal tumors (GISTs) . . GCTs. See Giant cell tumors Gene therapy . . . . . . . . . . . . . . . . . Genetic counseling . . . . . . . . . . . . . . Genetic testing . . . . . . . . . . . . . . . . Genetics of cancer . . . . . . . . . . . . . . Geography and cancer . . . . . . . . . . . . Germ-cell tumors . . . . . . . . . . . . . . Gerson therapy . . . . . . . . . . . . . . . . Gestational trophoblastic tumors (GTTs) . . Giant cell tumors (GCTs) . . . . . . . . . . Ginseng, panax. . . . . . . . . . . . . . . . GISTs. See Gastrointestinal stromal tumors Gleason grading system . . . . . . . . . . . Gliomas . . . . . . . . . . . . . . . . . . . Glomus tumors . . . . . . . . . . . . . . . . Glossectomy . . . . . . . . . . . . . . . . . Glutamine . . . . . . . . . . . . . . . . . . Gonioscopy . . . . . . . . . . . . . . . . . Grading of tumors . . . . . . . . . . . . . . Graft-versus-host disease (GVHD) . . . . . Granulosa cell tumors . . . . . . . . . . . . Green tea . . . . . . . . . . . . . . . . . . . Grief and bereavement . . . . . . . . . . . .
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493 495 497 498 499 500 501 502
. . . . 484 . . . . 484
. . . . 506 . . . . 508 . . . . 511 . . . . . . . . . .
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512 515 517 519 522 525 527 527 530 531
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532 533 534 535 536 536 537 538 540 540 541
Salem Health: Cancer GTTs. See Gestational trophoblastic tumors GVHD. See Graft-versus-host disease Gynecologic cancers . . . . . . . . . . . . . . . . . 543 Gynecologic oncology . . . . . . . . . . . . . . . . 547 H. pylori. See Helicobacter pylori HAI. See Hepatic arterial infusion Hair dye . . . . . . . . . . . . . . . . . . . . . . Hairy cell leukemia . . . . . . . . . . . . . . . . Hand-foot syndrome (HFS) . . . . . . . . . . . . HBV. See Hepatitis B virus HCG. See Human chorionic gonadotropin HCV. See Hepatitis C virus Head and neck cancers . . . . . . . . . . . . . . . Health maintenance organizations (HMOs) . . . . Helicobacter pylori. . . . . . . . . . . . . . . . . Hemangioblastomas . . . . . . . . . . . . . . . . Hemangiopericytomas . . . . . . . . . . . . . . . Hemangiosarcomas . . . . . . . . . . . . . . . . Hematemesis . . . . . . . . . . . . . . . . . . . . Hematologic oncology . . . . . . . . . . . . . . . Hematuria . . . . . . . . . . . . . . . . . . . . . Hemochromatosis . . . . . . . . . . . . . . . . . Hemolytic anemia . . . . . . . . . . . . . . . . . Hemoptysis. . . . . . . . . . . . . . . . . . . . . Hemorrhoids . . . . . . . . . . . . . . . . . . . . Hepatic arterial infusion (HAI) . . . . . . . . . . Hepatitis B virus (HBV) . . . . . . . . . . . . . . Hepatitis C virus (HCV) . . . . . . . . . . . . . . Hepatomegaly . . . . . . . . . . . . . . . . . . . HER2/neu protein . . . . . . . . . . . . . . . . . Herbs as antioxidants . . . . . . . . . . . . . . . Hereditary cancer syndromes . . . . . . . . . . . Hereditary diffuse gastric cancer . . . . . . . . . Hereditary leiomyomatosis and renal cell cancer (HLRCC) . . . . . . . . . . . . . . . . Hereditary mixed polyposis syndrome . . . . . . Hereditary non-VHL clear cell renal cell carcinomas . . . . . . . . . . . . . . . . . . . Hereditary pancreatitis . . . . . . . . . . . . . . . Hereditary papillary renal cell carcinomas . . . . Hereditary polyposis syndromes . . . . . . . . . . Herpes simplex virus. . . . . . . . . . . . . . . . Herpes zoster virus. . . . . . . . . . . . . . . . . HFS. See Hand-foot syndrome Hispanics and cancer. See Latinos/Hispanics and cancer Histamine 2 antagonists . . . . . . . . . . . . . . Histiocytosis X . . . . . . . . . . . . . . . . . . . HIV/AIDS-related cancers . . . . . . . . . . . . .
HLRCC. See Hereditary leiomyomatosis and renal cell cancer HMOs. See Health maintenance organizations Hodgkin disease . . . . . . . . . . . . . . . . . Home health services . . . . . . . . . . . . . . Hormonal therapies . . . . . . . . . . . . . . . Hormone receptor tests . . . . . . . . . . . . . Hormone replacement therapy (HRT) . . . . . . Horner syndrome. . . . . . . . . . . . . . . . . Hospice care . . . . . . . . . . . . . . . . . . . Hot flashes . . . . . . . . . . . . . . . . . . . . HPV. See Human papillomavirus HRAS gene testing . . . . . . . . . . . . . . . . HRT. See Hormone replacement therapy HTLV. See Human T-cell leukemia virus Human chorionic gonadotropin (HCG) . . . . . Human growth factors and tumor growth . . . . Human immunodeficiency virus-related cancers. See HIV/AIDS-related cancers Human papillomavirus (HPV) . . . . . . . . . . Human T-cell leukemia virus (HTLV) . . . . . Hydatidiform mole . . . . . . . . . . . . . . . . 5-Hydroxyindoleacetic acid (5HIAA) test . . . . Hypercalcemia . . . . . . . . . . . . . . . . . . Hypercoagulation disorders . . . . . . . . . . . Hyperthermia therapy . . . . . . . . . . . . . . Hyperthermic perfusion . . . . . . . . . . . . . Hypopharyngeal cancer . . . . . . . . . . . . . Hysterectomy . . . . . . . . . . . . . . . . . . Hysterography . . . . . . . . . . . . . . . . . . Hystero-oophorectomy. . . . . . . . . . . . . . Hysteroscopy. . . . . . . . . . . . . . . . . . .
. 550 . 550 . 552
. . . . . . . . . . . . . . . . . . . . .
554 557 558 559 559 560 561 562 564 565 566 566 567 568 569 570 571 573 573 574 576
IEP. See Immunoelectrophoresis iFOBT. See Immunochemical fecal occult blood test Ileostomy. . . . . . . . . . . . . . . . . . . . . Imaging tests . . . . . . . . . . . . . . . . . . . Immune response to cancer . . . . . . . . . . . Immunochemical fecal occult blood test (iFOBT) . . . . . . . . . . . . . . . . . . . . Immunocytochemistry and immunohistochemistry . . . . . . . . . . . . Immunoelectrophoresis (IEP) . . . . . . . . . . Immunotherapy . . . . . . . . . . . . . . . . . IMRT. See Intensity-modulated radiation therapy Indoles . . . . . . . . . . . . . . . . . . . . . . Infection and sepsis . . . . . . . . . . . . . . . Infectious cancers . . . . . . . . . . . . . . . . Infertility and cancer . . . . . . . . . . . . . . .
. 577 . 579 . . . . . .
580 580 581 582 584 586
. 587 . 588 . 590 xlii
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593 597 599 601 603 605 606 608
. . 609
. . 609 . . 610
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611 612 612 613 614 615 617 618 619 620 621 622 623
. . 625 . . 626 . . 629 . . 632 . . 633 . . 634 . . 635
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638 638 641 643
Complete List of Contents Inflammatory bowel disease . . . . . . . . . . Informed consent. . . . . . . . . . . . . . . . Infusion therapies . . . . . . . . . . . . . . . Insurance . . . . . . . . . . . . . . . . . . . . Integrative oncology . . . . . . . . . . . . . . Intensity-modulated radiation therapy (IMRT) Interferon. . . . . . . . . . . . . . . . . . . . Interleukins. . . . . . . . . . . . . . . . . . . Invasive cancer. . . . . . . . . . . . . . . . . Invasive ductal carcinomas . . . . . . . . . . Invasive lobular carcinomas . . . . . . . . . . Ionizing radiation . . . . . . . . . . . . . . . Iridium seeds . . . . . . . . . . . . . . . . . . Islet cell tumors . . . . . . . . . . . . . . . . Isoflavones . . . . . . . . . . . . . . . . . . . Itching . . . . . . . . . . . . . . . . . . . . .
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645 646 647 648 651 652 653 654 655 656 657 657 658 659 661 661
Lambert-Eaton myasthenic syndrome (LEMS) Laparoscopy and laparoscopic surgery . . . . Laryngeal cancer . . . . . . . . . . . . . . . . Laryngeal nerve palsy . . . . . . . . . . . . . Laryngectomy . . . . . . . . . . . . . . . . . Laryngoscopy . . . . . . . . . . . . . . . . . Laser therapies . . . . . . . . . . . . . . . . . Latinos/Hispanics and cancer . . . . . . . . . Laxatives . . . . . . . . . . . . . . . . . . . . LCIS. See Lobular carcinoma in situ LDH test. See Lactate dehydrogenase test Leiomyomas . . . . . . . . . . . . . . . . . . Leiomyosarcomas . . . . . . . . . . . . . . . LEMS. See Lambert-Eaton myasthenic syndrome Leptomeningeal carcinomas . . . . . . . . . . Leukapharesis . . . . . . . . . . . . . . . . . Leukemia, Down syndrome and. See Down syndrome and leukemia Leukemia, eosinophilic. See Eosinophilic leukemia Leukemia, hairy cell. See Hairy cell leukemia Leukemias . . . . . . . . . . . . . . . . . . . Leukoencephalopathy . . . . . . . . . . . . . Leukopenia. . . . . . . . . . . . . . . . . . . Leukoplakia . . . . . . . . . . . . . . . . . . Leydig cell tumors . . . . . . . . . . . . . . . Li-Fraumeni syndrome (LFS) . . . . . . . . . Limb salvage . . . . . . . . . . . . . . . . . . Linear accelerator . . . . . . . . . . . . . . . Lip cancers . . . . . . . . . . . . . . . . . . . Liposarcomas . . . . . . . . . . . . . . . . . Liver biopsy . . . . . . . . . . . . . . . . . . Liver cancers . . . . . . . . . . . . . . . . . .
Jonsson Comprehensive Cancer Center (JCCC) . . . . . . . . . . . . . . . . . . . . . . 664 Journaling . . . . . . . . . . . . . . . . . . . . . . 665 Juvenile polyposis syndrome . . . . . . . . . . . . 665 Kaposi sarcoma . . . . . . . . . . . . . Karnofsky performance status (KPS) . . Keratosis . . . . . . . . . . . . . . . . . Ki67 test . . . . . . . . . . . . . . . . . Kidney cancer . . . . . . . . . . . . . . Klinefelter syndrome and cancer . . . . KPS. See Karnofsky performance status Krukenberg tumors . . . . . . . . . . .
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667 669 670 670 671 674
. . . . . . 675
Lacrimal gland tumors . . . . . . . . . . . . . . . . 677 Lactate dehydrogenase (LDH) test . . . . . . . . . 678 Laetrile . . . . . . . . . . . . . . . . . . . . . . . . 679
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679 681 682 685 686 687 688 690 692
. . . 693 . . . 694
. . . 696 . . . 698
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698 702 704 704 706 706 708 709 710 712 714 715
Volume 3 Lumps . . . . . . . . . . . . . . Lung cancer, brochoalveolar. See Bronchoalveolar lung cancer Lung cancers . . . . . . . . . . . Lutein . . . . . . . . . . . . . . Lycopene . . . . . . . . . . . . . Lymphadenectomy. . . . . . . . Lymphangiography . . . . . . . Lymphangiosarcomas . . . . . . Lymphedema. . . . . . . . . . . Lymphocytosis . . . . . . . . . . Lymphomas . . . . . . . . . . .
Contents . . . . . . . . . . . . . . . . . . . . . . . . lv Complete List of Contents . . . . . . . . . . . . . . lix Living will . . . . . . . . . . . . . . . . . Living with cancer . . . . . . . . . . . . . Lobectomy . . . . . . . . . . . . . . . . . Lobular carcinoma in situ (LCIS) . . . . . Long-distance caregiving . . . . . . . . . Loop electrosurgical excisional procedure (LEEP) . . . . . . . . . . . . . . . . . Lumbar puncture . . . . . . . . . . . . . . Lumpectomy . . . . . . . . . . . . . . . .
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719 720 723 725 726
. . . . . 727 . . . . . 728 . . . . . 730 xliii
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733 737 737 738 740 741 742 743 744
Salem Health: Cancer M. D. Anderson Cancer Center . . . . . . . . . Macrobiotic diet . . . . . . . . . . . . . . . . . Magnetic resonance imaging (MRI) . . . . . . . Malignant fibrous histiocytoma (MFH) . . . . . Malignant rhabdoid tumor of the kidney . . . . Malignant tumors . . . . . . . . . . . . . . . . MALT lymphomas. See Mucosa-associated lymphoid tissue lymphomas Mammography . . . . . . . . . . . . . . . . . . Managed care . . . . . . . . . . . . . . . . . . Mantle cell lymphoma (MCL) . . . . . . . . . . Mastectomy . . . . . . . . . . . . . . . . . . . Mastocytomas . . . . . . . . . . . . . . . . . . Matrix metalloproteinase inhibitors . . . . . . . Mayo Clinic Cancer Center . . . . . . . . . . . MCC. See Merkel cell carcinomas MCL. See Mantle cell lymphoma MDR. See Drug resistance and multidrug resistance Mediastinal tumors. . . . . . . . . . . . . . . . Mediastinoscopy . . . . . . . . . . . . . . . . . Medical marijuana . . . . . . . . . . . . . . . . Medical oncology . . . . . . . . . . . . . . . . Medicare and cancer . . . . . . . . . . . . . . . Medullary carcinoma of the breast. . . . . . . . Medulloblastomas . . . . . . . . . . . . . . . . Melanomas . . . . . . . . . . . . . . . . . . . . Melphalan . . . . . . . . . . . . . . . . . . . . Memorial Sloan-Kettering Cancer Center . . . . MEN 1. See Multiple endocrine neoplasia type 1 MEN 2. See Multiple endocrine neoplasia type 2 Meningeal carcinomatosis . . . . . . . . . . . . Meningiomas. . . . . . . . . . . . . . . . . . . Merkel cell carcinomas (MCC) . . . . . . . . . Mesenchymomas, malignant. . . . . . . . . . . Mesothelioma . . . . . . . . . . . . . . . . . . Metastasis . . . . . . . . . . . . . . . . . . . . Metastatic squamous neck cancer with occult primary . . . . . . . . . . . . . . . . . . . . MFH. See Malignant fibrous histiocytoma Microcalcifications. . . . . . . . . . . . . . . . Microwave hyperthermia therapy . . . . . . . . Mineral oils . . . . . . . . . . . . . . . . . . . Mistletoe . . . . . . . . . . . . . . . . . . . . . Mitochondrial DNA mutations. . . . . . . . . . MLH1 gene. . . . . . . . . . . . . . . . . . . . Mohs surgery. . . . . . . . . . . . . . . . . . . Molecular oncology . . . . . . . . . . . . . . . Moles. . . . . . . . . . . . . . . . . . . . . . . Monoclonal antibodies . . . . . . . . . . . . . . Motion sickness devices . . . . . . . . . . . . .
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748 750 750 752 753 754
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754 757 759 761 763 764 765
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766 768 768 770 772 774 775 776 779 780
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MRI. See Magnetic resonance imaging MSH genes . . . . . . . . . . . . . . . . . . . . Mucinous carcinomas . . . . . . . . . . . . . . Mucosa-associated lymphoid tissue (MALT) lymphomas . . . . . . . . . . . . . . . . . . Mucositis . . . . . . . . . . . . . . . . . . . . . Mucous membranes, epidermoid cancers of. See Epidermoid cancers of mucous membranes Multiple endocrine neoplasia type 1 (MEN 1). . Multiple endocrine neoplasia type 2 (MEN 2). . Multiple myeloma . . . . . . . . . . . . . . . . Mustard gas . . . . . . . . . . . . . . . . . . . Mutagenesis and cancer . . . . . . . . . . . . . Myasthenia gravis . . . . . . . . . . . . . . . . MYC oncogene . . . . . . . . . . . . . . . . . . Mycosis fungoides . . . . . . . . . . . . . . . . Myelodysplastic syndromes . . . . . . . . . . . Myelofibrosis . . . . . . . . . . . . . . . . . . Myeloma . . . . . . . . . . . . . . . . . . . . . Myeloproliferative disorders. . . . . . . . . . . Myelosuppression . . . . . . . . . . . . . . . . 2-Naphthylamine. . . . . . . . . . . . . . . . Nasal cavity and paranasal sinus cancers . . . National Cancer Institute (NCI) . . . . . . . . National Science Foundation (NSF) . . . . . . Native North Americans and cancer . . . . . . Nausea and vomiting. . . . . . . . . . . . . . NCI. See National Cancer Institute Needle biopsies . . . . . . . . . . . . . . . . Needle localization. . . . . . . . . . . . . . . Nephroblastomas. . . . . . . . . . . . . . . . Nephrostomy . . . . . . . . . . . . . . . . . . Neuroblastomas . . . . . . . . . . . . . . . . Neuroectodermal tumors. . . . . . . . . . . . Neuroendocrine tumors . . . . . . . . . . . . Neurofibromatosis type 1 (NF1) . . . . . . . . Neurologic oncology. . . . . . . . . . . . . . Neutropenia . . . . . . . . . . . . . . . . . . NF1. See Neurofibromatosis type 1 Nickel compounds and metallic nickel . . . . Night sweats . . . . . . . . . . . . . . . . . . Nijmegen breakage syndrome . . . . . . . . . Nipple discharge . . . . . . . . . . . . . . . . Non-Hodgkin lymphoma . . . . . . . . . . . Nonsteroidal anti-inflammatory drugs (NSAIDs) . . . . . . . . . . . . . . . . . . NSAIDs. See Nonsteroidal anti-inflammatory drugs NSF. See National Science Foundation Nuclear medicine scan . . . . . . . . . . . . .
781 782 783 785 786 788
. . 790 . . . . . . . . . . .
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790 791 792 793 794 795 796 796 798 800 802 xliv
. . 803 . . 803 . . 804 . . 806
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807 808 809 812 813 815 817 817 819 820 822 823 825
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826 826 829 830 832 834
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836 838 839 839 841 842 844 845 847 849
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851 852 853 854 855
. . . 858
. . . 859
Complete List of Contents Pediatric oncology and hematology . . . . . . . . . 938 Pelvic examination . . . . . . . . . . . . . . . . . . 940 Penile cancer . . . . . . . . . . . . . . . . . . . . . 941 Percutaneous transhepatic cholangiography (PTHC) . . . . . . . . . . . . . . . . . . . . . . 943 Pericardial effusion . . . . . . . . . . . . . . . . . 944 Pericardiocentesis . . . . . . . . . . . . . . . . . . 946 Peritoneovenous shunts . . . . . . . . . . . . . . . 946 Personality and cancer . . . . . . . . . . . . . . . . 947 Pesticides and the food chain . . . . . . . . . . . . 948 PET. See Positron emission tomography Peutz-Jeghers syndrome (PJS) . . . . . . . . . . . . 951 Pharmacy oncology . . . . . . . . . . . . . . . . . 952 Phenacetin . . . . . . . . . . . . . . . . . . . . . . 955 Phenolics . . . . . . . . . . . . . . . . . . . . . . . 955 Pheochromocytomas . . . . . . . . . . . . . . . . . 956 Pheresis . . . . . . . . . . . . . . . . . . . . . . . 958 Photodynamic therapy (PDT) . . . . . . . . . . . . 959 Phyllodes tumors. . . . . . . . . . . . . . . . . . . 960 Phytoestrogens . . . . . . . . . . . . . . . . . . . . 962 Pineoblastomas. . . . . . . . . . . . . . . . . . . . 963 Pituitary tumors . . . . . . . . . . . . . . . . . . . 965 PJS. See Peutz-Jeghers syndrome Placental alkaline phosphatase (PALP) . . . . . . . 968 Plant alkaloids and terpenoids in chemotherapy . . . . . . . . . . . . . . . . . . . 968 Plasticizers . . . . . . . . . . . . . . . . . . . . . . 971 Pleural biopsy . . . . . . . . . . . . . . . . . . . . 972 Pleural effusion . . . . . . . . . . . . . . . . . . . 973 Pleurodesis . . . . . . . . . . . . . . . . . . . . . . 975 Pleuropulmonary blastomas . . . . . . . . . . . . . 975 PMS genes . . . . . . . . . . . . . . . . . . . . . . 976 Pneumonectomy . . . . . . . . . . . . . . . . . . . 977 Pneumonia . . . . . . . . . . . . . . . . . . . . . . 979 Polycyclic aromatic hydrocarbons . . . . . . . . . . 981 Polycythemia vera . . . . . . . . . . . . . . . . . . 981 Polypectomy . . . . . . . . . . . . . . . . . . . . . 982 Polyps . . . . . . . . . . . . . . . . . . . . . . . . 983 Polyps, colon. See Colon polyps Polyps, gastric. See Gastric polyps Positron emission tomography (PET) . . . . . . . . 984 Poverty and cancer . . . . . . . . . . . . . . . . . . 987 PPOs. See Preferred provider organizations Prayer and cancer support . . . . . . . . . . . . . . 989 Preferred provider organizations (PPOs) . . . . . . 990 Pregnancy and cancer . . . . . . . . . . . . . . . . 992 Premalignancies . . . . . . . . . . . . . . . . . . . 994 Prevent Cancer Foundation . . . . . . . . . . . . . 997 Prevention . . . . . . . . . . . . . . . . . . . . . . 999 Primary care physician . . . . . . . . . . . . . . . 1001
Nutrition and cancer prevention . . . . . . . . . . . 861 Nutrition and cancer treatment. . . . . . . . . . . . 864 Obesity-associated cancers . . . . . Occupational exposures and cancer . Occupational therapy . . . . . . . . OCs. See Organochlorines Oligodendrogliomas . . . . . . . . . Omega-3 fatty acids . . . . . . . . . Ommaya reservoir . . . . . . . . . . Oncogenes . . . . . . . . . . . . . . Oncogenic viruses . . . . . . . . . . Oncology . . . . . . . . . . . . . . . Oncology clinical nurse specialist . . Oncology social worker . . . . . . . Oophorectomy . . . . . . . . . . . . Ophthalmic oncology . . . . . . . . Opioids . . . . . . . . . . . . . . . . Oral and maxillofacial surgery. . . . Oral and oropharyngeal cancers . . . Orbit tumors . . . . . . . . . . . . . Orchiectomy . . . . . . . . . . . . . Organ transplantation and cancer . . Organochlorines (OCs) . . . . . . . Oropharyngeal cancers. See Oral and oropharyngeal cancers Orthopedic surgery. . . . . . . . . . Otolaryngology . . . . . . . . . . . Ovarian cancers . . . . . . . . . . . Ovarian cysts. . . . . . . . . . . . . Ovarian epithelial cancer . . . . . . Overtreatment . . . . . . . . . . . .
. . . . . . . . 868 . . . . . . . . 871 . . . . . . . . 873 . . . . . . . . . . . . . . . . .
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875 877 878 878 881 882 885 887 888 889 892 893 894 897 898 899 901
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902 903 905 908 909 911
Paget disease of bone . . . . . . . . . . . . . Pain management medications. . . . . . . . . Palliative treatment . . . . . . . . . . . . . . PALP. See Placental alkaline phosphatase Palpation . . . . . . . . . . . . . . . . . . . . Pancolitis . . . . . . . . . . . . . . . . . . . . Pancreatectomy . . . . . . . . . . . . . . . . Pancreatic cancers . . . . . . . . . . . . . . . Pancreatitis . . . . . . . . . . . . . . . . . . . Pap test . . . . . . . . . . . . . . . . . . . . . Paracentesis . . . . . . . . . . . . . . . . . . Paranasal sinus cancers. See Nasal cavity and paranasal sinus cancers Paraneoplastic syndromes . . . . . . . . . . . Parathyroid cancer . . . . . . . . . . . . . . . Pathology . . . . . . . . . . . . . . . . . . . PC-SPES . . . . . . . . . . . . . . . . . . . . PDT. See Photodynamic therapy
. . . 912 . . . 914 . . . 917 . . . . . . .
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920 920 921 923 927 928 929
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931 932 934 937 xlv
Salem Health: Cancer Primary central nervous system lymphomas . . . . . . . . . . . . . . . . Progesterone receptor assay . . . . . . . . Prostate cancer . . . . . . . . . . . . . . . Prostate-specific antigen (PSA) test . . . . Prostatectomy. . . . . . . . . . . . . . . . Prostatitis . . . . . . . . . . . . . . . . . . Proteasome inhibitors. . . . . . . . . . . . Protein electrophoresis . . . . . . . . . . . Proteomics and cancer research . . . . . . Proton beam therapy . . . . . . . . . . . . Proto-oncogenes and carcinogenesis . . . . PSA test. See Prostate-specific antigen test Psycho-oncology . . . . . . . . . . . . . . Psychosocial aspects of cancer . . . . . . . PTHC. See Percutaneous transhepatic cholangiography Radiation, ionizing. See Ionizing radiation Radiation oncology . . . . . . . . . . . . . Radiation therapies . . . . . . . . . . . . . Radiation therapy, afterloading. See Afterloading radiation therapy Radical neck dissection . . . . . . . . . . . Radiofrequency ablation . . . . . . . . . . Radionuclide scan . . . . . . . . . . . . . Radiopharmaceuticals . . . . . . . . . . . Radon . . . . . . . . . . . . . . . . . . . . RB1 gene . . . . . . . . . . . . . . . . . . Receptor analysis . . . . . . . . . . . . . .
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1003 1003 1004 1006 1008 1009 1010 1010 1012 1014 1015
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1027 1027 1030 1030 1032 1032 1033
Reconstructive surgery . . . . . . . . . . . . . . Rectal cancer . . . . . . . . . . . . . . . . . . . Recurrence . . . . . . . . . . . . . . . . . . . . Rehabilitation . . . . . . . . . . . . . . . . . . . Relationships . . . . . . . . . . . . . . . . . . . Renal pelvis tumors. . . . . . . . . . . . . . . . Report on Carcinogens (RoC) . . . . . . . . . . Resveratrol . . . . . . . . . . . . . . . . . . . . Retinoblastomas . . . . . . . . . . . . . . . . . Rhabdomyosarcomas . . . . . . . . . . . . . . . RhoGD12 gene . . . . . . . . . . . . . . . . . . Richter syndrome . . . . . . . . . . . . . . . . . Risk assessment, family history and. See Family history and risk assessment Risks for cancer. . . . . . . . . . . . . . . . . . Robert H. Lurie Cancer Center . . . . . . . . . . RoC. See Report on Carcinogens Rothmund-Thomson syndrome . . . . . . . . . .
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Salivary gland cancer . . . . . . . . . . . . . Salpingectomy and salpingo-oophorectomy . Sarcomas, soft-tissue . . . . . . . . . . . . . Saw palmetto . . . . . . . . . . . . . . . . . Schwannoma tumors . . . . . . . . . . . . . SCLC1 gene. . . . . . . . . . . . . . . . . . Screening, colorectal cancer. See Colorectal cancer screening Screening for cancer . . . . . . . . . . . . . Second opinions . . . . . . . . . . . . . . . Self-image and body image. . . . . . . . . .
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1034 1036 1038 1038 1041 1043 1044 1045 1046 1048 1050 1050
. 1052 . 1054 . 1056 1058 1060 1062 1065 1066 1067
. . . 1067 . . . 1070 . . . 1071
Volume 4 Sjögren syndrome. . . . . . . . . . . . . . . . Skin cancers . . . . . . . . . . . . . . . . . . SLN biopsy and mapping. See Sentinel lymph node biopsy and mapping Small intestine cancer . . . . . . . . . . . . . Smoking cessation . . . . . . . . . . . . . . . Social Security Disability Insurance (SSDI) . . Soft-tissue fibrosarcomas. See Fibrosarcomas, soft-tissue Soots . . . . . . . . . . . . . . . . . . . . . . Soy foods . . . . . . . . . . . . . . . . . . . . Spermatocytomas . . . . . . . . . . . . . . . . Spinal axis tumors . . . . . . . . . . . . . . . Spinal cord compression . . . . . . . . . . . . Splenectomy . . . . . . . . . . . . . . . . . . Sputum cytology . . . . . . . . . . . . . . . .
Contents . . . . . . . . . . . . . . . . . . . . . . lxxvii Complete List of Contents . . . . . . . . . . . . . lxxix Sentinel lymph node (SLN) biopsy and mapping . . . . . . . . . . . . . . . Sepsis. See Infection and sepsis Sertoli cell tumors . . . . . . . . . . . Sexuality and cancer . . . . . . . . . . Sézary syndrome . . . . . . . . . . . . SIADH. See Syndrome of inappropriate antidiuretic hormone production Side effects . . . . . . . . . . . . . . . Sigmoidoscopy . . . . . . . . . . . . . Silica, crystalline . . . . . . . . . . . . Simian virus 40 . . . . . . . . . . . . . Singlehood and cancer . . . . . . . . .
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1078 1082 1083 1084 1084 xlvi
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1097 1098 1099 1100 1102 1103 1105
Complete List of Contents Squamous cell carcinomas . . . . . . . . . . . SRS. See Stereotactic radiosurgery SSDI. See Social Security Disability Insurance Staging of cancer . . . . . . . . . . . . . . . . Statistics of cancer . . . . . . . . . . . . . . . Stem cell transplantation . . . . . . . . . . . . Stent therapy . . . . . . . . . . . . . . . . . . Stereotactic needle biopsy . . . . . . . . . . . Stereotactic radiosurgery (SRS) . . . . . . . . Sterility . . . . . . . . . . . . . . . . . . . . . Stomach cancers . . . . . . . . . . . . . . . . Stomatitis . . . . . . . . . . . . . . . . . . . . Stress management . . . . . . . . . . . . . . . Sunlamps . . . . . . . . . . . . . . . . . . . . Sun’s soup . . . . . . . . . . . . . . . . . . . Sunscreens . . . . . . . . . . . . . . . . . . . Superior vena cava syndrome . . . . . . . . . Support groups . . . . . . . . . . . . . . . . . Surgical biopsies . . . . . . . . . . . . . . . . Surgical oncology. . . . . . . . . . . . . . . . Survival rates . . . . . . . . . . . . . . . . . . Survivorship issues . . . . . . . . . . . . . . . Symptoms and cancer. . . . . . . . . . . . . . Syndrome of inappropriate antidiuretic hormone production (SIADH) . . . . . . . . Synovial sarcomas . . . . . . . . . . . . . . . Taste alteration . . . . . . . . . . . . . . Teratocarcinomas . . . . . . . . . . . . . Teratomas . . . . . . . . . . . . . . . . . Testicular cancer . . . . . . . . . . . . . Testicular self-examination (TSE) . . . . Thermal imaging . . . . . . . . . . . . . Thiotepa. . . . . . . . . . . . . . . . . . Thoracentesis . . . . . . . . . . . . . . . Thoracoscopy . . . . . . . . . . . . . . . Thoracotomy . . . . . . . . . . . . . . . Throat cancer . . . . . . . . . . . . . . . Thrombocytopenia . . . . . . . . . . . . Thymomas . . . . . . . . . . . . . . . . Thymus cancer . . . . . . . . . . . . . . Thyroid cancer . . . . . . . . . . . . . . Thyroid nuclear medicine scan . . . . . . TNF. See Tumor necrosis factor TNM staging . . . . . . . . . . . . . . . Tobacco, chewing. See Chewing tobacco Tobacco-related cancers . . . . . . . . . Topoisomerase inhibitors . . . . . . . . . TP53 protein . . . . . . . . . . . . . . . Tracheostomy . . . . . . . . . . . . . . . Transfusion therapy. . . . . . . . . . . .
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Transitional care . . . . . . . . . . . Transitional cell carcinomas . . . . . Transrectal ultrasound . . . . . . . . Transvaginal ultrasound . . . . . . . Trichilemmal carcinomas. . . . . . . TSE. See Testicular self-examination Tuberous sclerosis . . . . . . . . . . Tubular carcinomas . . . . . . . . . . Tumor flare . . . . . . . . . . . . . . Tumor lysis syndrome . . . . . . . . Tumor markers . . . . . . . . . . . . Tumor necrosis factor (TNF) . . . . . Tumor-suppressor genes . . . . . . . Turcot syndrome . . . . . . . . . . . Tyrosine kinase inhibitors . . . . . .
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1108 1111 1114 1116 1118 1119 1120 1121 1124 1125 1127 1128 1129 1130 1132 1135 1138 1140 1143 1144
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1151 1152 1153 1154 1156 1157 1158 1158 1160 1161 1162 1164 1166 1167 1169 1172
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1182 1183 1185 1186 1187
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1187 1188 1189 1189 1191 1193 1194 1195 1196
Ultrasound, breast. See Breast ultrasound Ultrasound, endorectal. See Endorectal ultrasound Ultrasound, transrectal. See Transrectal ultrasound Ultrasound, transvaginal. See Transvaginal ultrasound Ultrasound tests . . . . . . . . . . . . . . . Ultraviolet radiation and related exposures Umbilical cord blood transplantation. . . . Upper gastrointestinal (GI) endoscopy . . . Upper gastrointestinal (GI) series . . . . . Urethral cancer . . . . . . . . . . . . . . . Urinalysis . . . . . . . . . . . . . . . . . . Urinary system cancers . . . . . . . . . . . Urography . . . . . . . . . . . . . . . . . Urologic oncology . . . . . . . . . . . . . Urostomy . . . . . . . . . . . . . . . . . . Uterine cancer . . . . . . . . . . . . . . .
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1199 1200 1201 1202 1203 1205 1207 1209 1213 1214 1216 1217
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1220 1221 1223 1225 1226
Vaccines, preventive . . . . . . . . . . . Vaccines, therapeutic . . . . . . . . . . . Vaginal cancer . . . . . . . . . . . . . . Vascular access tubes. . . . . . . . . . . Vasectomy and cancer . . . . . . . . . . Vegetables, cruciferous. See Cruciferous vegetables Veterinary oncology . . . . . . . . . . . VHL disease. See Von Hippel-Lindau disease Vinyl chloride . . . . . . . . . . . . . . Viral oncology . . . . . . . . . . . . . . Virus-related cancers . . . . . . . . . . . Von Hippel-Lindau (VHL) disease. . . . Vulvar cancer . . . . . . . . . . . . . . .
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1174 1175 1177 1179 1180 xlvii
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1230 1230 1232 1235 1237
Salem Health: Cancer WAGR syndrome. See Wilms’ tumor aniridiagenitourinary anomalies-mental retardation syndrome and cancer Waldenström macroglobulinemia (WM) . . . . . . 1240 Watchful waiting . . . . . . . . . . . . . . . . . . 1242 Weight loss . . . . . . . . . . . . . . . . . . . . . 1243 Wilms’ tumor . . . . . . . . . . . . . . . . . . . . 1245 Wilms’ tumor aniridia-genitourinary anomaliesmental retardation (WAGR) syndrome and cancer . . . . . . . . . . . . . . . . . . . . . . 1248 Wine and cancer . . . . . . . . . . . . . . . . . . 1250 Wire localization . . . . . . . . . . . . . . . . . . 1250 WM. See Waldenström macroglobulinemia Wood dust . . . . . . . . . . . . . . . . . . . . . 1251
Yolk sac carcinomas . . . . . . . . . . . . . . . . 1256 Young adult cancers . . . . . . . . . . . . . . . . 1256 Zollinger-Ellison syndrome . . . . . . . . . . . . 1260 Drugs by Generic Name . . . Drugs by Trade Name . . . . Associations and Agencies . . Cancer Centers and Hospitals Cancer Support Groups . . . . Carcinogens. . . . . . . . . . Glossary . . . . . . . . . . . Bibliography . . . . . . . . .
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1265 1309 1348 1352 1357 1362 1383 1400
Category List . . . . . . . . . . . . . . . . . . . . 1409 Index . . . . . . . . . . . . . . . . . . . . . . . . 1419
X-ray tests . . . . . . . . . . . . . . . . . . . . . 1252 Xeroderma pigmentosa . . . . . . . . . . . . . . . 1254
xlviii
Volume III Living will — Self-image and body image
Editor
Jeffrey A. Knight, Ph.D. Mount Holyoke College
Medical Consultants
Laurie Jackson-Grusby, Ph.D. Children’s Hospital Boston, Harvard Medical School
Wendy White-Ryan, M.D., FAAP Golisano Children’s Hospital at Strong Memorial Hospital
SALEM PRESS, INC. Pasadena, California Hackensack, New Jersey
Editor in Chief: Dawn P. Dawson Editorial Director: Christina J. Moose Project Editors: Tracy Irons-Georges, Rowena Wildin Dehanke Editorial Assistant: Dana Garey
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Copyright © 2009, by Salem Press, Inc. All rights in this book are reserved. No part of this work may be used or reproduced in any manner whatsoever or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without written permission from the copyright owner except in the case of brief quotations embodied in critical articles and reviews or in the copying of images deemed to be freely licensed or in the public domain. For information address the publisher, Salem Press, Inc., P.O. Box 50062, Pasadena, California 91115. ∞ The paper used in these volumes conforms to the American National Standard for Permanence of Paper for Printed Library Materials, Z39.48-1992 (R1997). Note to Readers The material presented in Salem Health: Cancer is intended for broad informational and educational purposes. Readers who suspect that they or someone whom they know or provide caregiving for suffers from cancer or any other physical or psychological disorder, disease, or condition described in this set should contact a physician without delay; this work should not be used as a substitute for professional medical diagnosis or staging. Readers who are undergoing or about to undergo any treatment or procedure described in this set should refer to their physicians and other health care team members for guidance concerning preparation and possible effects. This set is not to be considered definitive on the covered topics, and readers should remember that the field of health care is characterized by a diversity of medical opinions and constant expansion in knowledge and understanding. Library of Congress Cataloging-in-Publication Data Salem health : cancer / Jeffrey A. Knight, Laurie Jackson-Grusby, Wendy White-Ryan. p. cm. Includes bibliographical references and index. ISBN 978-1-58765-505-0 (set : alk. paper) — ISBN 978-1-58765-506-7 (vol. 1 : alk. paper) — ISBN 978-1-58765-507-4 (vol. 2 : alk. paper) — ISBN 978-1-58765-508-1 (vol. 3 : alk. paper) — ISBN 978-1-58765-509-8 (vol. 4 : alk. paper) 1. Cancer. I. Knight, Jeffrey A., 1948- II. Jackson-Grusby, Laurie. III. White-Ryan, Wendy. RC265.S32 2008 616.99′4—dc22 2008030861
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printed in the united states of america
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Contents Medullary carcinoma of the breast. . . . . . . . Medulloblastomas . . . . . . . . . . . . . . . . Melanomas . . . . . . . . . . . . . . . . . . . . Melphalan . . . . . . . . . . . . . . . . . . . . Memorial Sloan-Kettering Cancer Center . . . . MEN 1. See Multiple endocrine neoplasia type 1 MEN 2. See Multiple endocrine neoplasia type 2 Meningeal carcinomatosis . . . . . . . . . . . . Meningiomas. . . . . . . . . . . . . . . . . . . Merkel cell carcinomas (MCC) . . . . . . . . . Mesenchymomas, malignant. . . . . . . . . . . Mesothelioma . . . . . . . . . . . . . . . . . . Metastasis . . . . . . . . . . . . . . . . . . . . Metastatic squamous neck cancer with occult primary . . . . . . . . . . . . . . . . . . . . MFH. See Malignant fibrous histiocytoma Microcalcifications. . . . . . . . . . . . . . . . Microwave hyperthermia therapy . . . . . . . . Mineral oils . . . . . . . . . . . . . . . . . . . Mistletoe . . . . . . . . . . . . . . . . . . . . . Mitochondrial DNA mutations. . . . . . . . . . MLH1 gene. . . . . . . . . . . . . . . . . . . . Mohs surgery. . . . . . . . . . . . . . . . . . . Molecular oncology . . . . . . . . . . . . . . . Moles. . . . . . . . . . . . . . . . . . . . . . . Monoclonal antibodies . . . . . . . . . . . . . . Motion sickness devices . . . . . . . . . . . . . MRI. See Magnetic resonance imaging MSH genes . . . . . . . . . . . . . . . . . . . . Mucinous carcinomas . . . . . . . . . . . . . . Mucosa-associated lymphoid tissue (MALT) lymphomas . . . . . . . . . . . . . . . . . . Mucositis . . . . . . . . . . . . . . . . . . . . . Mucous membranes, epidermoid cancers of. See Epidermoid cancers of mucous membranes Multiple endocrine neoplasia type 1 (MEN 1). . Multiple endocrine neoplasia type 2 (MEN 2). . Multiple myeloma . . . . . . . . . . . . . . . . Mustard gas . . . . . . . . . . . . . . . . . . . Mutagenesis and cancer . . . . . . . . . . . . . Myasthenia gravis . . . . . . . . . . . . . . . . MYC oncogene . . . . . . . . . . . . . . . . . . Mycosis fungoides . . . . . . . . . . . . . . . . Myelodysplastic syndromes . . . . . . . . . . . Myelofibrosis . . . . . . . . . . . . . . . . . . Myeloma . . . . . . . . . . . . . . . . . . . . . Myeloproliferative disorders. . . . . . . . . . . Myelosuppression . . . . . . . . . . . . . . . .
Complete List of Contents . . . . . . . . . . . . . . lix Living will . . . . . . . . . . . . . . . . . Living with cancer . . . . . . . . . . . . . Lobectomy . . . . . . . . . . . . . . . . . Lobular carcinoma in situ (LCIS) . . . . . Long-distance caregiving . . . . . . . . . Loop electrosurgical excisional procedure (LEEP) . . . . . . . . . . . . . . . . . Lumbar puncture . . . . . . . . . . . . . . Lumpectomy . . . . . . . . . . . . . . . . Lumps . . . . . . . . . . . . . . . . . . . Lung cancer, brochoalveolar. See Bronchoalveolar lung cancer Lung cancers . . . . . . . . . . . . . . . . Lutein . . . . . . . . . . . . . . . . . . . Lycopene . . . . . . . . . . . . . . . . . . Lymphadenectomy. . . . . . . . . . . . . Lymphangiography . . . . . . . . . . . . Lymphangiosarcomas . . . . . . . . . . . Lymphedema. . . . . . . . . . . . . . . . Lymphocytosis . . . . . . . . . . . . . . . Lymphomas . . . . . . . . . . . . . . . .
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719 720 723 725 726
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733 737 737 738 740 741 742 743 744
M. D. Anderson Cancer Center . . . . . . . Macrobiotic diet . . . . . . . . . . . . . . . Magnetic resonance imaging (MRI) . . . . . Malignant fibrous histiocytoma (MFH) . . . Malignant rhabdoid tumor of the kidney . . Malignant tumors . . . . . . . . . . . . . . MALT lymphomas. See Mucosa-associated lymphoid tissue lymphomas Mammography . . . . . . . . . . . . . . . . Managed care . . . . . . . . . . . . . . . . Mantle cell lymphoma (MCL) . . . . . . . . Mastectomy . . . . . . . . . . . . . . . . . Mastocytomas . . . . . . . . . . . . . . . . Matrix metalloproteinase inhibitors . . . . . Mayo Clinic Cancer Center . . . . . . . . . MCC. See Merkel cell carcinomas MCL. See Mantle cell lymphoma MDR. See Drug resistance and multidrug resistance Mediastinal tumors. . . . . . . . . . . . . . Mediastinoscopy . . . . . . . . . . . . . . . Medical marijuana . . . . . . . . . . . . . . Medical oncology . . . . . . . . . . . . . . Medicare and cancer . . . . . . . . . . . . .
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766 768 768 770 772 lv
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774 775 776 779 780
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781 782 783 785 786 788
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790 791 792 793 794 795 796 796 798 800 802
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807 808 809 812 813 815 817 817 819 820 822 823 825
Salem Health: Cancer 2-Naphthylamine. . . . . . . . . . . . . . . . Nasal cavity and paranasal sinus cancers . . . National Cancer Institute (NCI) . . . . . . . . National Science Foundation (NSF) . . . . . . Native North Americans and cancer . . . . . . Nausea and vomiting. . . . . . . . . . . . . . NCI. See National Cancer Institute Needle biopsies . . . . . . . . . . . . . . . . Needle localization. . . . . . . . . . . . . . . Nephroblastomas. . . . . . . . . . . . . . . . Nephrostomy . . . . . . . . . . . . . . . . . . Neuroblastomas . . . . . . . . . . . . . . . . Neuroectodermal tumors. . . . . . . . . . . . Neuroendocrine tumors . . . . . . . . . . . . Neurofibromatosis type 1 (NF1) . . . . . . . . Neurologic oncology. . . . . . . . . . . . . . Neutropenia . . . . . . . . . . . . . . . . . . NF1. See Neurofibromatosis type 1 Nickel compounds and metallic nickel . . . . Night sweats . . . . . . . . . . . . . . . . . . Nijmegen breakage syndrome . . . . . . . . . Nipple discharge . . . . . . . . . . . . . . . . Non-Hodgkin lymphoma . . . . . . . . . . . Nonsteroidal anti-inflammatory drugs (NSAIDs) . . . . . . . . . . . . . . . . . . NSAIDs. See Nonsteroidal anti-inflammatory drugs NSF. See National Science Foundation Nuclear medicine scan . . . . . . . . . . . . . Nutrition and cancer prevention . . . . . . . . Nutrition and cancer treatment. . . . . . . . . Obesity-associated cancers . . . . Occupational exposures and cancer Occupational therapy . . . . . . . OCs. See Organochlorines Oligodendrogliomas . . . . . . . . Omega-3 fatty acids . . . . . . . . Ommaya reservoir . . . . . . . . . Oncogenes . . . . . . . . . . . . . Oncogenic viruses . . . . . . . . . Oncology . . . . . . . . . . . . . . Oncology clinical nurse specialist . Oncology social worker . . . . . . Oophorectomy . . . . . . . . . . . Ophthalmic oncology . . . . . . . Opioids . . . . . . . . . . . . . . . Oral and maxillofacial surgery. . . Oral and oropharyngeal cancers . . Orbit tumors . . . . . . . . . . . . Orchiectomy . . . . . . . . . . . .
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836 838 839 839 841 842 844 845 847 849
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851 852 853 854 855
Organ transplantation and cancer . . Organochlorines (OCs) . . . . . . . Oropharyngeal cancers. See Oral and oropharyngeal cancers Orthopedic surgery. . . . . . . . . . Otolaryngology . . . . . . . . . . . Ovarian cancers . . . . . . . . . . . Ovarian cysts. . . . . . . . . . . . . Ovarian epithelial cancer . . . . . . Overtreatment . . . . . . . . . . . .
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Paget disease of bone . . . . . . . . . . . . . Pain management medications. . . . . . . . . Palliative treatment . . . . . . . . . . . . . . PALP. See Placental alkaline phosphatase Palpation . . . . . . . . . . . . . . . . . . . . Pancolitis . . . . . . . . . . . . . . . . . . . . Pancreatectomy . . . . . . . . . . . . . . . . Pancreatic cancers . . . . . . . . . . . . . . . Pancreatitis . . . . . . . . . . . . . . . . . . . Pap test . . . . . . . . . . . . . . . . . . . . . Paracentesis . . . . . . . . . . . . . . . . . . Paranasal sinus cancers. See Nasal cavity and paranasal sinus cancers Paraneoplastic syndromes . . . . . . . . . . . Parathyroid cancer . . . . . . . . . . . . . . . Pathology . . . . . . . . . . . . . . . . . . . PC-SPES . . . . . . . . . . . . . . . . . . . . PDT. See Photodynamic therapy Pediatric oncology and hematology . . . . . . Pelvic examination . . . . . . . . . . . . . . . Penile cancer . . . . . . . . . . . . . . . . . . Percutaneous transhepatic cholangiography (PTHC) . . . . . . . . . . . . . . . . . . . Pericardial effusion . . . . . . . . . . . . . . Pericardiocentesis . . . . . . . . . . . . . . . Peritoneovenous shunts . . . . . . . . . . . . Personality and cancer . . . . . . . . . . . . . Pesticides and the food chain . . . . . . . . . PET. See Positron emission tomography Peutz-Jeghers syndrome (PJS) . . . . . . . . . Pharmacy oncology . . . . . . . . . . . . . . Phenacetin . . . . . . . . . . . . . . . . . . . Phenolics . . . . . . . . . . . . . . . . . . . . Pheochromocytomas . . . . . . . . . . . . . . Pheresis . . . . . . . . . . . . . . . . . . . . Photodynamic therapy (PDT) . . . . . . . . . Phyllodes tumors. . . . . . . . . . . . . . . . Phytoestrogens . . . . . . . . . . . . . . . . . Pineoblastomas. . . . . . . . . . . . . . . . . Pituitary tumors . . . . . . . . . . . . . . . .
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875 877 878 878 881 882 885 887 888 889 892 893 894 897 898 lvi
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902 903 905 908 909 911
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951 952 955 955 956 958 959 960 962 963 965
Contents PJS. See Peutz-Jeghers syndrome Placental alkaline phosphatase (PALP) . . . . . . . 968 Plant alkaloids and terpenoids in chemotherapy . . . . . . . . . . . . . . . . . . . 968 Plasticizers . . . . . . . . . . . . . . . . . . . . . . 971 Pleural biopsy . . . . . . . . . . . . . . . . . . . . 972 Pleural effusion . . . . . . . . . . . . . . . . . . . 973 Pleurodesis . . . . . . . . . . . . . . . . . . . . . . 975 Pleuropulmonary blastomas . . . . . . . . . . . . . 975 PMS genes . . . . . . . . . . . . . . . . . . . . . . 976 Pneumonectomy . . . . . . . . . . . . . . . . . . . 977 Pneumonia . . . . . . . . . . . . . . . . . . . . . . 979 Polycyclic aromatic hydrocarbons . . . . . . . . . . 981 Polycythemia vera . . . . . . . . . . . . . . . . . . 981 Polypectomy . . . . . . . . . . . . . . . . . . . . . 982 Polyps . . . . . . . . . . . . . . . . . . . . . . . . 983 Polyps, colon. See Colon polyps Polyps, gastric. See Gastric polyps Positron emission tomography (PET) . . . . . . . . 984 Poverty and cancer . . . . . . . . . . . . . . . . . . 987 PPOs. See Preferred provider organizations Prayer and cancer support . . . . . . . . . . . . . . 989 Preferred provider organizations (PPOs) . . . . . . 990 Pregnancy and cancer . . . . . . . . . . . . . . . . 992 Premalignancies . . . . . . . . . . . . . . . . . . . 994 Prevent Cancer Foundation . . . . . . . . . . . . . 997 Prevention . . . . . . . . . . . . . . . . . . . . . . 999 Primary care physician . . . . . . . . . . . . . . . 1001 Primary central nervous system lymphomas . . . . 1003 Progesterone receptor assay . . . . . . . . . . . . 1003 Prostate cancer . . . . . . . . . . . . . . . . . . . 1004 Prostate-specific antigen (PSA) test . . . . . . . . 1006 Prostatectomy. . . . . . . . . . . . . . . . . . . . 1008 Prostatitis . . . . . . . . . . . . . . . . . . . . . . 1009 Proteasome inhibitors. . . . . . . . . . . . . . . . 1010 Protein electrophoresis . . . . . . . . . . . . . . . 1010 Proteomics and cancer research . . . . . . . . . . 1012 Proton beam therapy . . . . . . . . . . . . . . . . 1014 Proto-oncogenes and carcinogenesis . . . . . . . . 1015 PSA test. See Prostate-specific antigen test Psycho-oncology . . . . . . . . . . . . . . . . . . 1016 Psychosocial aspects of cancer . . . . . . . . . . . 1018 PTHC. See Percutaneous transhepatic cholangiography
Radiation, ionizing. See Ionizing radiation Radiation oncology . . . . . . . . . . . . . . . . Radiation therapies . . . . . . . . . . . . . . . . Radiation therapy, afterloading. See Afterloading radiation therapy Radical neck dissection . . . . . . . . . . . . . . Radiofrequency ablation . . . . . . . . . . . . . Radionuclide scan . . . . . . . . . . . . . . . . Radiopharmaceuticals . . . . . . . . . . . . . . Radon . . . . . . . . . . . . . . . . . . . . . . . RB1 gene . . . . . . . . . . . . . . . . . . . . . Receptor analysis . . . . . . . . . . . . . . . . . Reconstructive surgery . . . . . . . . . . . . . . Rectal cancer . . . . . . . . . . . . . . . . . . . Recurrence . . . . . . . . . . . . . . . . . . . . Rehabilitation . . . . . . . . . . . . . . . . . . . Relationships . . . . . . . . . . . . . . . . . . . Renal pelvis tumors. . . . . . . . . . . . . . . . Report on Carcinogens (RoC) . . . . . . . . . . Resveratrol . . . . . . . . . . . . . . . . . . . . Retinoblastomas . . . . . . . . . . . . . . . . . Rhabdomyosarcomas . . . . . . . . . . . . . . . RhoGD12 gene . . . . . . . . . . . . . . . . . . Richter syndrome . . . . . . . . . . . . . . . . . Risk assessment, family history and. See Family history and risk assessment Risks for cancer. . . . . . . . . . . . . . . . . . Robert H. Lurie Cancer Center . . . . . . . . . . RoC. See Report on Carcinogens Rothmund-Thomson syndrome . . . . . . . . . . Salivary gland cancer . . . . . . . . . . . . . Salpingectomy and salpingo-oophorectomy . Sarcomas, soft-tissue . . . . . . . . . . . . . Saw palmetto . . . . . . . . . . . . . . . . . Schwannoma tumors . . . . . . . . . . . . . SCLC1 gene. . . . . . . . . . . . . . . . . . Screening, colorectal cancer. See Colorectal cancer screening Screening for cancer . . . . . . . . . . . . . Second opinions . . . . . . . . . . . . . . . Self-image and body image. . . . . . . . . .
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Complete List of Contents Volume 1 Alkylating agents in chemotherapy . . . . . . . ALL. See Acute lymphocytic leukemia Allicin, garlic and. See Garlic and allicin Alopecia . . . . . . . . . . . . . . . . . . . . . ALP. See Alkaline phosphatase test Alpha-fetoprotein (AFP) levels . . . . . . . . . Alternative therapies. See Complementary and alternative therapies Alveolar soft-part sarcomas . . . . . . . . . . . Amenorrhea . . . . . . . . . . . . . . . . . . . American Association for Cancer Research (AACR) . . . . . . . . . . . . . . . . . . . . American Cancer Society (ACS) . . . . . . . . American Institute for Cancer Research (AICR) 4-Aminobiphenyl . . . . . . . . . . . . . . . . AML. See Acute myelocytic leukemia Amputation . . . . . . . . . . . . . . . . . . . Amyloidosis . . . . . . . . . . . . . . . . . . . Anal cancer . . . . . . . . . . . . . . . . . . . Androgen drugs . . . . . . . . . . . . . . . . . Anemia . . . . . . . . . . . . . . . . . . . . . Anemia, aplastic. See Aplastic anemia Anemia, hemolytic. See Hemolytic anemia Angiogenesis . . . . . . . . . . . . . . . . . . Angiogenesis inhibitors . . . . . . . . . . . . . Angiography. . . . . . . . . . . . . . . . . . . Angiosarcomas . . . . . . . . . . . . . . . . . Anoscopy . . . . . . . . . . . . . . . . . . . . Anthraquinones . . . . . . . . . . . . . . . . . Anthrax . . . . . . . . . . . . . . . . . . . . . Antiandrogens . . . . . . . . . . . . . . . . . . Antidiarrheal agents . . . . . . . . . . . . . . . Antiestrogens . . . . . . . . . . . . . . . . . . Antifungal therapies . . . . . . . . . . . . . . . Antimetabolites in chemotherapy . . . . . . . . Antinausea medications . . . . . . . . . . . . . Antineoplastics in chemotherapy . . . . . . . . Antioxidants . . . . . . . . . . . . . . . . . . . Antiperspirants and breast cancer . . . . . . . . Antiviral therapies. . . . . . . . . . . . . . . . Anxiety . . . . . . . . . . . . . . . . . . . . . APBI. See Accelerated partial breast irradiation APC gene testing . . . . . . . . . . . . . . . . Aplastic anemia . . . . . . . . . . . . . . . . . Appendix cancer . . . . . . . . . . . . . . . . Appetite loss. . . . . . . . . . . . . . . . . . .
Contents . . . . . . . . . . . . . . . . . . . . . . . . v Publisher’s Note . . . . . . . . . . . . . . . . . . . . ix About the Editors . . . . . . . . . . . . . . . . . . . xi Contributors . . . . . . . . . . . . . . . . . . . . . xiii Complete List of Contents . . . . . . . . . . . . . . xv AACR. See American Association for Cancer Research ABCD. . . . . . . . . . . . . . . . . . . . . . . . . . 1 ACC. See Adenoid cystic carcinoma Abdominoperineal resection (APR) . . . . . . . . . . 1 Accelerated partial breast irradiation (APBI). . . . . . 3 Achlorhydria . . . . . . . . . . . . . . . . . . . . . . 4 Acoustic neuromas . . . . . . . . . . . . . . . . . . . 4 Acquired immunodeficiency disease-related cancers. See HIV/AIDS-related cancers Acrylamides . . . . . . . . . . . . . . . . . . . . . . 6 ACS. See American Cancer Society Acupuncture and acupressure for cancer patients . . . 8 Acute lymphocytic leukemia (ALL) . . . . . . . . . 11 Acute myelocytic leukemia (AML) . . . . . . . . . . 13 Adenocarcinomas . . . . . . . . . . . . . . . . . . . 16 Adenoid cystic carcinoma (ACC) . . . . . . . . . . . 17 Adenomatoid tumors . . . . . . . . . . . . . . . . . 18 Adenomatous polyps . . . . . . . . . . . . . . . . . 18 Adenoviruses . . . . . . . . . . . . . . . . . . . . . 19 Adjuvant therapy . . . . . . . . . . . . . . . . . . . 20 Adrenal gland cancers . . . . . . . . . . . . . . . . . 21 Adrenocortical cancer . . . . . . . . . . . . . . . . . 23 Advance directives . . . . . . . . . . . . . . . . . . 24 Aflatoxins . . . . . . . . . . . . . . . . . . . . . . . 26 AFP levels. See Alpha-fetoprotein levels African Americans and cancer . . . . . . . . . . . . 28 Africans and cancer . . . . . . . . . . . . . . . . . . 31 Afterloading radiation therapy . . . . . . . . . . . . 32 Agent Orange . . . . . . . . . . . . . . . . . . . . . 34 Aging and cancer . . . . . . . . . . . . . . . . . . . 34 AICR. See American Institute for Cancer Research Aids and devices for cancer patients . . . . . . . . . 38 AIDS-related cancers. See HIV/AIDS-related cancers Air pollution . . . . . . . . . . . . . . . . . . . . . . 39 Alcohol, alcoholism, and cancer . . . . . . . . . . . 42 Aleukemia . . . . . . . . . . . . . . . . . . . . . . . 43 Alkaline phosphatase test (ALP) . . . . . . . . . . . 44 lix
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64 66 68 69 70 71 71 72 73 75 76 78 81 83 86 88 90 93
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Salem Health: Cancer APR. See Abdominoperineal resection Arsenic compounds . . . . . . . . . . Arterial embolization . . . . . . . . . Artificial sweeteners . . . . . . . . . . Asbestos . . . . . . . . . . . . . . . . Ascites . . . . . . . . . . . . . . . . . Ashkenazi Jews and cancer . . . . . . Asian Americans and cancer. . . . . . Astrocytomas. . . . . . . . . . . . . . Ataxia telangiectasia (AT) . . . . . . . Autologous blood transfusion . . . . . Axillary dissection . . . . . . . . . . . Azathioprine . . . . . . . . . . . . . .
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100 101 102 103 105 107 109 112 114 115 116 117
Bacillus Calmette Guérin (BCG) . . . . . . . . Bacteria as causes of cancer . . . . . . . . . . . Barium enema . . . . . . . . . . . . . . . . . . Barium swallow . . . . . . . . . . . . . . . . . Barrett esophagus . . . . . . . . . . . . . . . . Basal cell carcinomas . . . . . . . . . . . . . . BCG. See Bacillus Calmette Guérin Beckwith-Wiedemann syndrome (BWS) . . . . Benign prostatic hyperplasia (BPH) . . . . . . . Benign tumors . . . . . . . . . . . . . . . . . . Benzene . . . . . . . . . . . . . . . . . . . . . Benzidine and dyes metabolized to benzidine . . Benzodiazepines . . . . . . . . . . . . . . . . . Bereavement, grief and. See Grief and bereavement Beryllium and beryllium compounds . . . . . . Beta-carotene . . . . . . . . . . . . . . . . . . Bethesda criteria . . . . . . . . . . . . . . . . . BHDS. See Birt-Hogg-Dubé syndrome Bile duct cancer . . . . . . . . . . . . . . . . . Bilobectomy . . . . . . . . . . . . . . . . . . . Bioflavonoids . . . . . . . . . . . . . . . . . . Biological therapy . . . . . . . . . . . . . . . . Biopsy. See also Computed tomography-guided biopsy; Core needle biopsy; Liver biopsy; Needle biopsies; Pleural biopsy; Stereotactic needle biopsy; Surgical biopsies . . . . . . . Birt-Hogg-Dubé syndrome (BHDS) . . . . . . . Birth control pills and cancer . . . . . . . . . . Bis(chloromethyl) ether and technical-grade chloromethyl methyl ether . . . . . . . . . . Bisphenol A (BPA) . . . . . . . . . . . . . . . Bisphosphonates . . . . . . . . . . . . . . . . . Bladder cancer . . . . . . . . . . . . . . . . . . Blood cancers . . . . . . . . . . . . . . . . . . BMT. See Bone marrow transplantation BNCT. See Boron neutron capture therapy
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118 118 120 121 123 124
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126 128 128 130 131 132
Body image. See Self-image and body image Bone cancers . . . . . . . . . . . . . . . . . . . Bone marrow aspiration and biopsy . . . . . . . Bone marrow transplantation (BMT) . . . . . . Bone pain . . . . . . . . . . . . . . . . . . . . Bone scan . . . . . . . . . . . . . . . . . . . . Boron neutron capture therapy (BNCT) . . . . . Bowen disease . . . . . . . . . . . . . . . . . . BPA. See Bisphenol A BPH. See Benign prostatic hyperplasia BPI. See Brief Pain Inventory Brachytherapy . . . . . . . . . . . . . . . . . . BRAF gene . . . . . . . . . . . . . . . . . . . . Brain and central nervous system cancers . . . . Brain scan . . . . . . . . . . . . . . . . . . . . BRCA1 and BRCA2 genes . . . . . . . . . . . . Breakthrough pain . . . . . . . . . . . . . . . . Breast, calcifications of. See Calcifications of the breast Breast, medullary carcinoma of. See Medullary carcinoma of the breast Breast cancer, cutaneous. See Cutaneous breast cancer Breast cancer, estrogen-receptor-sensitive. See Estrogen-receptor-sensitive breast cancer Breast cancer in children and adolescents . . . . Breast cancer in men . . . . . . . . . . . . . . . Breast cancer in pregnant women . . . . . . . . Breast cancers . . . . . . . . . . . . . . . . . . Breast implants. . . . . . . . . . . . . . . . . . Breast reconstruction. . . . . . . . . . . . . . . Breast self-examination (BSE). . . . . . . . . . Breast ultrasound. . . . . . . . . . . . . . . . . Breslow’s staging . . . . . . . . . . . . . . . . Brief Pain Inventory (BPI) . . . . . . . . . . . . Brompton cocktail . . . . . . . . . . . . . . . . Bronchial adenomas . . . . . . . . . . . . . . . Bronchoalveolar lung cancer . . . . . . . . . . Bronchography. . . . . . . . . . . . . . . . . . Bronchoscopy . . . . . . . . . . . . . . . . . . BSE. See Breast self-examination Burkitt lymphoma . . . . . . . . . . . . . . . . 1,3-Butadiene . . . . . . . . . . . . . . . . . . 1,4-Butanediol dimethanesulfonate . . . . . . . BWS. See Beckwith-Wiedemann syndrome
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136 138 138 139
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148 149 151 151 154
CA 15-3 test . CA 19-9 test . CA 27-29 test CA 125 test. . Cachexia . . . lx
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158 161 163 165 166 167 168
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180 182 184 185 188 190 193 194 195 196 196 197 197 199 199
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205 205 206 206 207
Complete List of Contents Cadmium and cadmium compounds. . . . . . . . Caffeine . . . . . . . . . . . . . . . . . . . . . . Calcifications of the breast. . . . . . . . . . . . . Calcium . . . . . . . . . . . . . . . . . . . . . . Cancell . . . . . . . . . . . . . . . . . . . . . . . Cancer biology . . . . . . . . . . . . . . . . . . . Cancer care team . . . . . . . . . . . . . . . . . . Cancer clusters . . . . . . . . . . . . . . . . . . . Cancer education. . . . . . . . . . . . . . . . . . Candidiasis . . . . . . . . . . . . . . . . . . . . . Carcinoembryonic antigen antibody (CEA) test . . . . . . . . . . . . . . . . . . . . . . . . Carcinogens, known . . . . . . . . . . . . . . . . Carcinogens, reasonably anticipated. . . . . . . . Carcinoid tumors and carcinoid syndrome . . . . Carcinoma of unknown primary origin (CUP) . . Carcinomas. . . . . . . . . . . . . . . . . . . . . Carcinomas, invasive ductal. See Invasive ductal carcinomas Carcinomas, invasive lobular. See Invasive lobular carcinomas Carcinomas, leptomeningeal. See Leptomeningeal carcinomas Carcinomatosis. . . . . . . . . . . . . . . . . . . Carcinomatous meningitis . . . . . . . . . . . . . Carcinosarcomas . . . . . . . . . . . . . . . . . . Cardiomyopathy in cancer patients . . . . . . . . Cardiopulmonary resuscitation (CPR) . . . . . . . Caregivers and caregiving . . . . . . . . . . . . . Caregiving, long-distance. See Long-distance caregiving Carney complex . . . . . . . . . . . . . . . . . . Carotenoids . . . . . . . . . . . . . . . . . . . . Cartilage supplements . . . . . . . . . . . . . . . Case management . . . . . . . . . . . . . . . . . Castleman disease . . . . . . . . . . . . . . . . . CBC. See Complete blood count CBE. See Clinical breast exam CDKN2A. See Cyclin-dependent kinase inhibitor-2A CEA test. See Carcinoembryonic antigen antibody test Cell phones. . . . . . . . . . . . . . . . . . . . . Cervical cancer. . . . . . . . . . . . . . . . . . . Chemoembolization . . . . . . . . . . . . . . . . Chemoprevention . . . . . . . . . . . . . . . . . Chemotherapy . . . . . . . . . . . . . . . . . . . Chemotherapy, cognitive effects of. See Cognitive effects of cancer and chemotherapy Chewing tobacco. . . . . . . . . . . . . . . . . . Childbirth and cancer . . . . . . . . . . . . . . .
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208 209 211 212 212 213 216 218 220 221
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223 224 227 230 232 233
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235 237 238 239 240 242
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245 245 246 247 248
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Childhood cancers . . . . . . . . . . . . . . . . Chlorambucil. . . . . . . . . . . . . . . . . . . 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)1-nitrosourea (MeCCNU) . . . . . . . . . . . Cholecystectomy . . . . . . . . . . . . . . . . . Chordomas . . . . . . . . . . . . . . . . . . . . Choriocarcinomas . . . . . . . . . . . . . . . . CHPP. See Continuous hyperthermic peritoneal perfusion Chromium hexavalent compounds. . . . . . . . Chromosomes and cancer . . . . . . . . . . . . Chronic lymphocytic leukemia (CLL) . . . . . . Chronic myeloid leukemia (CML). . . . . . . . Cigarettes and cigars . . . . . . . . . . . . . . . Clinical breast exam (CBE) . . . . . . . . . . . Clinical trials . . . . . . . . . . . . . . . . . . . CLL. See Chronic lymphocytic leukemia CML. See Chronic myeloid leukemia Coal tars and coal tar pitches . . . . . . . . . . Cobalt 60 radiation. . . . . . . . . . . . . . . . Coenzyme Q10. . . . . . . . . . . . . . . . . . Cognitive effects of cancer and chemotherapy . Coke oven emissions. . . . . . . . . . . . . . . Cold nodule . . . . . . . . . . . . . . . . . . . Colectomy . . . . . . . . . . . . . . . . . . . . Coloanal anastomosis . . . . . . . . . . . . . . Colon polyps . . . . . . . . . . . . . . . . . . . Colonoscopy and virtual colonoscopy . . . . . . Colony-stimulating factors (CSFs) . . . . . . . Colorectal cancer. . . . . . . . . . . . . . . . . Colorectal cancer screening . . . . . . . . . . . Colostomy . . . . . . . . . . . . . . . . . . . . Colposcopy. . . . . . . . . . . . . . . . . . . . Comedo carcinomas . . . . . . . . . . . . . . . Complementary and alternative therapies . . . . Complete blood count (CBC) . . . . . . . . . . Computed tomography (CT)-guided biopsy . . . . . . . . . . . . . . . . . . . . . Computed tomography (CT) scan . . . . . . . . Conization . . . . . . . . . . . . . . . . . . . . Continuous hyperthermic peritoneal perfusion (CHPP) . . . . . . . . . . . . . . . . . . . . Cordectomy . . . . . . . . . . . . . . . . . . . Cordotomy . . . . . . . . . . . . . . . . . . . . Core needle biopsy. . . . . . . . . . . . . . . . Corticosteroids . . . . . . . . . . . . . . . . . . Coughing . . . . . . . . . . . . . . . . . . . . . Counseling for cancer patients and survivors . . Cowden syndrome . . . . . . . . . . . . . . . . COX-2 inhibitors. See Cyclooxygenase 2 inhibitors
249 251 253 254 257
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274 274 276 279 281 283 285
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288 289 289 290 292 292 293 294 296 297 299 300 304 306 308 309 309 312
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318 318 319 321 321 322 324 326
Salem Health: Cancer CPR. See Cardiopulmonary resuscitation Craniopharyngiomas . . . . . . . . . . . . Craniosynostosis . . . . . . . . . . . . . . Craniotomy. . . . . . . . . . . . . . . . . Crohn disease . . . . . . . . . . . . . . . Cruciferous vegetables . . . . . . . . . . . Cryoablation . . . . . . . . . . . . . . . . Cryptorchidism. . . . . . . . . . . . . . . CSFs. See Colony-stimulating factors CT scan. See Computed tomography scan CTCL. See Cutaneous T-cell lymphoma Culdoscopy. . . . . . . . . . . . . . . . . CUP. See Carcinoma of unknown primary origin Curcumin. . . . . . . . . . . . . . . . . . Cushing syndrome and cancer . . . . . . . Cutaneous breast cancer . . . . . . . . . . Cutaneous T-cell lymphoma (CTCL) . . .
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Cyclin-dependent kinase inhibitor-2A (CDKN2A). . . . . . . . . . . . . . . Cyclooxygenase 2 (COX-2) inhibitors . Cyclophosphamide. . . . . . . . . . . . Cyclosporin A . . . . . . . . . . . . . . Cystography . . . . . . . . . . . . . . . Cystoscopy . . . . . . . . . . . . . . . . Cytogenetics . . . . . . . . . . . . . . . Cytokines . . . . . . . . . . . . . . . . Cytology . . . . . . . . . . . . . . . . . Cytology, sputum. See Sputum cytology
327 329 331 332 335 336 338
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344 344 345 346 347 347 348 350 350
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D&C. See Dilation and curettage Dana-Farber Cancer Institute . . . . . . . . . . . . 354 DCIS. See Ductal carcinoma in situ DEA. See Diethanolamine DEHP. See Di(2-ethylhexyl) phthalate Delta-9-tetrahydrocannabinol . . . . . . . . . . . . 355
339 340 341 342
Volume 2 Down syndrome and leukemia. . . . . . . . DPC4 gene testing . . . . . . . . . . . . . . DRE. See Digital rectal exam Drug resistance and multidrug resistance (MDR) . . . . . . . . . . . . . . . . . . . Dry mouth . . . . . . . . . . . . . . . . . . DSRCT. See Desmoplastic small round cell tumor Duct ectasia . . . . . . . . . . . . . . . . . Ductal carcinoma in situ (DCIS). . . . . . . Ductal lavage. . . . . . . . . . . . . . . . . Ductogram . . . . . . . . . . . . . . . . . . Duke Comprehensive Cancer Center . . . . Dukes’ classification . . . . . . . . . . . . . Duodenal carcinomas . . . . . . . . . . . . Dye, hair. See Hair dye Dysplastic nevus syndrome . . . . . . . . .
Contents . . . . . . . . . . . . . . . . . . . . . . xxxiii Complete List of Contents . . . . . . . . . . . . xxxvii Denys-Drash syndrome and cancer . . . . . . Depression . . . . . . . . . . . . . . . . . . . Dermatofibrosarcoma protuberans (DFSP) . . Dermatology oncology. . . . . . . . . . . . . DES. See Diethylstilbestrol Desmoid tumors . . . . . . . . . . . . . . . . Desmoplastic small round cell tumor (DSRCT) . . . . . . . . . . . . . . . . . . Developing nations and cancer . . . . . . . . DFSP. See Dermatofibrosarcoma protuberans Di(2-ethylhexyl) phthalate (DEHP) . . . . . . Diarrhea . . . . . . . . . . . . . . . . . . . . DIC. See Disseminated intravascular coagulation Dietary supplements . . . . . . . . . . . . . . Diethanolamine (DEA) . . . . . . . . . . . . Diethylstilbestrol (DES) . . . . . . . . . . . . Digital rectal exam (DRE) . . . . . . . . . . . Dilation and curettage (D&C) . . . . . . . . . Dioxins . . . . . . . . . . . . . . . . . . . . . Disseminated intravascular coagulation (DIC) . . . . . . . . . . . . . . . . . . . . Diverticulosis and diverticulitis . . . . . . . . DNR. See Do-not-resuscitate order Do-not-resuscitate (DNR) order . . . . . . . .
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357 357 360 362
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370 373 373 374 375 376
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386 387 389 389 390 392 393
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Eaton-Lambert syndrome. See Lambert-Eaton myasthenic syndrome EBRT. See External beam radiation therapy Edema . . . . . . . . . . . . . . . . . . . . . Education, cancer. See Cancer education Elderly and cancer . . . . . . . . . . . . . . . Electrolarynx . . . . . . . . . . . . . . . . . . Electromagnetic radiation . . . . . . . . . . . Electroporation therapy . . . . . . . . . . . . Electrosurgery . . . . . . . . . . . . . . . . .
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396 399 399 400 401
Complete List of Contents Embolization . . . . . . . . . . . . . . . . . . . . Embryonal cell cancer . . . . . . . . . . . . . . . End-of-life care . . . . . . . . . . . . . . . . . . Endocrine cancers . . . . . . . . . . . . . . . . . Endocrinology oncology . . . . . . . . . . . . . . Endometrial cancer . . . . . . . . . . . . . . . . Endometrial hyperplasia . . . . . . . . . . . . . . Endorectal ultrasound . . . . . . . . . . . . . . . Endoscopic retrograde cholangiopancreatography (ERCP) . . . . . . . . . . . . . . . . . . . . . Endoscopy . . . . . . . . . . . . . . . . . . . . . Endoscopy, upper gastrointestinal. See Upper gastrointestinal endoscopy Endotheliomas . . . . . . . . . . . . . . . . . . . Enteritis . . . . . . . . . . . . . . . . . . . . . . Enterostomal therapy . . . . . . . . . . . . . . . Eosinophilic leukemia . . . . . . . . . . . . . . . Ependymomas . . . . . . . . . . . . . . . . . . . Epidemiology of cancer . . . . . . . . . . . . . . Epidermoid cancers of mucous membranes . . . . Epstein-Barr virus . . . . . . . . . . . . . . . . . ERCP. See Endoscopic retrograde cholangiopancreatography ERD. See Estrogen receptor downregulator Erionite. . . . . . . . . . . . . . . . . . . . . . . Erythroplakia. . . . . . . . . . . . . . . . . . . . Esophageal cancer . . . . . . . . . . . . . . . . . Esophageal speech . . . . . . . . . . . . . . . . . Esophagectomy . . . . . . . . . . . . . . . . . . Esophagitis . . . . . . . . . . . . . . . . . . . . . Essiac . . . . . . . . . . . . . . . . . . . . . . . Estrogen receptor downregulator (ERD) . . . . . Estrogen-receptor-sensitive breast cancer . . . . . Ethnicity and cancer . . . . . . . . . . . . . . . . Ethylene oxide . . . . . . . . . . . . . . . . . . . Ewing sarcoma . . . . . . . . . . . . . . . . . . . Exenteration . . . . . . . . . . . . . . . . . . . . Exercise and cancer . . . . . . . . . . . . . . . . External beam radiation therapy (EBRT) . . . . . Eye cancers . . . . . . . . . . . . . . . . . . . . Eyelid cancer. . . . . . . . . . . . . . . . . . . .
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Fallopian tube cancer . . . . . . . Family history and risk assessment Fanconi anemia . . . . . . . . . . Fatigue . . . . . . . . . . . . . . . Fecal occult blood test (FOBT) . . Fertility drugs and cancer . . . . . Fertility issues . . . . . . . . . . . Fever . . . . . . . . . . . . . . . . Fiber . . . . . . . . . . . . . . . .
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402 403 404 406 409 412 414 416
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433 433 434 436 438 439 441 441 442 444 447 447 450 451 454 455 458
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460 461 464 466 467 469 471 472 474 lxiii
Fibroadenomas . . . . . . . . . . . . . . . . Fibrocystic breast changes . . . . . . . . . . Fibrosarcomas, soft-tissue . . . . . . . . . . Financial issues . . . . . . . . . . . . . . . 5HIAA test. See 5-Hydroxyindoleacetic acid test 5Q minus syndrome . . . . . . . . . . . . . Flow cytometry . . . . . . . . . . . . . . . FOBT. See Fecal occult blood test Folic acid. . . . . . . . . . . . . . . . . . . Formaldehyde . . . . . . . . . . . . . . . . Fox Chase Cancer Center . . . . . . . . . . Fred Hutchinson Cancer Research Center . . Free radicals . . . . . . . . . . . . . . . . . Fruits . . . . . . . . . . . . . . . . . . . . .
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475 476 478 481
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486 486 487 488 490 491
Gallbladder cancer . . . . . . . . . . . . . . Gallium scan . . . . . . . . . . . . . . . . . Gamma Knife . . . . . . . . . . . . . . . . Gardner syndrome . . . . . . . . . . . . . . Garlic and allicin . . . . . . . . . . . . . . . Gastric polyps . . . . . . . . . . . . . . . . Gastrinomas . . . . . . . . . . . . . . . . . Gastrointestinal cancers . . . . . . . . . . . Gastrointestinal complications of cancer treatment. . . . . . . . . . . . . . . . . . Gastrointestinal oncology . . . . . . . . . . Gastrointestinal stromal tumors (GISTs) . . GCTs. See Giant cell tumors Gene therapy . . . . . . . . . . . . . . . . . Genetic counseling . . . . . . . . . . . . . . Genetic testing . . . . . . . . . . . . . . . . Genetics of cancer . . . . . . . . . . . . . . Geography and cancer . . . . . . . . . . . . Germ-cell tumors . . . . . . . . . . . . . . Gerson therapy . . . . . . . . . . . . . . . . Gestational trophoblastic tumors (GTTs) . . Giant cell tumors (GCTs) . . . . . . . . . . Ginseng, panax. . . . . . . . . . . . . . . . GISTs. See Gastrointestinal stromal tumors Gleason grading system . . . . . . . . . . . Gliomas . . . . . . . . . . . . . . . . . . . Glomus tumors . . . . . . . . . . . . . . . . Glossectomy . . . . . . . . . . . . . . . . . Glutamine . . . . . . . . . . . . . . . . . . Gonioscopy . . . . . . . . . . . . . . . . . Grading of tumors . . . . . . . . . . . . . . Graft-versus-host disease (GVHD) . . . . . Granulosa cell tumors . . . . . . . . . . . . Green tea . . . . . . . . . . . . . . . . . . . Grief and bereavement . . . . . . . . . . . .
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493 495 497 498 499 500 501 502
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512 515 517 519 522 525 527 527 530 531
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532 533 534 535 536 536 537 538 540 540 541
Salem Health: Cancer GTTs. See Gestational trophoblastic tumors GVHD. See Graft-versus-host disease Gynecologic cancers . . . . . . . . . . . . . . . . . 543 Gynecologic oncology . . . . . . . . . . . . . . . . 547 H. pylori. See Helicobacter pylori HAI. See Hepatic arterial infusion Hair dye . . . . . . . . . . . . . . . . . . . . . . Hairy cell leukemia . . . . . . . . . . . . . . . . Hand-foot syndrome (HFS) . . . . . . . . . . . . HBV. See Hepatitis B virus HCG. See Human chorionic gonadotropin HCV. See Hepatitis C virus Head and neck cancers . . . . . . . . . . . . . . . Health maintenance organizations (HMOs) . . . . Helicobacter pylori. . . . . . . . . . . . . . . . . Hemangioblastomas . . . . . . . . . . . . . . . . Hemangiopericytomas . . . . . . . . . . . . . . . Hemangiosarcomas . . . . . . . . . . . . . . . . Hematemesis . . . . . . . . . . . . . . . . . . . . Hematologic oncology . . . . . . . . . . . . . . . Hematuria . . . . . . . . . . . . . . . . . . . . . Hemochromatosis . . . . . . . . . . . . . . . . . Hemolytic anemia . . . . . . . . . . . . . . . . . Hemoptysis. . . . . . . . . . . . . . . . . . . . . Hemorrhoids . . . . . . . . . . . . . . . . . . . . Hepatic arterial infusion (HAI) . . . . . . . . . . Hepatitis B virus (HBV) . . . . . . . . . . . . . . Hepatitis C virus (HCV) . . . . . . . . . . . . . . Hepatomegaly . . . . . . . . . . . . . . . . . . . HER2/neu protein . . . . . . . . . . . . . . . . . Herbs as antioxidants . . . . . . . . . . . . . . . Hereditary cancer syndromes . . . . . . . . . . . Hereditary diffuse gastric cancer . . . . . . . . . Hereditary leiomyomatosis and renal cell cancer (HLRCC) . . . . . . . . . . . . . . . . Hereditary mixed polyposis syndrome . . . . . . Hereditary non-VHL clear cell renal cell carcinomas . . . . . . . . . . . . . . . . . . . Hereditary pancreatitis . . . . . . . . . . . . . . . Hereditary papillary renal cell carcinomas . . . . Hereditary polyposis syndromes . . . . . . . . . . Herpes simplex virus. . . . . . . . . . . . . . . . Herpes zoster virus. . . . . . . . . . . . . . . . . HFS. See Hand-foot syndrome Hispanics and cancer. See Latinos/Hispanics and cancer Histamine 2 antagonists . . . . . . . . . . . . . . Histiocytosis X . . . . . . . . . . . . . . . . . . . HIV/AIDS-related cancers . . . . . . . . . . . . .
HLRCC. See Hereditary leiomyomatosis and renal cell cancer HMOs. See Health maintenance organizations Hodgkin disease . . . . . . . . . . . . . . . . . Home health services . . . . . . . . . . . . . . Hormonal therapies . . . . . . . . . . . . . . . Hormone receptor tests . . . . . . . . . . . . . Hormone replacement therapy (HRT) . . . . . . Horner syndrome. . . . . . . . . . . . . . . . . Hospice care . . . . . . . . . . . . . . . . . . . Hot flashes . . . . . . . . . . . . . . . . . . . . HPV. See Human papillomavirus HRAS gene testing . . . . . . . . . . . . . . . . HRT. See Hormone replacement therapy HTLV. See Human T-cell leukemia virus Human chorionic gonadotropin (HCG) . . . . . Human growth factors and tumor growth . . . . Human immunodeficiency virus-related cancers. See HIV/AIDS-related cancers Human papillomavirus (HPV) . . . . . . . . . . Human T-cell leukemia virus (HTLV) . . . . . Hydatidiform mole . . . . . . . . . . . . . . . . 5-Hydroxyindoleacetic acid (5HIAA) test . . . . Hypercalcemia . . . . . . . . . . . . . . . . . . Hypercoagulation disorders . . . . . . . . . . . Hyperthermia therapy . . . . . . . . . . . . . . Hyperthermic perfusion . . . . . . . . . . . . . Hypopharyngeal cancer . . . . . . . . . . . . . Hysterectomy . . . . . . . . . . . . . . . . . . Hysterography . . . . . . . . . . . . . . . . . . Hystero-oophorectomy. . . . . . . . . . . . . . Hysteroscopy. . . . . . . . . . . . . . . . . . .
. 550 . 550 . 552
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554 557 558 559 559 560 561 562 564 565 566 566 567 568 569 570 571 573 573 574 576
IEP. See Immunoelectrophoresis iFOBT. See Immunochemical fecal occult blood test Ileostomy. . . . . . . . . . . . . . . . . . . . . Imaging tests . . . . . . . . . . . . . . . . . . . Immune response to cancer . . . . . . . . . . . Immunochemical fecal occult blood test (iFOBT) . . . . . . . . . . . . . . . . . . . . Immunocytochemistry and immunohistochemistry . . . . . . . . . . . . Immunoelectrophoresis (IEP) . . . . . . . . . . Immunotherapy . . . . . . . . . . . . . . . . . IMRT. See Intensity-modulated radiation therapy Indoles . . . . . . . . . . . . . . . . . . . . . . Infection and sepsis . . . . . . . . . . . . . . . Infectious cancers . . . . . . . . . . . . . . . . Infertility and cancer . . . . . . . . . . . . . . .
. 577 . 579 . . . . . .
580 580 581 582 584 586
. 587 . 588 . 590 lxiv
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593 597 599 601 603 605 606 608
. . 609
. . 609 . . 610
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611 612 612 613 614 615 617 618 619 620 621 622 623
. . 625 . . 626 . . 629 . . 632 . . 633 . . 634 . . 635
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638 638 641 643
Complete List of Contents Inflammatory bowel disease . . . . . . . . . . Informed consent. . . . . . . . . . . . . . . . Infusion therapies . . . . . . . . . . . . . . . Insurance . . . . . . . . . . . . . . . . . . . . Integrative oncology . . . . . . . . . . . . . . Intensity-modulated radiation therapy (IMRT) Interferon. . . . . . . . . . . . . . . . . . . . Interleukins. . . . . . . . . . . . . . . . . . . Invasive cancer. . . . . . . . . . . . . . . . . Invasive ductal carcinomas . . . . . . . . . . Invasive lobular carcinomas . . . . . . . . . . Ionizing radiation . . . . . . . . . . . . . . . Iridium seeds . . . . . . . . . . . . . . . . . . Islet cell tumors . . . . . . . . . . . . . . . . Isoflavones . . . . . . . . . . . . . . . . . . . Itching . . . . . . . . . . . . . . . . . . . . .
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645 646 647 648 651 652 653 654 655 656 657 657 658 659 661 661
Lambert-Eaton myasthenic syndrome (LEMS) Laparoscopy and laparoscopic surgery . . . . Laryngeal cancer . . . . . . . . . . . . . . . . Laryngeal nerve palsy . . . . . . . . . . . . . Laryngectomy . . . . . . . . . . . . . . . . . Laryngoscopy . . . . . . . . . . . . . . . . . Laser therapies . . . . . . . . . . . . . . . . . Latinos/Hispanics and cancer . . . . . . . . . Laxatives . . . . . . . . . . . . . . . . . . . . LCIS. See Lobular carcinoma in situ LDH test. See Lactate dehydrogenase test Leiomyomas . . . . . . . . . . . . . . . . . . Leiomyosarcomas . . . . . . . . . . . . . . . LEMS. See Lambert-Eaton myasthenic syndrome Leptomeningeal carcinomas . . . . . . . . . . Leukapharesis . . . . . . . . . . . . . . . . . Leukemia, Down syndrome and. See Down syndrome and leukemia Leukemia, eosinophilic. See Eosinophilic leukemia Leukemia, hairy cell. See Hairy cell leukemia Leukemias . . . . . . . . . . . . . . . . . . . Leukoencephalopathy . . . . . . . . . . . . . Leukopenia. . . . . . . . . . . . . . . . . . . Leukoplakia . . . . . . . . . . . . . . . . . . Leydig cell tumors . . . . . . . . . . . . . . . Li-Fraumeni syndrome (LFS) . . . . . . . . . Limb salvage . . . . . . . . . . . . . . . . . . Linear accelerator . . . . . . . . . . . . . . . Lip cancers . . . . . . . . . . . . . . . . . . . Liposarcomas . . . . . . . . . . . . . . . . . Liver biopsy . . . . . . . . . . . . . . . . . . Liver cancers . . . . . . . . . . . . . . . . . .
Jonsson Comprehensive Cancer Center (JCCC) . . . . . . . . . . . . . . . . . . . . . . 664 Journaling . . . . . . . . . . . . . . . . . . . . . . 665 Juvenile polyposis syndrome . . . . . . . . . . . . 665 Kaposi sarcoma . . . . . . . . . . . . . Karnofsky performance status (KPS) . . Keratosis . . . . . . . . . . . . . . . . . Ki67 test . . . . . . . . . . . . . . . . . Kidney cancer . . . . . . . . . . . . . . Klinefelter syndrome and cancer . . . . KPS. See Karnofsky performance status Krukenberg tumors . . . . . . . . . . .
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667 669 670 670 671 674
. . . . . . 675
Lacrimal gland tumors . . . . . . . . . . . . . . . . 677 Lactate dehydrogenase (LDH) test . . . . . . . . . 678 Laetrile . . . . . . . . . . . . . . . . . . . . . . . . 679
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679 681 682 685 686 687 688 690 692
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. . . 696 . . . 698
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698 702 704 704 706 706 708 709 710 712 714 715
Volume 3 Lumps . . . . . . . . . . . . . . Lung cancer, brochoalveolar. See Bronchoalveolar lung cancer Lung cancers . . . . . . . . . . . Lutein . . . . . . . . . . . . . . Lycopene . . . . . . . . . . . . . Lymphadenectomy. . . . . . . . Lymphangiography . . . . . . . Lymphangiosarcomas . . . . . . Lymphedema. . . . . . . . . . . Lymphocytosis . . . . . . . . . . Lymphomas . . . . . . . . . . .
Contents . . . . . . . . . . . . . . . . . . . . . . . . lv Complete List of Contents . . . . . . . . . . . . . . lix Living will . . . . . . . . . . . . . . . . . Living with cancer . . . . . . . . . . . . . Lobectomy . . . . . . . . . . . . . . . . . Lobular carcinoma in situ (LCIS) . . . . . Long-distance caregiving . . . . . . . . . Loop electrosurgical excisional procedure (LEEP) . . . . . . . . . . . . . . . . . Lumbar puncture . . . . . . . . . . . . . . Lumpectomy . . . . . . . . . . . . . . . .
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719 720 723 725 726
. . . . . 727 . . . . . 728 . . . . . 730 lxv
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733 737 737 738 740 741 742 743 744
Salem Health: Cancer M. D. Anderson Cancer Center . . . . . . . . . Macrobiotic diet . . . . . . . . . . . . . . . . . Magnetic resonance imaging (MRI) . . . . . . . Malignant fibrous histiocytoma (MFH) . . . . . Malignant rhabdoid tumor of the kidney . . . . Malignant tumors . . . . . . . . . . . . . . . . MALT lymphomas. See Mucosa-associated lymphoid tissue lymphomas Mammography . . . . . . . . . . . . . . . . . . Managed care . . . . . . . . . . . . . . . . . . Mantle cell lymphoma (MCL) . . . . . . . . . . Mastectomy . . . . . . . . . . . . . . . . . . . Mastocytomas . . . . . . . . . . . . . . . . . . Matrix metalloproteinase inhibitors . . . . . . . Mayo Clinic Cancer Center . . . . . . . . . . . MCC. See Merkel cell carcinomas MCL. See Mantle cell lymphoma MDR. See Drug resistance and multidrug resistance Mediastinal tumors. . . . . . . . . . . . . . . . Mediastinoscopy . . . . . . . . . . . . . . . . . Medical marijuana . . . . . . . . . . . . . . . . Medical oncology . . . . . . . . . . . . . . . . Medicare and cancer . . . . . . . . . . . . . . . Medullary carcinoma of the breast. . . . . . . . Medulloblastomas . . . . . . . . . . . . . . . . Melanomas . . . . . . . . . . . . . . . . . . . . Melphalan . . . . . . . . . . . . . . . . . . . . Memorial Sloan-Kettering Cancer Center . . . . MEN 1. See Multiple endocrine neoplasia type 1 MEN 2. See Multiple endocrine neoplasia type 2 Meningeal carcinomatosis . . . . . . . . . . . . Meningiomas. . . . . . . . . . . . . . . . . . . Merkel cell carcinomas (MCC) . . . . . . . . . Mesenchymomas, malignant. . . . . . . . . . . Mesothelioma . . . . . . . . . . . . . . . . . . Metastasis . . . . . . . . . . . . . . . . . . . . Metastatic squamous neck cancer with occult primary . . . . . . . . . . . . . . . . . . . . MFH. See Malignant fibrous histiocytoma Microcalcifications. . . . . . . . . . . . . . . . Microwave hyperthermia therapy . . . . . . . . Mineral oils . . . . . . . . . . . . . . . . . . . Mistletoe . . . . . . . . . . . . . . . . . . . . . Mitochondrial DNA mutations. . . . . . . . . . MLH1 gene. . . . . . . . . . . . . . . . . . . . Mohs surgery. . . . . . . . . . . . . . . . . . . Molecular oncology . . . . . . . . . . . . . . . Moles. . . . . . . . . . . . . . . . . . . . . . . Monoclonal antibodies . . . . . . . . . . . . . . Motion sickness devices . . . . . . . . . . . . .
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748 750 750 752 753 754
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754 757 759 761 763 764 765
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766 768 768 770 772 774 775 776 779 780
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MRI. See Magnetic resonance imaging MSH genes . . . . . . . . . . . . . . . . . . . . Mucinous carcinomas . . . . . . . . . . . . . . Mucosa-associated lymphoid tissue (MALT) lymphomas . . . . . . . . . . . . . . . . . . Mucositis . . . . . . . . . . . . . . . . . . . . . Mucous membranes, epidermoid cancers of. See Epidermoid cancers of mucous membranes Multiple endocrine neoplasia type 1 (MEN 1). . Multiple endocrine neoplasia type 2 (MEN 2). . Multiple myeloma . . . . . . . . . . . . . . . . Mustard gas . . . . . . . . . . . . . . . . . . . Mutagenesis and cancer . . . . . . . . . . . . . Myasthenia gravis . . . . . . . . . . . . . . . . MYC oncogene . . . . . . . . . . . . . . . . . . Mycosis fungoides . . . . . . . . . . . . . . . . Myelodysplastic syndromes . . . . . . . . . . . Myelofibrosis . . . . . . . . . . . . . . . . . . Myeloma . . . . . . . . . . . . . . . . . . . . . Myeloproliferative disorders. . . . . . . . . . . Myelosuppression . . . . . . . . . . . . . . . . 2-Naphthylamine. . . . . . . . . . . . . . . . Nasal cavity and paranasal sinus cancers . . . National Cancer Institute (NCI) . . . . . . . . National Science Foundation (NSF) . . . . . . Native North Americans and cancer . . . . . . Nausea and vomiting. . . . . . . . . . . . . . NCI. See National Cancer Institute Needle biopsies . . . . . . . . . . . . . . . . Needle localization. . . . . . . . . . . . . . . Nephroblastomas. . . . . . . . . . . . . . . . Nephrostomy . . . . . . . . . . . . . . . . . . Neuroblastomas . . . . . . . . . . . . . . . . Neuroectodermal tumors. . . . . . . . . . . . Neuroendocrine tumors . . . . . . . . . . . . Neurofibromatosis type 1 (NF1) . . . . . . . . Neurologic oncology. . . . . . . . . . . . . . Neutropenia . . . . . . . . . . . . . . . . . . NF1. See Neurofibromatosis type 1 Nickel compounds and metallic nickel . . . . Night sweats . . . . . . . . . . . . . . . . . . Nijmegen breakage syndrome . . . . . . . . . Nipple discharge . . . . . . . . . . . . . . . . Non-Hodgkin lymphoma . . . . . . . . . . . Nonsteroidal anti-inflammatory drugs (NSAIDs) . . . . . . . . . . . . . . . . . . NSAIDs. See Nonsteroidal anti-inflammatory drugs NSF. See National Science Foundation Nuclear medicine scan . . . . . . . . . . . . .
781 782 783 785 786 788
. . 790 . . . . . . . . . . .
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790 791 792 793 794 795 796 796 798 800 802 lxvi
. . 803 . . 803 . . 804 . . 806
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807 808 809 812 813 815 817 817 819 820 822 823 825
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826 826 829 830 832 834
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836 838 839 839 841 842 844 845 847 849
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851 852 853 854 855
. . . 858
. . . 859
Complete List of Contents Pediatric oncology and hematology . . . . . . . . . 938 Pelvic examination . . . . . . . . . . . . . . . . . . 940 Penile cancer . . . . . . . . . . . . . . . . . . . . . 941 Percutaneous transhepatic cholangiography (PTHC) . . . . . . . . . . . . . . . . . . . . . . 943 Pericardial effusion . . . . . . . . . . . . . . . . . 944 Pericardiocentesis . . . . . . . . . . . . . . . . . . 946 Peritoneovenous shunts . . . . . . . . . . . . . . . 946 Personality and cancer . . . . . . . . . . . . . . . . 947 Pesticides and the food chain . . . . . . . . . . . . 948 PET. See Positron emission tomography Peutz-Jeghers syndrome (PJS) . . . . . . . . . . . . 951 Pharmacy oncology . . . . . . . . . . . . . . . . . 952 Phenacetin . . . . . . . . . . . . . . . . . . . . . . 955 Phenolics . . . . . . . . . . . . . . . . . . . . . . . 955 Pheochromocytomas . . . . . . . . . . . . . . . . . 956 Pheresis . . . . . . . . . . . . . . . . . . . . . . . 958 Photodynamic therapy (PDT) . . . . . . . . . . . . 959 Phyllodes tumors. . . . . . . . . . . . . . . . . . . 960 Phytoestrogens . . . . . . . . . . . . . . . . . . . . 962 Pineoblastomas. . . . . . . . . . . . . . . . . . . . 963 Pituitary tumors . . . . . . . . . . . . . . . . . . . 965 PJS. See Peutz-Jeghers syndrome Placental alkaline phosphatase (PALP) . . . . . . . 968 Plant alkaloids and terpenoids in chemotherapy . . . . . . . . . . . . . . . . . . . 968 Plasticizers . . . . . . . . . . . . . . . . . . . . . . 971 Pleural biopsy . . . . . . . . . . . . . . . . . . . . 972 Pleural effusion . . . . . . . . . . . . . . . . . . . 973 Pleurodesis . . . . . . . . . . . . . . . . . . . . . . 975 Pleuropulmonary blastomas . . . . . . . . . . . . . 975 PMS genes . . . . . . . . . . . . . . . . . . . . . . 976 Pneumonectomy . . . . . . . . . . . . . . . . . . . 977 Pneumonia . . . . . . . . . . . . . . . . . . . . . . 979 Polycyclic aromatic hydrocarbons . . . . . . . . . . 981 Polycythemia vera . . . . . . . . . . . . . . . . . . 981 Polypectomy . . . . . . . . . . . . . . . . . . . . . 982 Polyps . . . . . . . . . . . . . . . . . . . . . . . . 983 Polyps, colon. See Colon polyps Polyps, gastric. See Gastric polyps Positron emission tomography (PET) . . . . . . . . 984 Poverty and cancer . . . . . . . . . . . . . . . . . . 987 PPOs. See Preferred provider organizations Prayer and cancer support . . . . . . . . . . . . . . 989 Preferred provider organizations (PPOs) . . . . . . 990 Pregnancy and cancer . . . . . . . . . . . . . . . . 992 Premalignancies . . . . . . . . . . . . . . . . . . . 994 Prevent Cancer Foundation . . . . . . . . . . . . . 997 Prevention . . . . . . . . . . . . . . . . . . . . . . 999 Primary care physician . . . . . . . . . . . . . . . 1001
Nutrition and cancer prevention . . . . . . . . . . . 861 Nutrition and cancer treatment. . . . . . . . . . . . 864 Obesity-associated cancers . . . . . Occupational exposures and cancer . Occupational therapy . . . . . . . . OCs. See Organochlorines Oligodendrogliomas . . . . . . . . . Omega-3 fatty acids . . . . . . . . . Ommaya reservoir . . . . . . . . . . Oncogenes . . . . . . . . . . . . . . Oncogenic viruses . . . . . . . . . . Oncology . . . . . . . . . . . . . . . Oncology clinical nurse specialist . . Oncology social worker . . . . . . . Oophorectomy . . . . . . . . . . . . Ophthalmic oncology . . . . . . . . Opioids . . . . . . . . . . . . . . . . Oral and maxillofacial surgery. . . . Oral and oropharyngeal cancers . . . Orbit tumors . . . . . . . . . . . . . Orchiectomy . . . . . . . . . . . . . Organ transplantation and cancer . . Organochlorines (OCs) . . . . . . . Oropharyngeal cancers. See Oral and oropharyngeal cancers Orthopedic surgery. . . . . . . . . . Otolaryngology . . . . . . . . . . . Ovarian cancers . . . . . . . . . . . Ovarian cysts. . . . . . . . . . . . . Ovarian epithelial cancer . . . . . . Overtreatment . . . . . . . . . . . .
. . . . . . . . 868 . . . . . . . . 871 . . . . . . . . 873 . . . . . . . . . . . . . . . . .
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875 877 878 878 881 882 885 887 888 889 892 893 894 897 898 899 901
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902 903 905 908 909 911
Paget disease of bone . . . . . . . . . . . . . Pain management medications. . . . . . . . . Palliative treatment . . . . . . . . . . . . . . PALP. See Placental alkaline phosphatase Palpation . . . . . . . . . . . . . . . . . . . . Pancolitis . . . . . . . . . . . . . . . . . . . . Pancreatectomy . . . . . . . . . . . . . . . . Pancreatic cancers . . . . . . . . . . . . . . . Pancreatitis . . . . . . . . . . . . . . . . . . . Pap test . . . . . . . . . . . . . . . . . . . . . Paracentesis . . . . . . . . . . . . . . . . . . Paranasal sinus cancers. See Nasal cavity and paranasal sinus cancers Paraneoplastic syndromes . . . . . . . . . . . Parathyroid cancer . . . . . . . . . . . . . . . Pathology . . . . . . . . . . . . . . . . . . . PC-SPES . . . . . . . . . . . . . . . . . . . . PDT. See Photodynamic therapy
. . . 912 . . . 914 . . . 917 . . . . . . .
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920 920 921 923 927 928 929
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931 932 934 937 lxvii
Salem Health: Cancer Primary central nervous system lymphomas . . . . . . . . . . . . . . . . Progesterone receptor assay . . . . . . . . Prostate cancer . . . . . . . . . . . . . . . Prostate-specific antigen (PSA) test . . . . Prostatectomy. . . . . . . . . . . . . . . . Prostatitis . . . . . . . . . . . . . . . . . . Proteasome inhibitors. . . . . . . . . . . . Protein electrophoresis . . . . . . . . . . . Proteomics and cancer research . . . . . . Proton beam therapy . . . . . . . . . . . . Proto-oncogenes and carcinogenesis . . . . PSA test. See Prostate-specific antigen test Psycho-oncology . . . . . . . . . . . . . . Psychosocial aspects of cancer . . . . . . . PTHC. See Percutaneous transhepatic cholangiography Radiation, ionizing. See Ionizing radiation Radiation oncology . . . . . . . . . . . . . Radiation therapies . . . . . . . . . . . . . Radiation therapy, afterloading. See Afterloading radiation therapy Radical neck dissection . . . . . . . . . . . Radiofrequency ablation . . . . . . . . . . Radionuclide scan . . . . . . . . . . . . . Radiopharmaceuticals . . . . . . . . . . . Radon . . . . . . . . . . . . . . . . . . . . RB1 gene . . . . . . . . . . . . . . . . . . Receptor analysis . . . . . . . . . . . . . .
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1003 1003 1004 1006 1008 1009 1010 1010 1012 1014 1015
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. . . . 1021 . . . . 1023
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1027 1027 1030 1030 1032 1032 1033
Reconstructive surgery . . . . . . . . . . . . . . Rectal cancer . . . . . . . . . . . . . . . . . . . Recurrence . . . . . . . . . . . . . . . . . . . . Rehabilitation . . . . . . . . . . . . . . . . . . . Relationships . . . . . . . . . . . . . . . . . . . Renal pelvis tumors. . . . . . . . . . . . . . . . Report on Carcinogens (RoC) . . . . . . . . . . Resveratrol . . . . . . . . . . . . . . . . . . . . Retinoblastomas . . . . . . . . . . . . . . . . . Rhabdomyosarcomas . . . . . . . . . . . . . . . RhoGD12 gene . . . . . . . . . . . . . . . . . . Richter syndrome . . . . . . . . . . . . . . . . . Risk assessment, family history and. See Family history and risk assessment Risks for cancer. . . . . . . . . . . . . . . . . . Robert H. Lurie Cancer Center . . . . . . . . . . RoC. See Report on Carcinogens Rothmund-Thomson syndrome . . . . . . . . . .
. . . . . . . . . . . .
Salivary gland cancer . . . . . . . . . . . . . Salpingectomy and salpingo-oophorectomy . Sarcomas, soft-tissue . . . . . . . . . . . . . Saw palmetto . . . . . . . . . . . . . . . . . Schwannoma tumors . . . . . . . . . . . . . SCLC1 gene. . . . . . . . . . . . . . . . . . Screening, colorectal cancer. See Colorectal cancer screening Screening for cancer . . . . . . . . . . . . . Second opinions . . . . . . . . . . . . . . . Self-image and body image. . . . . . . . . .
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1034 1036 1038 1038 1041 1043 1044 1045 1046 1048 1050 1050
. 1052 . 1054 . 1056 1058 1060 1062 1065 1066 1067
. . . 1067 . . . 1070 . . . 1071
Volume 4 Sjögren syndrome. . . . . . . . . . . . . . . . Skin cancers . . . . . . . . . . . . . . . . . . SLN biopsy and mapping. See Sentinel lymph node biopsy and mapping Small intestine cancer . . . . . . . . . . . . . Smoking cessation . . . . . . . . . . . . . . . Social Security Disability Insurance (SSDI) . . Soft-tissue fibrosarcomas. See Fibrosarcomas, soft-tissue Soots . . . . . . . . . . . . . . . . . . . . . . Soy foods . . . . . . . . . . . . . . . . . . . . Spermatocytomas . . . . . . . . . . . . . . . . Spinal axis tumors . . . . . . . . . . . . . . . Spinal cord compression . . . . . . . . . . . . Splenectomy . . . . . . . . . . . . . . . . . . Sputum cytology . . . . . . . . . . . . . . . .
Contents . . . . . . . . . . . . . . . . . . . . . . lxxvii Complete List of Contents . . . . . . . . . . . . . lxxix Sentinel lymph node (SLN) biopsy and mapping . . . . . . . . . . . . . . . Sepsis. See Infection and sepsis Sertoli cell tumors . . . . . . . . . . . Sexuality and cancer . . . . . . . . . . Sézary syndrome . . . . . . . . . . . . SIADH. See Syndrome of inappropriate antidiuretic hormone production Side effects . . . . . . . . . . . . . . . Sigmoidoscopy . . . . . . . . . . . . . Silica, crystalline . . . . . . . . . . . . Simian virus 40 . . . . . . . . . . . . . Singlehood and cancer . . . . . . . . .
. . . . . . 1073 . . . . . . 1073 . . . . . . 1074 . . . . . . 1076
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1078 1082 1083 1084 1084 lxviii
. . 1086 . . 1088
. . 1091 . . 1093 . . 1096
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1097 1098 1099 1100 1102 1103 1105
Complete List of Contents Squamous cell carcinomas . . . . . . . . . . . SRS. See Stereotactic radiosurgery SSDI. See Social Security Disability Insurance Staging of cancer . . . . . . . . . . . . . . . . Statistics of cancer . . . . . . . . . . . . . . . Stem cell transplantation . . . . . . . . . . . . Stent therapy . . . . . . . . . . . . . . . . . . Stereotactic needle biopsy . . . . . . . . . . . Stereotactic radiosurgery (SRS) . . . . . . . . Sterility . . . . . . . . . . . . . . . . . . . . . Stomach cancers . . . . . . . . . . . . . . . . Stomatitis . . . . . . . . . . . . . . . . . . . . Stress management . . . . . . . . . . . . . . . Sunlamps . . . . . . . . . . . . . . . . . . . . Sun’s soup . . . . . . . . . . . . . . . . . . . Sunscreens . . . . . . . . . . . . . . . . . . . Superior vena cava syndrome . . . . . . . . . Support groups . . . . . . . . . . . . . . . . . Surgical biopsies . . . . . . . . . . . . . . . . Surgical oncology. . . . . . . . . . . . . . . . Survival rates . . . . . . . . . . . . . . . . . . Survivorship issues . . . . . . . . . . . . . . . Symptoms and cancer. . . . . . . . . . . . . . Syndrome of inappropriate antidiuretic hormone production (SIADH) . . . . . . . . Synovial sarcomas . . . . . . . . . . . . . . . Taste alteration . . . . . . . . . . . . . . Teratocarcinomas . . . . . . . . . . . . . Teratomas . . . . . . . . . . . . . . . . . Testicular cancer . . . . . . . . . . . . . Testicular self-examination (TSE) . . . . Thermal imaging . . . . . . . . . . . . . Thiotepa. . . . . . . . . . . . . . . . . . Thoracentesis . . . . . . . . . . . . . . . Thoracoscopy . . . . . . . . . . . . . . . Thoracotomy . . . . . . . . . . . . . . . Throat cancer . . . . . . . . . . . . . . . Thrombocytopenia . . . . . . . . . . . . Thymomas . . . . . . . . . . . . . . . . Thymus cancer . . . . . . . . . . . . . . Thyroid cancer . . . . . . . . . . . . . . Thyroid nuclear medicine scan . . . . . . TNF. See Tumor necrosis factor TNM staging . . . . . . . . . . . . . . . Tobacco, chewing. See Chewing tobacco Tobacco-related cancers . . . . . . . . . Topoisomerase inhibitors . . . . . . . . . TP53 protein . . . . . . . . . . . . . . . Tracheostomy . . . . . . . . . . . . . . . Transfusion therapy. . . . . . . . . . . .
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Transitional care . . . . . . . . . . . Transitional cell carcinomas . . . . . Transrectal ultrasound . . . . . . . . Transvaginal ultrasound . . . . . . . Trichilemmal carcinomas. . . . . . . TSE. See Testicular self-examination Tuberous sclerosis . . . . . . . . . . Tubular carcinomas . . . . . . . . . . Tumor flare . . . . . . . . . . . . . . Tumor lysis syndrome . . . . . . . . Tumor markers . . . . . . . . . . . . Tumor necrosis factor (TNF) . . . . . Tumor-suppressor genes . . . . . . . Turcot syndrome . . . . . . . . . . . Tyrosine kinase inhibitors . . . . . .
. . 1106
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1108 1111 1114 1116 1118 1119 1120 1121 1124 1125 1127 1128 1129 1130 1132 1135 1138 1140 1143 1144
. . 1147 . . 1149 . . . . . . . . . . . . . . . .
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1151 1152 1153 1154 1156 1157 1158 1158 1160 1161 1162 1164 1166 1167 1169 1172
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1182 1183 1185 1186 1187
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1187 1188 1189 1189 1191 1193 1194 1195 1196
Ultrasound, breast. See Breast ultrasound Ultrasound, endorectal. See Endorectal ultrasound Ultrasound, transrectal. See Transrectal ultrasound Ultrasound, transvaginal. See Transvaginal ultrasound Ultrasound tests . . . . . . . . . . . . . . . Ultraviolet radiation and related exposures Umbilical cord blood transplantation. . . . Upper gastrointestinal (GI) endoscopy . . . Upper gastrointestinal (GI) series . . . . . Urethral cancer . . . . . . . . . . . . . . . Urinalysis . . . . . . . . . . . . . . . . . . Urinary system cancers . . . . . . . . . . . Urography . . . . . . . . . . . . . . . . . Urologic oncology . . . . . . . . . . . . . Urostomy . . . . . . . . . . . . . . . . . . Uterine cancer . . . . . . . . . . . . . . .
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1199 1200 1201 1202 1203 1205 1207 1209 1213 1214 1216 1217
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1220 1221 1223 1225 1226
Vaccines, preventive . . . . . . . . . . . Vaccines, therapeutic . . . . . . . . . . . Vaginal cancer . . . . . . . . . . . . . . Vascular access tubes. . . . . . . . . . . Vasectomy and cancer . . . . . . . . . . Vegetables, cruciferous. See Cruciferous vegetables Veterinary oncology . . . . . . . . . . . VHL disease. See Von Hippel-Lindau disease Vinyl chloride . . . . . . . . . . . . . . Viral oncology . . . . . . . . . . . . . . Virus-related cancers . . . . . . . . . . . Von Hippel-Lindau (VHL) disease. . . . Vulvar cancer . . . . . . . . . . . . . . .
. . . . . 1173 . . . . .
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1174 1175 1177 1179 1180 lxix
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1230 1230 1232 1235 1237
Salem Health: Cancer WAGR syndrome. See Wilms’ tumor aniridiagenitourinary anomalies-mental retardation syndrome and cancer Waldenström macroglobulinemia (WM) . . . . . . 1240 Watchful waiting . . . . . . . . . . . . . . . . . . 1242 Weight loss . . . . . . . . . . . . . . . . . . . . . 1243 Wilms’ tumor . . . . . . . . . . . . . . . . . . . . 1245 Wilms’ tumor aniridia-genitourinary anomaliesmental retardation (WAGR) syndrome and cancer . . . . . . . . . . . . . . . . . . . . . . 1248 Wine and cancer . . . . . . . . . . . . . . . . . . 1250 Wire localization . . . . . . . . . . . . . . . . . . 1250 WM. See Waldenström macroglobulinemia Wood dust . . . . . . . . . . . . . . . . . . . . . 1251
Yolk sac carcinomas . . . . . . . . . . . . . . . . 1256 Young adult cancers . . . . . . . . . . . . . . . . 1256 Zollinger-Ellison syndrome . . . . . . . . . . . . 1260 Drugs by Generic Name . . . Drugs by Trade Name . . . . Associations and Agencies . . Cancer Centers and Hospitals Cancer Support Groups . . . . Carcinogens. . . . . . . . . . Glossary . . . . . . . . . . . Bibliography . . . . . . . . .
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1265 1309 1348 1352 1357 1362 1383 1400
Category List . . . . . . . . . . . . . . . . . . . . 1409 Index . . . . . . . . . . . . . . . . . . . . . . . . 1419
X-ray tests . . . . . . . . . . . . . . . . . . . . . 1252 Xeroderma pigmentosa . . . . . . . . . . . . . . . 1254
lxx
Volume IV Sentinel lymph node (SLN) biopsy and mapping — Zollinger-Ellison syndrome Appendixes Indexes Editor
Jeffrey A. Knight, Ph.D. Mount Holyoke College Medical Consultants
Laurie Jackson-Grusby, Ph.D. Children’s Hospital Boston, Harvard Medical School
Wendy White-Ryan, M.D., FAAP Golisano Children’s Hospital at Strong Memorial Hospital
SALEM PRESS, INC. Pasadena, California Hackensack, New Jersey
Editor in Chief: Dawn P. Dawson Editorial Director: Christina J. Moose Project Editors: Tracy Irons-Georges, Rowena Wildin Dehanke Editorial Assistant: Dana Garey
Production Editor: Joyce I. Buchea Acquisitions Editor: Mark Rehn Photo Editor: Cynthia Breslin Beres Design and Graphics: James Hutson Layout: William Zimmerman
Copyright © 2009, by Salem Press, Inc. All rights in this book are reserved. No part of this work may be used or reproduced in any manner whatsoever or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without written permission from the copyright owner except in the case of brief quotations embodied in critical articles and reviews or in the copying of images deemed to be freely licensed or in the public domain. For information address the publisher, Salem Press, Inc., P.O. Box 50062, Pasadena, California 91115. ∞ The paper used in these volumes conforms to the American National Standard for Permanence of Paper for Printed Library Materials, Z39.48-1992 (R1997). Note to Readers The material presented in Salem Health: Cancer is intended for broad informational and educational purposes. Readers who suspect that they or someone whom they know or provide caregiving for suffers from cancer or any other physical or psychological disorder, disease, or condition described in this set should contact a physician without delay; this work should not be used as a substitute for professional medical diagnosis or staging. Readers who are undergoing or about to undergo any treatment or procedure described in this set should refer to their physicians and other health care team members for guidance concerning preparation and possible effects. This set is not to be considered definitive on the covered topics, and readers should remember that the field of health care is characterized by a diversity of medical opinions and constant expansion in knowledge and understanding. Library of Congress Cataloging-in-Publication Data Salem health : cancer / Jeffrey A. Knight, Laurie Jackson-Grusby, Wendy White-Ryan. p. cm. Includes bibliographical references and index. ISBN 978-1-58765-505-0 (set : alk. paper) — ISBN 978-1-58765-506-7 (vol. 1 : alk. paper) — ISBN 978-1-58765-507-4 (vol. 2 : alk. paper) — ISBN 978-1-58765-508-1 (vol. 3 : alk. paper) — ISBN 978-1-58765-509-8 (vol. 4 : alk. paper) 1. Cancer. I. Knight, Jeffrey A., 1948- II. Jackson-Grusby, Laurie. III. White-Ryan, Wendy. RC265.S32 2008 616.99′4—dc22 2008030861
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Contents Superior vena cava syndrome . . . . . Support groups . . . . . . . . . . . . . Surgical biopsies . . . . . . . . . . . . Surgical oncology. . . . . . . . . . . . Survival rates . . . . . . . . . . . . . . Survivorship issues . . . . . . . . . . . Symptoms and cancer. . . . . . . . . . Syndrome of inappropriate antidiuretic hormone production (SIADH) . . . . Synovial sarcomas . . . . . . . . . . .
Complete List of Contents . . . . . . . . . . . . . lxxix Sentinel lymph node (SLN) biopsy and mapping . . . . . . . . . . . . . . . . . . . Sepsis. See Infection and sepsis Sertoli cell tumors . . . . . . . . . . . . . . . Sexuality and cancer . . . . . . . . . . . . . . Sézary syndrome . . . . . . . . . . . . . . . . SIADH. See Syndrome of inappropriate antidiuretic hormone production Side effects . . . . . . . . . . . . . . . . . . . Sigmoidoscopy . . . . . . . . . . . . . . . . . Silica, crystalline . . . . . . . . . . . . . . . . Simian virus 40 . . . . . . . . . . . . . . . . . Singlehood and cancer . . . . . . . . . . . . . Sjögren syndrome. . . . . . . . . . . . . . . . Skin cancers . . . . . . . . . . . . . . . . . . SLN biopsy and mapping. See Sentinel lymph node biopsy and mapping Small intestine cancer . . . . . . . . . . . . . Smoking cessation . . . . . . . . . . . . . . . Social Security Disability Insurance (SSDI) . . Soft-tissue fibrosarcomas. See Fibrosarcomas, soft-tissue Soots . . . . . . . . . . . . . . . . . . . . . . Soy foods . . . . . . . . . . . . . . . . . . . . Spermatocytomas . . . . . . . . . . . . . . . . Spinal axis tumors . . . . . . . . . . . . . . . Spinal cord compression . . . . . . . . . . . . Splenectomy . . . . . . . . . . . . . . . . . . Sputum cytology . . . . . . . . . . . . . . . . Squamous cell carcinomas . . . . . . . . . . . SRS. See Stereotactic radiosurgery SSDI. See Social Security Disability Insurance Staging of cancer . . . . . . . . . . . . . . . . Statistics of cancer . . . . . . . . . . . . . . . Stem cell transplantation . . . . . . . . . . . . Stent therapy . . . . . . . . . . . . . . . . . . Stereotactic needle biopsy . . . . . . . . . . . Stereotactic radiosurgery (SRS) . . . . . . . . Sterility . . . . . . . . . . . . . . . . . . . . . Stomach cancers . . . . . . . . . . . . . . . . Stomatitis . . . . . . . . . . . . . . . . . . . . Stress management . . . . . . . . . . . . . . . Sunlamps . . . . . . . . . . . . . . . . . . . . Sun’s soup . . . . . . . . . . . . . . . . . . . Sunscreens . . . . . . . . . . . . . . . . . . .
. . 1073 . . 1073 . . 1074 . . 1076
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1078 1082 1083 1084 1084 1086 1088
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1097 1098 1099 1100 1102 1103 1105 1106
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1108 1111 1114 1116 1118 1119 1120 1121 1124 1125 1127 1128 1129 lxxvii
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1130 1132 1135 1138 1140 1143 1144
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Taste alteration . . . . . . . . . . . . . . Teratocarcinomas . . . . . . . . . . . . . Teratomas . . . . . . . . . . . . . . . . . Testicular cancer . . . . . . . . . . . . . Testicular self-examination (TSE) . . . . Thermal imaging . . . . . . . . . . . . . Thiotepa. . . . . . . . . . . . . . . . . . Thoracentesis . . . . . . . . . . . . . . . Thoracoscopy . . . . . . . . . . . . . . . Thoracotomy . . . . . . . . . . . . . . . Throat cancer . . . . . . . . . . . . . . . Thrombocytopenia . . . . . . . . . . . . Thymomas . . . . . . . . . . . . . . . . Thymus cancer . . . . . . . . . . . . . . Thyroid cancer . . . . . . . . . . . . . . Thyroid nuclear medicine scan . . . . . . TNF. See Tumor necrosis factor TNM staging . . . . . . . . . . . . . . . Tobacco, chewing. See Chewing tobacco Tobacco-related cancers . . . . . . . . . Topoisomerase inhibitors . . . . . . . . . TP53 protein . . . . . . . . . . . . . . . Tracheostomy . . . . . . . . . . . . . . . Transfusion therapy. . . . . . . . . . . . Transitional care . . . . . . . . . . . . . Transitional cell carcinomas . . . . . . . Transrectal ultrasound . . . . . . . . . . Transvaginal ultrasound . . . . . . . . . Trichilemmal carcinomas. . . . . . . . . TSE. See Testicular self-examination Tuberous sclerosis . . . . . . . . . . . . Tubular carcinomas . . . . . . . . . . . . Tumor flare . . . . . . . . . . . . . . . . Tumor lysis syndrome . . . . . . . . . . Tumor markers . . . . . . . . . . . . . . Tumor necrosis factor (TNF) . . . . . . .
. . 1091 . . 1093 . . 1096
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1151 1152 1153 1154 1156 1157 1158 1158 1160 1161 1162 1164 1166 1167 1169 1172
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1174 1175 1177 1179 1180 1182 1183 1185 1186 1187
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1187 1188 1189 1189 1191 1193
Salem Health: Cancer Tumor-suppressor genes . . . . . . . . . . . . . . 1194 Turcot syndrome . . . . . . . . . . . . . . . . . . 1195 Tyrosine kinase inhibitors . . . . . . . . . . . . . 1196 Ultrasound, breast. See Breast ultrasound Ultrasound, endorectal. See Endorectal ultrasound Ultrasound, transrectal. See Transrectal ultrasound Ultrasound, transvaginal. See Transvaginal ultrasound Ultrasound tests . . . . . . . . . . . . . . . Ultraviolet radiation and related exposures Umbilical cord blood transplantation. . . . Upper gastrointestinal (GI) endoscopy . . . Upper gastrointestinal (GI) series . . . . . Urethral cancer . . . . . . . . . . . . . . . Urinalysis . . . . . . . . . . . . . . . . . . Urinary system cancers . . . . . . . . . . . Urography . . . . . . . . . . . . . . . . . Urologic oncology . . . . . . . . . . . . . Urostomy . . . . . . . . . . . . . . . . . . Uterine cancer . . . . . . . . . . . . . . . Vaccines, preventive . . . . . . . . . . . Vaccines, therapeutic . . . . . . . . . . . Vaginal cancer . . . . . . . . . . . . . . Vascular access tubes. . . . . . . . . . . Vasectomy and cancer . . . . . . . . . . Vegetables, cruciferous. See Cruciferous vegetables Veterinary oncology . . . . . . . . . . . VHL disease. See Von Hippel-Lindau disease Vinyl chloride . . . . . . . . . . . . . . Viral oncology . . . . . . . . . . . . . . Virus-related cancers . . . . . . . . . . .
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1199 1200 1201 1202 1203 1205 1207 1209 1213 1214 1216 1217
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1220 1221 1223 1225 1226
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Von Hippel-Lindau (VHL) disease. . . . . . . . . 1235 Vulvar cancer . . . . . . . . . . . . . . . . . . . . 1237 WAGR syndrome. See Wilms’ tumor aniridiagenitourinary anomalies-mental retardation syndrome and cancer Waldenström macroglobulinemia (WM) . . . . . . 1240 Watchful waiting . . . . . . . . . . . . . . . . . . 1242 Weight loss . . . . . . . . . . . . . . . . . . . . . 1243 Wilms’ tumor . . . . . . . . . . . . . . . . . . . . 1245 Wilms’ tumor aniridia-genitourinary anomaliesmental retardation (WAGR) syndrome and cancer . . . . . . . . . . . . . . . . . . . . . . 1248 Wine and cancer . . . . . . . . . . . . . . . . . . 1250 Wire localization . . . . . . . . . . . . . . . . . . 1250 WM. See Waldenström macroglobulinemia Wood dust . . . . . . . . . . . . . . . . . . . . . 1251 X-ray tests . . . . . . . . . . . . . . . . . . . . . 1252 Xeroderma pigmentosa . . . . . . . . . . . . . . . 1254 Yolk sac carcinomas . . . . . . . . . . . . . . . . 1256 Young adult cancers . . . . . . . . . . . . . . . . 1256 Zollinger-Ellison syndrome . . . . . . . . . . . . 1260 Drugs by Generic Name . . . Drugs by Trade Name . . . . Associations and Agencies . . Cancer Centers and Hospitals Cancer Support Groups . . . . Carcinogens. . . . . . . . . . Glossary . . . . . . . . . . . Bibliography . . . . . . . . .
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Category List . . . . . . . . . . . . . . . . . . . . 1409 Index . . . . . . . . . . . . . . . . . . . . . . . . 1419
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Complete List of Contents Volume 1 Alkylating agents in chemotherapy . . . . . . . ALL. See Acute lymphocytic leukemia Allicin, garlic and. See Garlic and allicin Alopecia . . . . . . . . . . . . . . . . . . . . . ALP. See Alkaline phosphatase test Alpha-fetoprotein (AFP) levels . . . . . . . . . Alternative therapies. See Complementary and alternative therapies Alveolar soft-part sarcomas . . . . . . . . . . . Amenorrhea . . . . . . . . . . . . . . . . . . . American Association for Cancer Research (AACR) . . . . . . . . . . . . . . . . . . . . American Cancer Society (ACS) . . . . . . . . American Institute for Cancer Research (AICR) 4-Aminobiphenyl . . . . . . . . . . . . . . . . AML. See Acute myelocytic leukemia Amputation . . . . . . . . . . . . . . . . . . . Amyloidosis . . . . . . . . . . . . . . . . . . . Anal cancer . . . . . . . . . . . . . . . . . . . Androgen drugs . . . . . . . . . . . . . . . . . Anemia . . . . . . . . . . . . . . . . . . . . . Anemia, aplastic. See Aplastic anemia Anemia, hemolytic. See Hemolytic anemia Angiogenesis . . . . . . . . . . . . . . . . . . Angiogenesis inhibitors . . . . . . . . . . . . . Angiography. . . . . . . . . . . . . . . . . . . Angiosarcomas . . . . . . . . . . . . . . . . . Anoscopy . . . . . . . . . . . . . . . . . . . . Anthraquinones . . . . . . . . . . . . . . . . . Anthrax . . . . . . . . . . . . . . . . . . . . . Antiandrogens . . . . . . . . . . . . . . . . . . Antidiarrheal agents . . . . . . . . . . . . . . . Antiestrogens . . . . . . . . . . . . . . . . . . Antifungal therapies . . . . . . . . . . . . . . . Antimetabolites in chemotherapy . . . . . . . . Antinausea medications . . . . . . . . . . . . . Antineoplastics in chemotherapy . . . . . . . . Antioxidants . . . . . . . . . . . . . . . . . . . Antiperspirants and breast cancer . . . . . . . . Antiviral therapies. . . . . . . . . . . . . . . . Anxiety . . . . . . . . . . . . . . . . . . . . . APBI. See Accelerated partial breast irradiation APC gene testing . . . . . . . . . . . . . . . . Aplastic anemia . . . . . . . . . . . . . . . . . Appendix cancer . . . . . . . . . . . . . . . . Appetite loss. . . . . . . . . . . . . . . . . . .
Contents . . . . . . . . . . . . . . . . . . . . . . . . v Publisher’s Note . . . . . . . . . . . . . . . . . . . . ix About the Editors . . . . . . . . . . . . . . . . . . . xi Contributors . . . . . . . . . . . . . . . . . . . . . xiii Complete List of Contents . . . . . . . . . . . . . . xv AACR. See American Association for Cancer Research ABCD. . . . . . . . . . . . . . . . . . . . . . . . . . 1 ACC. See Adenoid cystic carcinoma Abdominoperineal resection (APR) . . . . . . . . . . 1 Accelerated partial breast irradiation (APBI). . . . . . 3 Achlorhydria . . . . . . . . . . . . . . . . . . . . . . 4 Acoustic neuromas . . . . . . . . . . . . . . . . . . . 4 Acquired immunodeficiency disease-related cancers. See HIV/AIDS-related cancers Acrylamides . . . . . . . . . . . . . . . . . . . . . . 6 ACS. See American Cancer Society Acupuncture and acupressure for cancer patients . . . 8 Acute lymphocytic leukemia (ALL) . . . . . . . . . 11 Acute myelocytic leukemia (AML) . . . . . . . . . . 13 Adenocarcinomas . . . . . . . . . . . . . . . . . . . 16 Adenoid cystic carcinoma (ACC) . . . . . . . . . . . 17 Adenomatoid tumors . . . . . . . . . . . . . . . . . 18 Adenomatous polyps . . . . . . . . . . . . . . . . . 18 Adenoviruses . . . . . . . . . . . . . . . . . . . . . 19 Adjuvant therapy . . . . . . . . . . . . . . . . . . . 20 Adrenal gland cancers . . . . . . . . . . . . . . . . . 21 Adrenocortical cancer . . . . . . . . . . . . . . . . . 23 Advance directives . . . . . . . . . . . . . . . . . . 24 Aflatoxins . . . . . . . . . . . . . . . . . . . . . . . 26 AFP levels. See Alpha-fetoprotein levels African Americans and cancer . . . . . . . . . . . . 28 Africans and cancer . . . . . . . . . . . . . . . . . . 31 Afterloading radiation therapy . . . . . . . . . . . . 32 Agent Orange . . . . . . . . . . . . . . . . . . . . . 34 Aging and cancer . . . . . . . . . . . . . . . . . . . 34 AICR. See American Institute for Cancer Research Aids and devices for cancer patients . . . . . . . . . 38 AIDS-related cancers. See HIV/AIDS-related cancers Air pollution . . . . . . . . . . . . . . . . . . . . . . 39 Alcohol, alcoholism, and cancer . . . . . . . . . . . 42 Aleukemia . . . . . . . . . . . . . . . . . . . . . . . 43 Alkaline phosphatase test (ALP) . . . . . . . . . . . 44 lxxix
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64 66 68 69 70 71 71 72 73 75 76 78 81 83 86 88 90 93
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Salem Health: Cancer APR. See Abdominoperineal resection Arsenic compounds . . . . . . . . . . Arterial embolization . . . . . . . . . Artificial sweeteners . . . . . . . . . . Asbestos . . . . . . . . . . . . . . . . Ascites . . . . . . . . . . . . . . . . . Ashkenazi Jews and cancer . . . . . . Asian Americans and cancer. . . . . . Astrocytomas. . . . . . . . . . . . . . Ataxia telangiectasia (AT) . . . . . . . Autologous blood transfusion . . . . . Axillary dissection . . . . . . . . . . . Azathioprine . . . . . . . . . . . . . .
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Bacillus Calmette Guérin (BCG) . . . . . . . . Bacteria as causes of cancer . . . . . . . . . . . Barium enema . . . . . . . . . . . . . . . . . . Barium swallow . . . . . . . . . . . . . . . . . Barrett esophagus . . . . . . . . . . . . . . . . Basal cell carcinomas . . . . . . . . . . . . . . BCG. See Bacillus Calmette Guérin Beckwith-Wiedemann syndrome (BWS) . . . . Benign prostatic hyperplasia (BPH) . . . . . . . Benign tumors . . . . . . . . . . . . . . . . . . Benzene . . . . . . . . . . . . . . . . . . . . . Benzidine and dyes metabolized to benzidine . . Benzodiazepines . . . . . . . . . . . . . . . . . Bereavement, grief and. See Grief and bereavement Beryllium and beryllium compounds . . . . . . Beta-carotene . . . . . . . . . . . . . . . . . . Bethesda criteria . . . . . . . . . . . . . . . . . BHDS. See Birt-Hogg-Dubé syndrome Bile duct cancer . . . . . . . . . . . . . . . . . Bilobectomy . . . . . . . . . . . . . . . . . . . Bioflavonoids . . . . . . . . . . . . . . . . . . Biological therapy . . . . . . . . . . . . . . . . Biopsy. See also Computed tomography-guided biopsy; Core needle biopsy; Liver biopsy; Needle biopsies; Pleural biopsy; Stereotactic needle biopsy; Surgical biopsies . . . . . . . Birt-Hogg-Dubé syndrome (BHDS) . . . . . . . Birth control pills and cancer . . . . . . . . . . Bis(chloromethyl) ether and technical-grade chloromethyl methyl ether . . . . . . . . . . Bisphenol A (BPA) . . . . . . . . . . . . . . . Bisphosphonates . . . . . . . . . . . . . . . . . Bladder cancer . . . . . . . . . . . . . . . . . . Blood cancers . . . . . . . . . . . . . . . . . . BMT. See Bone marrow transplantation BNCT. See Boron neutron capture therapy
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Body image. See Self-image and body image Bone cancers . . . . . . . . . . . . . . . . . . . Bone marrow aspiration and biopsy . . . . . . . Bone marrow transplantation (BMT) . . . . . . Bone pain . . . . . . . . . . . . . . . . . . . . Bone scan . . . . . . . . . . . . . . . . . . . . Boron neutron capture therapy (BNCT) . . . . . Bowen disease . . . . . . . . . . . . . . . . . . BPA. See Bisphenol A BPH. See Benign prostatic hyperplasia BPI. See Brief Pain Inventory Brachytherapy . . . . . . . . . . . . . . . . . . BRAF gene . . . . . . . . . . . . . . . . . . . . Brain and central nervous system cancers . . . . Brain scan . . . . . . . . . . . . . . . . . . . . BRCA1 and BRCA2 genes . . . . . . . . . . . . Breakthrough pain . . . . . . . . . . . . . . . . Breast, calcifications of. See Calcifications of the breast Breast, medullary carcinoma of. See Medullary carcinoma of the breast Breast cancer, cutaneous. See Cutaneous breast cancer Breast cancer, estrogen-receptor-sensitive. See Estrogen-receptor-sensitive breast cancer Breast cancer in children and adolescents . . . . Breast cancer in men . . . . . . . . . . . . . . . Breast cancer in pregnant women . . . . . . . . Breast cancers . . . . . . . . . . . . . . . . . . Breast implants. . . . . . . . . . . . . . . . . . Breast reconstruction. . . . . . . . . . . . . . . Breast self-examination (BSE). . . . . . . . . . Breast ultrasound. . . . . . . . . . . . . . . . . Breslow’s staging . . . . . . . . . . . . . . . . Brief Pain Inventory (BPI) . . . . . . . . . . . . Brompton cocktail . . . . . . . . . . . . . . . . Bronchial adenomas . . . . . . . . . . . . . . . Bronchoalveolar lung cancer . . . . . . . . . . Bronchography. . . . . . . . . . . . . . . . . . Bronchoscopy . . . . . . . . . . . . . . . . . . BSE. See Breast self-examination Burkitt lymphoma . . . . . . . . . . . . . . . . 1,3-Butadiene . . . . . . . . . . . . . . . . . . 1,4-Butanediol dimethanesulfonate . . . . . . . BWS. See Beckwith-Wiedemann syndrome
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CA 15-3 test . CA 19-9 test . CA 27-29 test CA 125 test. . Cachexia . . . lxxx
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Complete List of Contents Cadmium and cadmium compounds. . . . . . . . Caffeine . . . . . . . . . . . . . . . . . . . . . . Calcifications of the breast. . . . . . . . . . . . . Calcium . . . . . . . . . . . . . . . . . . . . . . Cancell . . . . . . . . . . . . . . . . . . . . . . . Cancer biology . . . . . . . . . . . . . . . . . . . Cancer care team . . . . . . . . . . . . . . . . . . Cancer clusters . . . . . . . . . . . . . . . . . . . Cancer education. . . . . . . . . . . . . . . . . . Candidiasis . . . . . . . . . . . . . . . . . . . . . Carcinoembryonic antigen antibody (CEA) test . . . . . . . . . . . . . . . . . . . . . . . . Carcinogens, known . . . . . . . . . . . . . . . . Carcinogens, reasonably anticipated. . . . . . . . Carcinoid tumors and carcinoid syndrome . . . . Carcinoma of unknown primary origin (CUP) . . Carcinomas. . . . . . . . . . . . . . . . . . . . . Carcinomas, invasive ductal. See Invasive ductal carcinomas Carcinomas, invasive lobular. See Invasive lobular carcinomas Carcinomas, leptomeningeal. See Leptomeningeal carcinomas Carcinomatosis. . . . . . . . . . . . . . . . . . . Carcinomatous meningitis . . . . . . . . . . . . . Carcinosarcomas . . . . . . . . . . . . . . . . . . Cardiomyopathy in cancer patients . . . . . . . . Cardiopulmonary resuscitation (CPR) . . . . . . . Caregivers and caregiving . . . . . . . . . . . . . Caregiving, long-distance. See Long-distance caregiving Carney complex . . . . . . . . . . . . . . . . . . Carotenoids . . . . . . . . . . . . . . . . . . . . Cartilage supplements . . . . . . . . . . . . . . . Case management . . . . . . . . . . . . . . . . . Castleman disease . . . . . . . . . . . . . . . . . CBC. See Complete blood count CBE. See Clinical breast exam CDKN2A. See Cyclin-dependent kinase inhibitor-2A CEA test. See Carcinoembryonic antigen antibody test Cell phones. . . . . . . . . . . . . . . . . . . . . Cervical cancer. . . . . . . . . . . . . . . . . . . Chemoembolization . . . . . . . . . . . . . . . . Chemoprevention . . . . . . . . . . . . . . . . . Chemotherapy . . . . . . . . . . . . . . . . . . . Chemotherapy, cognitive effects of. See Cognitive effects of cancer and chemotherapy Chewing tobacco. . . . . . . . . . . . . . . . . . Childbirth and cancer . . . . . . . . . . . . . . .
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208 209 211 212 212 213 216 218 220 221
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Childhood cancers . . . . . . . . . . . . . . . . Chlorambucil. . . . . . . . . . . . . . . . . . . 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)1-nitrosourea (MeCCNU) . . . . . . . . . . . Cholecystectomy . . . . . . . . . . . . . . . . . Chordomas . . . . . . . . . . . . . . . . . . . . Choriocarcinomas . . . . . . . . . . . . . . . . CHPP. See Continuous hyperthermic peritoneal perfusion Chromium hexavalent compounds. . . . . . . . Chromosomes and cancer . . . . . . . . . . . . Chronic lymphocytic leukemia (CLL) . . . . . . Chronic myeloid leukemia (CML). . . . . . . . Cigarettes and cigars . . . . . . . . . . . . . . . Clinical breast exam (CBE) . . . . . . . . . . . Clinical trials . . . . . . . . . . . . . . . . . . . CLL. See Chronic lymphocytic leukemia CML. See Chronic myeloid leukemia Coal tars and coal tar pitches . . . . . . . . . . Cobalt 60 radiation. . . . . . . . . . . . . . . . Coenzyme Q10. . . . . . . . . . . . . . . . . . Cognitive effects of cancer and chemotherapy . Coke oven emissions. . . . . . . . . . . . . . . Cold nodule . . . . . . . . . . . . . . . . . . . Colectomy . . . . . . . . . . . . . . . . . . . . Coloanal anastomosis . . . . . . . . . . . . . . Colon polyps . . . . . . . . . . . . . . . . . . . Colonoscopy and virtual colonoscopy . . . . . . Colony-stimulating factors (CSFs) . . . . . . . Colorectal cancer. . . . . . . . . . . . . . . . . Colorectal cancer screening . . . . . . . . . . . Colostomy . . . . . . . . . . . . . . . . . . . . Colposcopy. . . . . . . . . . . . . . . . . . . . Comedo carcinomas . . . . . . . . . . . . . . . Complementary and alternative therapies . . . . Complete blood count (CBC) . . . . . . . . . . Computed tomography (CT)-guided biopsy . . . . . . . . . . . . . . . . . . . . . Computed tomography (CT) scan . . . . . . . . Conization . . . . . . . . . . . . . . . . . . . . Continuous hyperthermic peritoneal perfusion (CHPP) . . . . . . . . . . . . . . . . . . . . Cordectomy . . . . . . . . . . . . . . . . . . . Cordotomy . . . . . . . . . . . . . . . . . . . . Core needle biopsy. . . . . . . . . . . . . . . . Corticosteroids . . . . . . . . . . . . . . . . . . Coughing . . . . . . . . . . . . . . . . . . . . . Counseling for cancer patients and survivors . . Cowden syndrome . . . . . . . . . . . . . . . . COX-2 inhibitors. See Cyclooxygenase 2 inhibitors
249 251 253 254 257
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288 289 289 290 292 292 293 294 296 297 299 300 304 306 308 309 309 312
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318 318 319 321 321 322 324 326
Salem Health: Cancer CPR. See Cardiopulmonary resuscitation Craniopharyngiomas . . . . . . . . . . . . Craniosynostosis . . . . . . . . . . . . . . Craniotomy. . . . . . . . . . . . . . . . . Crohn disease . . . . . . . . . . . . . . . Cruciferous vegetables . . . . . . . . . . . Cryoablation . . . . . . . . . . . . . . . . Cryptorchidism. . . . . . . . . . . . . . . CSFs. See Colony-stimulating factors CT scan. See Computed tomography scan CTCL. See Cutaneous T-cell lymphoma Culdoscopy. . . . . . . . . . . . . . . . . CUP. See Carcinoma of unknown primary origin Curcumin. . . . . . . . . . . . . . . . . . Cushing syndrome and cancer . . . . . . . Cutaneous breast cancer . . . . . . . . . . Cutaneous T-cell lymphoma (CTCL) . . .
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Cyclin-dependent kinase inhibitor-2A (CDKN2A). . . . . . . . . . . . . . . Cyclooxygenase 2 (COX-2) inhibitors . Cyclophosphamide. . . . . . . . . . . . Cyclosporin A . . . . . . . . . . . . . . Cystography . . . . . . . . . . . . . . . Cystoscopy . . . . . . . . . . . . . . . . Cytogenetics . . . . . . . . . . . . . . . Cytokines . . . . . . . . . . . . . . . . Cytology . . . . . . . . . . . . . . . . . Cytology, sputum. See Sputum cytology
327 329 331 332 335 336 338
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344 344 345 346 347 347 348 350 350
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D&C. See Dilation and curettage Dana-Farber Cancer Institute . . . . . . . . . . . . 354 DCIS. See Ductal carcinoma in situ DEA. See Diethanolamine DEHP. See Di(2-ethylhexyl) phthalate Delta-9-tetrahydrocannabinol . . . . . . . . . . . . 355
339 340 341 342
Volume 2 Down syndrome and leukemia. . . . . . . . DPC4 gene testing . . . . . . . . . . . . . . DRE. See Digital rectal exam Drug resistance and multidrug resistance (MDR) . . . . . . . . . . . . . . . . . . . Dry mouth . . . . . . . . . . . . . . . . . . DSRCT. See Desmoplastic small round cell tumor Duct ectasia . . . . . . . . . . . . . . . . . Ductal carcinoma in situ (DCIS). . . . . . . Ductal lavage. . . . . . . . . . . . . . . . . Ductogram . . . . . . . . . . . . . . . . . . Duke Comprehensive Cancer Center . . . . Dukes’ classification . . . . . . . . . . . . . Duodenal carcinomas . . . . . . . . . . . . Dye, hair. See Hair dye Dysplastic nevus syndrome . . . . . . . . .
Contents . . . . . . . . . . . . . . . . . . . . . . xxxiii Complete List of Contents . . . . . . . . . . . . xxxvii Denys-Drash syndrome and cancer . . . . . . Depression . . . . . . . . . . . . . . . . . . . Dermatofibrosarcoma protuberans (DFSP) . . Dermatology oncology. . . . . . . . . . . . . DES. See Diethylstilbestrol Desmoid tumors . . . . . . . . . . . . . . . . Desmoplastic small round cell tumor (DSRCT) . . . . . . . . . . . . . . . . . . Developing nations and cancer . . . . . . . . DFSP. See Dermatofibrosarcoma protuberans Di(2-ethylhexyl) phthalate (DEHP) . . . . . . Diarrhea . . . . . . . . . . . . . . . . . . . . DIC. See Disseminated intravascular coagulation Dietary supplements . . . . . . . . . . . . . . Diethanolamine (DEA) . . . . . . . . . . . . Diethylstilbestrol (DES) . . . . . . . . . . . . Digital rectal exam (DRE) . . . . . . . . . . . Dilation and curettage (D&C) . . . . . . . . . Dioxins . . . . . . . . . . . . . . . . . . . . . Disseminated intravascular coagulation (DIC) . . . . . . . . . . . . . . . . . . . . Diverticulosis and diverticulitis . . . . . . . . DNR. See Do-not-resuscitate order Do-not-resuscitate (DNR) order . . . . . . . .
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386 387 389 389 390 392 393
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Eaton-Lambert syndrome. See Lambert-Eaton myasthenic syndrome EBRT. See External beam radiation therapy Edema . . . . . . . . . . . . . . . . . . . . . Education, cancer. See Cancer education Elderly and cancer . . . . . . . . . . . . . . . Electrolarynx . . . . . . . . . . . . . . . . . . Electromagnetic radiation . . . . . . . . . . . Electroporation therapy . . . . . . . . . . . . Electrosurgery . . . . . . . . . . . . . . . . .
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396 399 399 400 401
Complete List of Contents Embolization . . . . . . . . . . . . . . . . . . . . Embryonal cell cancer . . . . . . . . . . . . . . . End-of-life care . . . . . . . . . . . . . . . . . . Endocrine cancers . . . . . . . . . . . . . . . . . Endocrinology oncology . . . . . . . . . . . . . . Endometrial cancer . . . . . . . . . . . . . . . . Endometrial hyperplasia . . . . . . . . . . . . . . Endorectal ultrasound . . . . . . . . . . . . . . . Endoscopic retrograde cholangiopancreatography (ERCP) . . . . . . . . . . . . . . . . . . . . . Endoscopy . . . . . . . . . . . . . . . . . . . . . Endoscopy, upper gastrointestinal. See Upper gastrointestinal endoscopy Endotheliomas . . . . . . . . . . . . . . . . . . . Enteritis . . . . . . . . . . . . . . . . . . . . . . Enterostomal therapy . . . . . . . . . . . . . . . Eosinophilic leukemia . . . . . . . . . . . . . . . Ependymomas . . . . . . . . . . . . . . . . . . . Epidemiology of cancer . . . . . . . . . . . . . . Epidermoid cancers of mucous membranes . . . . Epstein-Barr virus . . . . . . . . . . . . . . . . . ERCP. See Endoscopic retrograde cholangiopancreatography ERD. See Estrogen receptor downregulator Erionite. . . . . . . . . . . . . . . . . . . . . . . Erythroplakia. . . . . . . . . . . . . . . . . . . . Esophageal cancer . . . . . . . . . . . . . . . . . Esophageal speech . . . . . . . . . . . . . . . . . Esophagectomy . . . . . . . . . . . . . . . . . . Esophagitis . . . . . . . . . . . . . . . . . . . . . Essiac . . . . . . . . . . . . . . . . . . . . . . . Estrogen receptor downregulator (ERD) . . . . . Estrogen-receptor-sensitive breast cancer . . . . . Ethnicity and cancer . . . . . . . . . . . . . . . . Ethylene oxide . . . . . . . . . . . . . . . . . . . Ewing sarcoma . . . . . . . . . . . . . . . . . . . Exenteration . . . . . . . . . . . . . . . . . . . . Exercise and cancer . . . . . . . . . . . . . . . . External beam radiation therapy (EBRT) . . . . . Eye cancers . . . . . . . . . . . . . . . . . . . . Eyelid cancer. . . . . . . . . . . . . . . . . . . .
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Fallopian tube cancer . . . . . . . Family history and risk assessment Fanconi anemia . . . . . . . . . . Fatigue . . . . . . . . . . . . . . . Fecal occult blood test (FOBT) . . Fertility drugs and cancer . . . . . Fertility issues . . . . . . . . . . . Fever . . . . . . . . . . . . . . . . Fiber . . . . . . . . . . . . . . . .
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402 403 404 406 409 412 414 416
. 417 . 417
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420 421 422 424 425 426 429 431
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433 433 434 436 438 439 441 441 442 444 447 447 450 451 454 455 458
. . . . . . . . .
460 461 464 466 467 469 471 472 474
Fibroadenomas . . . . . . . . . . . . . . . . Fibrocystic breast changes . . . . . . . . . . Fibrosarcomas, soft-tissue . . . . . . . . . . Financial issues . . . . . . . . . . . . . . . 5HIAA test. See 5-Hydroxyindoleacetic acid test 5Q minus syndrome . . . . . . . . . . . . . Flow cytometry . . . . . . . . . . . . . . . FOBT. See Fecal occult blood test Folic acid. . . . . . . . . . . . . . . . . . . Formaldehyde . . . . . . . . . . . . . . . . Fox Chase Cancer Center . . . . . . . . . . Fred Hutchinson Cancer Research Center . . Free radicals . . . . . . . . . . . . . . . . . Fruits . . . . . . . . . . . . . . . . . . . . .
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486 486 487 488 490 491
Gallbladder cancer . . . . . . . . . . . . . . Gallium scan . . . . . . . . . . . . . . . . . Gamma Knife . . . . . . . . . . . . . . . . Gardner syndrome . . . . . . . . . . . . . . Garlic and allicin . . . . . . . . . . . . . . . Gastric polyps . . . . . . . . . . . . . . . . Gastrinomas . . . . . . . . . . . . . . . . . Gastrointestinal cancers . . . . . . . . . . . Gastrointestinal complications of cancer treatment. . . . . . . . . . . . . . . . . . Gastrointestinal oncology . . . . . . . . . . Gastrointestinal stromal tumors (GISTs) . . GCTs. See Giant cell tumors Gene therapy . . . . . . . . . . . . . . . . . Genetic counseling . . . . . . . . . . . . . . Genetic testing . . . . . . . . . . . . . . . . Genetics of cancer . . . . . . . . . . . . . . Geography and cancer . . . . . . . . . . . . Germ-cell tumors . . . . . . . . . . . . . . Gerson therapy . . . . . . . . . . . . . . . . Gestational trophoblastic tumors (GTTs) . . Giant cell tumors (GCTs) . . . . . . . . . . Ginseng, panax. . . . . . . . . . . . . . . . GISTs. See Gastrointestinal stromal tumors Gleason grading system . . . . . . . . . . . Gliomas . . . . . . . . . . . . . . . . . . . Glomus tumors . . . . . . . . . . . . . . . . Glossectomy . . . . . . . . . . . . . . . . . Glutamine . . . . . . . . . . . . . . . . . . Gonioscopy . . . . . . . . . . . . . . . . . Grading of tumors . . . . . . . . . . . . . . Graft-versus-host disease (GVHD) . . . . . Granulosa cell tumors . . . . . . . . . . . . Green tea . . . . . . . . . . . . . . . . . . . Grief and bereavement . . . . . . . . . . . .
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493 495 497 498 499 500 501 502
lxxxiii
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475 476 478 481
. . . . 484 . . . . 484
. . . . 506 . . . . 508 . . . . 511 . . . . . . . . . .
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512 515 517 519 522 525 527 527 530 531
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532 533 534 535 536 536 537 538 540 540 541
Salem Health: Cancer GTTs. See Gestational trophoblastic tumors GVHD. See Graft-versus-host disease Gynecologic cancers . . . . . . . . . . . . . . . . . 543 Gynecologic oncology . . . . . . . . . . . . . . . . 547 H. pylori. See Helicobacter pylori HAI. See Hepatic arterial infusion Hair dye . . . . . . . . . . . . . . . . . . . . . . Hairy cell leukemia . . . . . . . . . . . . . . . . Hand-foot syndrome (HFS) . . . . . . . . . . . . HBV. See Hepatitis B virus HCG. See Human chorionic gonadotropin HCV. See Hepatitis C virus Head and neck cancers . . . . . . . . . . . . . . . Health maintenance organizations (HMOs) . . . . Helicobacter pylori. . . . . . . . . . . . . . . . . Hemangioblastomas . . . . . . . . . . . . . . . . Hemangiopericytomas . . . . . . . . . . . . . . . Hemangiosarcomas . . . . . . . . . . . . . . . . Hematemesis . . . . . . . . . . . . . . . . . . . . Hematologic oncology . . . . . . . . . . . . . . . Hematuria . . . . . . . . . . . . . . . . . . . . . Hemochromatosis . . . . . . . . . . . . . . . . . Hemolytic anemia . . . . . . . . . . . . . . . . . Hemoptysis. . . . . . . . . . . . . . . . . . . . . Hemorrhoids . . . . . . . . . . . . . . . . . . . . Hepatic arterial infusion (HAI) . . . . . . . . . . Hepatitis B virus (HBV) . . . . . . . . . . . . . . Hepatitis C virus (HCV) . . . . . . . . . . . . . . Hepatomegaly . . . . . . . . . . . . . . . . . . . HER2/neu protein . . . . . . . . . . . . . . . . . Herbs as antioxidants . . . . . . . . . . . . . . . Hereditary cancer syndromes . . . . . . . . . . . Hereditary diffuse gastric cancer . . . . . . . . . Hereditary leiomyomatosis and renal cell cancer (HLRCC) . . . . . . . . . . . . . . . . Hereditary mixed polyposis syndrome . . . . . . Hereditary non-VHL clear cell renal cell carcinomas . . . . . . . . . . . . . . . . . . . Hereditary pancreatitis . . . . . . . . . . . . . . . Hereditary papillary renal cell carcinomas . . . . Hereditary polyposis syndromes . . . . . . . . . . Herpes simplex virus. . . . . . . . . . . . . . . . Herpes zoster virus. . . . . . . . . . . . . . . . . HFS. See Hand-foot syndrome Hispanics and cancer. See Latinos/Hispanics and cancer Histamine 2 antagonists . . . . . . . . . . . . . . Histiocytosis X . . . . . . . . . . . . . . . . . . . HIV/AIDS-related cancers . . . . . . . . . . . . .
. 550 . 550 . 552
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554 557 558 559 559 560 561 562 564 565 566 566 567 568 569 570 571 573 573 574 576
. 577 . 579 . . . . . .
580 580 581 582 584 586
. 587 . 588 . 590
HLRCC. See Hereditary leiomyomatosis and renal cell cancer HMOs. See Health maintenance organizations Hodgkin disease . . . . . . . . . . . . . . . . . Home health services . . . . . . . . . . . . . . Hormonal therapies . . . . . . . . . . . . . . . Hormone receptor tests . . . . . . . . . . . . . Hormone replacement therapy (HRT) . . . . . . Horner syndrome. . . . . . . . . . . . . . . . . Hospice care . . . . . . . . . . . . . . . . . . . Hot flashes . . . . . . . . . . . . . . . . . . . . HPV. See Human papillomavirus HRAS gene testing . . . . . . . . . . . . . . . . HRT. See Hormone replacement therapy HTLV. See Human T-cell leukemia virus Human chorionic gonadotropin (HCG) . . . . . Human growth factors and tumor growth . . . . Human immunodeficiency virus-related cancers. See HIV/AIDS-related cancers Human papillomavirus (HPV) . . . . . . . . . . Human T-cell leukemia virus (HTLV) . . . . . Hydatidiform mole . . . . . . . . . . . . . . . . 5-Hydroxyindoleacetic acid (5HIAA) test . . . . Hypercalcemia . . . . . . . . . . . . . . . . . . Hypercoagulation disorders . . . . . . . . . . . Hyperthermia therapy . . . . . . . . . . . . . . Hyperthermic perfusion . . . . . . . . . . . . . Hypopharyngeal cancer . . . . . . . . . . . . . Hysterectomy . . . . . . . . . . . . . . . . . . Hysterography . . . . . . . . . . . . . . . . . . Hystero-oophorectomy. . . . . . . . . . . . . . Hysteroscopy. . . . . . . . . . . . . . . . . . . IEP. See Immunoelectrophoresis iFOBT. See Immunochemical fecal occult blood test Ileostomy. . . . . . . . . . . . . . . . . . . . . Imaging tests . . . . . . . . . . . . . . . . . . . Immune response to cancer . . . . . . . . . . . Immunochemical fecal occult blood test (iFOBT) . . . . . . . . . . . . . . . . . . . . Immunocytochemistry and immunohistochemistry . . . . . . . . . . . . Immunoelectrophoresis (IEP) . . . . . . . . . . Immunotherapy . . . . . . . . . . . . . . . . . IMRT. See Intensity-modulated radiation therapy Indoles . . . . . . . . . . . . . . . . . . . . . . Infection and sepsis . . . . . . . . . . . . . . . Infectious cancers . . . . . . . . . . . . . . . . Infertility and cancer . . . . . . . . . . . . . . .
lxxxiv
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593 597 599 601 603 605 606 608
. . 609
. . 609 . . 610
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611 612 612 613 614 615 617 618 619 620 621 622 623
. . 625 . . 626 . . 629 . . 632 . . 633 . . 634 . . 635
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638 638 641 643
Complete List of Contents Inflammatory bowel disease . . . . . . . . . . Informed consent. . . . . . . . . . . . . . . . Infusion therapies . . . . . . . . . . . . . . . Insurance . . . . . . . . . . . . . . . . . . . . Integrative oncology . . . . . . . . . . . . . . Intensity-modulated radiation therapy (IMRT) Interferon. . . . . . . . . . . . . . . . . . . . Interleukins. . . . . . . . . . . . . . . . . . . Invasive cancer. . . . . . . . . . . . . . . . . Invasive ductal carcinomas . . . . . . . . . . Invasive lobular carcinomas . . . . . . . . . . Ionizing radiation . . . . . . . . . . . . . . . Iridium seeds . . . . . . . . . . . . . . . . . . Islet cell tumors . . . . . . . . . . . . . . . . Isoflavones . . . . . . . . . . . . . . . . . . . Itching . . . . . . . . . . . . . . . . . . . . .
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645 646 647 648 651 652 653 654 655 656 657 657 658 659 661 661
Lambert-Eaton myasthenic syndrome (LEMS) Laparoscopy and laparoscopic surgery . . . . Laryngeal cancer . . . . . . . . . . . . . . . . Laryngeal nerve palsy . . . . . . . . . . . . . Laryngectomy . . . . . . . . . . . . . . . . . Laryngoscopy . . . . . . . . . . . . . . . . . Laser therapies . . . . . . . . . . . . . . . . . Latinos/Hispanics and cancer . . . . . . . . . Laxatives . . . . . . . . . . . . . . . . . . . . LCIS. See Lobular carcinoma in situ LDH test. See Lactate dehydrogenase test Leiomyomas . . . . . . . . . . . . . . . . . . Leiomyosarcomas . . . . . . . . . . . . . . . LEMS. See Lambert-Eaton myasthenic syndrome Leptomeningeal carcinomas . . . . . . . . . . Leukapharesis . . . . . . . . . . . . . . . . . Leukemia, Down syndrome and. See Down syndrome and leukemia Leukemia, eosinophilic. See Eosinophilic leukemia Leukemia, hairy cell. See Hairy cell leukemia Leukemias . . . . . . . . . . . . . . . . . . . Leukoencephalopathy . . . . . . . . . . . . . Leukopenia. . . . . . . . . . . . . . . . . . . Leukoplakia . . . . . . . . . . . . . . . . . . Leydig cell tumors . . . . . . . . . . . . . . . Li-Fraumeni syndrome (LFS) . . . . . . . . . Limb salvage . . . . . . . . . . . . . . . . . . Linear accelerator . . . . . . . . . . . . . . . Lip cancers . . . . . . . . . . . . . . . . . . . Liposarcomas . . . . . . . . . . . . . . . . . Liver biopsy . . . . . . . . . . . . . . . . . . Liver cancers . . . . . . . . . . . . . . . . . .
Jonsson Comprehensive Cancer Center (JCCC) . . . . . . . . . . . . . . . . . . . . . . 664 Journaling . . . . . . . . . . . . . . . . . . . . . . 665 Juvenile polyposis syndrome . . . . . . . . . . . . 665 Kaposi sarcoma . . . . . . . . . . . . . Karnofsky performance status (KPS) . . Keratosis . . . . . . . . . . . . . . . . . Ki67 test . . . . . . . . . . . . . . . . . Kidney cancer . . . . . . . . . . . . . . Klinefelter syndrome and cancer . . . . KPS. See Karnofsky performance status Krukenberg tumors . . . . . . . . . . .
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667 669 670 670 671 674
. . . . . . 675
Lacrimal gland tumors . . . . . . . . . . . . . . . . 677 Lactate dehydrogenase (LDH) test . . . . . . . . . 678 Laetrile . . . . . . . . . . . . . . . . . . . . . . . . 679
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679 681 682 685 686 687 688 690 692
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. . . 696 . . . 698
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698 702 704 704 706 706 708 709 710 712 714 715
Volume 3 Lumps . . . . . . . . . . . . . . Lung cancer, brochoalveolar. See Bronchoalveolar lung cancer Lung cancers . . . . . . . . . . . Lutein . . . . . . . . . . . . . . Lycopene . . . . . . . . . . . . . Lymphadenectomy. . . . . . . . Lymphangiography . . . . . . . Lymphangiosarcomas . . . . . . Lymphedema. . . . . . . . . . . Lymphocytosis . . . . . . . . . . Lymphomas . . . . . . . . . . .
Contents . . . . . . . . . . . . . . . . . . . . . . . . lv Complete List of Contents . . . . . . . . . . . . . . lix Living will . . . . . . . . . . . . . . . . . Living with cancer . . . . . . . . . . . . . Lobectomy . . . . . . . . . . . . . . . . . Lobular carcinoma in situ (LCIS) . . . . . Long-distance caregiving . . . . . . . . . Loop electrosurgical excisional procedure (LEEP) . . . . . . . . . . . . . . . . . Lumbar puncture . . . . . . . . . . . . . . Lumpectomy . . . . . . . . . . . . . . . .
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719 720 723 725 726
. . . . . 727 . . . . . 728 . . . . . 730 lxxxv
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733 737 737 738 740 741 742 743 744
Salem Health: Cancer M. D. Anderson Cancer Center . . . . . . . . . Macrobiotic diet . . . . . . . . . . . . . . . . . Magnetic resonance imaging (MRI) . . . . . . . Malignant fibrous histiocytoma (MFH) . . . . . Malignant rhabdoid tumor of the kidney . . . . Malignant tumors . . . . . . . . . . . . . . . . MALT lymphomas. See Mucosa-associated lymphoid tissue lymphomas Mammography . . . . . . . . . . . . . . . . . . Managed care . . . . . . . . . . . . . . . . . . Mantle cell lymphoma (MCL) . . . . . . . . . . Mastectomy . . . . . . . . . . . . . . . . . . . Mastocytomas . . . . . . . . . . . . . . . . . . Matrix metalloproteinase inhibitors . . . . . . . Mayo Clinic Cancer Center . . . . . . . . . . . MCC. See Merkel cell carcinomas MCL. See Mantle cell lymphoma MDR. See Drug resistance and multidrug resistance Mediastinal tumors. . . . . . . . . . . . . . . . Mediastinoscopy . . . . . . . . . . . . . . . . . Medical marijuana . . . . . . . . . . . . . . . . Medical oncology . . . . . . . . . . . . . . . . Medicare and cancer . . . . . . . . . . . . . . . Medullary carcinoma of the breast. . . . . . . . Medulloblastomas . . . . . . . . . . . . . . . . Melanomas . . . . . . . . . . . . . . . . . . . . Melphalan . . . . . . . . . . . . . . . . . . . . Memorial Sloan-Kettering Cancer Center . . . . MEN 1. See Multiple endocrine neoplasia type 1 MEN 2. See Multiple endocrine neoplasia type 2 Meningeal carcinomatosis . . . . . . . . . . . . Meningiomas. . . . . . . . . . . . . . . . . . . Merkel cell carcinomas (MCC) . . . . . . . . . Mesenchymomas, malignant. . . . . . . . . . . Mesothelioma . . . . . . . . . . . . . . . . . . Metastasis . . . . . . . . . . . . . . . . . . . . Metastatic squamous neck cancer with occult primary . . . . . . . . . . . . . . . . . . . . MFH. See Malignant fibrous histiocytoma Microcalcifications. . . . . . . . . . . . . . . . Microwave hyperthermia therapy . . . . . . . . Mineral oils . . . . . . . . . . . . . . . . . . . Mistletoe . . . . . . . . . . . . . . . . . . . . . Mitochondrial DNA mutations. . . . . . . . . . MLH1 gene. . . . . . . . . . . . . . . . . . . . Mohs surgery. . . . . . . . . . . . . . . . . . . Molecular oncology . . . . . . . . . . . . . . . Moles. . . . . . . . . . . . . . . . . . . . . . . Monoclonal antibodies . . . . . . . . . . . . . . Motion sickness devices . . . . . . . . . . . . .
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748 750 750 752 753 754
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754 757 759 761 763 764 765
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766 768 768 770 772 774 775 776 779 780
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781 782 783 785 786 788
. . 790 . . . . . . . . . . .
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790 791 792 793 794 795 796 796 798 800 802
MRI. See Magnetic resonance imaging MSH genes . . . . . . . . . . . . . . . . . . . . Mucinous carcinomas . . . . . . . . . . . . . . Mucosa-associated lymphoid tissue (MALT) lymphomas . . . . . . . . . . . . . . . . . . Mucositis . . . . . . . . . . . . . . . . . . . . . Mucous membranes, epidermoid cancers of. See Epidermoid cancers of mucous membranes Multiple endocrine neoplasia type 1 (MEN 1). . Multiple endocrine neoplasia type 2 (MEN 2). . Multiple myeloma . . . . . . . . . . . . . . . . Mustard gas . . . . . . . . . . . . . . . . . . . Mutagenesis and cancer . . . . . . . . . . . . . Myasthenia gravis . . . . . . . . . . . . . . . . MYC oncogene . . . . . . . . . . . . . . . . . . Mycosis fungoides . . . . . . . . . . . . . . . . Myelodysplastic syndromes . . . . . . . . . . . Myelofibrosis . . . . . . . . . . . . . . . . . . Myeloma . . . . . . . . . . . . . . . . . . . . . Myeloproliferative disorders. . . . . . . . . . . Myelosuppression . . . . . . . . . . . . . . . . 2-Naphthylamine. . . . . . . . . . . . . . . . Nasal cavity and paranasal sinus cancers . . . National Cancer Institute (NCI) . . . . . . . . National Science Foundation (NSF) . . . . . . Native North Americans and cancer . . . . . . Nausea and vomiting. . . . . . . . . . . . . . NCI. See National Cancer Institute Needle biopsies . . . . . . . . . . . . . . . . Needle localization. . . . . . . . . . . . . . . Nephroblastomas. . . . . . . . . . . . . . . . Nephrostomy . . . . . . . . . . . . . . . . . . Neuroblastomas . . . . . . . . . . . . . . . . Neuroectodermal tumors. . . . . . . . . . . . Neuroendocrine tumors . . . . . . . . . . . . Neurofibromatosis type 1 (NF1) . . . . . . . . Neurologic oncology. . . . . . . . . . . . . . Neutropenia . . . . . . . . . . . . . . . . . . NF1. See Neurofibromatosis type 1 Nickel compounds and metallic nickel . . . . Night sweats . . . . . . . . . . . . . . . . . . Nijmegen breakage syndrome . . . . . . . . . Nipple discharge . . . . . . . . . . . . . . . . Non-Hodgkin lymphoma . . . . . . . . . . . Nonsteroidal anti-inflammatory drugs (NSAIDs) . . . . . . . . . . . . . . . . . . NSAIDs. See Nonsteroidal anti-inflammatory drugs NSF. See National Science Foundation Nuclear medicine scan . . . . . . . . . . . . .
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. . 803 . . 803 . . 804 . . 806
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807 808 809 812 813 815 817 817 819 820 822 823 825
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826 826 829 830 832 834
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836 838 839 839 841 842 844 845 847 849
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851 852 853 854 855
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Complete List of Contents Nutrition and cancer prevention . . . . . . . . . . . 861 Nutrition and cancer treatment. . . . . . . . . . . . 864 Obesity-associated cancers . . . . . Occupational exposures and cancer . Occupational therapy . . . . . . . . OCs. See Organochlorines Oligodendrogliomas . . . . . . . . . Omega-3 fatty acids . . . . . . . . . Ommaya reservoir . . . . . . . . . . Oncogenes . . . . . . . . . . . . . . Oncogenic viruses . . . . . . . . . . Oncology . . . . . . . . . . . . . . . Oncology clinical nurse specialist . . Oncology social worker . . . . . . . Oophorectomy . . . . . . . . . . . . Ophthalmic oncology . . . . . . . . Opioids . . . . . . . . . . . . . . . . Oral and maxillofacial surgery. . . . Oral and oropharyngeal cancers . . . Orbit tumors . . . . . . . . . . . . . Orchiectomy . . . . . . . . . . . . . Organ transplantation and cancer . . Organochlorines (OCs) . . . . . . . Oropharyngeal cancers. See Oral and oropharyngeal cancers Orthopedic surgery. . . . . . . . . . Otolaryngology . . . . . . . . . . . Ovarian cancers . . . . . . . . . . . Ovarian cysts. . . . . . . . . . . . . Ovarian epithelial cancer . . . . . . Overtreatment . . . . . . . . . . . .
. . . . . . . . 868 . . . . . . . . 871 . . . . . . . . 873 . . . . . . . . . . . . . . . . .
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875 877 878 878 881 882 885 887 888 889 892 893 894 897 898 899 901
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902 903 905 908 909 911
Paget disease of bone . . . . . . . . . . . . . Pain management medications. . . . . . . . . Palliative treatment . . . . . . . . . . . . . . PALP. See Placental alkaline phosphatase Palpation . . . . . . . . . . . . . . . . . . . . Pancolitis . . . . . . . . . . . . . . . . . . . . Pancreatectomy . . . . . . . . . . . . . . . . Pancreatic cancers . . . . . . . . . . . . . . . Pancreatitis . . . . . . . . . . . . . . . . . . . Pap test . . . . . . . . . . . . . . . . . . . . . Paracentesis . . . . . . . . . . . . . . . . . . Paranasal sinus cancers. See Nasal cavity and paranasal sinus cancers Paraneoplastic syndromes . . . . . . . . . . . Parathyroid cancer . . . . . . . . . . . . . . . Pathology . . . . . . . . . . . . . . . . . . . PC-SPES . . . . . . . . . . . . . . . . . . . . PDT. See Photodynamic therapy
. . . 912 . . . 914 . . . 917 . . . . . . .
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920 920 921 923 927 928 929
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931 932 934 937
Pediatric oncology and hematology . . . . . . . . . 938 Pelvic examination . . . . . . . . . . . . . . . . . . 940 Penile cancer . . . . . . . . . . . . . . . . . . . . . 941 Percutaneous transhepatic cholangiography (PTHC) . . . . . . . . . . . . . . . . . . . . . . 943 Pericardial effusion . . . . . . . . . . . . . . . . . 944 Pericardiocentesis . . . . . . . . . . . . . . . . . . 946 Peritoneovenous shunts . . . . . . . . . . . . . . . 946 Personality and cancer . . . . . . . . . . . . . . . . 947 Pesticides and the food chain . . . . . . . . . . . . 948 PET. See Positron emission tomography Peutz-Jeghers syndrome (PJS) . . . . . . . . . . . . 951 Pharmacy oncology . . . . . . . . . . . . . . . . . 952 Phenacetin . . . . . . . . . . . . . . . . . . . . . . 955 Phenolics . . . . . . . . . . . . . . . . . . . . . . . 955 Pheochromocytomas . . . . . . . . . . . . . . . . . 956 Pheresis . . . . . . . . . . . . . . . . . . . . . . . 958 Photodynamic therapy (PDT) . . . . . . . . . . . . 959 Phyllodes tumors. . . . . . . . . . . . . . . . . . . 960 Phytoestrogens . . . . . . . . . . . . . . . . . . . . 962 Pineoblastomas. . . . . . . . . . . . . . . . . . . . 963 Pituitary tumors . . . . . . . . . . . . . . . . . . . 965 PJS. See Peutz-Jeghers syndrome Placental alkaline phosphatase (PALP) . . . . . . . 968 Plant alkaloids and terpenoids in chemotherapy . . . . . . . . . . . . . . . . . . . 968 Plasticizers . . . . . . . . . . . . . . . . . . . . . . 971 Pleural biopsy . . . . . . . . . . . . . . . . . . . . 972 Pleural effusion . . . . . . . . . . . . . . . . . . . 973 Pleurodesis . . . . . . . . . . . . . . . . . . . . . . 975 Pleuropulmonary blastomas . . . . . . . . . . . . . 975 PMS genes . . . . . . . . . . . . . . . . . . . . . . 976 Pneumonectomy . . . . . . . . . . . . . . . . . . . 977 Pneumonia . . . . . . . . . . . . . . . . . . . . . . 979 Polycyclic aromatic hydrocarbons . . . . . . . . . . 981 Polycythemia vera . . . . . . . . . . . . . . . . . . 981 Polypectomy . . . . . . . . . . . . . . . . . . . . . 982 Polyps . . . . . . . . . . . . . . . . . . . . . . . . 983 Polyps, colon. See Colon polyps Polyps, gastric. See Gastric polyps Positron emission tomography (PET) . . . . . . . . 984 Poverty and cancer . . . . . . . . . . . . . . . . . . 987 PPOs. See Preferred provider organizations Prayer and cancer support . . . . . . . . . . . . . . 989 Preferred provider organizations (PPOs) . . . . . . 990 Pregnancy and cancer . . . . . . . . . . . . . . . . 992 Premalignancies . . . . . . . . . . . . . . . . . . . 994 Prevent Cancer Foundation . . . . . . . . . . . . . 997 Prevention . . . . . . . . . . . . . . . . . . . . . . 999 Primary care physician . . . . . . . . . . . . . . . 1001
lxxxvii
Salem Health: Cancer Primary central nervous system lymphomas . . . . . . . . . . . . . . . . Progesterone receptor assay . . . . . . . . Prostate cancer . . . . . . . . . . . . . . . Prostate-specific antigen (PSA) test . . . . Prostatectomy. . . . . . . . . . . . . . . . Prostatitis . . . . . . . . . . . . . . . . . . Proteasome inhibitors. . . . . . . . . . . . Protein electrophoresis . . . . . . . . . . . Proteomics and cancer research . . . . . . Proton beam therapy . . . . . . . . . . . . Proto-oncogenes and carcinogenesis . . . . PSA test. See Prostate-specific antigen test Psycho-oncology . . . . . . . . . . . . . . Psychosocial aspects of cancer . . . . . . . PTHC. See Percutaneous transhepatic cholangiography Radiation, ionizing. See Ionizing radiation Radiation oncology . . . . . . . . . . . . . Radiation therapies . . . . . . . . . . . . . Radiation therapy, afterloading. See Afterloading radiation therapy Radical neck dissection . . . . . . . . . . . Radiofrequency ablation . . . . . . . . . . Radionuclide scan . . . . . . . . . . . . . Radiopharmaceuticals . . . . . . . . . . . Radon . . . . . . . . . . . . . . . . . . . . RB1 gene . . . . . . . . . . . . . . . . . . Receptor analysis . . . . . . . . . . . . . .
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1003 1003 1004 1006 1008 1009 1010 1010 1012 1014 1015
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1027 1027 1030 1030 1032 1032 1033
Reconstructive surgery . . . . . . . . . . . . . . Rectal cancer . . . . . . . . . . . . . . . . . . . Recurrence . . . . . . . . . . . . . . . . . . . . Rehabilitation . . . . . . . . . . . . . . . . . . . Relationships . . . . . . . . . . . . . . . . . . . Renal pelvis tumors. . . . . . . . . . . . . . . . Report on Carcinogens (RoC) . . . . . . . . . . Resveratrol . . . . . . . . . . . . . . . . . . . . Retinoblastomas . . . . . . . . . . . . . . . . . Rhabdomyosarcomas . . . . . . . . . . . . . . . RhoGD12 gene . . . . . . . . . . . . . . . . . . Richter syndrome . . . . . . . . . . . . . . . . . Risk assessment, family history and. See Family history and risk assessment Risks for cancer. . . . . . . . . . . . . . . . . . Robert H. Lurie Cancer Center . . . . . . . . . . RoC. See Report on Carcinogens Rothmund-Thomson syndrome . . . . . . . . . .
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Salivary gland cancer . . . . . . . . . . . . . Salpingectomy and salpingo-oophorectomy . Sarcomas, soft-tissue . . . . . . . . . . . . . Saw palmetto . . . . . . . . . . . . . . . . . Schwannoma tumors . . . . . . . . . . . . . SCLC1 gene. . . . . . . . . . . . . . . . . . Screening, colorectal cancer. See Colorectal cancer screening Screening for cancer . . . . . . . . . . . . . Second opinions . . . . . . . . . . . . . . . Self-image and body image. . . . . . . . . .
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1034 1036 1038 1038 1041 1043 1044 1045 1046 1048 1050 1050
. 1052 . 1054 . 1056 1058 1060 1062 1065 1066 1067
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Volume 4 Contents . . . . . . . . . . . . . . . . . . . . . . lxxvii Complete List of Contents . . . . . . . . . . . . . lxxix Sentinel lymph node (SLN) biopsy and mapping . . . . . . . . . . . . . . . Sepsis. See Infection and sepsis Sertoli cell tumors . . . . . . . . . . . Sexuality and cancer . . . . . . . . . . Sézary syndrome . . . . . . . . . . . . SIADH. See Syndrome of inappropriate antidiuretic hormone production Side effects . . . . . . . . . . . . . . . Sigmoidoscopy . . . . . . . . . . . . . Silica, crystalline . . . . . . . . . . . . Simian virus 40 . . . . . . . . . . . . . Singlehood and cancer . . . . . . . . .
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1078 1082 1083 1084 1084
Sjögren syndrome. . . . . . . . . . . . . . . . Skin cancers . . . . . . . . . . . . . . . . . . SLN biopsy and mapping. See Sentinel lymph node biopsy and mapping Small intestine cancer . . . . . . . . . . . . . Smoking cessation . . . . . . . . . . . . . . . Social Security Disability Insurance (SSDI) . . Soft-tissue fibrosarcomas. See Fibrosarcomas, soft-tissue Soots . . . . . . . . . . . . . . . . . . . . . . Soy foods . . . . . . . . . . . . . . . . . . . . Spermatocytomas . . . . . . . . . . . . . . . . Spinal axis tumors . . . . . . . . . . . . . . . Spinal cord compression . . . . . . . . . . . . Splenectomy . . . . . . . . . . . . . . . . . . Sputum cytology . . . . . . . . . . . . . . . .
lxxxviii
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1097 1098 1099 1100 1102 1103 1105
Complete List of Contents Squamous cell carcinomas . . . . . . . . . . . SRS. See Stereotactic radiosurgery SSDI. See Social Security Disability Insurance Staging of cancer . . . . . . . . . . . . . . . . Statistics of cancer . . . . . . . . . . . . . . . Stem cell transplantation . . . . . . . . . . . . Stent therapy . . . . . . . . . . . . . . . . . . Stereotactic needle biopsy . . . . . . . . . . . Stereotactic radiosurgery (SRS) . . . . . . . . Sterility . . . . . . . . . . . . . . . . . . . . . Stomach cancers . . . . . . . . . . . . . . . . Stomatitis . . . . . . . . . . . . . . . . . . . . Stress management . . . . . . . . . . . . . . . Sunlamps . . . . . . . . . . . . . . . . . . . . Sun’s soup . . . . . . . . . . . . . . . . . . . Sunscreens . . . . . . . . . . . . . . . . . . . Superior vena cava syndrome . . . . . . . . . Support groups . . . . . . . . . . . . . . . . . Surgical biopsies . . . . . . . . . . . . . . . . Surgical oncology. . . . . . . . . . . . . . . . Survival rates . . . . . . . . . . . . . . . . . . Survivorship issues . . . . . . . . . . . . . . . Symptoms and cancer. . . . . . . . . . . . . . Syndrome of inappropriate antidiuretic hormone production (SIADH) . . . . . . . . Synovial sarcomas . . . . . . . . . . . . . . . Taste alteration . . . . . . . . . . . . . . Teratocarcinomas . . . . . . . . . . . . . Teratomas . . . . . . . . . . . . . . . . . Testicular cancer . . . . . . . . . . . . . Testicular self-examination (TSE) . . . . Thermal imaging . . . . . . . . . . . . . Thiotepa. . . . . . . . . . . . . . . . . . Thoracentesis . . . . . . . . . . . . . . . Thoracoscopy . . . . . . . . . . . . . . . Thoracotomy . . . . . . . . . . . . . . . Throat cancer . . . . . . . . . . . . . . . Thrombocytopenia . . . . . . . . . . . . Thymomas . . . . . . . . . . . . . . . . Thymus cancer . . . . . . . . . . . . . . Thyroid cancer . . . . . . . . . . . . . . Thyroid nuclear medicine scan . . . . . . TNF. See Tumor necrosis factor TNM staging . . . . . . . . . . . . . . . Tobacco, chewing. See Chewing tobacco Tobacco-related cancers . . . . . . . . . Topoisomerase inhibitors . . . . . . . . . TP53 protein . . . . . . . . . . . . . . . Tracheostomy . . . . . . . . . . . . . . . Transfusion therapy. . . . . . . . . . . .
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1108 1111 1114 1116 1118 1119 1120 1121 1124 1125 1127 1128 1129 1130 1132 1135 1138 1140 1143 1144
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1151 1152 1153 1154 1156 1157 1158 1158 1160 1161 1162 1164 1166 1167 1169 1172
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1174 1175 1177 1179 1180
Transitional care . . . . . . . . . . . Transitional cell carcinomas . . . . . Transrectal ultrasound . . . . . . . . Transvaginal ultrasound . . . . . . . Trichilemmal carcinomas. . . . . . . TSE. See Testicular self-examination Tuberous sclerosis . . . . . . . . . . Tubular carcinomas . . . . . . . . . . Tumor flare . . . . . . . . . . . . . . Tumor lysis syndrome . . . . . . . . Tumor markers . . . . . . . . . . . . Tumor necrosis factor (TNF) . . . . . Tumor-suppressor genes . . . . . . . Turcot syndrome . . . . . . . . . . . Tyrosine kinase inhibitors . . . . . .
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1182 1183 1185 1186 1187
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1187 1188 1189 1189 1191 1193 1194 1195 1196
Ultrasound, breast. See Breast ultrasound Ultrasound, endorectal. See Endorectal ultrasound Ultrasound, transrectal. See Transrectal ultrasound Ultrasound, transvaginal. See Transvaginal ultrasound Ultrasound tests . . . . . . . . . . . . . . . Ultraviolet radiation and related exposures Umbilical cord blood transplantation. . . . Upper gastrointestinal (GI) endoscopy . . . Upper gastrointestinal (GI) series . . . . . Urethral cancer . . . . . . . . . . . . . . . Urinalysis . . . . . . . . . . . . . . . . . . Urinary system cancers . . . . . . . . . . . Urography . . . . . . . . . . . . . . . . . Urologic oncology . . . . . . . . . . . . . Urostomy . . . . . . . . . . . . . . . . . . Uterine cancer . . . . . . . . . . . . . . .
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1199 1200 1201 1202 1203 1205 1207 1209 1213 1214 1216 1217
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1220 1221 1223 1225 1226
Vaccines, preventive . . . . . . . . . . . Vaccines, therapeutic . . . . . . . . . . . Vaginal cancer . . . . . . . . . . . . . . Vascular access tubes. . . . . . . . . . . Vasectomy and cancer . . . . . . . . . . Vegetables, cruciferous. See Cruciferous vegetables Veterinary oncology . . . . . . . . . . . VHL disease. See Von Hippel-Lindau disease Vinyl chloride . . . . . . . . . . . . . . Viral oncology . . . . . . . . . . . . . . Virus-related cancers . . . . . . . . . . . Von Hippel-Lindau (VHL) disease. . . . Vulvar cancer . . . . . . . . . . . . . . .
lxxxix
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1230 1230 1232 1235 1237
Salem Health: Cancer WAGR syndrome. See Wilms’ tumor aniridiagenitourinary anomalies-mental retardation syndrome and cancer Waldenström macroglobulinemia (WM) . . . . . . 1240 Watchful waiting . . . . . . . . . . . . . . . . . . 1242 Weight loss . . . . . . . . . . . . . . . . . . . . . 1243 Wilms’ tumor . . . . . . . . . . . . . . . . . . . . 1245 Wilms’ tumor aniridia-genitourinary anomaliesmental retardation (WAGR) syndrome and cancer . . . . . . . . . . . . . . . . . . . . . . 1248 Wine and cancer . . . . . . . . . . . . . . . . . . 1250 Wire localization . . . . . . . . . . . . . . . . . . 1250 WM. See Waldenström macroglobulinemia Wood dust . . . . . . . . . . . . . . . . . . . . . 1251
Yolk sac carcinomas . . . . . . . . . . . . . . . . 1256 Young adult cancers . . . . . . . . . . . . . . . . 1256 Zollinger-Ellison syndrome . . . . . . . . . . . . 1260 Drugs by Generic Name . . . Drugs by Trade Name . . . . Associations and Agencies . . Cancer Centers and Hospitals Cancer Support Groups . . . . Carcinogens. . . . . . . . . . Glossary . . . . . . . . . . . Bibliography . . . . . . . . .
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1265 1309 1348 1352 1357 1362 1383 1400
Category List . . . . . . . . . . . . . . . . . . . . 1409 Index . . . . . . . . . . . . . . . . . . . . . . . . 1419
X-ray tests . . . . . . . . . . . . . . . . . . . . . 1252 Xeroderma pigmentosa . . . . . . . . . . . . . . . 1254
xc
Salem Health: Cancer
u ABCD Category: Procedures Also known as: Jewett staging system or the WhitmoreJewett staging system (for prostate cancer) Definition: There are two distinct ABCD rating systems for cancer. The first uses the symbols A, B, C, and D to define the stages of prostate cancer. The second uses these designations to describe the early warning signs of melanoma, the most serious type of skin cancer.
Abdominoperineal resection (APR)
•
A (asymmetry): The two halves of the skin lesion are dissimilar. • B (border irregularity): The lesion has ragged or poorly defined edges. • C (color): The color of the lesion is uneven with different shades of brown or black. • D (diameter): The lesion is usually greater than 6 millimeters or 0.25 inch. Anna Binda, Ph.D. See also Melanomas; Moles; Premalignancies; Prostate cancer.
Cancers monitored: Prostate cancer and melanoma (each with its own distinct ABCD rating) Why performed: After detecting prostate cancer, the physician will evaluate the stage of the tumor according to its size, its location, and the extent to which it may have spread to other parts of the body. This information is important for choosing the best treatment plan. Staging of prostate cancer is based on the findings of clinical tests, mainly a digital rectal examination, a test to measure the level of prostate-specific antigen (PSA) in the blood, and transrectal ultrasonography. For melanoma prevention, the American Cancer Society recommends monthly skin self-examinations. The ABCD guideline serves as a reference when looking for any suspicious changes in the appearance of spots or sores that do not heal. Usually, this means monitoring any variation in the size, shape, or color of a mole. Any suspicious mole should be checked by a physician, who may decide to resect an abnormal-looking lesion and send the tissue for pathological review. Results: The ABCD rating for prostate cancer is used to classify the disease into four basic stages. • Stage A: Localized disease in which the cancer is very small, confined to the prostate gland, not palpable during a rectal examination, and identified by high PSA levels and biopsy. • Stage B: Localized disease in which the cancer is larger and confined to the prostate gland, but a lump is palpable during a rectal examination. • Stage C: Regional disease in which the cancer has grown through the prostate capsule and into surrounding tissues, perhaps into the seminal vesicles. • Stage D: Metastatic disease in which the cancer has grown into the pelvic area or has spread to the lymph nodes, bones, or other parts of the body. The ABCD rule for melanoma detection lists the four usual warning signs of the disease for most types of melanoma.
u Abdominoperineal resection
(APR) Category: Procedures Also known as: Abdominoperineal excision, anorectal excision, anoproctectomy Definition: Abdominoperineal resection (APR) is the surgical removal of the anus, rectum, and surrounding membrane called the mesentery, as well as the lower part of the colon supported by that mesentery. The upper part of the colon is rerouted through a new opening (ostomy) in the lower abdomen, forming an opening called a stoma. Cancers treated: Low rectal cancer, advanced anal cancer, metastatic pelvic disease Why performed: APR is performed to remove cancerous tissue, thereby curing or controlling the cancer or relieving symptoms of advanced disease. APR is the preferred procedure for large rectal tumors and tumors near the anal sphincter, but other tumor characteristics and patientspecific factors are also considered. Patient preparation: A series of medical tests are completed to plan effective treatment and to evaluate the patient’s fitness for major surgery. A specialist counsels the patient and helps choose the location for the stoma required by an APR. Radiation therapy, chemotherapy, or both may be recommended before the procedure. Certain patient medications may need to be stopped, the patient’s bowel must be cleaned, and the patient’s stomach must be empty. Steps of the procedure: APR is scheduled in a hospital. Sensors are placed to monitor the patient’s condition. An intravenous line is started, and an antibiotic is infused. General anesthetic is administered, and a breathing tube is 1
Abdominoperineal resection (APR) placed. The patient is positioned, a urinary catheter is inserted, and the incision sites are prepared. APR is a complex operation requiring incisions first on the abdomen (abdominal resection) and then on the perineum (perineal resection), which may be performed by one or two surgeons. Abdominal resection prepares the lower colon and rectum for removal during the perineal resection and forms the stoma. Perineal resection frees the anus and removes all the diseased tissue. In some instances, the abdominal resection may be performed laparoscopically; however, this approach will remain controversial until long-term studies prove its safety and efficacy for APR. To begin, the surgeon makes an midline incision in the abdomen large enough to see the tumor and to examine lymph nodes and other organs for metastases. If the tumor is removable, then the procedure continues. Within the abdomen, rectal blood vessels are tied, and the mesentery is clamped. The lower colon is freed from attachments. The peritoneum is divided, enabling the surgeon to free the rectum. The tied blood vessels and clamped mesentery are divided and sealed. Then, the ostomy opening is made in the abdomen. The colon is divided. The lower end of the colon is covered and tucked below the peritoneum for removal during the perineal resection, and the peritoneum is closed. The upper end of the colon is passed through the ostomy opening, the colon segment is sized to an appropriate length, and the edge of the cut end is folded back and stitched to the abdomen, forming a stoma. Next, other organs are examined for cancer; if other lesions or metastases are found, then they may also be removed. Finally, the abdominal cavity is inspected and cleaned, and the abdominal incision is closed. On the perineum, the surgeon makes an elliptical incision around the anus. Blood vessels are clamped, then tied as needed. The anus is freed from attachments, including as much surrounding tissue as possible without disturbing major blood vessels, nerves, and healthy organs; however, if the cancer has spread into these structures, then part or all of these structures may be included. The anus is pulled out, as well as the rectum and lower colon freed during the abdominal resection. All tissues are taken to the laboratory for histopathologic evaluation. Finally, the pelvic cavity is inspected and cleaned, and the perineal incision is closed, with a small tube inserted to drain excess fluid. After the procedure: Anesthetic is stopped, and the breathing tube is removed. The urinary catheter and the intravenous line are kept. A clear collection pouch (ostomy appliance) is fitted over the stoma. The patient is trans2
Salem Health: Cancer ferred to the recovery room, then to a hospital room. Medications are given to control pain and infection. The patient slowly progresses to a normal diet. The ostomy is monitored; once it starts functioning, the patient learns how to care for the stoma, empty and change pouches, and manage bowel function. At home, the patient follows the physician’s instructions about medications, activities, and diet. Further treatment with radiation therapy, chemotherapy, or both may be recommended. Risks: APR is moderately safe, with low mortality. Risks relate to anesthesia, infection, and inadvertent damage to other structures. Side effects are common because of the complex anatomy and the difficulty of operating within the bony pelvis. The most frequent side effects are urinary dysfunction and infection, perineal infections or bleeding, and ostomy-related problems. Less frequent side effects are male impotence and infertility, abdominal wound infection, and intestinal obstruction. Results: The long-term outcome varies considerably with patient-specific factors (such as disease stage, overall health, and body characteristics), among medical institutions (as a result of surgical protocol and specialized experience), and with therapeutic combinations. The five-year survival rate has increased as the recurrence rate has decreased because of more complete removal of diseased tissue and more effective therapeutic combinations. Survival is improved significantly by the removal of metastases. Patricia Boone, Ph.D. u
For Further Information American Cancer Society. Detailed Guide: Colon and Rectum Cancer Surgery. Available online at http:// www.cancer.org. American Cancer Society and National Comprehensive Cancer Network. Colon and Rectal Cancer: Treatment Guidelines for Patients. Version IV. Atlanta: American Cancer Society, 2005. Available online at http://www .nccn.org. Levin, Bernard, et al., eds. American Cancer Society’s Complete Guide to Colorectal Cancer. Atlanta: American Cancer Society, 2006. See also Anal cancer; Anoscopy; Appendix cancer; Colectomy; Coloanal anastomosis; Colorectal cancer; Colostomy; Crohn disease; Enterostomal therapy; Ileostomy; Laparoscopy and laparoscopic surgery; Rectal cancer; Sexuality and cancer.
Salem Health: Cancer
u Accelerated partial breast
irradiation (APBI) Category: Procedures Definition: Accelerated partial breast irradiation (APBI) is an alternative to traditional radiation therapy after lumpectomy that can reduce the time of treatment from weeks to days. It is considered an experimental procedure by many doctors. Cancers treated: Breast cancer Why performed: Radiation therapy is given after a lumpectomy to kill any cancer cells that remain in the breast. Accelerated partial breast irradiation is an alternative therapy that delivers radiation in a way that reduces the time and number of treatments required. Radiation therapy usually requires visits to the outpatient center or clinic five days a week for six or seven weeks. APBI reduces the amount of time required for treatment to about five days in total. Patient preparation: Patients who are undergoing accelerated partial breast irradiation treatment are generally enrolled in a clinical trial, because the procedure is still considered experimental. A clinical trial is a carefully controlled study, supervised by doctors who are also researchers, that is designed to investigate the risks or benefits of a new or experimental procedure. Different types of APBIs are being investigated in clinical trials, using different methods and techniques. As a result, the patient preparation for APBI will differ depending on the specifics of the therapy. In general, the preparation for APBI is the same as for any other radiation therapy treatment. Steps of the procedure: Just as with traditional radiation therapy, the actual time elapsed during a treatment of accelerated partial breast irradiation is usually very short. The time that it takes to get the equipment and patient set up, however, may be significant. First, the patient and the patient’s breast are positioned appropriately for the machine. During traditional radiation therapy, the entire breast receives radiation. During APBI, however, the only part of the breast that receives radiation is the area around the lumpectomy site. Therefore, the breast must be positioned very exactly so that the right area receives the radiation. To place the breast in the correct position, the cancer care team may label the breast with marker or tattooing. The patient should check with her cancer care team to see if these marks are temporary. Once the breast and equipment are correctly positioned, a dose of radiation is given to the breast. Radiation machines deliver beams of high-energy particles to the tis-
Accelerated partial breast irradiation (APBI) sue that destroy cancer cells. Accelerated partial breast irradiation uses amounts of radiation during treatment that are higher than those used by traditional radiation therapy. This is part of the reason that the treatment time of APBI is so short. After the procedure: After the procedure, the patient may experience fatigue, as well as pain or swelling in the breast. Aftercare depends on the procedure that is used. Patients should discuss aftercare with their cancer care team before the day of the first procedure so that anything needed, such as transportation home after the procedure, can be arranged in advance. Risks: Some risks are associated with any procedure involving radiation. With an experimental therapy such as APBI, ongoing clinical trials are trying to determine any long-term side effects that may result from the procedure. Most studies, however, have found the risks associated with APBI to be relatively mild, not greater than risks associated with traditional radiation therapy, and decreasing over time. The most common side effects of APBI are believed to be fatigue, skin changes similar to sunburn in the treated area, swelling in the breast, breast heaviness, and breast discoloration. The creation of small, hard nodes in the breast is also possible. These nodes are not dangerous, but they can occasionally be mistaken for a return of the breast cancer when felt or seen on a mammogram. A very rare but extremely serious possible complication of any radiation to the breast is the development of angiosarcoma, an aggressive form of cancer. Results: Studies done comparing women who received APBI and those who received traditional radiation therapy after lumpectomy have generally found comparable rates of recurrence, even after many years. Researchers, however, are still conducting more studies and clinical trials. Most studies have been conducted only on very specific groups of women, and more research is being done to study the larger population of women with breast cancer to help determine whether APBI is a technique that could be beneficial to all women, and should be integrated into standard breast cancer treatment practices. The results that any individual woman experiences after APBI will depend on many different factors, including genetics, the type of original cancer, and the size of the original cancer. Helen Davidson, B.A. u
For Further Information Pasqualini, Jorge R., ed. Breast Cancer: Prognosis, Treatment, and Prevention. 2d ed. New York: Informa Healthcare, 2008. 3
Achlorhydria Smith, Terry L. Breast Cancer: Current and Emerging Trends in Detection and Treatment. New York: Rosen, 2006. Torosian, Michael H., ed. Breast Cancer: A Guide to Detection and Multidisciplinary Therapy. Totowa, N.J.: Humana Press, 2002. Winchester, David J., et al. Breast Cancer. 2d ed. Hamilton, Ont.: BC Decker, 2006. See also Afterloading radiation therapy; Breast cancer in children and adolescents; Breast cancer in men; Breast cancer in pregnant women; Breast cancers; Cutaneous breast cancer; Ductal carcinoma in situ (DCIS); Invasive ductal carcinomas; Invasive lobular carcinomas; Lobular carcinoma in situ (LCIS); Lumpectomy; Lumps; Mastectomy; Medullary carcinoma of the breast; Radiation therapies; Radiofrequency ablation.
u Achlorhydria Category: Diseases, symptoms, and conditions Also known as: Profound hypochlorhydria Related conditions: Helicobacter pylori infection, chronic atrophic gastritis, gastric adenocarcinoma, gastric carcinoid Definition: Achlorhydria is the absence of acid secretion by the stomach caused by either atrophy of the acid-producing parietal cells or direct inactivation of the protonpumping enzyme in parietal cells responsible for acid secretion. Risk factors: The risk of achlorhydria increases with age and with long-term, untreated infection with the bacteria Helicobacter pylori. Patients with autoimmune conditions are also at increased risk. The condition has no predilection for sex or race. Etiology and the disease process: Chronic inflammation of the stomach in response to untreated H. pylori infection lasting many years leads to the atrophy of stomach cells and a corresponding loss of acid-secreting capacity. Some patients may be more predisposed to achlorhydria in the presence of H. pylori because they respond to the infection by producing a specific inflammatory agent that is also a potent proton pump inhibitor. Autoimmune disease can also produce achlorhydria if the body makes antibodies that inactivate parietal cell proteins. Achlorhydria is associated with the development of malignant cancer of the stomach. Over 60 percent of patients with gastric cancer have achlorhydria compared with 20 percent of healthy individuals. Acid normally acts 4
Salem Health: Cancer as a disinfectant to prevent overgrowth of harmful bacteria; achlorhydria contributes to cancer development because the bacteria synthesize carcinogenic chemicals from nitrates present in food. Achlorhydria is also associated with the formation of gastric carcinoid tumors. If acid output by the stomach is disrupted, the body overproduces the hormone gastrin, which stimulates overgrowth of enterochromaffinlike (ECL) cells in the stomach. This overgrowth may progress to carcinoid formation. Incidence: Gastric carcinoids constitute 0.5 percent of gastric cancers. They are typically associated with autoimmune conditions and have a low risk of malignancy. Symptoms: Achlorhydria itself causes no symptoms; rather, symptoms are secondary to the absence of acid. Lack of acid can cause vitamin B12 or calcium deficiency. Diarrhea may occur because of the overgrowth of bacteria. Screening and diagnosis: Diagnosis is made by measuring the acidity of a stomach fluid sample after an intravenous injection of pentagastrin, which stimulates acid secretion in normal patients. Acidity will not increase in the stomach fluid of achlorhydric patients. Treatment and therapy: Treatment focuses on addressing the underlying condition causing achlorhydria. Because vitamin B12 and calcium absorption are decreased, supplementation or injections of B12 may be necessary. Prognosis, prevention, and outcomes: Restoration of normal acid production depends on prognosis and treatment for the underlying condition responsible for achlorhydria. Pamela S. Cooper, Ph.D. See also Adenocarcinomas; Bacteria as causes of cancer; Gastric polyps; Gastrointestinal cancers; Helicobacter pylori; Hereditary diffuse gastric cancer; Premalignancies; Stomach cancers.
u Acoustic neuromas Category: Diseases, symptoms, and conditions Also known as: Vestibular schwannomas Related conditions: Neurofibromatosis type 2 Definition: Acoustic neuromas are benign (or nonmalignant) tumors that originate from Schwann cells surrounding the vestibular nerve (eighth cranial nerve) in the internal auditory canal. The term “neuroma” is somewhat misleading, as the tumors are not neuromas, nor do they
Salem Health: Cancer arise from the acoustic or cochlear nerve. Acoustic neuroma typically occurs as unilateral (one-sided) sporadic tumors in 95 percent of all cases, but in rare cases tumors can be bilateral (two-sided) and are associated with an inherited syndrome called neurofibromatosis type 2 (NF2). Approximately 2 to 4 percent of patients diagnosed with acoustic neuromas have NF2 type, a prevalence of 1 in 50,000 in the general population. Risk factors: Although high-dose ionizing radiation is a known risk factor of acoustic neuroma, environmental factors including noise exposure, radio frequency electromagnetic fields, and allergens have been reported as potential sources that may contribute to the formation of acoustic neuroma. One publication has reported the findings from an international multicenter case-control study that investigated the effects of these environmental factors in ninety-seven patients with acoustic neuroma and in agematched control subjects. The study reported that increased risks were found for exposure to persistent noise and hay fever, but not for ionizing radiation or for regular mobile phone use. Etiology and the disease process: Currently, the etiology of acoustic neuroma is not known. However, as an anomaly, it is rarely inherited. Nonetheless, neurofibromatosis type 2 should be suspected in young patients and those with family history. Neurofibromatosis is an autosomal dominant disease; thus patients who inherit a defective copy of the NF2 tumor-suppressor gene have a 95 percent chance of developing bilateral tumors; however, half of the cases have no family history of NF2, which could indicate mutations in the germline that were not inherited. Incidence: Sporadic acoustic tumors, the most common form of manifestation, occur in approximately 10 per 1 million persons per year—in other words the chance of an average person developing an acoustic neuroma in his or her lifetime is about 1 in 100,000. Neurofibromatosis is rarer, with only several thousand affected persons in the entire United States, corresponding to 1 in 40,000 individuals. However, a study has highlighted that the true incidence of acoustic neuroma may be higher than what has been envisaged, as 7 unsuspected schwannomas per 10,000 brain magnetic resonance imaging studies were identified, an equivalent of 0.07 percent. Acoustic neuromas, or schwannomas, occur largely in adults, typically in the fourth and fifth decades, with a mean presentation age of fifty years. They are uncommon in children; only thirty-nine cases had been reported as of 2007. Symptoms: Acoustic neuromas are histologically benign; however, if large, they can cause hydrocephalus, brain-
Acoustic neuromas stem compression, herniation, and eventually death. Hearing loss is the most prevalent symptom, occurring in more than 95 percent of patients, and the duration of hearing loss may extend to three or four years before clinical diagnosis is made—a majority of the patients experience one-sided, slowly progressing hearing impairment associated with high-frequency sounds. Alternative complaints or accompanying symptoms include tinnitus, dizziness, vertigo, and a sensation of fullness in the ear. With the progression of the tumor, patients may experience facial numbness, headaches, loss of coordination, and difficulty in swallowing. Vertigo is prevalent with smaller tumors, while unsteadiness, headache, and facial sensory disturbance are associated with large tumors. Screening and diagnosis: Acoustic neuroma can be diagnosed by a number of screening methods. These include conventional audiometry, auditory brainstem response (ABR), and gadolinium-enhanced magnetic resonance imaging (MRI). Among these, gadolinium-enhanced MRI is the optimal diagnostic test. Typically, on MRI scans acoustic neuromas appear as dense and uniformly enhanced. Acoustic neuromas are staged according to their location and size. Small tumors are less than 1.5 centimeters (cm), moderate tumors between 1.5 and 3 cm, and large tumors greater than 3 cm in size. Based on the location, they are staged as intracanalicular (located in the internal auditory canal), cisternal (extending outside the internal auditory canal), compressive (having progressed to touch the cerebellum or brainstem), and hydrocephalus (having progressed to obstruct the drainage of cerebrospinal fluid in the fourth ventricle). Treatment and therapy: The treatment options for acoustic neuroma include observation, microsurgery, stereotactic radiosurgery, and radiotherapy. Patients with advanced age or those deemed unfit for surgical intervention with small tumors at diagnosis are observed; treatment is withheld while tumor progression is monitored in serial imaging studies. However, treatment by observation has its own risks, as there is a greater risk of losing useful hearing. If microsurgery is the choice for treatment, many factors need to be assessed when evaluating its primary and secondary outcomes. First, there are three standard surgical approaches, each with its own advantages and disadvantages: suboccipital, middle fossa, and translabyrinthine. In the suboccipital approach, the tumor is reached through the skull behind the ear. As the procedure involves the retraction of the cerebellum, the approach is intrinsically dangerous and prone to complications. Although the middle fossa method can preserve hearing in theory, this 5
Acrylamides approach is also dangerous as it too requires the retraction of part of the brain. In the translabyrinthine approach, the tumor is accessed through the inner ear, and thus hearing loss is expected and inevitable. However, this method is unsuitable for large tumors. Second, microsurgery is technically challenging; therefore the rate of success is lower with a less experienced surgeon. Third, large tumors (greater than 3 cm) are difficult to resect without concomitant morbidity, such as facial palsy. Some of the complications that may arise from microsurgery are cerebrospinal fluid leak (12 percent of all cases), meningitis (5 percent), intracranial hemorrhage (2 percent), facial weakness with complete paralysis (31 percent), and delayed or partial paresis (50 percent). Radiosurgery refers to the administration of a single fraction of radiotherapy using stereotactic techniques to localize the tumor and align the fields. Radiosurgery may be performed either with a Gamma Knife or a linear accelerator (linac) based system. Gamma Knife is an emerging treatment option for those who are at high risk during microsurgery. High-dose Gamma Knife procedures are less favored due to the possibility of radiation complications; thus low-dose radiation (for example, 13 gray, or Gy) therapies are advised because of safety and lower risk of facial weakness. Radiotherapy refers to the administration of fractionated radiotherapy and includes stereotactic radiotherapy (radiation with other than gamma rays) and conventional radiotherapy techniques. Complications of Gamma Knife radiosurgery include injury to facial and trigeminal nerves. However, with the current dosing regimen of 12.5 Gy, the risk of trigeminal or facial nerve injury has decreased significantly. Although the potential for complications is higher with microsurgical procedures than with radiotherapy or radiosurgery, an important issue that should be considered with irradiation therapies is the low risk of inducing malignancies within the radiation area. Current recommendations are to offer microsurgery and radiosurgery options for patients with definite treatment indications. While microsurgery is the treatment of choice for large tumors because of the low risk of radiation-induced malignancies, microsurgery is also considered for younger patients. Prognosis, prevention, and outcomes: The microsurgical techniques for acoustic neuroma have improved the anatomical and functional preservation of the facial and cochlear nerves. These techniques, accompanied by continuous electrophysiological monitoring, have resulted in marked changes in the primary goals of management. In the past, the primary goal of acoustic neuroma manage6
Salem Health: Cancer ment was to preserve the patient’s life, whereas the objective today is to preserve the neurological function. Long-term follow-ups show negligible recurrence rates, suggesting that the preservation of neurological function does not restrict the tumor removal. Despite these advances, loss of nerve function and even deafness may occur postoperatively in some cases. Bagirathy Ravishankar, Ph.D. u
For Further Information Battaglia, A., et al. “Comparisons of Growth Patterns of Acoustic Neuromas with and Without Radiosurgery.” Otology and Neurotology 27 (2006): 705-712. Mendenhall, W., et al. “Management of Acoustic Schwannoma.” American Journal of Otolaryngology 25 (2004): 38-47. Neff, B., et al. “The Molecular Biology of Vestibular Schwannomas: Dissecting the Pathogenic Process at the Molecular Level.” Otology and Neurotology 27 (2006): 197-208. Schlehofer, B., et al. “Environmental Risk Factors for Sporadic Acoustic Neuroma.” European Journal of Cancer 43 (2007): 1741-1747. Yohay, K. “Neurofibromatosis Types 1 and 2.” The Neurologist 12 (2006): 86-93.
u
Other Resources
Acoustic Neuroma Association http://anausa.org American Cancer Society http://www.cancer.org See also Ependymomas; Neurofibromatosis type 1 (NF1); Schwannoma tumors; Stereotactic radiosurgery (SRS).
u Acrylamides Category: Carcinogens and suspected carcinogens RoC status: Reasonably anticipated human carcinogen since 1991 Also known as: 2-propenamide, propenamide, acrylic amide, vinyl amide, ethylene carboxamide Related cancers: Although an acrylamide-cancer connection in humans has not been established with certainty, the level of suspicion is high because under laboratory conditions in rats and mice, the following cancers have been associated with acrylamide: adrenal pheochromocytomas and mesotheliomas in the testes; adenomas in the
Salem Health: Cancer
Acrylamides
pituitary and mammary glands; adenocarcinomas of the clitoris, uterus, and thyroid gland; squamous cell carcinoma of the skin; and adenomas of the lung. Definition: Acrylamide is a compound of carbon, hydrogen, nitrogen, and oxygen resulting in the chemical formula, C3H5NO. This white, odorless, and crystalline compound is soluble in water, ethanol, ether, and chloroform, accounting for not only its many industrial uses but also its potential for uncomplicated entry into the human body. Many of its industrial and agricultural uses require the conversion of acrylamide to the polymer polyacrylamide. Exposure routes: Experimentally in rats and mice, cancer-inducing exposure routes include administration in the drinking water, intraFrench fries contain high levels of acrylamide. (©Birgit Reitz-hofmann/ Dreamstime.com) peritoneal injection, and topical application. In humans, during everyday activity and work, acrylamide gains entrance through unbroken At risk: Because of its almost ubiquitous presence at skin, mucous membranes, lungs, and the gastrointestinal the dinner table and its known neurotoxic and carcinotract. The primary occupational exposure routes are skin genic potential, acrylamide poses a health risk to humans. contact and through the inhalation of dust and vapor. Microwaving, baking, and frying will produce acrylamide, and as the food continues to cook, ever larger amounts Where found: Acrylamides are used in the treatment of of acrylamide are produced. As the risk potential for wastewater, drinking water, and sewage; in the production acrylamides in foods becomes more publicized, some of paper, plastics, and dyes; and in the manufacture of persteps are under way to modify food production methods, manent press fabrics, adhesives, and food packaging. It is such as using vacuum frying at lower temperatures. Raw also fundamental to ore processing. Acrylamide finds its or boiled foods pose little risk for acrylamides. way into a number of everyday products such as building Workers engaged in oil drilling, paper and pulp manumaterials, contact lenses, textiles, soap, food, and gelatin facture, general construction, plastics manufacture, mincapsules. Acrylamides have also established a place on ing, food processing, textile and cosmetics processing, and people’s dining tables: It is found in fried and baked agricultural industries are at increased risk of acrylamide goods, coffee, olives, and prune juice. Smoking is also a exposure. major acrylamide producer. Some acrylamide contaminates drinking water because Etiology and symptoms of associated cancers: Although of its use in water treatment facilities, but curiously, the research has not firmly established the acrylamide-cancer amount of acrylamide in a large order of fast-food french connection in humans, there is no question that acrylamide fries is more than three hundred times what the U.S. Enviis a serious neurotoxin. Depending on dosage levels, exporonmental Protection Agency allows in a single glass of sure can cause damage to the male reproductive glands, water. This pervasiveness of acrylamide prompted Dale skin, and eyes. Additionally, it may result in urinary inconHattis, a risk analysis expert at Clark University, to specutinence, numbness, weakening in the legs and hands, and late that “acrylamide causes several thousand cancers per irritation of the mucous membranes. year in Americans.” The National Institute for Occupational Health and Additionally, polyacrylamide, the polymer of acrylamSafety (NIOSH) lists the common acrylamide exposure ide, finds widespread global use in pesticides and in soil symptoms in an industrial setting: irritation of the eyes and treatment formulations. This has resulted in notable resiskin, ataxia, numbness of the limbs, paresthesia, muscle dues of polyacrylamide in the most widely consumed vegeweakness, absent deep tendon reflex, hand sweating, lassitables such as potatoes and grains. There is little governtude (weakness, exhaustion), drowsiness, and reproducment oversight or measurement of polyacrylamide in foods. 7
Acupuncture and acupressure for cancer patients tive effects. The institute further cautions that acrylamide is a potential occupational carcinogen. History: Production of acrylamide in the United States exceeds one million pounds per year. It was not until 2002 that Swedish scientists found high levels of acrylamide in certain fried and baked starchy foods. In the same year, the Center for Science in the Public Interest in the United States reported finding high levels of acrylamide in popular brands of snack chips, french fries, taco shells, and breakfast cereals. Government action concerning these findings has been very slow, but in 2005 the California attorney general filed a lawsuit requiring a warning label for french fries and potato chips. Although NIOSH considers the compound dangerous to life and health, the Food and Drug Administration allows acrylamide to be used for packaging, in plastics that are in contact with food, and in treating food to maximum levels ranging up to 0.20 percent. Although research has firmly established the canceracrylamide connection in rats and mice, the findings are still mixed in human studies. Some experts claim the very pervasiveness of acrylamide in the Western diet confuses the results. Richard S. Spira, D.V.M. u For Further Information Brown, L., M. M. Rhead, K. C. C. Bancroft, and N. Allen. “Model Studies of the Degradation of Acrylamide Monomer.” Water Research 14, no. 7 (1980): 775-778. Rice, Jerry M. “The Carcinogenicity of Acrylamide.” Mutation Research/Genetic Toxicology and Environmental Mutagenesis 580, nos. 1/2 (2005): 3-20. Smith, E., S. Prues, and F. Ochme. “Environmental Degradation of Polyacrylamides: Effect of Artificial Environmental Conditions.” Ecotoxicology and Environmental Safety 35 (1996): 121-135. Tareke, E., et al. “Analysis of Acrylamide, a Carcinogen Formed in Heated Foodstuffs.” Journal of Agriculture and Food Chemistry 50, no. 17 (2002): 4998-5006. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Eleventh Report on Carcinogens. Research Triangle Park, N.C.: Author, 2005. Weiss, G. “Acrylamide in Food: Uncharted Territory.” Science 27 (2002): 297. u
Other Resources
National Institute for Occupational Safety and Health http://www.cdc.gov/niosh 8
Salem Health: Cancer National Library of Medicine Toxicology Data Network http://toxnet.nlm.nih.gov U.S. Food and Drug Administration Draft Action Plan for Acrylamide in Food http://www.cfsan.fda.gov/~dms/acrypla3.html See also Adenocarcinomas; Endocrine cancers; Testicular cancer; Vulvar cancer.
u Acupuncture and acupressure
for cancer patients Category: Procedures Also known as: Traditional Chinese medicine (TCM), complementary and alternative medicine (CAM), Oriental medicine (OM) Definition: Acupuncture is a technique in which hair-thin, sterile, disposable needles of varying lengths are inserted into the skin and muscles at specific anatomical points (called acupoints) in order to treat ailments, including pain and certain diseases. It is one branch of traditional Chinese medicine (TCM) that originated in China around four thousand years ago to prevent, diagnose, and treat diseases in both humans and animals. Acupressure is a variation of acupuncture, in which therapists or patients press on acupoints with their fingers instead of inserting needles. Only specifically trained, licensed professionals can treat patients using acupuncture needles, but patients can be taught (preferably by a licensed professional) to perform acupressure on themselves. In 1996, the Food and Drug Administration (FDA) approved the acupuncture needle as a medical device. In 1997, the National Institutes of Health (NIH) began evaluating the safety and effectiveness of acupuncture as a complementary and alternative treatment. According to TCM principles, fourteen meridians are theorized to course invisibly along the body surface, including six paired and two unpaired channels. These meridians correspond to and connect with certain internal organs and physiological systems as understood in both traditional Chinese and Western medicine. Every acupoint is named and numbered according to its location on a specific meridian (for example, P6, or pericardium 6). Upon needling, the acupuncturist attempts to unblock, move, or alter what TCM refers to as the qi or chi (pronounced “chee”) of the body. This qi is a vital force that is thought to flow along the meridians and throughout the
Salem Health: Cancer body and organ systems. TCM posits that qi is formed from a merging of yin and yang, which are opposite energy states that permeate the universe. An imbalance of yin and yang in the body is thought to lead to a disruption of qi, leading to disharmony in physical and psychic well-being and thus to certain ailments or diseases. The acupuncturist (or acupressure practitioner) tries to restore a healthier balance of yin and yang in the patient. Many Western and Eastern acupuncturists currently blend TCM theory with modern understanding of neuroanatomy and the immune and other physiological systems. Cancers diagnosed or treated: In Western cancer management, acupuncture and acupressure are primarily used to mitigate the side effects related to conventional cancer treatments such as chemotherapy, radiation treatment, and surgery, or side effects of the disease itself. These side effects include chemotherapy-related nausea and vomiting, dyspnea (shortness of breath in advanced cancer cases), pain (either from a conventional treatment or the cancer itself), fatigue, depression, vasomotor symptoms (hot flashes), and treatment- or cancerrelated immunosuppression. In most instances, the acupuncture or acupressure interventions are used in addition to state-of-the-art pharmaceutical treatments, such as antiemetic therapy (such as Odansetron) for nausea and vomiting. Why performed: Cancer patients and their clinicians often resort to acupuncture and acupressure (and other alternative medical treatment modalities) for symptoms that are not amenable or are unresponsive to traditional therapies. Sometimes they are used to augment the effectiveness of conventional medicines, as in the case of antiemetic therapies for nausea and vomiting, which can lead to weight loss and depression. Some patients (and their clinicians) are seeking a more holistic approach to healing, viewing acupuncture and acupressure as methods that restore harmony to the body, treating the whole person instead of just the disease. Often patients take solace in the “mysterious” mechanisms underlying alternative treatments. Many acupuncturists are intrigued by the TCM philosophies and theories, at the same time applying current Western knowledge of anatomy and neurophysiology to their techniques. Most acupoints correspond to specific nerve pathways or receptors and/or highly vascular areas. There is strong evidence that acupuncture modulates neurotransmitters, leading to the release of endogenous opioids (endorphins and
Acupuncture and acupressure for cancer patients enkephalins) for analgesia (pain relief). Manipulation of certain acupoints stimulates the autonomic nervous system, leading to changes in blood circulation and engaging components of the immune and endocrine systems (proteins called cytokines or the release of endogenous corticosteroids and other hormones). These procedures can also alter blood pressure, heart rhythms, and body temperature. Not all the mechanisms involved in successful acupuncture and acupressure treatment are understood, and they remain a subject of scientific investigation. Some skeptics still believe that they work primarily via the placebo effect. Patient preparation: Very little patient preparation is required for these procedures. The patient disrobes to the extent required for examination and the placement of acupuncture needles or accessibility to acupressure points. Some acupuncturists will take a patient’s medical history
A patient receives an acupuncture treatment. (PhotoDisc)
9
Acupuncture and acupressure for cancer patients and ask questions about diet and exercise. Some will also look at the patient’s tongue and feel his or her pulse in order to make a TCM diagnosis and appropriate acupoint prescription tailored to the patient’s needs. A more Westernized approach would be to apply a standard point prescription for a particular malady, omitting such TCM elements as tongue and pulse exams. Steps of the procedure: The acupuncturist will feel for the appropriate acupoints, often massaging the area prior to needle insertion. The skin is then cleaned with an alcohol wipe and the needle is inserted until the practitioner feels some resistance and/or the patient feels a tingling or cramping sensation. This is referred to as “obtaining the qi,” or De Qi. Many practitioners then manipulate the needle, using hand technique (shou fa) to move, supplement or drain the qi and/or yin and yang. The needles are then usually left in place for ten to twenty minutes. In acupressure, the patient or practitioner applies pressure to the acupoints for a few minutes, repeating this action at intermittent intervals over a specified period of time. Sometimes a band with an attached stud is applied over an acupoint and the patient is instructed to press the stud into the point at prescribed intervals in an effort to obtain a De Qi response during point stimulation. Sometimes an acupuncturist will apply a small electric current to the needles in a technique called electroacupuncture. This is another method of stimulating the acupoints. Various other methods of stimulation are employed as well. Moxibustion applies heat to the acupoints using burning mugwort herb (Artemisia vulgaris). Aquapuncture is a technique in which acupoints are injected with drugs, vitamins, flower essences, herbal extracts, or other fluids for longer-term stimulation of acupoints. After the procedure: A properly treated patient should experience relaxation, deeper respiration, and increased vitality following acupuncture, since energetic balance has supposedly been restored. For treatment of specific cancer-related symptoms, some immediate relief is expected, followed by delayed improvement, especially after multiple acupuncture or acupressure sessions. Risks: Acupuncture should be avoided in patients with thromobocytopenia or aplasia or in those treated with anticoagulants. Some common side effects are bruising, local bleeding, and mild pain in the treated areas. The risk of infection is small if sterile, disposable needles are used. There is a very small risk that the lungs or other internal organs can be punctured if a needle is placed too deep. 10
Salem Health: Cancer Results: The results of many random, controlled clinical trials have demonstrated that acupuncture is effective for reducing episodes of acute vomiting following chemotherapy for breast and other cancers. The same and other studies have shown that acupressure at certain acupoints is effective for reducing episodes of acute nausea following chemotherapy. Both acupuncture and acupressure have been more effective for prophylactic treatment of vomiting and nausea following conventional cancer treatment rather than stopping these symptoms once they have started. One study indicated that the effectiveness of acupuncture for reducing vomiting episodes following chemotherapy was increased for up to twenty-four hours when acupressure followed needling therapy. One review of acupuncture for the relief of cancerrelated pain found that ear acupuncture (stimulation of acupoints corresponding to different body areas on the ear) was effective for reducing cancer-related pain. Other clinical trials have shown that acupuncture helps reduce the number of hot flashes in men being treated with hormones or surgery for prostate cancer and women being treated with tamoxifen or related hormone therapies for breast cancer. Investigators, however, have noted a dearth of random, double-blind, controlled clinical trials for proving the effectiveness of these alternative therapies. The development of a sham acupuncture needle (the needle withdraws into the shaft upon “insertion” at true acupoints) is expected to improve the rigorousness of these trials and to provide substantive evidence for or against acupuncturerelated therapies. Lisa J. Shientag, V.M.D. u
For Further Information Ezzo, J. M., M. A. Richardson, and A. Vickers. “Acupuncture Point Stimulation for Chemotherapy-Induced Nausea or Vomiting.” The Cochrane Database of Systematic Reviews 2 (2007). Hyangsook, L., K. Schmidt, and E. Ernst. “Acupuncture for the Relief of Cancer-Related Pain: A Systematic Review.” European Journal of Pain 9, no. 4 (August, 2005): 437-444. Sagar, Stephen M. Restored Harmony: An Evidence Based Approach for Integrating Traditional Chinese Medicine into Complementary Cancer Care. Hamilton, Ont.: Dreaming DragonFly Communications, 2001. See also Bone cancers; Bone pain; Complementary and alternative therapies; Home health services; Integrative oncology; Living with cancer; Pneumonia; Side effects; Smoking cessation.
Salem Health: Cancer
Acute lymphocytic leukemia (ALL)
u Acute lymphocytic leukemia
(ALL) Category: Diseases, symptoms, and conditions Also known as: Acute childhood leukemia, acute lymphoblastic leukemia, acute lymphoid leukemia Related conditions: Acute myeloid leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia Definition: Acute lymphocytic leukemia (ALL) is a cancer of the white blood cells. A lymphocyte is a type of white blood cell made in the bone marrow that helps fight infection. In this fast-growing type of cancer, for unknown reasons, the bone marrow begins to make lymphocytes that develop abnormally. “Acute” means that the disease affects lymphocytes before they are fully formed and that it progresses rapidly if not treated. Risk factors: Few risk factors exist for ALL. Receiving high doses of radiation, usually as treatment for another type of cancer, is one risk factor. Exposure to benzene may also be a factor. Risk increases in people with certain other diseases, such as Down syndrome, Fanconi anemia, Bloom syndrome, and some other genetic diseases. In about 25 percent of ALL cases, the patient has a chromosome mutation in which parts of chromosome 9 and chromosome 22 have changed places. Having a sibling, especially a twin, with ALL also increases the risk for this disease. Researchers are exploring lifestyle or environmental relationships, but it appears that many factors, including a combination of genetic and environmental factors, may be involved in developing ALL.
and slightly more common in white children than in children of other races. ALL occurs in people of all ages but has a peak incidence in children between the ages of two and five. After age five, risk decreases, then increases again in people over age fifty. It is the most common type of leukemia in children under the age of fifteen, accounting for about 80 percent of childhood leukemias. It occurs more often in developed countries and in people with higher socioeconomic status. Symptoms: Symptoms of ALL include anemia, body aches, bone pain, bruises without any injury, enlarged lymph nodes, an enlarged spleen, excessive bleeding from minor injuries, fever with no illness or lasting low-grade fever, frequent infections, headaches, joint pain, nosebleeds, paleness, shortness of breath during activity, tiredness, vomiting, and unexplained weight loss. Screening and diagnosis: There is no screening test for ALL. Blood and bone marrow tests are necessary to diagnose ALL. These tests look for abnormal lymphocyte cells. A bone marrow aspirate test (using a long needle to take marrow out of the bone) and a bone marrow biopsy (surgical removal of some bone marrow) are two possible tests. The bone marrow aspirate test looks for abnormal
Etiology and the disease process: Through a genetic process that is not completely understood, cells in bone marrow begin to form abnormally. ALL can begin in two different types of lymphocytes, either B cells or T cells. As the abnormal lymphocytes quickly grow, they crowd out the red and white blood cells and platelets that the body needs and that are also created in the bone marrow. The symptoms of ALL come from the crowding out of these normal, healthy cells. These cells may then spread into the lining of the spine and brain. Incidence: About 5,200 people in the United States were diagnosed with ALL in 2007. It is slightly more common in men than in women
A nine-year-old girl with acute lymphocytic leukemia describes her condition to a health care worker. (Simon Fraser/Photo Researchers, Inc.)
11
Acute lymphocytic leukemia (ALL)
Age at Death for Acute Lymphocytic Leukemia, 2001-2005 Age Group
Deaths (%)
Under 20 20-34 35-44 45-54 55-64 65-74 75-84 85 and older
21.4 15.9 9.7 11.2 11.7 12.7 11.5 5.8
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 Note: The median age of death from 2001 to 2005 was fortyseven, with an age-adjusted death rate of 0.5 per 100,000 men and women.
cells in the bone marrow and can also be used for other types of analysis. A bone marrow biopsy can show how much disease is already in the bone marrow. The results of these tests help determine which type of drug therapy to use and how long treatment should last. If a patient has been diagnosed with ALL, a lumbar puncture may be performed to see if the abnormal cells have moved into the fluid surrounding the spine and brain. Chest X rays, ultrasounds, or additional blood tests may also be used to determine the spread of the disease. Depending on where the cancer started and the results of testing, ALL may be categorized into early pre-B-cell ALL, common ALL, pre-B-cell ALL, mature B-cell ALL, pre-T-cell ALL, or mature T-cell ALL. The type of ALL helps determine which therapy to use and how long treatment should last. About 85 percent of ALL cases begin in B cells, and these cases are generally classified as lower risk. ALL may also be classified or staged using the FrenchAmerican-British (FAB) classification system. In this older system, ALL is classified according to the type of abnormal cells as follows: • ALL-11: small, uniform abnormal cells • ALL-12: large, varied abnormal cells • ALL-13: large, varied, bubble-like cells Treatment and therapy: Patients diagnosed with ALL should start treatment immediately. The course and length of treatment chosen depend on the results of the patient’s bone marrow tests, the patient’s age, the number of ALL cells in the blood, whether certain chromosomal changes 12
Salem Health: Cancer have already happened, whether ALL cells began in the B cells or the T cells, and whether ALL has spread to the brain covering or spinal cord. During therapy, bone marrow tests may be done again to make sure the treatment is destroying the cancer cells. The first part of treatment for ALL is called induction therapy. This therapy helps kill ALL cells and get a patient’s blood counts back to normal (remission). Some of the drugs used in induction therapy are given by mouth. Others are given in a vein, usually through the patient’s chest. Most often, this chemotherapy for ALL involves combining drugs to improve the effects of the drugs. Often, ALL spreads into the lining of the spinal cord and the brain. To kill these ALL cells, drugs are injected directly into the spinal fluid. Radiation therapy may be used on the spine and brain either with or without the injected drugs. Post-induction therapy, the second part of treatment for ALL, begins when a patient has reached remission. This type of therapy is needed because usually some ALL cells that cannot be detected by tests remain in the body. Postinduction therapy usually happens in two- or three-year cycles. The drugs used in post-induction therapy are usually different from those used in induction therapy, and the type of drugs used depends on how the patient responded to induction therapy and whether the patient has certain chromosome abnormalities. A patient may also need maintenance therapy after post-induction therapy to prevent the cells from regrowing. T-cell ALL, infant ALL, and adult ALL are all forms of high-risk ALL. These types of ALL are usually treated with higher doses of drugs during both induction and postinduction therapy. Some patients with high-risk types of ALL may respond well to bone marrow or cord blood transplant therapy. A bone marrow or cord blood transplant may be used when high doses of drugs are given to kill the ALL cells. These high doses of drugs may also kill healthy cells in the bone marrow. This transplant gives a patient healthy cells to replace the killed bone marrow cells. A transplant is a high-risk procedure and will probably not be used unless a patient does not have a good possibility of long-term remission with chemotherapy. High-risk ALL patients are more likely to have a transplant. The timing of a transplant is important; a patient has a better chance of a successful transplant when he or she is in remission at the time of transplant. Prognosis, prevention, and outcomes: There is no known way to prevent ALL. Most children with ALL can be cured of this disease with proper treatment. The overall survival rate for children after chemotherapy is nearly 80 percent.
Salem Health: Cancer Children with low-risk ALL have even higher survival rates. Most adults also improve with treatment; the number of adults who have remissions has increased, and the length of adult remissions has improved. The overall survival rate for adults after chemotherapy is about 40 percent, and adults with low-risk ALL have even higher survival rates. Marianne M. Madsen, M.S. u For Further Information Abeloff, M. D., et al. Clinical Oncology. 3d ed. Orlando, Fla.: Churchill Livingstone, 2004. Hoffman, R., et al. Hematology: Basic Principles and Practice. 4th ed. Orlando, Fla.: Churchill Livingstone, 2005. Lichtman, M. A., et al., eds. William’s Hematology. 7th ed. New York: McGraw-Hill, 2006. Pui, C-H, ed. Childhood Leukemias. 2d ed. New York: Cambridge University Press, 2006. u
Other Resources
Association of Cancer Online Resources http://www.acor.org CureSearch: National Childhood Cancer Foundation, Children’s Oncology Group http://www.curesearch.org Leukemia and Lymphoma Society http://www.leukemia-lymphoma.org National Cancer Institute http://www.cancer.gov/cancertopics/treatment/ See also Acute myelocytic leukemia (AML); Aleukemia; Blood cancers; Childhood cancers; Chronic lymphocytic leukemia (CLL); Chronic myeloid leukemia (CML); Hemolytic anemia; Leukemias; Myelodysplastic syndromes; Myelofibrosis; Myeloproliferative disorders; Topoisomerase inhibitors.
u Acute myelocytic leukemia
(AML) Category: Diseases, symptoms, and conditions Also known as: Acute myeloid leukemia, acute myelogenous leukemia, acute myeloblastic leukemia, acute myelomonocytic leukemia, granulocytic leukemia, acute nonlymphocytic leukemia, acute promyelocytic leukemia
Acute myelocytic leukemia (AML) Related conditions: Acute lymphoblastic leukemia, myelodysplastic syndrome Definition: Acute myelocytic leukemia (AML) describes a malignant proliferation in the bone marrow of an undifferentiated blood-forming cell of the myeloid line. AML begins with the genetic alteration of a single cell. That cell, called a blast cell, is the foundation from which the leukemia follows. The process of normal blood cell formation, or hematopoiesis, begins with undifferentiated cells, known as stem cells, inside the bone marrow. Stem cells differentiate into blasts, and these primitive blast cells give rise to red blood cells, platelets, and white blood cells. It is the accumulation of blast cells in the bone marrow and their failure to differentiate that has lethal consequences within just a few weeks or months if unchecked. Although the rate of cure has improved, treatment is still associated with high morbidity and mortality. Risk factors: Certain genetic disorders have an associated AML risk, including Down syndrome, Fanconi anemia, and Shwachman-Diamond syndrome. Other risk factors include some forms of chemotherapy, radiation therapy, and exposure to tobacco smoke and benzene. Etiology and the disease process: The process leading to acute myelocytic leukemia involves the interruption in the progression of an undifferentiated progenitor cell in the bone marrow that normally matures into red blood cells, white blood cells (neutrophils, eosinophils, basophils, and monocytes), and megakaryocytes. Megakaryocytes are bone marrow cells responsible for the production of the blood platelets necessary for blood clotting. Bone marrow is the soft interior of some bones, such as the skull, shoulder blades, ribs, pelvis, and backbones. It comes in two varieties: red marrow and yellow marrow. The red marrow, also called myeloid tissue, is the source of AML activity. Red blood cells, platelets, and most white blood cells arise from a parent cell in the red marrow. Many references limit discussion of AML to only the direct descendants of the myeloid line; these are the neutrophils, eosinophils, and basophils. When blast cells do not mature properly, they accumulate in the bone marrow. It is the proliferation and the accumulation of this hemopoietic cell in the bone marrow that defines AML. Although research has not completely unraveled the process of this leukemic transformation, there is strong evidence of underlying chromosomal damage. For example, a variety of mutations are associated with AML, with damage to the gene for FMS-related tyrosine kinase (FLT3) being the most prominent. Normally, the receptor encoded by FLT3 signals undifferentiated blast 13
Acute myelocytic leukemia (AML) cells in the bone marrow to proliferate when there is a need for additional circulating blood cells. The signal stops when the supply is sufficient, but in AML, the switch stays on, and unconstrained blast cell proliferation follows. Although AML begins with defective bone marrow cells, it generally moves quickly into the peripheral blood and may spread to other parts of the body, such as the liver, spleen, testes, brain, spinal cord, and lymph nodes. Incidence: Because AML is associated with accumulating genetic defects, the incidence increases with age. AML ranges from 0.7 to 3.9 cases per 100,000 in people up through the age of sixty and increases to 6.7 to 19.2 cases per 100,000 in people who are over sixty. The median age of onset is more than sixty-seven years. Each year AML will strike about 13,400 adults and 650 children in the United States. Symptoms: Clinical findings reflect the replacement of normal bone marrow elements with malignant blast cells. Probably the most consistent early complaints in AML are a history of increasing lethargy later followed by skin, soft-tissue, or respiratory infection. Some patients will have small red or purple spots on the body, called petichia, resulting from broken blood vessels. Liver, spleen, and lymph node enlargement is common, as is weight loss. Some symptoms are nonspecific but quite common in AML patients. These include swollen gums; pale skin; black-and-blue marks; achiness in the knees, hips, or shoulder; mild fever; shortness of breath during even light exertion; and the slow healing of cuts. Screening and diagnosis: The diagnostician must distinguish AML from other myeloproliferative disorders,
Age at Diagnosis for Acute Myelocytic Leukemia, 2001-2005 Age Group
Diagnosed (%)
Under 20 20-34 35-44 45-54 55-64 65-74 75-84 85 and older
6.3 6.3 6.8 10.9 14.8 21.1 24.6 9.2
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008
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Salem Health: Cancer chronic myelogenous leukemia, and myelodysplastic syndrome. Although many supporting tests and symptoms point toward a diagnosis, the definitive finding of AML will require bone marrow aspirate and biopsy. Short of biopsy examination, other indicators will raise suspicion. About one-third of AML patients will have an enlarged spleen and high levels of uric acid in the blood. The peripheral white blood cell count is not a good indicator, as it may be increased, decreased, or normal. However, there usually will be reduced numbers of granulocytes (neutrophils, basophils, and eosinophils) and platelets in the blood. Blast cells in the peripheral blood appear in only 15 percent of AML patients initially, but this number rises to half of those patients with decreased number of circulating white blood cells (leukopenia). There is no standard staging system for AML. Generally, doctors describe the status of the condition as untreated, in remission, or recurrent. However, bone marrow examination more closely defines AML as belonging to one of eight cell subtypes. Doctors tailor the treatment to the subtype. The subtypes are as follows:
• • • • • • • •
M0: Myeloblastic, on special analysis M1: Myeloblastic, without maturation M2: Myeloblastic, with maturation M3: Promyeloctic M4: Myelomonocytic M5: Monocytic M6: Erythroleukemic M7: Megakaryocytic
Treatment and therapy: The goal of AML treatment is the destruction of the leukemic cells. However, this requires the suppression of bone marrow activity, which brings unfortunate side effects. With the bone marrow suppressed, fewer white cell are available to fight infection and fewer red cells and platelets are present to maintain a healthy oxygen exchange and clot formation. This almost always requires treatment with antibiotics and blood transfusions. Initial treatment or induction therapy begins with a hospital stay of about a week using chemotherapy in a combination of drug types. Generally induction therapy requires more than one round of treatment, as it is likely that some AML cells will survive. Even if the induction therapy seems successful, the doctors assume that leukemic cells still exist though unrevealed on biopsy examination. In the unusual event that leukemia has spread to the brain or spinal cord, chemotherapy is also introduced into the cerebrospinal fluid. At a later date, a follow-up round of less intensive treat-
Salem Health: Cancer
Acute myelocytic leukemia (AML)
ments called consolidation therapy brings the patient back to the hospital to maintain remission status. Remission describes a normal peripheral blood profile, a normal bone marrow free of excess blasts, and a normal clinical status. Doctors generally reserve stem cell transplantation with more vigorous chemotherapy for those patients susceptible to relapse, although it is sometimes part of the consolidation regimen. However, there is some debate among doctors as to the risks and benefits of this treatment. For relapsed patients who are unable to undergo the rigors of stem cell transplantation, additional chemotherapy is generally not well tolerated or effective. Doctors adapt specific chemotherapies Human cells with acute myelocytic leukemia in the pericardial fluid. (National Cancer Institute) to the subtype of the leukemia. Usually this will be some combination of an anthracycline class agent with cytabrine. In u For Further Information some cases a third drug, 6-thioguanine, is added. Also facEzzone, Susan, and Kim Schmit-Pokorny, eds. Blood and tored into the treatment strategy are the patient’s age, cliniMarrow Stem Cell Transplantation: Principles, Praccal status, and leukemia profile. Although quite variable, tices, and Nursing Insights. Sudbury, Mass.: Jones and hospital stays for induction and consolidation therapies Bartlett, 2007. may require weeks or even months. Typically, chemotherHoffman, Ronald, et al. Hematology: Basic Principles and apy will drive the patient’s blood cell counts down to danPractice. 4th ed. St. Louis: Elsevier Churchill Livinggerously low levels. This will require drugs to elevate stone, 2005. white blood cell counts as well as antibiotics and blood Hutton, John J. “The Leukemias and Polcythemia Vera.” transfusions to protect against complications. In Internal Medicine, edited by Jay H. Stein. 5th ed. St. Louis: Mosby, 1998. Prognosis, prevention, and outcomes: The prognosis of Lichtman, Marshall A., and Jane A. Liesvelt. “Acute patients with AML largely depends on the patient’s age. In Myelogenous Leukemia.” In Williams Hematology, part this is due to chemoresistance or the biological reedited by Marshall A. Lichtman, et al. 7th ed. New sponse of cells to survive the toxic stress of chemotherapy. York: McGraw-Hill, 2006. Because chemoresistance tends to increase with age, important therapies are less effective in older patients. Also, the difference in the mechanisms of chromosome translou Other Resources cations in the young and older patients allows for a more The Leukemia and Lymphoma Society favorable outcome in the younger patient. Acute Lyelogenous Leukemia In the absence of treatment, most people stricken with http://www.leukemia-lymphoma.org/all_mat_toc AML will die less than two months after the diagnosis. .adp?item_id=3113 With therapy, between 20 and 40 percent of people survive for at least five years. The poorest prognoses are reserved National Marrow Donor Program for those patients older than sixty and for those developing Acute Myelogenous Leukemia AML following chemotherapy and radiation therapy for http://www.marrow.org/PATIENT/Undrstnd_ other cancers. In general, four years following consolidaDisease_Treat/Lrn_about_Disease/AML/index.html tion therapy, approximately 40 percent of patients under sixty years of age will be free of any signs of leukemia, See also Acute lymphocytic leukemia (ALL); Blood cancers; Childhood cancers; Chronic lymphocytic leukemia with that number dropping to 15 percent in older patients. (CLL); Chronic myeloid leukemia (CML); Fanconi aneRichard S. Spira, D.V.M. 15
Adenocarcinomas mia; Genetics of cancer; Leukemias; Leukopenia; Myelodysplastic syndromes; Myeloproliferative disorders; Myelosuppression.
u Adenocarcinomas Category: Diseases, symptoms, and conditions Also known as: Malignant adenomas, other names vary by type Related conditions: Lung cancer, breast cancer, colon cancer, renal cell carcinomas Definition: Adenocarcinoma is a type of cancer that develops in the epithelial tissue of glandular (secretory) organs. Although it is commonly associated with lung cancer (and is the most common form of lung cancer), adenocarcinoma can also develop in such organs as the breast, colon, kidney, liver, pancreas, prostate, and stomach. It is classified according to the kind of tissue from which it
Salem Health: Cancer arose (such as lung or breast) or according to a particular product of the cells (such as mucinous adenocarcinoma). Adenocarcinoma can spread (metastasize) to other parts of the body and also destroy surrounding tissues. Risk factors: Smoking increases the risk of almost every type of cancer. Other risk factors for adenocarcinoma vary by organ site. Age, race, family history, medication use, and lifestyle factors such as diet have been implicated in certain forms of adenocarcinoma. Etiology and the disease process: Etiology of and the disease process for adenocarcinoma vary with the involved organ. Incidence: Incidence of adenocarcinoma varies by type. Adenocarcinoma is the most common form of lung, pancreatic, prostate, and stomach cancer. Symptoms: Symptoms of adenocarcinoma vary by type. Small adenocarcinomas may produce only mild symptoms that go undetected. Large adenocarcinomas produce more noticeable symptoms that vary with the site of in-
A surgical specimen showing colonic adenocarcinoma. (Centers for Disease Control and Prevention)
16
Salem Health: Cancer volvement. The first signs of adenocarcinoma may be a noticeable lump and pain or discomfort. Screening and diagnosis: Diagnosis of adenocarcinoma begins with a medical history and physical examination. Lumps are commonly biopsied, and specialized imaging techniques, such as X rays and computed tomography (CT) scans, are used to determine the extent of the disease (staging). Staging of adenocarcinoma varies by type. Treatment and therapy: Specific treatment protocols vary by adenocarcinoma type and other factors, such as overall patient health and extent of the disease. Conventional treatment options include surgery, chemotherapy, and radiation therapy. Early-stage, localized disease may be treated by surgery alone (surgical removal of the tumor and surrounding tissue) or surgery with adjuvant chemotherapy or radiation therapy. Advanced adenocarcinoma has no cure. Newly emerging treatments for adenocarcinoma include hormone therapy and stem cell transplantation. Prognosis, prevention, and outcomes: Without treatment, adenocarcinoma is fatal. Routine physical examinations and avoidance of risk factors, such as smoking, are keys to early detection and prevention. Jaime Stockslager Buss, M.S.P.H., ELS See also Adenoid cystic carcinoma (ACC); Appendix cancer; Bile duct cancer; Breast cancer in children and adolescents; Bronchoalveolar lung cancer; Carcinomas; Duodenal carcinomas; Esophageal cancer; Fallopian tube cancer; Gallbladder cancer; Gastrointestinal cancers; Granulosa cell tumors; Head and neck cancers; Helicobacter pylori; Lung cancers; Mesothelioma; Mucinous carcinomas; Nasal cavity and paranasal sinus cancers; Oncogenic viruses; Pancreatic cancers; Prostate cancer; Rectal cancer; Salivary gland cancer; Small intestine cancer; Stomach cancers; Throat cancer; Urethral cancer; Urinary system cancers; Uterine cancer; Vaginal cancer; Vulvar cancer.
u Adenoid cystic carcinoma
(ACC) Category: Diseases, symptoms, and conditions Also known as: Adenocystic carcinoma, cribriform carcinoma, cylindroma, malignant cylindroma, AdCC Related conditions: Adenoma, adenocarcinoma Definition: Adenoid cystic carcinoma (ACC) is a rare malignant cancer of the secretory glands. Neoplasms usually
Adenoid cystic carcinoma (ACC) originate in the major and minor salivary glands of the head and neck region but can also occur in places such as in the trachea, lacrimal glands, breast, skin, and vulva. Risk factors: Environmental and genetic risk factors have not been identified. Etiology and the disease process: There is little information available regarding pathogenesis except for some evidence suggesting that the TP53 tumor-suppressor gene is inactivated in the most aggressive forms or stages of ACC. Incidence: Both children and adults may develop ACC; however, most patients are diagnosed between the fourth and sixth decades of life. ACC affects more women than men at a ratio of approximately 3:2. Symptoms: Signs and symptoms depend on the origin of the neoplasm. Screening and diagnosis: Unfortunately, no screening tests exist because of a lack of serum markers. Diagnosis is made after histologic analysis obtained through biopsy or resection of a tumor. ACC is classified into three major groups according to distinctive histologic growth pattern: cribriform, tubular, and solid. Treatment and therapy: The primary treatment option for adenoid cystic carcinoma is surgery. Postoperative radiotherapy or neutron beam therapy is sometimes recommended to help limit local failure. There is no effective chemotherapy for metastatic or unresectable ACC; however, several clinical trials are testing the effectiveness of new chemotherapeutic drugs (for example, paclitaxel and gemcitabine) when used alone or in combination with other drugs. Radiofrequency ablation and cryoablation are also being explored as treatment options. Prognosis, prevention, and outcomes: ACC growth and disease progression tend to be slow but relentless. ACC is atypical of carcinomas and seldom metastasizes to regional lymph nodes. Distant metastasis is the predominant reason for treatment failure and occurs most frequently in the lung, followed by the liver. Tumors with solid growth patterns and perineural invasion of major nerves or positive margins tend to have poor prognosis. In one study that followed 160 ACC patients, disease-specific survival was 89 percent at five years and 40 percent at fifteen years. Rena C. Tabata, M.Sc. See also Bronchial adenomas; Lacrimal gland tumors; Lung cancers; Nasal cavity and paranasal sinus cancers; Salivary gland cancer; Throat cancer. 17
Adenomatoid tumors
u Adenomatoid tumors Category: Diseases, symptoms, and conditions Also known as: Adenofibromyomas, Recklinghausen’s tumors Related conditions: None Definition: An adenomatoid tumor is a small benign tumor of mesothelial origin usually occurring in the male epididymis or female Fallopian tube, ovary, or uterus. Rarely, these tumors can be seen within the testes and prostate. Extragenital adenomatoid tumors have also been identified in the heart, mesentery, pleura, lymph nodes, omentum, and adrenal glands. Because of its glandular appearance, it may be confused with an adenocarcinoma or metastatic carcinoma, especially signet ring cell carcinoma. Risk factors: There are no known risk factors for adenomatoid tumors. Etiology and the disease process: An adenomatoid tumor is a benign hamartoma that is a malformation resulting from faulty development in an organ and is made up of an abnormal mixture of tissue elements normally present at that site. Most adenomatoid tumors are composed of fibrous tissue separated by numerous slitlike pseudotubular spaces crossed by peculiar threadlike bridging strands, which are their typical morphologic feature. The most common benign tumor of the epididymis, adenomatoid tumors usually arise in the tail of the epididymis and may rarely invade adjacent testicular parenchyma. Although they may occur at any age, they are most commonly seen in patients between twenty and fifty years of age and are usually asymptomatic. Although usually under 5 centimeters (cm) in size, they can grow quite large under hormonal influence. Incidence: In one study, the reported incidence of adenomatoid tumors is 1.2 percent, although the true incidence is probably greater, as most tumors are never biopsied because of their small size and similarity to leiomyomas of the uterus. When found in the male genital tract, these tumors are usually seen in an extratesticular location, usually involving the epididymis, representing approximately 30 percent of tumors arising in the paratesticular area. Symptoms: Adenomatoid tumors usually are asymptomatic. However, when adenomatoid tumors occur in the genital tract, they can grow quite large and can be painful. Screening and diagnosis: Often mistaken for uterine fibroids on magnetic resonance imaging, the radiologic appearance can vary from solid to cystic depending on the 18
Salem Health: Cancer relative amounts of cystic spaces, smooth muscle, and fibrous tissue contained within the tumor. Ultrasound is useful in diagnosing adenomatoid tumors of epididymal origin. They usually appear as a round or oval, solitary, solid, well-circumscribed mass of variable echogenicity measuring between 5 millimeters (mm) and 5 cm. Occasionally they may appear cystic sonographically and rarely appear plaquelike and ill-defined. Treatment and therapy: Surgical removal. Prognosis, prevention, and outcomes: Excellent. Debra B. Kessler, M.D., Ph.D. See also Endometrial cancer; Fallopian tube cancer; Fibrosarcomas, soft-tissue; Gynecologic cancers; Oophorectomy; Ovarian cancers; Ovarian cysts; Testicular cancer.
u Adenomatous polyps Category: Diseases, symptoms, and conditions Also known as: Colorectal adenomas Related conditions: Colon cancer, benign polyps, familial adenomatous polyposis (FAP) Definition: Polyps are abnormal tissue growths stemming from the lining of mucous membranes. Colorectal adenomatous polyps are benign (noncancerous) polyps that project from the inner lining of the colon or rectum and protrude into the lumen of the intestines. Despite their benign characteristics, adenomatous polyps can become cancerous if not removed. Risk factors: Adenomatous polyps are one of the most common types of colon polyp. Individuals over the age of fifty years are much more likely to develop these growths, as are those people with a family history of colon polyps. Additionally, having a mutation in the APC gene can cause a condition named familial adenomatous polyposis (FAP), a disorder that causes numerous polyps to grow in the intestines and almost always develop into tumors. Etiology and the disease process: Adenomatous polyps are a collection of cells that display uncontrolled proliferation, forming a growth that stems from the inner lining of the colon. Incidence: The prevalence of adenomatous polyps ranges from 10 to 25 percent of the population, depending on the type of screening procedure used. Symptoms: Most adenomatous polyps are asymptomatic, and patients are unaware of their presence until they are
Salem Health: Cancer identified through screening. When adenomatous polyps are not removed and continue to grow larger, they can eventually induce rectal bleeding, diarrhea, or constipation. Screening and diagnosis: The most common screening method to detect adenomatous polyps is colonoscopy, a procedure by which a doctor inserts a viewing tube into the colon and removes any visually identified polyps. Other screening methods that may be used are flexible sigmoidoscopy and barium enema. Removed polyps are then biopsied to determine if they are benign or have developed into precancerous or cancerous lesions. Treatment and therapy: When identified through screening, the general treatment is immediate removal of adenomatous polyps to prevent their possible development into cancer. Most doctors recommend that patients undergo subsequent colorectal screening on a regular basis for several years following the removal of adenomatous polyps. Prognosis, prevention, and outcomes: When discovered and removed, adenomatous polyps do not significantly change a patient’s quality of life. However, if left undetected, some of these polyps can develop into colon cancer, which has a higher mortality rate than any other cancer type in the United States. Some possible ways to prevent the development of adenomatous polyps is to maintain a diet that is high in fiber and low in fat, as well as refraining from smoking and excessive drinking. Lisa M. Cockrell, B.S.
Adenoviruses human viruses in the family Adenoviridae. Adenoviruses can be genetically engineered to serve as vectors that deliver targeted gene therapy to human cells. Cancers treated: Breast, colorectal, head and neck, liver, and prostate cancers Delivery routes: Injection How these agents work: Adenoviruses are nonenveloped, or naked, viruses, meaning that they lack a lipid and protein outer covering. Counterintuitively, viruses without this outer covering are better able to withstand environmental stressors such as an acidic environment, drying, and heat—and therefore may live longer outside a host cell. Most adenoviruses cause respiratory illnesses, conjunctivitis (pinkeye), or gastroenteritis and are transmitted via respiratory droplets or through fecal-oral transmission. Adenoviruses are well suited to gene therapy because of their environmental robustness, the ease of manipulating the adenovirus genome, and their ability to infect a number of different kinds of tissue. The DNA inside the adenovirus may one day be altered to encode up to forty genes.
See also Colon polyps; Colorectal cancer; Desmoid tumors; Duodenal carcinomas; Enterostomal therapy; Gardner syndrome; Gastric polyps; Genetics of cancer; Hereditary cancer syndromes; Hereditary polyposis syndromes; Polyps; Small intestine cancer; Stomach cancers; Turcot syndrome.
u Adenoviruses Category: Chemotherapy and other drugs Also known as: Adenoviridae viruses Definition: An adenovirus is a twenty-sided symmetrical icosahedron measuring between 80 and 100 nanometers in diameter with 252 capsomers forming its outside “capsid,” or protein shell. Adenoviruses contain double-stranded, linear deoxyribonucleic acid (DNA), sometimes referred to as dsDNA. These viruses are named for the the adenoids, as they were first isolated from human tonsils in the 1950’s. There are now more than forty identified types of
An electron micrograph of an adenovirus. (Centers for Disease Control and Prevention)
19
Adjuvant therapy In cancer therapy, adenoviruses are first inactivated to make them incapable of causing infection once inside the body. When injected into cancer cells, the virus can cause cell death or tumor suppression by producing toxic proteins, flagging cells for destruction by the immune system, breaking the cell apart (cell lysis), or activating genes that will cause the cell to die (apoptosis) or stop replicating. To gain access to host cells, adenoviruses attach to a receptor on the host cell, which triggers the host cell to surround, engulf, and coat the virus with chemicals. Once the virus is inside the host, the coating dissolves and the virus releases into the host cell cytoplasm. The virus makes its way to the host cell nucleus, where it disassembles itself and releases viral DNA into the host’s nuclear pores. Soon the host cell nucleus stops replicating its DNA and instead begins replicating the DNA of the adenovirus. Eventually the host cell breaks apart (lyses) and releases the newly created adenoviruses. Since most people have been exposed to adenoviruses, the immune system can mount an immune response to the adenoviruses before they have a chance to target the cancer cells. With more research into the specific targeting of cancer cells, however, a vigorous immune response may serve as a beneficial side effect of treatment. Side effects: The side effects of adenovirus use in cancer therapy include inflammation at site of injection, inappropriate immune response, fever, and coldlike symptoms. Pamela Richardson, M.S. See also Gene therapy; Oncogenes; Oncogenic viruses; Simian virus 40.
u Adjuvant therapy Category: Procedures Definition: An adjuvant therapy is any treatment given after the primary treatment to increase the likelihood of killing all cancer cells. Cancers treated: Many types, including cancers of the breast, colon, kidney, ovary, and testicle Why performed: After the primary treatment removes or kills a detected primary tumor, additional cancerous cells or microtumors may still be present in the body. Adjuvant therapy may be administered to help prevent the recurrence of cancer after the primary tumor is removed. Generally, the larger the primary tumor size at detection, the larger is the probability that residual cancer cells may be left behind following surgery. Cancer cells can break away 20
Salem Health: Cancer from the primary tumor and metastasize even when the disease is in an early stage, and they exist in a form too small to detect by radiological or laboratory testing. Patient preparation: In the decision regarding whether to undergo adjuvant therapy, a number of prognostic factors enter into the determination, such as patient age, size of primary tumor, spread to lymph nodes, and microscopic appearance of the cancer cells. Doctors consider these factors and others in order to estimate the likelihood of recurrence. The higher the risk for recurrence, the greater is the motivation to pursue adjuvant therapy options. Local adjuvant radiation treatment typically commences about three to six weeks following the primary treatment. If a combination of chemotherapy and radiotherapy as adjuvant therapy is chosen, then usually chemotherapy is received first followed by radiation, although they may be administered simultaneously in some cases. It is not known how effective adjuvant therapy may be if started later than six weeks following primary therapy. Steps of the procedure: The term “adjuvant therapy” actually encompasses many different treatment forms, including chemotherapy, radiation, hormonal therapy, targeted therapy, or some combination thereof. Adjuvant therapy can be either systemic or local. Chemotherapy, for instance, is given by mouth or injected into the bloodstream. Adjuvant chemotherapy is administered in cycles of treatment followed by recovery and typically lasts for three to six months. Side effects from adjuvant therapy such as chemotherapy or radiation may be experienced. For example, the effects of adjuvant chemotherapy may include loss of hair, loss of appetite, vomiting, diarrhea, mouth sores, psychological distress, and some loss of cognitive brain function. Medications are available to help control vomiting and nausea induced by chemotherapy. Researchers at the University of Rochester have reported that treatment with modafinil (Provigil) can alleviate the cognitive symptoms of so-called chemo brain experienced in certain cancer treatment regimens. Longer-term side effects may include infertility. Another example of adjuvant therapy is hormone adjuvant therapy to treat breast cancer. Hormone adjuvant therapy is used on breast cancer cells that have been found to be estrogen or progesterone receptor positive. Some standard hormone therapies include the synthetic hormone tamoxifen and aromatase inhibitors. Tamoxifen as an adjuvant therapy has been found to decrease the chance of recurrence in women with early-stage hormone receptor positive breast cancer. It is also used to treat women who are at risk of one day developing breast cancer. Aromatase inhibitors are used as adjuvants to reduce the levels of es-
Salem Health: Cancer trogen in postmenopausal women; they include anastrozole (Arimidex), exemestane (Aromasin), and letrozole (Femara). These drugs are not to be used by premenopausal women. Combination adjuvant therapies comprising hormone treatment together with chemotherapy are also available for some patients. After the procedure: It is advised that patients undergo regular checkups following adjuvant therapy in order to monitor any cancer recurrence. Hormone adjuvant therapy, such as used to treat some forms of breast cancer, involves longer-term procedures, with five-year regimens recommended. Risks: The risks associated with different forms of adjuvant therapy are similar to the risks of corresponding primary treatments with chemotherapy, radiotherapy, or hormone therapy. The main risk of declining to participate in adjuvant therapy is the possibility of cancer cells spreading undetected to other parts of the body. While patients with invasive cancers are often urged to consider undergoing adjuvant therapy, other options are available. Patients who turn down the option of adjuvant therapy are advised to participate in regular follow-up clinical examinations to facilitate the detection of new tumors. This alternative is often referred to as “watchful waiting.” Some of the side effects of hormone adjuvant therapy mimick the symptoms of menopause, such as hot flashes and an increased risk for the development of osteoporosis. Results: The goal of adjuvant therapy is to make primary treatment more effective and result in years of disease-free survival. Successful adjuvant therapy is marked by a lack of detectable tumor recurrence or metastasis formation in the months and years following primary therapy. Michael R. King, Ph.D. u For Further Information Henderson, I. Craig, ed. Adjuvant Therapy of Breast Cancer. Boston: Kluwer Academic, 1992. Kirkwood, John M., ed. Strategies in Adjuvant Therapy. Malden, Mass.: Blackwell, 2000. Murphy, Kevin. Adjuvant Chemotherapy Guide. Available online at http://www.cancerguide.org. Salmon, Charles G. Adjuvant Therapy of Cancer. Philadelphia: Lippincott Williams & Wilkins, 1993. u
Other Resources
Mayo Clinic Adjuvant Therapy for Breast Cancer Guide http://www.MayoClinic.com
Adrenal gland cancers National Cancer Institute http://www.cancer.gov See also Biological therapy; Chemotherapy; Hormonal therapies; Pain management medications; Radiation therapies; Watchful waiting.
u Adrenal gland cancers Category: Diseases, symptoms, and conditions Also known as: Pheochromocytoma, adrenal cortical cancer, adrenocortical cancer, neuroblastoma Related conditions: Cushing syndrome, Conn syndrome, adrenogenital syndrome Definition: The adrenal glands are hormone-producing endocrine glands located directly above the kidneys. The outer layer of each gland is called the adrenal cortex. Hormones produced in the adrenal cortex include cortisol (aids in regulating blood sugar level), aldosterone (aids in regulating fluid and electrolyte balance and blood pressure), and testosterone and estrogen (male and female sex hormones). A primary malignant tumor in the adrenal cortex—one that originates in that location—is called adrenocortical cancer. The inner area of each gland is called the adrenal medulla. Hormones produced in the medulla include epinephrine and norepinephrine, which help regulate the body’s response to physical and emotional stress. A primary malignant tumor that originates in the medulla is called a pheochromocytoma. Another form of cancer that originates in the medulla is neuroblastoma, typically found in infants and children younger than age ten. Adrenal tumors are commonly classified by their effect on hormone production in the affected area. Adrenal tumors that increase hormone production are called functioning tumors; those that do not produce hormones are called nonfunctioning tumors. Risk factors: Although specific risk factors for adrenal cancers have not been identified, they have been associated with genetically linked familial syndromes, such as Li-Fraumeni syndrome, Beckwith-Wiedemann syndrome, and Carney complex. Etiology and the disease process: The cause of adrenal cancer is unknown. Functioning tumors that secrete hormones produce changes in the body systems affected by those hormones. Nonfunctioning tumors typically grow large enough to produce pressure on other organs, causing discomfort or pain in the abdomen or flank. 21
Adrenal gland cancers
Salem Health: Cancer
Incidence: Primary adrenal gland cancers are rare, affecting only 1 or 2 persons per 1 million people. Approximately 60 to 80 percent of adrenal cancers are functional, secreting large amounts of adrenal hormones. Adrenocortical cancer is most common in men between the ages of forty and fifty; neuroblastoma most commonly affects children younger than age five; and pheochromocytoma is most common between ages thirty and forty. Symptoms: A functioning adrenocortical cancer tumor typically produces excess amounts of cortisol and aldosterone, which can cause elevated blood pressure, weight gain, thirst, urinary frequency, facial swelling (moon face), cramping of the muscles in the arms and legs, and increased hair growth on the face, arms, and back. If the tu-
mor produces sex hormones, men may develop a loss of sex drive, impotence, and enlarged breasts; women may develop a deeper voice, menstrual irregularities, and increased facial hair; and children may experience early puberty. A neuroblastoma can cause an unusual abdominal lump or fullness, weight loss, extreme tiredness, persistent diarrhea, flushing, sweating, elevated blood pressure, and behavior indicating the presence of abdominal pain. A pheochromocytoma can cause elevated blood pressure that is resistant to treatment, excessive sweating, severe headaches, tremors, rapid pulse, palpitations, and extreme anxiety. A nonfunctioning adrenal cancer may not produce symptoms until the cancer is advanced or has metastasized. Typical symptoms are caused by the tumor pressing on
Adrenal Glands
Kidney
Kidney
The adrenal glands are located on top of the kidneys. (LifeART© 2008 Wolters Kluwer Health, Inc.-Lippincott Williams &Wilkins. All rights reserved.)
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Salem Health: Cancer
Adrenocortical cancer therapy may be used after surgery or to treat metastatic pheochromocytoma.
Relative Survival Rates for Adrenal Gland Cancers, 1988-2001
Prognosis, prevention, and outcomes: There is no known prevention for adrenal cancer. The prognosis for adrenal cancer depends on the type of tumor and the stage of the disease. The five-year survival rate after surgery for adrenocortical cancer is approximately 10 to 35 percent; for localized pheochromocytomas it is about 95 percent. The prognosis for neuroblastoma varies widely depending on the child’s risk grouping. The five-year survival rate ranges from about 95 percent for a low-risk child to about 30 percent for a high-risk child. Metastatic tumors of all types have a poor prognosis. Dorothy P. Terry, R.N.
Survival Rates (%) Cancer Type Adrenal gland (all) Adrenocorticol Pheochromocytoma
1-Year
3-Year
5-Year
10-Year
59.4 66.0 84.5
45.5 48.5 73.0
38.7 41.2 64.8
29.6 31.3 44.0
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007)
other abdominal organs, causing pain or an abnormal feeling of fullness. Tiredness, fever, and weight loss may also be present. Screening and diagnosis: There are no screening tests for adrenal cancer. Diagnosis begins with a thorough patient and family medical history and physical examination. If adrenal cancer is suspected, the patient’s blood and urine are tested for elevated levels of adrenal hormones, and computed tomography scanning and magnetic resonance imaging are performed to identify tumors. The metaiodobenzylguanidine (MIBG) scan, during which images are taken after the injection of small amounts of radioactive materials, is used to detect the presence and location of a pheochromocytoma. Staging of adrenal cancer depends on the specific type of tumor. Treatment and therapy: Treatment for adrenal cancer usually includes surgery to remove the affected gland, followed by chemotherapy to destroy any remaining cancer cells. The type and combination of chemotherapeutic drugs used varies with the type of tumor. Mitotane, most commonly used after surgery for adrenocortical cancer, blocks hormone production and destroys adrenal cancer cells. It is also used to treat inoperable, recurrent, and metastatic adrenocortical cancer. If the patient cannot tolerate mitotane therapy or it is ineffective, cisplatin is typically used, either alone or combined with cyclophosphamide and doxorubicin, fluorouracil and doxorubicin, or VP-16. Following surgery, neuroblastoma may be treated with chemotherapy using carboplatin, doxorubicin, cyclophosphamide, and etoposide. Surgery to remove a pheochromocytoma is typically preceded by the administration of medication to block the secretion of adrenalin, which can cause very high blood pressure and serious surgical complications. MIBG radio-
u
For Further Information Bertagna, Xavier, ed. Adrenal Cancer. Montrouge, France: John Libbey Eurotext, 2006. Souhami, Robert, and Jeffrey Tobias. Cancer and Its Management. Malden, Mass.: Blackwell, 2005. Stern, Theodore A., and Mikkael A. Sekeres. Facing Cancer: A Complete Guide for People with Cancer, Their Families, and Caregivers. New York: McGraw-Hill, 2004.
u
Other Resources
American Cancer Society http://www.cancer.org Endocrine Web http://www.endocrineweb.com National Cancer Institute http://www.nci.nih.gov/cancertopics See also Adrenocortical cancer; Computed tomography (CT) scan; Cushing syndrome and cancer; Endocrine cancers; Endocrinology oncology; Hepatomegaly; Radiofrequency ablation.
u Adrenocortical cancer Category: Diseases, symptoms, and conditions Also known as: Adrenal cortex carcinoma Related conditions: Cushing syndrome, Conn syndrome, virilization Definition: Adrenocortical cancer is an aggressive malignancy that occurs when a tumor develops in the tissue of 23
Advance directives the adrenal cortex, the outer layer of tissues that surround the adrenal gland and produce steroid hormones. Risk factors: Certain hereditary diseases, including LiFraumeni syndrome, Beckwith-Wiedemann syndrome, and Carney complex, are the main known risk factors. Etiology and the disease process: The cause of these tumors is unknown. An adrenocortical cancer tumor is either nonfunctioning or functioning, meaning that it overproduces certain hormones that the adrenal cortex normally produces. These hormones include cortisol, aldosterone, testosterone, and estrogen. Adrenocortical cancer commonly becomes malignant, spreading to the lung, liver, bone, and peritoneum (lining of the abdominal cavity). Incidence: Adrenocortical cancer is relatively rare, affecting only 1 to 2 people out of 1 million every year. Although it generally occurs in adults between the ages of thirty and forty years, children can develop this cancer, usually under the age of six.
Salem Health: Cancer of the cancer at diagnosis, the general health of the patient, and whether the tumor is recurrent. Lisa M. Cockrell, B.S. See also Adrenal gland cancers.
u Advance directives Category: Social and personal issues Also known as: Living wills, durable powers of attorney for health care (DPOA), do-not-resuscitate (DNR) orders Definition: Advance directives are written instructions in the form of legal documents that allow people to communicate their desires about medical care and treatment if they cannot speak for themselves due to a terminal condition. Patients with advanced cancer may use them to allow their wishes to be known and followed.
Treatment and therapy: When discovered early, adrenocortical cancer can be cured through surgical removal of the tumor. However, because most tumors are not diagnosed until they are advanced, other treatment strategies such as radiation therapy and chemotherapy must be used. Most chemotherapy regimens to treat adrenocortical cancer include the drug mitotane, which is toxic to adrenal cortex cells, in addition to other chemotherapeutic agents such as cisplatin, doxorubicin, and etoposide.
Purposes: Advance directives are designed to allow competent patients an opportunity to express their wishes for future health decisions in the event that they are unable to participate in medical decision making because of their poor state of health. Advance directives take the pressure off family and friends by letting them know what care and services the cancer patient prefers and what treatment the patient would refuse in the event that communication is not possible. The patient can also designate a person or persons to make decisions. In families in which there is disagreement about what an ill relative would prefer, the advance directive provides clarification. If there is no advance directive and the patient becomes incapacitated with no surrogate designated, state law will dictate the order of surrogate decision makers, usually other family members. By designating a surrogate decision maker, the patient’s choice supersedes that of the state. This is particularly valuable for people without close family or in nontraditional relationships. Advance directives are important because complex choices about end-of-life care are difficult and can seem overwhelming if a someone close to the decision maker is involved. Avoiding these decisions during healthy times will place a heavy burden on family and friends later. Communicating wishes about end-of-life care will ensure that the cancer patient’s wishes are respected.
Prognosis, prevention, and outcomes: The prognosis for patients diagnosed with adrenocortical cancer is generally very poor, and dependent on several factors. These include the ability of the tumor to be surgically removed, the stage
Types: Advance directives emerged in the late 1960’s and early 1970’s as a major social and medical phenomenon resulting from the conflict between professional ethics based on the Hippocratic oath and the physician’s duty to
Symptoms: Nonfunctioning adrenocortical cancer tumors usually do not have symptoms. Functioning adrenocortical cancer tumors can generate many symptoms, owing to their overproduction of steroid hormones. Depending on the hormone, symptoms can include weight gain, high blood pressure, muscle weakness, acne, and changes in menstrual cycles. Screening and diagnosis: Laboratory testing can be used to confirm changes in steroid hormone production. Abdominal radiological examination, such as computed tomography scanning and magnetic resonance imaging, can be used to determine the exact location and extent of the tumor. Adrenocortical cancer tumors are staged on a scale of I to IV, according to the size of the tumor and the degree of invasion, both locally and to distant sites.
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Advance directives
dated, witnessed, notarized, copied, and incorporated into benefit the patient according to the physician’s own ability the patient’s medical record. A copy should be placed in and judgment and the patient’s autonomy. In Schloendorff the chart and given to the patient’s physician and attorney. v. Society of New York Hospital (1914), the Supreme Court Advance directives should be reviewed periodically and ruled that patients were entitled to complete information kept current. Some people even take their directives with about their illness and shared decision making. The Patient them when they travel. Advance directives remain in efSelf-Determination Act of 1991 mandated that all patients fect until they are revoked. admitted to acute care hospitals, long-term care facilities, health maintenance organizations, and home care proConditions: Advance directives are recognized in all fifty grams are to be informed about their rights under state law states and can be considered legally binding, provided to participate in health care decision making, including they are executed in accordance with state guidelines. their right to have written directives. Some directives are written only to apply in particular clinDespite widespread media attention, the majority of seical situations, such as when the patient has a terminal type riously ill patients do not have a written advance directive. of cancer or an incurable illness (advanced or aggressive For those without directives, family members collaborate cancers would fit these categories). Ambiguous terms with a health care provider to make decisions generally resuch as “extraordinary means” and “unnaturally prolongflective of substituted judgment or best-interest principles ing my life,” should be placed within the context of the pa(that is, what the patient would have wanted based on pretient’s values to be understood. Because these ambiguous vious statements and values). This approach, of course, is terms necessitate interpretation by caregivers, revised state problematic because often there is little evidence about the forms have attempted to overcome this problem by adpreferences of any particular patient. dressing specific interventions that are to be withheld in all Advance directives include living wills, durable powers circumstances (for example, blood transfusions, dialysis, of attorney for health care (DPOA), and do-not-resuscitate ventilators and respirators, CPR, artificial nutrition and (DNR) orders. There are two broad categories of advance hydration, withholding of food and fluids, and organ and directives: instructive and proxy. Instructive directives altissue donation). low an opportunity to express preferences regarding the It is important to understand that a decision not to reprovision of particular treatment options. Living wills ceive “aggressive medical care” is not the same as withare the most common examples of instructional directives holding all medical care. A cancer patient can still receive in which the patient’s preferences are specified, but there antibiotics, nutrition and hydration, medication, radiation are also other types such as no transfusion or no cardiopultherapy, and pain management (palliative or comfort care). monary resuscitation (CPR) directives. The proxy direcAnother approach can provide instructions in the event of tive, generally a durable power of attorney for health a specific circumstance or diagnosis (such as a prolonged care, allows the patient to designate a surrogate decision maker of the patient’s choosing. This surrogate makes health care decisions for the patient in the case of incapacity. Choosing a Surrogate Decision Maker It should be noted that advance directives Picking a proxy decision maker can be a difficult task. Generally, experts are applicable only in situations in which parecommend that the proxy has the following qualities: tients are unable to participate in their health care decision making. The assessment of ca• shares the patient’s values and beliefs about end-of-life care and death pacity for decision making is sometimes dif• is a person with whom the patient can comfortably talk about difficult ficult and may involve a psychiatric evaluaissues tion and even a legal determination. If a • is a responsible, calm, mature person patient is competent and communicative, • is willing to assume this responsibility however, the advance directive will not • ideally is a person who lives close or is able to travel to the patient’s apply. location A health care proxy or surrogate is a per• is not the patient’s health care provider (for legal reasons) son appointed to make a patient’s medical • is chosen separate from considerations of who will handle the patient’s financial issues decisions if and when the patient is unable to do so. The durable power of attorney for • is the person, whether relative or friend, that the patient trusts the most to make medical decisions health care is the legal document that names the health care proxy. It should be signed, 25
Aflatoxins state of unconsciousness, trauma, or a diagnosis of dementia). Some living wills state that patients do not want lifeprolonging treatments if their condition necessitates constant care and supervision. Alternatively, others can state that patients wish their lives to be prolonged as long as possible. Advance directives can be revised or revoked as long as the patient remains competent to participate in medical decisions. Decisions by competent patients always supersede written directives. If there is disagreement among family members about the interpretation or authority of a patient’s advance directive, the medical team or a medical ethicist should meet with the family, clarify, and attempt to resolve the issue. Limitations: Living wills cannot possibly be made allencompassing because of the great variability in end-oflife care. Pain alleviation or management is among the most controversial end-of-life issues. Laws regulating drug addiction are inconsistent among the states, and the role of lethal drugs in the management of end-of-life pain and discomfort is being debated in Congress. Cancer patients making or considering writing advance directives are encouraged to communicate their preferences with their medical providers and surrogate decision makers. Most states ensure that patients remain in charge of their medical care until at least two physicians declare them to be incapacitated. Health care providers may refuse to honor the patient’s stated wishes or decisions because of personal standards or institutional policies. If either is the case, it is up to the individual health care provider to inform the surrogate immediately and transfer the patient to another provider. Marcia J. Weiss, J.D. u
For Further Information King, Nancy. Making Sense of Advance Directives. Dordrecht, Netherlands: Kluwer, 1991. Mappes, Thomas A., and David De Grazia. Biomedical Ethics. 6th ed. New York: McGraw-Hill, 2006. Sass, Hans-Martin, Robert M. Veatch, and Ribito Kimura, eds. Advance Directives and Surrogate Decision Making in Health Care: United States, Germany, and Japan. Baltimore: Johns Hopkins University Press, 1998. Ulrich, Lawrence P. The Patient Self-Determination Act: Meeting the Challenges in Patient Care. Washington, D.C.: Georgetown University Press, 1999. Weir, Robert F. Abating Treatment with Critically Ill Patients: Ethical and Legal Limits to the Medical Prolongation of Life. New York: Oxford University Press, 1989. 26
Salem Health: Cancer u
Other Resources
American Cancer Society Advance Directives http://www.cancer.org/docroot/MIT/mit_3_1_1.asp National Cancer Institute End-of-Life Decisions http://www.cancer.gov/cancertopics/pdq/ supportivecare/transitionalcare/HealthProfessional/ page9 See also Cardiopulmonary resuscitation (CPR); Do-notresuscitate (DNR) order; End-of-life care; Living will; Long-distance caregiving; Transitional care.
u Aflatoxins Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1980 Also known as: Aflatoxin B1, aflatoxin B2, aflatoxin G1, aflatoxin G2, aflatoxin M1 Related cancers: Liver cancer, primary liver cell cancer, hepatocellular carcinoma, lung cancer Definition: Aflatoxins are naturally occurring toxic metabolites produced by certain fungi that grow on some agricultural products. At least thirteen different aflatoxins are produced in nature, with the four major aflatoxins called aflatoxin B1, B2, G1, and G2. Aflatoxin B1 is typically the most predominant as well as the most toxic. Aflatoxin M1 is found primarily in milk. Exposure routes: Ingestion and inhalation Where found: Numerous agricultural commodities, including corn and other grains, peanuts, tree nuts, and cottonseed meal. Milk, eggs, and meat products can be contaminated if animals consume aflatoxin-contaminated feed. At risk: Those living in countries where agricultural products that readily support the growth of aflatoxin-producing fungi are a dietary staple. Farmers and other agricultural workers are at risk for occupational exposure through inhalation of dust generated during handling of contaminated crops and feeds. Etiology and symptoms of associated cancers: Aflatoxin-producing fungi can grow on a wide range of agricultural products. Corn and groundnuts are major sources of human exposure because of greater susceptibility to contamination and widespread consumption. Worldwide,
Salem Health: Cancer
Aflatoxins
These peanuts are contaminated with aflatoxins. (AP/Wide World Photos)
corn is probably of greatest concern because it is grown in climates that readily support the growth of fungi and is a dietary staple in many countries. Aflatoxin-producing fungi often grow on crops in the field before harvest, particularly if the crops have experienced drought stress. After harvest, contamination can occur during storage. The growth of aflatoxin-producing fungi and subsequent production of aflatoxins are influenced by weather conditions such as temperature and humidity. As a result, aflatoxin contamination varies with geographic location, agricultural and agronomic practices, and the susceptibility of crops to fungal growth. Exposure to aflatoxins occurs primarily by consuming contaminated food. Aflatoxin consumption is commonplace in developing countries where food supplies are limited and regulations of aflatoxin levels are not enforced or nonexistent. In developed countries, food supplies are generally more abundant and diverse, and aflatoxin levels are monitored to limit toxin ingestion. Although the sale of heavily contaminated food supplies is not permitted in
developed countries, chronic exposure to low levels of aflatoxins may still be a concern. The most common aflatoxin-producing fungi are Aspergillus flavus and Aspergillus parasiticus. Although many aflatoxins are produced by these fungi, aflatoxin B1 is the most prevalent and the most toxic. Aflatoxin B1 is also the most potent naturally occurring carcinogen. Aflatoxins are both toxic and carcinogenic, with exposure to high levels resulting in toxic effects referred to as aflatoxicosis and chronic exposure to low levels potentially resulting in cancer. Susceptibility to aflatoxin-related diseases is influenced by many factors, including age, exposure level, duration of exposure, health, nutritional status, and exposure to other agents, such as the hepatitis B virus (HBV). The liver is the primary target organ of aflatoxin exposure, although other organs can also be affected. Metabolic activation by liver enzymes is required for the carcinogenic effects of aflatoxin B1. In the liver, aflatoxin B1 is metabolized to a highly reactive form that readily binds deoxyribonucleic acid (DNA) and proteins and can lead to 27
African Americans and cancer liver damage and subsequent formation of tumors in the liver. Exposure to aflatoxins in the diet has been shown to be one of the major etiological factors in the development of primary hepatocellular carcinoma in some countries, such as China and many African countries. Concurrent infection with HBV and exposure to aflatoxins results in significantly greater liver damage than either infection or exposure alone, a synergy that is likely produced because HBV interferes with the liver’s ability to detoxify aflatoxins. Although aflatoxin is most well known as an agent that promotes liver cancer, inhalation of contaminated grain dust has been associated with an increased incidence of lung cancer. Liver cancer is not associated with any symptoms in the early stages. As the cancer progresses, symptoms may include pain in the upper abdomen on the right side, which may also extend to the back and shoulder. Other symptoms include a swollen or bloated abdomen, weight loss, loss of appetite, feeling of fullness, weakness, fatigue, nausea and vomiting, yellowish skin and eyes, dark urine, and fever. History: Aflatoxins have been recognized as a significant contaminant since the 1960’s, when more than 100,000 young turkeys on poultry farms in England died from what was termed turkey X disease. The mortalities were traced to consumption of mold-contaminated peanut meal. In 1961 the toxin-producing fungus, A. flavus, was identified and the toxin given the name aflatoxin. The International Agency for Research on Cancer (IARC) first recognized aflatoxins as carcinogenic in 1976. In 1987 naturally occurring mixtures of aflatoxins and AFB1 were classified as Group I carcinogens. Aflatoxins are considered unavoidable contaminants of food and feed, even when good manufacturing practices have been followed. Although absolute safety can never be achieved, many countries have attempted to limit exposure to aflatoxins by imposing regulatory limits on commodities intended for consumption. The Food and Drug Administration has established specific guidelines that regulate this toxin to very low concentrations in human food and animal feed. Catherine J. Walsh, Ph.D. u
For Further Information Bennet, J. W., and M. Klich. “Mycotoxins.” Clinical Microbiology Reviews 16, no. 3 (2003): 497-516. Eaton, D. L., and J. D. Groopman. The Toxicology of Aflatoxins. New York: Academic Press, 1994. Goldblatt, L., ed. Aflatoxin: Scientific Background, Control, and Implications. New York: Academic Press, 1969. 28
Salem Health: Cancer U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Eleventh Report on Carcinogens. Research Triangle Park, N.C.: Author, 2005. u
Other Resources
Centers for Disease Control and Prevention http://www.cdc.gov National Cancer Institute http://www.cancer.gov National Toxicology Program http://ntp.niehs.nih.gov U.S. Food and Drug Administration Center for Food Safety and Nutrition http://www.cfsan.fda.gov See also Free radicals; Hepatomegaly; Infectious cancers; Liver cancers; Risks for cancer.
u African Americans and cancer Category: Social and personal issues Definition: Cancer is the second leading cause of death among African Americans. African Americans experience higher cancer rates than any other racial or ethnic group in the United States, as well as higher mortality rates from those cancers. Description of the population: The U.S. government identifies as African Americans “individuals whose origins are from any of the black racial groups of Africa,” including people who self-report their ethnicity as “Black, African American, or Negro” or who describe themselves as African American, Afro-American, Angolan, Negro, West Indian, Afro-Caribbean, Nigerian, Haitian, Gullah, Creole, West African, Afro-Latin, Afro-Brazilian, Congolese, Americo-Liberian, Bantu, Guinean, Moor, Pygmy, or Liberian. According to the Census Bureau, African Americans represented more than 13 percent of the U.S. population as of 2006. Incidence, death, and survival statistics: The average U.S. life expectancy was 49.2 years in the nineteenth century. The National Vital Statistics Reports (vol. 47, no. 28) note that African American life expectancy is 70.2 years, as opposed to 76.5 years for the U.S. population overall. African American men have a life expectancy of only 66.1 years; for all U.S. men it is 73.6 years. These statistics are
Salem Health: Cancer reflected in the cancer morbidity rates for African Americans: In 2003, for example, cancer was the second leading cause of death of African Americans (topped only by heart disease). The death rate outstripped that of whites, with 234.5 African Americans (versus 188.3 whites) dying of cancer per every 100,000 in the U.S. population. Overall, African Americans have higher cancer rates than any other racial or ethnic group in the United States, and their death rates from those cancers are also higher. The five-year survival rate among African Americans for all cancers improved from 27 percent in 1960-1963 to 57 percent in 1996-2002. Nevertheless, at more than 63 percent, whites were still more likely to survive five years after diagnosis. African American men are more likely to succumb to cancer than are white men, although this disparity, after peaking in the early 1990’s, has begun to decline. Death rates for African American women are closer to those for white women—although still higher. The fact that African Americans are more likely to be diagnosed with cancer later in the disease process and have less access to high-quality care in part explains their increased likelihood of death. The American Cancer Society reported that between 2000 and 2003, the cancers afflicting African American men most often were, from highest to lowest incidence, prostate cancer, lung and bronchial cancers, colorectal cancer, kidney and renal pelvic cancers, urinary bladder cancer, oral cavity and pharyngeal cancers, stomach cancer, non-Hodgkin lymphoma, pancreatic cancer, myeloma, leukemia, liver and intrahepatic bile duct cancers, laryngeal cancer, esophageal cancer, brain and other nervous system cancers, small intestinal cancer, soft-tissue (including heart) cancers, Hodgkin disease, Kaposi sarcoma, thyroid cancer, testicular cancer, melanoma of the skin, and mesothelioma. For all these cancers combined, African American men were afflicted, on average, 1.2 times more often than white men, with particularly noticeable disparities in Kaposi sarcoma, myeloma, and small intestinal cancers. For the same period, cancers afflicting African American women were, from highest to lowest incidence, breast cancer, colorectal cancer, lung and bronchial cancers, uterine corpus cancer, pancreatic cancer, non-Hodgkin lymphoma, uterine-cervical cancer, ovary, kidney and renal pelvic cancers, stomach cancer, myeloma, leukemia, urinary bladder cancer, thyroid cancer, oral cavity and pharyngeal cancers, brain and other nervous system cancers, liver and intrahepatic bile duct cancers, esophageal cancer, soft-tissue (including heart) cancers, small intestinal cancer, Hodgkin disease, laryngeal cancer, and melanoma of the skin. The overall incidence for African Amer-
African Americans and cancer
Five-Year Relative Survival Rates for Selected Cancers for African Americans and Whites in the United States, 1996-2002 Survival Rates (%) Cancer Type Prostate Female breast Bladder Uterus Cervix Colon and rectum Non-Hodgkin lymphoma Leukemia Mouth Lungs and bronchi Esophagus
African American
White
98 77 64 60 63 55 54 40 40 12 11
100 90 82 85 73 65 64 49 61 15 16
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 Note: Based on cancer patients diagnosed between 1996 and 2002 and followed through 2003
ican women was, on average, slightly less than for white women, although the incidence of myeloma, stomach cancer, and small intestinal cancer among African American women was more than twice that among white women— balanced by lower incidence rates for other cancers, including breast and uterine corpus. For 1996-2002 (in descending order), survival rates among African Americans as a whole were best for prostate, female breast, urinary bladder, uterine corpus, uterine cervical, colorectal, non-Hodgkin lymphoma, leukemia, oral cavity, lung and bronchial, and esophageal cancers. For these same cancers combined, white survival rates exceeded those of African Americans by an average of 11.45 percent (ranging from 2 to 25 percent). The greatest disparities in survival rates could be seen in uterine corpus and oral cavity cancers: Whites outlived blacks by 25 percent and 21 percent, respectively. For 2007, the cancers projected to be diagnosed most often in African American men were prostate (37 percent), lung (15 percent), and colorectal (12 percent) cancers. African American women were expected to be diagnosed most often with breast (27 percent), lung (13 percent), and colorectal (12 percent) cancers. Risk statistics: The major risk factors for cancer in all populations are socioeconomic status, tobacco use, and 29
African Americans and cancer being overweight or obese. African Americans are disproportionately poor: In 2004, more than 29 percent of African Americans fell below the poverty line, as opposed to 13 percent of whites. Because one-fifth of African Americans are uninsured, access to care, particularly preventive and screening care, is limited relative to the rest of the population. Limited detection, in turn, leads to later diagnoses and thus cancers that are more difficult to treat and to survive. Tobacco use—the biggest risk factor for the deadliest cancer, lung cancer—accounts for about 30 percent of cancer deaths overall. Among African Americans, lung cancer death rates are higher than those of whites, even though most African Americans begin smoking at a later age and smoke fewer cigarettes per day. The amount of each cigarette smoked, the type of cigarettes commonly smoked (mentholated, with higher concentrations of carbon monoxide), and the condition of the individuals who smoke (nutritional status and genetic differences) are predicted to account for the higher death rates. Overweight and obesity, which constitute a growing pandemic in American society generally, are defined as a body mass index (BMI) greater than 25 (overweight) or greater than 30 (obese). After tobacco use, obesity is the second leading cause of preventable deaths in the United States. According to the 2003 National Health and Nutrition Examination Survey, nearly 33 percent of U.S. adults were obese, and as early as 2002, overweight individuals formed 65 percent of the U.S. population. Among African Americans, 76 percent were either overweight or obese as of the year 2004. Obesity is positively correlated with certain cancers, particularly breast, endometrial, and colon cancers. Perspective and prospects: From the early 1970’s to 1992, rates of both incidence of and deaths from cancer increased among African Americans. After 1992, both death and incidence rates for all cancers among both sexes of African Americans, fortunately, declined. Five-year survival rates also improved, from only 27 percent in the early 1960’s to 57 percent by 2002. Nevertheless, to bring about parity with the rest of the population, some key factors must be addressed: The current health care system must educate, train, and prepare a health care workforce that is intimately aware of African American health issues and must be sensitive to perceptions, concerns, and fears that may exist in the African American population. A concerted effort must also be made to educate African Americans regarding the role they play in improving their own health. They must understand the importance of health care screenings, weight re30
Salem Health: Cancer duction and management, exercise, and regular physical examinations. Beyond prevention, however, African Americans continue to need better access to the health care system, improved medical insurance, more routine screenings, earlier detection, and better treatments upon diagnosis. With better access, informed African Americans can become empowered to take control of their health by seizing every opportunity to improve it. Christina J. Moose, M.A. u
For Further Information American Cancer Society. Cancer Facts and Figures for African Americans. Atlanta: Author, 2007. Bailey, Eric J. Medical Anthropology and African American Health. Westport, Conn.: Bergin & Garvey, 2000. Byrd, W. Michael, and Linda A. Clayton. A Medical History of African Americans and the Problem of Race, Beginnings to 1900. Foreword by Robert J. Blendon. New York: Routledge, 2000-2002. Collins, Catherine Fisher. African American Women’s Health and Social Issues. Foreword by Vivian W. Pinn. Westport, Conn.: Praeger, 2006. Rawls, George, Frank P. Lloyd, Jr., and Herbert Stern. Managing Cancer: The African American’s Guide to Prevention, Diagnosis, and Treatment. Roscoe, Ill.: Hilton, 2001. Reed, James, Neil Shulman, and Charlene Shucker. The Black Man’s Guide to Good Health: Essential Advice for the Special Concerns of African-American Men. New York: Berkley, 1994. Williams, Christopher Kwesi O., Olufunmilayo I. Olopade, and Carla I. Falkson, eds. Breast Cancer in Women of African Descent. London: Springer, 2006. u
Other Resources
African American Health Network http://www.aahn.com MedlinePlus African-American Health http://www.nlm.nih.gov/medlineplus/ africanamericanhealth.html National Cancer Institute Center to Reduce Cancer Health Disparities http://crchd.cancer.gov/index.html NetWellness African American Health Center http://www.netwellness.org/healthtopics/aahealth
Salem Health: Cancer
Africans and cancer
See also Africans and cancer; Asian Americans and cancer; Epidemiology of cancer; Ethnicity and cancer; Geography and cancer; Latinos/Hispanics and cancer; Polyps; Sézary syndrome; Smoking cessation; Statistics of cancer; Stomach cancers; Survival rates; Testicular cancer.
million people. In contrast, the average radiation machine in Europe serves a population of only about 250,000 people. Additionally, only fifteen countries in Africa have any radiation machines at all. The United Nations estimates that only about 20 percent of Africa’s population has any kind of radiation therapy available to them, and in many cases, available can mean hundreds of miles away.
u Africans and cancer
Problems of prevention and treatment: Africa faces many significant challenges to the successful prevention, early diagnosis, and treatment of cancer. Prevention of cancer requires education of the population about what types of things may increase the risks of developing cancer, and what things and lifestyle choices are believed to reduce the risk of cancer. Smoking and use of tobacco products in any form have been linked to cancer for many years. However, public education about the perils of smoking can be difficult, time-consuming, and expensive. Most African governments are already highly burdened, and there are rarely any budget dollars left to go to public education about something as intangible as smoking or tobacco use and its correlation with an increased risk for cancer. Another barrier to prevention in Africa is that what is considered a healthy lifestyle for cancer prevention is not accessible to many Africans. Most African countries have a per capita national income that labels them as low- or very low-income countries. Fresh, clean water and many different fruits, vegetables, whole grains, and lean proteins, all considered part of a healthy lifestyle in the United States and other developed countries, are not reasonably accessible to many people living in Africa. The opportunity for early diagnosis is severely lacking in most areas of Africa. Diagnosing cancer when it is in its earliest stages leads to the most positive prognosis. Many cancers that are treatable if found early are almost never treatable when diagnosed in a very late stage. Preventive health care is not readily accessible in most parts of Africa, and many people seek medical attention only when there is an obvious problem. Unfortunately, because many cancers produce severe symptoms only when in the later stages, this means that most cancers diagnosed in Africa are diagnosed at a stage too late to be treated successfully. This problem is caused by many interacting factors, including many people living too far from health care to reasonably get preventive screenings, lack of education about the benefits of early detection, and lack of medical professionals and facilities to do the screenings. The cost of preventive medicine and screenings is also often a barrier to early diagnosis. Even when an early diagnosis is made, there are many
Category: Social and personal issues Definition: According to the World Health Organization, cancer is the leading cause of death worldwide, and more than 70 percent of those deaths occur in countries that are considered low or middle income. Cancer is one of the top health problems in Africa, where access to quality health care is often barred by distance, availability, and income. Statistics: There are many barriers to good statistical analysis of cancer trends in Africa. There are no governmental agencies charged with the collection and monitoring of cancer statistics and trends as there are in the United States. In addition, many Africans live in remote areas and do not necessarily seek treatment in hospitals or clinics, so data about cancer incidence and mortality are difficult to collect and assess accurately. However, the World Health Organization (WHO) did compile statistics about cancer incidence and mortality in Africa as a whole in 2002. In that year, about 582,000 people (283,000 men and 299,000 women) living in sub-Saharan Africa developed cancer. Also in 2002, 412,100 in the same area died due to cancer. The most common forms of cancer in Africa among women were breast cancer, cervical cancer, and Kaposi sarcoma (a form of cancer common in individuals with acquired immunodeficiency syndrome, or AIDS). In men the most common cancers were Kaposi sarcoma, prostate cancer, and liver cancer. Lung cancer and stomach cancer were also very common and were especially likely to result in death. It is estimated that in 2020 804,000 people living in sub-Saharan Africa will develop cancer, and that 624,000 will die of it that year. There are many barriers to the successful treatment of cancer in Africa. In August, 2007, the World Health Organization estimated that 80 to 90 percent of the cancer cases that are encountered by doctors and hospital personnel in Africa are diagnosed when the cancer has developed and spread too far to be successfully treated. Additional difficulties occur because of significant lack of resources. According to the United Nations, Ethiopia did not receive a radiation therapy machine until 1997, and many years later it still had only one machine to serve a population of 65
31
Afterloading radiation therapy barriers to effective cancer care in Africa. There is a significant lack of the resources and equipment necessary for the treatment of cancer. Treating cancer is a process that requires many experts and technologically advanced equipment and drugs. Unfortunately, much of the necessary equipment is prohibitively expensive for most hospitals and clinics in Africa. Additionally, there is a lack of training programs and trained health professionals to run the equipment, administer medication, and oversee treatment. The dispersed nature of the population over most of Africa is also a barrier to effective care. Even if a country does have a few hospitals or centers with the staff and equipment necessary for cancer treatment, many millions of individuals may live too far from the center to be able to make effective use of what it offers. Another problem facing the African health care community in its attempts to successfully treat cancer is the AIDS epidemic. Millions of Africans are infected with the human immunodeficiency virus (HIV) or have AIDS, and it contributes to problems for cancer treatment in a number of ways. The AIDS epidemic is stretching the resources of the health care systems in most African countries very thin. Because AIDS impairs the immune system’s ability to function properly and ward off disease, individuals with AIDS need significant medical treatment for the many complications that occur. Individuals with AIDS are also more likely to develop cancer, especially Kaposi sarcoma, one of the most common cancers in Africa. This stretches the cancer resources that do exist even more thinly.
Salem Health: Cancer too bright, even small improvements in resources and education can make a huge difference in the number of Africans affected by cancer. Cancers that are usually detected early and cured in the United States and Europe could also be cured in Africa if they were detected early enough and the right treatment options were available. Progress made in improving the AIDS epidemic may also have beneficial effects on the rates of cancer incidence and mortality in Africa. As Kaposi sarcoma, a cancer common among those with AIDS, is one of the leading cancers in Africa, reducing the number of individuals infected with HIV should cause a reduction in the number of individuals with AIDS-related cancers. Helen Davidson, B.A. u
For Further Information O’Keefe, Stephen J. D., et al. “Why Do African Americans Get More Colon Cancer than Native Africans?” Journal of Nutrition 137, no. 1 (January, 2003): 175183. Sloan, Frank A., and Hellen Gelband, eds. Cancer Control Opportunities in Low- and Middle-Income Countries. Washington, D.C.: National Academies Press, 2007. U.S. Department of Health and Human Services, National Institutes of Health, and the National Cancer Institute. NCI International Portfolio: Addressing the Global Challenge of Cancer. Bethesda, Md.: National Cancer Institute, 2006.
u
Outlook for the future: The outlook for the future of cancer in Africa is not excellent, but it is improving. Although estimates suggest that there will be increasing numbers of cancer cases in Africa over the next decades, some organizations and groups are making strong efforts to stop the problem. Many of these efforts focus on increased access to prevention, early diagnosis, and access to treatment. In May, 2005, the World Health Organization adopted a resolution on cancer prevention and control. The resolution called on member states of the organization to take steps to reduce cancer incidence and mortality by creating and putting into action programs of cancer control. The WHO breaks down the areas of concern for countries that are working to stop cancer into four broad categories: prevention, early detection, diagnosis and treatment, and palliative care. Some private and corporate organizations are also working to help prevent and treat cancer in Africa. Various programs work to raise awareness of the problem of cancer in Africa and to raise money for desperately needed equipment, training, and education. Although the outlook is not 32
Other Resources
Cancer-Africa http://www.ialphan.com/cancerafrica/ World Health Organization http://www.who.int See also African Americans and cancer; HIV/AIDS-related cancers; Kaposi sarcoma; Rectal cancer.
u Afterloading radiation
therapy Category: Procedures Also known as: High dose rate remote afterloading (HDR) Definition: Afterloading radiation therapy is a form of high dose rate brachytherapy that uses a computer-controlled machine called an afterloader to deliver radiation from iridium 192 directly to a tumor. Iridium 192 is a radioac-
Salem Health: Cancer tive source that emits high-energy gamma rays, a type of radiation that is used to kill cancer cells. The radioactive source is contained in the lead-shielded machine and welded to a stainless steel cable that is inserted into the tumor through catheters, needles, or balloons placed in the tumor or tumor bed. Afterloading radiation therapy is considered a temporary implant because the radioactive source does not remain in the patient, and the patient is not radioactive. Cancers treated: Lung cancer, breast cancer, prostate cancer, head and neck cancers, uterine cancer, cervical cancer, esophageal and bile duct cancers, soft-tissue sarcoma, rectal cancer, others under study Why performed: The use of a high-dose remote afterloader provides more targeted therapy to the tumor, or to the tumor bed after the bulk of the tumor is removed in surgery. The afterloader provides more accurate dose delivery to the target site while better protecting normal tissue. Its use also provides a shorter course of therapy of approximately one week, as compared to external beam radiation therapy, which takes place over four to six weeks. The dose distribution is more even, and there are fewer hot (overdose) spots or cold (underdose) spots. Side effects occur less often with HDR therapy. Patient preparation: Planning for the use of afterloading radiation therapy often begins before an initial surgery, depending on the type of cancer and its site. The surgeon and the radiation oncologist will confer, as the catheters used in administering the radiation may be placed at the time of the initial surgery for the cancer. Catheters or needles may also be placed in an outpatient setting under local anesthesia or other sedation. Imaging or radiology studies may be used to assist in treatment planning for the optimal radiation dose delivery to the tumor site and to verify the location of the catheters, especially if it has been a few weeks since their placement. A simulation is done to visualize the tumor or tumor site in comparison to adjacent organs and tissues using a computed tomography (CT) scan or X ray. This procedure assists the radiation oncologist in planning the amount of dose that the afterloader will deliver. The simulation data are then loaded into a treatment-planning computer, which calculates the dose needed. Steps of the procedure: The patient arrives in the radiation oncology center and may change into a gown prior to receiving treatment. For some prostate treatments, needles may be placed prior to the treatment under local anesthesia. Upon entering the treatment room, the patient is assisted to a comfortable position that also allows access to
Afterloading radiation therapy the ends of the catheters or needles. The treatment catheters or needles from the patient are attached to the transfer tubes from the afterloader. The treatment personnel leave the room but can observe the patient using closed-circuit television and an intercom for communication. The treatment data loaded into the HDR unit control the movement of the source into the patient and the time that the source remains at various stops along the catheters or needles in order to achieve the distribution of dose planned. The source is placed in the patient for approximately ten to fifteen minutes, but a single treatment may take up to one hour or more. The complexity of the treatment, the site being treated, and the strength of the radioactive source will dictate the time involved. The radiation oncologist will discuss the number of treatments needed based on the disease, but treatment times vary from a few days to slightly more than a week. After the procedure: Depending on the site being treated, the patient may need to stay in the hospital or may be allowed to go home between treatments. A bandage may be placed over the catheters. After all treatments are complete, the catheters are removed by clipping the sutures holding the catheters, and they are withdrawn. A small amount of bleeding may occur, but it is quickly controlled with direct pressure, and a bandage is applied over the site. Risks: Risks are related to catheter movement out of the site being treated. It is important for patients to tell the radiation staff if a catheter seems to have moved, or if it gets snagged on clothing or the bandage at any time. A misplaced catheter or needle may deliver radiation to normal tissues or organs, causing radiation burns. There is a risk that cancer cells may be missed by the radiation. Results: Outcomes vary by the disease being treated, but success rates for HDR treatments are comparable to other forms of treatment in most instances. Patricia Stanfill Edens, R.N., Ph.D., FACHE u
For Further Information Hoskin, P. J., and P. Bownes. “Innovative Technologies in Radiation Therapy: Brachytherapy.” Seminars in Radiation Oncology 16, no. 4 (October, 2006): 209-217. Hoskin, P. J., K. Motohashi, P. Bownes, L. Bryant, and P. Ostler. “High Dose Rate Brachytherapy in Combination with External Beam Radiotherapy in the Radical Treatment of Prostate Cancer: Initial Results of a Randomized Phase Three Trial.” Radiotherapy & Oncology 84, no. 2 (August, 2007): 114-120. 33
Agent Orange National Cancer Institute. Radiotherapy and You: Support for People with Cancer. Available online at http://www .cancer.gov/cancertopics/radiation-therapy-and-you. u
Other Resources
American Cancer Society http://www.cancer.org American Society for Therapeutic Radiology and Oncology Patient Web Site http://www.rtanswers.org See also Brachytherapy; Cobalt 60 radiation; External beam radiation therapy (EBRT); Intensity-modulated radiation therapy (IMRT); Iridium seeds; Proton beam therapy; Radiation therapies; Radiofrequency ablation; Stereotactic radiosurgery (SRS).
u Agent Orange Category: Carcinogens and suspected carcinogens Also known as: Super Orange Related cancers: Soft-tissue sarcoma, non-Hodgkin lymphoma, Hodgkin disease, chronic lymphocytic leukemia (CLL), acute myelogenous leukemia (AML) Definition: Agent Orange was a chemical mixture used in the United States to control weeds and in Vietnam during the Vietnam War to remove forest cover. So named because of the orange stripes painted on its storage drums, Agent Orange is a blend of two herbicides: 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). Although 2,4,5-T is not highly poisonous, the manufacturing process generates a toxic by-product called TCDD, or 2,3,7,8-tetrachlorodibenzop-dioxin. This dioxin, classified as a human carcinogen, tainted Agent Orange formulations. Exposure routes: Inhalation, ingestion, skin contact, ocular absorption Where found: Herbicide mixtures formerly used for agricultural, forestry, and military purposes At risk: Combatants and civilians exposed to Agent Orange during the Vietnam War and their children, workers occupationally exposed to the chemical, and populations exposed through domestic herbicide spraying Etiology and symptoms of associated cancers: Because epidemiologic data on Vietnam veterans is limited, the 34
Salem Health: Cancer health effects of Agent Orange have been studied indirectly in certain populations highly exposed to dioxin or dioxin-tainted herbicides. These studies provide sufficient evidence linking Agent Orange to chloracne, an acnelike skin disorder, and to certain cancers, induced when TCDD activates a protein receptor in target cells. The soft-tissue sarcomas develop from fat, muscle, or deep body tissues and usually appear as a lump. Hodgkin disease (highly curable) and non-Hodgkin lymphoma originate in lymphatic tissue and result in painless swelling of lymph nodes under the skin. Chronic lymphocytic leukemia, which develops from white blood cells, is often asymptomatic, but later is marked by enlarged lymph nodes. Paternal exposure to Agent Orange has been associated with acute myelogenous leukemia in children. This fastgrowing cancer of the bone marrow produces abnormal white blood cells and results in fatigue, shortness of breath, and increased susceptibility to infection. Only limited evidence links Agent Orange to respiratory cancer, prostate cancer, and multiple myeloma. History: Phenoxy herbicides, including the 2,4,5-T component of Agent Orange, were developed in the 1940’s and widely used in agriculture and forestry. Starting in 1960 during the Vietnam War, the United States military sprayed Agent Orange onto lands in Vietnam and Laos. It suspended this activity in 1970, after a study in laboratory animals linked 2,4,5-T to birth defects. Since the 1980’s, various groups of Vietnam veterans have filed lawsuits against the makers of Agent Orange. The United States has permanently banned all uses of 2,4,5-T and, consequently, Agent Orange. Anna Binda, Ph.D. See also Dioxins; Multiple myeloma; Mycosis fungoides; Organochlorines (OCs); Pesticides and the food chain.
u Aging and cancer Category: Social and personal issues Definition: The most significant risk factor associated with developing cancer is age, with 60 percent of all cancers occurring in people who are sixty-five and over. Mortality rates are also highest in this age group; older individuals typically have additional chronic medical conditions that enhance the risk for simultaneously occurring psychiatric morbidity. These complex and potentiating trends are creating new clinical challenges that threaten to overwhelm the current health care system. Based on projections that 1 in 5 Americans will be over the age of
Salem Health: Cancer
Aging and cancer
Cancer is more common and deadlier in the elderly. (Digital Stock)
sixty-five by 2030, there is an immediate need to better understand the influence of age on cancer detection, diagnosis, and treatment, with the goal of modifying infrastructure, practices, and the educational preparation of future health care providers. Biology of aging and cancer: Based on the population trends, research aimed at illuminating the biology of aging and mechanisms that enhance cancer susceptibility are increasing. A clearer understanding of the well-documented age-related increase in cancer incidence is needed to develop well-conceived primary cancer prevention strategies. This line of research has been designated as a priority by the National Cancer Institute. At present, there are three major hypotheses that explain the association between cancer and age: Hypothesis 1 holds that the link between aging and cancer is simply related to duration of carcinogenesis. In other words, the high prevalence of cancer in older individuals simply reflects more prolonged exposure to carcinogens. Hypothesis 2 proposes that age-related, progressive changes within the human organism may provide an in-
creasingly favorable environment for the induction of new cancers and the growth of preexisting but latent malignant cells. These mechanisms may be related to proliferative senescence, whereby aging cells lose their ability to undergo apoptosis (a form of cell death that leads to the sequential elimination of cells without releasing harmful substances into the body). When apoptosis does not work right, cells that should be eliminated become immortal, stimulating cancer-related mutations at the cellular level. Hypothesis 3 combines aspects of the first two hypotheses and proposes that the aging, cancer-prone human phenotype is characterized by an accumulation of dysfunctional senescent cells. These cells proliferate via synergistic, simultaneous physiologic processes that foster progressive accumulation of cancer-prone mutations; silencing of genes that previously functioned to prevent cancerpredisposing mutations from developing in response to carcinogens (failure of epigenetic gene silencing); and telomere dysfunction (telomeres are specialized structures at chromosome ends that regulate their replication and stability). These changes are particularly relevant to the production of malignancies because they occur within the 35
Aging and cancer context of an aging microenvironment of surrounding tissues. Cancer, aging, and psychiatric comorbidity: As increased longevity contributes to rising cancer incidence, those diagnosed often have one or more additional chronic medical conditions. Paradoxically, new treatment discoveries have extended survival for multiple medical illnesses but often within the context of troubling side effects and consequences that in turn have led to documented increases in the incidence of psychiatric morbidity. The incidence of psychiatric morbidity is further enhanced as the burden of cancer care progressively shifts from the health care system to family caregivers. Family caregivers are usually aging spouses with medical problems of their own or adult children, with their own families, jobs, responsibilities, and problems. When the role of providing complex cancer care for a loved one is added to their already stressful lives, risk for psychiatric morbidity is significantly enhanced. Although the preceding issues have been largely ignored, they continue to strain the U.S. health care system to its limit. The preceding trends are occurring within a system in which mental health services are a low priority. Stigma, limited knowledge regarding the nature and intensity of psychiatric symptoms associated with clinical need, and inconsistent, generally inadequate reimbursement mechanisms are a sampling of the multiple issues contributing to
Problems to Consider in Treating Pain in Older Cancer Patients Other chronic illnesses: Patients taking multiple medications may be at risk for drug interactions. Impairments in hearing, vision, and mental function: Patients may need to be monitored more frequently and tests may need to be simplified. Patient-controlled analgesia: Patients are more sensitive to the side effects of these drugs, which remain in their bodies longer. Opioids: Patients may be more sensitive to the effects of these drugs and experience longer periods of pain relief. Side effects from nonsteroidal anti-inflammatory drugs (NSAIDs): Stomach and kidney toxicity, constipation, headaches, and difficulties with the ability to think may arise. Administration of medicine: Some older patients may not be able to administer some drugs as directed (for example, inserting a drug into the rectum). Source: National Cancer Institute
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Salem Health: Cancer our dismal state of mental health services. Research, professional education, and clinical services are most deficient with regard to the psychiatric morbidity that occurs within the context of a chronic medical illness. Psychiatric symptoms are typically treated only when they emerge as disease states within an expensive, fragmented, specialtyoriented system. Reimbursement for psychiatric treatment is difficult to obtain, yet paying out of pocket is prohibitive and biases care toward the affluent. Limited solutions to these consequential problems potentiate untold human suffering, negative clinical outcomes, and high resource utilization that could be avoided if problems were dealt with before they got out of hand. Cancer screening in the elderly: Considerable uncertainty regarding the use of cancer screening procedures in the elderly is illustrated by the range of age cutoffs recommended by various guideline panels. To address inconsistencies, it has been suggested that a comprehensive framework rather than specific age parameters should inform individual screening decisions in older cancer patients. Screening decisions should encompass estimates of life expectancy, risk of cancer death, documented screening outcomes, and a risk-benefit screening ratio. For example, harm may result from screening practices that detect and treat cancers that never would have become clinically significant. Because many cancer screening decisions in older adults cannot be answered solely by quantitative estimates of benefits and harms, consideration of predicted outcomes within the context of an individual’s values and preferences is an important aspect of informed screening decisions. Statistics reveal considerable underutilization of cancer screening practices in the United States. Having health insurance, a regular doctor, and a point of usual care all are associated with higher cancer screening rates and better preventive health care overall. When these supports are absent, cancer screening rates drop considerably. The lack of preventive services reimbursed by Medicare, the limited number of elders with comprehensive, employerprovided health coverage, and growing numbers of elders who are homebound or lack a regular physician and point of care make elderly Americans especially prone to lacking supports that facilitate cancer screening practices. Age-related differences in cancer treatment: Cancer treatments may produce different therapeutic and adverse responses based on patient age. For example, chemotherapy resistance and toxicity have been shown to vary by age, being more common and severe in the elderly. Treatment toxicities may develop in old versus young recipients because of increased vulnerability of target organs and de-
Salem Health: Cancer layed renal excretion of treatment agents and metabolites. These problems should be managed with treatment modifications determined by kidney function and other relevant parameters of individual health status and treatment response. Aging cancer patients often do not receive adequate information to assist with or inform a definitive treatment plan. Understanding why these deficiencies exist is vital to reducing disparities in cancer mortality between young and old. Studies suggest that treatment uncertainty could be better addressed if elderly cancer patients were offered a choice from a group of definitive therapies. Treatment discussions should also address common concerns related to the costs and functional consequences of each treatment in relation to expected benefits. Current understanding of age-related differences in pharmacokinetics, drug interactions, adverse events, and treatment adherence is extremely limited. Palliative cancer care of the elderly: Despite ambitious research, treatment, and educational initiatives, the quality of palliative care provided to the elderly has historically been and remains poor. Research consistently demonstrates unnecessary suffering among elderly patients with advanced cancer. Their suffering is related to myriad issues, including uncontrolled physical symptoms, depression, and unaddressed existential concerns. Wide gaps in palliative care services targeted to elderly patients with cancer occur across a range of settings, including hospice, where the approach to palliative care has been largely insufficient. Some studies report lower levels of psychological distress in elderly versus young cancer patients, which has been erroneously interpreted to mean that elders are better equipped to manage existential concerns because they are at a stage in life when death is expected. However, data may more accurately reflect age-related differences in exposure to prevention, screening, and treatment practices; the resultant cancer course; and symptom profiles. Results therefore indicate the need for ongoing research and education targeted to unraveling complex relationships between aging and cancer. Knowledge development and dissemination must be met aggressively with clinical initiatives throughout the twenty-first century and beyond as population, demographic, and clinical trends continue to outpace the availability of resources for elderly individuals with cancer. Jeannie V. Pasacreta, Ph.D., A.P.R.N. u For Further Information Hassett, M. J., et al. “Frequency and Cost of Chemotherapy-Related Serious Adverse Effects in a Population
Aging and cancer Sample of Women with Breast Cancer.” Journal of the National Cancer Institute 98, no. 16 (2006): 11081117. Kumar, H., P. Soares, L. Balducci, and B. Djulbegovic. “Treatment Tolerance and Efficacy in Geriatric Oncology: A Systematic Review of Phase III Randomized Trials Conducted by Five National Cancer InstituteSponsored Cooperative Groups.” Journal of Clinical Oncology 25, no. 10 (2007): 1272-1276. Lichtman, S. M., et al. “International Society of Geriatric Oncology Chemotherapy Taskforce: Evaluation of Chemotherapy in Older Patients—An Analysis of the Medical Literature.” Journal of Clinical Oncology 25, no. 14 (2007): 1832-1843. Muss, H. B. “Older Age: Not a Barrier to Cancer Treatment.” New England Journal of Medicine 345 (2001): 28-29. Talarico, Lilia, Gang Chen, and Richard Pazdur. “Enrollment of Elderly Patients in Clinical Trials for Cancer Drug Registration: A Seven-Year Experience by the U.S. Food and Drug Administration.” Journal of Clinical Oncology 22, no. 22 (2004): 4626-4631. Trimble, E. L., and M. C. Christian. “Cancer Treatment and the Older Patient.” Clinical Cancer Research 12, no. 7 (2006): 1956-1957. Yancik, R., et al. “Perspectives on Comorbidity and Cancer in Older Patients: Approaches to Expand the Knowledge Base.” Journal of Clinical Oncology 19 (2006): 1147-1151. u
Other Resources
AARP Foundation http://www.aarp.org/foundation American Cancer Society http://www.cancer.org American Geriatrics Society/Foundation http://www.americangeriatrics.org Family Caregiver Alliance http://www.caregiver.org Geriatric Mental Health Foundation http://www.gmhfonline.org/gmhf Medicare.gov http://www.medicare.gov National Institute on Aging http://www.nih.gov/nia See also Advance directives; Aids and devices for cancer patients; Caregivers and caregiving; Childbirth and can37
Aids and devices for cancer patients cer; Counseling for cancer patients and survivors; Do-notresuscitate (DNR) order; Elderly and cancer; End-of-life care; Living will; Medicare and cancer; Nutrition and cancer prevention; Occupational therapy; Overtreatment; Palliative treatment; Self-image and body image; Singlehood and cancer; Support groups; Survivorship issues; Young adult cancers.
u Aids and devices for cancer
patients Category: Social and personal issues Also known as: Prostheses, breast forms, positioning aids, nutritional aids, braces, canes, walkers, wheelchairs, aromatherapy products, music therapy products Definition: Aids and devices for cancer patients are designed to help a person live a more comfortable and enjoyable life in spite of the side effects of cancer treatment. Some aids and devices help temporarily hide the effects of a cancer treatment while others can improve mobility or provide comfort permanently.
Salem Health: Cancer Another side effect of cancer treatment can be difficulty swallowing and keeping food down. To help people facing this situation get proper nutrition, there are thickening products available to add substance to liquefied foods. These products include gelatin, tapioca flour, cornstarch, commercial thickeners, pureed vegetables, instant potatoes, and baby cereal. There are also a number of liquid nutritional supplement drinks, many available at local grocery stores, that can provide needed nutrition when other types of food cannot be eaten. Some cancer patients experience sun sensitivity. Sunscreen or protective clothing can help protect sensitive skin from the sun. Sunscreens can be found at drug and grocery stores, and a number of companies create clothing—pants, shirts, hats, and gloves—that has built-in sun protection. For both men and women, making an extra effort to maintain personal grooming routines can be a way to maintain a positive attitude. Organizations such as the American Cancer Society provide classes that address special concerns cancer patients may have about their grooming and beauty routines (for example, how to deal with thinning hair). Music can be a wonderful aid in lowering stress levels and helping cancer patients sleep better. It is also shown to reduce pain by increasing endorphins and boosting immunity. It is recommended that the music be sixty beats or less per minute to provide relaxation. Much classical music falls into this category. Many hospitals offer group music therapy sessions.
Comfort aids and devices: A number of products can help cancer patients with some of the physical and emotional discomfort they may experience because of their cancer treatment. Specialty positioning pillows and foam wedges can help patients on bed rest prevent bedsores. In addition, special seat cushions for wheelchair users can help distribute their weight evenly over a large area, preventing sores and easing discomfort. These cushions tend to be filled with either water or gel. Water-filled products help decrease body temperature and gel-filled help maintain body temperature. A simple straw can make drinking beverages easier for cancer patients with sores in the mouth. If dry mouth is a problem after the salivary glands have been removed or damaged by radiation, saliva substitute products can add moisture to a cancer patient’s mouth. A cool-mist humidifier can also help prevent dry mouth by moistening the air within a room. Note that it is important to keep the humidifier clean so that germs are not spread. A wheelchair can provide mobility for a cancer patient. (PhotoDisc) 38
Salem Health: Cancer Aromatherapy may also help ease discomfort. Scents are available to help with all kinds of ailments, from pain and discomfort to lethargy. For example, lavender is a calming scent and can help ease anxiety or sleeplessness. Aromatherapy products and books explaining how to use scents can be found at many health food stores and online. Patients should check for any side effects or interactions with medical conditions before using a particular scent. An inexpensive way that many cancer patients deal with their emotions is to keep a journal. Writing down their thoughts about their situation can be very therapeutic and make it easier to keep a positive outlook. Prosthetic devices: A second category of aids and devices includes prosthetic body parts. Prostheses are available for a large number of body parts, and cancer patients should discuss with their doctors the options available to them for replacing amputated extremities. These products can help individuals regain mobility or provide cosmetic benefits. Braces, canes, walkers, and wheelchairs can improve mobility, whether used on their own or in combination with prosthetic limbs. For breast cancer patients who have undergone mastectomies, prostheses provide more than cosmetic benefits. They can provide protection and pain relief during healing, help maintain proper posture, and help prevent back and shoulder pain. Breast forms made of silicone or fiber can be inserted into a specially made mastectomy bra or worn next to the skin with a special adhesive. Cooling pads can also be inserted into bras to help relieve pain while the area heals. Specialty vests with flat panels can provide post-radiation treatment comfort. In addition, special arm sleeves can be worn to help reduce swelling by providing graduated compression. Cancer patients experiencing hair loss may want to try using a satin pillowcase to help minimize loss and to provide comfort to their sensitive scalps. Head scarves and wigs can be worn to hide hair loss. Sleep and swim caps are also available to protect remaining hair and minimize additional hair loss. Cost and insurance coverage: Some comfort and prosthetic devices are covered by public and private insurance providers. Patients should contact the insurance company before purchasing an item to find out whether the device in question is covered and if any paperwork or special authorization is needed. Some companies may require a prescription from a physician and preauthorization before they will pay for a device. Other insurance companies ask patients to pay up front for an item and then be reimbursed. If an insurance company will not cover a product and the patient cannot afford it, sometimes local cancer sup-
Air pollution port agencies such as the American Cancer Society or CancerCare can help obtain the needed item or suggest other ways to get the necessary money to pay for the item. Jennifer M. Hickin, B.S. u
For Further Information Garrison, Kevin S. It’s Just a Matter of Balance. Baltimore: Gateway Press, 2005. Gaynor, Mitchell L. The Healing Power of Sound: Recovery from Illness by Using Sound, Voice, and Music. Boulder, Colo.: Shambhala, 2002. Kelly, Mary Olson. Number One Best Tools and Tips from the Trenches of Breast Cancer. Austin, Tex.: Books Beyond Borders, 2006. Klein, Karen. Mama Said There’d Be Days like This: A Twelve-Step Guide to Surviving a Mastectomy. Farmington, Conn.: Variegate Press, 2001. Oritz, Lori M. Facing the Mirror with Cancer: A Guide to Using Makeup to Make a Difference. Chicago: Belle Press, 2004. Shurr, Donald G., and John W. Michael. Prosthetics and Orthotics. Upper Saddle River, N.J.: Prentice Hall, 2001. Wilson, A. Bennett, Jr. A Primer on Limb Prosthetics. Springfield, Ill.: Charles C Thomas, 1998. u
Other Resources
American Cancer Society http://www.cancer.org CancerCare http://cancercare.org TLC http://www.tlcdirect.org See also Breast implants; Breast reconstruction; Caregivers and caregiving; Electrolarynx; Esophageal speech; Home health services; Hospice care; Integrative oncology; Living with cancer; Reconstructive surgery; Self-image and body image; Side effects.
u Air pollution Category: Carcinogens and suspected carcinogens RoC status: Asbestos, known human carcinogen since 1980; diesel exhaust particulate, reasonably anticipated human carcinogen since 2000. Other air pollutants that are known human carcinogens include benzene, 1,3-butadiene, radon, and tobacco smoke; 39
Air pollution
Salem Health: Cancer
those that are reasonably anticipated human carcinogens include formaldehyde and polycyclic aromatic hydrocarbons. Air pollutants such as ozone, oxides of nitrogen, and sulfur oxides are not listed in the Report on Carcinogens (RoC); however, epidemiologic studies (studies on populations) provide some evidence of their association with lung cancer. Of the many components of particulate matter (PM), only diesel exhaust particulate has been the subject of studies that led to its current classification. Also known as: Criteria air pollutants, toxic air pollutants Related cancers: Lung cancer, pleural and peritoneal mesotheliomas, gastrointestinal cancers, laryngeal cancer, cancers of the lymphatic and blood-forming systems (1,3butadiene) Definition: Air pollution is the presence of contaminants, many of which are carcinogens, in the air. Outdoors, pollution is largely a consequence of the combustion of fossil fuels for transport, power generation, and other human activities. Indoors, pollution is generated by burning solid
fuels, and the air may also contain asbestos, radon gas, environmental tobacco smoke, formaldehyde, and volatile organic compounds. Exposure routes: Inhalation Where found: Indoor and outdoor air. Outdoor pollutants can be carried far from their original source by air currents. At risk: Populations exposed to smog and particulate matter in air pollution, including inner-city residents; people living near electric-power-generating plants, factories, and refining plants; occupationally exposed railroad workers and synthetic rubber industry workers; people cooking indoors with solid fuels Etiology and symptoms of associated cancers: According to the World Health Organization, the air contains a complex mixture of pollutants, including primary emissions such as diesel soot particles and oxides of nitrogen produced during combustion processes, the products of atmospheric transformation such as ozone, and the sulfate particles formed by burning sulfur-containing fuels. Although air pollution is a minor contributor to lung
Exhaust from cars on congested freeways contains carcinogens. (©iStockphoto.com/Dan Eckert)
40
Salem Health: Cancer cancer compared with tobacco smoke, it can affect entire populations, and components of the pollutant mix might interact with other carcinogens, possibly increasing their effects. In 1995 researchers Aaron Cohen and C. Arden Pope III analyzed epidemiological studies and found that they consistently suggested that ambient air pollution, chiefly as a result of the incomplete combustion of fossil fuels, is responsible for increased rates of lung cancer. A study published in 1998 of nonsmoking adults over a fifteen-year period by David Abbey and his coworkers showed a strong association between ozone levels and lung cancer. The ozone at ground level (which people inhale) is not emitted directly into the air. It is created by chemical reactions between oxides of nitrogen, emitted in motor vehicle exhaust and by industrial facilities, and volatile organic compounds from many sources, including gasoline vapors and chemical solvents. The relation between ozone levels and lung cancer has been reported in many additional scientific studies. The major outdoor air pollutants linked to lung cancer are particulate matter, sulfur oxides, ozone, oxides of nitrogen, and volatile organic compounds. Particulate matter is the term for a mixture of solid particles and liquid droplets found in the air that come from soot, smoke, and diesel exhaust. The particles of most concern are those smaller than 10 micrometers in diameter. Once inhaled, the smaller particles can travel to the deepest regions of the lungs, where chemicals (such as those adsorbed to diesel exhaust particulate) can be released. Some of these chemicals cause deoxyribonucleic acid (DNA) mutations, which can lead to cancer. Many studies have demonstrated that exposure to indoor air pollutants has adverse effects on health. More than three billion people worldwide depend on solid fuels, including biomass fuels and coal, for their cooking and energy needs. Combustion of these materials indoors produces high levels of smoke that contains many pollutants, and there is consistent evidence of lung cancer in adults exposed to coal-generated pollutants, according to the World Health Organization. Inhaling asbestos fibers released from damaged or crumbled insulating materials or other products containing this material can lead to mesothelioma and several other cancers. Other common indoor air pollutants include formaldehyde, environmental tobacco smoke, radon gas, and polycyclic aromatic hydrocarbons (a class of volatile organic compounds). History: Many of the components of air pollution are recognized as known or reasonably anticipated carginogens, such as asbestos, benzene, 1,3-butadiene, radon, tobacco
Air pollution smoke, diesel exhaust particulate, formaldehyde, and polycyclic aromatic hydrocarbons. Other components have scientific research supporting their link to human cancer. The Clean Air Act as amended in 1990 requires the U.S. Environmental Protection Agency to set national ambient air quality standards for ozone, oxides of nitrogen, particulate matter, and sulfur oxides. The agency is mandated to work with state and local governments to reduce the release of other air pollutants classified as toxic air pollutants. Bernard Jacobson, Ph.D. u
For Further Information Beeson, W. L., D. E. Abbey, and S. F. Knutsen. “LongTerm Concentrations of Ambient Air Pollutants and Incident Lung Cancer in California Adults.” Environmental Health Perspectives 106 (1998): 813-822. Cohen, A. J., and C. Arden Pope III. “Lung Cancer and Air Pollution.” Environmental Health Perspectives 103, suppl. 8 (1995): 219-224. Jacobson, M. Z. Atmospheric Pollution. New York: Cambridge University Press, 2002. Krzyzanowski, M., B. Kunnadibbert, and J. Schneider, eds. Health Effects of Transport-Related Air Pollution. Geneva, Switzerland: World Health Organization, 2005. McGranahan, G., and F. Murray. Air Pollution and Health in Developing Countries. London: Earthscan, 2003. Pluschke, P., ed. Indoor Air Pollution. New York: Springer, 2004. Pope, C. Arden, III, et al. “Lung Cancer, Cardiopulmonary Mortality, and Long-Term Exposure to Fine Particulate Air Pollution.” Journal of the American Medical Association 287 (2002): 1132-1141. Ramachandran, G. Occupational Exposure Assessment for Air Contaminants. New York: CRC Press, 2005. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Eleventh Report on Carcinogens. Research Triangle Park, N.C.: Author, 2005. u
Other Resources
U.S. Environmental Protection Agency Pollutants/Toxics: Air Pollutants http://www.epa.gov/ebtpages/pollairpollutants.html World Health Organization Air Pollution http://www.who.int/topics/air_pollution/en/ See also Arsenic compounds; Bronchoalveolar lung cancer; 1,3-Butadiene; Cigarettes and cigars; Coke oven emis41
Alcohol, alcoholism, and cancer sions; Dioxins; Lung cancers; Occupational exposures and cancer; Polycyclic aromatic hydrocarbons; Radon; Smoking cessation; Soots; Tobacco-related cancers; Wood dust.
u Alcohol, alcoholism, and
cancer Category: Carcinogens and suspected carcinogens Definition: Alcohol is a chemical that is generated during fermentation of sugar. Ethyl alcohol is the specific chemical that is generally referred to as alcohol. Alcohol is the most commonly used intoxicating agent around the world. Alcoholism (also called alcohol-dependence syndrome) is a phenomenon of continuous intake of alcohol, with a compulsive need to consume it. Alcohol has been linked to several cancers but a direct causal relationship between the two has not been established. Alcohol as carcinogen: Intake of alcohol is considered a risk factor for developing various kinds of cancers, and therefore, alcohol has been classified as a carcinogen. Ethyl alcohol, the form in which alcohol is commonly consumed, undergoes an array of metabolic changes when ingested. The main enzymes that are involved in metabolism of alcohol are alcohol dehydrogenase and aldehyde dehydrogenase. A small amount (approximately 10 percent) is metabolized by microsomal cytochrome P4502E1 (CYP2E1). Alcohol dehydrogenase converts about 80 percent of ethanol to acetaldehyde. Acetaldehyde is a mutagen and a carcinogen and is considered a risk factor in many cancers of the upper gastrointestinal tract. Acetaldehyde is implicated in a variety of processes such as inflammation of the tracheal epithelium, delaying of cell cycle progression, induction of apoptosis, chromosomal damages and aberrations, and sister chromatid exchanges. Much of the carcinogenic effect of alcohol is attributed to this single metabolite. Direct association between the concentration of acetaldehyde in saliva and development of cancer has been reported. Acetaldehyde covalently bonds with deoxyribonucleic acid (DNA) and forms structures called DNA-adducts. The most common DNA-acetaldehyde adduct is N2-ethyl-dG, which is not mutagenic. Acetaldehyde also induces the formation of the mutagenic DNA adduct called Cr-PdG (alpha-methylgamma-hydroxy-1, N2-propano-2′-deoxyguanosine). Polyamines are one of the basic molecules essential for cells and are implicated in cell growth and differentiation, nucleic acid synthesis, and protection against oxidative 42
Salem Health: Cancer damage. Polyamines facilitate acetaldehyde-induced formation of Cr-PdG adducts. Cr-PdG adducts are highly mutagenic and interfere with DNA replication and repair, inducing cancer formation. Polyamines also react with acetaldehyde and form crotonaldehyde, which is highly carcinogenic. Response to alcohol is individualistic and differs among people and races. This is because of polymorphisms in the genes for the enzymes alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Presence of the ALDH2*1/2 allele significantly increases the risk of upper aerodigestive tract cancer. In addition to these enzymes, oral bacteria also generate acetaldehyde. High amounts of acetaldehyde are detected in saliva after alcohol consumption. Saliva is directly in contact with the upper aerodigestive tract, and this contact is considered a possible mechanism for its carcinogenic effects. Alcohol and breast cancer: Alcohol is one of the most ancient intoxicants known to humankind. Consuming one or two drinks a day is not just common but is also a social custom in many cultures. However, research suggests that even one or two drinks a day could put women at a greater risk for developing breast cancer. A study conducted at the
Alcohol has been linked to several cancers, although a direct causal relationship has not been established. (PhotoDisc)
Salem Health: Cancer
How Much Is Too Much? The risk for cancers of the mouth, esophagus, pharynx, larynx, and liver in men and women and breast cancer in women increases after about two drinks per day for men and one per day for women. One drink is defined as 12 ounces of beer, 5 ounces of wine, or 1.5 ounces of 80proof liquor. The risk for liver cancer goes up significantly after five or more drinks per day. Source: National Cancer Institute
National Cancer Institute tested postmenopausal women for differences in hormone levels after alcohol consumption (15 or 30 grams of alcohol per day) for eight weeks. Results showed a significant elevation of estrone sulfate (an estrogen metabolite) and the hormone DHEAS (dehydroepiandrosterone sulfate). DHEAS is secreted by the adrenal glands, and increased levels of DHEAS indicate induction of a process called adrenal steroidogenesis, reflecting stimulation of the hypothalamic-pituitaryadrenal axis in the brain as a response to alcohol consumption. Alcohol and liver cancers: Excessive consumption of alcohol leads to alcohol liver disease. One type of alcohol liver disease is called alcoholic cirrhosis of the liver, a condition in which normal liver tissue is completely destroyed. Cirrhosis of the liver is considered the primary risk factor for development of hepatocellular carcinoma (liver cancer). Even though alcohol does not seem to cause liver cancer directly, there is a strong association between alcohol and liver cancer.
Aleukemia all cancer-related deaths are caused by chronic alcohol consumption. Education to make people aware of the link between alcohol consumption and cancer should aid in prevention of such cancers. Geetha Yadav, Ph.D. u
For Further Information Cho, Chi Hin, and Vishnudutt Purohit, eds. Alcohol, Tobacco, and Cancer. New York: Karger, 2006. Dorgan, J. F., et al. “Serum Hormones and the AlcoholBreast Cancer Association in Postmenopausal Women.” Journal of the National Cancer Institute 93 (2001): 710-715. Seitz, H. K., B. Maurer, and F. Stickel. “Alcohol Consumption and Cancer of the Gastrointestinal Tract.” Digestive Diseases 23 (2005): 297-303. Seitz, H. K., and F. Stickel. “Molecular Mechanisms of Alcohol-Mediated Carcinogenesis.” Nature Reviews 7 (2007): 599-612. Yirmiya, Raz, and Anna N. Taylor, eds. Alcohol, Immunity, and Cancer. Boca Raton, Fla.: CRC Press, 1993.
u
Other Resources
American Cancer Society Alcohol and Cancer http://www.cancer.org/docroot/PRO/content/ PRO_1_1x_Alcohol.pdf.asp?sitearea=PRO National Cancer Institute Alcohol Consumption http://progressreport.cancer.gov/doc_detail .asp?pid=1&did=2007&chid=71&coid=706&mid= See also Esophageal cancer; Gastrinomas; Gastrointestinal cancers; Hepatomegaly; Laryngeal cancer; Liver cancers; Pancreatic cancers; Pancreatitis.
Alcohol and other cancers: Drinking two or more drinks per day increases the risk of oral and upper gastrointestinal tract (GI) cancers in both men and women. Alcoholrelated cancers include those of the mouth, esophagus, and larynx. Drinking alcohol together with smoking increases the risk of developing cancer more than drinking alone. Alcohol is addictive, and alcoholism leads to enhanced tolerance levels, loss of control, cravings for alcohol, and an inability to stop drinking even when people wish to stop or need to stop for their health. Evidence shows that the nutritional status of the body is also negatively affected by alcohol.
Related conditions: Acute and chronic myelogenous leukemia (AML and CML), acute and chronic lymphatic leukemia (ALL and CLL)
Perspectives and progress: According to World Health Organization statistics, alcohol is responsible for about 1.8 million deaths a year, and alcohol-related cancer is the most common cause of these deaths. Some 3.6 percent of
Definition: Aleukemia describes a condition in which a patient has a normal or reduced white blood cell count. Leukemia cells are present in the bone marrow. Leukemia cells may also be present in the blood. Aleukemia may be
u Aleukemia Category: Diseases, symptoms, and conditions Also known as: Aleukemic myelosis, aleukemic leukemia
43
Alkaline phosphatase test (ALP)
Salem Health: Cancer
present in any of the four major types of leukemia: AML, CML, ALL, and CLL.
u Alkaline phosphatase test
Risk factors: The risk factors are the same as those for leukemia. The risks include age, genetic diseases, prolonged exposure to some chemicals such as benzene, chemotherapies used to treat other forms of cancer, and exposure to high doses of radiation or tobacco smoke.
Category: Procedures Also known as: ALKP, alk phos, alkaline phosphatase total
Etiology and the disease process: Aleukemias start when there is damage to the deoxyribonucleic acid (DNA) of blood cells. Normal cell development is interrupted, causing a decrease of mature cells and an increase in immature cells. Incidence: Aleukemia is present at the start of about 25 to 30 percent of acute leukemias. It is more prevalent in hairy cell leukemia, which is a slow-growing subtype of CLL. Symptoms: There may be no symptoms present. Patients may experience fatigue, weight loss, easy bruising, fever, and infections. Screening and diagnosis: No specific screening test exists for aleukemia. A low white blood cell count found when a complete blood count (CBC) is done as part of a routine exam or in response to symptoms may lead to further testing and diagnosis. Diagnosis is made by the examination of blood smears and bone marrow for the presence of leukemia cells. Staging is not done for any of the leukemias except CLL. The staging of CLL is based on imaging studies, blood tests, and bone marrow examination. The stages, ranging from Stage 0 to IV, are based on the involvement of lymph nodes, spleen, and liver, and decreasing numbers of red blood cells. The other forms of leukemia are classified by cell type. Treatment and therapy: Treatment depends on the type of cell involved and the classification or staging level. In leukemias that progress slowly, treatment may not start until the disease is more advanced. Prognosis, prevention, and outcomes: Prognosis depends on the type of cell involved and the rate of progression. No method of prevention exists. Treatment may slow the progress of the disease or cause complete remission. Some types of leukemia may not respond to treatment. Wanda E. Clark, M.T. (ASCP) See also Acute lymphocytic leukemia (ALL); Acute myelocytic leukemia (AML); Anemia; Antiandrogens; Blood cancers; Chronic lymphocytic leukemia (CLL); Chronic myeloid leukemia (CML); Eosinophilic leukemia; Fanconi anemia; Leukemias. 44
(ALP)
Definition: Alkaline phosphatase (ALP) is an enzyme that helps in the process of digestion and bone development. All tissues contain ALP. Higher concentrations are found in the liver, bone, kidney, and intestines. Various processes within the tissues release ALP into the blood. By measuring ALP blood levels, doctors can determine the presence of liver and bone disease, including cancer. ALP levels are determined by testing serum or plasma on an automated chemistry analyzer. Cancers diagnosed: Cancers of the bone, renal cells, liver, gallbladder, and bile ducts Why performed: The test is done as a part of a chemistry or liver panel to detect liver or bone disease. Once a diagnosis has been made and treatment started, the test may be done to determine if treatment is effective or if disease has progressed or returned. Patient preparation: The patient may be asked not to eat or drink or take certain medications for six to twelve hours prior to the test. Steps of the procedure: A small sample of blood is collected from a vein and placed in a tube. In children, blood may be obtained from a capillary in the heel or finger. After the procedure: A small gauze or cotton ball is applied at the site of needle insertion. The patient is asked to apply pressure. The person collecting the blood observes the site for bleeding and may apply a bandage. The bandage may usually be removed in thirty to sixty minutes. Risks: Risks from the procedure include bleeding, bruising, hematoma (bleeding under the skin), fainting, lightheadedness, or the need for multiple needle sticks to obtain a sample. Results: Normal ALP levels vary by the patient’s sex and age and by the analyzer used. Each laboratory establishes a set of normal ranges based on this information. The physician receives a report of the test results with the normal values established by the testing laboratory. Elevated levels indicate the possibility of liver or bone disease, including the presence of a tumor. The test does not distinguish from which tissue the increased amount of alkaline phosphatase comes. The physician may order
Salem Health: Cancer
Alkylating agents in chemotherapy reactive compounds containing alkyl groups. They are employed as antineoplastics, drugs that kill neoplasms (cancerous tumor cells) by interfering with their deoxyribonucleic acid (DNA) and cell division.
other blood tests, including an alkaline phosphatase isoenzyme test that determines if the increased ALP comes from bone, liver, or intestine. Other procedures such as X rays may also be ordered. Following cancer treatment, ALP levels are expected to decrease. If levels remain high or increase, then some cancer may remain or has returned. Wanda E. Clark, M.T. (ASCP)
Cancers treated: Various, especially slow-growing cancers such as solid tumors and leukemias Subclasses of this group: Alkyl sulfonates, ethyleneimines and methylmelamines, nitrogen mustards, nitrosoureas, platinum compounds, triazenes
See also Immunocytochemistry and immunohistochemistry; Paget disease of bone; Placental alkaline phosphatase (PALP).
Delivery routes: These drugs are administered both intravenously and orally in capsule and tablet form, on an inpatient, outpatient, and at-home basis, depending on the specific drug, type of cancer, and its location and aggressiveness. When possible, these drugs are best delivered to the tumor site to limit damage to normal cells.
u Alkylating agents in
chemotherapy Category: Chemotherapy and other drugs ATC code: 101A
How these drugs work: One of the oldest classes of chemotherapeutic drugs, alkylating agents were discovered during World War II when physician Cornelius P. Rhoads drew a connection between the lowered white
Definition: Alkylating neoplastic agents form a class of chemotherapeutic drugs, all of which consist of highly
Common Alkylating Agents Subclass
Delivery Mode
Cancers Treated
Altretamine Hexalen (hexamethylmelamine)
Ethylenimines
Oral
Ovarian cancer
Busulfan
Alkyl sulfonates
Oral, IV
Chronic myelogenous leukemia, other blood cancers
Platinum compounds
IV
Ovarian carcinoma
Drug
Brands
Carboplatin (CBDCA)
Paraplatin
Carmustine (BCNU)
BiCNU, Nitrosoureas Gliadel Wafer
IV
Brain tumors, multiple myeloma, Hodgkin disease, non-Hodgkin lymphoma, malignant melanoma, breast cancer, gastrointestinal cancers, Ewing sarcoma, and Burkitt lymphoma; applied topically for mycosis fungoides
Chlorambucil
Leukeran
Nitrogen mustards
Oral
Chronic lymphocytic leukemia, some non-Hodgkin lymphomas, advanced Hodgkin disease
Cisplatin (CDDP)
Platinol-AQ
Platinum compounds
IV
Metastatic testicular tumors, metastatic ovarian tumors, advanced bladder carcinoma
Cyclophosphamide (CTX)
Cytoxan
Nitrogen mustards
Oral, IV
Lymphomas, multiple myelomas, leukemias, mycosis fungoides, neuroblastoma, ovarian carcinoma, retinoblastoma, breast cancer
Dacarbazine (DTIC)
DTIC-Dome
Triazenes
IV
Melanoma, Hodgkin disease
Ifosfamide (isophosphamide)
Ifex
Nitrogen mustards
IV
Germ cell testicular cancer, sarcomas
(continued on page 46)
45
Alkylating agents in chemotherapy
Salem Health: Cancer Side effects: Although alkylating agents are more toxic to cancer cells than to normal cells, these drugs are nonspecific. That is, they target normal as well as cancerous tissue, so they exhibit the “Janus effect”: They kill both bad and good cells. Therefore they have toxic side effects, depending on the specific drug, its dosage, the duration of administration, and the individual patient’s physical condition and attitude. Common side effects include depressed blood cell counts, tiredness and fatigue, diarrhea, alopecia (hair loss), nausea and vomiting, infertility (both amenorrhea in women and impaired spermatogenesis in men), damage to intestinal mucosa, exfoliation of the bladder epithelium resulting in fluid retention, and in extreme cases cardiotoxicity, which would mitigate the chemotherapy regimen. In addition, some alkylating agents increase the risk of future malignancies, such as acute myeloid leukemia, which may emerge years after treatment. Christina J. Moose, M.A.
blood cell counts in six hundred sailors (who had been exposed to mustard gas during the sinking of the Liberty in 1943) and the possibility that the nitrous mustards could be adopted for use in leukemia patients. It was later observed that alkylating agents substitute alkyl groups for the hydrogen groups in the DNA of tumor cells. The alkyl groups cross-link guanine nucleobases in the double-helix strands of DNA, which makes it impossible for the two DNA strands to uncoil and separate in preparation for replication. As a result, these drugs prevent tumor cells from dividing during mitosis, stopping the cells’ growth. They may also stimulate the natural process of cell death (apoptosis). Because DNA is more actively replicated and transcribed in rapidly dividing cancer cells than in normal cells, these drugs are more toxic to tumor tissue than to normal tissue. Alkylating agents are also known to add methyl or alkyl groups onto any of the four nitrogenous bases found in DNA(adenine, guanine, cytosine, thymine), frequently altering the base-pairing relationships and leading to new mutations.
Common Alkylating Agents (continued)
46
Drug
Brands
Subclass
Delivery Mode
Lomustine (CCNU)
CeeNU
Nitrosoureas
Oral
Brain tumors, Hodgkin disease, bronchogenic carcinoma, non-Hodgkin lymphomas, malignant melanoma, breast cancer, renal cell carcinoma, carcinoma of the GI tract
Mechlorethamine (nitrogen mustard)
Mustargen
Nitrogen mustards
IV
Hodgkin disease, lymphosarcoma, chronic myelocytic or chronic lymphocytic leukemia; polycythemia vera; mycosis fungoides, bronchogenic carcinoma, non-Hodgkin lymphomas, malignant melanoma, breast cancer, renal cell carcinoma, carcinoma of the GI tract; applied topically for mycosis fungoides
Melphalan (L-PAM)
Alkeran
Nitrogen mustards
Oral, IV
Multiple myeloma, ovarian carcinoma
Oxaliplatin (oxalatoplatin, oxalatoplatinum)
Eloxatin, Transplatine
Platinum compounds
IV
Advanced ovarian cancer; may be effective for head and neck cancers, skin cancer, lung cancers, and non-Hodgkin lymphomas
Procarbazine
Matulane, Natulane
Hydrazine derivatives
Oral
Hodgkin disease and other lymphomas, brain tumors, skin cancer, lung cancer, multiple myeloma, mycosis fungoides
Cancers Treated
Streptozocin
Zanosar
Nitrosoureas
IV
Pancreatic islet cell cancer
Temozolomide
Temodar
Triazenes
Oral
Brain tumors (astrocytomas)
Thiotepa
Thioplex
Ethylenimines
IV, spinal injection, bladder infusion
Bladder cancer, ovarian cancer, breast cancer, lymphomas, bronchogenic carcinoma, and metastatic pleural, pericardial, and peritoneal cancers
Salem Health: Cancer
Alopecia
u For Further Information Chabner, Bruce A., and Dan L. Longo, eds. Cancer Chemotherapy and Biotherapy: Principles and Practice. Philadelphia: Lippincott Williams & Wilkins, 2006. Fischer, David S., et al. The Cancer Chemotherapy Handbook. 6th ed. St. Louis: Mosby, 2003. Panasci, Lawrence C., and Moulay A. Alaoui-Jamali, eds. DNA Repair in Cancer Therapy. Totowa, N.J.: Humana Press, 2004. Podolsky, M. Lawrence. Cures out of Chaos. Newark, N.J.: Harwood Academic, 1997. Skeel, Roland T. Handbook of Cancer Chemotherapy. 6th ed. Philadelphia: Lippincott Williams & Wilkins, 2003. u
Other Resources
National Cancer Institute Drug Information Summaries http://www.cancer.gov/cancertopics/druginfo/ alphalist See also Antineoplastics in chemotherapy; Bis(chloromethyl) ether and technical-grade chloromethyl methyl ether; 1,4-Butanediol dimethanesulfonate; Carcinogens, known; Carcinogens, reasonably anticipated; Chemotherapy; Chlorambucil; 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (MeCCNU); Cyclophosphamide; Infertility and cancer; Mustard gas; Sterility; Thiotepa.
u Alopecia Category: Diseases, symptoms, and conditions Also known as: Alopecia disseminata, alopecia universalis, alopecia totalis, baldness, hair loss, acomia, pelade Related conditions: Anagen effluvium, telogen effluvium Definition: Alopecia is abnormal loss of hair, a common side effect of treatments for cancers, including chemotherapy and radiation therapy. There are many types of alopecia, with many causes, including certain skin cancers and other types of cancer that spread to the skin, although marked hair loss from skin cancer is extremely rare. Risk factors: Chemotherapy for any cancer greatly increases the risk of alopecia, and radiation therapy increases the risk of hair loss from the irradiated area. Etiology and the disease process: Each human hair grows from a hair follicle, an elongated pouch formed during fe-
Chemotherapy has caused this woman to lose her hair. (© Lisa F. Young/Dreamstime.com)
tal development by growth of the upper part of the skin, the epidermis, down into the lower part, the dermis. The lower part of the follicle, the hair bulb, contains the germinal matrix, the cells that form the hair. Each hair goes through a three-phase growth cycle: anagen, or active growth; catagen, or regression; and telogen, or resting. When the telogen phase for each hair is complete, a new anagen phase begins. Human hairs complete their recurring growth cycle, as old hairs are pushed out by new hairs, in random order. At any given time, about 85 percent of hairs are in the anagen, or active growth phase. Chemotherapeutic agents target rapidly reproducing cells, like cancer cells. Unfortunately, these agents do not know the difference between a cancer cell and the rapidly reproducing cells of the germinal matrix in a hair bulb. They stop cell division, or mitosis, in matrix cells, just as they do in cancer cells. The anagen phase comes to a stop, and in many cases, all the hair that is in the anagen phase is shed. Hair lost through chemotherapy almost always regrows, because the hair follicle is left intact. Radiation therapy also stops the reproduction of rapidly dividing cells, but in higher doses, 47
Alpha-fetoprotein (AFP) levels radiation can damage the hair follicles it touches, preventing regrowth of hair. Incidence: At least some degree of hair loss is likely with many forms of chemotherapy. Certain drugs or combinations of drugs are virtually certain to cause some degree of hair loss. A few drugs cause nearly complete hair loss. Symptoms: Symptoms of alopecia related to cancer range from temporary thinning or breakage of a small patch of hair to loss of hair all over the body (alopecia disseminata, alopecia universalis, alopecia totalis), and hair loss can be temporary or permanent, depending on the cause. Screening and diagnosis: Diagnosis of chemotherapyrelated alopecia follows visible hair loss within days or weeks of administration of chemotherapeutic drugs. Treatment and therapy: Therapies for alopecia caused by chemotherapy include administration of vitamins, minerals, or omega-3 and omega-6 fatty acids—substances that promote healthy hair. The benefit of these therapies on cancer-related hair loss is still being researched, and consumption of some vitamins and minerals may reduce the effectiveness of chemotherapy, so any treatment for hair loss during therapy should be approved by the treating physician. Treatment for cancer-caused alopecia includes treatment for the underlying cancer, which may include surgery or chemotherapy. Again, noticeable hair loss from cancer itself is extremely rare. Prognosis, prevention, and outcomes: The prognosis for alopecia caused by chemotherapy depends on the chemicals used, the dosage, and the frequency of treatment. More intensive treatment is likely to cause more extensive hair loss. Whatever the amount or type of hair loss from chemotherapy, the prognosis is eventual regrowth of hair. Patchy regrowth may begin before chemotherapy is completed, an average of three to five months after initial hair loss from the first treatment. Because chemotherapy disrupts the matrix from which the hair is formed, including the melanocytes, or cells that give hair its color, regrown hair may differ in color or texture from the original hair. There has been some limited success in preventing scalp hair loss from chemotherapy through use of scalp cooling or a hairline tourniquet during administration of the chemotherapy. These, however, have been successful with only certain chemical agents. Their use has been questioned by some oncologists because, while they protect scalp follicles from damage, they also protect any cancer cells present in the scalp. Research trials are being conducted on other treatments that may reduce hair loss from chemotherapy. The prognosis for alopecia caused by radi48
Salem Health: Cancer ation therapy depends on the dosage of radiation. High doses usually cause permanent hair loss to the irradiated area; low doses more often cause temporary, local hair loss. Cathy Anderson, R.N., B.A. u
For Further Information Bleiker, T. O., N. Nicolaou, J. Traulsen, and P. E. Hutchinson. “‘Atrophic Telogen Effluvium’ from Cytotoxic Drugs and a Randomized Controlled Trial to Investigate the Possible Protective Effect of Pretreatment with a Topical Vitamin D3 Analogue in Humans.” British Journal of Dermatology 153, no. 1 (2005): 103-112. Jothilakshmi, P. K., A. J. Watson, and E. Jude. “Acute Alopecia Due to Metformin Treatment for Polycystic Ovarian Syndrome.” Journal of Obstetrics and Gynaecology 26, no. 6 (2006): 584-585. Wang, J., Z. Lu, and J. L. Au. “Protection Against Chemotherapy-Induced Alopecia.” Pharmaceutical Research 23, no. 11 (2006): 2505-2514. Wyatt, A. J., G. D. Leonard, and D. L. Sachs. “Cutaneous Reactions to Chemotherapy and Their Management.” American Journal of Clinical Dermatology 7, no. 1 (2006): 45-63.
u
Other Resources
Chemotherapy.com http://www.chemotherapy.com Healthline http://www.healthline.com WebMD http://www.webmd.com See also Alkylating agents in chemotherapy; Chemotherapy; Cyclophosphamide; Paraneoplastic syndromes; Radiation therapies; Self-image and body image; Side effects.
u Alpha-fetoprotein (AFP) levels Category: Procedures Also known as: Total AFP, AFP-13 percent, alphafetoglobulin, αFP, AFP tumor marker Definition: Alpha fetoprotein (AFP) is a protein produced by fetal tissue and by tumors. There are several forms of AFP. The test for AFP generally measures total AFP. The test is performed on serum or plasma on an automated chemistry analyzer.
Salem Health: Cancer Cancers diagnosed: Cancers of the liver, testes, and ovaries Why performed: The AFP test is done to detect and monitor cancers of the liver, testes, and ovaries. Physicians may order the test for patients with chronic liver disease because of the high risk of developing liver cancer. Because AFP is also produced by a fetus, AFP levels are generally higher in pregnant women. A test for AFP done on pregnant women is not done to detect a tumor but is used with other data to detect possible abnormalities in the developing fetus. Patient preparation: No special preparation is necessary. Steps of the procedure: A small sample of blood is collected from a vein and placed in a tube. In children, blood may be obtained from a capillary in the heel or finger. After the procedure: A small gauze or cotton ball is applied at the site of needle insertion. The patient is asked to apply pressure. The person collecting the blood observes the site for bleeding and may apply a bandage. The bandage may usually be removed in thirty to sixty minutes. Risks: Risks include bleeding, bruising, hematoma (bleeding under the skin), fainting, light-headedness, or the need for multiple needle sticks to obtain a sample. Results: Normal AFP levels vary by the patient’s sex and age and by the analyzer used. Each laboratory establishes normal ranges based on this information. The physician receives a report of the test results with the normal values established by the testing laboratory. AFP decreases at birth, and adult levels are normally low. Elevated levels are present in liver cancer and in some cancers of the testes and ovaries. Generally, higher levels of AFP indicate a larger tumor. The test is not considered specific for diagnosis, but it is an indicator that a tumor may be present. Physicians may order imaging studies and additional laboratory tests to determine the presence of a tumor. Some physicians order a test called AFP-13 percent, as 13 is one of the forms of AFP that make up the total. An increased percentage of AFP-13 to total AFP indicates an increased risk of developing liver cancer or a poorer prognosis. AFP levels usually return to normal within a month of treatment. Wanda E. Clark, M.T. (ASCP) See also Ataxia telangiectasia (AT); Beckwith-Wiedemann syndrome (BWS); Germ-cell tumors; Pathology; Placental alkaline phosphatase (PALP); Proteomics and cancer research; Testicular cancer; Yolk sac carcinomas.
Alveolar soft-part sarcomas
u Alveolar soft-part sarcomas Category: Diseases, symptoms, and conditions Also known as: Nonrhabdomyosarcoma soft-tissue sarcomas, ASPS Related conditions: Soft-tissue sarcomas Definition: Alveolar soft-part sarcoma is a slow-growing, malignant tumor that develops in deep soft tissues and muscles, most often in the thighs and buttocks. It is also found in the arm, chest, bladder, abdomen, and—in children—the head and neck. It gets its name from the way the tumor cells are clustered, resembling alveoli, or the air sacs of the lungs. Risk factors: No risk factors are known, and alveolar softpart sarcoma is nonhereditary. Etiology and the disease process: The disease’s etiology is murky. Early development of alveolar soft-part sarcoma appears to be linked to a genetic mutation involving the separation of a gene from chromosome 17 and its attachment to the X chromosome. A wealth of blood vessels allows tumor cells to enter the bloodstream and spread to other areas, usually the lungs and brain. Childhood alveolar soft-part sarcoma appears to have a different, and generally less aggressive, biology. Incidence: Alveolar soft-part sarcoma is rare, with 40 to 80 new cases annually in the United States. About half of alveolar soft-part sarcoma patients are between the ages of fifteen and twenty-nine, and women generally outnumber men, especially among younger patients. Symptoms: Common symptoms include a soft, painless lump, soreness, reduced range of motion, and numbness. Because alveolar soft-part sarcoma grows slowly in deep, elastic tissues, patients often do not notice symptoms until the cancer is advanced or has spread. Screening and staging: Diagnostic procedures include laboratory tests and imaging studies such as computed tomography (CT) scans, magnetic resonance imaging (MRI), and bone scans. A biopsy is required, however, to confirm alveolar soft-part sarcoma. Tumors are staged based on size, grade, and degree of spread: • Stage I: Low grade, with little potential for spreading • Stages II and III: High grade, with increased potential for spreading • Stage IV: Metastasis to distant organs Other criteria are typically used for staging pediatric alveolar soft-part sarcoma. 49
Amenorrhea Treatment and therapy: Surgical removal of the tumor and surrounding tissue is the primary treatment. Radiation therapy may be used before to shrink the tumor and after to kill any remaining cells, although it is used in children only if surgery alone is ineffective. Chemotherapy is not generally beneficial. Other therapies are under study. Prognosis, prevention, and outcomes: The five-year survival rate for patients with localized tumors is around 80 percent. If the disease has metastasized, the rate drops to 20 percent. However, long-term survival is possible even with spread because alveolar soft-part sarcoma grows slowly. The prognosis for children is considerably better, as their tumors are generally smaller and localized. Alveolar soft-part sarcoma can recur more than ten years after initial diagnosis, so long-term follow-up is recommended. Judy Majewski, M.S. See also Dermatofibrosarcoma protuberans; Ewing sarcoma; Fibrosarcomas, soft-tissue; Hemangiosarcomas; Liposarcomas; Mesenchymomas, malignant; Rhabdomyosarcomas; Sarcomas, soft-tissue; Synovial sarcomas.
u Amenorrhea Category: Diseases, symptoms, and conditions Also known as: Primary amenorrhea, secondary amenorrhea, absent periods, absent menses, absent menarche Related conditions: Pregnancy, menopause, pituitary or gynecologic tumors Definition: Amenorrhea is the absence of menstruation, whether temporary or permanent. Amenorrhea is normal prior to puberty, during pregnancy and lactation, and after menopause. Amenorrhea may also occur as the symptom of a variety of abnormal conditions, including pituitary or gynecologic tumors, and is an expected result of many chemotherapeutic cancer drugs. Primary amenorrhea is the absence of menarche, the initial menstrual period, in women age sixteen and older. Menarche occurs normally in women between the eleventh and seventeenth year. The average age of menarche in the United States is 12.8 years. Secondary amenorrhea is absence of menses for three months in a woman with previously normal menstruation and for nine months in a woman with oligomenorrhea, which is infrequent periods and fewer than the normal eleven to thirteen a year. 50
Salem Health: Cancer Risk factors: Both primary and secondary amenorrhea can be influenced by a host of other factors, some of which include immunodeficiency, anorexia nervosa, congenital abnormalities of the reproductive tract, obesity, diabetes, dietary restriction, starvation, metabolic disorders, drugs, and excessive physical exercise. Amenorrhea can also signal a pituitary or a gynecologic tumor, and it is a common and even expected result of chemotherapy or radiation treatment for cancer. Etiology and the disease process: Amenorrhea is often due to the absence or change in hormones produced in the hypothalamus, the pituitary gland, or the ovaries (the triad that directs reproduction), and it can result from an abnormality in the outflow tract. In primary amenorrhea, in the presence of secondary sex characteristics and a uterus, the most common cause is outflow tract obstruction with a transverse vaginal septum or imperforate hymen, both easily correctable. However, primary amenorrhea can also have a genetic cause. The most common cause of secondary amenorrhea is pregnancy during a woman’s reproductive years. Secondary amenorrhea may also be related to lifestyle choices. Athletes and ballet dancers who train vigorously often experience missed periods. Stress, obesity, and starvation can also result in secondary amenorrhea. In these cases, women stop menstruating because the ovaries do not produce enough estrogen in a cyclic manner to cause the uterine lining to thicken and shed normally. If pregnancy is not the cause, the physician may test the patient’s levels of hormones produced by the thyroid and the pituitary glands. When amenorrhea is accompanied by elevated levels of prolactin, galactorrhea, headaches, or visual disturbances, a pituitary tumor may be the cause. Adenomas are the most common cause of anterior pituitary dysfunction. Gynecological tumors such as ovarian cancer must also be ruled out in the presence of amenorrhea. Cancer treatments such chemotherapy and radiation are often associated with amenorrhea. The greater the dose of the chemotherapeutic agent, the greater the chance of amenorrhea. Studies linking particular cancer treatments to the incidence of amenorrhea remain incomplete, but two drugs particularly linked to amenorrhea are doxorubicin and cyclophosphamide. Incidence: In the United States, the incidence of primary amenorrhea is 2.5 percent. The incidence of secondary amenorrhea is between 1 and 4 percent. Rarely, the cause of amenorrhea is a tumor of the pituitary. The true incidence of pituitary adenomas is difficult
Salem Health: Cancer to know with certainty because they are often asymptomatic; autopsy estimates range from 2.7 to 27 percent. Symptoms: The first sign of primary amenorrhea is the absence of menses. If the cause of absence of flow is an anomaly of the outflow tract of the blood, the patient may experience cramping and severe abdominal pain. In the case of secondary amenorrhea, other that the absence of menstruation, symptoms may include: • galactorrhea, in which case the breasts produce milk in a woman who is not pregnant or breastfeeding • headache or reduced peripheral vision as a potential sign of an intracranial tumor • hirsutism, or increased hair growth in a male pattern caused by excess androgen • vaginal dryness, hot flashes, night sweats, or disordered sleep, suggesting ovarian insufficiency or premature ovarian failure (premature menopause) • excessive weight gain or loss • anxiety Screening and diagnosis: With primary amenorrhea and the absence of secondary sex characteristics, the physician may order an ultrasound to determine if a uterus is present and measure the levels of two hormones produced by the anterior pituitary: the follicle stimulating hormone (FSH), which stimulates growth of the follicle in the ovary, and luteinizing hormone (LH), which triggers ovulation. Very low levels suggest that the gonads, or sex glands, have failed to develop or begin functioning. Karyotyping to study the chromosome arrangement may reveal a genetic reason for the absence of menarche. An example is Turner syndrome, which is a congenital endocrine disorder caused by failure of the ovaries to respond to pituitary hormone stimulation. In addition to primary amenorrhea and failure of sexual maturation, the physical examination may note short stature. About onethird of the patients show webbing of the neck, marled cubitus valgus (a deformity of the arm in which the forearm deviates laterally), and developmental disabilities. Often genetic studies reveal the presence of only 45 chromosomes, the second X chromosome being absent. Treatment and therapy: A thorough medical history often reveals the cause of amenorrhea, which can then be corrected by surgery, medication, or lifestyle changes. Secondary amenorrhea may be caused by some medications such as phenothiazines, some narcotics, and any condition related to pituitary insufficiency or thyroid dysfunction. For cases due to lifestyle choices, reducing the amount or intensity of exercise and maintaining a healthy
Amenorrhea weight should correct hormone levels and result in a return to regular periods. If is determined to be a symptom of a pituitary or gyencologic tumor, the patient will undergo tests for malignancy and follow-up treatment and therapy indicated for the particular cancer diagnosed. Prognosis, prevention, and outcomes: Most cases of amenorrhea are treatable, although some resulting from genetic conditions cannot be corrected. In women with low thyroid-stimulating hormone (TSH), or hypothyroidism, which is more often associated with hypermenorrhea or oligomenorrhea, the menstrual cycle is often returned to normal following hormone replacement therapy. If a pituitary tumor is causing the amenorrhea, these tumors are rare and often asymptomatic, seldom resulting in death. They are typically slow growing and benign. However, the numerous hormones produced in the pituitary orchestrate many bodily functions, so patients with these tumors may face a lifetime of hormone replacement and long-term follow-up care. Jane Adrian, M.P.H., Ed.M., M.T. (ASCP) u
For Further Information Bell, Ruth, et al. Changing Bodies, Changing Lives: A Book for Teens on Sex and Relationships. 3d ed. New York: Times Books, 1998. Hobart, Julie A., and Douglas R. Smucker. “The Female Athlete Triad.” American Family Physician 61, no. 11 (June 1, 2000). Master-Hunter, Tarannum, and Diana L. Heiman. “Amenorrhea: Evaluation and Treatment. ” American Family Physician 73, no. 8 (April 15, 2006). Slap, Gail B. “Amenorrhea.” In The Gale Encyclopedia of Childhood and Adolescence, edited by Jerome Kagan. Detroit: Gale, 1998.
u
Other Resources
American College of Obstetricians and Gynecologists http://www.acog.org American Society for Reproductive Medicine http://www.asrm.org See also Alkylating agents in chemotherapy; Chemotherapy; Endometrial cancer; Infertility and cancer; Neuroendocrine tumors; Ovarian cysts; Sterility. 51
American Association for Cancer Research (AACR)
u American Association for
Cancer Research (AACR) Category: Organizations Definition: Founded in 1907, the American Association for Cancer Research (AACR) is a nongovernmental organization of physicians, scientists, and advocates seeking to overcome the burden of cancer through research and dissemination of information. With more than 24,000 members in more than sixty countries, it is one of the largest organizations of its kind. Funding research: The AACR does not conduct cancer research itself but instead acts as a base of financial support for researchers. There are two basic types of support provided by the organization: direct research funding and scholarly or travel grants. As of 2007, the annual budget of the AACR was approximately $3.65 million. Approximately 69 percent of that went to funding research, while 15 percent went to education programs, and the remaining 16 percent was required for operational expenses. The AACR has provided more than $16 million dollars in research funding since 1993. The AACR provides three major grants that directly fund cancer research. The Jeannik M. Littlefield-AACR Grants in Metastatic Colon Cancer Research provide awards ranging from $500,000 to $1 million; four of these grants were given in 2007. The BCRF-AACR Grants for Translational Breast Cancer Research provide awards up to $250,000; three of these grants were given in 2007. The Avon Foundation-AACR International Scholar Awards in Breast Cancer Research provide up to $100,000; twelve of these grants were awarded in 2007. The AACR also has four other grants that range from $30,000 to $50,000. All of these awards pay for expenses such as laboratory equipment, materials, salaries, and limited travel. The other type of grant that the AACR provides helps students and scientists attend the many workshops and conferences offered by the AACR and other cancer research organizations. These types of grants may cover travel expenses, housing, and registration fees. Without such grants, many researchers, especially those who are younger or are just beginning to build a reputation in the field, would not be able to attend these collaborative events. Publications: Because dissemination of information is of vital importance, both to researchers seeking to make scientific progress and to the doctors and patients seeking treatment options, the AACR publishes five journals and one magazine. Each of these journals is peer-reviewed, 52
Salem Health: Cancer and together they contain approximately 23,000 pages each year. The AACR’s earliest journal, Cancer Research, was first published in January of 1949. It is the most highly quoted cancer journal worldwide. It accepts work from all areas of cancer research and is published bimonthly. Clinical Cancer Research focuses specifically on innovative clinical research, especially that which bridges the gap between laboratory research and clinical application. It began in January of 1995 and is also published on a bimonthly basis. Cancer Epidemiology, Biomarkers and Prevention was first published in November of 1991 and is published monthly. The journal focuses on the causes of cancer and cancer prevention. The AACR’s newest journals, Molecular Cancer Therapeutics and Molecular Cancer Research, were first published in 2001 and 2002, respectively. These journals focus on cancer research developments in molecular biology and are published on a monthly basis. CR magazine, which stands for “collaborations, results,” is intended not only for research scientists and physicians but also for people who have cancer, survivors of cancer, and anyone who is affected by the disease. The AACR hopes to help create community and camaraderie among people affected by cancer, providing the emotional support that many patients and family members need. The editorial board for the magazine is made up of cancer research scientists, cancer advocates, and cancer survivors. It began publication in the spring of 2006 and is published quarterly. CR magazine also provides podcasts of cancer news stories on its Web site. Events: To facilitate communication among scientists, the AACR holds numerous workshops, meetings, and conferences. The Annual Meeting of the AACR is the largest annual meeting in the field and is regarded by many cancer researchers as the most important. In 2007, it hosted more than 16,000 cancer scientists at the Los Angeles Convention Center. For five days, these scientists attended forty-six symposia, twenty forums, sixty-nine sessions, and more than forty minisymposia. Almost six thousand abstracts were presented at the seven poster sessions. The AACR publishes the proceedings of its annual meeting and also makes them available on its Web site, along with audio recordings and Webcasts from the event. In addition to the annual meeting, the AACR holds several large conferences and around a dozen smaller conferences. The larger conferences usually have between 500 and 3,000 attendees and focus on such topics as racial and ethnic disparities in cancer, molecular diagnostics, and cancer prevention. Smaller conferences usually attract be-
Salem Health: Cancer tween 150 and 400 people, and the topics tend to cover a great variety of special subjects, such as oncogenomics or proteomics in cancer research. The AACR also aids younger cancer researchers by organizing educational workshops throughout the year. These workshops are designed to provide opportunities for young investigators to develop essential research skills. Robert Bockstiegel, B.S. u For Further Information Jeffries, Lee P., ed. Leading Topics in Cancer Research. New York: Nova Science, 2007. Martakis, Ignatius K., ed. Cancer Research at the Leading Edge. New York: Nova Science, 2007. Pereira, Larissa S., ed. Cancer Research Perspectives. New York: Nova Science, 2008. u
Other Resources
American Association for Cancer Research http://www.aacr.org American Society of Clinical Oncology http://www.asco.org Association of American Cancer Institutes http://www.aaci-cancer.org See also American Cancer Society (ACS); American Institute for Cancer Research (AICR); Dana-Farber Cancer Institute; Duke Comprehensive Cancer Center; Fox Chase Cancer Center; Fred Hutchinson Cancer Research Center; Jonsson Comprehensive Cancer Center (JCCC); M. D. Anderson Cancer Center; Mayo Clinic Cancer Center; Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI); National Science Foundation (NSF); Prevent Cancer Foundation; Robert H. Lurie Cancer Center.
u American Cancer Society
(ACS) Category: Organizations Also known as: American Society for the Control of Cancer Definition: The American Cancer Society (ACS) is an organization that provides cancer information, aids cancer patients, and collects and contributes funds for cancer research. History: Several New York City physicians established the American Society for the Control of Cancer (ASCC),
American Cancer Society (ACS) the ACS’s predecessor, in 1913. At that time, approximately 75,000 people in the United States died of cancer each year. ASCC leaders strove to educate people, including medical professionals, regarding cancerous conditions and treatments. The ASCC published articles in both mainstream and professional periodicals. During the mid-1930’s, ASCC Women’s Field Army volunteers distributed cancer information directly to people and collected funds for the organization’s work. By 1938, approximately 150,000 people were affiliated with the ASCC. After World War II, the renamed American Cancer Society (ACS) embraced research to control cancer. The ACS introduced its list of seven cancer warnings in 1947. Services and procedures performed: The ACS emphasizes cancer prevention, mitigating physical and emotional pain, and survival. The society strives to decrease cancer occurrence and death rates. ACS funds from donors advance cancer research, create educational material, staff the National Cancer Information Center, provide such support services as housing near cancer centers for patients and people accompanying them, and publicize issues relevant to cancer control. The ACS Web site posts cancer information, and the organization distributes printed and visual media to individuals and health centers. The ACS’s Cancer Survivor Network enables people affected by cancer to communicate. The ACS seeks donors, ranging from individuals to corporations. Fund-raisers include the ACS’s Relay for Life. A board of directors oversees national ACS activities, including distribution of fellowships and grants. Divisions and local units also conduct ACS work. By 2006, about three million volunteers, representing both medical professionals and people from other walks of life, participated in providing ACS services. Research: The ACS invests the most private funds for oncology investigations in the United States. ACS leaders support innovative research seeking to identify causes of cancer and to improve prevention and treatment methods. By the early twenty-first century, the ACS had invested $3 billion for researchers to pursue investigations. As of 2007, the ACS awarded peer-evaluated projects $130 million yearly. ACS-supported achievements created better screening techniques such as the prostate-specific antigen (PSA) test. The ACS funded research evaluating the use of Pap smears to detect cervical cancer and mammograms to detect breast cancer. Treatment methods also benefited from ACS financial support. Funded by the ACS, Sidney Farber studied the use of aminopterin to accomplish remission of 53
American Institute for Cancer Research (AICR) cancer, enabling chemotherapy to become a viable method to treat many cancers. ACS-supported researchers focusing on pediatric oncology developed more effective methods to combat leukemia in children. Investigators used ACS research money to study genes associated with cancer. An ACS-financed study linked cigarettes and cancer. ACS research funds contributed to creation of anticancer pharmaceuticals. Education: The ACS creates and distributes educational information to enhance people’s awareness of cancer issues. The society stresses preventing cancers by embracing healthy behaviors. The ACS urges people to seek cancer screening to detect cancers and seek treatment expeditiously to aid survival. The society’s information is incorporated in health lessons taught in many U.S. schools. ACS advertisements in various media promote colorectal and breast cancer screening and stopping smoking. The ACS publishes three journals for medical professionals, educational guides devoted to specific cancers, and books for patients’ children and caregivers. The society’s cookbook has appeared in several editions as new information regarding nutritional aspects of cancer prevention is determined. The ACS distributes Cure: Cancer Updates, Research & Education. The society supports workshops and conferences where medical professionals learn about current oncology information and methods. Advocacy: In 2007, the ACS devoted $15 million to advertisements for print and television commercials stressing how lack of insurance affects cancer detection and treatment. The ACS allied with other health groups and the American Association of Retired Persons (AARP) to promote better health care access. The nonpartisan Cancer Action Network (CAN) complements the ACS, conducting lobbying, which the ACS cannot pursue. CAN’s political work includes securing nonsmoking areas, preparing voter guides, and sponsoring a hotline to contact politicians. Elizabeth D. Schafer, Ph.D. u For Further Information American Cancer Society. The American Cancer Society’s Healthy Eating Cookbook: A Celebration of Food, Friends, and Healthy Living. 3d ed. Atlanta: American Cancer Society, 2005. Herdman, Roger, and Leonard Lichtenfeld, eds. Fulfilling the Potential of Cancer Prevention and Early Detection: An American Cancer Society and Institute of Medicine Symposium. Washington, D.C.: National Academies Press, 2004.
54
Salem Health: Cancer Ross, Walter S. Crusade: The Official History of the American Cancer Society. New York: Arbor House, 1987. Stein, Kevin, et al. “The American Cancer Society’s Studies of Cancer Survivors.” American Journal of Nursing 106, no. 3 (March, 2006): 83-85. u
Other Resources
American Cancer Society http://www.cancer.org American Cancer Society Cancer Action Network http://www.acscan.org Cure: Cancer Updates, Research, and Education http://www.curetoday.com See also American Association for Cancer Research (AACR); American Institute for Cancer Research (AICR); Dana-Farber Cancer Institute; Duke Comprehensive Cancer Center; Fox Chase Cancer Center; Fred Hutchinson Cancer Research Center; Jonsson Comprehensive Cancer Center (JCCC); M. D. Anderson Cancer Center; Mayo Clinic Cancer Center; Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI); National Science Foundation (NSF); Prevent Cancer Foundation; Robert H. Lurie Cancer Center.
u American Institute for Cancer
Research (AICR) Category: Organizations Definition: The American Institute for Cancer Research (AICR) is a private charity that sponsors research into the relationship between diet and cancer and works to disseminate findings about that relationship. History: Before the 1980’s, most cancer research was focused on diagnosis and treatment of the disease. Many scientists believed that cancer operated like a virus that affected cell metabolism, and they focused on early intervention and chemotherapy as their main strategies. The AICR was established in 1982 around the principle that cancer is preventable and that the disease is not random but is affected by lifestyle choices. At the time of its founding, this principle was not widely accepted. Later that same year however, the National Academy of Sciences published a report entitled Diet, Nutrition, and Cancer, and this document became the initial basis for the AICR’s cancer education program. In 1997, the AICR collaborated with the World Cancer
Salem Health: Cancer
American Institute for Cancer Research (AICR)
Research Fund (WCRF), based in the United Kingdom, to publish a 670-page report called Food, Nutrition, and the Prevention of Cancer: A Global Perspective. The report was the work of sixteen scientists from eight countries, who spent three years reviewing studies on diet and cancer. It was developed with participation from experts at the National Cancer Institute and the World Health Organization and was peer-reviewed. The report indicated that between 30 and 40 percent of all cancers could be directly linked to lifestyle choices such as food, drink, exercise, and overall health. The AICR produced more than 30,000 copies of the report and freely distributed it to cancer researchers and politicians. In 1999 the AICR published Stopping Cancer Before It Starts, a book that brought the message of the report to the public. The AICR began to expand more rapidly after the publication of these works. Private donations, the primary source of funding for the organization, increased both in number and size. As of 2007, more than 12 million Americans had made a donation to the organization, which had a total annual revenue exceeding $38 million and had contributed more than $82 million to research projects.
AICR Recommendations for Cancer Prevention
Educating the public: Spreading the message that people can lower their risk of cancer is a major part of the AICR’s program. In 2006, approximately $20 million, over 50 percent of the organization’s annual budget, went to educational activities. One of the ways the AICR fulfills its mission is through a free quarterly newsletter, which the AICR sends to more than 1.5 million homes. The newsletter provides meal-planning suggestions, recipes, and basic nutritional health information. The organization also produces more than seventy brochures, covering a wide array of topics within the subject of nutrition and cancer. Its latest series, The New American Plate, encourages people to fill two-thirds of their plate with fruits, vegetables, and grains, and keep protein to one-third or less. The AICR has also produced public service announcements, which have been carried by hundreds of television stations across the United States. Newspapers and magazines have also been a resource for the AICR. The organization also maintains a Web site and a national nutrition hotline to provide more in-depth information about ways that people can reduce their risk of cancer. The institute also hosts educational seminars and an annual conference. These educational seminars are offered free of charge and presented by registered dieticians. As of 2007, more than 41,000 people had attended a seminar, and they had been offered in more than 133 cities. The AICR annual research conference is becoming a major event in the field of cancer research, as the 2005 con-
• • • •
Eat mostly plant-based foods, limit consumption of red meat (beef, pork, and lamb), and avoid processed meats. Engage in physical activity every day for at least thirty minutes. Maintain a healthy weight throughout life, preferably as lean as possible without being underweight. Do not smoke or chew tobacco.
ference hosted more than four hundred participants and speakers from twenty-five universities and research facilities. Research grants: The AICR works to contribute funding to scientists in the field of cancer research who focus on the connection between cancer and diet. Approximately 14 percent of the annual budget goes to funding proposed research. To decide which proposals to fund, the institute follows a set of grant review process standards, established by the National Cancer Institute. Proposals are reviewed by a panel of experts on the basis of scientific merit. Final decisions about funding are made by the AICR Board of Directors. The AICR Investigator Initiated Grants Program awards up to $75,000 per year for up to two years to be used for research into either diet and cancer or physical activity and cancer. The AICR Post Doctoral Awards Program is intended for less established researchers and provides up to $38,000 per year for up to two years. The AICR also provides matching funds grants. The institute also supports the Marilyn Gentry Fellowship Program at the University of North Carolina at Chapel Hill School for Public Health, department of nutrition. The fellowship is named after AICR president Marilyn Gentry and is intended to support researchers as they transition from postdoctoral work into assistant professorships. Robert Bockstiegel, B.S. u
For Further Information American Institute for Cancer Research. Diet and Health Recommendations for Cancer Prevention: Healthy Living and Lower Cancer Risk. Washington, D.C.: Author, 2006. _______. The New American Plate Cookbook: Recipes for a Healthy Weight and a Healthy Life. Berkeley: University of California Press, 2005. 55
4-Aminobiphenyl Weldon, Glen, ed. Dietary Options for Cancer Survivors: A Guide to Research on Foods, Food Substances, Herbals, and Dietary Regimens That May Influence Cancer. Washington, D.C.: American Institute for Cancer Research, 2002. u
Other Resources
American Institute for Cancer Research http://www.aicr.org American Society of Clinical Oncology Http://www.asco.org Association of American Cancer Institutes http://www.aaci-cancer.org See also American Association for Cancer Research (AACR); American Cancer Society (ACS); Dana-Farber Cancer Institute; Duke Comprehensive Cancer Center; Fox Chase Cancer Center; Fred Hutchinson Cancer Research Center; Jonsson Comprehensive Cancer Center (JCCC); M. D. Anderson Cancer Center; Mayo Clinic Cancer Center; Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI); National Science Foundation (NSF); Prevent Cancer Foundation; Robert H. Lurie Cancer Center.
u 4-Aminobiphenyl Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1980 Also known as: 4-Biphenylamine, p-aminobiphenyl, para-aminobiphenyl, p-aminodiphenyl Related cancers: Bladder cancer, liver cancer Definition: 4-Aminobiphenyl, an aromatic amine, occurs as a colorless to yellowish brown crystalline solid that turns purple in air and has an floral odor. Exposure routes: When heated, 4-aminobiphenyl emits toxic fumes. For the general public, exposure to 4-aminobiphenyl comes from inhalation of tobacco smoke. Occupational exposure occurs from inhalation by laboratory personnel who are doing research with 4-aminobiphenyl. When most of the 4-aminobiphenyl was disposed of by injection into underground wells in the late 1980’s, small amounts of it were released into the air, subjecting some individuals to possible contamination. Where found: 4-Aminobiphenyl is a by-product of tobacco smoke and is found as a contaminant in diphenylamine. Its use is confined to laboratory research, although 56
Salem Health: Cancer it may still be found in some dyes, particularly in cosmetics and drugs that contain yellow dye number 1 and in rubber compounds that were manufactured before the mid1950’s. At risk: Scientists and laboratory technicians who work where 4-aminobiphenyl is used in research as a chemical antioxidant have a high risk for 4-aminobiphenyl contamination. Because 4-aminobiphenyl is generated in tobacco smoke, people who smoke are at high risk for contamination. The general public is at risk for contamination from secondhand tobacco smoke. Etiology and symptoms of associated cancers: Inhalation of 4-aminobiphenyl can produce headaches, lethargy, urinary burning, and blood in the urine (hematuria). When metabolized, it can be activated by liver enzymes to form adducts with blood serum proteins, particularly hemoglobin and albumin. Hemoglobin adducts are associated with an increased risk for liver cancer. In some cases, 4-aminobiphenyl can undergo additional metabolism to form reactive compounds that are transported to the bladder, where they bind to deoxyribonucleic acid (DNA) molecules. In laboratory tests on cultured human cells, 4-aminobiphenyl caused genetic damage that included cell transformation and inhibition of DNA repair. 4-aminobiphenyl can cross the human placenta and has been detected in fetal blood. History: 4-Aminobiphenyl was commercially produced in the United States from the early 1930’s until the mid1950’s. It was used in the detection of sulfates, in the production of azo dyes and yellow-dye stuffs, and as an antioxidant in the production of rubber. There are still a few companies in the United States that manufacture 4-aminobiphenyl for use in laboratory research. Alvin K. Benson, Ph.D. See also Bladder cancer; Cigarettes and cigars; Diethanolamine (DEA); Liver cancers; Tobacco-related cancers.
u Amputation Category: Procedures Definition: Surgical removal of all or part of a limb as a result of peripheral vascular disease, trauma, tumor, infection, or congenital anomaly. Cancers treated: Soft-issue neoplasias (malignant fibrous histiocytoma, fibrosarcoma, rhabdomyosarcoma, synovial sarcoma); bone malignancies (osteosarcoma, chondrosarcoma, adamantinoma, Ewing sarcoma)
Salem Health: Cancer
Amputation
Why performed: Amputations are performed to remove extremities that are severely diseased, injured, or no longer functional. Amputation has five goals: removal of all diseased tissue; relief of pain; proper wound healing; prevention of metastatic spread of tumor cells; and construction of a stump that will permit useful function. Amputation as a musculoskeletal procedure is often accomplished as an alternative to limb salvage and should be considered a reconstructive maneuver. Because of the psychological implications and the alteration of body self-image with amputation, a multidisciplinary team approach should be taken to return the patient to a maximum level of independent function. The process should be considered the first step in the rehabilitation of the patient rather than a failure of treatment. Epidemiologic data on the incidence of amputation in the United States from 1993 to 2003 show that the number of lower-extremity amputations increased 14 percent, from 99,522 to 123,379 cases. Average hospital charge for this procedure increased 40 percent, from $24,332 to $34,046. Nearly two-thirds of amputations are performed in individuals with diabetes, even though these individuals represent only 6 percent of the entire population. Patient preparation: Amputation and subsequent healing depend on several factors, including vascular inflow, nutrition, and an adequate immune system. Prior to surgery, patients should be evaluated regarding these parameters. Patients with malnutrition or immune deficiency have a high rate of wound breakdown or infection. A serum albumin level below 3.5 grams per deciliter (g/dl) indicates a malnourished patient. An absolute lymphocyte count below 1,500 cubic millimeters is a sign of immune deficiency. If possible, amputation should be delayed in patients until these values can be improved by nutritional support. In severely affected patients, nasogastric or percutaneous gastric feeding tubes are necessary. Oxygenated blood is a prerequisite for wound healing. A hemoglobin level of more than 10 g/dl is required. Doppler ultrasonography has been used to measure vascular inflow and to predict the success of wound healing. An absolute Doppler pressure of 70 millimeters of mercury (mm Hg) and an ischemic index of 0.5 or greater are necessary at the surgical site. The transcutaneous partial pressure of oxygen (Tcp02) is now regarded as the gold standard in the measurement of vascular inflow. Values greater than 40 mm Hg correlate with acceptable healing rates. Steps of the procedure: With regard to tumor stage and desired functional outcome, there are a variety of surgical procedures pertaining to upper-limb, lower-extremity, or
Treatment of some cancers involves amputation, which requires the patient to learn new living skills. (Digital Stock)
axial skeletal amputation. Patients with musculoskeletal neoplasms face new choices in treatment with the development of limb salvage techniques and adjuvant chemotherapy and radiation therapy. If an amputation is chosen, then the incision must be planned carefully to achieve the appropriate surgical margin. These surgical margins are characterized by the relationship of the surgical incision to the lesion, to the inflammatory zone surrounding the lesion, and to the anatomic compartment in which the lesion is located. The four types of surgical margins include the following: • intralesional: the surgical incision enters the lesion • marginal: the surgical incision enters the inflammatory zone but not the lesion • wide margin: the incision enters the same anatomic compartment of the lesion but is outside the inflammatory zone • radical: the incision remains outside the anatomic compartment 57
Amyloidosis After the procedure: A variety of wound care methods are used after amputation, including rigid dressings, soft dressings, controlled environment chambers, air splints, and skin traction. The use of an immediate postoperative prosthesis (IPOP) has been shown to be effective in decreasing the time to limb maturation and definitive prosthetic fitting. Rehabilitation and prosthetic fitting remain the primary postoperative goals. Risks: The amputee is at risk for deep vein thrombosis (15 percent) and pulmonary embolism (2 percent). Prolonged postoperative immobilization, stagnation of blood due to ligation of large veins, delayed prosthetic fitting, and inactivity increase the overall risk of thromboembolism (clot). Approximately 80 to 90 percent of amputees experience some episodes of phantom limb pain, which are often severe but infrequent. Other major complications include failure of wound healing, infection, postoperative edema, joint contractures, and dermatological problems such as skin irritation as a result of improper prosthetic fit, breakdown over stump margins, and episodes of contact dermatitis. Results: There is an ongoing controversy when comparing limb salvage to amputation with regard to energy expenditure to ambulate, quality-of-life measures, and the performance of activities of daily living. Studies suggest that functional outcomes are comparable with either limb salvage or amputation. Overall survival remains comparable with either treatment. With some tumors, amputation may achieve better local disease control. Both treatment groups report qualityof-life problems involving employment, health insurance, social isolation, and poor self-esteem. John L. Zeller, M.D., Ph.D. u
For Further Information Bone, M., P. Critchley, and D. Buggy. “Gabapentin in Postamputation Phantom Limb Pain: A Randomized, Double-Blind Placebo-Controlled, Cross-Over Study.” Regional Anesthesia and Pain Medicine 27, no. 5 (2002): 481. Doherty, Gerard M., and Lawrence W. Way, eds. Current Surgical Diagnosis and Treatment. 12th ed. New York: Lange Medical Books/McGraw-Hill, 2006. Menendez, L. R., ed. Orthopaedic Knowledge Update: Musculoskeletal Tumors. Rosemont, Ill.: American Academy of Orthopedic Surgeons, 2002. Peabody, T. D., et al. “Evaluation and Staging of Musculoskeletal Neoplasms.” The Journal of Bone and Joint Surgery: American Volume 80, no. 8 (1998): 1204. Skinner, Harry B., ed. Current Diagnosis and Treatment 58
Salem Health: Cancer in Orthopedics. 4th ed. New York: Lange Medical Books/McGraw-Hill, 2006. u
Other Resources
American Academy of Orthopedic Surgeons http://www.aaos.org American College of Surgeons http://www.acs.org See also Bone cancers; Fibrosarcomas, soft-tissue; Hyperthermic perfusion; Juvenile polyposis syndrome; Limb salvage; Liposarcomas; Lymphangiosarcomas; Mastectomy; Neuroectodermal tumors; Occupational therapy; Orthopedic surgery; Sarcomas, soft-tissue; Surgical oncology; Synovial sarcomas; Veterinary oncology.
u Amyloidosis Category: Diseases, symptoms, and conditions Also known as: AL amyloidosis, immunoglobulin lightchain amyloidosis, primary amyloidosis Related conditions: Multiple myeloma Definition: Amyloidoses are a class of illnesses in which fibrillar protein deposits form throughout the body. Immunoglobulin-related (AL) amyloidosis, a disorder sometimes caused by cancerous antibody-secreting plasma cells, results when misfolded antibody chains form deposits that impair function of the heart, kidneys, and other organs. Risk factors: There are no known risk factors. Etiology and the disease process: In a minority of patients with multiple myeloma, antibody fragments that are produced by malignant plasma cells form insoluble fibrillar protein deposits. Deposits can form in many organs but are most often found in the kidney, heart, liver, and peripheral and autonomous nervous systems. These deposits ultimately lead to death, most commonly via heart disease and renal failure. Incidence: The overall incidence of AL amyloidosis is approximately 1 in 100,000 people per year. Men are more likely than women to develop AL amyloidosis. Approximately 15 percent of patients with multiple myeloma develop AL amyloidosis, but cases of myeloma-associated amyloidosis make up a small fraction of AL amyloidosis cases. Symptoms: Symptoms depend on the organs involved and vary among patients. Common symptoms include periph-
Salem Health: Cancer eral edema, proteinuria, hepatomegaly, hypotension, shortness of breath, irregular heartbeat, purpura, macroglossia, carpal tunnel syndrome, and peripheral neuropathy. Screening and diagnosis: Many amyloidoses are diagnosed by Congo Red staining of tissues biopsied from subcutaneous fat pads, rectal mucosa, bone marrow, or other sources. Once diagnosis of amyloidosis is established, a free light chain blood test is performed to confirm immunoglobulin chains as the cause of amyloid deposits. Treatment and therapy: Current treatments for amyloidosis parallel those used for multiple myeloma. Melphalan plus predisone reduces the number of malignant plasma cells and levels of circulating immunoglobulin light chains. This is often followed by autologous stem cell transplantation, aimed at rebuilding healthy bone marrow. In some patients, treatment results in a temporary resorption of amyloid fibrils and improvement in organ function. The malignant plasma cells are not completely eradicated, however, and remission is the usual course. IDOX (4′deoxy-4′-iododoxorubicin), a drug that binds to amyloid fibrils and promotes their disassembly, has shown promise in early trials. Prognosis, prevention, and outcomes: Prognosis for patients with AL amyloidosis depends on which organs are affected. Patients with cardiac involvement have the worst prognosis, while patients with involvement limited to other organs have longer median survival times. There is no known way to prevent amyloidosis. Kyle J. McQuade, Ph.D. See also Bone marrow transplantation (BMT); Crohn disease; Orbit tumors; Paraneoplastic syndromes; Stem cell transplantation.
Anal cancer
Stage at Diagnosis and Five-Year Relative Survival Rates for Cancer of the Anus, 1996-2004 Stage Localizeda Regionalb Distantc Unstaged
Individuals Diagnosed (%) Survival Rate (%) 49 32 10 10
81.7 61.1 2.8 57.6
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 a Cancer still confined to primary site b Cancer has spread to regional lymph nodes or directly beyond the primary site c Cancer has metastasized
Risk factors: There are several risk factors for anal cancer, including cigarette smoking and anal receptive sexual intercourse. Infection with the human papillomavirus (HPV16), the sexually transmitted disease that causes genital warts, can cause anal squamous intraepithelial lesions (ASIL), which may develop into anal cancer. People with a suppressed immune system from cancer, cancer treatments, organ transplantation, HIV, or AIDS have an increased risk of anal cancer. The number of people with both HIV and anal cancer is rising. Etiology and the disease process: Researchers do not know the exact cause of the genetic changes that make healthy cells turn into anal cancer cells, although multiple risk factors have been identified. The anal cancer cells multiply and form masses or tumors.
Related conditions: Anorectum cancer, anal squamous intraepithelial lesions (ASIL), human papillomavirus (HPV), human immunodeficiency virus (HIV), acquired immunodeficiency syndrome (AIDS)
Incidence: Anal cancer is a rare form of cancer; however, the number of new cases began to increase in the early 1980’s. The incidence of anal cancer is 1 in 100,000 people. New cases in 2007 in the United States were estimated to reach 4,650. Anal cancer occurs more frequently in women than in men. Women are more likely to develop cancer in the anal canal. Men are more likely to develop cancer tumors on the outside of the anus. Anal cancer occurs most frequently in adults in their early sixties, at a median age of sixty-one years.
Definition: Anal cancer is a rare cancer that forms in the anus, which is at the end of the rectum. The anus is about 1.5 inches long and contains sphincter muscles that control bowel movements. Stool passes through the anus as it leaves the body.
Symptoms: Anal cancer may not cause symptoms. Bleeding from the anus is a common early sign. This type of cancer may cause pain, itching, abnormal anal discharge, and changes in the diameter of stools. A mass or growth may develop in the anus. Nearby lymph nodes may
u Anal cancer Category: Diseases, symptoms, and conditions Also known as: Cancer of the anus, anal canal cancer
59
Anal cancer
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be swollen. The anus may feel unusually full. Screening and diagnosis: Screening tests for anal cancer are recommended for people with a high risk of anal cancer. Women should receive anal cancer screening as part of a yearly exam. Annual anal cancer screening is recommended for men after the age of fifty. Anal cancer is diagnosed with a series of tests and procedures. A digital rectal exam (DRE) is used to check for lumps, masses, or growths in the anus. Endoscopy, using an anoscope or rigid protosigmoidoscopy, allows inspection of the interior anal canal. An anoscope is a thin tube with a viewing instrument and light that is inserted into the anus. A protosigmoidoscope is longer and allows sections of the colon to be viewed as well. Ultrasound, computed tomography (CT) scans, positron emission (PET) scans, and magnetic resonance imaging (MRI) scans are used to provide images of the anal structures and to help determine if the cancer has spread. Fine needle aspiration and sentinel lymph node biopsy are used to obtain cells for examination to confirm if cancer is present. Staging is used to identify cancer growth and metastasis, plan treatment, and predict recovery. Fortunately, anal cancer rarely metastasizes. • Stage I: Anal cancer is 2 centimeters (cm) or less. • Stage II: Anal cancer is larger than 2 cm, is confined to the anus, and has not spread beyond the anus. • Stage IIIA: Anal cancer is any size with spread to nearby lymph nodes or close areas, such as the bladder, urethra, or vagina. • Stage IIIB: Anal cancer is any size with spread to nearby lymph nodes and close areas, or it has spread to lymph nodes in the pelvis. • Stage IV: Anal cancer has spread to distant locations in the body. Treatment and therapy: Chemoradiation is the treatment of choice for anal cancer. External radiation, brachytherapy, or both may be used. Chemotherapy 5-FU and Mutamycin (mitomycin) may be used in combination with radiation or surgery. Surgery is used for patients with residual anal cancer and includes local resection or abdominoperineal resection (APR). Prognosis, prevention, and outcomes: Anal cancer screening, HPV testing, HIV testing, quitting smoking, 60
Cancer of the anus. (BSIP/Photo Researchers, Inc.)
knowing the STD status of sexual partners before intercourse, and not participating in anal sex may help prevent anal cancer. Condoms may reduce the risk of HPV and HIV, but they are not a guarantee. HPV vaccination is available for girls and women. Many cases of anal cancer that are detected and treated early can be cured. However, anal cancer may recur even with treatment. It was estimated that 690 men and women with anal cancer would die in the United States in 2007, a rate of 0.2 per 100,000 people. Mary Car-Blanchard, O.T.D., B.S.O.T. u
For Further Information Cranston, R. D., et al. “The Prevalence, and Predictive Value, of Abnormal Anal Cytology to Diagnose Anal Dysplasia in a Population of HIV-Positive Men Who Have Sex with Men.” International Journal of STD and AIDS 18, no. 2 (February, 2007): 77-80. Das, P., C. H. Crane, and J. A. Ajani. “Current Treatment for Localized Anal Carcinoma.” Current Opinions in Oncology 19, no. 4 (July, 2007): 396-400. Meyer, J., B. Czito, F. F. Yin, and C. Willett. “Advanced Radiation Therapy Technologies in the Treatment of Rectal and Anal Cancer: Intensity-Modulated Photon Therapy and Proton Therapy.” Clinical Colorectal Cancer 6, no. 5 (January, 2007): 348-356. Uronis, H. E., and J. C. Bendell. “Anal Cancer: An Overview.” Oncologist 12, no. 5 (May, 2007): 524-534.
Salem Health: Cancer u
Androgen drugs
Other Resources
American Cancer Society How Is Anal Cancer Diagnosed? Http://www.cancer.org/docroot/CRI/content/CRI_ 2_4_3X_How_Is_Anal_Cancer_Diagnosed_47.asp National Cancer Institute Anal Cancer Treatment http://www.cancer.gov/cancertopics/pdq/treatment/ anal/patient See also Abdominoperineal resection (APR); Anoscopy; Colostomy; Computed tomography (CT) scan; Digital rectal exam (DRE); Endoscopy; Gastrointestinal cancers; Gastrointestinal oncology; Infectious cancers; Risks for cancer; Sexuality and cancer; Sigmoidoscopy.
u Androgen drugs Category: Chemotherapy and other drugs ATC code: G03B Definition: Androgens are steroid hormones produced by the adrenal glands and testes or ovaries, responsible for male sex characteristics in the body. Testosterone, an endogenous androgen, is converted to estrogen by the enzyme aromatase. Androgenic agents can be used in the treatment of breast cancer. Cancers treated: Metastatic hormone-responsive breast cancer in postmenopausal women, or in premenopausal women who have undergone ovary ablation Subclasses of this group: Anabolic steroids, alkylated androgens, testosterone esters Delivery routes: Administered orally as tablets or capsules, or by intramuscular injection How these drugs work: Testosterone esters are lipophilic compounds that, when dissolved in oil, are administered via intramuscular injection. Alkylated androgens can be
given orally as their metabolic deactivation is hindered by the alkyl group at the 17α position. The mechanism of action for androgenic agents in breast cancer has not been fully established, though they are believed to block the growth of estrogen-dependent tumors by inhibiting aromatase activity. Older drugs such as calusterone underwent clinical trials in the 1960’s and 1970’s, with response rates of approximately 20 percent. Androgen drugs are not considered first-line therapy for breast cancer, as they are more toxic than other hormonal agents in use and response rates remain low. Androgens, when used, are frequently given in combination with aromatase inhibitors to inhibit the production of estrogen in vivo. Side effects: Androgens are male sex hormones and can cause masculinizing effects in women, including deepening voice, hirsutism, acne, and clitoral enlargement. Alkylated androgens are less potent than testosterone and hence possess a lower risk of these side effects, but liver toxicity, cholestatic hepatitis, and jaundice can occur at relatively low doses. Androgen therapy should be discontinued following abnormal liver function tests until the cause has been determined. Androgen therapy in patients with preexisting cardiac, renal, or hepatic disease increases the risk of edema and progression to congestive heart failure. In such cases, dosing should be discontinued and administration of a diuretic considered. Breast cancer patients undergoing androgen therapy are at increased risk of bone breakdown and reabsorption, leading to hypercalcemia. If this occurs, then drug therapy should be discontinued and the patient evaluated, as hypercalcemia may also indicate the progression of bone metastases. Karen M. Nagel, Ph.D. See also Amenorrhea; Antiandrogens; Appetite loss; Bisphenol A (BPA); Breast cancer in men; Chemoprevention; Endocrine cancers; Fanconi anemia; Granulosa cell tumors; Hormonal therapies; Myelofibrosis; Receptor analysis; Tumor flare.
Androgen Drugs for Breast Cancer Treatment Drug
Brands
Subclass
Delivery Mode
Testolactone Testosterone enanthate Fluoxymesterone Methyltestosterone
Teslac Delatestryl Androxy, Halotestin, Ora-Testrylm Android-F, Hysterone Tested, Virilon, Android-10, Methitest
Anabolic steroid Testosterone ester Alkylated androgen Alkylated androgen
Oral Intramuscular Oral Oral
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Anemia
Salem Health: Cancer
u Anemia Category: Diseases, symptoms, and conditions Also known as: Low red blood cell count, erythropenia, iron-poor blood Related conditions: Cytopenia Definition: Anemia is a low number of red blood cells, decreased volume of red blood cells, or a reduced concentration of hemoglobin. Risk factors: For anemia of cancer, risk is associated with the type of cancer, stage of disease, and treatment regimen. Etiology and the disease process: Anemia may be caused by deficiencies of vitamin B12, folic acid, or iron; antibody formation; kidney failure; lead poisoning; bone-marrow dysfunction; chemotherapy; or radiation therapy. It can also result from infiltration of bone marrow by leukemia or lymphomas or from internal bleeding or excessive blood loss from repeated blood sampling. Anemias caused by deficiencies in folic acid, vitamin
B12, and iron are generally known as nutritional anemias. In these forms of anemia, the endogenous hormone erythropoietin, responsible for red blood cell production, appears to be present in adequate amounts. Patients with cancer, however, can be anemic because of deficiencies in these nutrients. The anemia of cancer, a subset of anemia of chronic disease, is marked by reduction in the amount of the hormone erythropoietin found in the circulation, suppression of bone marrow function, disturbances in iron metabolism, and activation of the inflammatory and immune systems in response to the insult of cancer that activates hormones, which in turn decrease the production of endogenous erythropoietin. Another form of anemia is aplastic anemia, which may be caused by chemotherapy, radiation therapy, or drugs. In the normal state of health, endogenous erythropoietin is released by peritubular cells in the kidney cortex when specialized cells sense hypoxia (low oxygen content of the blood). In the bone marrow, erythropoietin stimulates the proliferation and differentiation of primitive cells (that is, progenitor cells) that will mature and differentiate
Numerous types of anemia exist.
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Anemia
into red blood cells. As the cells mature and differentiate, they synthesize hemoglobin, the iron-containing pigment that is responsible for carrying oxygen to all cells in the body and carrying carbon dioxide away from cells.
sions. In cases of severe anemia, however, transfusions are routinely used because it takes several days for the erythropoiesis-stimulating proteins to increase red blood cell count and hemoglobin concentration.
Incidence: It is estimated that the frequency of severe anemia, marked by a hemoglobin concentration less than 8 grams per deciliter (g/dl) across a broad range of cancers, is 5 to 20 percent, and that of mild anemia, marked by a hemoglobin concentration of 8 to 11 g/dl, is 25 to 45 percent.
Prognosis, prevention, and outcomes: The prognosis for anemia depends greatly on the type of anemia. For anemia of cancer, anemia may be directly related to prognosis and survival. Research suggests that it may be important to maintain hemoglobin concentration at a high level to decrease the effects of hypoxia, especially during treatment. Because chemotherapy and radiation therapy target rapidly dividing cells, both cancer cells and bone marrow cells, it is difficult to prevent anemia due to treatment without reducing the efficacy of treatments. Also, the anemia of cancer involves endogenous inflammatory and immune functions, which cannot be prevented. Proper nutrition may be useful in preventing anemia caused by deficiencies in folic acid, iron, and vitamin B12. MaryAnn Foote, M.S., Ph.D.
Symptoms: Symptoms of anemia can include fatigue, pale skin (including nail beds and the lining of the eyelids), dizziness, chills, shortness of breath, rapid pulse, and chest pains. Screening and diagnosis: A blood test can measure the hemoglobin concentration, or hematocrit; hemoglobin concentration is generally used, as it is more accurate than hematocrit. Other tests that are often done at the same time are red blood cell indices, which include red blood cell count, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), and mean corpuscular hemoglobin (MCH). Iron parameters, which include serum iron, total iron-binding capacity, percent transferrin saturation, and serum ferritin, are measured. A test for occult blood in the stool as a possible source of blood loss is often done, particularly in the setting of gastrointestinal cancers. A normal red blood cell count is 3.5 to 5.0 × 1012/liter for women and 4.3 to 5.9 × 1012/liter for men. Hematocrit, the measure of the volume of red blood cells as a percentage of the total blood volume, is 37 to 47 percent for women and 45 to 57 percent for men. Normal concentration of hemoglobin is 14 to 17.5 g/dl for men and 12 to 16 g/dl for women. Treatment and therapy: While anemia of cancer can be treated with transfusions of packed red blood cells, the standard of care at most cancer treatment centers is the use of recombinant human erythropoiesis-stimulating proteins such as epoietin alfa (Epogen or Procrit) or darbepoietin alfa (Aranesp). The recombinant human erythropoiesisstimulating proteins are given as injections three times a week to once every three weeks depending on the patient’s needs and type of recombinant protein used. The use of these recombinant proteins allows oncologists the option of not using red blood cell transfusions, with their small but inherent risks of autoimmunization and infection. The possibility of failure of bone marrow or stem cell transplantation increases with the number of previous transfu-
u
For Further Information Crawford, C., et al. “Relationship Between Changes in Hemoglobin Level and Quality of Life During Chemotherapy in Anemic Cancer Patients Receiving Erythropoietin Therapy.” Cancer 95 (2002): 888-895. Molineux, G., M. A. Foote, and S. G. Elliott, eds. Erythropoietins and Erythropoiesis: Molecular, Cellular, Preclinical, and Clinical Biology. Basel, Switzerland: Birkhäuser, 2003.
u
Other Resources
Anemia.com http://www.anemia.com MedlinePlus Anemia http://www.nlm.nih.gov/medlineplus/anemia.html See also Acute lymphocytic leukemia (ALL); Acute myelocytic leukemia (AML); Angiogenesis inhibitors; Antifungal therapies; Aplastic anemia; Blood cancers; Bone marrow transplantation (BMT); Chronic lymphocytic leukemia (CLL); Chronic myeloid leukemia (CML); Colony-stimulating factors (CSFs); Fanconi anemia; Hairy cell leukemia; Hematologic oncology; Hemolytic anemia; Stem cell transplantation; Thrombocytopenia; Transfusion therapy; Waldenström macroglobulinemia (WM); Young adult cancers. 63
Angiogenesis
u Angiogenesis Category: Cancer biology Also known as: Blood vessel formation Definition: Angiogenesis is the formation of new blood vessels. It is a perfectly normal process in a developing or growing body, and during a woman’s reproductive years, it enables the menses and pregnancy. In addition, angiogenesis maintains health by developing a new blood supply in injured tissue, controlling inflammation, and even healing fractures of the bone. In health, the body controls angiogenesis, but in cancer, the body loses control. Angiogenesis is thought to be a process by which a cancer obtains its blood supply from its host. Without vascularization—the provision of blood vessels—no tissue in the body can live. Nearly every cancer known is associated with pathological angiogenesis. Relation of angiogenesis to cancer. In one way, a cancerous tumor is like any other bodily structure: Its survival de-
Tumor angiogenesis. (©ISM/Phototake—All rights reserved)
64
Salem Health: Cancer pends on the provision of oxygen and nutrients and the removal of waste. Cancerous tumors differ from normal tissue in that they tend to spread, or metastasize, without regard to normal borders between different tissues such as muscle, cartilage, and bone. Blood supply to a tumor enables it to spread. For its support and ability to grow, in effect the cancer must persuade the body to build vessels to and throughout the tumor, something that seems counterintuitive. In fact, the body contains defenses against this. As cancer develops, however, these defenses are short-circuited. The way the tumor fools its host into cooperation is chemically—with proteins and enzymes found naturally in the body but used by the tumor to its advantage. Proteins that induce growth are known as growth factors. Researchers have shown evidence that one chemical secreted by tumors, vascular endothelial growth factor (VEGF), in effect attracts blood vessels. Induced by growth factors and possibly hormones, new blood vessels actually sprout from existing vascular tracts into and around the cancer. Researchers also report that breast cancer cells produce interleukin-8 (IL-8), a protein that normally attracts white blood cells to injuries and inflammation, but which is also known to be angiogenic. Other researchers, exploring the role of certain enzymes in regulating angiogenesis in breast cancer, are focusing on the extracellular matrix, noncellular material that surrounds any tissue (picture the stuffing around mattress springs) and common not only to normal tissues but also to tumor cells. In addition to taking up space between cells (including cartilage, tendon, ligament, and bone), the extracellular matrix performs a critical function. Under normal circumstances after adulthood, the extracellular matrix prevents unauthorized (non-injury-related) angiogenesis and cell movement. Cancer short-circuits that inhibitory function. Compared with normal breast cells, some breast cancer cells have higher levels of two enzymes that degrade heparin, an important component of the extracellular matrix. A weakened and degraded extracellular matrix might well enable abnormal cell movement and angiogenesis. Not every researcher, however, is convinced that tumors depend on angiogenesis. Citing the “immature” vasculature of some tumors—meaning that the blood vessels are not as well organized as in normal body tissues— and the lack of consistent evidence from clinical trials, they question cancer’s angiogenesis dependency. Those who support the connection counter that cancer growth is by its very nature not only disorganized—it is growing a tumor rather than a kidney or a pancreas—but also, relative to other tissues, new in origin. Because cancer’s
Salem Health: Cancer
Angiogenesis
Known Angiogenic Growth Factors
• • • • • • • • • • •
Angiogenin Angiopoietin-1 Del-1 Fibroblast growth factors: acidic (aFGF) and basic (bFGF) Follistatin Granulocyte colony-stimulating factor (G-CSF) Hepatocyte growth factor (HGF) /scatter factor (SF) Interleukin-8 (IL-8) Leptin Midkine Placental growth factor
• • • • • • • • •
Platelet-derived endothelial cell growth factor (PD-ECGF) Platelet-derived growth factor-BB (PDGF-BB) Pleiotrophin (PTN) Progranulin Proliferin Transforming growth factor-alpha (TGF-alpha) Transforming growth factor-beta (TGF-beta) Tumor necrosis factor-alpha (TNF-alpha) Vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF)
Source: The Angiogenesis Foundation
growth, unlike that of healthy tissue, is continual, its vasculature might be expected to remain immature. Preventing cancer-related angiogenesis: If tumors do require angiogenesis to survive and spread, then it seems logical to discourage angiogenesis. Inhibitors of angiogenesis were first discovered in 1975 and since then have been detected in such diverse natural sources as tree bark, green tea, fungi, shark cartilage and muscle, sea coral, and various herbs. Ways to prevent or change the process of angiogenesis being investigated include blocking the chemical signals from the tumor, making these signals less effective; preventing the breaching of the extracellular matrix; and after a tumor has already been supplied with blood vessels, causing the vessels to normalize, or stop supplying the tumor. Another area being researched targets oncogenes, genes that cause normal cells to become cancerous and also, it is believed, activate the angiogenesis switch. Researchers are developing antioncogene drugs. Angiogenesis inhibitors, while promising, have yet to be proven as efficacious treatments, in part because of the complexity and diversity of the tumors themselves. What works for one tumor may not work for another. Another complication of agents that inhibit angiogenesis is the chaos they could produce in inflammation control and healing. Nevertheless, the possibility of inhibiting angiogenesis only where it is needed, with very targeted inhibitors and perhaps with the assistance of other drugs such as paclitaxel (Taxol) and cyclophosphamide (Cytoxan, Neosar) and such COX-2 inhibitors as celecoxib (Celebrex) and thalidomide, all of which interfere with angiogenesis, remains an attractive investigative path. Research and clinical trials are ongoing. Jackie Dial, Ph.D.
u
For Further Information Chan, David. Breast Cancer: Real Questions, Real Answers. New York: Marlowe & Company, 2006. Firedewald, Vincent, M. D. Buzdar, and Michael Bokulich. Ask the Doctor: Breast Cancer. Kansas City, Mo.: Andrews McMeel, 1997. Link, John. Breast Cancer Survival Manual: A Step-byStep Guide for the Woman with Newly Diagnosed Breast Cancer. 4th ed. New York: Holt, 2007.
u
Other Resources
American Cancer Society http://www.cancer.org Angiogenesis Foundation About Angiogenesis http://www.angio.org/understanding/ understanding.html MayoClinic.com Angiogenesis Inhibitors: New Cancer Drugs Stop Tumor Growth http://www.mayoclinic.com/health/angiogenesis/ CA00079 National Breast Cancer Foundation http://www.nationalbreastcancer.org See also Angiogenesis inhibitors; Bioflavonoids; Biological therapy; BRAF gene; Bronchoalveolar lung cancer; Cancer biology; Cartilage supplements; Chemotherapy; Gene therapy; Genetics of cancer; Hereditary leiomyomatosis and renal cell cancer (HLRCC); HIV/AIDS-related cancers; Human growth factors and tumor growth; Im65
Angiogenesis inhibitors munotherapy; Kidney cancer; Matrix metalloproteinase inhibitors; Oral and oropharyngeal cancers; Phenolics; Robert H. Lurie Cancer Center; Sarcomas, soft-tissue.
u Angiogenesis inhibitors Category: Chemotherapy and other drugs Definition: Angiogenesis inhibitors prevent the formation of new blood capillaries formed by the process called angiogenesis. As a result, cancer tumors are starved and die. Cancers treated: Multiple myeloma, mantle cell lymphoma, metastatic colorectal cancer, advanced renal cancer, gastrointestinal stromal tumors Delivery routes: Delivered intravenously on an inpatient basis (Velcade, Avastin) or orally in tablet (Sutent, Nexavar) and capsule (Thalomid) forms on an at-home basis How these drugs work: Angiogenesis is critical to normal growth, providing a network of new blood capillaries
Salem Health: Cancer that deliver oxygen and nutrients to developing tissues. Once formed, capillaries do not increase in size or number, because the endothelial cells that line them do not divide. In some normal conditions (wound repair, menstruation), however, they do. Tumors require a constant supply of newly formed blood capillaries in order to grow. Early in the angiogenesis process, tumors secrete “growth factors,” which signal the endothelial cells to proliferate. The new capillaries attach themselves to the tumor and deliver oxygen and nutrients. This blood supply also allows tumor cells to spread to other areas of the body (metastasize), a process that is a major cause of cancer deaths. Some scientists have long hypothesized that attacking angiogenesis might be a powerful tool in preventing tumor growth. Removing the blood supply might prevent the growth of new tumor cells and cause the tumors to grow more slowly or become smaller. In 1971, Dr. Judah Folkman, of Children’s Hospital in Boston, published a paper proposing the hypothesis that all tumor growth is angiogenesis-dependent. This founded the field of angiogenesis research and its control, a field of investigation that is now studied by many scientists.
A mouse with lung cancer, left, was treated with angiogenesis inhibitors in an experiment by Judah Folkman. Twelve days later, the tumor in the mouse, right, showed substantial improvement. (AP/Wide World Photos)
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Salem Health: Cancer
Angiogenesis inhibitors
Angiogenesis Inhibitors Drug
Brands
Subclass
Delivery Mode
Cancers Treated
Bevacizumab
Avastin
Monoclonal antibody
IV
Metastatic colorectal cancer
Bortezomib
Velcade
Dipeptide boronic acid analogue
IV
Multiple myeloma, mantle cell lymphoma
Sorafenib tosylate
Nexavar
Bi aryl urea
Oral
Advanced renal cell carcinoma
Sunitinib malate
Sutent
Malate salt of an indolinone-based tyrosine kinase inhibitor
Oral
Advanced kidney cancer, gastrointestinal stromal tumors
Thalidomide
Thalomid
Glutamic acid derivative
Oral
Multiple myeloma
In December, 2006, the United States’ National Cancer Institute (NCI) listed thirty angiogenesis inhibitors undergoing clinical trials. By 2007, the U.S. Food and Drug Administration (FDA) had approved five angiogenesis inhibitors for use in cancer treatment: Velcade, Avastin, Nexavar, Sutent, and Thalomid. Velcade was approved in 2003 for the treatment of multiple myeloma patients who had received at least two prior therapies with anticancer drugs and had demonstrated disease progression on the last therapy. It was approved in 2005 for multiple myeloma patients who had received one prior therapy and in 2006 for mantle cell lymphoma in patients who had received one prior therapy. Velcade interrupts various cell-signaling pathways critical to angiogenesis. Avastin was approved in 2004 to treat metastatic colorectal cancer. It is believed to act by attaching to a protein growth factor active in angiogenesis. When the growth factor is bound to Avastin, it cannot carry out its function in the angiogenesis process. Avastin enhances the effects of standard chemotherapy but does not appear to be effective when given alone to patients with colorectal cancer. Nexavar was approved in 2005 to treat adults with advanced renal cell carcinoma, an aggressive form of the disease and the most common of kidney cancers. It has not been studied in children. Nexavar is a small molecule, and as such, it enters endothelial cells and inhibits enzymes involved in intercellular signaling linked to cell division; it also acts by binding to vascular endothelial growth factor. Sutent was approved in 2006 for the treatment of gastrointestinal stromal tumors and advanced kidney cancer. Sutent is also a small molecule that enters tumor cells and prevents angiogenesis and cell proliferation by blocking the signaling activity of several growth factors. Thalomid (thalidomide) was approved in 2006 for the treatment of newly diagnosed multiple myeloma, in combination with the chemotherapy drug dexamethasone.
Thalidomide’s activity depends on its ability to block the growth factor signals necessary for angiogenesis. In 1994, Folkman and coworkers published a paper providing evidence that thalidomide is an angiogenesis inhibitor. Its ability to block the development of new blood vessels likely caused the limb malformations in babies of mothers who took the drug as a sedative during pregnancy. Both men and women taking the drug for cancer treatment are required to use contraception to avoid pregnancy. Side effects: The side effects of angiogenesis inhibitors depend on the medication. Some of the more common angiogenesis inhibitors have the following side effects: • Velcade: Fatigue, nausea, diarrhea, anorexia, constipation, thrombocytopenia, peripheral neuropathy, pyrexia, vomiting, and anemia • Avastin: High blood pressure, fatigue, blood clots, diarrhea, decreased white blood cells, headache, appetite loss, and mouth sores • Nexavar: Rash, diarrhea, high blood pressure, and redness, pain, swelling, or blisters on the palms of the hands or soles of the feet • Sutent: Diarrhea, skin discoloration, mouth irritation, weakness, altered taste, fatigue, high blood pressure, bleeding, swelling, and hypothyroidism • Thalomid: Somnolence, constipation, neuropathy, venous thromboembolism, and rash Bernard Jacobson, Ph.D. u
For Further Information D’Amato, R. J., M. S. Loughnan, E. Flynn, and J. Folkman. “Thalidomide Is an Inhibitor of Angiogenesis.” Proceedings of the National Academy of Sciences 91 (1994): 4082-4085. Davis, D. W., R. S. Herbst, and J. L. Abbruzzese, eds. Antiangiogenic Cancer Therapy. New York: CRC Press, 2007. 67
Angiography Folkman, J. “Tumor Angiogenesis: Therapeutic Implications.” New England Journal of Medicine 285 (1971): 1182-1186. Forough, R., ed. New Frontiers in Angiogenesis. New York: Springer, 2006. Sieman, D. W., ed. Vascular-Targeted Therapies in Oncology. Hoboken, N.J.: Wiley, 2006. Skinard, E. T., ed. New Research on Angiogenesis Inhibitors. Hauppage, N.Y.: Nova Science, 2006. u
Other Resources
Food and Drug Administration http://www.fda.gov National Cancer Institute Drug Information Summaries http://www.cancer.gov/cancertopics/druginfo/ alphalist See also Angiogenesis; Biological therapy; Chemotherapy; Oral and oropharyngeal cancers; Sarcomas, softtissue.
u Angiography Category: Procedures Also known as: Arteriography, angiogram, arteriogram Definition: Angiography is a general term for a minimally invasive imaging technique that uses real-time X rays and a special dye to see inside blood vessels, lymph nodes, and certain glands deep inside the body. The dye, known as a contrast medium, is injected into the body to highlight the vessels, lymph nodes, glands—and cancerous tumors— and make them easier to see. The contrast medium is a low-dose radioactive compound known as a radioisotope. The image created by the X ray is called an angiogram. Cancers diagnosed or treated: Cancers of the lymphatic system, the digestive system, the lungs, the brain, and certain glands Why performed: Doctors use angiography to detect and directly examine cancerous tumors and to show the blood flow to a tumor. A direct real-time view of a tumor and blood flow helps doctors diagnose and treat the cancer. With angiography, doctors can determine a tumor’s size, appearance, and relationship to nearby organs and tissues; whether the tumor is growing or extending into nearby parts of the body; and whether cancer cells are spreading to other parts of the body. In some cases, doctors use the procedure to deliver medicine to a tumor. 68
Salem Health: Cancer Patient preparation: Patient preparation varies slightly depending on the part of the body to be examined and whether the patient is already in the hospital (inpatient) or having the procedure done and then returning home the same day (outpatient). Nurses help the inpatient prepare. Outpatients stay several hours in a recovery room before going home. Most outpatients receive a mild sedative to help them relax during the procedure. The test may take up to several hours. Generally, patients should not eat or drink anything for eight hours before the procedure. Patients should tell their doctors if they are pregnant or breast-feeding; which medications they are taking, including aspirin; if they have any bleeding problems or are taking blood-thinning medications; if they have allergies to any substances or medications; if they suffer from asthma; if they have a history of kidney problems or diabetes; if they have blockage of the blood vessels caused by atherosclerosis (hardening of the arteries), high blood pressure, or aging; and if they think they will find it difficult to lie still during the procedure. Steps of the procedure: A team of technicians and nurses led by a radiologist (a doctor who diagnoses diseases by studying X rays and other images) conducts the procedure. The procedure takes place in the radiology laboratory of a medical center. The patient wears a hospital gown and receives a mild sedative but remains awake. The patient lies supine on a table much like an operating table. The surgeon makes a small incision near a blood vessel in the neck, chest, groin, or arm. Using real-time X rays displayed on a video screen for guidance, the surgeon then inserts a thin, flexible tube called a catheter into the vessel. The surgeon guides the catheter through the blood vessels until the tip reaches the area to be studied. Once the catheter is placed in the exact spot, the radiologist injects the dye. The dye travels through the catheter and to the blood vessels, making the target easier to see in the X ray. A round cylinder or rectangular box, known as a fluoroscope, takes the pictures. It moves both above and beneath the patient. After the procedure: After the test, a nurse applies a pressure bandage at the site where the catheter was inserted. Some patients feel tenderness or soreness at the site. Depending on where the catheter was inserted, the patient may have to remain in bed—in the hospital or at home— from several hours up to a day. The patient receives pain medicine if needed. Some people experience a headache, flushing of the face, or a salty or metallic taste in the mouth after the dye is inserted, but these feelings disappear quickly. Doctors generally recommend that patients drink extra fluids to help pass the dye from the body.
Salem Health: Cancer
Angiosarcomas
Risks: Angiography is a very common test. Both the X ray and the dye are safe. The exposure to radiation is low. There are, nevertheless, some small risks. There is a remote chance that a person may react to the contrast agent, or dye. Common contrast agents are iodine, barium, and gadolinium. In addition, patients may feel a slight burning sensation when the doctor injects the dye or some discomfort at the site where the catheter is inserted. Patients do not feel the catheter inside the body. There is a small risk of bleeding, pain, or infection at the site where the catheter is inserted. Results: The angiogram shows that there are no problems if the dye flows smoothly through the blood vessels and no tumors appear in the lymph nodes or glands studied. If the angiogram reveals that blood vessels are not in their normal position or the blood is flowing in an abnormal pattern, then a tumor may be present. Doctors will then conduct additional tests. Wendell Anderson, B.A. u
For Further Information Icon Health. Angiogram: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References. San Diego, Calif.: Author, 2004.
Pagana, Kathleen Deska, and Timothy J. Pagana. Mosby’s Manual of Diagnostic and Laboratory Tests. 3d ed. St. Louis: Mosby Elsevier, 2006. Welch, H. G. Should I Be Tested for Cancer? Maybe Not and Here’s Why. Berkeley: University of California Press, 2004. See also Bile duct cancer; Chemoembolization; Embolization; Endocrinology oncology; Exenteration; Eye cancers; Gallbladder cancer; Hemangioblastomas; Hematemesis; Hemoptysis; Imaging tests; Lymphadenectomy; Lymphangiography; Pancreatic cancers; Percutaneous transhepatic cholangiography (PTHC); Testicular cancer; X-ray tests.
u Angiosarcomas Category: Diseases, symptoms, and conditions Related conditions: Soft-tissue malignancy Definition: Angiosarcomas are cancers that develop from blood vessels. Although the most common sites where they occur are the arms, legs, neck, and head, these tumors can occur anywhere on the body, most frequently on the skin or in the soft tissue. Angiosarcomas are made up of
An angiosarcoma on the knee. (©Lester V. Bergman/Corbis)
69
Anoscopy malignant cells that are rapidly proliferating and capable of extensive infiltration. Risk factors: Some risk factors have been linked with the development of angiosarcoma. Primarily, these include previous exposure to radiation therapy or chemotherapy, as well as exposure to carcinogens such as certain polyester fibers or bone wax. Etiology and the disease process: In many cases, angiosarcoma develops as a complication of a preexisting condition. For example, a radical mastectomy can lead to the development of an angiosarcoma in the soft tissue and skin of the breast. Additionally, foreign materials in the body, such as shrapnel, have resulted in angiosarcomas. Incidence: Angiosarcoma is a very rare tumor type, occurring in only 2 to 3 patients out of 1 million individuals. Nearly half of all angiosarcomas develop in the head and neck regions, but they also can occur in the soft tissue of the lower and upper extremities. Least common of all angiosarcomas are those that occur in other areas of soft tissue, such as the breast, kidney, and liver. Symptoms: Angiosarcomas in the soft tissues of the extremities may be identified as growing masses, while those that occur on the skin generally appear as blue or black nodules. Angiosarcomas that develop in other areas of soft tissue, especially within the abdominal cavity, are capable of growing quite large and often are not diagnosed until the size of the tumor begins to affect the surrounding tissues and organs. Screening and diagnosis: Diagnosis occurs by recognizing the abnormal growths within the skin or extremities of the patient. Angiosarcomas within the abdominal cavity may remain undiagnosed until related symptoms become apparent, such as neuronal symptoms occurring from compression of the lumbar or pelvic nerves. Treatment and therapy: Surgery and radiation therapy are common methods to treat angiosarcomas. Depending on the location, chemotherapy may also be used in combination with these other strategies. The most common chemotherapeutic agent to treat angiosarcoma is Adriamycin (doxorubicin). Prognosis, prevention, and outcomes: Angiosarcomas are aggressive tumors that have a tendency to spread rapidly and frequently reoccur, even after treatment. The reported five-year survival rate for these patients is only 20 percent. Lisa M. Cockrell, B.S. 70
Salem Health: Cancer See also Accelerated partial breast irradiation (APBI); Endotheliomas; Fibrosarcomas, soft-tissue; Hemangiosarcomas; Liver cancers; Lymphangiosarcomas; Sarcomas, soft-tissue; Veterinary oncology.
u Anoscopy Category: Procedures Definition: Anoscopy is the examination of the anus, anal canal, and lower end of the rectum with an endoscope. Cancers diagnosed: Anal cancer, rectal cancer, cancer of an unknown primary site Why performed: Anoscopy is a diagnostic procedure to evaluate the presence of hemorrhoids, anal fissures, abscess, inflammation, tumors (malignant and benign), foreign bodies, infection such as condyloma or warts caused by human papillomaviruses (HPV), and anal squamous skin lesions associated with the human immunodeficiency virus (HIV). Patient preparation: The patient is instructed to clear stool from the rectal vault. A laxative, enema, or other preparation may be necessary for complete emptying of the rectum. For pediatric patients, their parents should be counseled on proper preparations for the procedure so that the patients’ anxiety may be reduced. In emergency cases, preparation for the procedure may not be possible. Steps of the procedure: The patient is asked to use a medical examination gown and to remove underwear. The position during the examination is either bending forward over the examining table or lying on the examination table on the patient’s left or right side with both lower limbs drawn up to the chest. The doctor performs a digital rectal examination wherein a gloved, lubricated index finger is inserted into the rectum to check for abnormalities and structures that can block visualization; the prostate is also examined in male patients. The external area of the anus is examined prior to the anoscope insertion. The doctor then uses the anoscope, a tubular instrument with a light source, to view the anus, anal canal, and lower rectum. The anoscope is lubricated prior to its insertion into the anus and anal canal; the patient may be asked to “bear down” during the insertion, as during a bowel movement. During the procedure, the patient may feel some pressure and the urge to defecate. A biopsy may be obtained during the procedure, as needed. The doctor slowly withdraws the anoscope as the anal canal is viewed carefully.
Salem Health: Cancer After the procedure: Patients can return to normal activities. If a biopsy was taken, then the patient may be instructed to have a sitz bath daily to relieve mild pain. Risks: No significant risk is associated with anoscopy. A small amount of bleeding and mild pain may occur if the patient has hemorrhoids or if a biopsy was obtained. Results: Normal results will show no structural or color abnormalities. Abnormal findings include hemorrhoids, fissures, infections, abscess, inflammation, or tumors. Miriam E. Schwartz, M.D., M.A., Ph.D., and Colm A. Ó’Moráin, M.A., M.D., M.Sc., D.Sc. See also Anal cancer; Hemorrhoids.
u Anthraquinones Categories: Complementary and alternative therapies; chemotherapy and other drugs Definition: Anthraquinones form a group of anticancer agents derived from plant products. Anthraquinones naturally occur in some plants, such as aloe, senna, rhubarb, Cascara buckthorn, and sheep sorrel. Indian rhubarb root (Rheum palmatum) contains several anthraquinones. Sheep sorrel (Rumex acetosella) contains several types of anthraquinones. Subclasses of this group are emodin, aloe emodin, and anthraquionone derivatives. A number of conventional chemotherapeutic agents, such as Adriamycin (doxorubicin), are derivatives of anthraquinones. Cancers treated or prevented: Prostate cancer, breast cancer, non-Hodgkin lymphoma, acute leukemia Delivery routes: Anthraquionones are typically consumed as a mixture of several botanicals, such as in a tea, although intravenous administration has been used in the past. How these drugs work: Anthraquionones are ingredients in herbal mixtures such as Essiac or Flor-Essence that are typically consumed as a tea. The primary herbs in these botanical mixtures, rhubarb and sheep sorrel, are thought to contain anthraquionones. Such herbal extracts have been in use as a cancer treatment since the 1920’s, when they were popularized by a Canadian nurse, Rene Caisse, who obtained the recipe from a woman who claimed that it cured her breast cancer. Caisse opened a clinic and treated patients for more than forty years. After her death, researchers at Memorial Sloan-Kettering in New York tested her product, with inconclusive results. Anthraquionones are alleged to have anti-inflamma-
Anthrax tory effects and cytotoxic effects against tumor cells. Proponents claim that they strengthen the immune system, reduce tumor size, and improve and prolong the lives of people with many types of cancer. Although they have been shown to have tumor inhibition properties, they have been shown to stimulate tumor cell growth as well. Anthraquinones have been shown to stimulate various cytokines that are important in tumor cell defense, including IL-1, IL-6, and TNF. In experimental settings, anthraquinones have been shown to potentiate the action of Adriamycin (doxorubicin), a widely used chemotherapy drug, but the clinical significance of this action is unknown. Anthraquionone derivatives, such as Adriamycin and mitoxantrone, have been shown to be effective as chemotherapeutics. Side effects: Natural anthraquinones and their derivatives have laxative properties. Therefore, a side effect associated with anthraquionones is diarrhea as well as hyperkalemia as a result of chronic diarrhea. They have also been reported to cause nausea, vomiting, and contact dermatitis. A principal danger of this and other unconventional therapies is that they may delay diagnosis and conventional treatment of serious disease. C. J. Walsh, Ph.D. See also Essiac; Green tea; Herbs as antioxidants.
u Anthrax Category: Chemotherapy and other drugs Definition: Anthrax (from the Greek word for coal, anthrako, for the characteristic black skin lesions seen in cutaneous anthrax) is an often fatal infectious disease caused by the bacterium Bacillus anthracis. This bacterium is particularly virulent because it is surrounded by a coating that prevents the immune system from killing it and it secretes a toxin lethal to certain white blood cells (macrophages). Anthrax toxin, the key virulent component of B. anthracis, is currently being studied for use as targeted biological therapy for drug-resistant tumors. B. anthracis is sensitive to a number of antibiotics, including doxicyclin, and fluoroquinolones. Most people, however, do not have preexisting immunity to anthrax because it is not a routine immunization—with the exception of some U.S. military personnel. Cancers treated: Melanoma, breast cancer, colon cancer Delivery routes: Injection 71
Antiandrogens
Salem Health: Cancer
How this substance works: Anthrax infection begins when the spores of the bacteria are inhaled or come into contact with the skin. Anthrax toxin, produced by the bacteria, is the primary virulent factor. The toxin is activated by furin, a protein found in all living cells. Anthrax toxin may be genetically engineered to eschew furin and instead target only cells with high levels of urokinase, a protein produced prolifically by human tumor cells. The anthrax toxin contains three proteins that are innocuous when separate but work together to create a lethal environment for cells. Protective antigen (PA) is an anthrax protein that adheres to a host cell surface and bores a hole into it. The other A number of Bacillus anthracis bacteria. (Centers for Disease Control and Prevention) two proteins released by the bacteria, edema factor (EF) and lethal factor (LF), are too large to penetrate the outside of the cell unblocking the effect of androgens, which are hormones reless PA chaperones them inside. For cellular intoxication, quired for the development and survival of both normal PA is always needed; once inside the cell, only EF or LF is and cancerous prostate cells. needed to speed up the reactions that ultimately lead to rendering inactive parts of the immune system and finally Cancers treated: Prostate cancer to cell suicide (apoptosis). The term “anthrax lethal toxin,” Subclasses of this group: Nonsteroidal antiandrogens when used in cancer therapy research, refers to the combiand synthetic steroids nation of PA and LF. PA is the substance in the anthrax vaccine. Delivery routes: Administered orally as either capsules or Cancer researchers hope to harness the cellular suicide tablets, can be taken on an at-home basis caused by the anthrax toxin to prevent tumors from growing and spreading. In animal studies, the toxin both destroyed How these drugs work: Androgens are male hormones, tumor cells and prevented vascularization of tumors— which include testosterone, dehydroepiandrosterone, and which typically need a lot of nutrients, via vascularization, dihydrotestosterone. Androgens bind to androgen recepto grow. The bioengineered anthrax toxin has not been tors on the surface of prostate cells and turn on signaling shown to damage deoxyribonucleic acid (DNA) or prepathways involved in cellular development and survival vent cell growth in normal cells, common occurrences in and normal prostate function. Most prostate cancers, howtraditional chemotherapy. ever, are also dependent on androgen signaling. Therefore, without it, tumors may stop growing. Side effects: The potential side effects of anthrax therapy Nonsteroidal antiandrogens and synthetic steroids comare not yet known. pete with natural androgens for binding sites on androgen Pamela Richardson, M.S. receptors, thereby blocking the activity of the natural anSee also Biological therapy; Clinical trials. drogens. Synthetic steroids can also act on the hypothalamus in the brain to reduce the production of testosterone. Although antiandrogens inhibit androgen activity, blood levels of testosterone and other androgens may still be u Antiandrogens high, which could promote cancer cell growth. Therefore, antiandrogens are commonly used in combination with Category: Chemotherapy and other drugs other drugs that lower androgen levels, such as luteinizing ATC code: 102BB, G03HA hormone-releasing hormone agonists, which can stop tesDefinition: Antiandrogens are a class of drugs used to tosterone production. Antiandrogens may also be combined with inhibitors of the 5-α reductase enzyme, which treat prostate cancer. They can cause tumor cell death by 72
Salem Health: Cancer
Antidiarrheal agents
Common Antiandrogens for Prostate Cancer Treatment Drug
Brands
Subclass
Delivery Mode
Bicalutamide Cyproterone acetate Flutamide Nilutamide
Casodex Androcur, Climen Eulexin Anandron, Nilandron
Nonsteroidal antiandrogen Synthetic steroid Nonsteroidal antiandrogen Nonsteroidal antiandrogen
Oral Oral Oral Oral
block the conversion of testosterone into dihydrotestosterone. Dihydrotestosterone is thought to be a more potent and active androgen than testosterone. Side effects: Because antiandrogens affect the prostate, they may cause low sperm counts or reduce fertility. Other common side effects include diarrhea, hot flashes, liver toxicity, constipation, decreased appetite, nausea or vomiting, and flulike symptoms. Long-term treatment may also cause osteoporosis, in which bones become weakened. There are also some drug-specific side effects. For example, nilutamide can temporarily cause the eyes to become light sensitive and take longer to adjust to changes in light and dark settings. Flutamide is also associated with the rare side effects of dizziness, fainting, and severe headaches. Elizabeth A. Manning, Ph.D. See also Antiestrogens; Breast cancer in men; Breast cancers; Chemoprevention; Hormonal therapies; Immunotherapy; Tumor flare.
u Antidiarrheal agents Category: Chemotherapy and other drugs ATC code: AO7DA Definition: Antidiarrheal agents are a class of drugs used for the treatment or symptomatic relief of diarrhea. Cancers treated: Antidiarrheal agents are typically used to treat diarrhea associated with carcinoid tumors, colon cancer, lymphoma, thyroid cancer, pancreatic cancer, and pheochromocytoma, as well as cancer treatment-induced diarrhea, caused by such treatments as chemotherapy, radiation therapy, surgery, and bone marrow transplantation. Other causes of diarrhea in patients with cancer include anxiety and stress associated with the diagnosis. For these patients, antidiarrheal agents may be used in combination with antianxiety drugs.
Patients who have diarrhea with a different underlying cause should receive treatment specific to the cause. For example, those who have diarrhea caused by Clostridium difficile should be treated with the antibiotic metronidazole. Antidiarrheal agents may be administered as adjunct therapy after the initiation of antibiotic therapy. Subclasses of this group: Adsorbents, bulk-forming agents, opioids, piperidine derivatives, synthetic octapeptides, mucosal prostaglandin inhibitors Delivery routes: Administered orally in tablet, caplet, capsule, suspension, and liquid form at home or in the hospital; octreotide is administered by subcutaneous injection or by continuous intravenous (IV) infusion while the patient is hospitalized How these drugs work: Adsorbents bind with intestinal contents, increasing their density. Adsorbents such as kaolin and charcoal may inhibit the absorption of other antidiarrheals, making them ineffective. Bulk-forming agents treat diarrhea by absorbing water within the bowel and producing a formed stool. Mucosal prostaglandin inhibitors stimulate the absorption of fluid and electrolytes through the intestinal wall. They also reduce intestinal inflammation and motility by inhibiting prostaglandin synthesis. Moreover the mucosal prostaglandin inhibitor bismuth subsalicylate is thought to have antimicrobial action against Escherichia coli, a bacterium that causes diarrhea. Opioids bind to receptor sites in the intestinal tract, slowing intestinal motility. Synthetic octapeptides inhibit the release of serotonin, gastrin, vasoactive intestinal peptide, secretin, motilin, and pancreatic polypeptide, slowing intestinal motility. Piperidine derivatives reduce peristolic activity by acting directly on the intestinal wall muscles. The reduction in peristolic activity delays intestinal content transit time, increases fecal density, and reduces fluid and electrolyte loss. Side effects: Side effects vary according to the drug class. Adsorbents such as bismuth subsalicylate may cause temporary darkening of the tongue and stools. Bulk-forming agents such as polycarbophil may cause abdominal dis73
Antidiarrheal agents
Salem Health: Cancer
Common Antidiarrheal Agents Drug (Other Names) Brands
Subclass
Delivery Mode Conditions Treated
Aspirin
Bayer aspirin, Ecotrin, Empirin, Halfprin, Norwich Extra Strength
Mucosal prostaglandin inhibitor
Oral
Radiation therapy-induced diarrhea
Bismuth subsalicylate
Bismatrol, Bismatrol Extra, Kaopectate, Extra strength Kaopectate, Pepto-Bismol, PeptoBismol Maximum Strength, Pink Bismuth
Adsorbent, mucosal prostaglandin inhibitor
Oral
Diarrhea associated with colon cancer; lymphoma; thyroid cancer; pancreatic cancer; pheochromocytoma; cancer treatment (antibiotic therapy, bone marrow transplantation, chemotherapy, radiation therapy)
Charcoal
Charcoal Plus DS, CharcoCaps
Adsorbent
Oral
Diarrhea associated with colon cancer; lymphoma; thyroid cancer; pancreatic cancer; pheochromocytoma; cancer treatment (antibiotic therapy, bone marrow transplantation, chemotherapy, radiation therapy)
Difenoxin hydrochloride and atropine sulfate
Motofen
Opioid
Oral
Diarrhea associated with colon cancer; lymphoma; thyroid cancer; pancreatic cancer; pheochromocytoma; cancer treatment (antibiotic therapy, bone marrow transplantation, chemotherapy, radiation therapy)
Diphenoxylate hydrochloride and atropine sulfate
Logen, Lomanate, Lomotil, Lonox
Opioid
Oral
Diarrhea associated with colon cancer; lymphoma; thyroid cancer; pancreatic cancer; pheochromocytoma; cancer treatment (antibiotic therapy, bone marrow transplantation, chemotherapy, radiation therapy)
comfort, bloating, dependence (with prolonged use), increased flatus, and intestinal blockage. Mucosal prostaglandin inhibitors such as aspirin may cause allergic reaction, bruising, gastrointestinal bleeding, hearing loss, hepatitis, itching, low platelet count, nausea, prolonged bleeding time, ringing in the ears, and rash. Opioids such as diphenoxylate hydrochloride and atropine sulfate may cause abdominal discomfort, allergic reaction, blurred vision, confusion, dizziness, dry mouth, dry skin, euphoria, headache, inability to urinate, increased heart rate, itching, loss of appetite, nausea, pancreatitis, rash, respiratory depression, restlessness, sedation, swollen gums, and vomiting. Piperidine derivatives such as loperamide may cause abdominal pain, distention or discomfort; allergic reaction; constipation; dizziness; dry mouth; drowsiness; fatigue; nausea; rash; and vomiting. 74
The synthetic octapeptide, octreotide, may cause abdominal discomfort, arrhythmias, backache, blurred vision, burning or pain at the injection site, cold symptoms, fat malabsorption, flatulence, flulike symptoms, flushing, gallbladder problems, hair loss, hyperglycemia, hypoglycemia, hypothyroidism, joint pain, low heart rate, nausea, pancreatitis, redness at the injection site, swelling, urinary tract infection, and vomiting. Collette Bishop Hendler, R.N., M.S. u
For Further Information Drug Facts and Comparisons 2008. 62d ed. St. Louis: Wolters Kluwer Health, 2008. Karch, Amy M. 2008 Lippincott’s Nursing Drug Guide. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins, 2008.
Salem Health: Cancer
Antiestrogens
Common Antidiarrheal Agents (continued) Drug (Other Names) Brands
Subclass
Delivery Mode Conditions Treated
Kaolin and pectin
Kao-Spen, Kapectolin, KP
Adsorbent
Oral
Diarrhea associated with colon cancer; lymphoma; thyroid cancer; pancreatic cancer; pheochromocytoma; cancer treatment (antibiotic therapy, bone marrow transplantation, chemotherapy, radiation therapy)
Loperamide
Imodium, Imodium A-D, Piperidine derivative Kaopectate II Caplets, Maalox Anti-Diarrheal Caplets, Pepto Diarrhea Control
Oral
Diarrhea associated with colon cancer; lymphoma; thyroid cancer; pancreatic cancer; pheochromocytoma; cancer treatment (antibiotic therapy, bone marrow transplantation, chemotherapy, radiation therapy)
Octreotide
Sandostatin, Sandostatin LAR
Synthetic octapeptide
Subcutaneous injection, IV
Diarrhea associated with colon cancer; lymphoma; thyroid cancer; pancreatic cancer; pheochromocytoma; cancer treatment (antibiotic therapy, bone marrow transplantation, chemotherapy, radiation therapy)
Paregoric
Camphorated Tincture of Opium
Opioid
Oral
Diarrhea associated with colon cancer; lymphoma; thyroid cancer; pancreatic cancer; pheochromocytoma; cancer treatment (antibiotic therapy, bone marrow transplantation, chemotherapy, radiation therapy)
Polycarbophil
Equalactin, Fiberall, FiberCon, Fiber-Lax, Konsyl Fiber, Mitrolan, Phillips’ Fibercaps
Bulk-forming agent
Oral
Diarrhea associated with colon cancer; lymphoma; thyroid cancer; pancreatic cancer; pheochromocytoma; cancer treatment (antibiotic therapy, bone marrow transplantation, chemotherapy, radiation therapy)
Nursing 2008 Drug Handbook. Philadelphia: Lippincott Williams & Wilkins, 2008.
mone-sensitive breast cancers because of their ability to inhibit estrogen-stimulated cancer growth.
See also Antinausea medications; Chemotherapy; Colorectal cancer; Crohn disease; Diarrhea; Enteritis; Gastrointestinal complications of cancer treatment; Inflammatory bowel disease; Laxatives; Side effects; Symptoms and cancer.
Cancers treated: Breast cancer
u Antiestrogens Category: Chemotherapy and other drugs ATC code: 102BA Definition: Antiestrogens interfere with the function of estrogen receptors. They are used in the treatment of hor-
Subclasses of this group: Selective estrogen receptor modulators (SERMs), estrogen receptor downregulators Delivery routes: Administered either intramuscularly or orally in capsule, tablet, or solution form on an inpatient, outpatient, or at-home basis How these drugs work: In 1962, ICI Pharmaceuticals synthesized the antiestrogen tamoxifen, what they hoped to be a new oral contraceptive. Although tamoxifen did not prove effective as a contraceptive, the discovery of hormone receptors in breast tissue by Elwood V. Jensen in 1966 led some researchers to believe that tamoxifen could 75
Antifungal therapies
Salem Health: Cancer
Common Antiestrogens for Breast Cancer Treatment Drug
Brands
Subclass
Delivery Mode
Fulvestrant Raloxifene Tamoxifen Toremifene
Faslodex Evista Nolvadex, Soltamox Fareston
Estrogen receptor downregulators SERMs SERMs SERMs
Intramuscular Oral Oral Oral
be a therapeutic option in hormone-sensitive breast cancer. Clinical research in the early 1970’s produced evidence that tamoxifen was effective in advanced breast cancers, and by the 1980’s it became the treatment option of choice for hormone-sensitive breast cancers in pre- and postmenopausal women as well as men. Later it was approved for use in reducing the risk of breast cancer in patients who are susceptible to the disease. Tamoxifen is a selective estrogen receptor modulator (SERM), a subclass of antiestrogens that act by binding to and changing estrogen receptors, resulting in both estrogenic and antiestrogenic effects depending on cell type. Antiestrogenic effects result in a slowing of cancer cell cycling and impaired deoxyribonucleic acid (DNA) replication. Estrogen receptor downregulators are used as a second-line treatment in hormone-sensitive breast cancer and act similarly to SERMs in that they antagonize the estrogen receptors of breast cells. These drugs, however, are pure estrogen receptor antagonists: Independent of cell type, they completely degrade the estrogen receptor, resulting in a total loss of transcriptional activity in cancer cells.
u Antifungal therapies
Side effects: Common side effects of antiestrogens are menopausal symptoms (hot flashes, night sweats), vaginal discharge, vaginal irritation, vaginal bleeding, gastrointestinal (GI) symptoms (nausea and vomiting, constipation, diarrhea), fatigue, muscle cramps, joint pain, and thromboembolism. Although tamoxifen inhibits estrogen receptors in breast cells, it is a partial agonist in the endometrium and can cause endometrial changes, such as endometrial cancer, polyps, endometriosis, uterine fibroids, and ovarian cysts. Amber L. Fields, M.S.
Delivery routes: Antifungal agents can be administered orally in capsules, tablets, or liquid suspension or vaginally by vaginal tablet. The can be administered in the hospital or at home. Some antifungal agents are administered by intravenous (IV) infusion while the patient is hospitalized. As the patient’s condition improves, IV infusions may be administered at home or in an outpatient treatment center.
See also Antiandrogens; Breast cancer in men; Breast cancers; Chemoprevention; Ductal carcinoma in situ (DCIS); Estrogen receptor downregulator (ERD); Estrogenreceptor-sensitive breast cancer; Fertility drugs and cancer; Hormonal therapies; Hormone receptor tests; Hormone replacement therapy (HRT); Isoflavones; Mastectomy; Phytoestrogens; Progesterone receptor assay; Receptor analysis; Soy foods. 76
Category: Chemotherapy and other drugs ATC code: J02 Definition: Antifungal therapies form a class of antiinfective drugs that are effective against fungi such as Aspergillus, Candida, Cryptococcus, Fusarium, and Scedosporium apiospermum. Cancers treated: Antifungal agents are used to treat fungal infections that develop in patients with any type of cancer. Fungal infections commonly occur in patients with acute lymphoblastic leukemia and acute myelocytic and monocytic leukemia. Antifungal agents are also used to prevent fungal infections in patients who have undergone bone marrow or stem cell transplantation. Subclasses of this group: Polyene antibiotics, echinocandins, bis-triazole derivatives, fluorinated pyrimidines, synthetic triazoles, imidazole derivatives, polyene macrolides
How these drugs work: Polyene antibiotics bind to components of the fungal cell membrane and alter the cell’s permeability, causing fungal cell death. Echinocandins work by inhibiting an enzyme that is essential to the fungal cell wall. Bis-triazole derivatives inhibit the fungal cytochrome P-450 and weaken the fungal cell wall, causing fungal cell death. Fluorinated pyrimidines interfere with protein synthesis within the fungal cells, causing cell death. Synthetic triazoles inhibit fungal cell wall synthesis, causing cell wall instability and eventually cell death. Imidazole derivatives inhibit the formation of ergosterol, a
Salem Health: Cancer
Antifungal therapies
sterol necessary for fungal cell-wall synthesis. Without ergosterol, the fungal cell wall becomes permeable and unstable, causing cell death. Polyene macrolides bind to sterols, making the fungal cell wall permeable. This increased permeability allows intracellular components to leak from the fungal cell, causing fungal cell death. Side effects: Side effects vary according to the antifungal agent. The amphotericans are potent antifungals that have toxic side effects, including kidney and liver failure. Side effects that may occur with antifungal agents include abdominal pain, abnormal dreams, allergic reaction, anemia, anxiety, back pain, bacterial bloodstream infection, bloody nose, bloody urine, blurred vision, cardiac arrest, chest pain, chills, cholestatic jaundice, confusion, constipation, cough, cytomegalovirus (CMV) infection, diar-
rhea, dyspepsia, edema, elevated sodium levels, enlarged breasts with tenderness, epigastric pain, fatigue, flushing, hives, gum disease, gastrointestinal bleeding, hallucinations, headache, heart failure, herpes simplex infection, hypotension, hyperglycemia, hypertension, hyperventilation, infection, insomnia, impotence, itching, light sensitivity, low calcium levels, low magnesium levels, low phosphorus levels, low potassium levels, low white blood cell count, loss of appetite, mouth ulceration, muscle aches, nausea, nervousness, petechiae, pulmonary edema, rash, respiratory failure, rhinitis, rigors, severe depression, severe vaginal bleeding, shortness of breath, sinusitis, sore throat, suicidal tendencies, sweating, taste perversion, upper respiratory tract infection, urinary tract infection, vomiting, and weakness. Collette Bishop Hendler, R.N., M.S.
Common Antifungal Agents Drug (Other Names) Brands
Subclass
Delivery Mode Conditions Treated
Amphotericin B cholesteryl sulfate complex
Amphotec
Polyene antibiotic
Continuous or Invasive aspergillosis in patients with cancer intermittent IV (especially those with acute leukemia) who cannot infusion tolerate amphotericin B deoxycholate
Amphotericin B desoxycholate
Polyene Amphocin, Amphotericin B antibiotic for injection, Fungizone
IV infusion
Prevention of fungal infection in bone marrow transplant patients; treatment of systemic infections caused by histoplasmosis, coccidioidomycosis, blastomycosis, cryptococcosis, disseminated candidiasis, aspergillosis, phycomycosis, zygomycosis, or meningitis in patients with cancer
Amphotericin B lipid complex
Abelcet
Polyene antibiotic
IV infusion
Fungal infections including Aspergillus and Candida in cancer patients who cannot tolerate amphotericin B desoxycholate
Amphotericin B liposomal
AmBisome
Polyene antibiotic
IV infusion
Suspected fungal infections in patients with low white blood cell count and fever; fungal infections caused by Aspergillus, Candida, or Cryptococcus species in cancer patients who cannot tolerate amphotericin B desoxycholate
Anidulafungin
Eraxis
Echinocandin IV infusion
Bloodstream infection and intra-abdominal abscess or peritonitis caused by Candida in patients with cancer
Caspofungin
Cancidas
Echinocandin IV infusion
Bloodstream infection and intra-abdominal abscess or peritonitis or pleural space infections caused by Candida in patients with cancer; aspergillosis in cancer patients who cannot tolerate all forms of amphotericin B (continued on page 78)
77
Antimetabolites in chemotherapy
Salem Health: Cancer
Common Antifungal Agents (continued) Drug (Other Names) Brands
Subclass
Delivery Mode Conditions Treated
Fluconazole
Diflucan
Bis-triazole derivative
Oral, IV infusion
Prevention of candidiasis in bone marrow transplant patients; cryptococcal meningitis or oropharyngeal, vulvovaginal, or systemic candidiasis
Flucytosine (5-FC, 5-fluorocytosine)
Ancobon
Fluorinated pyrimidine
Oral
Bloodstream infection, endocarditis, urinary tract infection, or lung infection caused by Candida or Cryptococcus in patients with cancer; meningitis caused by Cryptococcus in patients with cancer
Itraconazole
Sporanox
Synthetic triazole
Oral, IV infusion
Aspergillosis, oropharyngeal and esophageal candidiasis, blastomycosis, or nonmeningeal histoplasmosis in patients with cancer
Ketoconazole
Nizoral
Imidazole derivative
Oral
Oral candidiasis, systemic candidiasis, coccidioidomycosis, blastomycosis, histoplasmosis, chromomycosis, paracoccidioidomycosis, and severe dermatophyte infections that do not respond to other therapy in patients with cancer
Micafungin sodium
Mycamine
Echinocandin IV
Prevention of Candida infection in stem cell transplant patients and treatment of esophageal candidiasis
Nystatin
Mycostatin, Nilstat, Nystex
Polyene macrolide
Oral, vaginal
Intestinal, oral, or vaginal candidiasis in patients with cancer
Posaconazole
Noxafil
Triazole derivative
Oral
Prevention of Aspergillus and Candida infections in cancer patients
Voriconazole
Vfend
Synthetic triazole derivative
Oral, IV infusion
Candida infections of the bloodstream, esophagus, kidney, abdomen, bladder wall, wound, and skin in patients with cancer. Aspergillosis and serious infections caused by Fusarium and Scedosporium apiospermum in patients with cancer who cannot tolerate other antifungal therapy.
u For Further Information Drug Facts and Comparisons 2008. 62d ed. St. Louis: Wolters Kluwer Health, 2008. Karch, Amy M. 2008 Lippincott’s Nursing Drug Guide. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins, 2008. Nursing 2008 Drug Handbook. Philadelphia: Lippincott Williams & Wilkins, 2008.
See also Aflatoxins; Candidiasis; Infection and sepsis; Neutropenia; Side effects.
78
u Antimetabolites in
chemotherapy Category: Chemotherapy and other drugs ATC code: 101B Definition: Antimetabolites are drugs that interfere with deoxyribonucleic acid (DNA) replication processes in cells. These agents have a structure very similar to that of some of the components involved in the synthesis of nucleotides, the structural units of DNA. This similarity causes the cell to mistake the antimetabolite for a natural component, allowing the drug to effectively inhibit nucleotide synthesis. Nucleotide synthesis and subsequent DNA replication are processes that a cell must undergo before it can divide, and therefore quickly growing tumor cells are
Salem Health: Cancer particularly susceptible to interference with DNA replication. Further, inhibiting DNA replication triggers the activation of death-promoting pathways in these cells, causing the antimetabolite to decrease the tumor size. Cancers treated: Many solid tumors, including breast, colon, lung (small-cell and non-small-cell), ovarian, and head and neck cancers; several leukemias and lymphomas, including acute lymphocytic leukemia, indolent B-cell lymphoma, and non-Hodgkin lymphoma Subclasses of this group: Folic acid antagonists, pyrimidine antagonists, purine antagonists, sugar-modified analogs, ribonucleotide reductase inhibitors Delivery routes: Intravenous (IV), oral, intra-arterial (into an artery), intrathecal (into the spinal canal) How these drugs work: The development of antimetabolite therapy was based on the understanding of the importance of DNA replication in cell division and proliferation. Antimetabolites inhibit DNA replication through one or both of two mechanisms. First, these drugs can inhibit the synthesis of nucleotides, the structural molecules that make up the DNA strand. The four nucleotides that are used to replicate DNA are divided into two categories. The two purine nucleotides are adenine and guanine, while the two pyrimidines are cytosine and thymine. With the exception of thymine, these nucleotides also serve as the structural units for ribonucleic acid (RNA). In RNA, thymine is replaced with another nucleotide, uracil. When the synthesis of these molecules is inhibited, the cellular pool of nucleotides is reduced, limiting the ability of the cell to synthesize new DNA strands. The second mechanism of action is the actual incorporation of the antimetabolite into the DNA itself. It is known that the enzymes responsible for DNA replication can mistake the agents for DNA nucleotides, but the direct consequences of this mistaken identity are as of yet unknown. There are four main subclasses of antimetabolites: folic acid antagonists, pyrimidine and purine antagonists, sugar-modified analogs, and ribonucleotide reductase inhibitors. Folic acid (folate) antagonists are thought to act primarily through inhibition of the dihydrofolate reductase (DHFR) enzyme. DHFR functions to change the structure of folic acid, also known as vitamin B9, allowing it to be used in various metabolic processes that result in the formation of nucleotides. Inhibition of DHFR therefore reduces the production of many of the nucleotides essential for DNA replication. Methotrexate is the prototypical folate antagonist, and it has been successfully used as an anticancer drug in the clinic for decades. One of the reasons that methotrexate is so efficacious is that once it en-
Antimetabolites in chemotherapy ters the cell, it is chemically modified in such a way that it is unable to exit the cell. This causes the intracellular concentration of methotrexate to remain very high. Pyrimidine and purine antagonists target tumor cells via a dual mechanism of action-inhibition of nucleotide synthesis and incorporation into DNA. To inhibit nucleotide synthesis, pyrimidine antagonists can directly inhibit the thymidylate synthase protein, a critical enzyme in the formation of the thymine nucleotide. When thymidylate synthase mistakes pyrimidine antagonists for their natural substrate, the agent inhibits and traps the enzyme in the middle of the catalysis reaction. A stable complex of the enzyme and drug are formed, decreasing the number of enzymes available for the further formation of thymine. Because there is a relatively small concentration of thymine normally in the cell, reducing these pools can drastically inhibit DNA synthesis. The most common pyrimidine antagonists, fluoropyrimidines, have also been found to incorporate into DNA and RNA, replacing the nucleic acids thymine and uracil, respectively. This incorporation occurs at a relatively low level, however, and is not thought to be the primary cause for cell death. Fluoropyrimidines, especially 5-fluorouracil, are used to treat many commonly occurring cancers, including colorectal, breast, gastric, pancreatic, and head and neck tumors. Compared with pyrimidine antagonists, purine antagonists incorporate more readily into nucleic acids. Purine antagonists also inhibit the synthesis of nucleic acids. Each purine antagonist may inhibit purine synthesis at different points along the metabolic pathway, but their effects are perhaps most notable on the enzymes PRPP amidotransferase and IMP dehydrogenase. Purine antagonists are considered to be self-limiting, meaning that the biochemical effects produced by the agent can antagonize each other. For example, when purine synthesis is inhibited, total DNA replication is reduced, thereby diminishing the potential for incorporation of the drug into the DNA. The main purine antagonists are mercaptopurine and thioguanine, and they are used primarily to treat leukemia, especially in children. Sugar-modified analogs were discovered in screening programs established after the clinical success of pyrimidine and purine antagonists was established. Widely used in leukemia therapy, the sugar-modified analog cytarabine was isolated from a species of sponge from the Caribbean Sea. It is characterized by a modification of the sugar moiety, not the base portion, of the nucleotide analog. Unlike the other pyrimidine and purine antagonists, which can affect both DNA and RNA, cytarabine almost exclusively affects DNA. The primary mechanism of action of cytarabine is incorporation into the DNA in place of the 79
Antimetabolites in chemotherapy
Salem Health: Cancer
cytosine nucleotide. The other main sugar-modified analog, fludarabine, has a modification in both the base and sugar moiety. Hydroxyurea is the prototypical ribonucleotide reduc-
tase inhibitor. The enzyme ribonucleotide reductase has a global effect on all DNA synthesis, as it is the enzyme responsible for converting the precursor ribonucleoside diphosphates to deoxyribonucleotide diphosphates.
Common Antimetabolites
80
Drug (Other Names)
Brands
Subclass
Delivery Mode
Cancers Treated
Azacytidine (Aza-C, 5-AC)
Vidaza
Pyrimidine antagonist
IV
Chronic myelocytic leukemia
Capecitabine Xeloda (prodrug of fluorouracil)
Pyrimidine antagonist
Oral
Metastatic colorectal cancer, metastatic breast cancer
Chlorodeoxyadenosine (CdA)
Cladribine, Leustatin
Purine antagonist
IV
Indolent B-cell lymphocytic leukemia (especially hairy cell leukemia); may have activity in chronic lymphocytic leukemia and non-Hodgkin lymphoma
Cytarabine (ara-C)
Cytosar-U, DepoCyt
Sugar-modified analog
IV, intrathecal, subcutaneous
Acute nonlymphocytic leukemia, advanced non-Hodgkin lymphoma, chronic myelocytic leukemia, meningeal leukemia
Fludarabine (F-ara-A)
Fludara
Sugar-modified analog
IV, oral
Refractory chronic lymphocytic leukemia, non-Hodgkin lymphoma
Fluorodeoxyuridine (FdUrd, 5-FUdR, FdUMP)
FUDR, Floxuridine
Pyrimidine antagonist
Hepatic arterial infusion
Cancer of the gastrointestinal tract, especially tumors that have metastasized to the liver
Fluorouracil (FUra, 5-FU)
Adrucil
Pyrimidine antagonist
IV
Many solid cancers, including colorectal, breast, head and neck, gastric, and pancreatic tumors
Gemcitabine
Gemzar
Pyrimidine antagonist
IV
Locally advanced or metastatic lung cancer, pancreatic cancer, ovarian cancer, metastatic breast cancer
Hydroxyurea (HU, hydroxycarbamide)
Droxia, Hydrea
Ribonucleotide reductase inhibitors
oral
Chronic myelocytic leukemia, head and neck cancer, cervical cancer, ovarian cancer, melanoma
Mercaptopurine (MP, 6-MP)
Purinethol
Purine antagonist
Oral
Acute lymphocytic leukemia
Methotrexate (MTX, amethopterin)
Trexall, Rheumatrex
Folic acid antagonist
Oral, IV, intra-arterial, intrathecal
Breast cancer, bone cancers including osteogenic sarcoma, acute lymphocytic leukemia, head and neck cancer, bladder cancer, and several other solid tumors including lung, uterine, and cervical cancer
Pentostatin (2′-deoxycoformycin, dCF)
Nipent
Purine antagonist
IV
Indolent B-cell lymphocytic leukemia (especially hairy cell leukemia); may have activity in chronic lymphocytic leukemia
Thioguanine (TG, 6-TG)
Thioguanine Tabloid
Purine antagonist
Oral
Acute nonlymphocytic leukemia
Tiazofurin
Riboxamide
Purine antagonist
IV
Currently in clinical testing for several leukemias, especially chronic myelocytic leukemia
Salem Health: Cancer Side effects: In general, antimetabolites are more toxic to cells that are actively dividing, compared to cells that are not. Because tumor cells rapidly proliferate, antimetabolites can target these cells quite effectively. The drugs cannot differentiate, however, between cancer cells and rapidly dividing healthy cells, such as those that occur in the bone marrow, the lining of the gastrointestinal tract, and hair follicles. Therefore, most side effects induced by these drugs are dependent on which normal cells are affected. Methotrexate toxicity is mainly confined to the bone marrow and the gastrointestinal tissue lining. The side effects that can result in systemic therapy with pyrimidine and purine antagonists are mainly bone marrow suppression, although gastrointestinal toxicity can occur. Fluoropyrimidines, in particular, induce nausea, vomiting, anorexia, and diarrhea. Lisa M. Cockrell, B.S. u For Further Information Jackman, Ann L., ed. Antifolate Drugs in Cancer Therapy. Totowa, N.J.: Humana Press, 1999. Kantarjian, Hagop M., et al. The MD Anderson Manual of Medical Oncology. New York: McGraw-Hill, 2006. Kufe, Donald W., et al., eds. Holland Frei Cancer Medicine 7. 7th ed. Hamilton, Ont.: BC Decker, 2006. Pratt, William B., et al. The Anticancer Drugs. 2d ed. New York: Oxford University Press, 1994. Rustum, Youcef M., ed. Fluoropyrimidines in Cancer Therapy. Totowa, N.J.: Humana Press, 2003. Skeel, Roland T. Handbook of Cancer Chemotherapy. 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2007. u
Other Resources
National Cancer Institute Drug Information Summaries http://www.cancer.gov/cancertopics/druginfo/ alphalist See also Antineoplastics in chemotherapy; Chemotherapy.
u Antinausea medications Category: Chemotherapy and other drugs ATC code: A04A Definition: Antinausea agents, or antiemetics, encompass a range of drug classes that act on the peripheral and central nervous systems to prevent nausea and vomiting. In patients with cancer, antiemetics are used to control acute, delayed, and anticipatory nausea and vomiting that result from chemotherapy.
Antinausea medications Cancers treated: Indirectly used in the treatment of many cancers to control nausea and vomiting associated with many chemotherapy regimens Subclasses of this group: Serotonin-3 antagonists, substituted benzamides, corticosteroids, pheothiazines, benzodiazepines, butyrophenones, cannabinoids, neurokinin-1 antagonists Delivery routes: Administered to inpatients and outpatients as oral tablets, capsules, or liquids; as intravenous or intramuscular solutions; or as rectal suppositories How these drugs work: Nausea and vomiting, or emesis, are the most common chemotherapy-associated toxicities, affecting more than 75 percent of patients, especially with the development of combination regimens. The effective use of antinausea agents to improve chemotherapy tolerance is one of the most important advances of supportive cancer care. Among the first of agents to deter emesis was metoclopramide, a substituted benzamide that acts as a dopamine receptor antagonist and, at higher doses, as an additional serotonin receptor antagonist. Although the exact mechanisms of nausea and vomiting reflexes have not been determined, neurotransmitter blockade at dopaminergic, serotonergic, neurokinin-1, and other receptors in the central nervous system or peripherally in the gastrointestinal tract successfully controls the reactions. Like metoclopramide, phenothiazines such as chlorpromazine and butyrophenones such as haloperidol also prevent nausea and vomiting by dopaminergic blockade. Dopamine antagonism from these three subclasses provides relief of moderate emesis. The more newly developed serotonin-3 (5HT-3) receptor antagonists work peripherally, especially in the small intestine, and are extremely effective for the treatment and prevention of acute emesis. Ondansetron, granisetron, and dolasetron are equivalent in efficacy and may provide total receptor blockade, as evidenced by their dose-related efficacy plateaus. Palonsetron, a newer agent, is longer acting than others in the subclass. Because acute emesis is associated with peripheral control and delayed emesis is associated with central control, 5HT-3 antagonists are more effective in treating acute nausea and vomiting, which occurs in the first twenty-four hours after chemotherapy is administered. Benzodiazepines such as lorazepam have some antiemetic activity by blocking cortical input to the emetic center but are more useful for their sedative and anxiolytic effects, which make the agents ideal for combination regimens. In addition, these drugs induce retrograde amnesia, which is successful in preventing anticipatory nausea and 81
Antinausea medications
Salem Health: Cancer
Common Antinausea Agents Drug
Brands
Subclass
Delivery Mode
Type of Nausea Treated
Aprepitant
Emend
Neurokinin-1 receptor antagonist
Oral
Delayed prophylaxis, primarily (combined with corticosteroid)
Chlorpromazine, prochlorperazine, promethazine
Thorazine, Compazine, Phenergan
Phenothiazines
Oral, IV, rectal
Mild-to-moderate acute (combined with corticosteroid or 5HT-3 antagonist); breakthrough
Dexamethasone, methylprednisolone
Decadron, Medrol, MethaPred
Corticosteroids
Oral, IV
Mild-to-moderate acute as monotherapy; moderate-to-severe acute when combined with 5HT-3 antagonist; delayed prophylaxis when combined with NK-1 inhibitor; delayed postchemotherapy when combined with substituted benzamide; anticipatory
Cannabinoids
Oral
Anticipatory, breakthrough, or refractory nausea and vomiting
Dronabinol Haolperidol, droperidol
Haldol, Inapsine
Butyrophenones
Oral, IV, intramuscular
Mild-to-moderate acute (not recommended agents because of toxicities)
Lorazepam
Ativan
Benzodiazepine
Oral, IV, intramuscular
Anticipatory or breakthrough
Metoclopramide
Reglan
Substituted benzamide
Oral, IV
Acute or anticipatory (not as first-line agent); delayed when combined with corticosteroid
Ondansetron, granisetron, dolasetron, palonosetron
Zofran, Kytril, Anzemet,
Serotonin-3 receptor antagonists
Oral, IV
Uncontrolled mild, moderate, or severe acute; Moderate-to-severe acute (combined with corticosteroid); Delayed (less effective than NK-1 inhibitor)
vomiting that may occur with repeat chemotherapy administration. Neurokinin-1 (NK-1) receptors are more recently studied targets of nausea mechanisms; the only currently approved agent in the NK-1 antagonist class is aprepitant. Because NK-1 mediates substance P activation of NK-1 receptors in the brainstem, aprepitant’s NK-1 receptor antagonism is useful for the treatment of delayed emesis, which is more centrally mediated. Although its efficacy alone is not yet confirmed, aprepitant successfully prevents acute and delayed nausea and vomiting when combined with serotonin antagonists and corticosteroids. Corticosteroids, especially dexamethasone, methylprednisolone, and prednisone, have a confirmed effect, alone or in combination, against moderate nausea and vomiting, despite an unknown mechanism of action and a lack of receptor blockade. Corticosteroids are often the second drug in a combination regimen with dopamine, serotonin, or NK-1 receptor antagonists. Lastly, cannabinoids such as dronabinol act centrally 82
with psychotropic activity to provide limited but affirmed antinausea activity. They can be used for patients with moderate emesis and poor tolerance or response to other agents or for patients who need control of breakthrough pain. Side effects: Each subclass of antinausea agents is associated with different side effects; successful combination regimens provide greater efficacy without overlapping drug toxicities. Metoclopramide side effects are primarily related to dopamine antagonism and include extrapyramidal reactions, including acute dystonic reactions. Akathisia, or restlessness, is common and may persist for hours. Drowsiness and diarrhea are also possible. Phenothiazines and butyrophenones also cause dopaminerelated drowsiness, diarrhea, and extrapyramidal reactions. In addition, constipation, dizziness, and hypotension have been noted. Lorazepam is associated with sedation in addition to amnesia, confusion, transient enuresis, and blurred vision. Serotonin antagonists all have similar side effects
Salem Health: Cancer of mild to moderate headache in 20 to 30 percent of patients and mild, uncommon occurrences of constipation or diarrhea. Corticosteroids may cause insomnia, hyperglycemia, gastrointestinal upset, and, rarely, psychosis. NK-1 antagonism leads to fatigue, dizziness, headache, and gastrointestinal disturbances. Side effects of dronabinol include dysphoria, hallucinations, dizziness, dry mouth, sedation, and disorientation. Nicole M. Van Hoey, Pharm.D. u For Further Information Grunberg, S. M. “Antiemetic Activity of Corticosteroids in Patients Receiving Cancer Chemotherapy: Dosing, Efficacy, and Tolerability Analysis.” Annals of Oncology 18, no. 2 (February, 2007): 233-240. Jordan, K., H. J. Schmoll, and M. S. Aapro. “Comparative Activity of Antiemetic Drugs.” Critical Reviews in Oncology/Hematology 61, no. 2 (February, 2007): 162175. Roila, F., S. Fatigoni, and G. Ciccarese. “Daily Challenges in Oncology Practice: What Do We Need to Know About Antiemetics?” Annals of Oncology 17, suppl. 10 (September, 2006): 90-94.
See also Chemotherapy; Gastrointestinal complications of cancer treatment; Nausea and vomiting; Topoisomerase inhibitors.
u Antineoplastics in
chemotherapy Category: Chemotherapy and other drugs ATC code: 101 Also known as: Chemotherapeutic agents, antitumor compounds, cytotoxic antibiotics Definition: Antineoplastics are anticancer drugs used to treat malignancies and cancerous growths. Cancers treated: Various types of cancers Subclasses of this group: Alkylating agents, antimetabolites, mitotic inhibitors, topoisomerase inhibitors, cytotoxic antibiotics Delivery routes: Oral, intravenous, intramuscular, or subcutaneous injection How these drugs work: Antineoplastics are chemicals used to treat cancer and inhibit tumor cell growth. The term “neoplastic” refers to cancer cells, so the term “antineoplastic” literally means “anticancer cell.” Antineo-
Antineoplastics in chemotherapy plastic agents are used to stop tumor development or prevent the spread of cancer and to relieve some symptoms associated with cancer or to prolong patient survival. Antineoplastics are also sometimes referred to as chemotherapeutic agents, antitumor compounds, or cytotoxic antibiotics. The first antineoplastic agents were used in the 1940’s and either were made from synthetic chemicals or were derived from natural plants. More than fifty antineoplastic agents are approved by the Food and Drug Administration (FDA) for use in the United States. There are several major categories of antineoplastic agents based on their origins, chemical structures, and the how they work. These classifications include alkylating agents, antimetabolites, cytotoxic antibiotics, mitotic inhibitors, and topoisomerase inhibitors. Antineoplastic agents inhibit tumor cell growth using different mechanisms, with many affecting deoxyribonucleic acid (DNA) synthesis and interfering with cell division. Others work by altering immune function or affecting hormonal status of tumors. Antineoplastic drugs are either cycle specific or non-cycle specific, with cycle specific drugs acting only during certain phases of the cell cycle while non-cycle specific drugs may act during any cell cycle phase. The largest group of antineoplastic compounds is the alkylating agents, which were among the first anticancer drugs used. These compounds are the most commonly used agents in chemotherapy. Alkylating agents work by cross-linking DNA and preventing DNA bases from pairing up correctly, which interferes with DNA synthesis. Categories of alkylating agents include busulfans, alkylating-like drugs, nitrogen mustards, ethylenimines, and nitrosureas. Nitrogen mustards comprise the largest group of alkylating drugs and are particularly useful for treating neoplasms that increase white blood cells, such as lymphomas and leukemias, because they result in leukopenia. Unlike most other types of antineoplastic agents, nitrosureas can cross the blood-brain barrier and thus are useful for treating brain tumors. Also included among the alkylating agents are the metal salts, such as carboplatin and cisplatin. Other examples of alkylating agents include chlorambucil, cyclophosamide, and thiotepa. Antimetabolites work by interfering with cancer cell metabolism. Antimetabolites are analogs of normal metabolites (nucleic acids) and act by replacing natural substances. Since these compounds structurally resemble DNA base pairs, they become incorporated into DNA, thus interfering with DNA synthesis. Antimetabolites are cell-cycle specific and attack cells only during certain cell cycle phases. Most antimetabolites are preferentially effective against cells that are actively synthesizing DNA. 83
Antineoplastics in chemotherapy
Salem Health: Cancer
Antimetabolites are classified by the metabolite that they affect and include folic acid, purine, and pyrimidine analogs. All these compounds function by interfering with DNA synthesis in some way, either by directly inhibiting important enzymes or by being converted into substances that impair DNA synthesis. Methotrexate, a folic acid analog, inhibits an enzyme necessary for regeneration of intermediates required for DNA synthesis. Pyrimidine and purine analogs are converted into compounds that inhibit enzymes involved in DNA synthesis. 5-Fluorouracil and cytarabine are examples of pyrimidine analogs. Purine analogs include 6-mercaptopurine and pentostatin. Some antineoplastic drugs are considered antimitotics or mitotic inhibitors and bind to tubulin, preventing polymerization of microtubules necessary for mitotic spindle formation. This prevents mitosis and arrests cells during metaphase. Many of the vinca alkaloids function as mitotic inhibitors. Topoisomerase inhibitors interfere with
DNA synthesis by disrupting the function of the enzymes topoisomerases I and II, which are important in tubulin formation. Topoisomerases control the structure of DNA necessary for replication, and compounds that inhibit these enzymes work by preventing DNA from being unwound, a step required for DNA synthesis. Topoisomerase inhibitors include ironotecan, topotecan, etoposide, and teniposide. Many antineoplastic compounds are derived from plants and are known as natural products. They vary mechanistically, with some functioning as alkylating agents, some inhibiting mitosis, and some affecting enzymes important in DNA synthesis. The vinca alkaloids, made from the periwinkle plant (Catharanthus rosea), and the taxanes, made from the Pacific yew tree (Taxus), work as mitotic inhibitors by disrupting microtubule formation. Podophyllotoxins, derived from the mayapple plant (Podophyllum peltatum), and camptothecans, from the Asian “Happy
Common Antineoplastic Agents
84
Drug (Other Names)
Brands
Subclass
Delivery Mode
Cancers Treated
Asparaginase
Elspar
Miscellaneous
IV, intramuscular, subcutaneous
Acute lymphoblastic leukemia
Bleomycin
Blenoxane
Cytotoxic antibiotic
IV
Testicular cancer, squamous cell carcinoma, Hodgkin disease
Busulfan
Busulfex
Alkylating agent
Oral, IV
Chronic myelogenous leukemia, other blood cancers
Carboplatin (CBDCA)
Paraplatin
Alkylating agent
IV
Ovarian carcinoma
Cisplatin (CDDP)
Platinol-AQ Alkylating agent
IV
Testicular, ovarian, and bladder cancers
Chlorambucil
Leukeran
Alkylating agent
IV, oral
Leukemias, lymphomas, various cancers, Hodgkin disease
Cyclophosphamide (CTX)
Cytoxan
Alkylating agent
IV, oral
Leukemias, lymphomas, ovarian and breast cancers
Cytarabine (Ara C)
Cytostar-U
Antimetabolite
IV, subcutaneous
Leukemias, non-Hodgkin lymphoma
Dactinomycin (actinomycin D)
Cosmogen
Cytotoxic antibiotic
IV
Testicular carcinomas, sarcomas, other solid tumors
Doxorubicin Adriamycin, Cytotoxic (hydroxyldaunorubicin) Rubex antibiotic
IV
Leukemias, Hodgkin lymphoma, bladder cancer, breast cancer, other solid tumors
Etoposide
Etophos, Vepesid
Mitotic inhibitor
Oral, IV
Leukemias, lymphomas, lung, ovarian, and testicular cancers
5-fluorouracil (5-FU)
Adrucil
Antimetabolite
IV
Colon, rectal, breast, stomach, pancreatic cancers
Ifosfamide (isophosphamide)
Ifex
Alkylating agent
IV
Germ-cell testicular cancer, sarcomas
Salem Health: Cancer
Antineoplastics in chemotherapy
Tree” (Camptotheca acuminate), function as topoisomerase inhibitors. Most of these compounds are effective against tumor cells during various cell cycle phases. Another category of antineoplastics includes the antitumor or cytotoxic antibiotics, many of which are produced by species of the soil fungus Streptomyces. There are several cytotoxic antibiotics, such as Dactinomycin (actinomycin D), bleomycin, and doxorubicin. Cytotoxic antibiotics generally act during various phases of the cell cycle. Dactinomycin works by binding to DNA and preventing ribonucleic acid (RNA) synthesis, an important step in making proteins. Doxorubicin works by causing DNA to uncoil, which prevents the cell from reproducing. Bleomycin acts by fragmenting DNA. There are also many compounds that do not fit into these categories but are still useful antineoplastic agents, such as hormones, enzymes, and reagents used in immunotherapy. Hormones work by altering the cellular envi-
ronment, making it unfavorable for tumor growth. Enzymes, such as L-asparaginase, break down substances such as asparagine that tumor cells need for survival. Mitotane is a chemical related to the insecticide dichlorodiphenyl-trichloroethane (DDT) and interferes with the formation of adrenocortical steroids, with selective cyototoxic effects toward cells of the adrenal cortex. Other compounds include retinoids, such as bexarotene and tretinoid. Side effects: Antineoplastic compounds can destroy normal cells as well as neoplastic cells, although generally antineoplastic agents have greater effects on tumor cells because they grow rapidly. Many side effects associated with antineoplastic agents occur because of their effects on normal cells, especially those that divide rapidly, such as the cells of hair follicles, ovaries, testes, and blood-forming organs. Hair loss is common as a result of effects on
Common Antineoplastic Agents (continued) Drug (Other Names)
Brands
Subclass
Delivery Mode
Cancers Treated
Irinotecan
CPT-11
Topoisomerase inhibitor
IV
Metastatic colorectal cancer, bowel cancer
Mercaptopurine (6-MP)
Purinethol
Antimetabolite
Oral
Leukemia
Methotrexate (amethopterin)
Rheumatrex Antimetabolite
Oral, IV, subcutaneous
Acute lymphoblastic leukemia
Mitomycin (mitomycin C)
Mutamycin
Cytotoxic antibiotic
IV
GI, bladder, and breast cancers
Mitotane (o,p’-DDD)
Lysodren
Miscellaneous
Oral
Adrenocortical carcinoma
Oxaliplatin (oxalatoplatin)
Eloxatin, Alkylating agent Transplatine
IV
Advanced ovarian cancer, head and neck cancers
Pentostatin (deoxycoformycin)
Nipent
Antimetabolite
IV
Leukemias
Tenisopide
Vumon, VM-26
Mitotic inhibitor
IV
Leukemias, lymphomas, neuroblastoma
Thiotepa
Thioplex
Alkylating agent
IV, spinal injection
Bladder cancer, ovarian cancer, breast cancer, lymphomas
Topotecan
Hycamtin
Topoisomerase inhibitor
IV
Ovarian, small-cell lung cancers
Vincristine
Mitotic inhibitor Oncovin, Cytocristin, Vincristine sulfate
IV
Non-Hodgkin lymphoma, leukemias, smallcell lung cancer, cervical and breast cancers
Vinorelbine
Navelbine
IV
Leukemia, lymphoma, melanoma, breast and lung cancers
Mitotic inhibitor
85
Antioxidants hair follicles. Anemia, immune system impairment, and clotting problems result from adverse effects on bloodforming organs, which lead to decreased red blood cell, white blood cell, and platelet numbers. Nausea and vomiting are among the most common adverse side effects. Other side effects may include blood in the urine, diarrhea, fever or chills, cough, wheezing, shortness of breath, unusual bruising, problems with urination, dizziness, irregular heartbeat, skin rash, fatigue, loss of taste, headache, swelling, allergic reactions, or body aches. C. J. Walsh, Ph.D. u
For Further Information Clinical Pharmacology Made Incredibly Easy. 3d ed. Philadelphia: Lippincott Williams & Wilkins, 2008. Dawson, James S., Magali N. F. Taylor, and Peter J. W. Reide. Pharmacology. Philadelphia: Elsevier Health Sciences, 2002. Portable Pathophysiology. Philadelphia: Lippincott Williams & Wilkins, 2007. Skidmore-Roth, Linda. Mosby’s 2007 Nursing Drugs Reference. St. Louis: C. V. Mosby, 2006. Vardanyan, Ruben, and Victor Hruby. Synthesis of Essential Drugs. Philadelphia: Elsevier, 2006. u
Other Resources
Cancer Backup General Information on Chemotherapy http://www.cancerbackup.org.uk/Treatments/ Chemotherapy/Generalinformation/Overview MedlinePlus http://www.nlm.nih.gov/medlineplus/ druginformation.html National Cancer Institute Drug Information Summaries http://www.cancer.gov/cancertopics/druginfo/ alphalist See also Alkylating agents in chemotherapy; Chemotherapy; Immunotherapy; Proteasome inhibitors.
u Antioxidants Category: Lifestyle and prevention; complementary and alternative therapies Definition: Antioxidants are a class of compounds that help prevent damage to deoxyribonucleic acid (DNA), cellular proteins, and cell membranes by combining with 86
Salem Health: Cancer potentially damaging molecules called free radicals and neutralizing them. The body naturally makes many antioxidants, while others are found in fruits, vegetables, and grains. Antioxidants are also produced synthetically as dietary supplements. Cancers treated or prevented: Antioxidants are used to treat most types of cancer, although their effectiveness is questionable. They are usually taken for cancer prevention, although the link between antioxidant consumption and cancer prevention in humans is not proven. Delivery routes: Oral, as tablets, caplets, capsules, powder, or tea; some fruits and vegetables are high in antioxidants How these compounds work: Free radicals are formed during normal cellular metabolism. Free radicals are compounds that are unstable because they contain an unpaired electron. This unpaired electron causes the free radical to react with other molecules in order to gain another electron, creating an electron pair and a more stable molecule. The process of gaining an electron is called oxidation. Antioxidants in the body react with free radicals and make them harmless to cells. Cells naturally make many antioxidants such as glutathione and coenzyme Q10 (ubiquinone). When the number of free radicals exceeds the antioxidants available to neutralize them, however, the body develops a condition called oxidative stress. Oxidative stress appears to make cells especially susceptible to damage. Free radical formation and oxidation are normal processes. Oxidation and oxidative stress, however, are thought to contribute to aging, as well as to cancer, cardiovascular disease, and other chronic diseases. In the absence of adequate antioxidant compounds, free radicals most often combine with and damage DNA, cellular proteins, and molecules in cell membranes. This damage can cause gene mutations and change cellular metabolism, which may lead to cancer and other diseases. Exposure to ultraviolet (UV) light, radiation, cigarette smoke, and other known carcinogens increases the number of free radicals that are formed, suggesting another link between free radicals, oxidative stress, and cancer. In theory, increasing the amount of antioxidants in the body should decrease the amount of damage to DNA and cells and reduce the risk of cancer. Antioxidants have been shown to prevent or slow the development of some cancers in cell cultures grown in the laboratory and in some animal studies. The results in human studies have been mixed. Despite claims by some manufacturers of antioxidant dietary supplements, no clear link between antioxidant
Salem Health: Cancer
Antioxidants
consumption and cancer prevention or treatment has been established in humans. The role of antioxidants in the prevention and treatment of cancer is of high interest to research scientists. Many clinical trials are being conducted, and there is no cost for qualified individuals to participate in a clinical trial. The body makes some antioxidants, but others must be acquired through diet. Common antioxidants that the body does not make include vitamins A, C, and E, carotenoids, and flavonoids. Selenium is a mineral that is not strictly an antioxidant but is essential to many antioxidant reactions and often classed with the antioxidants. Coenzyme Q10 and glutathione are antioxidants naturally produced by the body that are also manufactured sold as high-dose supplements. Vitamin A (retinol) is a fat-soluble vitamin found in liver, egg yolks, whole milk, and dairy products made with whole milk. It is also sold as a dietary supplement and is included in most multivitamin tablets and in special antioxidant formulations such as ACE, a combination of vitamins A, C, and E. Vitamin Ais essential to health, but its role in cancer prevention and treatment is unclear. All-trans-retinoic acid (ATRA, Vesanoid) is a pharmaceutical drug that is a derivative of vitamin A. It is successfully used to treat promyelocytic leukemia and is being studied in Berries contain flavonoids, a group of antioxidant compounds. (U.S. Deindividuals with breast and skin cancers. To date, partment of Agriculture) however, vitamin A alone has not shown the same cancer-reducing effects as ATRA. min C has very strong antioxidant activities. Nevertheless, Alpha-carotene, beta-carotene, beta-cryptoxanthin, lumultiple human studies have failed to find a significant tein, zeaxanthin, and lycopene are all carotenoids that link between cancer prevention and vitamin C intake. show antioxidant activity in laboratory tests. These comVitamin E is a group of related compounds, the most pounds are found in red, yellow, and orange plants such as active of which is alpha-tocopherol. Vitamin E is a fatcarrots, cantaloupe, mango, and tomato. Beta-carotene soluble vitamin with antioxidant properties. It is found in and lycopene are also sold as dietary supplements either olive, sunflower, and safflower oils and in many nuts. The individually or in combination with other antioxidants. In role of vitamin E in cancer prevention is controversial. In the body, carotenoids are converted into vitamin A. An ex2004, researchers at The Johns Hopkins University Mediamination of twenty-one studies relating lycopene concal School did a meta-analysis of nineteen clinical trials sumption and prostate cancer found that men with the that included more than 136,000 individuals. This analysis highest lycopene intake had a modest decrease in the incishowed that taking more than 400 international units (IU) dence of prostate cancer. The role of carotenoids in cancer prevention is actively being studied. of synthetic vitamin E daily increased the chance of dying Vitamin C (ascorbic acid) is a water-soluble vitamin by about 4 percent. This amount is less than the safe daily found in citrus fruits. For centuries, it has been known that upper limit of 1,500 IU recommended by the United States vitamin C is essential for preventing the disease scurvy. Institute of Medicine for adults age nineteen and older. Dietary supplements of vitamin C are often promoted as a The Johns Hopkins analysis has been criticized because it preventive or treatment for the common cold, although did not differentiate between individuals taking different clinical studies have not proved its effectiveness. Vitaforms of vitamin E, such as the dietary supplement alpha87
Antiperspirants and breast cancer tocopherol acetate. This is a significant criticism because different forms of vitamin E have different activity levels in the body. Flavonoids are a group of antioxidant compounds found primarily in brewed tea, red wine, dark chocolate, apples, berries, and citrus fruits. These compounds have antioxidant activity. Traditional Chinese medicine has promoted the health effects of green tea for centuries, and recent studies show that dark (bitter) chocolate in small quantities may promote heart health, but the role of flavonoids in cancer prevention is unclear. Selenium is a mineral found in fish, shellfish, grains, Brazil nuts, and many vegetables that are grown in selenium-rich soils. By itself, selenium is not an antioxidant, but it plays a critical role in antioxidant activity and is often classified with the antioxidants that must be acquired through diet. Selenium deficiency has been linked to increases in colorectal, lung, and prostate cancers. Increased selenium intake in people who are not selenium deficient, however, does not decrease the risk of developing cancer. Additionally, selenium is toxic in large doses. Coenzyme Q10 and glutathione are the main antioxidants made by the body. They are also sold as dietary supplements. Studies of individuals who supplemented their diet with synthetic coenzyme Q10 or glutathione found no evidence that these supplements protected against cancer. Individuals who maintain a healthy weight and eat a diet low in fats and high in fruits, vegetables, and whole grains develop cancer at a lower rate than individuals who eat a more traditional American diet high in fat and low in fruits and vegetables. The American Cancer Society and the National Cancer Institute recommend that individuals meet as many of their vitamin, mineral, and antioxidant needs as possible by eating a healthy, varied diet rather than by taking dietary supplements. As of 2008, neither organization recommended the use of antioxidant supplements to treat or prevent cancer. Side effects: In 2007, a peer-reviewed meta-analysis of antioxidant studies was published in the Journal of the American Medical Association. Researchers looked at the data from sixty-eight clinical trials involving 232,606 individuals. They found that taking dietary supplements of vitamin A, beta-carotene, and vitamin E increased the risk of death from all causes by 5 percent. This increase was not seen in individuals who took vitamin C dietary supplements. The study did not look at individuals who increased their intake of these antioxidants through diet. Martiscia Davidson, A.M.
88
Salem Health: Cancer u
For Further Information DeCava, Judith A. The Real Truth About Vitamins and Antioxidants. 2d ed. Fort Collins, Colo.: Selene River Press, 2006. Frei, Balz, ed. Natural Antioxidants in Human Health and Disease. San Diego, Calif.: Academic Press, 2006. Panglossi, Harold V., ed. Antioxidants: New Research. New York: Nova Science, 2006. Quillin, Patrick. Beating Cancer with Nutrition. 4th ed. Tulsa, Okla.: Nutrition Times Press, 2005.
u
Other Resources
American Cancer Society Antioxidants and Cancer: The Jury’s Still Out http://www.cancer.org/docroot/NWS/content/ NWS_2_1x_Antioxidants_and_Cancer_The_ Jurys_Still_Out.asp MedlinePlus Antioxidants http://www.nlm.nih.gov/medlineplus/ antioxidants.html National Cancer Institute Antioxidants and Cancer Prevention: Fact Sheet http://www.cancer.gov/cancertopics/factsheet/ antioxidantsprevention See also Beta-carotene; Bioflavonoids; Carotenoids; Chemoprevention; Coenzyme Q10; Complementary and alternative therapies; Curcumin; Dietary supplements; Essiac; Free radicals; Fruits; Garlic and allicin; Green tea; Herbs as antioxidants; Isoflavones; Lutein; Lycopene; Nutrition and cancer prevention; Phenolics; Phytoestrogens; Resveratrol; Wine and cancer.
u Antiperspirants and breast
cancer Category: Social and personal issues Definition: Breast cancer is a cancer of the breast tissue, more common among women than men. In the United States, breast cancer is the third most common cause of death in women. Antiperspirants have been studied for a possible link to breast cancer. Looking at the link: Antiperspirants and deodorants are common over-the-counter cosmetics that are used to significantly reduce perspiration and to control body odor. Most commercially available antiperspirants contain alu-
Salem Health: Cancer
Antiperspirants and breast cancer
minum or aluminum-zirconium salts or complexes. These aluminum complexes react with salts in the sweat and form a plug that blocks the sweat duct. As a result, the duct cannot release liquid sweat. Blockage of a number of sweat ducts minimizes the sweat produced by underarms. The plugs are removed over time when the skin sloughs them off naturally. During the past decade, there have been numerous reports on the Internet and in the news claiming that underarm deodorant or antiperspirant use increases the risk of breast cancer, especially in women. However, there is no conclusive scientific evidence linking underarm antiperspirant use and subsequent development of breast cancer. Although there are no published scientific reports delineating a possible mechanism by which the use of underarm antiperspirants could cause breast cancer, public concern regarding this issue persists. Studies that looked at the correlation between antiperspirant use and the development of breast cancer have not been conclusive. The results of a 2002 study investigating the relationship between underarm antiperspirant use and breast cancer did not show an increased risk for women who reported regularly using underarm antiperspirants or deodorant. However, a 2003 study that examined the frequency of underarm shaving and antiperspirant or deodorant use among 437 breast cancer survivors found that those who shaved frequently and used these products were diagnosed with breast cancer at an earlier age. In addition, the study found that those who started the shaving and antiperspirant or deodorant use earlier than sixteen years of age were diagnosed at an earlier age with breast cancer than those who started these habits later in life. These results suggest, though not conclusively, that there could be a link between underarm hygiene habits and breast cancer.
More research is needed in this area to enable women to make informed choices.
Aluminum: Aluminum salts or complexes are one of the major constituents of many commercial antiperspirants and deodorants. Estrogen is a naturally occurring female hormone that is known to promote the growth and division of breast cells. Aluminum salts are classified as metalloestrogens (metals with estrogen hormone-like properties). Research studies have shown that aluminum salts cause an increase in estrogen-related gene expression in human breast cancer cells grown in the laboratory. However, this result has not yet been translated into human breast cancer cells in the body. Aluminum was detected at varying concentrations in human breast cancer tissue from one study of women with breast cancer. The source of the aluminum was not conclusively established, and hence a definite correlation between aluminum from antiperspirants and breast cancer cannot be made from this study.
u
Parabens: Esters of the chemical p-hydroxybenzoic acid are commonly called parabens and are used as preservatives in antiperspirants and many other skin-care cosmetics. Research has demonstrated that parabens possess estrogenic properties both in laboratory-grown cells and in cells within the body (in vitro and in vivo). Scientists have put forth the hypothesis that parabens can be absorbed by breast tissue from topical application of cosmetics such as antiperspirants and could accumulate there, causing the development and spread of breast cancer. A 2004 study that detected parabens in breast tumor tissue partially proved the hypothesis that parabens can accumulate in breast tissue. However, the study did not prove that the accumulated parabens caused breast cancer. Moreover, the study did not prove that the parabens originated from the antiperspirants. It also did not involve an analysis of healthy breast tissue for parabens and hence did not prove that parabens were found only in cancerous tissue and not in healthy tissue. More specific well-designed research is needed to address the absorption of parabens by the skin and objectively evaluate whether they increase the risk of breast cancer. The rising incidence of breast cancer in younger women combined with the fact that it is a major killer of women in the United States makes it a major public health issue. Considering the fact that a majority of young women use antiperspirants and deodorants, the importance of wellfunded, case-controlled research investigations to conclusively establish the proposed link between their use and breast cancer development cannot be overemphasized. Lalitha Krishnan, Ph.D. For Further Information “Antiperspirants Don’t Cause Breast Cancer.” Harvard Women’s Health Watch 10, no. 5 (2003): 7. Harvey, P. W., and D. J. Everett. “Significance of the Detection of Esters of P-hydroxybenzoic Acid (Parabens) in Human Breast Tumours.” Journal of Applied Toxicology 24 (2004): 1-4. McGrath, K. G. “An Earlier Age of Breast Cancer Diagnosis Related to More Frequent Use of Antiperspirants/ Deodorants and Underarm Shaving.” European Journal of Cancer Prevention 12, no. 6 (2003): 479-485. Mirick, D. K., S. Davis, and D. B. Thomas. “Antiperspirant Use and the Risk of Breast Cancer.” Journal of the National Cancer Institute 94, no. 20 (2002): 15781580. Surendran, A. “Studies Linking Breast Cancer to Deodor89
Antiviral therapies
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ants Smell Rotten, Experts Say.” Nature Medicine 10, no. 3 (2004): 216.
u Antiviral therapies
Other Resources
Category: Chemotherapy and other drugs ATC code: J05
American Cancer Society Antiperspirants and Breast Cancer Risk http://www.cancer.org/docroot/MED/content/ MED_6_1x_Antiperspirants.asp?sitearea=PED National Cancer Institute Antiperspirants/Deodorants and Breast Cancer: Questions and Answers http://www.cancer.gov/cancertopics/factsheet/Risk/ AP-Deo See also Carcinogens, known; Carcinogens, reasonably anticipated; Diethanolamine (DEA).
Definition: Antiviral agents are used to treat infections caused by viruses. In patients with cancer, they are also used in combination with other medications to treat human papillomavirus (HPV)-positive cervical cancer and head and neck squamous cell cancer. Antiviral agents known as protease inhibitors, nucleoside reverse transcriptase inhibitors, and nonnucleoside reverse transcriptase inhibitors are indicated for human immunodeficiency virus (HIV) infection. Cancers treated: Cervical cancer, head and neck cancers, HIV infection and opportunistic viral infections associated with all types of cancer. (continued on page 92)
Common Antiviral Agents Drug (Other Names)
Brands
Subclass
Delivery Mode Conditions Treated
Abacavir sulfate
Ziagen
Nucleoside reverse transcriptase inhibitor
Oral
Human immunodeficiency (HIV) infection in patients with Kaposi sarcoma, other opportunistic cancers
Acyclovir, acyclovir sodium
Zovirax
Synthetic purine nucleoside
Oral, IV
Varicella and herpes zoster in cancer patients
Adefovir dipivoxil
Hepsera
Acyclic nucleotide analog Oral
Chronic hepatitis in cancer patients
Amantadine hydrochloride
Symmetrel
Synthetic cyclic primary amine
Oral
Prevention or treatment of influenza A in cancer patients
Amprenavir
Agenerase
Protease inhibitor
Oral
Kaposi sarcoma for treatment of HIV infection
Atazanavir sulfate
Reyataz
Protease inhibitor
Oral
HIV infection in patients with Kaposi sarcoma, other opportunistic cancers
Cidofovir
Vistide
Nucleotide analog
IV
Cytomegalovirus (CMV) retinitis
Darunavir ethanolate
Prezista
Protease inhibitor
Oral
Kaposi sarcoma for treatment of HIV infection
Delavirdine mesylate
Resciptor
Nonnucleoside reverse transcriptase inhibitor
Oral
Kaposi sarcoma for treatment of HIV infection
Didanosine (ddl)
Videx, Videx EC
Nucleoside reverse transcriptase inhibitor
Oral
HIV infection in patients with Kaposi sarcoma, other opportunistic cancers
Efavirenz
Sustiva
Nonnucleoside reverse transcriptase inhibitor
Oral
HIV infection in patients with Kaposi sarcoma, other opportunistic cancers (continued)
90
Salem Health: Cancer
Antiviral therapies
Common Antiviral Agents (continued) Drug (Other Names)
Brands
Subclass
Delivery Mode Conditions Treated
Emtricitabine
Emtriva
Nucleoside reverse transcriptase inhibitor
Oral
HIV infection in patients with Kaposi sarcoma, other opportunistic cancers
Enfuvirtide
Fuzeon
Fusion inhibitor
Subcutaneous injection
HIV infection in patients with Kaposi sarcoma, other opportunistic cancers
Entecavir
Baraclude
Guanosine nucleoside analog
Oral
Chronic hepatitis B in patients with cancer
Famciclovir
Famvir
Synthetic acyclic guanine Oral derivative
Acute herpes zoster infection and recurrent genital herpes in patients with cancer
Fosamprenavir calcium Lexiva
Protease inhibitor
Oral
HIV infection in patients with Kaposi sarcoma, other opportunistic cancers
Foscarnet sodium Foscavir (phosphonoformic acid)
Pyrophosphate analog
IV
CMV retinitis in patients with cancer
Gangciclovir
Cytovene
Synthetic purine Oral, IV nucleoside guanine analog
CMV retinitis in patients with cancer
Indinavir sulfate
Crixivan
Protease inhibitor
Oral
HIV infection in patients with Kaposi sarcoma, other opportunistic cancers
Lamivudine
Epivir
Nucleoside reverse transcriptase inhibitor
Oral
HIV infection in patients with Kaposi sarcoma and other opportunistic cancers; chronic hepatitis B infection in cancer patients
Lopinavir and ritonavir
Kaletra
Protease inhibitor
Oral
HIV infection in patients with Kaposi sarcoma, other opportunistic cancers
Nelfinavir mesylate
Viracept
Protease inhibitor
Oral
HIV infection in patients with Kaposi sarcoma, other opportunistic cancers
Nevirapine
Viramune
Nonnucleoside reverse transcriptase inhibitor
Oral
HIV infection in patients with Kaposi sarcoma, other opportunistic cancers
Oseltamivir phosphate
Tamiflu
Selective neuraminidase inhibitor
Oral
Prevention and treatment of influenza infection
Ribavirin
Copegus, Rebetol, Synthetic nucleoside Ribaspheres, Virazole
Oral, inhalation
Chronic hepatitis infection
Ritonavir
Norvir
Oral
HIV infection in patients with Kaposi sarcoma, other opportunistic cancers
Protease inhibitor
(continued on page 92)
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Antiviral therapies
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Common Antiviral Agents (continued) Drug (Other Names)
Brands
Subclass
Delivery Mode Conditions Treated
Saquinavir mesylate
Invirase
Protease inhibitor
Oral
HIV infection in patients with Kaposi sarcoma, other opportunistic cancers
Stavudine (2,3 didehydro3deoxythymidine, d4T)
Zerit, Zerit XR
Nucleoside reverse transcriptase inhibitor
Oral
HIV infection in patients with Kaposi sarcoma, other opportunistic cancers
Tenofovir disoproxil fumarate
Viread
Nucleoside reverse transcriptase inhibitor
Oral
HIV infection in patients with Kaposi sarcoma, other opportunistic cancers
Tipranavir
Aptivus
Protease inhibitor
Oral
HIV infection in patients with Kaposi sarcoma, other opportunistic cancers
Valacyclovir hydrochloride
Valtrex
Synthetic purine nucleoside
Oral
Herpes zoster and genital herpes in cancer patients
Valganciclovir
Valcyte
Synthetic nucleoside
Oral
CMV retinitis in cancer patients
Zanamivir
Relenza
Selective neuraminidase inhibitor
Inhalation
Prevention and treatment of influenza virus A and B
Zidovudine (azidothymidine, AZT)
Retrovir
Nucleoside reverse transcriptase inhibitor
Oral, IV
HIV infection in patients with Kaposi sarcoma, other opportunistic cancers
Subclasses of this group: Nucleotide analogs, purine nucleoside analogs, acyclic guanine derivatives, pyrophosphate analogs, purine nucleoside guanine derivatives, protease inhibitors, nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors Delivery routes: Administered orally in the form of capsules, tablets, and solutions at home or in the hospital; some also administered in the hospital by intravenous (IV) infusion or subcutaneous injection How these drugs work: The first successful antiviral drug, acyclovir, was discovered in the 1960’s for the treatment of herpesvirus infection. The increased incidence of HIV infection in the 1980’s initiated the development of a variety of antiviral agents that are available today. Antiviral agents work in a variety of ways depending on the drug type. Some competitively inhibit an enzyme located on the viral deoxyribonucleic acid (DNA) chain, halting growth of the viral DNA. Some work on viral ribonucleic acid (RNA), preventing the virus from penetrating healthy cells. Others inhibit viral nucleic acid synthesis by interacting directly with the DNA enzymes. Protease inhibitors 92
inhibit the enzyme needed for viral replication. Reverse transcriptase inhibitors also inhibit viral replication after incorporating themselves into the viral DNA. Side effects: The most common side effects associated with antiviral therapy include gastrointestinal symptoms such as anorexia, abdominal pain, diarrhea, dyspepsia, flatulence, nausea, and vomiting. Other side effects that may occur with antiviral therapy include headache, dizziness, insomnia, depression, suicidal ideation, peripheral neuropathy, weakness, rash, sweating, back pain, chest pain, fever, muscle ache, pneumonia, weight loss, anxiety, elevated or decreased blood pressure, pancreatitis, tremor, cough, shortness of breath, chills, low white blood cell count, low platelet count, anemia, hypoglycemia, seizures, hepatitis, and liver toxicity. Collette Bishop Hendler, R.N., M.S. u
For Further Information Drug Facts and Comparisons 2008. St. Louis: Wolters Kluwer Health, 2008. Lorigan, Paul, ed. Lung Cancer. Dana-Farber Cancer Institute Handbook. New York: Mosby Elsevier, 2007.
Salem Health: Cancer Nursing 2008 Drug Handbook. Philadelphia: Lippincott Williams & Wilkins 2008. See also Antidiarrheal agents; Antifungal therapies; Aplastic anemia; Herpes simplex virus; Herpes zoster virus; Infection and sepsis; Leukoencephalopathy; Viral oncology; Virus-related cancers.
u Anxiety Category: Social and personal issues Definition: Anxiety encompasses a complex set of behavioral, cognitive, and physiological responses to a perceived threat. Symptoms of anxiety include apprehension or fearfulness toward a future event or outcome, physical signs (such as muscle tension, elevated heart rate, breathing changes, and sweating), and often concern about the meaning or implications of the anxious reaction itself. Description of the problem: A key feature of anxiety is the perception of an imminent or future threat, regardless of the accuracy of the perception. Although it is easy to imagine exaggerated or unrealistic appraisals of threat in many circumstances, in the case of cancer, anxiety is a normal and expected reaction to a true threat—a serious and often life-threatening disease. Therefore, distinguishing a normal anxious reaction from a pathological one is difficult in cancer patients as well as in their caregivers and loved ones. Excessive anxiety is a marker of poor coping among cancer patients and warrants further evaluation. Vital to the assessment of clinically significant anxiety is the extent to which anxiety meaningfully impairs the ability to function. For example, extreme anxiety may prevent an otherwise able patient or loved one from continuing to work, or it may interfere with medical care when a patient’s fearful avoidance prevents or delays receipt of tests or treatments. The American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders: DSM-IV-R (4th rev. ed., 2000) recognizes several distinct types of anxiety disorders, including generalized anxiety disorder, panic disorder, specific phobia, social phobia, obsessivecompulsive disorder, and post-traumatic stress disorder. Anxiety may also be a prominent feature of depression or an adjustment disorder (a short-term psychological reaction to a stressful event), both of which are common among cancer patients. The experience of being a cancer patient can contribute to the development of anxiety disorders in several ways.
Anxiety For example, a patient may develop a phobia of particular objects or procedures such as needles or diagnostic tests that were associated with highly stressful experiences. After cancer care, some patients may experience symptoms of post-traumatic stress disorder, characterized by recurrent intrusive memories and flashbacks, avoidance of reminders of stressful events, and hyperarousal symptoms such as sleep difficulties and irritability. Anxiety may also have origins in medical causes such as certain types of tumors or physiological side effects from some treatments. Prevalence: Not surprisingly, research suggests that the vast majority of cancer patients experience anxiety at some point during their illness. Far fewer develop clinical anxiety disorders. Although several studies have suggested an increased prevalence of anxiety disorders among cancer patients, others suggest little or no difference in this prevalence when cancer patients are compared with the
While receiving chemotherapy, a young boy plays a virtual reality game in an effort to distract him from the treatment and relieve his anxiety. (AP/Wide World Photos)
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APC gene testing general population. Reported rates of anxiety disorders are usually lower when assessed using formal diagnostic criteria and range from 10 to 30 percent. Assessment: In the clinical setting, anxiety is most commonly assessed face to face by a primary care provider or by a provider with special expertise in mental health, such as a psychiatrist or a clinical psychologist. The assessment is usually in the form of an interview to establish the nature, duration, and severity of symptoms according to established criteria, whether according to the diagnostic standards set out by the American Psychiatric Association or some other diagnostic system. Numerous standardized questionnaires are also available to measure anxiety in clinical and research settings. These questionnaires ask respondents to self-report the frequency or severity of various symptoms commonly associated with anxiety. Examples of anxiety assessment questionnaires that have been used with cancer patients include the Beck Anxiety Inventory, the State-Trait Anxiety Inventory, and the Hospital Anxiety and Depression Scale. Treatment and therapy: Anxiety related to medication or disease is usually first treated by managing the underlying condition causing symptoms. However, in many cases, anxiety is treated as a condition in its own right. Effective interventions for anxiety include both medical and psychological treatment options. Medical management of anxiety usually entails treatment with an anxiolytic (antianxiety) or antidepressant medication, the latter particularly when signs of a depressed mood are present. The most commonly prescribed anxiolytic medications belong to the class of drugs known as benzodiazepines, which includes clonazepam (Klonopin), alprazolam (Xanax), and diazepam (Valium). Commonly prescribed antidepressants include selective serotonin reuptake inhibitors (SSRIs) such as paroxetine and sertraline (Zoloft), serotonin-norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine (Effexor) and duloxetine (Cymbalta), and to a lesser extent tricyclic antidepressants such as imipramine (Tofranil) and clomipramine (Anafranil). Psychological treatments include individual psychotherapy (talk therapy), group therapy, family therapy, and certain mind-body interventions. In particular, research heavily supports the efficacy of cognitive-behavioral therapy, which encompasses a variety of therapeutic techniques. Broadly speaking, the goals of cognitive-behavioral therapy for anxiety are to guide patients toward a more balanced and rational appraisal of their concerns and to encourage behaviors that reduce or neutralize anxieties rather than exacerbate them. Other frequently used thera94
Salem Health: Cancer peutic approaches include training in relaxation techniques, mindfulness meditation, and hypnosis. Biofeedback may also be effective in helping patients recognize and manage physical symptoms of anxiety by, for example, reducing muscle tension and cardiovascular reactivity to stress. Andrea Bradford, M.A. u
For Further Information American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-IV-TR. 4th rev. ed. Washington, D.C.: Author, 2000. Antony, Martin M., Susan M. Orsillo, and Lizabeth Roemer, eds. Practitioner’s Guide to Empirically Based Measures of Anxiety. New York: Kluwer Academic/Plenum, 2001. Baum, Andrew, and Barbara L. Andersen, eds. Psychosocial Interventions for Cancer. Washington, D.C.: American Psychological Association, 2001.
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Other Resources
American Psychiatric Association http://www.psych.org American Psychological Association http://www.apa.org Anxiety Disorders Association of America http://www.adaa.org National Cancer Institute Anxiety Disorder http://www.cancer.gov/cancertopics/pdq/ supportivecare/anxiety See also Counseling for cancer patients and survivors; Depression; End-of-life care; Grief and bereavement; Living with cancer; Medical marijuana; Pain management medications; Palliative treatment; Psycho-oncology; Psychosocial aspects of cancer; Relationships; Self-image and body image; Sexuality and cancer; Side effects; Stress management; Support groups; Survivorship issues.
u APC gene testing Category: Procedures Also known as: Adenomatosis polyposis coli gene testing Definition: The APC gene is a tumor-suppressor gene that is often mutated in colorectal and other cancers. Most mutations leading to colorectal cancer occur spontaneously in
Salem Health: Cancer
Aplastic anemia
the digestive tracts of affected individuals, but approximately 5 percent of cases result from inherited mutations in APC. Testing for mutations in APC usually involves determining the deoxyribonucleic acid (DNA) sequence of a patient’s APC gene, but other screens are sometimes used.
See also Adenomatous polyps; Colorectal cancer; Desmoid tumors; Gardner syndrome; Genetic counseling; Genetic testing; Hereditary cancer syndromes; Hereditary polyposis syndromes; Tumor markers; Turcot syndrome.
Cancers diagnosed: Familial adenomatous polyposis, familial colon cancer
u Aplastic anemia
Why performed: Testing for mutations in the APC gene is performed to diagnose familial adenomatous polyposis (FAP), an inherited condition in which precancerous polyps form in the colon. Although these polyps are initially benign, they may develop into cancer if untreated. The DNA of patients exhibiting symptoms of FAP is sequenced to confirm diagnosis and to characterize the mutation in APC. Because FAP is an inherited disorder, genetic testing is often done in relatives of those afflicted with FAP in order to determine whether prophylactic treatment is required.
Category: Diseases, symptoms, and conditions Also known as: Bone marrow failure
Patient preparation: Patients considering genetic testing may meet with a genetic counselor to discuss the benefits and risks of the test and the significance of negative, positive, and inconclusive tests. The material required for genetic testing is obtained from a blood sample. Steps of the procedure: Blood samples are sent to a clinical laboratory that offers APC screening. DNA is purified from the blood sample, and the DNA that encodes for APC is amplified by polymerase chain reaction (PCR) and sequenced using standard, automated methods. After the procedure: The patient may consult with a physician or genetic counselor to discuss the implications of the test results.
Related conditions: Thrombocytopenia (low platelet count), neutropenia (low white count) Definition: The bone marrow is responsible for producing all of the blood cells in the body. Aplastic anemia is a lifethreatening condition caused when the bone marrow stops producing enough new cells to create new blood cells. The typical life span of red blood cells is 120 days, platelets about 6 days, and white blood cells about 1 day. The bone marrow needs to produce cells continuously to replace the dying cells. Aplastic anemia can be acquired or hereditary. The more common acquired aplastic anemia can be a temporary condition caused by exposure to toxic chemicals, pesticides, and benzenes. Common causes for the cancer patient are chemotherapy and radiation. Hereditary aplastic anemia is rare and can be associated with Fanconi anemia, Shwachman-Diamond syndrome, and dyskeratosis congenita. Etiology and the disease process: Although the cause of most aplastic anemia is unknown, those cases induced by chemotherapy and radiation result from the therapy’s suppression of bone marrow function. The bone marrow is not able to manufacture the cells that are needed to create red blood cells, platelets, and white blood cells.
Risks: Complications from drawing blood are rare but may include pain, bleeding, hematoma, or infection. Because the information obtained from APC screening may have dramatic psychological effects, it is essential that patients be offered genetic counseling.
Incidence: Aplastic anemia is a rare condition with only about 500 to 1,000 new cases each year in the United States. Of patients who are diagnosed with aplastic anemia, 20 percent have an inherited disorder as well.
Results: Sequence analysis allows clinicians to identify the specific DNA mutation(s) present in a FAP patient. Once the mutation has been identified, close relatives can be screened to determine if they share the FAP-causing mutation. Patients who do not carry the mutation are at no greater risk for colon cancer than the general population. Colectomy (surgical resection of the colon) and other prophylactic treatment are recommended for individuals who carry cancer-causing mutations in the APC gene. Kyle J. McQuade, Ph.D.
Symptoms: The signs and symptoms of aplastic anemia may be seen immediately or can be slow to develop and be dependent on the blood counts themselves. Common symptoms include fatigue, dizziness, an irregular heart rate, fevers, frequent infections, frequent nose bleeds, oozing gums, blood in the stool, bruising, difficulty in stopping bleeding from a cut, and petechiae (similar to a red pinpoint rash, located on the arms, legs, and trunk). Patients may also complain of severe shortness of breath even while at rest. 95
Aplastic anemia
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can be given to help the bone marrow release immature red blood cells from the bone marrow to mature and become functioning red cells. Not all forms of aplastic anemia will respond to growth factors. Platelet transfusions will help the patient be able to form clots to stop bleeding. White blood cells are not typically transfused because of their short life span; however, they may be given to patients who have a severe infection. Patients with a low white blood cell count may receive filgrastim, a white blood cell growth factor, to stimulate the release of the immature white blood cells so that they can mature and fight off infections. Like the red cell growth factor, filgrastim may not be applicable for all forms of aplastic anemia. This pinpoint rash on the palm of the hand is a symptom of aplastic anemia. (Custom Patients may receive medications such Medical Stock Photo) as antithymocyte globulin (ATG), cyclosporine, and methylprednisolone. TradiScreening and diagnosis: Aplastic anemia is typically tional therapy consists of the patient taking all three medifound when patients complain of fatigue to their physications. It may take a few months before an improvement cians. The physical assessment includes looking for pale in blood counts is apparent. Patients may say that they are or yellow-tinted skin; listening to the heart, lungs, and feeling better before their counts actually reflect an imbreathing patterns; feeling the liver and spleen for enlargeprovement. Antibiotics and antivirals may also be given to ment; and checking for signs of bleeding. The physician prevent infection. may also assess the patient’s environment to determine Bone marrow transplants are more commonly used whether exposure to toxic chemicals or other triggers has with younger patients to replace damaged bone marrow. occurred. Diagnostic testing includes analysis of blood, Research is ongoing to develop additional treatments for urine, and stool samples, and bone marrow aspiration and aplastic anemia. biopsy. The patient may also have images taken (X rays, Prognosis, prevention, and outcomes: Historically computed tomography scans, and ultrasound) to look for aplastic anemia has had a poor prognosis. However, great enlarged organs. Once testing is complete, the aplastic strides have been made on the treatments available for anemia is staged according to how many cells are seen in aplastic anemia, and modern therapy has cured or manthe bone marrow. The three stages are moderate, severe, or aged the disease in many patients. Treatment can be effecvery severe. tive but may take months before results are seen. Patients may also need to try different therapies to find one that Treatment and therapy: The treatment for aplastic aneworks for them. Some forms of aplastic anemia can be premia depends on the severity and the patient’s symptoms. vented by avoiding exposure to toxins, radiation, and medThe patient’s overall health also determines what type of ication, but other forms cannot be prevented. treatment can be tolerated. Moderate aplastic anemia is not Katrina Green, R.N., B.S.N., O.C.N. treated, but the physician keeps a close eye on the blood counts and the patient’s symptoms. If the aplastic anemia is caused by chemotherapy or radiation, the patient is treated with transfusions and growth factors. Transfusions of red blood cells and platelets are the most common. Red blood cell transfusions help raise the hematocrit and hemoglobin, which improves the anemia symptoms. Epoietin alfa, a red blood cell growth factor, 96
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For Further Information Klag, Michael J, ed. Johns Hopkins Family Health Book. New York: HarperCollins, 1999. Schrezenmeier, Hubert, and Andrea Bacigalupo, eds. Aplastic Anemia: Pathophysiology and Treatment. New York: Cambridge University Press, 2000.
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Other Resources
Aplastic Anemia & MDS International Foundation http://www.aplastic.org National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov See also Anemia; Bone marrow transplantation (BMT); Fanconi anemia; Hairy cell leukemia; Hematologic oncology; Leukemias; Leukopenia; Myelodysplastic syndromes; Neutropenia; Transfusion therapy.
u Appendix cancer Category: Diseases, symptoms, and conditions Also known as: Carcinoid tumor, colonic adenocarcinoma, mucinous cyst adenocarcinoma, signet-ring cell adenocarcinoma Related conditions: Appendicitis, peritoneal carcinomatosis, disseminated peritoneal adenomucinosis Definition: Appendix cancer is a cancerous tumor in the appendix, the pouchlike, thin tube with a closed end that is located in the lower right quadrant of the abdomen. The appendix, also called the vermiform appendix because its appearance is wormlike, is attached to the cecum, the first section of the large intestine, close to where it joins with the small intestine. It is not known to have a significant function in the body but may play a role in the immune system. Cancerous tumors that originate in the appendix are part of the larger grouping of colorectal or gastrointestinal cancers. Types of appendix cancer include carcinoid tumor, mucinous cyst adenocarcinoma, colonic-type adenocarcinoma, and signet-ring cell adenocarcinoma. Risk factors: Because appendix cancer is not common, no specific risk factors have been identified. However, risk factors for colorectal cancers in general include a diet high in red meat, lack of exercise, obesity, and cigarette smoking. Etiology and the disease process: The cause of appendix cancer is unknown. It often goes undiagnosed until it causes appendicitis or the appendix ruptures. In a majority of patients, appendix tumors spread in a process called peritoneal seeding, in which multiple, initially small, tumors are produced throughout the abdominal cavity. Lowgrade tumors grow more slowly and are generally less invasive, whereas high-grade tumors are faster growing and considerably more invasive.
Appendix cancer Incidence: Cancer that starts in the appendix, or primary appendix cancer, is uncommon. Therefore, these cancers are usually included in the statistical data for colorectal cancer. and actual incidence rates are not available. One estimate is that about 1 percent of colorectal cancer cases in the United States are primary appendix cancer, with about 1,100 new cases diagnosed in 2007. About 66 percent of appendix tumors are carcinoid tumors, 20 percent are mucinous cyst adenocarcinoma, and 10 percent are colonic-type adenocarcinoma. Signet-ring cell adenocarcinoma, which is very rare, is an aggressive cancer that is more difficult to treat than other adenocarcinomas. Symptoms: People with appendix cancer may not experience symptoms until the disease is far advanced. The first reported symptoms are typically those of appendicitis, which include fever, pain in the lower right quadrant of the abdomen, nausea, and vomiting. Other symptoms may include bowel changes, abdominal bloating, pelvic pain, infertility, and an increase in waistline size, with possible navel protrusion. Some people experience no symptoms at all, and the cancer is found incidentally during surgery for another condition such as ovarian tumors. Screening and diagnosis: There are no screening tests for appendix cancer. Most often it is found during surgery for another abdominal condition, either when a biopsy is performed on the tissue that has been removed or when the surgeon observes abnormalities or tumors in the abdomen. Computed tomography scanning, magnetic resonance imaging, and ultrasound can be performed if appendix cancer is suspected or to determine the extent of the cancer’s spread. Radionuclide scanning is performed to determine the spread of a carcinoid tumor. No standard staging system exists for appendix cancer. Instead, appendix tumors are usually classified by whether the cancer is confined to the appendix or has spread and how far: to distant organs or only to nearby tissues. Treatment and therapy: The treatment of appendix cancer depends on the type of tumor, its size, and whether the cancer has spread. Surgery to remove the tumor along with nearby blood vessels, lymph nodes, and part of the large bowel is the most common treatment for tumors that are low grade and slow growing. Currently, the most effective treatment for higher-grade, more aggressive tumors and tumors that have seeded the abdomen is a procedure called cytoreductive or debulking surgery. During this procedure, the surgeon removes as much of the cancer in the abdomen as possible. When complete, it means that all visible tumors were removed; when incomplete, it means 97
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Stage at Diagnosis and Relative Survival Rates for Appendix Cancer, 1988-2001 Survival Rates (%) Stage Stage I Stage II Stage III Stage IV
1-Year
5-Year
10-Year
97.4 92.6 87.2 65.9
89.9 73.9 48.3 25.4
83.2 63.9 37.0 16.2
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007)
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Other Resources
American Cancer Society http://www.cancer.org Appendix Cancer (Appendiceal Carcinoma) & Peritoneal Surface Malignancy http://www.appendix-cancer.com Cancer.Net http://www.cancer.net/portal/site/patient See also Carcinoid tumors and carcinoid syndrome; Continuous hyperthermic peritoneal perfusion (CHPP); Small intestine cancer; Stomach cancers.
u Appetite loss that some tumors could not be removed. This surgery is typically combined with intraoperative hyperthermic intraperitoneal chemotherapy; a high concentration of a chemotherapy solution is instilled in the abdomen during surgery. The solution, heated to just above normal body temperature, has been found to be effective because it destroys cancer cells and tumors that are too small to be seen and also because it can reach all surfaces in the abdomen. Postoperative intraperitoneal chemotherapy is also used in some cases. Prognosis, prevention, and outcomes: The prognosis for appendix cancer varies greatly and depends on several factors, including the type of tumor, whether it has spread, and how it is treated. Complete cytoreductive surgery combined with intraoperative hyperthermic intraperitoneal chemotherapy has been found to be effective in increasing survival rates, especially with mucinous cyst adenocarcinoma. Appendix cancer has no known method of prevention. Dorothy P. Terry, R.N. u
For Further Information Carmignani, C. P., and P. H. Sugarbaker. “Synchronous Extraperitoneal and Intraperitoneal Dissemination of Appendix Cancer.” European Journal of Surgical Oncology 30, no. 8 (October, 2004): 864-868. Holland, Jimmie C., and Sheldon Lewis. The Human Side of Cancer. New York: HarperCollins, 2000. Sugarbaker, Paul H. “New Standard of Care for Appendiceal Epithelial Neoplasms and Pseudomyxoma Peritonei Syndrome?” Lancet Oncology 7, no. 1 (January, 2006): 69-76. 98
Category: Diseases, symptoms, and conditions Also known as: Anorexia Related conditions: Cachexia Definition: Loss of appetite in cancer patients, referred to by medical professionals as anorexia, may result from either the cancer itself or the treatments used to combat the disease. Cancer-related anorexia is associated with weight loss and has been shown to correlate with a poorer outcome and a lower quality of life. Risk factors: Those with cancer and undergoing chemotherapy for cancer are at risk. Etiology and the disease process: Because many cancer treatments affect not only cancer cells but also healthy cells, several unwanted side effects may result. For instance, chemotherapy may reduce the turnover of taste receptor cells in the tongue, which may alter the flavor of food. Additional damage to other cell types in the mouth may result in sores, gum disease, dry mouth, and sore throat. Cells in the digestive tract may also be injured, resulting in abnormal gut motility and difficulty swallowing. Together, these effects may change the way food tastes and decrease the desire to eat. Emotional side effects, such as fear and depression, as well as psychological effects, such as food aversion, can also contribute to the loss of appetite. Furthermore, many cancer patients with anorexia report early satiety, meaning that they feel full after eating only a small amount of food. Biological causes for cancer-related anorexia also exist. Cytokines released by tumor cells or produced by immune cells in response to cancer may affect the central nervous system and the gastrointestinal tract to promote
Salem Health: Cancer appetite loss. Specifically, the central nervous system is responsible for controlling food intake and energy homeostasis, while effects on the gastrointestinal tract can influence feelings of fullness. Examples of cytokines that may affect appetite include tumor necrosis factor-alpha (TNF-α), C-reactive protein, interleukin-1 beta (IL-1 beta), IL-6, and tumor-derived lipid mobilizing factor (LMF). However, there is some conflicting data as to whether blood levels of these cytokines correlate with, or are responsible for, the loss of appetite. Incidence: In general, approximately 25 percent of cancer patients report loss of appetite. The incidence can be as high as 90 percent for patients with advanced cancers. However, different types of cancers tend to have different rates of anorexia. For example, approximately 60 to 80 percent of patients with cancers of the lung, stomach, pancreas, or esophagus have significant weight loss caused, in part, by anorexia. However, loss of appetite is not as frequent in patients with breast or prostate cancer. Treatment and therapy: Cancer-related anorexia may be managed by either changing eating habits or taking medication. There are several dietary suggestions for cancer patients who struggle with loss of appetite. Liquid or powdered meal replacements as well as juice, soups, and milkbased drinks or shakes may be used in place of solid food to provide nutrients. Eating several small meals or snacks instead of three large meals per day may also be more feasible for patients with cancer-related anorexia. Additionally, drinking a glass of wine or exercising regularly may also stimulate the appetite. However, patients should consult with their doctors before consuming alcohol or beginning an exercise regimen. The pharmacological treatment of cancer-related anorexia can be broadly divided into three groups: appetite stimulants, anticatabolic agents, and anabolic agents. Examples of appetite stimulants include progestational agents (such as megestrol acetate and medroxyprogesterone), which can improve caloric intake. Corticosteroids (such as prednisolone and methylprednisolone) may improve appetite because of their inhibition of prostaglandin metabolism and IL-1 signaling. Cyproheptadine, an antihistamine, is also a serotonin antagonist, and its effects on this neurotransmitter in the brain can also promote an increase in appetite. A more controversial appetite stimulant is cannabis (marijuana), as it can stimulate CB1 receptors in the brain to enhance appetite. Anticatabolic agents, which inhibit the production or activity of appetite-decreasing cytokines, are also important in combating cancer-related anorexia. Examples include thalidomide (a potent inhibitor of TNF-α produc-
Appetite loss tion) and eicosapentaenoic acid (an inhibitor of adenylate cyclase activity and tumor-derived LMF activity). Anabolic agents such as oxandrolone and fluoxymesterone have been studied as well, and they may build lean tissue mass by increasing muscle protein synthesis. The hormone androgen may also be useful in cancer patients (except for those with hormone-dependent tumors) as it can promote muscle growth and strength and may also induce the secretion of leptin, a hormone produced by adipose tissue to stimulate appetite. Prognosis, prevention, and outcomes: Generally appetite loss resolves itself when its underlying cause is remedied. Although appetite loss can interfere with the healing process, it does not usually cause death in patients with early-stage cancers. However, cancer-related anorexia is often associated with cachexia, a wasting syndrome characterized by not only the loss of appetite but also weight loss, breakdown of muscle tissues, depletion of reserves within fat (adipose) tissue, fatigue, and weakness. In advanced-stage cancer, the cancer anorexia-cachexia syndrome is observed in about 80 percent of patients and is one of the most frequent causes of death. u
For Further Information Behl, D., and A. Jatoi. “Pharmacological Options for Advanced Cancer Patients with Loss of Appetite and Weight.” Expert Opinion on Pharmacotherapy 8, no. 8 (June, 2007): 1085-1090. Perboni, S., and A. Inui. “Anorexia in Cancer: Role of Feeding-Regulatory Peptides.” Philosophical Transactions of the Royal Society B: Biolocial Sciences 361, no. 1471 (July 29, 2006): 1281-1289. Poole, K., and K. Froggatt. “Loss of Weight and Loss of Appetite in Advanced Cancer: A Problem for the Patient, the Carer, or the Health Professional?” Palliative Medicine 16, no. 6 (November, 2002): 499-506. Rubin, H. “Cancer Cachexia: Its Correlations and Causes.” Proceedings of the National Academy of Sciences of the United States of America 100, no. 9 (April 29, 2003): 5384-5389.
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Cancer.Net Appetite Loss http://www.ascocancerfoundation.org/patient/ Diagnosis+and+Treatment/Treating+Cancer/ Managing+Side+Effects/Appetite+Loss 99
Arsenic compounds National Cancer Institute Eating Hints for Cancer Patients: Before, During, and After Treatment http://cancer.gov/cancertopics/eatinghints/page3 Elizabeth A. Manning, Ph.D. See also Antidiarrheal agents; Cachexia; End-of-life care; Gastrointestinal cancers; Gerson therapy; Living with cancer; Medical marijuana; Pain management medications; Palliative treatment; Side effects; Taste alteration; Weight loss.
u Arsenic compounds Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1980 Also known as: Arsenic pentoxide, arsenic trioxide, arsenic acid Related cancers: Lung cancer, bladder cancer, liver cancer, kidney cancer, prostate cancer, colon cancer, certain types of skin cancer Definition: Arsenic occurs in small concentrations in earth and minerals. Leaching effects of water and wind erosion continuously release trace amounts, which can be transported over long distances via windblown dust, surface water, and groundwater flow. Inorganic arsenic compounds are naturally occurring combinations of arsenic and oxygen, sulfur, or chlorine. These and the complex minerals they are associated with are generally water soluble and occur as white, odorless solids. They typically have high melting and boiling points and can be extremely toxic, even fatal, if inhaled or ingested in large quantities. Exposure routes: Arsenic compounds in the form of dust and fumes can be absorbed through dermal layers of the skin or can be inhaled and absorbed in respiratory passageways. Arsenic can be ingested orally as a contaminant in food or water. Where found: Arsenic is a naturally occurring material in soil and water and also in various ores, especially copper and lead. Therefore, arsenic compounds are found throughout the environment. Arsenic naturally combines with other naturally occurring elements including sulfur, oxygen, and chlorine to create relatively stable inorganic arsenic compounds. Often the most concentrated environmental forms of arsenic are released into the atmosphere via volcanoes and mineral and ore erosion. Because arsenic compounds cannot be destroyed, a fairly constant 100
Salem Health: Cancer level of toxic inorganic compounds of arsenic always exists in the environment, either in soil, water, or as airborne particulate matter. Because most arsenic compounds are soluble in water, airborne arsenic may be transported great distances before being removed via precipitation to return to soil and water. At risk: Compounds of inorganic arsenic are used in the manufacture of semiconductors and as a wood preservative. They are also used in making special glass. People involved in these industries are especially at risk because of direct occupational exposure. Because many arsenic compounds occur in ores, people who work in metal smelters are often exposed to higher levels of arsenic. Similarly, carpenters and contractors and others may be exposed to the fumes of burning wood treated with an arsenic preservative or inhale sawdust from treated wood. The most common arsenic poisoning incidents occur among workers involved in the production of arsine, an extremely toxic gas produced by combining arsenic and hydrogen. Finally, people who live in areas with high levels of arsenic in rock or in water are at greater risk. Etiology and symptoms of associated cancers: Studies conducted on humans testing positive for high levels of inorganic arsenic compounds show significant correlations with various cancers, including skin, liver, lung, and bladder cancer. Studies show an especially strong positive correlation between an increase in toxicity levels of arsenic in air, soil, and water and an increase in nonmelanoma skin cancer. Internal cancers, including liver, kidney, and bladder cancer, probably result from exposure to arsenic via ingestion of food and liquid contaminated with high levels of inorganic arsenic and its compounds. As plants fairly readily absorb inorganic arsenic and its compounds, plants in habitats with high levels of arsenic will be contaminated with higher than normal amounts of this highly toxic mineral. Digestion of plant food in the gastrointestinal tract increases exposure to and absorption of certain arsenic compounds, which then are carried to the liver, kidney, aorta, and skin before they are transferred to the bladder for excretion. Note that this list of exposed organs equates to the more common types of arsenic-induced cancers. The two most common types of nonmelanoma skin cancers associated with toxic arsenic levels are basal cell carcinoma and squamous cell carcinoma. Basal cell carcinoma begins in the lowest layer of the epidermis, called the basal cell layer. It is highly unusual for a basal cell cancer to spread to lymph nodes or to distant parts of the body. However, if a basal cell cancer is left untreated, it can grow into nearby areas and invade the bone or other tissues be-
Salem Health: Cancer neath the skin. Squamous cell carcinomas tend to be more aggressive than basal cell cancers. They are more likely to invade fatty tissues just beneath the skin, and slightly more likely to spread to lymph nodes or distant parts of the body, although this is still uncommon. Symptoms include changes in skin texture, size, or color, and the area may become sore or ooze. Very high levels of arsenic exposure and absorption via all routes may lead to a decrease in blood cell production, lymphatic cancer, brain damage, and, in women, infertility and miscarriages. History: In industry, inorganic arsenic compounds were used as pesticides as early as the middle of the nineteenth century. Within the next century, however, use of such compounds was curbed because of noticeable environmental effects. The most common use for inorganic arsenic since the 1980’s is in wood preservation. Pressuretreated wood is made by immersing wood in chromated copper arsenate (CCA) or applying it to the wood under pressure. The arsenic component helps protect the treated wood from weather damage, insects, and decay. CCA is no longer used for residential projects but is used for industrial building. Although the United States has not produced arsenic since 1985, it is still the world’s leading arsenic consumer. This puts people at risk in nontraditional ways. For example, people with decks and other housing structures constructed with preserved wood are automatically at increased risk of arsenic exposure, as are farmers who used arsenic-containing pesticides. In medicine, diseases such as syphilis and psoriasis, leukemia, and asthma were commonly treated with inorganic arsenic solutions until the 1970’s. Even in the twenty-first century, it is still used as an antiparasitic agent in veterinary medicine, especially in many countries outside the United States. Continued use of arsenic in all its forms has actually increased environmental levels in soil, water, and air—-a trend that is likely to continue with increased industrial demands for this highly valuable but also highly toxic mineral. Dwight G. Smith, Ph.D. u
For Further Information Battacharyua, Prosun, et al., eds. Biogeochemical Interactions, Health Effects, and Remediation. Vol. 9 in Arsenic in Soil and Groundwater Environment. Cambridge, Mass.: Elsevier, 2007. Frost, Floyd J. Cancer Risks Associated with Elevated Levels of Drinking Water Arsenic Exposure. Washington, D.C.: AWWA Research Foundation and U.S. Environmental Protection Agency, 2004.
Arterial embolization Naidu, R., et al., eds. Managing Arsenic in the Environment: From Soil to Human Health. Enfield, N.H.: CSIRO and Science, 2006. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Eleventh Report on Carcinogens. Research Triangle Park, N.C.: Author, 2005. u
Other Resources
National Library of Medicine Environmental Health and Toxicology: Enviro-Health Links—Arsenic and Human Health http://sis.nlm.nih.gov/enviro/arsenicandhumanhealth .html See also Basal cell carcinomas; Bowen disease; Chewing tobacco; Cigarettes and cigars; Coke oven emissions; Fibrosarcomas, soft-tissue; Free radicals; Hemangiosarcomas; Hepatomegaly; Liver cancers; Lung cancers; Melanomas; Nickel compounds and metallic nickel; Occupational exposures and cancer; Pesticides and the food chain; Soots; Squamous cell carcinomas.
u Arterial embolization Category: Procedures Also known as: Transarterial bland embolization, transarterial chemotherapy, transarterial chemo embolization (TACE) Definition: Arterial embolization is the intentional blockage of an artery, thus depriving a tumor of a blood supply, oxygen, and nutrients. In some cases, embolization is used to deliver drugs or other chemotherapeutic agents via blood vessels to induce the cytotoxicity of tumors. Cancers treated: Hepatocellular carcinoma, tongue carcinoma Why performed: In patients whose cancer is significantly advanced and for whom surgical options cannot be considered, or in conditions of metastasis outside the liver and inadequate hepatic reserves, arterial embolization is preferred as a viable alternative. This option is generally chosen when the tumor is greater than 4 centimeters in size and there are multiple lesions. Arterial embolization takes advantage of the fact that the liver receives its blood supply from two main sources, the hepatic artery and hepatic portal vein, and that the major supplier of blood to liver is the hepatic artery. During the embolization procedure, the hepatic artery is blocked. Embolization may be combined 101
Artificial sweeteners with chemotherapy or radiotherapy to enhance the effects of treatments. Patient preparation: Patients are briefed on all the steps and options involved in the procedure. A hospital stay is generally required. Patients receive intravenous sedation to cause numbness and to mitigate pain. Steps of the procedure: During the procedure, an angiographic catheter is introduced in the branches of the hepatic artery. Usually a dye is injected for contrast and to acquire images. The hepatic artery is then blocked with occluding agents such as polyvinyl alcohol beads, which are transported to terminal hepatic arteries and occlude the vessels. The liver can still be healthy and functional using a blood supply derived from the alternative route of portal veins. In cases where arterial embolization is combined with chemotherapy (as in transarterial chemo embolization, or TACE), an anticancer drug (such as doxorubicin) is injected through the catheter and then the artery is blocked. Pressure is applied to prevent bleeding after the procedure is performed. Sometimes radiotherapy is combined with arterial embolization. After the procedure: An overnight stay in the hospital may be required. Generally, patients are advised to take adequate rest and avoid strenuous activities for at least twenty-four hours. The procedure may be repeated every six to eight weeks. Risks: Total liver failure, although not common, is a risk associated with this procedure. Side effects termed “embolization syndrome,” including nausea, abdominal pain, and mild fever, may ensue. Results: Increasing evidence shows that this procedure increases the rates of survival in liver cancer patients. In cases where it is combined with chemotherapy, recovery is expedited as a result of the presence of increased and prolonged concentrations of drugs around tumors. Geetha Yadav, Ph.D. See also Carcinoid tumors and carcinoid syndrome; Chemoembolization; Embolization; Hereditary leiomyomatosis and renal cell cancer (HLRCC); Hereditary nonVHL clear cell renal cell carcinomas; Hereditary papillary renal cell carcinomas; Kidney cancer; Leiomyomas; Living will; Urinary system cancers; Virus-related cancers.
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u Artificial sweeteners Category: Lifestyle and prevention Also known as: Aspartame, saccharin Definition: Artificial sweeteners are nonnutritive chemical substances that have virtually no or very low caloric value and are used as substitutes in food products for natural sweeteners such as sugar and honey. Artificial sweeteners are commonly used for controlling weight and insulin levels. Government-approved artificial sweeteners: Artificial sweeteners are nonnutritive in nature since they provide no calories or energy to the body. There are five artificial sweeteners—aspartame (NutraSweet, Equal), saccharin (Sweet’N Low, Sweet Twin, Necta Sweet), acesulfame K (Sunnet, Sweet One), neotame, and sucralose (Splenda)— approved for use in the United States by the U.S. Food and Drug Administration (FDA). Two artificial sweeteners that the FDAhas not approved are alitame and cyclamate. Aspartame is two hundred times sweeter than sugar and was approved for use as a general-purpose sweetener in all foods and drinks in 1996. Saccharin is two hundred to seven hundred times sweeter than sugar. It is used as a tabletop sweetener and in soft drinks and chewing gum. Acesulfame K was first approved by the FDA as a tabletop sweetener and is about two hundred times sweeter than sugar. Neotame, which is about seven thousand to fourteen thousand times sweeter than sugar, was approved in 2002 as a general-purpose sweetener in a wide variety of food products. Sucralose is the only artificial sweetener that has three chlorine atoms in its chemical structure and is six hundred times sweeter than sugar. It was approved in 1998 for use in food products, such as beverages, chewing gum, and frozen desserts. Sucralose was approved by the FDAas a general-purpose sweetener in all foods in 1999. Metabolism: Sucrose, the chemical entity in natural table sugar, binds to special receptor proteins in the taste buds. This binding initiates a cascade of events that finally results in a signal sent to the brain that causes the sensation of sweet taste. Additionally, sugar is a carbohydrate that is metabolized by the body to provide calories. Artificial sweeteners have a greater affinity for the receptor proteins and work by binding two hundred to fourteen hundred times more strongly to the receptor proteins than sucrose. As a result of their stronger binding capacity, the artificial sweeteners are needed in much lower quantities than sugar to produce the same degree of sweetness. The artificial sweeteners are either excreted by the body or converted to by-products with little or no caloric
Salem Health: Cancer output. Saccharin, sucralose, and acesulfame K are excreted unchanged by the body and do not provide any calories. The enzymes in the body hydrolyze neotame and produce methanol as a by-product. Aspartame is broken down in the body to produce methanol and the amino acids aspartic acid and phenylalanine and very few calories compared with sugar. Methanol is further degraded to formaldehyde in the body. Both methanol and formaldehyde are toxic to human beings at high doses. People with the genetic disease phenylketonuria (PKU) lack the enzyme that breaks down phenylalanine. Because phenylalanine is produced as a by-product of aspartame digestion, people with PKU should not ingest aspartame. Foods containing aspartame must carry a label warning consumers with PKU that the product is a source of phenylalanine. Cancer risk: Questions regarding the risk of cancer associated with the consumption of artificial sweeteners arose when early studies indicated that saccharin caused bladder cancer in test animals. Subsequent epidemiological studies of groups of people did not find a definitive correlation between saccharin use and bladder cancer. There are two more controversial reports on the correlation between aspartame use and cancer. One study found more lymphomas and leukemias in rats fed very high doses of aspartame while the other study did not find a link between aspartame use and cancer. Artificial sweeteners are regulated by the Food and Drug Administration. Before artificial sweeteners can be launched in the U.S. market, the FDA reviews numerous safety studies conducted with them, including the studies that assess their potential cancer risk. The reviews have not conclusively demonstrated any strong positive correlation between various cancers and artificial sweetener use. Studies continue to be conducted, and the FDA will continue to review and evaluate the results. Artificial sweeteners are beneficial for people with diabetes and for people on weight-loss plans. The effects of their long-term use on weight-maintenance and cancer risk are controversial because they are not clearly understood. In the light of insufficient experimental data and all the controversy swirling around the use of artificial sweeteners, moderation should be the watchword for everyone using them. Lalitha Krishnan, Ph.D. u
For Further Information Abegaz, E. M. “Aspartame Not Linked to Cancer.” Environmental Health Perspectives 115, no. 1 (January, 2007): A16-17. Gallus, S., et al. “Artificial Sweeteners and Cancer Risk in
Asbestos a Network of Case-Control Studies.” Annals of Oncology 18, no. 1 (January, 2007): 40-44. Lim, U., et al. “Consumption of Aspartame-Containing Beverages and Incidence of Hematopoietic and Brain Malignancies.” Cancer Epidemiology Biomarkers and Prevention 15 (September, 2006): 1654-1659. Soffritti, Morando, et al. “First Experimental Demonstration of the Multi-potential Carcinogenic Effects of Aspartame Administered in the Feed to Sprague-Dawley Rats.” Environmental Health Perspectives 114, no. 3 (March, 2006): 379-385. u
Other Resources
Green Facts http://www.greenfacts.org/en/aspartame/artificialsweeteners.htm MayoClinic.com Artificial Sweeteners: A Safe Alternative to Sugar http://www.mayoclinic.com/health/diabetes-diet/ NU00592 National Cancer Institute Artificial Sweeteners and Cancer: Questions and Answers http://www.cancer.gov/cancertopics/factsheet/Risk/ artificial-sweeteners See also Dietary supplements; Nutrition and cancer prevention; Obesity-associated cancers; Weight loss.
u Asbestos Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1980 Also known as: Chrysotile, actinolite, amosite, anthophyllite, crocidolite, tremolite Related cancers: Pleural and peritoneal mesothelioma, gastrointestinal cancers, laryngeal cancer, possibly kidney and other cancers Definition: Asbestos refers to six naturally occurring fibrous silicate minerals: the serpentine mineral chrysotile and the amphibole minerals actinolite, amosite, anthophyllite, crocidolite, and tremolite. The fire-resistant properties of these minerals have been known since antiquity. Their fibers are released into the environment from both natural and human sources and are found in indoor and outdoor air, soil, drinking water, food, and even some medicines. Although there are a variety of forms of asbes103
Asbestos tos, some more associated with cancer than others, all forms of asbestos share a common characteristic: Because asbestos consists of silica crystals, the fibers are inherently irritating to human tissue. Exposure routes: Inhalation and ingestion Where found: Materials for roofing, thermal and electrical insulation, cement pipe and sheets, flooring, gaskets, friction materials, coatings, plastics, textiles, paper, and other products At risk: Workers in asbestos mining and milling, shipyards, building demolition, insulation, brake repair, and asbestos abatement, and their families Etiology and symptoms of associated cancers: Several asbestos-related conditions are nonmalignant, including asbestos warts (callus-like growths that form when asbestos fibers become embedded in the skin), asbestosis, pleural plaques, pleural thickening, and pleural effusions (the collection of fluid around the lung a few years after asbestos exposure). Inhaled or ingested asbestos fibers lead to the two most serious asbestos-related disorders: the noncancerous asbestosis, in which scarred and increasingly stiff lung tissue progressively reduces breathing capacity, and the cancer known as malignant mesothelioma. These diseases may take years or decades to develop, although there have been cases of adolescents developing mesothelioma within only a few months of initial asbestos exposure.
Salem Health: Cancer Malignant mesothelioma takes two main forms: pleural mesothelioma, in which tumors form on the outer lining of the lungs, and peritoneal mesothelioma, in which tumors form on the peritoneum, the sac containing the abdominal organs. Both have a high mortality rate because mesothelioma is rarely detected in its early stages; the average age of diagnosis is sixty. Symptoms—chest pain, cough, weight loss, and shortness of breath—are often attributed to more common diseases such as asthma. As the cancer spreads, lung capacity is diminished, and the patient eventually succumbs to the inability to take in sufficient oxygen, if not to the failure of other organs after the cancer metastasizes. Asbestos exposure has also been associated with cancers of the stomach, liver, and other organs. Researchers have observed digestive-tract cancers in workers exposed to crocidolite, amosite, and chrysotile, although study results are inconsistent. An excess of laryngeal cancer has been reported in shipyard workers, chrysotile miners, insulation workers, and others exposed to asbestos. People living near asbestos factories or mines or living with asbestos workers have also developed mesothelioma; however, there is no clear association between cancer risk and exposure to asbestos in drinking water. Smokers who are also exposed to asbestos are at a synergistically (rather than additively) greater risk of developing lung cancer.
History: In the 1930’s, researchers established that asbestos presented especially high risks of causing lung diseases in miners, shipyard workers, and others who either manufactured or worked with materials incorporating asbestos, such Asbestosis: Most Frequently Recorded Occupations as insulation. It soon became evident on Death Certificate that exposure to minute amounts of asbestos could lead to asbestos-related Occupation Number of Deaths Percent disorders. Miners’ spouses developed Plumbers, pipefitters, and steamfitters 238 8.3 mesothelioma after being exposed to Managers and administrators 129 4.5 asbestos through doing laundry, for exElectricians 125 4.4 ample, while children became victims Carpenters 120 4.2 through exposure to their parents’ work Insulation workers 108 3.8 clothes in the home. Laborers, except construction 95 3.3 In the United States, asbestos was Supervisors, production occupations 85 3.0 one of the first hazardous air pollutants Welders and cutters 78 2.7 regulated by the Clean Air Act of 1970. Janitors and cleaners 74 2.6 The first lawsuits resulting from occuTruck drivers 66 2.3 All other occupations 1,639 57.3 pational exposures began in the late Occupation not reported 102 3.6 1960’s and increased in 1973 when the Total 2,859 100.0 Fifth Circuit Court of Appeals applied strict liability in Borel v. Fibreboard Source: Multiple cause of death data from the National Center for Health Statistics Paper Prods. Corp. (493 F.2d 1076). In Note: U.S. residents age fifteen and over, selected states and years, 1990-1999. 1976, Congress passed the Toxic Sub-
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Ascites Bowker, Michael. Fatal Deception: The Untold Story of Asbestos—Why It Is Still Legal and Still Killing Us. Emmaus, Pa.: Rodale, 2003. Harris, L. V., and I. A. Kahwa. “Asbestos: Old Foe in Twenty-First Century Developing Countries.” Science of the Total Environment 307, nos. 1-3 (2003): 1-9. Institute of Medicine of the National Academies. Board on Population Health and Public Health Practices. Committee on Asbestos: Selected Health Effects. Asbestosis: Selected Cancers. Washington, D.C.: National Academies Press, 2006. Pass, Harvey I. One Hundred Questions and Answers About Mesothelioma. Sudbury, Mass.: Jones & Bartlett, 2004. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Eleventh Report on Carcinogens. Research Triangle Park, N.C.: Author, 2005. u
Other Resources
’Lectric Law Library A History of Asbestos Use and Asbestos Litigation http://www.lectlaw.com/files/med40.htm National Toxicology Program http://ntp.niehs.nih.gov An X ray of a lung showing cancer caused by asbestos. (James Cavallini/Photo Researchers, Inc.)
stances Control Act, which imposed regulations regarding asbestos, including a requirement that asbestos abatement occur in schools. The International Labour Organization’s Asbestos Convention of 1986 mandated that national laws should “prescribe the measures to be taken for the prevention and control of, and protection of workers against, health hazards due to occupational exposure to asbestos.” The widespread use of asbestos fibers in multiple applications means that exposure remains a concern in the twenty-first century. Although asbestos is no longer as widely used in industry, which has reduced exposure in the workplace, people still risk asbestos exposure when engaging in home improvement projects as they rip out old flooring or replace ceiling tiles. Christina J. Moose, M.A. u
For Further Information Bartrip, Peter. Beyond the Factory Gates: Asbestos and Health in Twentieth Century America. New York: Continuum, 2006.
See also Air pollution; Bronchoalveolar lung cancer; Cancer clusters; Carcinomatosis; Epidermoid cancers of mucous membranes; Free radicals; Head and neck cancers; Kidney cancer; Laryngeal cancer; Lung cancers; Mesothelioma; Occupational exposures and cancer; Risks for cancer; Sarcomas, soft-tissue; Statistics of cancer; Throat cancer; Urinary system cancers.
u Ascites Category: Diseases, symptoms, and conditions Also known as: Peritoneal cavity fluid or peritoneal fluid excess, hydroperitoneum, abdominal dropsy, peritoneal carcinomatosis, malignant ascites Related conditions: Late-stage cancer or liver disease, associated with ovarian, endometrial, breast, gastrointestinal (stomach, colon, pancreatic) cancer Definition: Ascites is an abnormal accumulation of excess fluid in the abdominal (peritoneal) cavity that causes swelling or bloating. In late-stage cancer, tumor cells may be isolated from the fluid. Ascites can also occur with liver disease. 105
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Risk factors: Ascites is not uncommon in cancer patients; 15 to 50 percent develop this condition at some time during their illness. Ascites is most common in patients with ovarian cancer but may also be present in patients with uterine, breast, colon, stomach, and pancreatic cancers. Liver involvement with cancer can increase the problem with ascites. Noncancerous conditions that can result in ascites include hepatitis, kidney failure, heart failure, and constrictive pericarditis (inflammation of the sac around the heart). Etiology and the disease process: A lining of tissue, the peritoneum, supports the organs in the abdomen and covers the peritoneal cavity. Normally a small amount of body fluid lubricates this cavity and is kept in correct proportion by a pressure gradient. The liver stores blood and fluid depending on the pressure in the venous and arterial blood system. Under normal conditions, the lymphatic system drains 80 percent of the peritoneal fluid, so minimal accumulation occurs. When pathological or disease conditions
occur, the fluid accumulates and edema settles in the peritoneal cavity. In malignant ascites, a tumor may obstruct the lymphatic system so that drainage cannot occur. Liver involvement can cause a backup of fluid into the peritoneal cavity. In severe cases of ascites, gallons of liquid can fill the peritoneal cavity, pressing on the diaphragm (the muscles that separate the chest from the abdomen and allow a person to breathe). Ascites is not actually a disease but a symptom of some pathological condition within the body. Some of the conditions that can result in ascites include cirrhosis of the liver (80 percent of ascites cases), pancreatic ascites, chylous ascites (a symptom of lymphoma), and cancer. Renal and endocrine ascites occur in rare instances. Incidence: Approximately 10 percent of all cases of ascites occur in cancer patients. As many as half of all cancer patients will experience ascites. About 30 percent of all ovarian cancer patients have ascites, with as many as 60 per-
Abdomen distended by ascites. (Custom Medical Stock Photo)
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Salem Health: Cancer cent presenting with ascites at death. Most cases result from disease that starts in the peritoneum or spreads from other body organs (metastasis). Symptoms: Mild ascites may not be noticeable or present any symptoms. As the disease progresses, the abdomen can become more distended and swollen to the point of discomfort and pain. The patient may experience a feeling of heaviness. The patient may have trouble sitting, walking, or moving around. Fluid buildup may cause indigestion, nausea, or vomiting. The patient may experience diminished appetite with weight loss and general fatigue. When the fluid becomes excessive, the patient may have weight gain and shortness of breath. Some patients complain of swelling in the legs and ankles or experience hemorrhoids. Changes may occur in the navel as fluid collects. The severity of symptoms depends on the progression of the disease.
Ashkenazi Jews and cancer the problem. Generally, unless the cause is corrected, the fluid will return after draining with paracentesis. In fact, rapid reduction through the draining of fluid can result in rapid reaccumulation of fluid. Removing more than five liters at one time can result in hypotension, shock, and death. Robert W. Koch, D.N.S., R.N. u
For Further Information Ginès, Pere, et al., eds. Ascites and Renal Dysfunction in Liver Disease: Pathogenesis, Diagnosis, and Treatment. 2d ed. Malden, Mass.: Blackwell Publishing, 2005. Hawkins, Rebecca. “Clinical Focus: Ascites.” Clinical Journal of Oncology Nursing 5, no. 1 (January/February, 2001).
u
Other Resources
Screening and diagnosis: Diagnosis is confirmed using a physical exam and patient history along with X rays, ultrasound, computed tomography, or paracentesis with fluid analysis (removing fluid through a thin needle into the abdomen). Simple measuring of abdominal girth can provide a baseline for continued assessment.
Cancer.Net Fluid in the Abdomen or Ascites http://www.cancer.net/patient/Diagnosis+and+ Treatment/Treating+Cancer/Managing+Side+Effects/ Fluid+in+the+Abdomen+or+Ascites+-+ASCO+ curriculum#mainContent idmainContent
Treatment and therapy: Treatment is targeted to the symptoms and to improve quality of life. One approach is to reduce sodium and fluid intake to decrease fluid buildup. Another is the use of diuretic drugs that promote removal of fluid through the kidneys as urination. Caution must be taken in the use of diuretics as the patient may experience hypovolemia (a drop in circulating blood volume through large loss of blood or fluid) with a severe drop in blood pressure or a potassium imbalance that can threaten the regular beat of the heart. If discomfort is severe, a therapeutic paracentesis can be performed by the health care provider. This procedure drains fluid from the abdomen through a thin needle inserted into the peritoneal cavity. This procedure is generally performed with a local anesthesia. Rarely, surgery to shunt the fluid away from the abdominal cavity (peritoneovenous shunt) or specific chemotherapy may help. Repeated paracentesis as can be tolerated by the patient may be the only effective approach long term. Few alternative or complementary approaches are effective for ascites. Diet can be modified to minimize sodium intake. The patient should consume potassium-rich foods such as low-fat yogurt, cantaloupe, or baked potatoes to assist with proper heart function.
MedlinePlus Ascites http://www.nlm.nih.gov/medlineplus/ency/article/ 000286.htm
Prognosis, prevention, and outcomes: The prognosis for ascites depends on the underlying cause and intensity of
See also Cytology; Gallbladder cancer; Gastrointestinal cancers; Hepatomegaly; Krukenberg tumors; Mesothelioma; Paracentesis; Peritoneovenous shunts; Ultrasound tests.
u Ashkenazi Jews and cancer Category: Social and personal issues Also known as: German or Eastern European Jews Definition: Although the major cancer risk factors in all populations are socioeconomic status, diet, lifestyles, and environment (which Jews in general share with other ethnic and racial groups), Ashkenazi Jews, originally from central, northern, and Eastern Europe, have some specific gene mutations that increase their susceptibility to certain forms of cancer. Description of the population: In the ninth or tenth century, Ashkenazi (meaning “German” in Hebrew) Jews began settling in northern France and western Germany. Toward the beginning of the sixteenth century, their com107
Ashkenazi Jews and cancer munity became centered in Poland-Lithuania. For centuries the religious and political isolation of the Ashkenazim (plural of Ashkenazi) within the larger host communities ensured their genetic purity, all the more so as they tended to intermarry. This means that the term “Jewish,” in addition to religious and cultural denotations, can also refer to a common biological background distinct from that of others. There are about 10 million Jews in the world, the majority of whom are Ashkenazi rather than Sephardic Jews. Sephardic Jews, also known as Spanish or Oriental Jews, hail from Spain, Portugal, and North Africa and are in a minority in the United States as in most parts of the world. Although American Jews, mostly Ashkenazim, are generally health conscious and respect medical science and its providers so that they tend to practice preventive health care, they are nevertheless more affected by certain disorders than members of other ethnic groups. Cancer researchers, starting in the 1990’s, began to discover that specific gene mutations leading to cancers of the breast, ovaries, colon, and rectum were more prevalent among Ashkenazi Jews than in the population at large. This suggested a genetic origin. Cancers of genetic origin: Ashkenazi Jews can trace their roots back to a small number of founders—several hundreds or thousands of them—who originally lived in a confined environment and tended to intermarry. Geneticists theorize that if even just a few of these founders had a gene mutation, this mutation would have been amplified in later generations of Ashkenazim, largely because of intermarriage. This theory is confirmed by the fact that people of Ashkenazi Jewish descent have a higher incidence of a number of specific mutations, including those that increase the risk of developing certain types of cancer. Such childhood neurological dysfunctions as Tay-Sachs disease and Bloom syndrome are caused by gene mutations and are more prevalent among Ashkenazi Jews. Breast and ovarian cancer: Isolated in 1994, BRCA1 is a major gene that, when one of its two copies is inherited in an altered form, predisposes individuals to breast (and ovarian) cancer. BRCA1 (for breast cancer 1) was found in 1 percent of the general Jewish population (mostly Ashkenazim) in the United States compared with 0.1 to 0.6 percent in Americans at large. Soon another breast cancer gene, BRCA2 (for breast cancer 2), was also discovered to have greater prevalence among the Ashkenazim, bringing the overall risk factor among them even higher. Three distinct mutations in the BRCA1 and BRCA2 genes were found in 1 out of 40 Ashkenazi Jewish women, increasing their odds of getting breast or ovarian cancer. When these 108
Salem Health: Cancer mutated genes are inherited from both parents rather than one, the risk of the disease is increased even further. Astudy by the Journal of the American Medical Association (JAMA) published in June, 2007, pointed out that in the case of breast cancer, the gene mutation may have originated from a woman’s father rather than from her female antecedents. Half of genetic mutations for breast cancer are inherited from a father, not a mother. However, unless the father has female relatives with breast cancer, the faulty gene may have passed down unnoticed and without causing cancer (because breast cancer among men is rare). Accordingly, when a woman has few aunts or older sisters, a gene mutation can hide in a family tree so that it appears that her breast or ovarian cancer struck out of nowhere when it really originated from a mutation handed down by her father. A woman with breast cancer who has a BRCA1 or BRCA2 gene mutation has a four times greater chance of developing cancer in the other breast and a ten times greater risk of developing ovarian cancer than a woman with breast cancer who has no BRCA gene alteration. This finding argues that women at greater risk, such as the Ashkenazim, should have genetic testing because three commonly used predictive methods do not accurately estimate the genetic breast cancer risk without a family history of such carcinomas. However, Orthodox Jewish rabbis may oppose genetic testing on the grounds that it might cause couples to refrain from marriage and procreation. It must be borne in mind, too, that the Ashkenazim, like others, are subject to breast cancer risks independent of genetic causes. Colorectal cancer: Ashkenazi Jews have a lifetime risk of colorectal cancer of 9 to 15 percent, one of the highest in the world, compared with 5 to 6 percent for non-Ashkenazi populations. Although rare in the general population, the A636P mutation is detected in up to 7 percent of Ashkenazi Jews with early-onset colorectal cancer. Hereditary nonpolyposis colorectal cancer (HNPCC) is a dominantly inherited syndrome attributable to mutations in one of several deoxyribonucleic acid (DNA) mismatch repair genes, most commonly MLH1 and MSH2. Although rare in the general population, among Ashkenazi Jews, the MSH2 mutation is found to a greater degree with early-onset colorectal cancer and may account for up to one-third of HNPCC. Pancreatic and other cancers: Pancreatic cancer is the most fatal of all gastrointestinal cancers. Its survival rate of only 1 to 3 percent in the West disproportionately affects the Ashkenazim. Approximately 5 to 10 percent of this cancer shows familial clustering, and there are no pan-
Salem Health: Cancer creatic cancer screening programs with acceptable sensitivity and specificity. Men who inherit the altered BRCA1 gene are slightly more at risk to experience prostate cancer as well. Similarly, carcinomas of the stomach and nonHodgkin lymphoma have a higher incidence among the Ashkenazim. Interpreting statistics: Although Ashkenazi Jews have one of the highest lifetime colorectal cancer risks of any ethnic group in the world, carcinoma of the uterine cervix occurs very infrequently among them, and lung cancer among the Ashkenazim is also low, probably because of decreased tobacco use. The interpretation of statistics that portray variations in the incidence of cancer in any ethnic or religious group, including Ashkenazi Jews, must be carefully evaluated in view of the greater picture. Peter B. Heller, Ph.D. u
For Further Information Brandt-Rauf, Sherry I., et al. “Ashkenazi Jews and Breast Cancer: The Consequences of Linking Ethnic Identity to Genetic Disease.” American Journal of Public Health 96, no. 11 (2006): 1979-1988. Goodman, Richard, and Arno G. Motulsky, eds. Genetic Diseases Among Ashkenazi Jews. New York: Raven Press, 1979. Kedar-Barnes, I., and P. Rozen. “The Jewish People: Their Ethnic History, Genetic Disorders, and Specific Cancer Susceptibility.” Familial Cancer 3, nos. 3/4 (2004): 193-199. Kolata, Gina. “Using Genetic Tests: Ashkenazi Jews Vanquish a Disease.” The New York Times, February 18, 2003, Sec. F, pp. 1, 6. Lippe, Scott D. “Ashkenazi Jews and Colon Cancer.” American Journal of Gastroenterology 94, no. 10 (1999): 3085. Locker, G. Y., and H. T. Lynch. “Genetic Factors and Colorectal Cancer in Ashkenazi Jews.” Familial Cancer 3, nos. 3/4 (2004): 215-221. Lynch, H. T., et al. “Cancer in Jews: Introduction and Overview.” Familial Cancer 3, nos. 3/4 (2004): 177192. _______. “Familial Pancreatic Carcinoma in Jews.” Familial Cancer 3, nos. 3/4 (2004): 233-240. Mahowald, Mary B. “Ethnicity, Cultural Differences, and Sex Selection.” In Genes, Women, Equality. New York: Oxford University Press, 2000. Vadlamani, Lalit, et al. “Colorectal Cancer in RussianSpeaking Jewish Emigrés: Community-Based Screening.” American Journal of Gastroenterology 96, no. 9 (2001): 2755-2760.
Asian Americans and cancer u
Other Resources
Genetics Home Reference http://ghr.nlm.nih.gov National Cancer Institute Cancer Risk in Ashkenazi Jews Who Carry a Specific Mutation in a Gene Previously Associated with Colon Cancer http://www.cancer.gov/newscenter/Ashkenaziestimating-risk-colon-QA See also BRCA1 and BRCA2 genes; Ethnicity and cancer; Family history and risk assessment; Fanconi anemia; Geography and cancer; Hairy cell leukemia; Pancreatic cancers; Rectal cancer.
u Asian Americans and cancer Category: Social and personal issues Definition: Cancer is one of the leading causes of death in Asian Americans. Cancer kills more Asian American women than women of any other ethnicity in the United States. Asian Americans have higher incidence and mortality rates for certain cancers, with wide disparities between Asian ethnic groups. Overall, there are disproportionately high rates of liver, breast, cervical, and lung cancer in the largest Asian American and Pacific Islander groups. Description of the population: There are approximately 11.9 million Asian Americans living in the United States, and more than twenty-five Asian ethnicities are represented. Asian Americans and Pacific Islanders refer to people who originate in many countries and represent myriad ethnicities. Major ethnic groups included by the U.S Census Bureau are Chinese, Japanese, Korean, Malayan, Mien, Cambodian, Indonesian, Burmese, Bhutanese, Bangladeshi, Filipino, Hmong, Sikh, Sri Lankan, Laotian, Pakistani, Nepalese, Thai, Vietnamese, Tongan, Samoan, Marianan, Guamanian, and Chuukese. Cancer statistics are very limited in some Asian American and Pacific Islander ethnic subgroups. In fact, many of the statistics represent cancer incidence and mortality only in Chinese, Vietnamese, Filipino, Korean, Japanese, Tongan, and Samoan peoples; national statistics on Mien and Hmong are scarce. Asian Americans and Pacific Islanders are considered a health disparity population, which is defined as “a population displaying a significant disparity in the overall rate of disease incidence, prevalence, morbidity, mortality or sur109
Asian Americans and cancer vival rates in the population as compared to the health status of the general population,” according to the Minority Health and Health Disparities Research and Education Act of 2000. Incidence, death, and survival statistics: Asian Americans and Pacific Islanders have the fourth highest incidence rates of cancer of all ethnicities (329.3 per 100,000 people for men and 263.9 per 100,000 for women). The most common cancers in Asian American and Pacific Islander women are breast (79.7 per 100,000), colorectal (32.1 per 100,000), and lung (26.9 per 100,000). The highest cancer incidences in Asian American and Pacific Islander men are prostate (79.8 per 100,000), lung (49.7 per 100,000), and colorectal (42.0 per 100,000). Vietnamese women have the highest rates of cervical cancer. The rates are not only the highest of all Asian American and Pacific Islander groups, but five times higher than the rates for white women. Vietnamese men
Cancer kills more Asian American women than women of any other ethnicity in the United States. (PhotoDisc)
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Salem Health: Cancer have incidence and death rates from liver cancer that are seven times higher than those of white men. Native Hawaiians have the second highest all-site cancer mortality (207.2 per 100,000), while African Americans have the highest rates (209.8 per 100,000). Asian American and Pacific Islander men and women have the highest incidence rates of stomach cancer (9.3 per 100,000 for women and 17.5 per 100,000 for men) and intrahepatic bile duct cancer (11.0 per 100,000 for women and 20.1 per 100,000 for men) of all ethnicities. Breast cancer is the leading cause of cancer deaths in Asian American and Pacific Islander women, and Koreans have the highest incidence and mortality from stomach cancer. Lung cancer rates are 18 percent higher for Southeast Asians than whites. Japanese have the highest incidence and mortality rates for stomach and uterine cancers, while Koreans have the lowest colorectal cancer screening rates. Hmong have elevated rates of multiple cancers, including liver, cervical, nasopharyngeal, leukemia, and nonHodgkin lymphoma. Risk statistics: Socioeconomic status, hepatitis B infection, tobacco use, language barriers, and low rates of participation in cancer screening are major challenges. Recent immigrants who are monolingual have difficulty accessing medical care. Further, the concept of disease prevention is alien to many who had limited or no access to medical care in their native countries. Most Asian American subgroups are diagnosed with cancer at a more advanced stage than whites. A cancer diagnosis is frightening for most people, regardless of ethnicity. Adding to the challenge in Asian American and Pacific Islander groups are cultural beliefs promoting fear of cancer. A cancer diagnosis can result in ostracism, loss of friendships, and being regarded as the carrier of bad luck. These common occurrences prevent many Asian Americans from seeking early medical attention and participating in cancer prevention screening. Smoking is relatively common in Asian Americans and Pacific Islanders (17.8 percent of men and 4.8 percent of women). Immigrants arrive in the United States with smoking habits in place. Social and work formalities override concerns about lung cancer. Also, commercial advertising for tobacco products is great in stores that serve a large Asian American and Pacific Islander customer base. Hepatitis B infection is widespread in China and Southeast Asia, so it is also present in immigrants from these areas. An infected person might not have symptoms for decades. Infection is most commonly transmitted at childbirth, when the infant is exposed to the infected mother’s
Salem Health: Cancer
Asian Americans and cancer
Top Ten Cancer Sites: Incidence and Death Rates for Asian Americans and Pacific Islanders, 2004 Incidence Cancer Site Prostate Female breast Lung and brochus Colon and rectum Corpus and uterus Liver and intrahepatic bile duct Stomach Non-Hodgkin lymphoma Thyroid Ovary
Rate per 100,000 People 79.8 79.7 36.7 36.4 15.6 13.5 12.8 11.9 9.1 8.7
Death Cancer Site Lung and brochus Female breast Prostate Colon and rectum Liver and intrahepatic bile duct Pancreas Stomach Ovary Non-Hodgkin lymphoma Leukemias
Rate per 100,000 People 26.3 12.6 11.4 11.2 10.2 7.7 7.0 4.6 4.5 3.8
Source: U.S. Cancer Statistics Working Group, United States Cancer Statistics: 1999-2004 Incidence and Mortality Web-Based Report (Atlanta: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute, 2007)
blood. Other routes of transmission include drug use (sharing needles) and tattoos. Although the hepatitis B vaccine is effective in preventing infection, in many Asian countries the vaccine is expensive and not always available at rural clinics. Very limited public health education exists in many Asian countries. People are unaware of the association between chronic hepatitis B infection and liver cancer and do not know that infection can be asymptomatic and that treatment is available. Asian American and Pacific Islander women have very low participation rates for mammography, Pap smears, and performance of breast self-exams. Participation has increased with awareness based on language-appropriate information regarding availability of Medicare coverage for screening, centers where native languages are spoken, and ways to prevent and detect cancer in its early stages. Perspective and prospects: Screening, early detection of cancer, and treatment are the core approach to dealing effectively with cancer, regardless of the person’s race or ethnicity. However, achieving this goal within myriad Asian American and Pacific Islander groups involves enormous complexity. Asian Americans born in the United States and those with higher levels of education and jobs providing medical insurance are more likely to be aware of and participate in prevention and early cancer screening practices. Hawaiians and Pacific Islanders have more dietary and obesity-related medical issues than Vietnamese and Chinese. Hmong and Mien communities maintain health beliefs that do not easily blend with West-
ern medicine. Physical isolation and language barriers among immigrants are persistent challenges. Modifiable behaviors and factors that lead to higher rates of certain cancers in Asian American and Pacific Islander communities include hepatitis B infection (liver cancer), tobacco use (lung and bronchial cancers), and low participation in cancer screenings such as Pap smears (cervical cancer), mammography testing (breast cancer), and fecal occult blood testing, colonoscopy, and bariumcontrast X ray (colorectal cancer). High-fat diets, certain environmental exposures including radiation, and genetic factors also are known to increase the risk of certain cancers. Organizations such as the Asian American Network for Cancer Awareness, Research and Training (AANCART), have been major sources of data on cancer incidence and mortality in specific Asian American communities. Clearly, health education that is culture- and languageappropriate plays a major role in prevention and early detection of cancer in all Asian American communities. Distrust of Western medicine is a major barrier in Hmong and some other groups. Language-appropriate materials stressing mammograms, fecal occult blood tests, prostatespecific antigen (PSA) tests, and Pap testing must be widely distributed within Asian American communities, followed up by health workers who are able to explain the role of screening and early detection. There are no studies indicating that Asian Americans have a genetic predisposition for any particular cancer. Therefore, economic and cultural disparities are the main issues facing anyone 111
Astrocytomas
Salem Health: Cancer
intent on lowering cancer rates in these communities. Bilingual community health workers have had success in reaching many immigrant populations. University medical centers and public health departments in cities with large Asian American communities have been addressing specific issues such as hepatitis B antigen/antibody screening, identification and treatment of individuals with chronic hepatitis B, Vietnamese-language cervical cancer screening programs, and antismoking programs. The greatest challenge continues within monolingual communities. Janet R. Green, M.S.P.H. u
For Further Information Haynes, M. Alfred, and Brian D. Smedley, eds. The Unequal Burden of Cancer: An Assessment of NIH and Research Programs for Ethnic Minorities and the Medically Underserved. Washington, D.C.: National Academy Press, 1999. Smedley, Brian D., Adrienne Y. Steth, and Alan P. Nelson eds. Unequal Treatment: Confronting Racial and Ethnic Disparities in Health Care. Washington D.C.: National Academy Press, 2003. Wong, S. T., et al. “Disparities in Colorectal Cancer Screening Rates Among Asian Americans and NonLatino Whites.” Cancer 104, no. 12 (2005): S2,940S2,947. u
Stanford School of Medicine—Asian Liver Center http://liver.stanford.edu Vietnamese Community Health Promotion Project— University of California, San Francisco http://www.suckhoelavang.org/main.html See also Chewing tobacco; Choriocarcinomas; Ethnicity and cancer; Krukenberg tumors; Statistics of cancer; Stomach cancers.
u Astrocytomas Category: Diseases, symptoms, and conditions Also known as: Gliomas Related conditions: Primary brain tumors Definition: Astrocytomas, the most common gliomas, are primary malignant brain tumors that can occur in most parts of the brain and occasionally in the spinal cord. As the name implies, astrocytomas are derived from astrocytes—nonneural support cells of the central nervous system. The types of astrocytomas based on clinical pathology include pilocytic astrocytoma, fibrillary astrocytoma, anaplastic astrocytoma, and glioblastoma multiforme. Because astrocytomas are primary brain tumors formed in the brain, they rarely spread to other parts of the body;
Other Resources
American Cancer Society http://www.cancer.org Asian American Cancer Support Network http://www.aacsn.org Asian American Network for Cancer Awareness, Research and Training (AANCART). http://www.aancart.org Asian American Pacific Islander Health Foundation http://www.apiahf.org Centers for Disease Control and Prevention Highlights in Minority Health and Health Disparities http://www.cdc.gov/omhd National Cancer Institute SEER Cancer Statistics Review 1975-2005 http://seer.cancer.gov/csr/1975_2005 112
An MRI of the brain of a man with a cerebellar glioma. The tumor appears in bright contrast to the surrounding brain tissue. (Simon Fraser/Photo Researchers, Inc.)
Salem Health: Cancer however, they usually grow rapidly and invade surrounding normal brain tissue and therefore are life-threatening. Risk factors: Brain tumors are caused by mutated or missing genes that result in abnormal cells. High-dose ionizing radiation used over time to treat brain tumors may on occasion cause secondary tumors. Exposure to certain chemicals such as pesticides, petrochemicals, and formaldehyde, and to electromagnetic fields over time increase the risk of developing astrocytomas. Etiology and the disease process: Generally, malignant brain tumors are caused by changes in genetic structure due to inherited or environmental factors. It was thought that only 5 percent of primary brain tumors, including astrocytomas, are inherited; however, one study has shown that 80 percent of patients with grade IV astrocytoma (glioblastoma multiforme) had anomalous copies of chromosome 7. Familial clustering of gliomas is also associated with defined inherited tumor syndrome, including Li-Fraumeni syndrome, Turcot syndrome, and the neurofibromatosis I syndrome. Incidence: Gliomas of both benign and malignant tumors account for 45 to 50 percent of all primary brain tumors; grade I and II astrocytomas account for 25 to 30 percent of all gliomas. Approximately 13,000 people in the United States die of malignant brain tumors every year, which represents about 2 percent of all cancer-related deaths. Symptoms: Various symptoms may occur with astrocytomas, which depend largely on the location and size of the tumor. Seizure, focal neurologic deficits such as weakness or speech problems, and headaches are common symptoms. The headaches that are associated with brain tumors are typically worse in the morning and accompanied by vomiting. Sometimes increased pressure on the brain tissue can cause blurred, double, or even loss of vision. Behavioral changes may also follow with changes in mood and general state of well-being. Screening and diagnosis: Methods of screening and diagnosing astrocytomas include computed tomography (CT) scans, magnetic resonance imaging (MRI), angiograms, X rays of the head and skull, and biopsies. Other brain scans, such as magnetic resonance spectroscopy (MRS), single-photon emission computed tomography (SPECT), or positron emission tomography (PET), provide a gauge of brain activity and blood flow. Brain tumors are graded based on the following criteria: mitotic index (growth rate), vascularity (blood supply), presence of necrotic center, invasive potential (border distinctness), and similarity to normal cells.
Astrocytomas
Relative Survival Rates for Astrocytomas, 1988-2001 Years 1 2 3 5 8 10
Survival Rate (%) 62.3 48.4 42.7 35.8 30.7 27.8
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007)
Accordingly, astrocytomas can be graded into four levels. Pilocytic astrocytoma are grade I tumors that are slow growing and do not invade the surrounding normal tissue, and are commonly diagnosed in children and young adults. Low-grade astrocytomas, including fibrillary or protoplasmic astrocytomas, are grade II tumors that grow slightly faster than grade I tumors and are invasive, with high incidence in the cerebrums of young adults and in the brain stems of children. Anaplastic astrocytomas are grade III, malignant and invasive tumors that occur in the same location as the low-grade astrocytomas and have a high recurrence rate. Glioblastomas multiforme are grade IV, a malignant type that is by far the most common glioma: Approximately 50 percent of astrocytomas are glioblastomas. The common sites of tumors are cerebral hemispheres in adults and the brain stem in children, and they typically contain more than one cell type. Treatment and therapy: Treatment options differ according to size, grade, and location of the tumor. Tumors may be removed by craniotomy, an open-skull procedure. They may also be removed by ultrasonic aspiration, in which ultrasonic waves fragment the tumors, which are then aspirated. Alternatively, stereotactic radiosurgery may be performed with a Gamma Knife on benign, malignant, or metastatic tumors that are around 4 centimeters (cm) in size. Chemotherapy may be used as a primary therapy in young children or as an adjuvant after tumor removal with radiosurgery. For pilocytic and fibrillary astrocytomas, complete resection of the tumor is achieved; however, if excision is not possible because of the tumor’s location, chemotherapy is indicated in young children and radiotherapy in adults. The treatment options for anaplastic astrocytoma and glioblastoma multiforme include total re113
Ataxia telangiectasia (AT) section followed by radiotherapy and chemotherapy after surgery. Prognosis, prevention, and outcomes: The prognosis and outcome of astrocytomas largely depend on the age of the patient, histological features of the tumor, and degree of neurologic or functional impairment. In low-grade astrocytomas, the mean survival time after surgery is six to eight years with the prognosis depending on whether the tumor undergoes progression to a malignant phenotype. Complete recovery is possible in pilocytic astrocytoma if total resection is achieved, while fibrillary astrocytomas show frequent recurrence. In patients with anaplastic astrocytomas and glioblastoma multiforme, the extent of resection is a prognostic factor; generally, younger patients below the age of forty-five have a better prognosis. Bagirathy Ravishankar, Ph.D. u For Further Information Arjona, D., et al. “Early Genetic Changes Involved in Low-Grade Astrocytic Tumor Development.” Current Molecular Medicine 6 (September, 2006): 645-650. Compostella, A., et al. “Prognostic Factors for Anaplastic Astrocytomas.” Journal of Neuro-Oncology 81 (February, 2007): 295-303. Miller, C. R., and A. Perry. “Glioblastoma.” Archives of Pathology and Laboratory Medicine 131 (March, 2007): 397-406. Robins, H. Ian, et al. “Therapeutic Advances for Glioblastoma Multiforme: Current Status and Future Prospects.” Current Oncology Reports 9, no. 1 (2007): 66-70. Szeifert, G., et al. “The Role of the Gamma Knife in the Management of Cerebral Astrocytomas.” Progress in Neurological Surgery 20 (2007): 150-163. u
Other Resources
Mayo Clinic Gliomas http://www.mayoclinic.org/glioma/astrocytomas.html Neurosurgery Today Astrocytoma Tumors http://www.neurosurgerytoday.org/what/patient_e/ tumors.asp See also Brain and central nervous system cancers; Cell phones; Craniotomy; Gamma Knife; Gliomas; Oligodendrogliomas; Spinal axis tumors.
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u Ataxia telangiectasia (AT) Category: Diseases, symptoms, and conditions Also known as: A-T, Louis-Bar syndrome, BoderSedgwick syndrome Related conditions: Nijmegen breakage syndrome Definition: Ataxia telangiectasia (AT) is a rare primary immunodeficiency disease that causes ataxia (Greek for “lack of order”), or uncoordinated movements. This symptom is caused by dysfunction of the central nervous system that coordinates movement. Telangiectasias are small, red spider veins caused by dilation of blood vessels. In AT these appear in the eyes, cheeks, and other skin surfaces. Risk factors: AT is caused by mutations in the ATM gene (ataxia telangiectasia, mutated) located on chromosome 11q22-23, which codes for a 370kDa protein kinase. The ATM gene is 150kb with 66 exons. Etiology and the disease process: The ATM protein kinase responds to double-stranded deoxyribonucleic acid (DNA) breaks, by autophosphorylation to an active form. This active ATM kinase is involved in the assembly of a multiprotein complex that helps the cell respond to DNA damage. ATM is also involved in triggering the accumulation of the tumor-suppressor protein p53 that is a master control switch to prevent cells from dividing. If the ATM protein is lacking, there is a delay in the accumulation of p53, so the cell continues to divide without DNA repair and increases the chances of mutations leading to cancer. Incidence: AT is a rare recessive genetic disease with an incidence of 1 in 40,000 to 1 in 100,000. Symptoms: AT symptoms include neurodegeneration, causing uncoordinated movements; immunodeficiency, such as a lack or reduced level of immunoglobulin A (IgA), immunoglobulin E (IgE), and immunoglobulin G2 (IgG2); extreme sensitivity to ionizing radiation; and an increased risk of cancer. Telangiectasias are not always present. Those with AT have frequent sinus and respiratory infections and can have recurring severe lung infections. The neurological problems result in delayed development of motor skills and poor balance, which are typically noted by two years of age. As the neurological degeneration continues, with progressive loss of muscle control, patients usually require a wheelchair for mobility in their teenage years. Slurred speech is generally present by age ten. AT patients also may have mild diabetes mellitus, premature gray hair, difficulty swallowing, and de-
Salem Health: Cancer layed physical and sexual development. Their intelligence quotient (IQ) is normal. People with AT have an increased risk of developing cancer, especially leukemia and lymphoma. Other cancers, such as stomach, brain, ovary, skin, liver, larynx, and breast, are also associated with AT. Screening and diagnosis: Ataxia, uncoordinated movements, is typically the symptom noted first. Telangiectasia may or may not be observed. Lab tests show a low lymphocyte count, especially of T and B lymphocytes. A screen of serum immunoglobulins may show low levels of IgA, IgG2, immunoglobulin G4 (IgG4), and IgE. Magnetic resonance imaging (MRI) and computed tomography (CT) scans may show cerebellar atrophy. Those with AT also have elevated levels of alpha-fetoprotein and carcinoembryonic antigen in the serum. The size of the thymus may be examined by X rays. A molecular diagnosis of AT includes sequencing of the ATM gene or examining closely linked markers if there is a family history of the disease. A test of protein function or a cytogenetic test to look for specific breakpoints can also be done. Treatment and therapy: There is no specific treatment for AT; rather the specific symptoms are treated. Antibiotics are given to control infections. Gamma-globulin injections can help the dysfunctional immune system. Physical, occupational, and speech therapy can be of benefit. Because of the sensitivity to ionizing radiation, AT patients with cancer should not receive radiation therapy. They should not have unnecessary X rays for screening tests. Prognosis, prevention, and outcomes: There is no cure for ataxia telangiectasia. Life expectancy varies, but often those with AT die in their twenties, although some live to their forties. Almost half of AT deaths are due to lung infections. If the frequent infections can be controlled, about 20 percent of those with AT die from cancer. About 28 percent of AT deaths are due to both pulmonary infections and malignancies. The parents of an AT child can have molecular diagnoses to assess their risk of having another child with AT. If both parents are carriers of a mutated ATM gene, there is a 25 percent risk of having a child with AT. Prenatal testing can be done to determine if the fetus has AT. There are suggestions that those who are carriers of a mutant ATM gene may be at a greater risk of developing cancers, especially leukemia and lymphoma, so more frequent cancer screenings may be beneficial to carriers. There is evidence that ATM mutations are breast cancer susceptibility alleles. AT is a rare disease, but the study of the ATM gene has led to a better understanding of how the cell responds to double-stranded DNA damage. Susan J. Karcher, Ph.D.
Autologous blood transfusion u
For Further Information Ahmed, M., and N. Rahman. “ATM and Breast Cancer Susceptibility.” Oncogene 25 (2006): 5906-5911. Andreassen, C. N. “Can Risk of Radiotherapy-Induced Normal Tissue Complications Be Predicted from Genetic Profiles?” Acta Oncologica 44 (2005): 801-815. Lavin, M. F., and S. Kozlov. “ATM Activation and DNA Damage Response.” Cell Cycle 6, no. 8 (2007): 931942. Lee, Y., and P. J. McKinnon. “Responding to DNA Double Strand Breaks in the Nervous System.” Neuroscience 145 (2007): 1365-1374. McKinnon, P. J. “ATM and Ataxia Telangiectasia.” EMBO Reports 5 (2004): 772-776. Niida, H., and M. Nakanishi. “DNA Damage Checkpoints in Mammals.” Mutagenesis 21 (2006): 3-9. Shiloh, Y. “The ATM-Mediated DNA-Damage Response: Taking Shape.” Trends in Biochemical Sciences 31 (2006): 402-410. u
Other Resources
National Cancer Institute Ataxia Telangiectasia: Fact Sheet http://www.cancer.gov/cancertopics/factsheet/ ataxiaqa National Institute of Neurological Disorders and Stroke Ataxia Telangiectasia Information Page http://www.ninds.nih.gov/disorders/a_t/a-t.htm See also Family history and risk assessment; Genetic testing; Nijmegen breakage syndrome.
u Autologous blood transfusion Category: Procedures Also known as: Preoperative autologous blood donation (PABD), intraoperative blood salvage, postoperative blood salvage, acute normovolemic hemodilution (ANH) Definition: Autologous blood transfusion is the collecting and reinfusing of a patient’s own blood. Collection is done before surgery and/or during or after the surgical procedure. Cancers treated: All types of cancer, based on the physician’s decision Why performed: Autologous blood transfusion is performed to replace blood lost as a result of surgery. 115
Axillary dissection Patient preparation: A physician evaluates the patient to determine whether autologous transfusion is appropriate. The decision is based on established standards. The criteria that the physician uses include the likelihood of the patient needing blood during or after surgery, the type of cancer, and other medical conditions that the patient has. There must also be an autologous donor/transfusion program available to the patient, adequate time to collect blood prior to surgery, and equipment available for the collection and reinfusion of blood during surgery. Steps of the procedure: The physician writes an order for autologous transfusion. For preoperative autologous blood donation (PABD), the patient donates one or more units of blood at a blood donor center. The donor center staff attaches special labels to the unit of blood indicating it is for a specific patient. Blood collected prior to surgery is stored for up to forty-two days, separately from other blood. Two systems are available for the collection and reinfusion of blood during surgery. One system is semiautomated: Blood is collected, washed, and transfused to the patient. The other system is a suction system that collects the blood and returns it to the patient without washing. The patient is constantly monitored by anesthesia staff. In acute normovolemic hemodilution, blood is removed, and, at the same time, a solution to maintain fluid volume is infused. The blood is collected into blood bags and may be stored for up to twenty-four hours if properly refrigerated. The patient is monitored by anesthesia staff during surgery and by nursing staff after surgery. Postoperative blood salvage is not usually used for cancer patients. After the procedure: Following the donation of blood prior to surgery, the donor center staff gives the patient refreshments and observes the patient for any signs of an adverse reaction. During and following the transfusion of autologous blood, anesthesia staff or a nurse monitors the patient for any signs of an adverse reaction. Risks: The risks of PABD are infusion of the wrong unit of blood, which is very low. The risks of intraoperative blood salvage include reinfusing cancer cells and the reduction of platelets and other clotting factors. The risks of acute normovolemic hemodilution include a reduction of hemoglobin and oxygen-carrying capacity and the dilution of clotting factors. Results: Ideally, autologous blood transfusion results in a decrease in blood loss and a better surgical outcome. Wanda E. Clark, M.T. (ASCP) See also Transfusion therapy. 116
Salem Health: Cancer
u Axillary dissection Category: Procedures Also known as: Axillary lymph node dissection Definition: Axillary dissection is a surgical procedure carried out to remove and examine underarm lymph nodes through an incision in the armpit region (axilla). Cancers treated: Carcinoma of the breast, melanoma Why performed: For persons with operable breast cancer or melanoma, axillary dissection is used to determine whether cancer has spread beyond the primary tumor. Because these primary tumor cells usually infiltrate axillary lymph nodes before invading distant organs, physicians recommend that nodes be removed and examined histologically for the absence or presence of malignant cells. The results will guide the treatment course. Patient preparation: A few days before surgery, the patient undergoes a blood test, chest X ray, and electrocardiogram in order to assess general health. To avoid excessive bleeding, any blood-thinning medications are usually suspended at this time. Patients are cautioned not to eat or drink in the eight hours before surgery and, on admission to the hospital, are asked to sign an informed consent form. Steps of the procedure: The operation, performed under general anesthesia, lasts up to two hours. The surgeon makes an incision under the arm and removes a section of fat that contains a cluster of lymph nodes. The incision is sutured, and a drain is generally inserted to remove excess fluid. After the procedure: Most patients remain in the hospital overnight, longer if complications develop. Nurses monitor the patient until the anesthetic wears off and vital signs stabilize. The drain may be left in place until the first follow-up visit. Postoperative measures include medication to relieve pain, preventive care to avoid infection at the incision site, the use of compression bandages to reduce fluid retention, and stretching exercises to rehabilitate arm movement. No heavy lifting is allowed during the recovery period of up to six weeks. Risks: The most common complications of axillary dissection are numbness under the arm, swelling of the arm (lymphedema) with feelings of tightness and reduced range of motion, and infection at the incision site. Results: Before proceeding with an axillary dissection, the surgeon may decide to biopsy the sentinel lymph node (the very first node that drains fluid from the tumor). If no cancer cells are found, then no other nodes or only a few
Salem Health: Cancer adjacent key nodes are removed. If tumor cells are detected, however, then a more extensive axillary dissection is performed to excise six to ten nodes or more. The greater the number of cancerous nodes, the less favorable is the prognosis for survival. Anna Binda, Ph.D. See also Breast cancers; Cutaneous breast cancer; Lobular carcinoma in situ (LCIS); Lumpectomy; Lymphedema; Mastectomy; Melanomas; Mucinous carcinomas; Sentinel lymph node (SNL) biopsy and mapping.
u Azathioprine Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1985 Also known as: Azasan, Imuran Related cancers: Non-Hodgkin lymphoma, cancers of the skin and liver Definition: Azathioprine is a drug prescribed for transplant patients and those whose immune systems attack their own tissues, but long-term usage causes cancer. Exposure routes: Ingestion, intravenous injection, and inhalation Where found: The drug is found in hospitals, used for transplant and autoimmune disease patients, and in manufacturing plants that make and package the drug. At risk: Patients who take azathioprine and workers who manufacture it. Etiology and symptoms of associated cancers: In the liver, azathioprine is converted to 6-mercaptopurine, which inhibits deoxyribonucleic acid (DNA) synthesis. This suppresses the immune system but can also cause a dangerous decrease in the number of white blood cells (leukopenia)
Azathioprine and platelets (thrombocytopenia), increased risk of infection and bleeding, gastrointestinal disturbances, and liver damage. The substance 6-mercaptopurine also inserts between adjacent nucleotide bases in DNA molecules and causes mutations that lead to various types of cancer. Azathioprine increases the risk of developing squamous cell carcinoma, a type of skin cancer that appears as persistent wartlike growths, scaly patches, or open sores that crust over and bleed; non-Hodgkin lymphoma, a blood-based cancer of white blood cells called T cells, the most common symptoms of which are painless swelling of the neck, or underarm lymph nodes, unexplained fever, loss of weight and appetite, itchy skin with reddened patches, and constant fatigue; and cancer of the bile ducts or hepatobiliary carcinomas, whose symptoms include jaundice, itching, stomach pain, weight loss, and fever. History: The pioneer of liver transplantation, Sir Roy Yorke Calne, first used azathioprine to prevent organ rejection in liver transplant patients. Azathioprine was the standard antirejection drug in the 1970’s for organ transplants and was later enlisted to treat patients who suffer from diseases that result when the immune system attacks the patient’s own body (autoimmune diseases). Several epidemiological studies have shown that transplant patients who took azathioprine were at a high risk for different types of tumors. Other patients who took azathioprine but were not transplant patients, including those with rheumatoid arthritis, systemic lupus, inflammatory bowel disease, and certain skin and renal diseases, have also shown higher incidences of such malignancies, but not as high as those observed in transplant patients, since the dosages to treat autoimmune diseases are lower than those used for transplant patients. Mycophenolate mofetil, which is not as carcinogenic, is gradually replacing azathioprine as the antirejection drug of choice. Michael A. Buratovich, Ph.D. See also Crohn disease; Myasthenia gravis; Pancolitis.
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Bacillus Calmette Guérin (BCG)
u Bacillus Calmette Guérin
(BCG) Category: Chemotherapy and other drugs ATC code: 103AX03 Also known as: BCG Live, Pacis BCG Live, TICE BCG Definition: Bacillus or bacille Calmette Guérin (BCG) solution is an immunotherapeutic agent containing live, weakened bacteria. It is currently approved by the U.S. Food and Drug Administration (FDA) as a primary therapy for carcinoma in situ of the urinary bladder. The BCG solution for bladder cancer contains water, saline, and a freeze-dried and live (but avirulent) strain of Mycobacterium bovis, an organism that causes tuberculosis in cattle. The BCG vaccine is used throughout the world to immunize humans against tuberculosis, with varying rates of efficacy; the BCG vaccine is not routinely administered in the United States. BCG is named for the two Pasteur Institute researchers who discovered the vaccine against human tuberculosis: physician Léon Charles Albert Calmette (1863-1933) and bacteriologist Jean-Marie Camille Guérin (1872-1961). Cancers treated: Superficial or early-stage bladder cancer in which tumors have not entered the muscle layer of the bladder wall Delivery routes: Instillation How this substance works: Generally BCG treatment follows surgery to remove tumors from the surface (epithelium) of the inside of the bladder (lumen). A health care provider inserts a catheter to deliver the BCG solution to the bladder. The solution remains in the bladder for at least two hours. The millions of M. bovis bacteria in BCG solution stimulate the immune system to seek out and destroy cancer cells. Patients usually have a series of weekly instillations over a number of months followed by maintenance instillations, depending on the treatment plan. The exact mechanism of action of the BCG solution is unknown. It is thought that certain proteins in the bacteria adhere to the urothelium or lining of the bladder wall. The urothelium then releases a number of cytokines or inflammatory substances that alert the immune system that a pathogen is present. The bacteria may also enter the cancer cells and break down proteins to display on the cancer cell surface, thus flagging it for destruction by the immune system. Approximately 70 percent of patients respond to initial treatment, and 75 percent of those patients remain free of 118
Salem Health: Cancer bladder cancer for more than five years. Because BCG contains live bacteria, patients with compromised immune systems should not be treated with BCG solution. Patients should also not take antibiotics, which would kill the live bacteria and prevent effective treatment. Side effects: Most patients (80 to 90 percent) who receive successive treatments with BCG solution experience one or more side effects, including the urgent need to urinate, blood in the urine, pain during urination, fatigue, nausea, chills, and a low-grade fever that lasts twenty-four to seventy-two hours. Pamela Richardson, M.S. See also Biological therapy; Bladder cancer; Immunocytochemistry and immunohistochemistry; Immunotherapy.
u Bacteria as causes of cancer Category: Carcinogens and suspected carcinogens Also known as: Helicobacter pylori, Salmonella typhi, Streptococcus bovis, Chlamydophila (previously Chlamydia) pneumoniae Related cancers: Gastrointestinal cancers, lung cancer Definition: Although no bacterium has been shown to be absolutely responsible for causing cancer, very strong evidence implicates two types of bacteria in the process of cancer formation, and less convincing evidence implicates others. Each of these types of bacteria has been shown to cause a persistent (chronic) infection in which the organisms are in contact with the tissue over a long period of time. During that time, genes for cell division and other cell maintenance functions, the same ones that are damaged by other known chemical and physical carcinogens, are damaged by the metabolic and toxic products produced by these bacteria. Equally important are immune system defenses and additional genetic and environmental factors that make only certain individuals susceptible to these organisms. The two types of bacteria are Helicobacter (associated with gastric cancer) and Salmonella typhi (gallbladder cancer). Additional bacteria probably associated with different cancers include Streptococcus bovis (colorectal cancer), Chlamydophilia pneumoniae (lung cancer), strains of Escherichia coli (colorectal cancer associated with Crohn disease and ulcerative colitis), and different types of oral streptococci (oral cancers). Exposure routes: Ingestion and inhalation Where found: Infected and uninfected persons carrying certain bacteria; contaminated water, air, and surfaces
Salem Health: Cancer At risk: Genetically susceptible individuals specific to each type of bacteria Etiology and symptoms of associated cancers: Cancer caused by H. pylori is characterized by tumors in the protective layer of mucus in the stomach, including the immune tissue. Continued high incidence of stomach cancer in areas of Asia suggests that a diet high in salted, smoked, and pickled foods is a contributory factor. Transmission of H. pylori is thought to be by the fecal-oral route. The second strongest case for bacterial causation of cancer involves S. typhi and its role in causing cancer of the gallbladder. It has been known since the famous case of Typhoid Mary that survivors (or carriers without symptoms) of typhoid fever carry S. typhi for at least a year and can transmit the pathogen in their feces. The organism resides in the gallbladder during that entire time, thus fulfilling one of the conditions necessary to cause cancer (long exposure). Cancer formation in the gallbladder is frequently associated with gallstone formation (solid deposits of cholesterol or calcium salts). Symptoms that may indicate a diseased gallbladder include chronic indigestion, upper abdominal pain, nausea and vomiting, and fever. All of these symptoms may also be associated with additional gastrointestinal problems, so they are not definitive for gallbladder problems, including gallbladder cancer. Associated risk factors include cholelithiasis (especially untreated symptomatic chronic gallstones), obesity, reproductive factors, environmental exposure to toxic chemicals, congenital malformation of bile ducts, and chronic infections affecting the gallbladder. The most significant risk factor for those cancers associated with S. typhi appears to be chronic infection of the gallbladder. Data show that patients with chronic infections with this organism are eight times more likely to have cancer of the gallbladder than those who had acute infections in which the organisms were cleared from their body. Genetic susceptibility of American Indians and Mexican Americans, especially women (in all populations), to gallbladder cancer suggest that these groups are predisposed to develop it primarily or secondarily due to an increased incidence of cholesterol gallstones. A secondary pathway of cancer development revolves around congenital malformation of the bile duct, and is seen primarily in people from Japan, Korea, and possibly China. History: The first indication that a relationship existed between bacteria and cancer occurred in 1951, when researchers found that patients frequently had both infective endocarditis (infection of the heart) and colonic carcinoma. It took until 1974 to identify S. bovis as the bacte-
Bacteria as causes of cancer rium associated with the colonic cancer and bacteremia (bacteria in blood). It is known today that S. bovis is a natural inhabitant of the human gastrointestinal tract and causes both endocarditis and bacteremia. Patients having colon carcinoma frequently also harbor S. bovis, and these cancerous lesions may develop years after having endocarditis or bacteremia. Further research has focused on the bacteria naturally found in the gastrointestinal tract and their ability to metabolize nutrients into carcinogens. Experiments done using gastrointestinal flora from rats determined that metabolic products are mutagenic (cause mistakes in deoxyribonucleic acid, or DNA). The fact that germ-free rats did not develop tumors as frequently as normal animals was also significant in defining the relationship between diet and gastrointestinal flora. Data from later experiments have suggested that the presence of microorganisms as a causative agent for cancer formation may be more complicated than first thought. Conflicting reports suggest that the presence of H. pylori is both detrimental and beneficial in the development of esophageal cancer. The ability to use the presence of microorganisms as an indication that cancer may also be present (in situations in which the cancer is not easily diagnosed at an early stage) is being examined. This is the case with oral tumors and specific oral bacteria. Therefore, the precise relationship between microorganisms and different types of cancer is still unclear and remains to be determined. Steven A. Kuhl, Ph.D. u
For Further Information Hope, Mari, et al. “Sporadic Colorectal Cancer: Role of the Commensal Microbiota.” FEMS Microbiology Letters 244 (2005): 1-7. Lax, Alistair, and Warren Thomas. “How Bacteria Could Cause Cancer: One Step at a Time.” Trends in Microbiology 10 (2002): 293-299. Mager, Dixie. “Bacteria and Cancer: Cause, Coincidence, or Cure? A Review.” Journal of Translational Medicine 4 (2006): 14.
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Other Resources
Centers for Disease Control and Prevention Helicobacter pylori http://www.cdc.gov/ncidod/aip/research/hp.html National Cancer Institute H. pylori and Cancer: Fact Sheet http://www.cancer.gov/cancertopics/factsheet/ HPylori 119
Barium enema
Salem Health: Cancer
See also Achlorhydria; Alcohol, alcoholism, and cancer; Diverticulosis and diverticulitis; Esophagitis; Ethnicity and cancer; Helicobacter pylori; Infectious cancers; Mucosa-associated lymphoid tissue (MALT) lymphomas; Poverty and cancer; Prostatitis; Risks for cancer; Stomach cancers; Virus-related cancers.
u Barium enema Category: Procedures Also known as: Lower gastrointestinal (GI) series, single-contrast barium enema, double-contrast barium enema, air contrast barium enema Definition: A barium enema involves the insertion of barium sulfate, a radiopaque contrast medium, into the colon, the first section of the large intestine. This procedure is used with X rays as a diagnostic and screening test for colon cancer, colorectal cancer, and colon polyps, growths that are sometimes a precursor to colon cancer.
A barium enema is an outpatient procedure that is performed at a hospital radiology department or an outpatient radiology center. A barium enema does not require anesthesia, and patients are awake. A single-contrast barium enema takes about forty-five minutes, and a doublecontrast study takes about an hour to complete. Patients disrobe and wear an examination gown for the procedure. Steps of the procedure: Patients lie on an X-ray table. An X ray is taken before the barium is inserted. Patients lie on their side for the barium insertion process. Awell-lubricated plastic tube is gently inserted through the anus and into the rectum. Barium is slowly poured through the tube to fill the colon. The barium is monitored on a barium fluoroscope monitor. A balloon at the end of the enema tube is inflated to keep the barium in the colon. Patients may receive medication to relieve cramping. X rays are taken from a variety of angles. Patients are asked to change positions, and the X-ray table may be tilted. Pressure may be applied to the patient’s abdomen to help move the barium through the colon.
Cancers diagnosed: Colon cancer, colorectal cancer, colon polyps Why performed: A barium enema with X rays is used to screen for and help diagnose colon cancer, colorectal cancer, and colon polyps. The American Cancer Society recommends screening beginning at the age of fifty, earlier for people with risk factors. Barium sulfate shows up on X rays and highlights the shape of the colon better than X rays alone. A single-contrast barium enema uses barium sulfate that is inserted into the colon. A double-contrast barium enema involves inserting barium into the colon, emptying the colon, and then expanding the colon with air. The barium remains on the lining of the colon, and the air expands the folds of the colon to allow a better view. Patient preparation: Patients consume a clear liquid diet for one to three days before the test. Patients are instructed to consume large amounts of water and to use laxatives and enemas on the day before the test. An enema may be repeated on the day of the test to make sure the bowel is clear of stool and gas. For women, a pregnancy test may be used to ensure that the patient is not pregnant. Patients should tell their doctor if they have a latex allergy. 120
An X ray of the abdomen (frontal view), showing cancer of the left descending colon, after a barium enema. (©ISM/Phototake—All rights reserved)
Salem Health: Cancer At the end of the procedure, the enema tube is gently removed. Patients empty the barium from the colon by using a bedpan or going to the bathroom. After the barium is removed, a few final X rays are taken. For a double-contrast barium enema, the colon is drained of barium. The colon is then filled with air, and X rays are taken. When the procedure is complete, the enema tube is removed, and patients empty the colon of barium. Afew final X rays are taken. After the procedure: Patients should drink plenty of fluids to help remove the barium from their bodies. Bowel movements will contain barium for one to two days following the tests. The barium may make bowel movements appear pink or white in color.
Barium swallow European Journal of Radiology 61, no. 3 (March, 2007): 382-387. Rosman, A. S., and M. A. Korsten. “Meta-analysis Comparing CT Colonography, Air Contrast Barium Enema, and Colonoscopy.” American Journal of Medicine 120, no. 3 (March, 2007): 203-210. See also Adenomatous polyps; Barium swallow; Colon polyps; Colonoscopy and virtual colonoscopy; Colorectal cancer screening; Crohn disease; Diverticulosis and diverticulitis; Gallium scan; Imaging tests; Medicare and cancer; Ovarian cancers; Pancolitis; Premalignancies; Small intestine cancer; X-ray tests.
Risks: A barium enema is a low-risk procedure. Occasionally, the barium may harden, resulting in constipation. Drinking extra fluids and using a laxative may relieve constipation. In rare cases, the bowel may become inflamed or perforated. Patients should contact their doctor if they experience bleeding, severe pain, fever, or no bowel movements within two days of the procedure.
u Barium swallow
Results: The X-ray films are read by a radiologist. The ordering doctor may review the films as well. A healthy colon and rectum are free of abnormal growths or polyps. Any abnormalities, such as cancer or precancerous tissues, are visible on the films. Abnormal results are followed with colonoscopy. Mary Car-Blanchard, O.T.D., B.S.O.T.
Definition: A barium swallow is a diagnostic test in which the patient ingests barium sulfate, a radiopaque contrast medium. It is used with X rays to detect mouth, throat, vocal cords, esophagus, stomach, and small intestine cancers.
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For Further Information Etzioni, D. A., et al. “Measuring the Quality of Colorectal Cancer Screening: The Importance of Follow-Up.” Diseases of the Colon and Rectum 49, no. 7 (July, 2006): 1002-1010. Fenton, J. J., et al. “Delivery of Cancer Screening: How Important Is the Preventive Health Examination?” Archives of Internal Medicine 167, no. 6 (March 26, 2007): 580-585. Jimbo, M., et al. “Effectiveness of Complete Diagnostic Examination in Clinical Practice Settings.” Cancer Detection and Prevention 30, no. 6 (2006): 545-551. Pickhardt, P. J. “The Natural History of Colorectal Polyps and Masses: Rediscovered Truths from the Barium Enema Era.” American Journal of Roentgenology 188, no. 3 (March, 2007): 619-621. Rollandi, G. A., E. Biscaldi, and E. DeCicco. “Double Contrast Barium Enema: Technique, Indications, Results, and Limitations of a Conventional Imaging Methodology in the MDCT Virtual Endoscopy Era.”
Category: Procedures Also known as: Barium swallow X ray, barium swallow exam, barium swallow test, barium meal, doublecontrast barium swallow, upper gastrointestinal (GI) series, esophagraphy, esophagogram, esophagram
Cancers diagnosed: Oral cavity (mouth) cancer; oropharyngeal (throat) cancer; vocal cord cancer, including laryngeal and hypopharyngeal cancer, glottic cancer, supraglottic cancer, subglottic cancer; esophageal cancer; stomach cancer; stomach polyps, which may precede stomach cancer; small intestine cancer, including carcinoid tumors, gastrointestinal stromal tumors, lymphomas, and adenocarcinoma Why performed: A barium swallow with X rays is performed to help diagnose cancer of the mouth, throat, vocal cords, esophagus, stomach, and small intestine. When swallowed, barium sulfate shows up on X rays and highlights the linings of the above-mentioned structures. A double-contrast barium swallow involves swallowing substances that create air in the stomach to expand it, allowing a better view. Patient preparation: Patients may be placed on a restricted diet a few days before the test. Patients should not eat, drink, chew gum, or smoke after midnight before the test. Patients receive instructions from their doctors about swallowing medications. The stomach needs to be empty for the procedure. In some cases, the stomach contents are removed through a tube placed in the nose. For women, a 121
Barium swallow
Salem Health: Cancer taken. Then, patients drink sixteen to twenty ounces of barium sulfate. The barium sulfate is mixed in a thick drink that may have flavor added to it; otherwise, the drink is described as tasting chalky. The examination table may be tilted or pressure may be applied to the patient’s abdomen to help spread the barium. The barium is viewed on a barium fluoroscope monitor as it travels through the upper digestive tract. Still X-ray images can be taken at any time. Patients may need to drink more barium sulfate as the test progresses. For a double-contrast barium swallow, the patient swallows baking soda crystals. The baking soda creates gas, and the air expands the stomach. Additional images are taken, and the patient is repositioned or the examination table is tilted as necessary. After the procedure: Patients should drink plenty of fluids to help remove the barium from their bodies. Patients can eat a regular diet unless instructed otherwise. Bowel movements will contain barium for one to two days following the tests. The barium may make bowel movements appear white, gray, or pink in color.
Extended, infiltrating, and mild stenosing esophageal cancer are revealed by a barium X ray. (©ISM/Phototake—All rights reserved)
pregnancy test may be performed to ensure that the patient is not pregnant. Abarium swallow is an outpatient procedure that is performed at a hospital radiology department, outpatient radiology center, or doctor’s office. The test does not require anesthesia, and patients are awake. A barium swallow usually takes from thirty to sixty minutes, depending on the extent of the procedure. Patients disrobe and wear a gown for the test. Patients need to remove metal objects that may interfere with the X rays, including glasses, dentures, and jewelry. Steps of the procedure: The patient’s vital signs are taken before the test and monitored during the test. Patients may sit, stand, or lie on an X-ray table for the procedure. Patients may be secured to the X-ray table if it is tilted to allow images to be taken from various angles. X rays of the patient’s heart, lungs, and abdomen are 122
Risks: A barium swallow is considered a low-risk procedure. The radiation exposure is low, but it carries a small risk of cancer. Patients may be allergic to the flavorings that are mixed with the barium drink. Occasionally, the barium may harden, resulting in intestinal blockage or constipation. Patients should contact their doctor if they have not had a bowel movement within one to two days of the procedure. Results: The X-ray films are read by a radiologist. The ordering doctor may review the films as well. The linings of healthy structures are free of abnormal growths or polyps. Any abnormalities, such as cancer or precancerous tissues, appear as growths or polyps. Mary Car-Blanchard, O.T.D., B.S.O.T. u
For Further Information Drop, A., et al. “The Modern Methods of Gastric Imaging.” Annales Universitatis Mariae Curie-Skuodowska 59, no. 1 (2004): 373-381. Gore, R. M., et al. “Upper Gastrointestinal Tumours: Diagnosis and Staging.” Cancer Imaging 29, no. 6 (December, 2006): 213-217. Hosaka, K. “Radiological Investigation of the Mucosae Around Early Gastric Cancers.” Journal of Gastroenterology 41, no. 10 (October, 2006): 943-953. Kunisaki, C., et al. “Outcomes of Mass Screening for Gastric Carcinoma.” Annuals Surgical Oncology 13, no. 2 (February, 2006): 221-228.
Salem Health: Cancer Levine, M. S., and S. E. Rubesin. “Diseases of the Esophagus: Diagnosis with Esophagography.” Radiology 237, no. 2 (November, 2005): 414-427. Pasuawski, M., J. Zuomaniec, E. Ruci½ska, and W. Koutyk. “Synchronous Primary Esophageal and Gastric Cancers.” Annales Universitatis Mariae Curie-Skuodowska 59, no. 1 (2004): 406-410. Summers, D. S., M. D. Roger, P. L. Allan, and J. T. Murchison. “Accelerating the Transit Time of Barium Sulphate Suspensions in Small Bowel Examinations.” European Journal of Radiology 62, no. 1 (April, 2007): 122-125. See also Diarrhea; Esophageal cancer; Gastrointestinal cancers; Gastrointestinal complications of cancer treatment; Imaging tests; Laryngeal cancer; Laryngectomy; Small intestine cancer; Stomach cancers; Throat cancer; Upper gastrointestinal (GI) series; X-ray tests.
u Barrett esophagus Category: Diseases, symptoms, and conditions Also known as: Barrett’s esophagus, Barrett’s metaplasia, Barrett’s mucosa, Barrett’s syndrome, columnar epithelium lined lower oesophagus (CELLO), columnar-lined esophagus Related conditions: Esophageal adenocarcinoma, gastroesophageal reflux disease (GERD), hiatal hernia
Barrett esophagus people with GERD, some of the acid of the stomach leaks into the esophagus, possibly because of a weakness in the sphincter. In about 10 to 15 percent of these people, the acid changes the color and makeup of the cells lining the esophagus. These cells are much like cells in the intestines; they are darker than the normal esophagus tissue and more resistant to stomach acid. Rarely, Barrett esophagus cells develop into a precancerous state called dysplasia. Dysplasia, in some cases, then develops into esophageal cancer. Incidence: About 700,000 adults in the United States have Barrett esophagus. It is very uncommon in children; the average age of diagnosis is sixty. It is twice as common in men as in women. Caucasians and Hispanics are more likely to develop this condition than those of other ethnic backgrounds. Symptoms: Symptoms include chronic heartburn, chronic acid reflux, trouble swallowing or a feeling that something is stuck in the throat, weight loss, spitting up food, excessive burping, hoarseness, sore throat, and bleeding. Sometimes people with chronic heartburn will get some relief from their symptoms when they develop Barrett esophagus. The intestinal metaplasia may help protect the esophagus from the stomach acid because those cells are normally found in the intestines and are better able to withstand stomach acid. Screening and diagnosis: Adults over the age of forty who have had chronic heartburn or acid reflux may be
Definition: Barrett esophagus is a condition in which some of the cells lining the esophagus (tube that carries food to the stomach) are replaced with a different type of cell similar to those lining the intestines, a process called intestinal metaplasia. Rarely, these cells develop into cancer of the esophagus (esophageal adenocarcinoma). This condition is named after Norman Barrett, who first described it in 1957. Risk factors: Developing Barrett esophagus is linked to chronic heartburn and another common condition called gastroesophageal reflux disease (GERD). However, the chances of heartburn or GERD developing into Barrett esophagus are very small. Sometimes people who develop GERD have a part of the stomach that bulges through the diaphragm (hiatal hernia). This kind of hernia may trap acid in the esophagus and cause more damage, eventually leading to GERD and progressing into Barrett esophagus. Etiology and the disease process: Normally, a round muscle (sphincter) near the bottom of the esophagus keeps stomach acid from washing back up into the esophagus. In
Barrett esophagus has produced two areas of dysplasia. (Custom Medical Stock Photo)
123
Basal cell carcinomas screened with an endoscopy to see whether they have Barrett esophagus. However, screening for this disease is not commonly recommended as an endoscopy is expensive and the rate of discovering the condition is very low. People who have no symptoms should not have an endoscopy just to see if they have this condition. Barrett esophagus can be diagnosed only by performing a biopsy on suspected tissue. There is no staging for Barrett esophagus. Treatment and therapy: Treatment for Barrett esophagus involves avoiding further damage. Therapies that keep the acid in the stomach from moving up into the esophagus may include antacid-type medications or other medications that stop stomach acid production. Lifestyle changes, such as losing weight, stopping smoking, and avoiding certain foods, also help. Other ways to keep the acid in the stomach include eating smaller meals more often, wearing loose-fitting clothing, waiting two to three hours after eating before lying down, and elevating the head of the bed 8 to 10 inches. A type of surgery that reinforces the sphincter that keeps acid in the stomach may also help. There is no cure for Barrett esophagus other than surgically removing the esophagus. This type of surgery is only performed on those who have already developed esophageal adenocarcinoma or are at very high risk for developing it. With this surgery, the affected part of the esophagus is removed, and the stomach is brought up and attached to the nonaffected part of the esophagus. Possible treatments for removing Barrett esophagus cells are being investigated. These include various ways of destroying those cells with lasers or chemicals. However, removing the cells has not yet been proven to reduce the risk of Barrett esophagus recurring or developing into esophageal cancer. Removing the Barrett esophagus cells is usually recommended only when a patient has highly developed precancerous or already cancerous cells. Prognosis, prevention, and outcomes: Barrett esophagus may not cause any problems or symptoms in those who have it. It is only significant because it is a precursor to esophageal adenocarcinoma, but even those who have Barrett esophagus have a less than 1 percent chance of developing this type of cancer. Those who have been diagnosed with Barrett esophagus should be screened regularly, every one to three years, to ensure that the cells are not developing into cancer. Some ways of attempting to prevent further damage to the esophagus are to eat a diet low in fat and high in fruits, vegetables, and fiber. Avoiding smoking and maintaining a healthy weight may also help. Marianne M. Madsen, M.S. 124
Salem Health: Cancer u
For Further Information Parker, James, and Philip M. Parker, eds. The Official Patient’s Sourcebook on Barrett’s Esophagus: A Revised and Updated Directory for the Internet Age. San Diego, Calif.: Icon Health, 2004. Shalauta, Saad R. “Barrett’s Esophagus.” American Family Physician 69, no. 9 (May 1, 2004): 2113-2118. Sharma, Prateek, and Richard E. Sampliner, eds. Barrett’s Esophagus and Esophageal Adenocarcinoma. 2d ed. Malden, Mass.: Blackwell, 2006. u
Other Resources
Barrett’s Oesophagus Foundation http://www.barrettsfoundation.org.uk MedicineNet.com Barrett’s Esophagus http://www.medicinenet.com/barretts_esophagus/ article.htm National Digestive Diseases Information Clearinghouse Barrett’s Esophagus http://digestive.niddk.nih.gov/ddiseases/pubs/barretts See also Esophageal cancer; Esophagectomy; Esophagitis; Histamine 2 antagonists; Premalignancies; Upper gastrointestinal (GI) endoscopy.
u Basal cell carcinomas Category: Diseases, symptoms, and conditions Also known as: Basal cell cancer, BCC Related conditions: Basal cell epitheliomas Definition: Basal cell carcinoma is a cancer in which the cancerous cells resemble the basal cells of the epidermis, the outer layer of the skin. It is the most common type of skin cancer. Risk factors: Exposure to ultraviolet light is the primary risk factor. People with light skin and eyes are more susceptible because they have less melanin, the pigment that colors skin and blocks the sun’s radiation. People who are exposed to more ultraviolet light because they work outdoors or use tanning booths are also at greater risk. Children are particularly susceptible to skin damage from the sun because they burn more readily. Arsenic exposure, usually from contaminated drinking water, is another risk factor.
Salem Health: Cancer
Basal cell carcinomas
Etiology and the disease process: Basal cell carcinomas are thought to begin in the upper part of the skin, the epidermis, or in a hair follicle. The basal cell layer forms the base of the epidermis. Basal cells continually divide to form new cells of skin, hair, or glands. They become cancerous when something disrupts their deoxyribonucleic acid (DNA) instructions for making normal new cells. The most common cause is ultraviolet radiation, probably UVB. These rays can hit the nuclei of skin cells and damage chromosomes or DNA. The body repairs most of the damage to chromosomes, but cells that are not repaired can begin to divide wildly and become cancer cells, which destroy surrounding cells or tissues. Basal cell carcinomas are slow growing and rarely spread to other parts of the body. If left untreated, however, they can do extensive damage to surrounding tissue. Incidence: Basal cell carcinoma is the most common skin cancer in the United States, making up about 75 percent of skin cancers. Nearly a million new cases are reported each year, and about 90 percent of those are attributed to solar radiation, although some cases occur in skin rarely exposed to the sun. Men are at higher risk than women, probably because they have, in the past, worked outdoors more. Basal cell carcinoma is more common in adults than in children, and the elderly are the most likely candidates, as these cancers can take twenty to fifty years to manifest after radiation exposure. Symptoms: The most common symptom of basal cell carcinoma is a skin lesion, which is a superficial growth or a sore that does not heal. There are many types of basal cell carcinoma and nearly as many types of lesions. Lesion size varies from a few millimeters to several centimeters, and some lesions are larger than they appear on the skin because they invade underlying tissues. The lesions are usually painless, though the surrounding skin can become irritated and tender. Some lesions are flat, reddish or crusty patches that can be mistaken for psoriasis or eczema. The color and appearance of lesions varies widely, from white or yellow and scarlike to pink, red, tan, brown, or black. Lesions are often waxy or translucent in appearance, and many are described as pearly. Some lesions are smooth and symmetrical, while others have irregular borders or a bumpy surface with superficial blood vessels. Other lesions have rolled edges with a crater in the middle. Many lesions bleed easily. Screening and diagnosis: The U.S. Preventive Services Task Force evaluated routine screening for skin cancers in 2001 and did not find evidence to recommend whole-body
A patient with basal cell carcinoma. (Custom Medical Stock Photo)
skin examination for skin cancer, so health care providers look for skin cancers as circumstances allow or warrant. The diagnosis of basal cell carcinoma is made by histologic, or microscopic, examination of lesional cells from a sample of the lesion or from examination of the entire lesion. The type and variety of cancer are determined by the makeup and differentiation of cells. Treatment and therapy: The most common treatment for basal cell carcinoma is surgical excision, or removal, of the lesion. Some normal tissue is taken all around the lesion so that the physician can be sure no cancer cells are left. Mohs surgery, which allows for better margin control, is the treatment of choice for sclerosing basal cell carcinoma. Other treatments include curettage and electrodesiccation, or scraping of the lesion and destroying the remaining tissue with electric current; cryosurgery, or freezing with liquid nitrogen; topical chemotherapy; radiation; laser surgery; and photodynamic therapy, in which a 125
Beckwith-Wiedemann syndrome (BWS) sensitizer is absorbed into the lesion, which is then exposed to a laser beam. Prognosis, prevention, and outcomes: The cure rate is about 85 to 99 percent for primary tumors. One variant of basal cell carcinoma, called sclerosing, morpheaform, or infiltrating, is more likely to recur after treatment. This variant, which usually resembles a scar, is more difficult to treat because it grows in thin strands that may be missed in the tissue sample. Though death from basal cell carcinoma is extremely rare, untreated lesions can cause extensive damage and disfigurement, sometimes requiring skin grafts or reconstructive surgery. Early detection and treatment give the best outcomes. Basal cell carcinoma is also highly preventable through avoidance of excessive sun exposure, particularly in childhood. Childhood exposure to ultraviolet radiation can result in skin cancer that appears decades later. Limiting sun exposure, using sunscreen, and wearing sun-protective clothing and hats are useful methods of preventing damage to the skin from ultraviolet light. Cathy Anderson, R.N., B.A. u For Further Information Burns, C. A., and M. D. Brown. “Imiquimod for the Treatment of Skin Cancer.” Dermatology Clinics 23, no. 1 (2005): 151-164. Neale, R. E., et al. “Basal Cell Carcinoma on the Trunk Is Associated with Excessive Sun Exposure.” Journal of the American Academy of Dermatology 56, no. 3 (2007): 380-386. Noble, J. Textbook of Primary Care Medicine. 3d ed. St. Louis: Mosby, 2001.
u
Other Resources
Medem Medical Library http://www.medem.com Skin Cancer Foundation http://www.skincancer.org See also Arsenic compounds; Bowen disease; Choriocarcinomas; Dermatology oncology; Electroporation therapy; Exenteration; Eye cancers; Eyelid cancer; Lip cancers; Medulloblastomas; Melanomas; Mohs surgery; Moles; Neuroectodermal tumors; Radical neck dissection; Skin cancers; Squamous cell carcinomas; Sunlamps; Turcot syndrome; Vulvar cancer. 126
Salem Health: Cancer
u Beckwith-Wiedemann
syndrome (BWS) Category: Diseases, symptoms, and conditions Also known as: Wiedemann-Beckwith syndrome, exomphalos-macroglossia-gigantism (EMG) syndrome Related conditions: Hemihypertrophy (enlargement of one side of the body); hypoglycemia (low blood sugar); exomphalos (a protrusion of the umbilicus) or other abdominal wall defects such as umbilical hernia, omphalocele, and diastasis recti; visceromegaly (enlarged organs) or enlarged tongue or skeleton; adrenal gland abnormalities such as adrenocortical cytomegaly (enlarged cells of the adrenal cortex); dysplasia of the renal medulla; and embryonal cancerous tumors (tumors that arise from embryonic or fetal tissue) such as nephroblastoma (Wilms’ tumor affecting the kidney, about 75 percent), hepatoblastoma (liver malignancy, about 1 to 11 percent), rhabdomyosarcoma (a soft-tissue tumor most commonly found in the head and neck, arms, and legs, and the renal and genital tracts, about 5 percent), and neuroblastoma (affecting primitive neuronal cells in the adrenal gland and behind the peritoneum, the serous tissue that lines the abdomen, about 4 percent) Definition: Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth disorder caused by abnormalities in the 11p15.5 region of chromosome 11. The expression of the involved chromosome is variable and the penetrance (the degree to which features or characteristics resulting from the person’s genetic makeup are seen by others) is incomplete. Penetrance is affected by either paternal or maternal transmission of information and gene control. Risk factors: De novo mutations and inheritance through familial linkage are the primary risk factors. Analysis of the chromosomes is diagnostic in familial heritance, and all show transmission through the mother. Analysis of paternally derived BWS shows duplication or trisomy of the 11p15.5 region. These multiple copies result in a varying phenotype. Thus, different patterns of inheritance have been documented. Etiology and the disease process: The overexpression of insulin-like growth factor-2 (IGF-2) is a key determinant of BWS. This overexpression occurs in the following manner. One set of chromosomes is inherited from the father, and the other is inherited from the mother. Each set of
Salem Health: Cancer chromosomes contains a gene or a set of genes responsible for the characteristics of the new individual. Often, a gene on either the maternal or paternal chromosome is expressed, while the corresponding gene on the other parent’s chromosome is silent. The expression of a gene on one parent’s chromosome and the silence of the corresponding gene on the other parent’s chromosome is termed imprinting. BWS develops when the normally expressed maternal gene is overactive. Deregulation of imprinted growth regulatory genes on chromosome 11, region 11p15.5, results in an imbalance between maternal and paternal allele expression. This region contains the genes for insulin and insulin-like growth factor-2 (IGF-2), both potent stimulators of fetal growth. This genetic aberration triggers exaggerated growth in the fetus, both in overall size as well as the enlargement of various structures and organs. Other tissues sensitive to abnormal growth factors respond by producing a high incidence of embryonal tumors and other anomalies. The loss of IGF-2 imprinting results in an overexpression of IGF-2 and leads to an enlarged body, organs, and overstimulation of embryonic tissues, which are the basis for various tumors affecting the kidneys, liver, and adrenal glands. Incidence: BWS occurs in approximately 1 in 14,000 live births in the regular population in the United States. The incidence is higher with in vitro births (assisted reproductive technology). Because of phenotypic variation, many individuals with BWS may go undiagnosed, especially if the penetrance is mild or subtle. Symptoms: Major symptoms include macroglossia (large tongue), pre- or postnatal growth greater than the ninetieth percentile, and abdominal wall defects. Minor symptoms include hypoglycemia, ear creases or helical indentations, facial nevus flammeus (port-wine stain), a large placenta at birth, and polyhydramnios (excessive amniotic fluid). Abnormalities in all body systems have been reported in association with BWS. Screening and diagnosis: Because of the high incidence of embryonal tumor formation, abdominal ultrasonographic examinations are necessary every three months, especially in the first six years of life (the period when most embryonal tumors manifest). Wilms’ tumor is rapidly progressive, and even individuals who have been examined every six months have been found to have latestage disease. Diagnosis is by imaging studies (ultrasound, magnetic resonance imaging, computed tomography, bone scans), biopsy, laboratory tests (complete blood count, blood smear, alpha-fetoprotein, tests to evaluate functioning of the involved organs).
Beckwith-Wiedemann syndrome (BWS) Staging is a process to determine whether the cancer has spread (metastasized) to other sites. Classification includes: • Stage I: The cancer can be completely removed by surgery. • Stage II: A majority of the cancer is removed by surgery with a small amount remaining at the primary site. • Stage III: The cancer has spread to the lymph nodes. • Stage IV: The cancer has spread to distant sites in the body. • Recurrent: The cancer has returned after it has been treated. Treatment and therapy: Hypoglycemia must be prevented and, if present, rapidly treated to prevent central nervous system abnormalities, especially mental retardation. Embryonic tumors require treatment (surgery, radiation, chemotherapeutic drug administration). Macroglossia is treated with surgery to ensure a patent (open) airway and normal mouth and speech development. Other anomalies are given standard treatment for the problem. Prognosis, prevention, and outcomes: Prevention requires a decision by affected individuals not to reproduce. Prenatal genetic testing is currently not available. Prenatal ultrasound examination may lead to early detection of an affected fetus. If the pregnancy is continued, medical personnel can be alerted, thus allowing prompt attention to the infant at birth to detect problems and intervene in a timely manner, hopefully preventing some complications. Prognosis depends on the range of morbidities and their management. Wanda Todd Bradshaw, R.N.C., M.S.N. u
For Further Information Cohen, M. Michael. “Beckwith-Wiedemann Syndrome: Historical, Clinicopathological, and Etiopathogenetic Perspectives.” Pediatric and Developmental Pathology 8 (2005): 287-304. Smith, Adam C., Sanaa Choufani, José C. Ferreira, and Rosanna Weksberg. “Growth Regulation, Imprinted Genes, and Chromosome 11p15.5.” Pediatric Research 61, no. 5 (2007): 43R-47R. Weksberg, Rosanna, Cheryl Shuman, and Adam C. Smith. “Beckwith-Wiedemann Syndrome.” American Journal of Medical Genetics, Part C 137C (2005): 12-23.
u
Other Resources
Beckwith-Wiedemann Syndrome Family Forum http://www.beckwith-wiedemann.info 127
Benign prostatic hyperplasia (BPH) Online Mendelian Inheritance in Man http://www.ncbi.nlm.nih.gov/sites/entrez?db=OMIM See also Adrenal gland cancers; Adrenocortical cancer; Nephroblastomas; Rhabdomyosarcomas; Wilms’ tumor.
u Benign prostatic hyperplasia
(BPH) Category: Diseases, symptoms, and conditions Also known as: Benign enlargement of the prostate (BEP), lower urinary tract symptoms (LUTS) Related conditions: Prostate cancer, urinary retention Definition: Benign prostatic hyperplasia (BPH) refers to an enlarged prostate gland. The prostate is a reproductive gland in men that produces semen, the fluid that nourishes and transports sperm. It is about the size and shape of a walnut and is located below the bladder. The gland surrounds the urethra, the tube that carries urine outside the body. The prostate grows in size in most men as they age. Risk factors: Increasing age and a family history of BPH contribute to the risk of developing this condition. Etiology and the disease process: The exact cause of BPH is unknown. It is not cancerous, nor does it increase the risk of developing prostate cancer. Incidence: Approximately 50 percent of men between the ages of fifty-one and sixty and 90 percent over age eighty develop BPH. About half of all men diagnosed with BPH have moderate to severe symptoms. Symptoms: The enlarged prostate presses down on the urethra and irritates or obstructs the bladder. Common symptoms include frequent urination two or more times per night, a sudden urge to urinate, a weak urine stream, dribbling after urinating, straining to urinate, the inability to prevent urine leakage, or the sensation that the bladder is not empty even after urinating. In extreme cases, urinary retention, the complete inability to urinate, is a problem. Screening and diagnosis: The evaluation typically consists of a complete medical history, a digital rectal exam to feel the size of the prostate, a urinalysis to check for blood or infection in the urine, a prostate-specific antigen (PSA) blood test to screen for prostate cancer, and questions to assess the severity of symptoms. Additionally, urine flow rate, a post-void residual urine test, a pressure-flow study, 128
Salem Health: Cancer an X ray of the urinary tract, or cystoscopy (a test using a scope inserted into the urethra and bladder) may be recommended. Treatment and therapy: Depending on the severity of symptoms, treatment can include lifestyle modifications, such as decreasing the intake of fluid before bedtime and limiting the consumption of alcohol and caffeine, or medication to increase urine flow. In extreme cases, surgery to remove part of the prostate may be recommended. Prognosis, prevention, and outcomes: Many men with BPH have only minor symptoms and are able to manage their discomfort with lifestyle modifications. A yearly exam is recommended to monitor symptoms and the impact of BPH on daily life. Vonne Sieve, M.A. See also Digital rectal exam (DRE); Prostate cancer; Prostate-specific antigen (PSA) test; Prostatectomy; Prostatitis; Saw palmetto; Transrectal ultrasound; Urologic oncology.
u Benign tumors Category: Diseases, symptoms, and conditions Also known as: Mass, benign neoplasm, noncancerous tumor Related conditions: Lipoma, chondroma, adenoma, hemangioma Definition: A benign tumor is a noncancerous growth that does not invade nearby tissue or spread to other parts of the body. Benign tumors are caused by cell overgrowth and are thus distinct from other tissue formations, such as cysts or abscesses. A tumor is a mass of tissue that serves no useful purpose and exists at the expense of healthy tissues. Benign tumors do not exhibit any of the three characteristics of malignant tumors: Benign tumors do not invade nearby tissues, do not metastasize, and do not grow in an unlimited, accelerated manner. Risk factors: The specific risk factors for benign tumors vary depending on the location of the tumor and the tissue type. For example, risk factors for benign breast tumors include such factors as body mass index, height, and breast size. Problems with the body’s immune system can cause tumors, both malignant and benign. Certain viruses can also play a role in tumor formation, as in cervical cancer and hepatocellular carcinoma. Exposure to loud sounds or music can increase the risk of developing benign tumors in
Salem Health: Cancer
Benign tumors
the ears, as can repeated exposure to cold water. Smoking can cause benign tumors to appear in the lower lip. Etiology and the disease process: The source of most benign tumors is a discrete population of cells that have been altered through acquired genetic defects. Such abnormal tissue masses are termed benign neoplasms. Benign tumors are usually encapsulated, meaning that they are confined to a specific, localized area and surrounded by a thin layer of tissue. This limits the growth rate and invasive potential of the tumor. In the liver, the most common benign tumors are hemangiomas. These tumors are made of abnormal blood vessels, most likely present at birth but only detected later when they cause symptoms or are identified on an ultrasound or computed tomography (CT) imBenign tumor nevus pigmented lesions. (Custom Medical Stock Photo) age obtained for another reason. Hemangiomas occur more frequently in women. Screening and diagnosis: When a tumor is found, a biInfections can cause benign tumors to appear in the larynx, opsy is performed to determine whether the tumor is bewhich can be detected by symptoms of hoarseness. nign or malignant. Although usually not life-threatening, Incidence: Benign tumors are common and usually not once diagnosed, benign tumors should be monitored regulife-threatening. However, benign tumors cause more than larly, as a benign tumor may progress and become a malig13,000 deaths annually, compared with more than 500,000 nant tumor. For instance, a colon polyp is a type of benign annual deaths due to malignant tumors. Benign tumors can tumor, but most incidences of colon cancer develop from cause serious injury or death by pressing on vital organs colon polyps. The most common benign tumors of the ear (such as the brain), tissues, or nerves in the vicinity of the occur behind the ear. They can also occur within the ear growth. Benign tumors in the kidneys can range in size canal or on the scalp and can be discovered during a roufrom 1 millimeter to several centimeters without causing tine ear examination, which includes audiometry (hearing any symptoms or requiring treatment. Benign tumors in tests) and tympanometry (middle ear testing). When lookthe lungs are relatively rare, making up only 7 to 10 pering into the ear, the doctor may observe cysts or benign tucent of all tumors in the lungs. Benign tumors in the stommors within the ear canal. ach account for 5 to 10 percent of all stomach tumors, afTreatment and therapy: Often a benign tumor will reflicting many people between the ages of forty and fifty. quire no treatment if it is located in a low-risk area where it Men are two to four times more likely to develop benign will not cause symptoms or disturb proper function of an stomach tumors compared with women. organ. If causing symptoms, benign tumors are usually Symptoms: Benign tumors may be asymptomatic or may treated by surgery. Benign tumors may also be removed cause one or more of the following symptoms depending for cosmetic reasons. The incidence of recurrence after on their location and their specific tissue type: itching, obsurgery is typically low. Chemotherapy and radiation therstruction of the intestines, bleeding or occult blood loss reapy are usually ineffective in the treatment of benign tusulting in anemia, cosmetic changes, hormonal syndromes mors. Benign tumors of the brain may be surgically recaused by hormones secreted by the tumor, compression moved to prevent harmful effects on the surrounding of the blood vessels or vital organs, and pain or dysfuncnormal brain tissue. tion induced by pressure. Benign tumors in the nose have Prognosis, prevention, and outcomes: Benign tumors the following symptoms: hard breathing, bleeding, headache, or severe eye pain and blurring. tend to grow more slowly than malignant tumors and are 129
Benzene less likely to threaten health. If a tumor is benign, the prognosis is generally very good. The situation can be more serious if the tumor is located in the brain. Michael R. King, Ph.D. u For Further Information Black, Peter McL. Living with a Brain Tumor: Dr. Peter Black’s Guide to Taking Control of Your Treatment. New York: Henry Holt, 2006. DeMonte, Franco, et al., eds. Tumors of the Brain and Spine. New York: Springer, 2007. Moore, Stephen W. Griffith’s Instructions for Patients. 7th ed. Philadelphia: Elsevier Saunders, 2005. u
Other Resources
Genetics Home Reference Benign Tumors http://ghr.nlm.nih.gov/conditionGroup=benigntumors Medline Plus Benign Tumors http://www.nlm.nih.gov/medlineplus/ benigntumors.html See also Acoustic neuromas; Adenomatoid tumors; BirtHogg-Dubé syndrome (BHDS); Brachytherapy; BRAF gene; Carcinogens, known; Carney complex; Castleman disease; Chemoprevention; Cowden syndrome; Craniopharyngiomas; Endotheliomas; Fibroadenomas; Gastrointestinal stromal tumors (GISTs); Gestational trophoblastic tumors (GTTs); Glomus tumors; Hemangioblastomas; Hystero-oophorectomy; Lacrimal gland tumors; Leiomyomas; Metastasis; Multiple endocrine neoplasia type 1 (MEN 1); Multiple endocrine neoplasia type 2 (MEN 2); Phyllodes tumors; Pineoblastomas; Radical neck dissection; Sertoli cell tumors; Tuberous sclerosis.
u Benzene Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1980 Also known as: Benzol, phenyl hydride, 1,3,5cyclohexatriene Related cancers: Cancers of the blood and blood-forming organs, including acute myelogenous, monocytic, erythroblastic and lymphocytic leukemias, lymphomas, and Zymbal gland carcinomas Definition: Benzene (chemical formula C6H6) is a clear, colorless to light yellow, volatile and flammable liquid 130
Salem Health: Cancer that has an aromatic odor. It is slightly soluble in water, is sensitive to heat, and mixes easily with alcohol, ether, chloroform, acetone, carbon tetrachloride, carbon disulfide, oils, and glacial acetic acid. It forms a solid below 42 degrees Fahrenheit. In the United States, the Safe Drinking Water Act (1976) has legal control over benzene levels in drinking water, which cannot exceed 5 parts per billion (ppb). Exposure at 19,000-20,000 parts per million for five to ten minutes is fatal. Exposure routes: Inhalation, skin contact, and oral ingestion are the most toxic and dangerous routes. Where found: Benzene is an industrial chemical that is widely used as a solvent and used in inks, rubber, lacquers, paint removers, gas additives, glue backing for carpeting, high solvent paints, some furniture wax, automobile exhaust, tobacco smoke, secondhand smoke, taxidermy, firefighting, metal preparation and pouring, petroleum refining, industrial cleaning, drinking water, and closed processes to synthesize organic chemicals. It is also used to make dyes and insecticides and in the processing of numerous chemicals. At risk: Children and pregnant woman are at higher risk. However, anyone exposed to benzene is at risk. For example, the presence of benzene in gasoline makes exposure to it a risk for anyone filling an automobile gas tank. Etiology and symptoms of associated cancers: It is not clear how benzene causes damage to the blood-forming organs, which then leads to leukemias and lymphomas. Interaction between breakdown products (metabolites) is being studied as a likely cause. Exposure to as little as 1 part per million lowers white cell counts. Symptoms of leukemias and lymphomas include fever, night sweats, fatigue, bleeding and easy bruising, bone pain, frequent infections, swollen lymph nodes, and weight loss. History: Benzene is a natural component of crude oil. In 1825 Michael Faraday performed distillation experiments and extracted a gas from the oil. The gas burned, and he named it “bicarburet of hydrogen.” The chemical structure of benzene remained elusive until 1865, when Friedrich August Kekulé von Stradonitz hypothesized a hexagonal structure. Benzene was derived from the distillation of coal by A. W. Hoffman in 1846. The uses of and demand for benzene increased along with oil exploration as its usefulness in many industrial applications became apparent. Linus Pauling, the Nobel Prize-winning physicist, was
Salem Health: Cancer one of many scientists to attempt to elucidate the unique hybrid structure of benzene that was confirmed in 1931. The main use of benzene prior to World War I was in gasoline blending, as it increased octane. It was used extensively in industry in World War II, and almost all organic-chemistry-related industry involves petroleum (benzene-containing) products. Janet R. Green, M.S.P.H. See also Acute lymphocytic leukemia (ALL); Acute myelocytic leukemia (AML); Air pollution; Aleukemia; Aplastic anemia; Bioflavonoids; Blood cancers; 1,3-Butadiene; Carcinogens, known; Carcinogens, reasonably anticipated; Chlorambucil; Cigarettes and cigars; Coal tars and coal tar pitches; Coke oven emissions; Dioxins; Free radicals; Leukemias; Myelodysplastic syndromes; Myelofibrosis; Organochlorines (OCs); Phenolics; Urinary system cancers.
u Benzidine and dyes
metabolized to benzidine Category: Carcinogens and suspected carcinogens RoC status: Benzidine, known human carcinogen since 1980; dyes metabolized to benzidine, known human carcinogens since 2000 Also known as: Direct Blue 6, Direct Black 38, Direct Brown 95 Related cancers: Bladder cancer, and less frequently cancer of the stomach, liver, kidney, central nervous system, and pancreas Definition: Benzidine is an organic compound used to make dyes. It is usually found in the form of a powder that is white, reddish gray, or grayish yellow. Exposure routes: Benzidine can enter into the human body in many ways. If air containing molecules of benzidine is inhaled, the benzidine can enter into a person’s system. Benzidine can also be ingested, either directly or in contaminated drinking water. It is also possible for benzidine to enter the human body through the skin if direct contact is made with benzidine or a benzidine-based dye. Where found: For many years, benzidine was used in the production of dyes and dyeing compounds. It was also used occasionally in some clinical and laboratory settings, for example, in blood detection. Dyes that metabolize to benzidine were used in many different dyeing applica-
Benzidine and dyes metabolized to benzidine tions. Benzidine was used especially often to dye paper products, textiles, and leather goods. Plants manufacturing dyes were likely to contain large quantities of benzidine or dyes that metabolize to benzidine, as were plants that produced goods using such dyes. Beginning in the late 1970’s use of these dyes was phased out. Because of long usage, there remains the possibility of benzidine contamination in areas around plants and factories that once used benzidine or related dyes. Benzidine that is released into or makes its way into rivers or streams generally settles quickly on the bottom of the riverbed or streambed. Benzidine that was released into the environment through accidental contamination or as a waste product that ends up in the soil bonds strongly to particles found in the soil. It is not likely to seep into the groundwater and contaminate drinking water sources because of these strong bonds. Because its use in dyeing was phased out, benzidine and related dyes are used in only very small quantities in mostly research and laboratory settings in the United States. At risk: People who worked in industries that manufactured dyes or regularly used dyes in the production of other goods before the late 1970’s were at risk of exposure to high levels of benzidine and dyes that metabolize to benzidine. According to the Occupational Health and Safety Administration, in 1979 there were sixty-three separate occupations in which workers were at risk for benzidine exposure. Also at risk are people living near factories or plants that manufactured or used benzidine or benzidinebased dyes, especially if by-products of the plant were released into the air or water. Some residual benzidine may continue to exist at such locations. Benzidine and related dyes have also been identified as existing at many hazardous waste disposal sites and people who live near such areas may be at risk of exposure. Etiology and symptoms of associated cancers: Benzidine and related dyes have been shown to cause cancer in laboratory animals. Studies of humans who have a history of working with benzidine or related dyes have also shown that prolonged benzidine exposure is a significant risk factor for developing bladder cancer. Scientists do not clearly understand all the complex mechanisms involved in how benzidine causes cancer, but benzidine is believed to interfere with normal cellular processes. Bladder cancer is the cancer most commonly associated with benzidine exposure. The first signs and symptoms of bladder cancer are usually changes in bladder function or habits. This may include a person’s often feeling the urge to urinate without actually being able to do so. Needing to urinate much more frequently than usual is also 131
Benzodiazepines a possible symptom of bladder cancer, as is blood in the urine. History: Benzidine has a long history as an important industrial dye. It was first made in 1845. Its first use as a dye was in 1884, when a dye named Congo Red was created for the first time. Benzidine and related dyes were extremely useful in dyeing because of the way they adhere to cotton and cotton products. In the 1920’s some physicians and researchers began to suspect a relationship between exposure to benzidine and the development of bladder cancer. It was not until 1976, however, that major commercial production of benzidine and benzidine-based dyes ceased in the United States. There are no major manufacturers of benzidine for the purposes of dyeing or of benzidine-based dyes in the United States; however, there are still some small manufacturers of benzidine because it has some research and laboratory applications. It is considered a possible occupational carcinogen by the Occupational Safety and Health Administration. Personal protection is required for work with benzidine and related products, and it is necessary to take precautions to ensure that no benzidine is released into the environment. Benzidine is also considered a hazardous substance that requires special labeling and precautions when it is transported. Robert Bockstiegel, B.S. u For Further Information Bozzone, Donna M. Causes of Cancer. New York: Chelsea House, 2007. Pohanish, Richard P. Sittig’s Handbook of Toxic and Hazardous Chemicals and Carcinogens. 5th ed. Norwich, N.Y.: William Andrew, 2008. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Eleventh Report on Carcinogens. Research Triangle Park, N.C.: Author, 2005. Williams, Nerys R. Atlas of Occupational Health and Disease. New York: Oxford University Press, 2004. u
Other Resources
International Agency for Research on Cancer http://www.iarc.fr/index.html Occupational Safety and Health Administration http://www.osha.gov See also Carcinogens, known; Carcinogens, reasonably anticipated; Immunocytochemistry and immunohistochemistry. 132
Salem Health: Cancer
u Benzodiazepines Category: Chemotherapy and other drugs ATC code: N05BA Also known as: Alprazolam (Xanax), diazepam (Valium), lorazepam (Ativan) Definition: Benzodiazepines are a class of drugs with antianxiety, sedative, and muscle-relaxing properties. Cancers treated: Adjuvant therapy for many types of cancer Delivery routes: Orally by capsule or tablet, intramuscularly by injection How these drugs work: Benzodiazepines are a class of medications that act primarily on the gamma aminobutyric acid-α (GABA-A) receptors in the brain. Medications within the class vary according to their rapidness of onset, potency, frequency of dosing, length of effect, and halflife. They are typically used in the general medical population to alleviate anxiety or treat insomnia. Benzodiazepines are put to similar uses with cancer patients, as well as directed toward disease-specific conditions. When choosing among benzodiazepines, physicians consider the unique properties of specific medications (such as speed of onset, duration of effect, side effects), as well as patient characteristics (age, vigor, pain tolerance,
Common Benzodiazepines The following common benzodiazepines are used to treat acute mania, alcohol dependence, seizures, anxiety, insomnia, and muscular disorders. Trade Name
Generic Name
Ativan Dalmane Dormicum Halcion Klonopin Lexotanil Librium Loramet Mogadon ProSom Restoril Rohypnol Sedoxil Serax Valium Xanax
lorazepam flurazepam midazolam triazolam clonazepam bromazepam chlordiazepoxide lormetazepam nitrazepam estazolam temazepam flunitrazepam mexazolam oxazepam diazepam alprazolam
Salem Health: Cancer coping skills) and the types of cancer and treatments involved. Short-acting medications with rapid onset are often employed to treat acute anxiety, panic, and phobic responses to therapy. Longer-acting medications may be selected to assist patients engaging in painful or aversive cancer treatments (such as chemotherapy) to promote relaxation, reduce anticipatory anxiety, suppress recall of treatment, and alleviate nausea and restlessness (akisthisia). Long-acting benzodiazepines may also be employed to treat generalized anxiety and grief reactions stemming from cancer. Highly sedating benzodiazepines are often used to treat anxiety-related insomnia. Side effects: A number of side effects are associated with benzodiazepines. Long-term use can lead to drowsiness and deficits in memory, concentration, and motor coordination. Though safe for most in recommended dosages, benzodiazepines can potentially cause respiratory depression, and patients should be monitored closely as they initiate treatment. All benzodiazepines, especially those with rapid onsets and short durations of action, have the potential to cause dependence and, in rare cases in the cancer patient population, abuse. Consequently, physicians must closely supervise patients’ use of these medications. Abrupt discontinuation of benzodiazepines may cause withdrawal symptoms that, while severe, are usually managed with appropriate medical intervention. These symptoms include “rebound” anxiety, confusion, agitation, seizures, and, rarely, death. Paul F. Bell, Ph.D. See also Antinausea medications; Anxiety; Pain management medications.
u Beryllium and beryllium
compounds Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 2002 Also known as: Glucinium. Glucinium is a rarely used term, but it is noteworthy because, although the name describes beryllium’s tempting, sugary flavor, it does not warn of its poisonous nature, and those working with the alkaline earth metal should be cautioned. Related cancers: Lung cancer Definition: Beryllium is an alkaline earth metal found in ore deposits and in some precious stones. It was discovered in 1798 in emeralds and beryl and isolated in 1828.
Beryllium and beryllium compounds The metal did not see large-scale industrial use until the late 1950’s. In the twenty-first century, however, because of its high melting point, great elasticity, exceptional thermal conductivity, high permeability to X rays, and resistance to oxidation, beryllium finds uses across a wide range of products. Exposure routes: Inhalation of beryllium compounds that are found in dust and fumes combined with prolonged exposure elevate the risk of pulmonary disease and lung cancer. Beryllium can also enter the body through food and drinking water, but these routes seem less harmful because of its poor absorption. However, contact through abraded skin may result in local irritation, ulceration, or granulomatous growths. Where found: Beryllium has found uses across a variety of industries due to its properties as a light, high-strength metal combined with great elasticity and high melting point. A brief list includes uses in X-ray diagnostics; as a lightweight structural material required by the aerospace and missile industries; and as an alloying agent found in applications requiring high strength and first-rate electrical conductivity. Additionally, beryllium and its compounds find use in nonsparking tools, telecommunication devices, electrical contacts, nuclear reactors, ceramics, microwave equipment, communication satellites, space vehicles, aircraft, semiconductors, electrical insulators, everyday items such as golf clubs and bicycle frames, and many other applications requiring a hardening agent found in alloys such as beryllium copper. At risk: Workers experiencing chronic exposure to beryllium compounds are most at risk. This would include beryllium miners (the United States is the world’s largest producer); workers involved with beryllium alloys, ceramics, nuclear reactors, phosphorus manufacture, electronic equipment, and missiles; and garment workers exposed to beryllium dust. According to Environmental Protection Agency (EPA) estimates, work facilities in the United States release approximately 1 million pounds of beryllium and beryllium compounds into the environment annually, but the risk to the general population remains poorly understood. What is understood is that lung cancer risk rises with exposure time and beryllium dust concentration. Etiology and symptoms of associated cancers: The nonmalignant disease associated with beryllium and its compounds is called berylliosis. When exposed to high levels of beryllium, the immediate response is characterized by inflammation of the nose, larynx, trachea, bronchioles, 133
Beryllium and beryllium compounds and lungs. This is the acute form of beryllium disease and requires air levels of the metal on the order of 100 micrograms/cubic meter (mcg/m3) or more. Normally, ambient air levels are thousands of times less. As the exposure becomes more chronic, and typically from contact at much lower levels just exceeding 0.02 mcg/m3 over ten or more years, berylliosis takes the form of a granulomatous disease of the lungs and possibly other organs. Granulomas are nodular inflammatory lesions packed with immune cells (macrophages). Both the acute and chronic forms of berylliosis are usually not fatal. The beryllium lymphocyte proliferation test (BeLPT) is an effective blood test that measures beryllium sensitization. Although most people with beryllium sensitization will eventually develop berylliosis, further testing must be done to establish the individual’s disease status. This is an important diagnostic tool because chronic berylliosis is not only a serious illness but also a significant pathway to malignancy. The progression to chronic berylliosis follows a continuing, overzealous, and ultimately destructive immune response that leads to lung scarring and loss of respiratory capacity. This cascade of events is triggered by chemical messengers called cytokines, which repeatedly call in more immune cells than the lungs can process. This overzealous immune response leads to severe lung damage. The terrible number of deaths from the 1918 flu epidemic was a result of just such a cytokine storm and not from the destructive properties of the virus itself. The progression to lung cancer is not completely understood, and there is some debate over just how lung cancer arises from berylliosis, but most experts accept that chronic berylliosis is a strong marker for events leading to malignancy. History: Cancer arising from beryllium or its compounds depends on length and level of exposure. In general these exposure risks have been significantly reduced since the 1950’s, when workers might have been exposed to hundreds of times the levels found in twenty-first century working conditions. In 1991 researchers confirmed the carcinogenicity of beryllium and its compounds, and in 2002 the Department of Health and Human Services officially recognized beryllium as a carcinogen. The Occupational Safety and Health Administration (OSHA) sets permissible peak exposure limits for beryllium at 0.025 mcg/ m3; however, independent occupational health organizations are urging the reduction of these limits even further. To confuse the issue, there is even some minor debate on just how well previous data support the connection between cancer risk and beryllium exposure. 134
Salem Health: Cancer What is known is that certain factors may affect the progression of chronic beryllium disease (CBD). These factors include the individual’s work environment, the duration and intensity of exposure, and the particle size and solubility of the beryllium dust. Also the individual’s genetic makeup, lifestyle habits, and general health are contributing issues. Richard S. Spira, D.V.M. u
For Further Information American Conference of Governmental Industrial Hygienists. 1999 TLVs and BEIs: Threshold Limit Values for Chemical Substances and Physical Agents—Biological Exposure Indices. Cincinnati, Ohio: Author, 1999. American Industrial Hygiene Association. The AIHA 1998 Emergency Response Planning Guidelines and Workplace Environmental Exposure Level Guides Handbook. Fairfax, Va.: Author, 1998. Kelleher, P. C., et al. “Beryllium Particulate Exposure and Disease Relations in a Beryllium Machining Plant.” Journal of Occupational and Environmental Medicine 43 (2001): 238-249. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Eleventh Report on Carcinogens. Research Triangle Park, N.C.: Author, 2005. U.S. Environmental Protection Agency. Integrated Risk Information System (IRIS) on Beryllium. Washington, D.C.: National Center for Environmental Assessment, Office of Research and Development, 1999. _______. Toxicological Review of Beryllium and Compounds. Washington, D.C.: Author, 1998. U.S. Occupational Safety and Health Administration. Occupational Safety and Health Standards, Toxic and Hazardous Substances. Code of Federal Regulations 29 CFR 1910.1000. Washington, D.C.: Author, 1998.
u
Other Resources
Agency for Toxic Substances and Disease Registry ToxFAQS for Beryllium http://www.atsdr.cdc.gov/tfacts4.html U.S. Environmental Protection Agency CICAD Report on Beryllium and Beryllium Compounds http://www.inchem.org/documents/cicads/cicads/ cicad32.htm See also Carcinogens, known; Cytokines; Lung cancers.
Salem Health: Cancer
u Beta-carotene Category: Lifestyle and prevention ATC code: A11CA02 Also known as: A-Caro-25, betacarotene, carotene, carotenoid, Lumitene, retinal, retinol Definition: Beta-carotene is a member of a family of nutrients called carotenoids, which are found in many red, orange, yellow, and green fruits and vegetables (such as carrots, sweet potatoes, squash, spinach, apricots, and broccoli). The body converts beta-carotene into vitamin A, which plays a role in vision, bone development, cell division, and cell differentiation. Cancers treated or prevented: Studies have found that a diet high in fruits and vegetables containing beta-carotene reduces the risk of certain types of cancer, including those of the prostate and lung. Researchers believe that betacarotene and other antioxidants in fruits and vegetables work together to lower cancer risk.
Bethesda criteria It was thought that beta-carotene supplements might reduce the risk of certain cancers, especially lung cancer, but there is no evidence of any cancer preventive benefit when beta-carotene is taken alone in supplement form. In fact, studies have found that smokers and people who have been exposed to asbestos who take beta-carotene supplements have a significantly higher risk of developing lung cancer and of dying from their cancer than those who do not take the supplements. In addition, the National Cancer Institute’s Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (1992-2001) found that men with the highest levels of beta-carotene in their blood were at increased risk for developing more aggressive and deadly prostate cancer. Delivery routes: Oral in capsule and tablet forms. Eating five servings of fruits and vegetables daily provides 6 to 8 milligrams of beta-carotene. How this substance works: Beta-carotene is an antioxidant. It protects cells and deoxyribonucleic acid (DNA) from damage caused by unstable molecules called free radicals, which are produced during metabolic processes as cells burn up oxygen for energy. Free radicals are believed to contribute to cancer and other diseases. Vitamin A, which the body produces from beta-carotene, helps prevent the uncontrolled cell growth that occurs with cancer. Side effects: Beta-carotene may increase the risk of lung cancer or prostate cancer in people who smoke or drink alcohol heavily or who have been exposed to asbestos. It also may increase the risk of more aggressive prostate cancers. In high doses, beta-carotene may interact with some types of chemotherapy drugs or radiation. Stephanie Watson, B.S. See also Antioxidants; Carotenoids; Chemoprevention; Free radicals; Fruits; Nutrition and cancer prevention; Stomach cancers.
u Bethesda criteria Category: Procedures Definition: Bethesda criteria are a standardized set of criteria that are used to identify potential cases of hereditary nonpolyposis colorectal cancer (HNPCC), or Lynch syndrome. Carrots contain beta-carotene, among other nutrients. (U.S. Department of Agriculture)
Hereditary nonpolyposis colorectal cancer: HNPCC is an autosomal dominant disease that is characterized by early age of onset (average is before the age of forty-five), 135
Bile duct cancer tumor formation in a variety of tissues (endometrial, gastric, renal, ovarian, and skin), and microsatellite instability. HNPCC accounts for only about 3 to 5 percent of the cases of colorectal cancer, and the molecular and genetic testing that is required to diagnose this form of cancer can be quite time-consuming and costly. Therefore, it became important to set down a standardized set of criteria for identifying potential cases of HNPCC and to separate them from sporadic, noninherited forms of colorectal cancer. History: In 1997, a group of experts met at the National Institutes of Health to discuss the state of research on HNPCC. They came up with a set of criteria, the Bethesda criteria, which expanded the previous Amsterdam criteria to include extracolonic tumor formation as well as more specific histological characterization. In 2002, the criteria were further revised to define tumors that should be tested for microsatellite instability (MSI), which is the frequent mutation of repetitive deoxyribonucleic acid (DNA) sequences due to defects in the mismatch repair machinery in the cell. Criteria: Currently, the criteria for identifying a potential case of HNPCC are as follows: • Colorectal cancer diagnosed prior to age fifty • Presence of synchronous or metachronous HNPCCassociated tumors • High microsatellite instability (MSI-H) histology diagnosed prior to age sixty • One or more first-degree relatives diagnosed with an HNPCC-related tumor prior to age fifty • Colorectal cancer diagnosed in two or more first- or second-degree relatives Testing: If a patient meets the Bethesda criteria, a number of molecular and genetic tests are recommended. The ideal set of tests would include evaluation of microsatellite instability status as well as immunohistochemical analysis of tumors. In patients who show high levels of microsatellite instability and loss of expression of one or more of the DNA mismatch repair proteins, DNA sequencing of MSH2 and MLH1, the two genes most commonly mutated in HNPCC, should be performed. Patients who have mutations in either of these genes show an increased risk of developing cancer, and they should therefore undergo frequent screening. Lindsay Lewellyn, B.S. See also Ashkenazi Jews and cancer; Endometrial cancer; Ethnicity and cancer; Family history and risk assessment; MLH1 gene; MSH genes; Pancreatic cancers; PMS genes; Turcot syndrome. 136
Salem Health: Cancer
u Bile duct cancer Category: Diseases, symptoms, and conditions Also known as: Intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, perihilar cancer, Klatskin tumors Related conditions: Sclerosing cholangitis, liver cancer Definition: Bile is a fluid produced by the liver that aids in the digestion of fats. Bile is transported from the liver through a series of tubes, called bile ducts, to either the gallbladder, which stores and concentrates the bile, or directly to the small intestine. Bile duct cancer forms in the inner layer of these ducts. It can develop in the smaller ducts within the liver, where it is called intrahepatic cholangiocarcinoma, or in ducts outside the liver, where it is called extrahepatic cholangiocarcinoma. Extrahepatic cholangiocarcinoma is divided into two types, depending on where the cancer originates. Perihilar cancer develops in the bile duct close to its exit point from the liver. Distal bile duct cancer develops close to where the bile duct empties into the small intestine. Approximately 95 percent of cholangiocarcinomas are adenocarcinomas. Risk factors: Conditions that irritate the bile ducts have been linked to an increased risk of developing cholangiocarcinoma. These disorders include bile duct stones, congenital bile duct cysts, viral hepatitis, sclerosing cholangitis (especially in people who smoke), and nonviral cirrhosis. Other risk factors include ulcerative colitis, liver flukes (parasites found in Asian countries), and obesity. Exposure to some chemicals, including polychlorinated biphenyls, dioxin, and Thorotrast (previously used in X-ray diagnosis), also increase the risk of developing this cancer. Etiology and the disease process: The exact cause of most cholangiocarcinomas is unknown. Patients with no known risk factors often develop this cancer. Cholangiocarcinoma is a slow-growing cancer that can remain undetected until it has reached an advanced stage. It originates in the mucosal cells that line the ducts and spreads throughout the layers of the ducts. Eventually, the ducts become blocked, preventing the flow of bile. When the cancer grows through the walls of the ducts, it can invade the liver, gallbladder, small and large intestines, and blood vessels that serve the liver. Incidence: Primary cholangiocarcinoma is a rare disease that is most common in Asian countries because of its association with liver flukes. Approximately 90 percent of cholangiocarcinomas are extrahepatic, with about 65 percent perihilar tumors and 25 percent distal cancers. About
Salem Health: Cancer
Bile duct cancer
4,000 people in the United States develop this cancer each year, most of whom are men, and about 70 percent of them are older than age sixty-five. The American Cancer Society has noted an increase in the incidence of intrahepatic cholangiocarcinoma, possibly because of improved diagnostic testing.
Relative Survival Rates for Bile Duct Cancer, 1988-2001 Survival Rates (%)
Symptoms: Most cholangiocarcinomas do not produce symptoms until they are in the advanced stages. Jaundiced and itchy skin, dark urine, and pale bowel movements may occur if the ducts become blocked and bilirubin, a chemical in bile, is forced into the blood vessels. Other symptoms include fever, bloating, loss of appetite, weight loss, and fatigue. Screening and diagnosis: There are no screening tests for cholangiocarcinoma. Diagnosis typically is made during surgery for a gallbladder disorder or during diagnostic tests for other conditions. Blood chemistry and liver function tests, though not specific for this cancer, may show abnormal results. Tumor-marker studies may show the presence of carcinoembryonic antigen and cancer antigen 19-9 (CA 19-9). Ultrasound, computed tomography scanning, magnetic resonance imaging, endoscopic retrograde cholangiopancreatography, positron emission tomography, and percutaneous transhepatic cholangiography are imaging studies used to diagnose cholangiocarcinoma, determine treatment options, and assess the spread of the disease. Biopsy and biliary brushing may be performed to obtain cells for differential testing. Staging is based on the number of tumors present and the extent of their spread to other organs. Treatment and therapy: Traditional treatment for cholangiocarcinoma includes surgery, chemotherapy, and radiation therapy. Surgery for intrahepatic cholangiocarcinoma always involves the removal of part of the liver and is a difficult procedure. In many cases, the cancer is too far advanced at the time of diagnosis for surgery to be successful or safe for the patient. Surgery for extrahepatic cholangiocarcinoma usually involves the removal of the bile duct, gallbladder, and parts of the liver and small intestine. It may also include the resection of part or all of the pancreas. When the cancer cannot be removed, symptoms may be relieved by creating a bypass around the tumor blocking the bile duct or inserting a biliary drain. Chemotherapy and radiation therapy may be used before surgery to shrink a tumor, in place of surgery when the tumor is inoperable, and after surgery to destroy cells that may have spread. Common chemotherapeutic agents used include fluorouracil, cisplatin, doxorubicin, and gemcitabine. Radiation is commonly administered in the form of
Years
Intrahepatic
Extrahepatic
1 2 3 5 8 10
27.9 19.5 8.5 4.8 3.4 3.2
43.7 25.4 17.5 12.8 9.8 9.7
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007) Note: The median survival time for bile duct cancer is 5.6 months, for extrahepatic bile duct cancer, 9.4 months.
tiny seeds that are implanted into the duct, delivering highdose radiation directly to the tumor. Other forms of treatment that are being tested include using a person’s own immune system to fight the cancer, introducing viruses that seek out and destroy cancer cells, and photodynamic therapy, in which a special light is used to activate a drug that has been administered for the purpose of destroying cancer cells. Prognosis, prevention, and outcomes: The overall survival rate for cholangiocarcinoma is poor, with fewer than 20 percent surviving five years after diagnosis. Although there is no definitive way to prevent this disease, reducing exposure to its risk factors may prevent its development. Dorothy P. Terry, R.N. u
For Further Information Holland, Jimmie C., and Sheldon Lewis. The Human Side of Cancer. New York: HarperCollins, 2000. Souhami, Robert, and Jeffrey Tobias. Cancer and Its Management. Malden, Mass.: Blackwell, 2005. Stern, Theodore A., and Mikkael A. Sekeres. Facing Cancer: A Complete Guide for People with Cancer, Their Families, and Caregivers. New York: McGraw-Hill, 2004. u
Other Resources
American Cancer Society http://www.cancer.org 137
Bilobectomy
Salem Health: Cancer
Cancer.Net http://www.cancer.net/portal/site/patient
to be kept clean, and a gradual return to physical activity is recommended.
See also Afterloading radiation therapy; Alkaline phosphatase test (ALP); Carcinoid tumors and carcinoid syndrome; Cholecystectomy; Computed tomography (CT) scan; Endoscopic retrograde cholangiopancreatography (ERCP); Endoscopy; Gallbladder cancer; Gastrointestinal cancers; Infection and sepsis; Infectious cancers; Iridium seeds; Klinefelter syndrome and cancer; Liver cancers; Pancreatectomy; Pancreatic cancers; Percutaneous transhepatic cholangiography (PTHC).
Risks: The risks of a bilobectomy procedure are a narrowing of the bronchi (the large air passages leading from the windpipe to the lungs), scar formation, injury to nerves during surgery that may cause numbness and tingling in the chest area, and leakage of air from the surgical site with partial or complete collapse of the lung.
u Bilobectomy Category: Procedures Also known as: Lobectomy, thoracotomy Definition: A bilobectomy is a surgical procedure to remove two lobes of the lung.
Results: Surgery, including bilobectomy, is most effective for Stage I and Stage II non-small-cell lung cancer. Smoking cessation is of utmost importance to maximize surgical treatment as it improves wound healing and allows for the best outcome when additional therapies, such as radiation and chemotherapy, are used. Vicki Miskovsky, B.S., R.D. See also Bronchoalveolar lung cancer; Esophagectomy; Lobectomy; Lung cancers; Mesothelioma; Pleural effusion; Pleurodesis; Pneumonectomy; Surgical biopsies; Thoracoscopy; Thoracotomy.
Cancers treated: Various types of lung cancer Why performed: A bilobectomy is performed to remove diseased lung tissue. Patient preparation: Bilobectomy is performed under general anesthesia in a hospital with the usual preoperative preparation, such as physical examination, blood testing, and consultation with an anesthesiologist. In addition, an examination and additional lung tests will be done by a pulmonologist (a lung specialist). Steps of the procedure: The surgical procedure is performed by a thoracic surgeon making a cut in the side; the rib cage is separated or cut away to allow the lungs to be seen, and the pleura (a membrane around the lungs) is also cut away. The lung being operated on may be deflated, and the other lung continues to work with the help of a breathing tube. The lobes of the lung are pulled apart and separated, and the diseased lobes are cut free and removed. Arteries and veins that have been cut are sealed or reconnected. A drainage tube is left in the chest wall to drain or suction out fluid and air. The procedure may take from two to five hours. After the procedure: Pain medication will be used to make the patient more comfortable after the surgery. A hospital stay of about one week is to be expected; during hospitalization, breathing exercises as well as exercises for movement (range of motion) will be taught. Recovery at home can take several weeks, during which time pain medications may be used, the surgical incision site needs 138
u Bioflavonoids Category: Lifestyle and prevention Also known as: Flavonoids Definition: Flavonoids are the most common plant phenolic compounds. Their basic chemical structure consists of two benzene rings linked by a chain of three carbon atoms that can itself form a heterocyclic ring with oxygen. Variations of this chemical theme give rise to thousands of different bioflavonoids, which can be grouped in several families. Six families include bioflavonoids particularly common in the diet: flavonols, flavanols, flavonones (or flavanones), isoflavones, flavones, and anthocyanidines. Examples of bioflavonoids from each of these families are quercetin, cathechin, hesperitin, genistein, apigenin, and cyanidine, respectively. Most of the plant bioflavonoids occur as glycosides, that is, they have a sugar attached. Nutrition: The principal food sources of bioflavonoids are apples, celery, onions, green and black tea, citrus fruits, berries, soy, red wine, and cocoa. Although bioflavonoids are resistant to heat, certain food manipulations, such as the peeling of fruits or boiling, can cause some loss of their content or bioavailability. After the sugar moiety is removed by enzymes of the gastrointestinal tract, a variable portion of the ingested bioflavonoids is readily absorbed. The absorbed bioflavonoids are metabolized in the liver by conjugation with other chemical groups (for example,
Salem Health: Cancer
Biological therapy
glucuronic acid, sulfate, or methyl groups) and converted to smaller compounds.
eases, or to help lessen side effects from other cancer treatments such as chemotherapy.
Bioflavonoids and cancer: Numerous studies in experimental models, both in vivo and in vitro, have suggested that bioflavonoids have anticarcinogenic potential. As effective antioxidants, they prevent mutagenesis and tumor promotion by protecting deoxyribonucleic acid (DNA) and proteins from oxidative damage. By acting on signal transduction pathways that control the cell cycle, bioflavonoids inhibit proliferation and stimulate apoptosis, that is, programmed death, of human cancer cells. Cell cycle-related actions performed by bioflavonoids include suppressing nuclear factor kappa B activation, inhibiting mitogen-activated protein kinases, and blocking epidermal growth factor signaling. Bioflavonoids also stimulate detoxifying enzymes, such as cytochrome P450, which convert carcinogens into water-soluble compounds that can be eliminated from the body. In addition, they inhibit inflammation and angiogenesis. There is also strong scientific evidence that diets rich in fruits and vegetables protect against various forms of cancer. Some epidemiological studies have shown significant associations between high consumption of bioflavonoids and a reduced risk of certain forms of cancer, such as lung, rectal, and prostate cancers. However, several other epidemiological studies have failed to find such significant associations. Although bioflavonoids are gaining increasing acceptance as cancer-preventing agents, more consistent epidemiological data is needed before issuing specific public health guidelines. Reyniel Cruz-Aguado, Ph.D.
Cancers treated: A number of cancers, including melanoma, leukemia, breast, ovarian, colon, lung, and kidney cancers
See also Antioxidants; Beta-carotene; Carotenoids; Chemoprevention; Coenzyme Q10; Complementary and alternative therapies; Curcumin; Dietary supplements; Essiac; Free radicals; Fruits; Garlic and allicin; Green tea; Herbs as antioxidants; Isoflavones; Lutein; Lycopene; Nutrition and cancer prevention; Phenolics; Phytoestrogens; Resveratrol; Wine and cancer.
u Biological therapy Category: Chemotherapy and other drugs Also known as: Immunotherapy, biological response modifier therapy, biotherapy, biologic agents, biologic therapies, biologicals Definition: Biological therapy is an emerging, growing class of cancer drugs that work to help optimize the ability of the body’s immune system to fight cancer or other dis-
Subclasses of this group: Cytokines, monoclonal antibodies, colony-stimulating factors, antiangiogenesis agents, cancer vaccines Delivery routes: The delivery route varies depending on which biological therapy is being used. Various biological therapies may be given by mouth, by intravenous (IV) drip (infusion), by subcutaneous or intramuscular injection, or by delivery directly into a body cavity to treat a specific site. How these drugs work: The cells, antibodies, and organs of the immune system work to protect and defend the body against foreign invaders, such as bacteria or viruses. The immune system is a complex network of cells and organs that work together in a variety of ways. White blood cells are a very important part of the immune system. Lymphocytes are a type of white blood cell found in the blood and many other parts of the body that are intimately involved with the way that most biologic agents work. Types of lymphocytes include B cells, T cells, and natural killer (NK) cells. B cells mature into plasma cells that secrete proteins called antibodies, which recognize and attach to foreign substances known as antigens. Each type of B cell makes one specific antibody that recognizes one specific antigen. T cells produce proteins called cytokines, which include interferons, interleukins, and colony-stimulating factors. Cytokines are proteins that activate the immune system and that play an important role in communication between immune system cells. NK cells produce powerful cytokines that attach to and kill many foreign invaders, infected cells, and cancerous cells. Advances in techniques of molecular biology since the 1980’s have brought about a revolution in the understanding of many biological processes at a molecular level, including mechanisms involved in immunity and the pathogenesis of many diseases. In many cases, it has become possible to identify discrete specific molecular targets for therapeutic intervention and to design therapies to block or interact with those targets. At the same time, technological advances have made it possible to engineer and to produce these targeted therapeutic molecules for medical use. Physicians and researchers have found that, in addition to protecting the body against foreign invaders, the immune system might be able to differentiate between healthy 139
Biological therapy
Salem Health: Cancer
Common Biological Therapies Drug (Other Names)
Brands
Subclass
Delivery Mode Cancers Treated
Aldesleukin (interleukin-2)
Proleukin
Cytokine
Subcutaneous
Kidney cancer, melanoma
Alemtuzumab
Campath
Monoclonal antibody
IV
Chronic lymphocytic leukemia
Bacillus Calmette-Guérin vaccine
TheraCys BCG, TICE BCG
Vaccine
Introduction into bladder
Bladder cancer
Bevacizumab
Avastin
Monoclonal antibody
IV
Lung cancer, colorectal cancer
Cetuximab
Erbitux
Monoclonal antibody
IV
Head and neck cancers, colorectal cancer
Epoetin alfa, erythropoietin
Procrit
Colony-stimulating factor
Subcutaneous
Boosts red blood cell level during chemotherapy
Epratuzumab
LymphoCide
Monoclonal antibody
IV
B-cell leukemia
Filgrastim, granulocyte colony-stimulating factor
Neupogen
Colony-stimulating factor
Subcutaneous, Boosts white blood cell level during IV chemotherapy
Gemtuzumab ozogamicin
Mylotarg
Monoclonal antibody
IV
Acute myelogenous leukemia
Ibritumomab tiuxetan
Zevalin
Monoclonal antibody
IV
B-cell lymphoma
Interferon alpha-2a
Roferon-A
Cytokine
Subcutaneous
Hairy cell leukemia
Interferon alpha-2b
Intron-A
Cytokine
Subcutaneous
Melanoma, hairy cell leukemia, non-Hodgkin lymphoma, Kaposi sarcoma
Lym-1
Oncolym
Monoclonal antibody
IV
Lymphoma
Oprelvekin (interleukin-11)
Neumega
Cytokine
Subcutaneous
Boosts platelet level during chemotherapy
Panitumumab
Vectibix
Human monoclonal antibody
IV
Colorectal cancer
Quadrivalent human papillomavirus recombinant vaccine
Gardasil
Vaccine
Intramuscular
Cervical cancer
Rituximab
Rituxan
Monoclonal antibody
IV
Non-Hodgkin lymphoma
Tositumomab
Bexxar
Monoclonal antibody
IV
B-cell lymphoma
Trastuzumab
Herceptin
Monoclonal antibody
IV
Breast cancer
cells and cancer cells in the body and to eliminate cancerous ones. Biological therapies are designed to repair, stimulate, or enhance the immune system, either directly or indirectly, by assisting in the following ways: making cancer cells more recognizable by the immune system, boosting the killing power of immune system cells, changing the way in which cancer cells grow such that they act more like healthy cells, stopping the process that changes a normal cell into a cancerous cell, enhancing the body’s ability to repair or replace normal cells damaged or destroyed by other forms of cancer treatment such as chemotherapy or 140
radiation, and preventing cancer cells from spreading to other parts of the body. Biological therapies involve molecules that the body normally produces in small amounts in response to infection and disease and the use of modern recombinant deoxyribonucleic acid (DNA) technology to produce these molecules in large amounts for use in the treatment of cancers and other diseases. Molecular splicing of genes or portions of genes of interest to form DNA sequences that code for recombinant or fusion proteins is performed. These recombinant DNA sequences are spliced into plas-
Salem Health: Cancer mid vector molecules that can be introduced into host cells, which can be used in scaled-up production of large amounts of the purified recombinant or fusion protein. Important types of biological therapies are cytokines (interferons and interleukins), monoclonal antibodies, growth factors, colony-stimulating factors, antiangiogenesis agents, and cancer vaccines. Interferons were the first cytokines to be produced in the laboratory for use as biological therapies. Several types of inferons occur naturally in the body, of which interferon alpha is the most widely used in cancer treatment. Interferons can improve the immune system function against cancer cells and may in addition directly slow the growth of cancer cells or promote their development into cells with more normal behavior. There is some evidence that interferons may also stimulate NK cells and T cells, thereby boosting the immune system’s function against cancer cells. Intron A (interferon alpha) has been approved by the Food and Drug Administration (FDA) for cancer treatment; it is used for the treatment of hairy cell leukemia, melanoma, chronic myeloid leukemia, and AIDS-related Kaposi sarcoma and non-Hodgkin lymphoma. Interleukins are also cytokines that occur naturally in the body. Many types have been identified. Interleukin-2, which stimulates the growth and activity of many immune cells which can destroy cancer cells, has been the most widely studied in cancer treatment. Proleukin (interleukin-2) has been approved for use in the treatment of metastatic melanoma and metastatic renal cell carcinoma. Monoclonal antibodies are a single species of antibody that is produced in the laboratory from a single type of cell and is specific for a particular antigen. The production of monoclonal antibodies involves the creation of a hybrid cell line specific for that antibody molecule, called a hybridoma. Once produced, a hybridoma can be perpetuated in the laboratory to produce as much of the pure monoclonal antibody as desired. Monoclonal antibodies may be used in several ways. They may be used to boost the immune response to cancer cells, they may be designed to act against growth factors to inhibit the growth of cancer cells, and they may be linked to anticancer drugs, radioactive substances, or toxins to act as a vector to deliver these toxic agents directly to cancer cells. Rituxan (rituxamab) and Herceptin (trastuzumab) are examples of monoclonal antibodies that have been approved by the FDA, Rituxan for the treatment of non-Hodgkin lymphoma and Herceptin to treat metastatic breast cancer. Colony-stimulating factors (CSFs) stimulate bone marrow cells to divide and develop into white blood cells, red blood cells, and platelets. CSFs may be helpful for some patients undergoing treatment for cancer because many
Biological therapy anticancer drugs used in chemotherapy can damage the body’s ability to make these important cells in the bone marrow. Thus patients receiving chemotherapy have an increased risk of developing infections, anemia, and bleeding more easily. The dose of chemotherapy that a patient receives, and therefore the chemotherapy regimen’s effectiveness in fighting cancer, can sometimes be increased by using CSFs to eliminate or reduce the risk of infection or the need for transfusions. Neupogen (filgrastim) and Procrit (epoetin alfa) are colony-stimulating factors that the FDA has approved for use in cancer patients, Neupogen to boost the number of white blood cells during chemotherapy and Procrit to boost the number of red blood cells during chemotherapy. Antiangiogenesis agents, also called angiogenesis inhibitors, are an emerging type of biological therapy that show promise in fighting cancer. Cancer cells are rapidly dividing cells that depend on a rich network of small blood vessels to supply them with oxygen and nutrients. Tumors must generate this network of new blood vessels, a process called angiogenesis. Several types of molecules and antibodies have been shown to prevent angiogenesis and shrink tumors. Avastin (bevacizumab) is an antiangiogenic monoclonal antibody that has been approved for the treatment of lung and colorectal cancers. Cancer vaccines are another type of biological therapy being studied. Vaccines for infectious diseases work by exposing an uninfected individual to a weakened form of the infectious agent. The vaccine stimulates the immune system to mount an immune response to the agent but cannot cause the disease. The immune system produces antibodies specific to antigens present on the surface of the infectious agent. The immune system is also stimulated to produce certain types of T cells, which remember the exposure to the antigen. If the individual is subsequently challenged with the same infectious agent, then these T cells will orchestrate a quick and effective immune response, protecting the individual from contracting the disease. Cancer vaccines to treat existing cancers (therapeutic vaccines) or to protect healthy individuals from developing cancer (prophylactic vaccines) are being studied. Therapeutic vaccines may be effective in stopping the growth of existing cancer cells, in preventing cancer from recurring, or in killing existing cancer cells. Prophylactic vaccines are administered to healthy individuals to protect against cancers that are caused by viruses. Gardisil (quadrivalent human papillomavirus recombinant vaccine) is a prophylactic vaccine that has been approved by the FDA for the prevention of cervical cancer caused by human papillomavirus. Some biological therapies have been approved by the 141
Biopsy FDA for certain types of cancer, while many, still in development, are offered in clinical research studies to measure the effects of the treatment. In these cases, study results are often used as part of the FDA evaluation of the drug’s efficacy and safety. Side effects: The side effects of biological therapy regimens are variable from patient to patient. The most common side effects are a result of stimulation of the immune system and are similar to flulike symptoms, including fever, chills, body aches, nausea, vomiting, loss of appetite, and fatigue. Some patients may experience a rash or swelling at the injection site. Most side effects diminish one to two days after treatment. For patients who receive multiple doses of a biological therapy, the side effects usually lessen over time. Jill Ferguson, Ph.D. u For Further Information Kimura, F. “Molecular Target Drug Discovery.” Internal Medicine 46 (2007): 87-89. Old, L. J. “Immunotherapy for Cancer.” Scientific American 275 (1996): 136-143. Reang, P., M. Gupta, and K. Kohli. “Biological Response Modifiers in Cancer.” Medscape General Medicine 14 (2006): 33. Rosenberg, Steven A., ed. Principles and Practice of the Biologic Therapy of Cancer. 3d ed. Philadelphia: Lippincott Williams & Wilkins, 2000. Sorscher, S. M. “Biological Therapy Update in Colorectal Cancer.” Expert Opinion on Biological Therapy 7 (2007): 509-519. Zafir-Lavie, I., Y. Michaeli, and Y. Reiter. “Novel Antibodies as Anticancer Agents.” Oncogene 28 (2007): 3714-3733.
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Other Resources
American Cancer Society Immunotherapy http://www.cancer.org/docroot/CRI/content/ CRI_2_4_4X_Biological_Therapy_Immunotherapy_ 50.asp?sitearea= Emory Healthcare Biologic Therapies for Cancer Care http://healthlibrary.epnet.com/ GetContent.aspx?token=8482e079-8512-47c2-960ca403c77a5e4c&chunkiid=32583 142
Salem Health: Cancer National Cancer Institute Biological Therapy http://www.cancer.gov/cancertopics/ biologicaltherapy Stanford Comprehensive Cancer Center Biological Therapy for Cancer Treatment http://www.cancer.gov/cancertopics/ biologicaltherapy See also Anthrax; Antineoplastics in chemotherapy; Bacillus Calmette Guérin (BCG); Cancer biology; Chemotherapy; Cytokines; Gene therapy; Immune response to cancer; Immunotherapy; Medical oncology; Metastasis; Monoclonal antibodies; Nutrition and cancer treatment; Stem cell transplantation; Tumor necrosis factor (TNF); Tyrosine kinase inhibitors; Vaccines, therapeutic.
u Biopsy Category: Procedures Also known as: Tissue sampling, fine needle aspiration, needle biopsy, percutaneous biopsy, core biopsy, incisional biopsy, excisional biopsy, endoscopic or laparoscopic biopsy, surgical biopsy, open biopsy, transvenous biopsy Definition: A biopsy is the removal of a tissue sample for laboratory analysis to detect the presence of cancer cells. There are several types of biopsy procedures. The type of biopsy procedure performed is dependent on the type of cancer suspected and the area of the body being examined. In fine needle aspiration (also called needle biopsy or percutaneous biopsy), a very fine needle is inserted into the area and a sample of fluid or tissue is withdrawn through the needle into an attached syringe. This type of biopsy procedure may be used to remove tissue from an organ that is otherwise accessible only via surgery, such as the liver, pancreas, or lung. The advantage of fine needle aspiration is that it does not require a surgical incision. To place the needle accurately, ultrasound or computed tomography (CT) guidance may be used. Similar to fine needle aspiration, core biopsy uses a larger needle to withdraw a greater sample of fluid or tissue. Ultrasound or CT guidance may be used. In incisional biopsy, a scalpel or similar instrument is used to remove a portion of the suspected cancerous tissue via an incision made in the skin. Incisional biopsies are most commonly used to remove soft tissue, such as skin, connective tissue, muscle, and fat. For skin lesions, an in-
Salem Health: Cancer
Biopsy
In incisional biopsy, a scalpel is used to remove a sample of the suspected cancerous tissue through an incision made in the skin. (PhotoDisc)
cisional biopsy may be performed with a hollow, circularshaped instrument (punch biopsy), or a razor may be used (shave biopsy). Depending on the type of procedure, the patient may be under general or local anesthesia. In excisional biopsy (sometimes called open biopsy or surgical biopsy), a whole lump, tumor, or organ and a margin of normal tissue around it are removed. An excisional biopsy may be used to remove some types of tumors or suspected cancers that need to be removed entirely for an accurate diagnosis, such as the removal of lymph nodes to diagnose lymphoma accurately. General anesthesia is usually used for excisional biopsies. In endoscopic or laparoscopic biopsy, an endoscope (small camera on a thin tube) is used to view an internal area and to identify the tissue for removal. The endoscope transmits magnified images of the area onto a video monitor to guide the physician during the procedure. The endoscope can be inserted through a natural body opening, such as the throat to remove esophageal tissue, or it can be inserted through a small incision. Surgical instruments attached to the endoscope or inserted through other small in-
cisions can be used to remove the tissue. Endoscopic biopsy procedures are the most common type of biopsies. A laparoscopic biopsy procedure may be used when a tissue sample is needed from more than one area or when a larger tissue sample is needed. General or local anesthesia may be used, depending on the biopsy site. A capsule biopsy is a type of laparoscopic technique in which a patient swallows a capsule that is connected to a thin tube. X rays confirm the proper positioning of the capsule, and a syringe attached to the end of the tube is used to withdraw a tissue sample into the capsule. The capsule and tube are gently removed, and the tissue sample is taken to the laboratory for analysis. This type of biopsy procedure may be used to remove a sample of tissue from the lower gastrointestinal tract. Other biopsy procedures include colposcopic biopsies to identify and remove abnormal tissue from the cervix, transvenous biopsy to remove tissue via a catheter inserted into a vein in the neck, and bone marrow biopsy to remove a bone marrow sample through a needle inserted into the hip and withdrawn through a syringe. 143
Biopsy Cancers diagnosed: Various, including breast, bone, gynecological, liver, lung, lymph node, skin, thyroid, urological, and gastrointestional cancers Why performed: A biopsy is performed to diagnose and stage cancer when an abnormality is found during diagnostic tests. It also may be performed to determine the cause of unexplained symptoms or to match organ tissue before a transplant. Patient preparation: Tests before the procedure may include blood tests, urine tests, a chest X ray, an electrocardiogram, CT scanning, magnetic resonance imaging (MRI), and other imaging tests. The patient preparation for a biopsy procedure varies depending on the type of procedure and biopsy location. In some cases, no special preparation is required. In other cases, the patient must not eat or drink for eight hours beforehand and is required to stop taking anticoagulant medications for several days before the procedure. The patient will receive specific preparation instructions from the health care team. Steps of the procedure: Local or general anesthesia may be used, depending on the type of biopsy procedure and biopsy location. The biopsy site is cleansed, and a local anesthetic is injected into the area. In some cases, such as with sentinal node biopsy, a radioactive substance or dye is injected into the tumor and a scanner is used to locate the lymph node or tissue containing the radioactive substance or stained with the dye. The tissue sample or fluid is removed via one of the biopsy techniques. The sample is sent to a laboratory for microscopic analysis by a pathologist. There are a variety of methods for processing tissue samples. Histologic sections involve preparing stained, thin slices of tissue mounted on slides, a process that may take up to forty-eight hours. With the histologic method, the tissue sample is placed in a machine that replaces all water in the sample with paraffin wax. The sample is embedded into a larger block of paraffin, sliced into very thin sections, and stained with dye to aid microscopic analysis. Frozen tissue analysis involves freezing the tissue, slicing it into thin sections, and staining the sections to aid analysis. Smears are tissue samples that are spread onto a slide for examination. The results of smears can usually be obtained very quickly. After the procedure: The length of a patient’s recovery and the steps for recovery vary depending on the type of biopsy procedure and biopsy location. The patient may stay in a recovery room for a certain amount of time after the procedure. The biopsy site is usually covered with a bandage or dressing. Medication is prescribed as needed for relief of pain, which may include discomfort at the bi144
Salem Health: Cancer opsy site or muscle pain. An overnight hospital stay may be required for some fine needle aspiration, laparoscopic, and surgical biopsy procedures. Specific instructions for driving, activity, incision care, medications, nutrition, and follow-up care are provided to the patient, as applicable. In some cases, the patient is not permitted to drive home after the procedure. Depending on the physician’s instructions, the patient may be required to stay on bed rest at home for a certain amount of time after the procedure. Risks: The risks of biopsy procedures are dependent on the type of procedure performed and the biopsy location. Possible risks of all biopsy procedures include bleeding and infection. The risk of death associated with biopsy procedures is generally very low. The physician may discuss specific mortality rates and risks with the patient, depending on the type of procedure performed. Results: The tissue sample removed during the procedure is either normal, which means it is benign or noncancerous, or abnormal, which means it has unusual characteristics and may be malignant or cancerous. In some cases, the tissue that was obtained during the biopsy is not adequate to make a diagnosis, and a repeat biopsy procedure or a different type of biopsy procedure may be performed. The type of cancerous cells and extent of disease will help guide the patient’s treatment. Angela M. Costello, B.S. u
For Further Information DeVita, Vincent, Jr., Samuel Hellman, Steven A. Rosenberg, et al., eds. Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2005. McPhee, Stephen J. Maxine A. Papadakis, and Lawrence M. Tierney, eds. Current Medical Diagnosis and Treatment 2008. New York: McGraw-Hill Medical, 2007. Ota, D. M. “What’s New in General Surgery: Surgical Oncology.” Journal of the American College of Surgeons 196, no. 6 (2003): 926-932.
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Other Resources
American Cancer Society http://www.cancer.org National Cancer Institute http://www.cancer.gov RadiologyInfo http://www.radiologyinfo.org
Salem Health: Cancer Society of Interventional Radiology http://www.sirweb.org See also Anoscopy; Axillary dissection; Bone marrow aspiration and biopsy; Breslow’s staging; Bronchoscopy; Colonoscopy and virtual colonoscopy; Colorectal cancer screening; Colposcopy; Computed tomography (CT)guided biopsy; Conization; Core needle biopsy; Culdoscopy; Cystoscopy; Cytology; Dilation and curettage (D&C); Dukes’ classification; Endoscopic retrograde cholangiopancreatography (ERCP); Endoscopy; Flow cytometry; Gastric polyps; Gleason grading system; Grading of tumors; Hormone receptor tests; Hysteroscopy; Immunocytochemistry and immunohistochemistry; Ki67 test; Laparoscopy and laparoscopic surgery; Laryngoscopy; Liver biopsy; Loop electrosurgical excisional procedure (LEEP); Lumpectomy; Lymphadenectomy; Mediastinoscopy; Needle biopsies; Needle localization; Pap test; Paracentesis; Pathology; Pleural biopsy; Polypectomy; Premalignancies; Progesterone receptor assay; Prostate-specific antigen (PSA) test; Receptor analysis; Screening for cancer; Sentinel lymph node (SLN) biopsy and mapping; Sigmoidoscopy; Staging of cancer; Stereotactic needle biopsy; Surgical biopsies; Thoracoscopy; Thoracotomy; TNM staging; Upper gastrointestinal (GI) endoscopy; Wire localization.
u Birt-Hogg-Dubé syndrome
(BHDS) Category: Diseases, symptoms, and conditions Related conditions: Renal cell carcinoma, pulmonary cysts Definition: Birt-Hogg-Dubé syndrome (BHDS) is a rare, genetically linked syndrome named after the three Canadian doctors who first identified it as a skin disorder. It consists of three types of benign skin growths: fibrofolliculomas, white or flesh-colored tumors that occur in hair follicles; trichodiscomas, overgrowths of tissues in hair disks; and acrochordons, commonly called skin tags. These growths are typically found on the face, neck, chest, and scalp. Since the identification of BHDS in 1977, further study of patients with the syndrome has revealed additional abnormal conditions that characteristically develop in affected individuals. The most common of these conditions include benign and cancerous kidney tumors, lung cysts, and spontaneous pneumothorax.
Birt-Hogg-Dubé syndrome (BHDS) Risk factors: BHDS is genetically linked, meaning that it is associated with a defect in one or more genes. Although in most cases the gene responsible for BHDS has been passed through families, evidence of genetic mutation in people with no familial link has also been identified. People with a defective gene and who also smoke have a higher risk of developing kidney cancer. Etiology and the disease process: BHDS is caused by a mutation in the gene that is responsible for the body’s production of folliculin, a protein that acts as a tumor suppressor. When folliculin is absent or not functioning properly, it cannot control cellular growth and division, which leads to tissue overgrowth and the formation of tumors. Folliculin is present in many types of tissues but is primarily found in skin, lung, and kidney cells. The folliculin gene, otherwise know as FCLN, is located on chromosome 17p11.2. Normally, during conception, the body receives two copies of every gene, one from the mother and one from the father. In BHDS, a single defective copy of the gene, from either the mother or the father, results in a person’s being affected by the disease. BHDS usually begins with the formation of skin growths. As the disease progresses, these growths increase in number and size. Slow-growing kidney tumors can develop as single or multiple tumors in one or both kidneys. Several types of tumors have been associated with BHDS, including benign tumors such as renal oncocytomas and cancerous tumors such as chromophobe renal carcinoma and clear cell carcinoma. Benign tumors often become cancerous as the disease progresses. Research into kidney tumors associated with BHDS indicates that a genetic mutation occurs in the second gene of affected kidney cells, producing two defective genes, which allows these tumors to grow. Incidence: BHDS is very rare, having been identified only in about sixty families worldwide. A precise incidence rate is unknown because people are not routinely tested for the presence of the FCLN gene. There is no indication that race or gender influences a person’s risk of having the gene or developing the disease. The typical age that a person begins to display signs of BHDS is between the late twenties and early forties. The incidence of kidney cancer in people with BHDS may be as low as 15 percent; however, the incidence of lung cysts is estimated to be about 90 percent. Symptoms: Although some people with BHDS have no noticeable symptoms of the disease, the development of fibrofolliculomas or acrochordons is usually the first indication that the person is affected. Initially looking like 145
Birth control pills and cancer small, white pimples, fibrofolliculomas typically become larger and more prolific as time passes. The development of polyps in the mouth or colon may also indicate BHDS and should be investigated further. Lung cysts, which usually do not cause respiratory problems, or lung cancer may be detected during routine examinations or testing for other conditions. Multiple or bilateral kidney tumors are often the first indication of BHDS. Screening and diagnosis: Several recurrent tests are recommended for people with BHDS and those with family members who have BHDS. Recommendations include an annual kidney ultrasound and chest X ray, computed tomography scanning or magnetic resonance imaging every two years, and biopsies of suspicious skin growths. DNA (deoxyribonucleic acid) testing to check for genetic alterations should be considered for individuals who have family members with the disease. Genetic counseling should precede any such testing. The disease is typically diagnosed after skin lesion biopsies are positive for fibrofolliculomas or when multiple kidney tumors and lung cysts are identified. Treatment and therapy: There is no specific medical treatment recommended for the skin tumors associated with BHDS. Surgical removal, electrodesiccation, and dermabrasion have been used without long-term success, as the growths recur. A relatively new procedure for BHDS-related skin tumors is laser skin resurfacing, which has been successful in several cases; however, long-term results are unknown. Both benign and cancerous kidney tumors are removed surgically. However, new tumors often form in place of the ones removed. When possible, only part of the kidney is removed to prolong the patient’s kidney function. Experimental treatments to destroy the cancer cells may be used on recurrent tumors. These include cryoablation, freezing the tumor, and radio frequency ablation, killing the tumor with heat. Prognosis, prevention, and outcomes: The prognosis for BHDS depends on whether kidney cancer develops and the success of its treatment. BHDS cannot be prevented. Dorothy P. Terry, R.N. u For Further Information Lindor, Noralane M., et al. “Birt-Hogg-Dubé Syndrome: An Autosomal Dominant Disorder with Predisposition to Cancers of the Kidney, Fibrofolliculomas, and Focal Cutaneous Mucinosis.” International Journal of Dermatology 40, no. 10 (October, 2001): 653-656. Pavlovich, C. P., et al. “Renal Tumors in the Birt-Hogg-
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Salem Health: Cancer Dubé Syndrome.” American Journal of Surgical Pathology 26 (2002): 1542-1552. Pomery, Chris. DNA and Family History. Toronto: Dundurn Press, 2004. u
Other Resources
Birt Hogg Dube Family Alliance What Is BHD? http://www.birthoggdube.org/id1.html Genetics Home Reference Birt-Hogg-Dubé Syndrome http://ghr.nlm.nih.gov/ condition=birthoggdubesyndrome See also Hereditary leiomyomatosis and renal cell cancer (HLRCC); Kidney cancer; Urinary system cancers.
u Birth control pills and cancer Category: Carcinogens and suspected carcinogens RoC status: Most birth control pills contain two active ingredients, a form of estrogen and a form of progesterone. Collectively, estrogens have been classified as a known human carcinogen since 1985. Progesterone has been listed as a reasonably anticipated human carcinogen since 1985. Also known as: Oral contraceptives Related cancers: Breast cancer, cervical cancer Definition: A birth control pill is a tablet containing a synthetic estrogen, such as ethinylestradiol; a synthetic progesterone, such as norethindrone; or both. These compounds mimic the action of naturally occurring sex hormones and are administered to alter the function of tissues that respond to these hormones. For example, a moderate, consistent dose of estrogen will prevent the typical spike in estrogen that occurs naturally during the middle of the menstrual cycle. This in turn prevents the ovary from releasing an egg. Estrogen and progesterone have different effects on reproductive tissues that, in combination, are highly effective in preventing pregnancy. Although the majority of birth control pills contain a dose of each hormone, minipills that contain only a progesterone are also available. Although contraception is the most common reason for using birth control pills, the pill is also commonly prescribed for other purposes, such as bothersome menstrual symptoms and acne.
Salem Health: Cancer
Birth control pills and cancer
Exposure routes: Birth control pills are tablets that are ingested orally. Several alternative delivery systems, such as transdermal patches, contain similar active ingredients that are taken into the body through other routes. Where found: Birth control pills are manufactured by drug makers and prescribed by health providers. The World Health Organization estimates that approximately 10 percent of all women of reproductive age worldwide use birth control pills. At risk: At highest risk are women of reproductive age, particularly in developed countries where the pill is more widely available and pill use is more prevalent. A small minority of pill users are women who take the pills to manage menopausal symptoms. Etiology and symptoms of associated cancers: The majority of breast cancers, though not all, involve the abnormal growth and proliferation of cells that are responsive to estrogen. Studies in mice and rats indicate that exposure to either synthetic estrogen alone or synthetic progesterone alone caused maligEstrogen, an essential ingredient in birth control pills, is a known human carnant tumors to develop in mammary tissue. cinogen. (Object Gear) Likewise, combinations of synthetic estrogen and progesterone appear to cause developthe risk of cervical cancer even when HPV status is taken ment of both benign and malignant mammary tumors in into account. animals. In humans, breast cancer risk increases with proConversely, the use of birth control pills appears to relonged exposure to estrogen from both internal and exterduce the risk of some types of cancer. There is abundant nal sources, although not all studies of birth control pill usevidence suggesting that birth control pill use reduces a ers have demonstrated an increased risk of breast cancer. woman’s risk of developing ovarian cancer, possibly due Research suggests that breast cancer risk related to pill use to fewer cycles of ovulation over her life span. Birth conis greatest among women who use the pill for several years trol pill use also appears to decrease the risk of cancer of or more before their first full-term pregnancy. After longthe endometrium (the uterine lining), with protective efterm cessation of pill use, the risk of breast cancer appears fects lingering long after cessation of pill use. to decrease to a level comparable to that of women who never used the pill. The risk of cervical cancer is also increased with birth History: The first birth control pill became available in the control pill use and appears to be related to the duration of United States in 1960, and birth control pills were widely pill use, although the risk most likely declines over time adopted in the decades that followed. Early concern about after cessation of use. Research to date has yet to fully exthe safety of birth control pills linked the high doses of plain the relationship between cervical cancer and birth estrogen in birth control pills with an increased risk of control pills. Some researchers have argued that pill users serious cardiovascular events, including heart attack and differ from nonusers in risk factors for human papillostroke. Over time, drug manufacturers lowered the dosmavirus (HPV) infection, which is closely linked to the ages of estrogen in birth control pills. development of cervical cancer. However, to date several By the 1980’s researchers had observed associations studies have suggested that birth control pill use increases between birth control pill use and cancer risk. However, 147
Bis(chloromethyl) ether and technical-grade chloromethyl methyl ether
Salem Health: Cancer
studies were inconsistent in confirming this relationship, and a number of large population-based studies were undertaken to clarify the effect of pill use on cancer risk. After review of multiple such studies, the International Agency for Research on Cancer, a division of the World Health Organization, classified combined estrogenprogesterone birth control pills as carcinogenic to humans. Andrea Bradford, M.A.
u Bis(chloromethyl) ether and
u For Further Information Cerhan, James R. “Oral Contraceptive Use and Breast Cancer Risk: Current Status.” Mayo Clinic Proceedings 81, no. 10 (2006): 1287-1289. Parker, James M., and Philip M. Parker, eds. Birth Control Pills: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References. San Diego, Calif.: Icon Health, 2003. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Eleventh Report on Carcinogens. Research Triangle Park, N.C.: Author, 2005. Zonderman, Jon, and Laurel Shader. Birth Control Pills. New York: Chelsea House, 2006.
Related cancer: Lung cancer
u
Other Resources
Mayo Clinic Birth Control Pill Frequently Asked Questions: Benefits, Risks, and Choices http://www.mayoclinic.com/health/birth-control-pill/ WO00098 National Cancer Institute Oral Contraceptives and Cancer Risk: Questions and Answers http://www.cancer.gov/cancertopics/factsheet/Risk/ oral-contraceptives See also Antiestrogens; Cervical cancer; Endocrine cancers; Endometrial cancer; Endometrial hyperplasia; Estrogen-receptor-sensitive breast cancer; Fertility drugs and cancer; Fibrocystic breast changes; Gestational trophoblastic tumors (GTTs); Hormonal therapies; Hormone receptor tests; Hormone replacement therapy (HRT); Ovarian cancers; Ovarian cysts; Progesterone receptor assay; Receptor analysis; Screening for cancer; Vasectomy and cancer.
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technical-grade chloromethyl methyl ether Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1980 Also known as: BCME, chloro(chloromethoxy) methane dichloromethyl ether, CMME, dimethylchloroether, methyl chloromethyl ether
Definition: Bis (chloromethyl) ether (BCME) and technicalgrade chloromethyl methyl ether (CMME) are chemicals known as chloroalkyl ethers. Both are clear, flammable liquids with strong, unpleasant odors. Exposure routes: After BCME and CMME are released into the air, humans can be exposed by inhalation, dermal contact, and oral exposure via contaminated water. Potential exposure by inhalation can occur to workers who are involved in the production of BCME and CMME. Where found: BCME and CMME are found at production sites where they have been released into the air and at landfill sites where they have been transferred for disposal. Both are found in chemical plants where they are manufactured and in research laboratories where they are used to make other chemicals. They can also be found in plants where they have been used to make several types of polymers, resins, plastics, and textiles. Small quantities of BCME can be formed as an impurity during the production of CMME. CMME can be converted to BCME through hydrolysis. At risk: The greatest risk for contamination from BCME and CMME is to chemical plant workers, laboratory workers, ion-exchange resin makers, and polymer producers. The general public experiences some risk from both chemicals around sites where they are produced or where they are discarded, such as landfills and surface impoundments. Etiology and symptoms of associated cancers: Individuals exposed to BCME and CMME show significant increases in the incidence of lung carcinomas, mostly of the oat-cell type, which is generally not associated with smoking tobacco. The number of lung carcinomas is much higher in people exposed to just BCME, as compared with individuals who are exposed to both BCME and CMME. When exposed to BCME or CMME, individuals have shown a slight increase of incidence of chromosomal aberrations in peripheral lymphocytes. Both chemicals can
Salem Health: Cancer
Bisphenol A (BPA)
induce unscheduled synthesis of deoxyribonucleic acid (DNA) in human fibroblasts in vitro. History: Although BCME and CMME were previously manufactured in the United States, use of both chemicals in the United States has dropped significantly since 1976. Since 1982, only CMME is produced in the United States. In the past, BCME was used to treat vulcanized rubber to increase adhesion and in the production of flame-retardant fabrics. CMME is used as an alkylating agent and solvent in manufacturing polymers, ion-exchange resins, and water repellants. Alvin K. Benson, Ph.D. See also Carcinogens, known; Carcinogens, reasonably anticipated; Occupational exposures and cancer.
u Bisphenol A (BPA) Category: Carcinogens and suspected carcinogens Also known as: 4, 4′-(1-Methylethylidene)bisphenol; 2, 2-bis (4-hydroxyphenyl) propane Related cancers: Prostate and breast cancer Definition: Bisphenol A (BPA) is an organic compound belonging to the aromatic class known as phenols. It is the main monomer used for the manufacture of polycarbonate plastics, which are essentially long chains of individual BPAmolecules linked together. All the BPAmonomers do not react to form the polymer, as a result of which small amounts of the unpolymerized free units leach into the contents of the plastic containers. Exposure routes: Exposure to BPA is mainly through direct contact or by ingesting food or drink that has been in contact with plastic material containing bisphenol A. BPA is known to leach into the contents of polycarbonate containers under certain conditions. It is also released from epoxy resins that are used in dental sealants, food container linings, polyvinyl chloride (PVC) pipes, and flooring materials. As plastics are used ubiquitously in modern society, bisphenol A has many plausible exposure routes for humans. Where found: Bisphenol A is a high-production-volume chemical used as the main building block for the manufacture of many polymers such as polycarbonates and epoxy resins. Polycarbonates are widely used for making food and drink containers, baby bottles, milk containers, and water pipes, and epoxy resins are used in the linings of metal food containers and in dental sealants.
BPA, a suspected carcinogen, is known to leach into the contents of plastic bottles. (©Sean Macdiarmid/Dreamstime.com)
At risk: Infants, children, and adults Etiology and symptoms of associated cancers: The safety data on bisphenol A are controversial. A hazard assessment study by the National Toxicology Program is ongoing. The final peer-reviewed assessment results will be used as a basis for federal regulation of the compound. If the assessment indicates concern about carcinogenicity and other health risks associated with BPA exposure, appropriate measures will be formulated to protect public health and safety. BPA is a known hormone disrupter, and many studies have confirmed this effect. Most research data on the adverse effects of BPA exposure have been collected in rodent studies. Low-level chronic exposure to BPA has been reported to cause endocrine disruption even at levels of 2.3 micrograms per kilogram (mcg/kg) per day, leading to aberrant growth of mammary tissue in mice, which is a pre149
Bisphenol A (BPA) cursor to breast cancer. Additionally it has been reported that prenatal exposure to low levels of BPA causes breast cancer in adult rats. Research reports indicate that BPA at low levels causes adverse effects on the development of the prostate in fetal mice. Studies also suggest that exposure to BPA in the womb alters gene behavior in such a way as to lead to development of prostate cancer in adult rats. A small study involving Japanese women found that the serum levels of BPA were three times higher in women with a recurrent history of miscarriages, providing indirect evidence for BPA as an endocrine-disrupting chemical. History: Bisphenol A was first synthesized in 1891. In the 1930’s it was demonstrated that BPA mimicked the action of estrogens in rats. Around that time, diethylstilbestrol, a more potent estrogen, was discovered, relegating BPA to the background in terms of pharmacological use. In the 1950’s polymer chemists discovered that BPA could be polymerized readily to make plastics such as polycarbonate. BPA thus became a large-volume chemical used in the plastics industry. It is also used as an inert ingredient in antioxidants, pesticides, and flame retardants. Additionally it is used in materials for making reinforced pipes, water-main filters, floorings, and enamels. Its ubiquitous use creates various exposure routes for humans. BPA has been measured in river water, reservoirs, streams, and estuaries. There is ongoing debate about the safety limit for this compound. In the 1980’s the Environmental Protection Agency (EPA) set a reference dose of up to 50 mcg/kg per day in the United States and considers intake below this dose to be safe for health. However, based on research in the late 1990’s and early 2000’s, scientists are of the consensus that exposure to BPA well below the EPA guideline induces adverse effects in rodents in the fetal stage, and these effects are precursors to breast cancer and prostate cancer in adulthood. The cause for concern is that the low levels inducing carcinogenicity in the rodent experiments are within the range of daily human exposure to BPA. European and American regulatory agencies have maintained that exposure to BPA from polycarbonates and epoxy resins does not pose a health risk. Bisphenol A is one of two hundred compounds selected by the Canadian regulatory agency for further safety assessment studies. The U.S. Food and Drug Administration is aware of the need for an objective assessment of the experimental data on the health risks of BPA exposure. The assessment, which will form the basis for regulation of bisphenol A by federal toxicology agencies, will affect the health of millions of people. Lalitha Krishnan, Ph.D. 150
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For Further Information Haighton, L. A., et al. “An Evaluation of the Possible Carcinogenicity of Bisphenol A to Humans.” Regulatory Toxicology and Pharmacology 35 (2002): 238-254. Mittelstaedt, Martin. “‘Inherently Toxic’ Chemical Faces Its Future.” Globe and Mail, April 7, 2007. Stowell, Cheri L., et al. “A Role for Sulfation-Desulfation in the Uptake of Bisphenol A into Breast Tumor Cells.” Chemistry and Biology 13, no. 8 (2006): 891-897. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Eleventh Report on Carcinogens. Research Triangle Park, N.C.: Author, 2005. Vom Saal, Frederick S., et al. “Chapel Hill Bisphenol A Expert Panel Consensus Statement: Integration of Mechanisms, Effects in Animals and Potential to Impact Human Health at Current Levels of Exposure.” Reproductive Toxicology 24, no. 2 (2007): 131-138. Wetherill, Y. B., et al. “Bisphenol A Facilitates Bypass of Androgen Ablation Therapy in Prostate Cancer.” Molecular Cancer Therapeutics 5 (2006): 3181-3190.
u
Other Resources
American Cancer Society Federal Report Looks at Risks from Plastics Chemical http://www.cancer.org/docroot/NWS/content/ NWS_1_1x_Federal_Report_Looks_at_Risks_from_ Plastics_Chemical.asp Breast Cancer Fund Bisphenol A http://www.breastcancerfund.org/site/ pp.asp?c=kwKXLdPaE&b=2638145 National Toxicology Program Bisphenol A http://ntp.niehs.nih.gov/ index.cfm?objectid=BC9825E3-123F-79087BF465F9E25681B0 Toxicology and Chemical Substances/European Chemical Bureau http://ecb.jrc.it See also Acrylamides; Bis(chloromethyl) ether and technical-grade chloromethyl methyl ether; Cadmium and cadmium compounds; Carcinogens, known; Carcinogens, reasonably anticipated; Chromium hexavalent compounds; Di(2-ethylhexyl) phthalate (DEHP); Organochlorines (OCs); Pesticides and the food chain; Plasticizers; Vinyl chloride.
Salem Health: Cancer
Bladder cancer
u Bisphosphonates Category: Chemotherapy and other drugs ATC code: M05BA Definition: Bisphosphonates are medications that act primarily on bone to inhibit resorption or bone destruction resulting from cell-induced bone breakdown. They treat various bone-degenerating conditions. Cancers treated: Breast cancer, hypercalcemia of malignancy (HCM), metastatic bone cancer, multiple myeloma, bone pain, osteoporotic bone loss from cancer treatments Subclasses of this group: Aminobisphosphonates, nonaminobisphosphonates Delivery routes: Bisphosphonates are administered as oral tablets and as intravenous (IV) solutions to outpatients and inpatients. Bisphosphonates in any form are best administered without food to avoid decreased bioavailability. How these drugs work: Bone resorption is part of normal bone regeneration mediated by osteoclasts, or bone breakdown cells. Abnormal osteoclast activity results from lytic bone lesions of multiple myeloma, metastatic bone tumors from breast cancer or other solid tumors, or osteoporosis from glucocorticoids in chemotherapy regimens and from breast-cancer-induced menopause. Bisphosphonates inhibit resorption by decreasing osteoclast activity. This mechanism reduces further bone loss and fracture, minimizes pain associated with osteoclast lesions and weakened bone, and reverses hypercalcemia of malignancy (HCM), which can result when
bone breakdown releases calcium to the blood. Monthly bisphosphonate administration has been shown to reduce the incidence of bone metastases in women with breast cancer as well, and these drugs have substantially reduced the risk of bone loss and fracture in spinal vertebrae and the hip. Side effects: A major side effect of this drug class is irritation of the esophageal mucosa, which can be reduced by taking the drug with a full glass of water and by remaining in an upright position directly after drug ingestion. This side effect may occur even with IV administration. Other side effects include constipation, diarrhea, dyspnea, myalgia, fever, decreased calcium and phosphate, and altered magnesium. Impaired kidney function and renal failure are possible. IV administration causes fever, flulike syndrome, and local injection site reactions. Other side effects noted in trials of patients with cancer include anxiety, headache, insomnia, anorexia, and abdominal pain. Nicole M. Van Hoey, Pharm.D. See also Bone scan; Hypercalcemia; Paget disease of bone.
u Bladder cancer Category: Diseases, symptoms, and conditions Also known as: Transitional cell carcinoma Related conditions: Kidney cancer Definition: Bladder cancer is a cancer that forms in the inner lining of the bladder.
Common Bisphosphonate Agents Drug
Brands
Delivery Mode Cancers/Conditions Treated
Aledronate
Fosamax
Oral
Glucocorticoid-induced osteoporosis
Etidronate
Didronel
Oral, IV
Hypercalcemia of malignancy (HCM)
Ibandronate
Boniva
Oral, IV
Breast cancer bone metastases; menopause-induced osteoporosis
Pamidronate
Aredia
IV
HCM malignancy with or without bone metastases; breast cancer and multiple myeloma; off-label for pain associated with prostatic carcinoma; possible prevention of breast cancer-related bone loss
Risedronate
Actonel
Oral
Glucocorticoid-induced osteoporosis; possible prevention of breast cancer-related bone loss
Tiludronate
Skelid
Oral
Bone metastases
IV
Multiple myeloma; solid tumor bone metastases; HCM
Zoledronic acid Reclast, Zometa
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Bladder cancer Risk factors: Researchers do not completely understand the causes of bladder cancer; however, several carcinogens, family history, and prior diagnosis of bladder cancer remain the chief causes. Smokers are at greatest risk for developing bladder cancer as well as people with exposure to certain chemical dyes in the rubber- and leatherprocessing, textile, and printing industries. Etiology and the disease process: The wall of the bladder is lined with cells called transitional cells and squamous cells. More than 90 percent of bladder cancers begin in the transitional cells and are called transitional cell carcinomas. About 8 percent of bladder cancer patients have squamous cell carcinomas. Cancer that is only in cells in the lining of the bladder is called superficial bladder cancer and often recurs after treatment. Cancer that begins as a superficial tumor may grow through the lining and into the muscular wall of the bladder. This invasive cancer may extend through the bladder
An infiltrating tumor (upper right) in the muscular wall of the bladder. (John Bavosi/Photo Researchers, Inc.)
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Salem Health: Cancer wall into a nearby organ such as the uterus, vagina, or prostate gland or into nearby lymph nodes, in which case cancer cells may have spread to other lymph nodes or other organs such as the lungs and liver or to the bones. Incidence: Primarily occurring in men and women over the age of forty, bladder cancer is diagnosed in 38,000 men and 15,000 women each year in the United States. According to the National Cancer Institute, this is the fourth most common type of cancer in men, and the eighth most common in women. Caucasians get bladder cancer twice as often as African Americans and Hispanics. People with family members who have bladder cancer as well as people who have previously had bladder cancer are more likely to get the disease. Symptoms: Bladder cancer often causes no symptoms until it reaches an advanced state that is difficult to cure. The most common symptom of bladder cancer is blood in the urine (hematuria). Some patients experience pain or burning during urination, or a change in urinary habits, such as a frequent urge to urinate. Screening and diagnosis: Screening tests include a medical interview, a physical examination, urinalysis, urine cytology, and cystoscopy. The urinalysis determines if the urine contains abnormalities such as blood, protein, sugar, and solids. Urine cytology is a microscopic examination of urine to detect any abnormal cells that have sloughed off the bladder wall and have been released in the urine. If necessary, cytoscopy is performed with a very narrow tube with a light and camera inserted through the urethra to examine the inside of the bladder. If bladder cancer is suspected, a physician may order a computed tomography (CT) scan, pyelography, or biopsy. The CT scan is helpful for a three-dimensional view of the bladder and urinary tract to determine if any masses or tumors exist in the bladder or if the cancer has spread to other organs. Pyelography involves injecting a special dye into a vein or the urethra and examining a series of timed-interval X rays of the urinary system to determine if abnormalities exist. The biopsy is typically performed during cytoscopy, and abnormal cells can be detected with a microscope. Staging refers to the size of the cancer and the extent to which it has invaded the bladder wall and spread to other parts of the body. High-grade tumors are significantly more aggressive and life-threatening than low-grade tumors. Approximately 10 per-
Salem Health: Cancer cent of bladder cancer is found to be superficial bladder cancer in situ, which is a highly aggressive, early manifestation of bladder cancer.
Bladder cancer
Incidence of Bladder Cancer per 100,000 People, by Gender 45 Men
Women
40.5 Treatment and therapy: The physi40 cian may treat superficial bladder cancer with transurethral resection (TUR) 35 by inserting a cystoscope into the bladder through the urethra and using a tool 30 with a small wire loop on the end to remove the cancer and to burn away any remaining cancer cells with an electric 25 current. For invasive bladder cancer or 20.3 20.2 cancer involving a large portion of the 20 bladder, surgery is performed to remove 16.4 the entire bladder, nearby lymph nodes, 15 part of the urethra, and the nearby organs that may contain cancer cells. In 10.1 10 some cases of low-grade cancer, only 7.6 part of the bladder is removed in a pro5.5 cedure called segmental cystectomy. 5 3.9 Radiation therapy uses high-energy rays to kill localized cancer cells to 0 shrink the tumor before surgery or if White Black Hispanic Asian/Pacific surgery is not an option. Chemotherapy Islander uses one drug or a combination of drugs to kill cancer cells. Superficial bladder Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 cancer can be treated with local cheNote: Based on cases diagnosed in 2000-2004 motherapy; once per week for several weeks, a catheter is inserted through the urethra and remains in the bladder for several hours. If the cancer has deeply u For Further Information invaded the bladder or spread to lymph nodes or other orDunetz, Gary N. Bladder Cancer: A Resource Guide for gans, chemotherapy may be used to treat the entire body. Patients and Their Families. Bloomington, Ind.: Biological therapy, or immunotherapy, uses the body’s AuthorHouse, 2006. natural immune system to fight cancer by inserting a cathEllsworth, Pamela. One Hundred Questions and Answers eter with a solution containing live, weakened bacteria to About Bladder Cancer. Sudbury, Mass.: Jones & Bartkill cancer cells in the bladder. lett, 2005. Schoenberg, Mark P., et al. The Guide to Living with Prognosis, prevention, and outcomes: Bladder cancer Bladder Cancer. Baltimore: Johns Hopkins University has one of the highest recurrence rates of all cancers. If Press, 2000. treated once, patients must continue a course of follow-up screenings. The five-year survival rate for patients with early-stage bladder cancer is 85 percent. Most patients u Other Resources with bladder cancer (up to 80 percent) will be diagnosed with a superficial tumor. Patients with tumors invading Mayo Clinic the bladder wall have a five-year survival rate of 60 to 75 Bladder Cancer percent. http://www.mayoclinic.com/health/bladder-cancer/ Robert J. Amato, D.O. DS00177
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Blood cancers National Cancer Institute Bladder Cancer http://www.nci.nih.gov/cancertopics/types/bladder See also 4-Aminobiphenyl; Bacillus Calmette Guérin (BCG); Cystography; Cystoscopy; Gastrointestinal oncology; Kidney cancer; Squamous cell carcinomas; Transitional cell carcinomas; Urethral cancer; Urinary system cancers; Urography; Urostomy.
u Blood cancers Category: Diseases, symptoms, and conditions Also known as: Hematopoietic neoplasms, malignant neoplasms, bone marrow diseases Related conditions: Leukemia (acute myelogenous or myelocitic leukemia, or AML; acute lymphocytic or lymphoid leukemia, or ALL; chronic myelogenous or myelocitic leukemia, or CML; chronic lymphocytic or lymphoid leukemia, or CLL), lymphoma (Hodgkin disease, or HD; non-Hodgkin lymphoma, or NHL), and myeloma (plasma cell dyscrasia, plasma cell myeloma, multiple myeloma, myelomatosis) Definition: Blood cancers are those that arise from an abnormality in the production of any of the mature blood cells or their precursor stem cells. Not all bone marrow disorders, such as anemia, are cancers. The three main types of blood cancer are leukemia, lymphoma, and myeloma. Leukemia is a cancer of any of the five dominant types of white blood cells. It occurs when the bone marrow produces abnormal white blood cells, which replicate, limiting the ability of healthy cells to function. Chronic leukemia develops slowly, while acute leukemia develops quickly. Of the four subtypes of leukemia, the acute forms exhibit immature blood-forming cells or blasts, and the chronic forms exhibit few or no blast cells but changes in the presentation of marrow cells. Acute lymphocytic leukemia (ALL), also known as acute lymphoid leukemia, is the most common type of blood cancer among those under nineteen years of age. ALL is characterized by lymphoblasts replacing normal cells in the marrow and lymph nodes lowering the affected individual’s ability to fight infection. Chronic lymphocytic leukemia (CLL) is the most common type of blood cancer among those fifty years of age and older and the most prevalent type of leukemia. Acute myelogenous leukemia (AML), in which leukemic blast cells proliferate and block the production of normal marrow cells, results in a deficiency of red blood cells, 154
Salem Health: Cancer white cells, and platelets. Chronic myelogenous leukemia (CML) is seen mostly in adults and begins with a change in a single stem cell, a future red cell, white cell, or platelet. Lymphomas originate in malignant changes in the lymphatic or immune system. The primary types are Hodgkin disease and non-Hodgkin lymphoma. Hodgkin disease is characterized by abnormal T or B white blood cells. As the abnormal cells divide, they proliferate and can spread throughout the body. Non-Hodgkin lymphoma is a cancer of the lymphoid tissue, which is mostly made up of lymph nodes that manufacture and store lymphocytes, white blood cells that protect against infection. Myelomas are progressive blood cancers of plasma cells, which produce antibodies to fight against infections and regulate the immune system. Myeloma results from an overproduction of these antibodies, an impaired immune system, and invasive tumors. Risk factors: The risk factors and causes of many types of blood cancers are not well known, and most cases of blood cancer occur in individuals with no identifiable risk factors. However, for AML, which along with CLL is among the most common types of blood cancer seen in adults, these specific risk factors have been found: Down syndrome and other genetic disorders, chronic exposure to ionizing radiation and chemicals such as benzene in the workplace, high doses of radiation therapy and the chemotherapies used to treat lymphoma or other types of cancer, and tobacco smoke. Those who are immunosuppressed with certain human retroviruses and bacteria, such as the Epstein-Barr virus (EBV) in Africa; those with human immunodeficiency virus (HIV); and those with human T-cell leukemia virus (HTLV) are at greater risk of developing lymphomas. Familial clustering also has been associated with the development of lymphomas. Etiology and the disease process: Cancer develops as a result of a variety of factors and over a number of years. Blood cancers differ widely by group and within each subtype in their progression, causes, and molecular presentation. The leukemias begin in two types of white blood cells: neutrophils and monocytes, which are germ-ingesting cells, and lymphocytes, which are immune-defense cells. Abnormal white blood cells in the bone marrow multiply and enter the bloodstream, crowding out normal cells. Lymphomas develop when these immune-defense cells multiply and cause tumors in the lymph nodes or other parts of the immune system. Development of blood cells through the hematopoietic process is arrested, and abnormal blood cells proliferate. Every stage of hematopoietic development can result in a particular type of cancer. Non-Hodgkin lymphoma (NHL) is manifested by
Salem Health: Cancer well-differentiated cells with slow progression, while other forms are more aggressive with lymphocytes of limited differentiation. Tumors of the bone marrow are characteristic of myelomas. In myeloma, cells that are to become immune cells develop in the bone marrow from stem cells, as will all blood cells. A major type of white blood cells, B lymphocytes, which typically develop into plasma cells, undergo multiple genetic changes as they change into plasma cells, causing malignant plasma cells to develop. These myeloma cells travel throughout the bloodstream, reside in the bone marrow, and damage healthy tissue. The myeloma interferes with the plasma cell’s production of protective proteins called immunoglobulins or antibodies by producing M proteins or abnormal immunoglobulin, making those affected susceptible to infection.
Blood cancers for diagnosis of myeloma was seventy, with the majority, 28.1 percent, between the ages of seventy-five and eightyfour. Incidence rates for all types of leukemia are higher among men than women and higher among African Americans than those of European descent. New cases of multiple myeloma are estimated to be diagnosed at a rate of 5 to 6 per 100,000 people each year. The incidence rate of myeloma is higher for men than women across racial and ethnic groups. Symptoms: Signs and symptoms of blood cancers vary widely and may be similar to those of other, less severe illnesses. Symptoms vary based on the category and subtype of blood cancer; for example, symptoms of acute leukemia may include pallor, shortness of breath with exertion, lack of energy, night sweats or a mild fever, slow healing of cuts and bruises, unexplained weight loss, tiny red spots under the skin, bone and joint aches and pains, and low white blood cell count (especially neutrophils and mono-
Incidence: The most common forms of leukemia seen in adults aged fifty and over are chronic lymphocytic leukemia (CLL) and acute myelogenous leukemia (AML). The incidence of acute lymphocytic leukemia (ALL) increases in those over sixty years of age. In 2007, new cases of CLL were estimated at 15,340 and new cases of AML at 13,410. The National Cancer Institute (NCI) reports that between 2000 and 2004, the average median age at diagnosis for leukemia was sixty-seven, with 23.7 percent between the ages of seventy-five and eightyfour. Based on cases diagnosed during this period, the age-adjusted incidence rate for leukemia was 12.3 per 100,000 men and women per year. Chronic leukemias accounted for 7 percent more cases than acute leukemias. It was estimated that 71,380 cases of lymphoma would be diagnosed in the United States in 2007. The majority of these cases, 63,190, were projected to be of the non-Hodgkin type. Incidence rates of Hodgkin lymphoma tend to be higher among men than women. Non-Hodgkin lymphoma also is more commonly diagnosed among men, particularly those aged sixty to sixtyfour (52.3 in every 100,000 men in this age group). According to the NCI’s cancer surveillance data, the median age for diagnosis of lymphoma was sixty-four, with the majority of cases, 21.3 percent, diagnosed between the ages of seventy-five and eighty-four. Non-Hodgkin lymphoma is the fifth most common cancer among men and women. It was estimated that 19,900 new cases of myeloma would be diagnosed in the United States This X ray reveals a secondary tumor in the humerus; the primary is in the in 2007. NCI data indicated that the median age bronchus. (©Mediscan/Corbis)
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Blood cancers
Salem Health: Cancer
Estimated New Blood Cancer Cases and Deaths by Gender, 2007 New Cases Blood Cancer Type
Men Women
Deaths Total
Men Women
Total
Leukemias (all) Acute myeloid leukemia Chronic myeloid leukemia Acute lymphocytic leukemia Chronic lymphocytic leukemia Other leukemias
24,800 19,440 44,240 7,060 6,350 13,410 2,570 2,000 4,570 3,060 2,140 5,200 8,960 6,380 15,340 3,150 2,570 5,720
12,320 5,020 240 820 2,560 3,680
9,470 21,790 3,970 8,990 250 490 600 1,420 1,940 4,500 2,710 6,390
Lymphomas (all) Hodgkin disease Non-Hodgkin lymphoma
38,670 32,710 71,380 4,470 3,720 8,190 34,200 28,990 63,190
10,370 770 9,600
9,360 19,730 300 1,070 9,060 18,660
Multiple myeloma
10,960
5,550
5,240 10,790
8,940 19,900
Source: Data from American Cancer Society, Cancer Facts and Figures 2007 (Atlanta: Author, 2007)
cytes). Although specific bone marrow and blood tests are needed to diagnose any type of blood cancer, some of those affected with certain subtypes of leukemia may have enlarged lymph nodes in the neck, groin, or armpit, and they may suffer from frequent infections. Often individuals who have Hodgkin disease or nonHodgkin lymphoma experience painless, swollen lymph nodes, loss of appetite, vomiting, bloating, abdominal pain, fullness (due to enlargement of the liver, spleen or abdominal lymph nodes), pain in the lower back, bone pain, constant coughing, and unexplained lethargy. Early symptoms of myeloma are bone pain, particularly with movement, and infections involving the skin, the urinary tract, the bronchial tract, or lungs. These symptoms may also be accompanied by pallor resulting from anemia, weakness, and exaggerated fatigue. Screening and diagnosis: Blood tests and specific bone marrow tests are needed to diagnose blood cancer; however, individuals in early stages of the disease may not have symptoms suggesting cancer. Current evidence does not suggest that routine blood screening before the onset of symptoms will detect cases of blood cancer and lead to improved medical outcomes or be cost effective in those at average risk of developing cancer according to their medical, family, and occupational history. The first indication that a person has blood cancer may be the results of a blood test performed as part of an annual physical. The blood sample may reveal anemia or changes in white blood cells, a possible indicator of leukemia. If an individual has symptoms that suggest blood cancer, the physician will 156
take a medical history and check for swelling of the liver, spleen, or lymph nodes in the armpits, groin, or neck. Urinalysis will also be performed to detect substances or cellular material in the urine. Other tests include a blood test to assess blood cell count, a cytogenetic exam to analyze the number and shape of chromosomes to check for genetic abnormalities, a bone marrow aspirate to check for cancerous cells in liquid bone marrow, and a bone marrow biopsy to check for cancerous cells in the bone specimen. If cancerous cells are present, additional tests may be ordered to ascertain if the disease has spread and to organs or systems. These tests include tumor-marker tests (immunophenotyping, based on the type of antigen or marker on the surface of the cell), a spinal tap or lumbar puncture to obtain a sample of cerebrospinal fluid, chest X rays (for signs of infection or lymph node involvement), or ultrasound scans. Staging is used to assess the extent or severity of the disease, to plan treatment, and to predict the outcome or prognosis. Classification of each type of blood cancer into stages is based on the site that is affected, the progression of the disease, and the appearance of the affected cells. For example, CLL is staged according to the risk-based Rai classification system using symptoms such as blood lymphocyte count, presence of enlarged lymph nodes or organs, platelet count, and anemia. Other forms of leukemia, such as acute leukemia, are not staged because of acute onset, which typically means the cancer has spread to other organs at the time of diagnosis. Although leukemic cancerous cells circulate in the blood and bone marrow, in lymphomas cells form tumors
Salem Health: Cancer in lymphatic tissue. The Ann Arbor staging system is used for staging both Hodgkin disease and non-Hodgkin lymphomas on the basis of specificity of site of lymph node involvement. The TNM (tumor/lymph node/metastasis) system may be used to stage the size of a tumor, lymph node involvement, and existence or extent of spread through other parts of the body. The International Staging System (ISS) is used for staging multiple myelomas based on blood tests for two proteins, albumin and betamicroglobulin, which are markers for the disease. Treatment and therapy: Blood cancers are typically treated with one or more of the following: chemotherapy, radiation therapy, stem cell transplantation, and immunotherapy. A treatment plan is created using an anticancer agent such as chemotherapy, sometimes in combination with radiation therapy. The goal of chemotherapy, drugs given in combination and via different methods of delivery, is to destroy cancerous cells or to stop them from growing and multiplying, producing long-term remission or a cure. Radiation may be used to treat localized cancers such as lymphomas and certain types of leukemia, or it may be used to relieve symptoms when cancerous growths cause pain or pressure on bones, nerves, or organs. However, chemotherapy and radiation therapy can cause longterm or late effects, affecting fertility or growth and causing learning disabilities or illnesses secondary to the primary cancer such as leukemia. Chemotherapy doses considered tolerable by most patients may not be sufficient to arrest, cause remission in, or cure acute leukemia, myeloma, or lymphoma. In patients who may be at high risk of relapse, who relapse after a successful course of treatment, or who do not respond as expected to conventional treatment, stem cell transplantation (transplanting cells from which blood cells and immune cells arise) can enable production of normal blood cells such that intensive chemotherapy can bring about recovery. Immune treatments (using antibodies from the patient or a donor) may be used alone or in combination with other therapies to attack cells that remain after chemotherapy and that may attach to antigens on the malignant cells. They also are used as vaccines to suppress malignant cells that remain in the body following therapy. New chemotherapies, immunotherapies, vaccines, gene therapies, and types of bone marrow transplants to suppress the growth of cancerous cells and affect the course of the disease are always being developed and tested. Patients need to be reminded that pain and uncomfortable symptoms arising from the toxic effects of cancer treatments can be managed by consulting with their physicians. Supportive care to improve functioning and quality of life, transfusions,
Blood cancers antibiotics to protect against infection, and a healthy diet and lifestyle are critical for those undergoing cancer treatment. Prognosis, prevention, and outcomes: Many factors affect the outcome of a patient’s blood cancer, including the type, location, and stage of disease as well as individual and demographic factors such as the person’s general health, age, and response to treatment. A cancer survivor will undergo follow-up care, which includes frequent monitoring of blood counts, X rays, urine tests, imaging tests such as computed tomography (CT) or positron emission tomograph (PET) scans. Those whose remission lasts five years are considered cured. Survival rates for those with blood cancer have been rising since 1975 and the advent of more effective cancer treatments, according to the NCI’s Cancer Trend Report 2005 Update. No specific guidelines for preventing blood cancer exist, as its causes are not known and many types are relatively rare. Limiting exposure to environmental toxins and leading healthy lifestyles may help prevent blood cancers in those of average risk. The relative overall five-year survival rate of leukemia between 1996 and 2003 was nearly 50 percent, a survival rate that has more than tripled in patients diagnosed with leukemia since 1947. Relative survival rates vary by age of diagnosis, race, gender, and type of leukemia. Of all types of leukemia, those with CLL had the highest relative survival rate during this period, with 75.8 percent surviving. Hodgkin disease is considered one of the most curable cancers, with many patients cured after their initial treatment. The five-year survival rate has increased dramatically since the 1960’s, reaching 86 percent of patients of all races who were diagnosed with the disease between 1996 and 2003. Similarly, due to advances in treatment of non-Hodgkin lymphoma, the mortality rate has declined considerably since the 1980’s. Susan H. Peterman, M.P.H. u
For Further Information Adler, Elizabeth M. Living with Lymphoma: A Patient’s Guide. Baltimore: Johns Hopkins University Press, 2005. Hoffman, Barbara, ed. A Cancer Survivor’s Almanac: Charting Your Journey. Minneapolis: National Coalition for Cancer Survivorship, 1996. Mauch, Peter M., et al., eds. Hodgkin’s Disease. Philadelphia: Lippincott Williams & Wilkins, 1999. Wiernik, Peter Harris, ed. Neoplastic Diseases of the Blood. 4th ed. New York: Cambridge University Press, 2003. 157
Bone cancers u
Other Resources
American Cancer Society http://www.cancer.org International Myeloma Foundation http://www.myeloma.org The Leukemia and Lymphoma Society http://www.leukemia-lymphoma.org Memorial Sloan-Kettering Cancer Center http://www.mskcc.org National Cancer Institute http://www.cancer.gov See also Acute lymphocytic leukemia (ALL); Acute myelocytic leukemia (AML); Aleukemia; Amyloidosis; Anemia; Aplastic anemia; Bone marrow aspiration and biopsy; Bone marrow transplantation (BMT); Burkitt lymphoma; Chronic lymphocytic leukemia (CLL); Chronic myeloid leukemia (CML); Cutaneous T-cell lymphoma (CTCL); Disseminated intravascular coagulation (DIC); Down syndrome and leukemia; Eosinophilic leukemia; Fanconi anemia; 5Q minus syndrome; Hairy cell leukemia; Hemolytic anemia; Hodgkin disease; Human T-cell leukemia virus (HTLV); Hypercalcemia; Leukemias; Leukopenia; Leukoplakia; Lymphocytosis; Lymphomas; Multiple myeloma; Myelodysplastic syndromes; Myelofibrosis; Myeloma; Myeloproliferative disorders; Myelosuppression; Neutropenia; Pheresis; Polycythemia vera; Richter syndrome; Sézary syndrome; Stem cell transplantation; Superior vena cava syndrome; Thrombocytopenia; Thymomas; Thymus cancer; Transfusion therapy; Umbilical cord blood transplantation; Waldenström macroglobulinemia (WM).
u Bone cancers Category: Diseases, symptoms, and conditions Also known as: Osteosarcoma, osteogenic sarcoma, bone tumor Related conditions: Li-Fraumeni syndrome, Gardner syndrome, retinoblastoma, leukemia, human immunodeficiency virus (HIV) infection Definition: Bone cancers are malignant, unregulated proliferation of neoplasia (new tissue growth) in bone cells. The most common type of bone cancer is osteosarcoma, a highly malignant tumor composed of cells derived from growing connective tissue cells of bone. Osteochondromas are the most common cancerous primary bone tu158
Salem Health: Cancer mors, with giant cell tumors developing in the thighbone near the knee. Ewing sarcoma is the second most common form of childhood bone cancer and is found mostly in the extremities. Chondrosarcomas are cancerous bone tumors that appear in the cartilage of bone in middle age. Other rare sarcomas are parosteal osteosarcomas involving both the bone and membranous covering, fibrosarcomas originating in the ends of bones in the arm or leg and then spreading to soft tissue, and chordomas that develop on the skull or spinal cord. Multiple myeloma is a hematologic cancer that frequently causes bone tumors. Risk factors: The exact cause of osteosarcoma is not known, but inherited or acquired deoxyribonucleic acid (DNA) mutations are the suggested causes. Risk factors include the presence of a benign bone disease; previous treatment with radiation for another cancer, especially at a young age; teenage growth spurts; and disproportionate tallness with age. Certain rare, inherited cancers are also risk factors, such as Gardner syndrome, Li-Fraumeni syndrome (a rare family predisposition to multiple types of cancers caused by a mutation in a cancer-suppressing gene), and retinoblastoma (a malignant tumor of the retina that usually occurs in children younger than five years old). Studies suggest that occupational exposure to wood preservatives and certain herbicides increases the risk of developing soft-tissue sarcomas. Suggested risk factors for myeloma bone disease include age (it rarely occurs under the age of forty), family history, smoking, exposure to petroleum and other chemicals, and exposure to high amounts of radiation. Atomic radiation from nuclear explosions and high-dose exposure to ionizing radiation are known to be risk factors for bone cancer but on a small scale. Virus infections make relatively minor contributions to human bone cancer, except the human immunodeficiency virus (HIV), which causes sarcoma. Etiology and the disease process: Bone cancers are among the class of mesenchymal cancers that originate from the mesenchyme (bone and other tissues derived from embryonic mesoderm). Abnormal or partially differentiated cells develop in the bone marrow and can enter the general circulation and ultimately cause leukemia. (Leukemia can also result from blocked hemopoietic cell differentiation that causes abnormal cells to accumulate in bone marrow.) Initial mutation in a gene linked to DNA repair will cause other mutations to arise and spread more rapidly. Bone cancers usually develop rapidly and metastasize through the lymph channels of the body. Metastatic tumors frequently involve the axial more than the appendicular skeleton.
Salem Health: Cancer
Bone cancers
Malignant primary bone tumors originate in hard bone, in the soft tissue of blood vessels and nerves, or in tissues containing muscles, fat, or fiber. Osteosarcomas can grow quickly along the edge or end of a fast-growing long bone of the arms or legs, sometimes affecting the pelvis, shoulder, and skull. Osteosarcoma may metastasize into nearby tissues of the foot, tendons, and muscles, or spread through the bloodstream to other organs or bones in the body. Ewing sarcoma originates from immature nerve tissue in the bone marrow of the leg, hips, ribs, and arms, but it is mostly found in the extremities, rapidly infiltrating the lungs and metastasizing to other bones, kidneys, heart, adrenal glands, and other soft tissues. Chondrosarcomas usually originate in cartilage in ribs, legs, or hip bones. These grow slowly and take years to spread to other parts of the body. Incidence: In the United States, about 2,400 cases of cancers of bones and joints are reported annually. The American Cancer Society in 2004 reported incidence rates in the United States to be approximately 1 in 113,333 people, or 2,400 people. In 2005, 2,570 new cases An MRI scan of the spine of a seventy-two-year-old patient reveals myeloma of bone and joint cancer were reported, along that has caused one of the vertebrae (sixth from bottom) to collapse. (Zephyr/ Photo Researchers, Inc.) with 1,210 deaths. Osteosarcoma and Ewing sarcoma occur mostly in children, adolescents, and young Genetic association crops up with bone cancer but adults, accounting for 10 to 15 percent of all childhood scarcely accounts for more than 10 percent of cancers. bone cancers but constituting only 1 percent of all cancers. Most other types of bone cancers are usually found only in Symptoms: Pain is the most common symptom of bone adults. cancer, associated with weakened bones and fractures. Osteosarcoma occurs slightly more often in male than Symptoms may include swelling around the affected site, female children and youths, usually between the ages of increased pain with activity or lifting, limping, and deten and twenty, and represents one-fifth of all bone tumors. creased movement of the affected limb. The soft bone tisApproximately 900 new cases of osteosarcoma are resues grow very large and push aside normal tissue. The iniported each year in the United States. tial symptom is usually a painless lump or swelling, which Ewing sarcoma occurs in 0.6 in one million people in later becomes sore and painful as it presses against nearby the United States, more often in male than female children nerves and tissues. and youths between the ages of ten and twenty, and acSymptoms of Ewing sarcoma include pain, swelling counts for 16 percent of bone cancers. and redness around the site of the tumor, typical small Chronic leukemia, resulting from bone marrow cancer, round blue cells, fatigue, fever, paralysis and incontinence is the most common form of leukemia and is twice as com(if the tumor is in the spinal region), numbness, tingling, mon in men as in women. It is ten times more common in weight loss, and decreased appetite. adults than in children but accounts for 75 percent of childThe symptoms for myeloma bone disease are pain, conhood leukemias, with a five-year survival rate of 80 perstipation, nausea, vomiting, fractures in bones, weakness cent. 159
Bone cancers
Salem Health: Cancer
or numbness in legs, weight loss, weakness, fatigue, repeated infections, and problems with urination. Screening and diagnosis: In addition to a complete medical history and physical examination, diagnostic procedures for bone cancers such as osteosarcoma and Ewing sarcoma may include multiple imaging studies, such as X rays, of the tumor and sites of possible metastasis. Osteosarcomas are classified according to subtypes and grades determined by X rays and histological analysis: • Low grade: intraosseous low grade, parosteal • Intermediate grade: periosteal • High grade: conventional, telangiectatic, central, small cell, high-grade surface A radionuclide bone scan is used to determine the cause of pain or inflammation to rule out any infection or fractures. Magnetic resonance imaging (MRI) is done to rule out any associated abnormalities of the spinal cord and nerves. A computed tomography (CT) scan provides more detailed images than general X rays. A complete blood count (CBC) measures the size, number, and maturity of different blood cells in a specific volume of blood, and urine and blood tests (including blood chemistries) are also used for diagnosis. A biopsy is performed on a tissue specimen to determine if cancer or other abnormal cells are present and to determine other courses of action. Myeloma bone disease is additionally diagnosed with aspiration (an examination of a small amount of bone marrow fluid). Cell sorting devices can identify the number of proliferation cells or ploidy status of the nuclear DNA. Chemical proteins
Age at Death for Cancer of the Bones and Joints, 2001-2005 Age Group
Deaths (%)
Under 20 20-34 35-44 45-54 55-64 65-74 75-84 85 and older
14.8 14.3 7.1 9.5 11.5 13.7 18.3 10.7
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 Note: The median age at death from 2001 to 2005 was fiftyeight, with an age-adjusted death rate of 0.4 per 100,000 men and women.
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(serving as antigens) detected by specific antibodies provide information on the state of cancer cells. Polymerase chain reaction (PCR) kits, which amplify and detect altered DNA base sequences in minute samples of cells, provide additional tumor markers. They make it possible to diagnose cancer types that are difficult to categorize by conventional pathology. Screening of serum sample glycoprotein antigens in the general circulation reveals undetected cancer, and monitors established cancer. Treatment and therapy: Treatment of bone tumors depends on the type of tumor. Treatment is more likely to succeed if fewer cancer cells exist at the beginning of treatment. If the cancer has metastasized, chemotherapy or radiotherapy is used. Chemotherapy is used as a primary therapy or as an addition to other types of treatment and is the main method for treating advanced bone cancer. Typical drugs used are ifosfamide, cisplatin, methotrexate, and doxorubicin, plus some natural products. Drugs are more effective when used in combination. Treatment of osteosarcoma and Ewing sarcoma may include surgery (biopsy, bone/skin grafts, reconstructions, resections, limb salvage procedures), amputation, prosthesis fitting and training, rehabilitation including physical and occupational therapy, psychosocial adapting, supportive care (for the side effects of treatment), antibiotics (to prevent and treat infections), and continued follow-up care (to determine response to treatment, detect recurrent disease, and manage the side effects of treatment). Treatment of osteosarcoma depends on the subtype and grade of the tumor. Low-grade tumors are surgically removed and usually not treated with chemotherapy. Intermediate-grade tumors are treated with both surgery and chemotherapy. High-grade tumors consist of immature cells, which require aggressive chemotherapy. Most osteosarcomas do not respond to radiation therapy. Treatment of myeloma bone disease includes radiation therapy and medications (to control pain), chemotherapy, fracture treatment, bone marrow transplantation, and alpha interferon for immunotherapy. The most common treatment for soft-tissue sarcomas is surgical removal of the tumor, followed by radiation, chemotherapy, or both. Photodynamic therapy involves laser activation of sensitive compounds that generate free radicals. Dietary adjustments, massage, reflexology, acupuncture, and relaxation techniques can relieve pain, anxiety, tension, and depression. Regular exercise provides physical strength and also reduces mental and emotional stress. Prognosis, prevention, and outcomes: Prognosis for bone cancers involves predictions of the rate of growth, the
Salem Health: Cancer likelihood of the cancer to metastasize, the most effective drug or treatment procedure, and the patient’s needs. Prognosis for osteogenic, Ewing, and other sarcomas greatly depends on the extent of the disease; the size and location of the tumor; presence or absence of metastasis; the tumor’s response to therapy; the patient’s age, overall health, and tolerance of specific medications, procedures, and therapies; and continuous follow-up care for the side effects of radiation and chemotherapy as well as secondary malignancies that could occur. Prompt medical attention and aggressive therapy are important for the best prognosis. Five-year event-free survival is expected for 85 percent of patients whose lowgrade osteosarcoma tumors are surgically removed without chemotherapy and for 75 percent of patients with highgrade tumors requiring aggressive chemotherapy. About 50 percent of patients without metastatic Ewing sarcoma may have long-term disease-free survival. The five-year survival rate for sarcomas is about 90 percent if the cancer is discovered before spreading and less than 30 percent for sarcomas that have already metastasized at the time of diagnosis. Since sarcomas arise from chemical reactions within cells, chemoprevention (with minimal side effects) would presumably curb cancer. New legal requirements for carcinogen testing minimize the hazards associated with industrial products; carcinogens cause less than 1 percent of cancers in developed countries. Nevertheless, cancer is still the second highest cause of death in the Western world, suggesting the need for more research and effective controls. Lifestyle modifications for bone cancer prevention include diet management, control of food additive use, tobacco avoidance, regulation of reproductive factors such as contraception, reduction of alcohol consumption, screening for early detection of cancer, and appropriate use and disposal of industrial products. Samuel V. A. Kisseadoo, Ph.D. u
For Further Information Beers, Mark H., ed. The Merck Manual of Medical Information. 2d ed. Whitehouse Station, N. J.: Merck Publishing, 2003. King, Roger J. B., and Mike W. Robins. Cancer Biology. 3d ed. New York: Pearson/Prentice Hall, 2006. O’Neill, Catherine E., ed. New Developments in Bone Cancer Research. New York: Nova Biomedical Books, 2006. Pappo, A. S., ed. Pediatric Bone and Soft Tissue Sarcomas. New York: Springer, 2005. Singh, Gurmit, and Shafaat A. Rabbani, eds. Bone Metastasis. Totowa, N.J.: Humana, 2005.
Bone marrow aspiration and biopsy u
Other Resources
American Cancer Society http://www.cancer.org Free Health Encyclopedia Bone Cancers http://www.faqs.org/health/topics/75/Bonecancers.html Spectrum Health http://www.spectrum-health.org See also Amputation; Bone scan; Childhood cancers; Ewing sarcoma; Fibrosarcomas, soft-tissue; Giant cell tumors (GCTs); Laryngeal cancer; Li-Fraumeni syndrome (LFS); Limb salvage; Metastasis; Nasal cavity and paranasal sinus cancers; Nuclear medicine scan; Orthopedic surgery; Paget disease of bone; Rothmund-Thomson syndrome; Sarcomas, soft-tissue; Simian virus 40; Spinal axis tumors; Uterine cancer; Veterinary oncology; Young adult cancers.
u Bone marrow aspiration and
biopsy Category: Procedures Definition: Bone marrow aspiration involves the removal of a bone marrow sample for laboratory examination. The bone marrow is where all blood cells are created. It is the job of the bone marrow to replace dead and dying red blood cells, white blood cells, and platelets. At times, cancer or other disease may cause this bone marrow production to stop or decrease. Sites for bone marrow aspiration and biopsy are typically the pelvic bone (ilium) or the sternum, larger bones that provide the best samples. A bone marrow biopsy can be performed by a hematologist, medical oncologist, internist, pathologist, or specially trained technologist. The patient can have a bone marrow biopsy at the bedside, in interventional radiology, and even in the operating room. Cancers diagnosed: Leukemia, multiple myeloma, or polycythemia vera, cancers referred to as hematological malignancies; metastatic cancer Why performed: A bone marrow biopsy is done to evaluate the functioning of the bone marrow and to determine the presence or absence of cancer. Patient preparation: The patient will have the procedure explained and provide consent. A numbing medication is 161
Bone marrow aspiration and biopsy injected at the site; it may burn or sting a bit when first used. Once the numbing medication is injected, patients usually feel considerable pressure at the site but not necessarily pain during the procedure. When the biopsy is done in the hip, patients occasionally complain of a quick shooting pain down the leg, but it usually stops once the sample has been taken. A patient with a low platelet count may receive a platelet transfusion immediately before the procedure. Steps of the procedure: The patient will be positioned for the procedure and needs to remain still until its completion. A patient who is having the pelvic bone biopsied will be placed on one side with pillows or blankets used to maintain positioning. A patient who is having the sternum biopsied will lie flat in the bed or on the table. The patient may be given medication for pain and relaxation. The site is scrubbed and cleaned, and then the patient is given medication to numb the site. A small cut is made into the skin. The procedure is done with a device that consists of a large
Salem Health: Cancer hollow needle with an inner attachment (cannula) that allows for the bone to be accessed. The needle is used to make a hole into the bone. Once it is inside the bone, the middle of the needle is removed, and the large hollow needle is then resting in the center of the bone. A large syringe is used to extract a sample of the marrow (aspirate). The section of bone taken when the inner cannula was removed from the needle is also kept for pathology testing. The patient may have this procedure done on both hip bones or at multiple sites in order to establish staging of disease. The samples are placed on slides or in a liquid to preserve them until testing can be completed. After the procedure: Pressure may need to be applied to prevent bleeding. The patient may be asked to lie on that hip to provide extra pressure immediately after the biopsy for ten to fifteen minutes. The cut is typically small enough that a bandage and a little pressure is all that is needed. Some patients may not be able to stop bleeding after the biopsy, usually because their platelet counts are too low. These patients may require a stitch or two at the bone marrow site to stop the bleeding. Patients may remain sore at the site for two to three days after the procedure. If this procedure was performed on an outpatient, then the patient will not be able to drive home and will need a family member or friend to help. Risks: The risks from performing a bone marrow aspiration and biopsy are minimal. As with any invasive procedure, there is a risk for infection. There is also a risk for bleeding and bruising with this procedure. If the sample is taken from the sternum (breast bone), then there is a risk of injury to the heart, lungs, and major blood vessels.
A young patient is undergoing bone marrow aspiration. (National Cancer Institute)
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Results: Findings from the bone marrow aspiration and biopsy show what types of cells are in the bone marrow. The hematologist or pathologist will examine the samples with a microscope to determine what types of cells are present. The physicians are able to determine if these cells are normal, misshapen, or cancerous, as well as the stage of the cancer that may be present. Bone marrow biopsies are also done to evaluate therapy. This is typically seen in leukemia patients. They will have a bone marrow biopsy completed prior to therapy and then a biopsy done at or around day fourteen to determine if the chemotherapy has destroyed the cells in the bone marrow. Katrina Green, R.N., B.S.N., O.C.N.
Salem Health: Cancer u For Further Information Carrier, Ewa, and Gracy Ledinham. One Hundred Questions and Answers About Bone Marrow and Stem Cell Transplantation. Sudbury, Mass.: Jones and Bartlett, 2003. Klag, Michael J., et al., eds. Johns Hopkins Family Health Book. New York: HarperCollins, 1999. Weisbrot, Deborah M., and Alan B. Ettinger. The Essential Patient Handbook: Getting the Health Care You Need—from Doctors Who Know. New York: Demos Medical, 2004.
See also Acute lymphocytic leukemia (ALL); Acute myelocytic leukemia (AML); Aplastic anemia; Blood cancers; Childhood cancers; Chronic lymphocytic leukemia (CLL); Chronic myeloid leukemia (CML); Eosinophilic leukemia; Fanconi anemia; 5Q minus syndrome; Flow cytometry; Hairy cell leukemia; Hematologic oncology; Hemolytic anemia; Histiocytosis X; Hodgkin disease; Immunocytochemistry and immunohistochemistry; Medulloblastomas; Multiple myeloma; Myelofibrosis; Myeloma; Myeloproliferative disorders; Neuroblastomas; NonHodgkin lymphoma; Polycythemia vera; Retinoblastomas; Rhabdomyosarcomas; Stem cell transplantation; Thrombocytopenia; Veterinary oncology; Waldenström macroglobulinemia (WM).
u Bone marrow transplantation
(BMT) Category: Procedures Also known as: Peripheral blood stem cell transplantation (PBSCT) Definition: Bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT) are procedures used in cancer therapy to provide stem cells to a patient to replace those lost to disease, chemotherapy, and radiation. Stem cells may be obtained from patients themselves, a related or unrelated donor, or umbilical cord blood taken after the birth of a baby. Autologous transplants use the patient’s own stem cells. Allogeneic transplants use stem cells from a related person; the donor is most often a parent or sibling, but an unrelated but matched donor or umbilical cord blood may be used. A syngeneic transplant is done with stem cells from an identical twin. Cancers treated: Leukemia, lymphoma, multiple myeloma, aplastic anemia, and neuroblastoma; additional
Bone marrow transplantation (BMT) cancers eligible for transplant are being evaluated in clinical trials Why performed: Cancer patients are often treated by high doses of chemotherapy and radiation to rid the body of cancer cells. Chemotherapy and radiation therapy target rapidly dividing cells in the body. Because cancer cells and stem cells divide rapidly, they both may be killed by the therapy. BMT and PBSCT are used to rescue patients after high-dose chemotherapy and radiation by replacing destroyed stem cells with healthy stem cells. Transplanted stem cells allow the bone marrow to begin producing blood cells needed by the body. Additionally, white blood cells from the donor will identify any remaining cancer cells in the patient’s body and attack them as foreign, thus providing additional cancer cell kill. This graft-versustumor (GVT) effect—in this case, stem cells versus cancer cells—is important in some kinds of leukemia treated with allogeneic transplants and enhances the effectiveness of the transplant. To understand bone marrow transplantation, it is important to understand the role of stem cells. Stem cells are found in the bone marrow and can develop into different types of cells in the body, such as blood cells. Blood cells originally begin as immature cells, called hematopoietic stem cells, which are constantly and rapidly dividing. Stem cells used in transplantation are not embryonic stem cells, which are used in cloning experimentation. Mature stem cells are available to the body in the bone marrow, but some stem cells circulate in the bloodstream and are called peripheral blood stem cells. The role of stem cells in the body is to fight infection (stem cells that evolve into white blood cells), carry oxygen (stem cells that evolve into red blood cells), and prevent bleeding (stem cells that evolve into platelets). Patient preparation: The first step in the transplant procedure is determining the type of transplant that will be used by determining if the patient has a potential donor. Doctors try to minimize side effects by using stem cells that match as closely as possible the patient’s own stem cells. There are different proteins on the cell surface, called human leukocyte antigens (HLAs), which are identified with a blood test. The success of the transplant depends on how close a match can be made between the donor stem cells and the patient’s stem cells. Close relatives are the most likely sources of matching stem cells, but less than one-third of patients will have a matched sibling. Finding an unrelated, matched donor is possible in about one-half of cases, and the chance of a match increases if the donor and patient are of the same ethnic and racial 163
Bone marrow transplantation (BMT)
Salem Health: Cancer
Inner spongy layer Hard outer layer
Marrow Bone marrow transplantation is used to treat several types of lymphoma.
background. If a potential donor is identified, then blood work will be used to determine the level of the match. A donor registry may also be used to identify donors who have offered to provide stem cells for transplantation if they match a patient in need. If no donor match can be found, then the patient’s own stem cells may be used in an autologous transplant. Stem cells are obtained from the patient and then treated to remove any cancer cells. Extra stem cells are removed from the patient, as some healthy cells may be damaged when the cancer cells are removed. Once the type of transplant is determined, the stem cells are obtained or harvested. The liquid center of the bone is the source for stem cells used in BMT. The donor is given anesthesia to make the harvest procedure pain-free. General anesthesia or regional anesthesia, which numbs the area below the waist, is used. Large needles are inserted into the hip (pelvic) bone or, rarely, the breastbone (sternum), and marrow is drawn out. The harvest procedure takes approximately one hour. The bone marrow is then treated to remove blood and bone fragments, frozen with a preservative if not to be used immediately, and stored until it is time to administer the stem cells to the patient. Stem cells that are frozen (cryopreserved) can be stored for many years. If the doctor determines that a peripheral blood stem cell transplant is the best choice for the patient, then stem cells are harvested from the bloodstream rather than from the bone marrow. Autologous transplants often use peripheral blood stem cells (PBSCs). Apheresis is used to re164
move PBSCs with a machine that removes the stem cells and then returns the remainder of the blood, minus the stem cells, to the donor. Medicine that stimulates the growth of stem cells in the body may be given to the donor for several days before the harvest. Apheresis may take up to six hours. The cells are processed and frozen for future use. Umbilical cord blood may also be a source of stem cells for transplantation. The mother requests that cells be harvested when the birth occurs. Cord blood banks may store the cells for potential use by the family at a later date or may be given to a public cord blood bank for use by any matching patient. Blood is taken from the umbilical cord and placenta and then frozen for storage. Since only a small amount of blood may be available, cord blood transplants are usually most effective in children or small adults. Steps of the procedure: The patient usually receives high-dose chemotherapy (anticancer drugs) and radiation to rid the body of as many cancer cells as possible. Depending on the hospital program, the patient may be admitted to the hospital or may undergo the preoperative regimen as an outpatient. Once the regimen before the transplant is complete, the patient is ready to have the procedure. The stem cells are thawed and given through an intravenous line, as in a blood transfusion. The infusion of the stem cells may take from one to five hours. After the procedure: Once the infusion of the stem cells is complete, the wait begins for the cells to graft (or take)
Salem Health: Cancer and produce new blood cells for the patients. During this time, the patient may be in a room with special air filters and strict infection control guidelines. Because the patient has very few stem cells until the graft occurs, the body is unable to fight infection or control bleeding. The wait for engraftment ranges from two to six weeks. High fevers, chills, shortness of breath, coughing, low blood pressure, and weakness may occur. With allogeneic transplants, the most significant complication that occurs is graft-versushost disease. Once discharge from the hospital occurs, the patient may face a variety of problems. Fatigue, physical problems lingering after the transplant, and psychological problems may occur. Frequent visits to the physician to follow progress after the transplantation and to manage symptoms are expected. The recovery period may be a year in length. Risks: There is minimal risk involved with donating bone marrow or undergoing apheresis. If the match between donor and patient is not complete, then graft rejection may occur in rare instances. The most significant risk with an allogeneic transplant is graft-versus-host disease. Patients may be unable to have children after a transplant, and this topic should be discussed with the physician prior to the transplant. Results: Survival rates after transplantation vary by disease, type of transplant, and the age of the patient. In related donor patient transplants, survival rates are 55 to 70 percent and 25 to 50 percent if the donor is unrelated. Patricia Stanfill Edens, R.N., Ph.D., FACHE u
For Further Information Jenks Kettmann, J. D., and E. M. Altmaier. “Social Support and Depression Among Bone Marrow Transplant Patients.” Journal of Health Psychology 13 (2008): 39-46. Nadir, Y., and B. Brenner. “Hemorrhagic and Thrombotic Complications in Bone Marrow Transplant Recipients.” Thrombosis Research 120, suppl. 2 (2007): 92-98. u
Other Resources
American Cancer Society http://www.acs.org National Cancer Institute Bone Marrow Transplantation http://www.cancer.gov National Marrow Donor Program http://www.marrow.org
Bone pain See also Blood cancers; Graft-versus-host disease (GVHD); Immunocytochemistry and immunohistochemistry; Leukemias; Lymphomas; Organ transplantation and cancer; Pheresis; Stem cell transplantation; Umbilical cord blood transplantation.
u Bone pain Category: Diseases, symptoms, and conditions Also known as: Skeletal pain Related conditions: Bone metastasis, fracture Definition: Bone pain is an uncomfortable response to disease, infection, inflammation, or trauma to bone. Risk factors: Those at greatest risk for bone pain not caused by fracture or other trauma are those with bone disease, including bone cancers. Etiology and the disease process: Bone pain in cancer may be caused by tumors in or near bones or conditions that cause damage within the bone, such as multiple myeloma. Cancer that spreads, or metastasizes, to bone from another part of the body can result in bone pain. Medications given to stimulate the production of blood cells in the bone marrow may cause temporary bone pain. Incidence: Bone pain is experienced in more than half the cases of bone metastasis. There is a higher incidence in patients with advanced disease, particularly in those with breast and prostate cancers. Symptoms: Symptoms include limited mobility, swelling in the area of pain, fatigue, and lack of appetite. Loss of height is associated with bone compression in the vertebrae. Burning or tingling sensations may indicate nerve involvement. Fracture, a late sign of advanced disease, is another source of pain. Screening and diagnosis: Bone lesions are detected on X rays, positron emission tomography (PET) and computed tomography (CT) scans, and magnetic resonance imaging (MRI). A biopsy is necessary to determine if cancer has spread to the bone. The level of pain is assessed using a variety of scales. A commonly used scale uses a zero to ten rating, where zero correlates with no pain and ten with the worst possible pain. Other evaluations are employed to describe the type and quality of pain. Treatment and therapy: Chemotherapy and radiation alleviate or diminish pain by reducing tumor size. Bone pain is managed with medications, including nonsteroidal anti165
Bone scan inflammatory drugs (NSAIDs), steroids, muscle relaxants, opioids, antidepressants, and antianxiety drugs. Nonpharmaceutical interventions used alone or in conjunction with medication can be effective. Examples include physical therapy, exercise, acupuncture, aromatherapy, biofeedback, breathing exercises, hypnosis, massage, and nerve stimulation. Surgery may be necessary to stabilize weakened bones with rods or special cements. Prognosis, prevention, and outcomes: Prognosis depends on the ability to treat the underlying cause of the pain. An increase in bone pain may indicate disease progression that can lead to serious injury, including fracture, loss of bladder and bowel control, and paralysis. Chronic bone pain can be effectively managed to maximize functionality and quality of life in cases in which it cannot be completely eradicated. Linda August Vrooman, R.N., B.S.N., O.C.N. See also Acute lymphocytic leukemia (ALL); Amputation; Blood cancers; Bone cancers; Bone scan; Chronic lymphocytic leukemia (CLL); Chronic myeloid leukemia (CML); Limb salvage; Multiple myeloma; Myelofibrosis; Myeloma; Neuroblastomas; Neuroectodermal tumors; Orthopedic surgery; Paget disease of bone; Pain management medications; Radiopharmaceuticals; Waldenström macroglobulinemia (WM); Young adult cancers.
u Bone scan Category: Procedures Also known as: Bone scintigraphy Definition: A bone scan is a procedure that can detect abnormalities in the skeleton. A radioactive substance (known as a tracer) is injected into the body and taken up by the bone. The tracer emits radiation in the form of gamma rays, which can be detected by a special scanning camera. More tracer will accumulate in areas of the bone that are actively rebuilding or breaking down (such as that in the presence of cancer) compared to the inactive areas. Cancers diagnosed: Cancers that have spread to the bone (metastatic cancers), primarily breast, prostate, and lung cancers, and kidney and thyroid cancers to a lesser degree Why performed: Cancer cells can spread from their primary location to the bone in a multistep process known as metastasis. Metastatic bone disease can result in bone pain and an overall decrease in the quality of life. Tumor cells residing in the bone can also cause bone destruction (known as resorption) as a result of both direct effects of 166
Salem Health: Cancer the tumor and the activation of osteoclasts (a type of bone cell responsible for resorption). This process may result in weakened bones and a greater risk of bone fractures. Furthermore, calcium may be released from the bone as it breaks down, and elevated levels of calcium in the blood can cause loss of appetite, nausea, and exhaustion and can affect the heart and kidneys. A bone scan is one method to detect if cancer has spread to the bone and to identify where the cancer is located. Bone scans can also be used to determine the stage of disease, as well as to examine how much bone damage is present. Additionally, bone scans may be performed to monitor the response to treatment, as some cases of bone cancers are treated with drugs such as bisphosphonates in order to reduce bone resorption. Patient preparation: Very little prior preparation is required, and patients do not need to fast. At the time of the scan, patients must remove all metal objects (such as jewelry, zippers, and metal buttons), as they may interfere with the scan. In some cases, the clothes should be removed and the patients will wear a hospital gown. Steps of the procedure: A bone scan will usually be performed in a hospital. The two stages of this procedure are the tracer injection and the scan. A radioactive tracer will be injected into a vein in the patient’s arm. Patients will then wait one to four hours to allow the tracer to be incorporated into the bone tissue. Drinking several glasses of water (at least four) will help to eliminate excess tracer through the urine. Patients will be instructed to empty the bladder before the scan begins. For the scan, patients must lie still on a table while the scanning camera moves overhead and scans the body. The camera will detect the gamma rays emitted by the tracer that has concentrated in the bone. Sometimes the scans will be conducted when patients are in different positions in order to view the bones from various angles. On average, the bone scan lasts about thirty to sixty minutes. After the procedure: Care should be taken when sitting up at the completion of the scan, as dizziness or lightheadedness may result from the extended period of lying down. Patients will be instructed to drink plenty of fluids for at least forty-eight hours after the bone scan to help eliminate the remaining radioactive tracer. Patients who are breastfeeding should also discard their breast milk for the first two days after the procedure. Risks: Common risks include redness, soreness, or swelling at the injection site. In rare cases, patients have allergic reactions to the tracer.
Salem Health: Cancer Results: If the radioactive tracer is distributed equally throughout the bones, then the result will be considered normal. An abnormal result will occur when the tracer concentrates in distinct sites of the bone, resulting in “hot spots.” Hot spots indicate that there is a lot of activity in the bone, both building and resorption, which may be a sign of tumor cells within the bone. Hot spots, however, may also be caused by a fracture or bone infection. Therefore, if hot spots are detected, the doctor will often suggest blood tests, biopsies, or other imaging tests in order to confirm the presence of cancer. Elizabeth A. Manning, Ph.D. u For Further Information Coleman, R. E. “Clinical Features of Metastatic Bone Disease and Risk of Skeletal Morbidity.” Clinical Cancer Research 12, no. 20, pt. 2 (2006): 6243s-6249s. Even-Sapir, E. “Imaging of Malignant Bone Involvement by Morphologic, Scintigraphic, and Hybrid Modalities.” Journal of Nuclear Medicine 46, no. 8 (2005): 1356-1367. Hamaoka, T., et al. “Bone Imaging in Metastatic Breast Cancer.” Journal of Clinical Oncology 22, no. 14 (2004): 2942-2953. Rosenthal, D. I. “Radiologic Diagnosis of Bone Metastases.” Cancer 80, suppl. 8 (1997): 1595-1607. Yoneda, T., and T. Hiraga. “Crosstalk Between Cancer Cells and Bone Microenvironment in Bone Metastasis.” Biochem Biophys Res Commun 328, no. 3 (2005): 679-687. u
Other Resources
American Cancer Society How Is Bone Cancer Diagnosed? http://www.cancer.org/docroot/CRI/content/ CRI_2_4_3X_How_is_bone_cancer_diagnosed_2 .asp?sitearea= What Is Bone Metastasis? http://www.cancer.org/docroot/CRI/content/ CRI_2_4_1X_What_Is_bone_metastasis_66.asp Mayo Clinic Bone Scan: Using Nuclear Medicine to Find Bone Abnormalities http://www.mayoclinic.com/health/bone-scan/ CA00020 See also Alveolar soft-part sarcomas; Beckwith-Wiedemann syndrome (BWS); Bone cancers; Childhood cancers; Ewing sarcoma; Exenteration; Gallium scan; Glomus tumors; Imaging tests; Lacrimal gland tumors; Mantle cell
Boron neutron capture therapy (BNCT) lymphoma (MCL); Medulloblastomas; Myeloma; Nuclear medicine scan; Paget disease of bone; Pineoblastomas; Pneumonectomy; Radionuclide scan; Rhabdomyosarcomas; Richter syndrome; Spinal axis tumors.
u Boron neutron capture
therapy (BNCT) Category: Procedures Definition: Boron neutron capture therapy (BNCT) is a form of radiation therapy that brings together a stable isotope of boron (boron 10) and a beam of low-energy neutrons to target and destroy tumor cells while leaving adjacent tissue undamaged. Cancers treated: Glioblastoma multiforme (GBM); perhaps other brain tumors and skin melanomas Why performed: Treatments for high-grade gliomas are supportive but not curative. Patients with GBM die within three months when left untreated. Standard approaches using surgical resection, radiation therapy, and chemotherapy increase the median survival time to twelve months, with few patients surviving beyond five years. This is the case because tumor cells infiltrate into surrounding brain tissue and are not readily available to the surgeon, and because glioma cells tend to resist radiation and chemotherapy. Moreover, older patients respond poorly to all current therapies, and there has been no significant new approach to GBM treatment since the early 1980’s. Researchers hope that BNCT will offer some improvement. Patient preparation: Patient preparation is standard for radiation therapy. The size and location of the patient’s tumor are determined using imaging studies such as magnetic resonance imaging (MRI) or computed tomography (CT) scans. Prior to neutron targeting, the patient’s skin is marked to position the head correctly. Steps of the procedure: The patient first receives an intravenous injection of boron 10 that has been chemically tagged to bind with the tumor cells. Neutrons created in a nuclear reactor and modified for BNCT treatment are beamed into the targeted tissue. Neutron activity slows during the ensuing collisions, resulting in a transformation into low-energy thermal neutrons. The boron atoms are then able to capture the thermal neutrons, resulting in boron disintegration into energetic lithium 7 and alpha particles. These cancer-destroying particles react in a very small area, thus confining the ensuing tissue destruction to the tumor. 167
Bowen disease After the procedure: There are no special procedures following BNCT. Risks: The risks are minimal because the path length of the boron elements produced during the procedure is small, limiting the destructive properties to the size of a single cell and leaving nontargeted tissue unharmed. Results: Although work on boron neutron capture therapy continues to hold promise, in general it has proved no more successful than standard therapies and so is not now a routine approach to treatment. Richard S. Spira, D.V.M. See also Radiation oncology; Radiation therapies.
u Bowen disease Category: Diseases, symptoms, and conditions Also known as: Bowen’s disease, squamous cell carcinoma in situ Related conditions: Squamous cell carcinoma (SCC), Bowenoid papulosis, erythroplasia of Queyrat Definition: Bowen disease refers to a type of skin cancer considered squamous cell in situ, named after John Bowen, who documented it in 1912. It may arise anywhere on the skin or the mucous membranes. Bowen disease of the glans penis is called erythroplasia of Queyrat. Unlike other premalignant cancers, Bowen disease possesses a low potential for progression to invasive SCC (less than 5 percent) and an even lower potential for metastasis. Another characteristic feature of Bowen disease is its greater propensity to spread over skin than to invade deeper skin layers. Although its malignant potential is low, extensive skin damage can result from delays in treatment. Risk factors: Repeated exposure to the sun and exposure to the human papillomavirus (HPV), particularly HPV 16, and to arsenic have been implicated as risk factors for Bowen disease. However, more often than not, no risk factor can account for disease development. Etiology and the disease process: Bowen disease originates from the overproliferation of squamous cells, the flat superficial cells that make up the upper layer of the skin (epidermis). The entire epidermal layer is involved in Bowen disease. Triggers of this overproliferation include ultraviolet light from chronic sun exposure and exposure to HPV 16. Both can damage or alter cellular deoxyribo168
Salem Health: Cancer nucleic acid (DNA) and the cellular controls regulating cell division. The TP53 gene is particularly susceptible to ultraviolet light damage and has been implicated as one of many possible mechanisms of cancer proliferation apart from Bowen disease. Arsenic has been hypothesized to enhance the carcinogenic properties of ultraviolet irradiation, as it has a propensity to accumulate in the skin as well as the lungs, bladder, kidney and liver. Incidence: The incidence of Bowen disease has been estimated to range from 14 to 142 cases per 100,000. There is also a predilection for whites as well as older adults. Symptoms: Bowen disease manifests in an insidious manner and often mimics other diseases before being diagnosed. It often appears as a reddish, nonpigmented, raised, and scaly lesion that gradually enlarges. The lesion is easily identifiable as it is well demarcated from surrounding normal skin. The most common sites are the head, neck, and extremities, although any part of the skin or mucous membrane may be affected. As the lesion enlarges, it thickens and starts to exhibit crusting, fissures, or ulcers. These lesions are usually solitary unless malignancy is present. Nonetheless, a full skin examination is warranted. Screening and diagnosis: Bowen disease can easily be mistaken for other skin cancers such as invasive SCC and basal cell carcinoma. Therefore, a punch or shave biopsy of the lesion is essential to initiate appropriate treatment irrespective of location. The sample must include the full thickness of the epidermis and, as much as possible, hair structures in deeper layers. Staging of Bowen disease as a squamous cell carcinoma is not applicable unless invasion of the underlying dermis is seen during microscopic examination. Apart from routine skin examinations as part of a regular physical examination, there are no formal screening tests for Bowen disease. Treatment and therapy: Medical and surgical treatments are available, although the latter are preferred. Medical treatment consists of topical treatment with either 5fluorouracil (5-FU) or imiquimod 5 percent cream. 5-FU is used on the lesion after keratolytic therapy (controlled chemical breakdown) or cryotherapy (freezing). Iontophoresis can also be used to deliver the drug by inducing a drug “gradient” within the lesion. In women, 5-FU must not be taken during pregnancy. Radiotherapy using X rays or grenz rays is reserved for patients who cannot undergo surgery or those with multiple lesions. Lesions may also be treated with photodynamic therapy, in which a chemical agent increases photosensitivity only within tumor cells. This microenvironment is then exposed to a specific
Salem Health: Cancer
Bowen disease
Bowen disease may arise anywhere on the skin. Here it is in the groin. (Custom Medical Stock Photo)
wavelength of light, which causes local toxin and oxygen radical release and immune system activation, leading to tumor cell death. There are many surgical options including excision of both the lesion and a small margin (4 millimeters) of normal tissue, Mohs micrographic surgery, curettage and electrodesiccation, cryotherapy, and carbon dioxide laser ablation. Simple excision is preferred for small lesions in nonproblematic areas where deformities can be easily corrected. Mohs micrographic surgery, which is a very precise procedure also used in removing other skin cancers, is more suited to removing larger or recurring lesions and in areas where skin conservation is required for cosmetic reasons or functional preservation (for example, the face or joints). Curettage and electrodesiccation, cryotherapy, and carbon dioxide laser ablation are also effective treatments but do not provide pathologic specimens to confirm tumor eradication, particularly with deeper-lying lesions. Prognosis, prevention, and outcomes: The overall prognosis of patients after treatment is excellent. Recurrence
is often associated with inadequate removal of the lesion or malignant transformation and spread. Some of the sequelae of treatment include skin deformity, scarring, infection, and underlying damage to blood vessels and nerves. Prevention is aimed at decreasing unnecessary ultraviolet light exposure. This includes patient education regarding sun exposure and measures such as wearing protective clothing and sunscreen with an SPF of at least 15 and avoiding exposure to the sun between 10 a.m. and 4 p.m. Aldo C. Dumlao, M.D. u
For Further Information Fossel, Michael B. Cells, Aging, and Human Disease. Oxford, England: Oxford University Press, 2004. Gupta, Renu. Skin-Care. Delhi, India: Diamond Pocket Books, 2000. McCally, Michael. Life Support: The Environment and Human Health. Cambridge, Mass.: MIT Press, 2003. 169
Brachytherapy u
Other Resources
American Cancer Society Treating Bowen Disease http://www.cancer.org/docroot/CRI/content/ CRI_2_4_4X_Treatment_of_bowens_disease_51.asp American Osteopathic College of Dermatology Bowen’s Disease http://www.aocd.org/skin/dermatologic_diseases/ bowens_disease.html See also Complementary and alternative therapies; Penile cancer; Premalignancies; Skin cancers; Vulvar cancer.
u Brachytherapy Category: Procedures Also known as: Sealed source radiotherapy, endocurietherapy Definition: Brachytherapy is a form of radiation treatment in which the radioactive source consists of small pellets or seeds, ribbons, or wire, each about the size of a grain of rice, that are placed into or next to the area being treated. Brachytherapy is from a Greek word meaning “short,” so literally brachytherapy means “short distance treatment.” It is unlike radiation from an external source, such as a machine, in which the radioactive beam is directed at the tumor from outside the body. There are three types of brachytherapy delivery. Intracavity treatment involves radioactive implants that are placed inside a body cavity, such as the uterus. In interstitial treatment, radiation implants are placed directly in the tumor. They are often permanent and used in prostate cancer treatment. In unsealed internal radiation therapy, radioactive materials are injected into a vein or body cavity. Brachytherapy can be either permanent or temporary. Permanent brachytherapy, or low dose rate (LDR) brachytherapy, is often called seed implantation and involves placing small radioactive seeds at or near the tumor and leaving them there permanently. This is typically used in the treatment of prostate cancer. The radioactivity of the seeds decreases over time, and the seeds left inside the patient cause no discomfort or harm. Temporary brachytherapy, or high dose rate (HDR) brachytherapy, involves radioactive seeds that are left in the body only for a specific amount of time and then are removed. Treatments may consist of several visits to the physician to have the seeds placed and removed. This method is used in the treatment of most of the other cancers. 170
Salem Health: Cancer Radiation works by killing cancer cells when they are trying to multiply. The deoxyribonucleic acid (DNA) of cancer cells is more sensitive to radiation than that of normal cells, so the normal cells are able to repair themselves and the cancer cells die. Cancers treated: Brachytherapy is used for many types of cancer in the body, including prostate, cervical, head and neck, ovarian, breast, lung, gallbladder, uterine, and vaginal cancers, as well as anal/rectal tumors and sarcomas. It can also be used to treat noncancerous conditions such as benign tumors and coronary artery disease. Additionally, brachytherapy can be used in conjunction with other cancer treatments, including chemotherapy and external beam radiation. It can be used as both a curative and a palliative form of treatment. Why performed: Brachytherapy has been in use since the early twentieth century, and it has been proven to be safe and effective. It allows a higher dose of radioactivity to be used with decreased risk of damage to healthy tissue, quicker healing times, and decreased risk of infection. In breast brachytherapy, for example, the therapy is quicker than external beam radiation, and it only treats a portion of the breast. Brachytherapy often can be performed in five days as opposed to five to seven weeks. The patient has a better cosmetic result and healthy tissue is preserved. Patient preparation: Before the treatment begins, patients meet with the physician and receive instructions on how to care for themselves after the treatment. The physician will determine what tests should be done prior to brachytherapy, which may include blood tests, electrocardiograms (ECG or EKG), and X rays. The actual prepping of the patient depends on where the seeds are being placed. Typically, a radiation oncologist, a radiation physicist, a dosimetrist, and a radiation therapist are involved in planning the treatment. The radiation oncologist determines the type of treatment needed and is responsible for the overall treatment plan, including the area to be treated and the dose to be delivered. The physicist calculates the dose to be prescribed. The dosimetrist assists in dose calculation and helps in delivering the prescribed dose. The radiation therapist operates the equipment and delivers the dose. Through special computer programs, the dose, duration, and delivery method of the treatment are determined. Without this specific calculation, the cancer cells might receive too little radiation and the normal tissue could receive too much. Steps of the procedure: The steps of the procedure also vary depending on where the seeds are being placed in the body. The seeds are generally inserted into the site of the
Salem Health: Cancer tumor through a needle or catheter. Sometimes a device to hold the seeds is placed near the tumor. Often, X rays, ultrasound, computed tomography (CT) scans, or even surgery is used to help position and verify placement of the radioactive material or device. Some doses are delivered to the patient on an outpatient basis, in which radiation is delivered to the tumor in a short amount of time and then the delivery device is removed and the patient goes home. The patient may return at intervals for more treatment. Alternatively, a patient may spend a couple of nights in the hospital so that the delivery device can remain in place and the radioactivity can be delivered at a continuous rate. These patients are placed in private rooms, usually with limited or no visitors allowed. The hospital staff will continue to take care of the patient, but they limit the amount of time that they spend with the patient in order to keep their radiation exposure low. A patient may have an intravenous line inserted in order to receive medications. Sedatives or anesthesia may also be used to place the delivery device, again depending on the location of the treatment. After the procedure: Patients typically can go home after the LDR procedure. The physician will give the patient detailed instructions for self-care at home, which may include limiting contact with pregnant women or children for a limited amount of time so as not to expose them to the radioactivity. The patient may have some pain, swelling, or bleeding at the site of the procedure. Educational materials may be very helpful to the patient and family after the procedure. Side effects and precautions can be outlined. Generally, the patient is to avoid heavy lifting or strenuous physical activity for a few days after the procedure. Sometimes the radiation precautions include instructing the patient to sleep alone for a period of time, to avoid sexual relations for a period of time, and to use tweezers, not bare hands, to pick up any seed that may become dislodged. Instructions on what to do with a dislodged seed are also given. HDR patients are usually in the hospital for forty-eight to seventy-two hours and then are discharged once the radiation device is removed. They also receive detailed instructions on how to protect family members from exposure and to watch for side effects such as pain and bleeding. Risks: Like the preparation of the patient and the steps of the procedure, the risks from brachytherapy also vary depending on the area treated. Although relatively safe, brachytherapy is not totally without risks. Patients with permanent brachytherapy seeds continue to give off small amounts of radiation for several weeks. With this type of
Brachytherapy treatment, there is a risk that the seeds will move out of place. Patients are often told to strain their urine at home in case in seeds do migrate. Patients are given special instructions from their doctor about protecting family members from exposure. Brachytherapy for prostate cancer can cause sexual dysfunction such as impotence and bowel problems such as diarrhea, although these are not very common. Urinary irritation is a more common side effect because the urine stream becomes obstructed by swelling in the prostate after therapy. A urinary catheter or Foley catheter is placed to allow urine to flow. The prostate usually returns to normal size and the blockage disappears after several weeks, and the catheter can then be removed. Patients may continue to have some urinary burning for a few weeks, but this also resolves. Results: The physician may order scans or X rays after brachytherapy in order to determine if the treatment was successful. The effectiveness of brachytherapy varies depending on the location of the treatment and the type of cancer that was treated. It has proven to be effective in many types of cancer, especially cervical and prostate cancer. In early prostate cancer, brachytherapy offers ten-year survival rates comparable to surgical removal of the prostate, according to several studies. In general, patients have fewer side effects and a quicker recovery time with this therapy as compared to external beam radiation or surgery. There is also less risk of infection than with surgery. As a result, patients typically have a better quality of life with this procedure, which is easier to tolerate. Michelle Kasprzak, R.N., B.S.N., O.C.N. u
For Further Information Merrick, G. S., et al. “Long Term Rectal Function After Permanent Prostate Brachytherapy.” Cancer Journal 13, no. 2 (March/April, 2007): 95-104. Mitchell, I. “Patient Education at a Distance.” Radiology 13, no. 1 (February, 2007): 30-34. Nag, Subir, ed. Principles and Practices of Brachytherapy. Malden, Mass.: Blackwell, 1997.
u
Other Resources
American Brachytherapy Society (ABS) http://www.americanbrachytherapy.org American Cancer Society http://www.cancer.org National Cancer Institute http://www.cancer.gov 171
BRAF gene See also Afterloading radiation therapy; Anal cancer; Carcinomas; Cervical cancer; Endometrial cancer; Iridium seeds; Mayo Clinic Cancer Center; Neurologic oncology; Radiation oncology; Radiation therapies; Rhabdomyosarcomas; Veterinary oncology.
u BRAF gene Category: Cancer biology Also known as: BRAF1, RAFB1, v-raf murine sarcoma viral oncogene homolog B1 Definition: BRAF is an internal part of a cellular signaling pathway. This signaling pathway results in cell growth when the correct chemical message is sent. The mutated form of the BRAF gene has a single base (letter) of deoxyribonucleic acid (DNA) changed; this changes the activity of the BRAF protein. This mutant BRAF protein is broken and is continuously on, sending growth signals even when there are no chemical messages and causing runaway growth of cells. The result is like a broken light switch that will not turn off. Etiology and symptoms of associated cancers: The BRAF protein is central to causing many types of cancer, including melanoma, colon cancer, ovarian cancer, thyroid cancer, and gliomas. Knowledge of the BRAF gene, which was first described as a proto-oncogene in 2002, is useful in diagnosing cancer and deciding what type of treatment to use. The advanced state of knowledge in modern biology and medicine makes it likely that drugs that attack cancers with BRAF mutations will be quickly developed. Tumors are called benign (not harmful) or malignant (harmful). Benign tumors can acquire mutations that change them into malignant cancers. Experts believe that cancer requires multiple steps to form. Many normal functions of cells need to be damaged to create a malignant cancer. Cellular functions typically damaged are cell growth (unregulated cell growth), telomere maintenance (cell aging), apoptosis (cell death), angiogenesis (the ability to grow blood vessels), and metastasis (the ability of cells to detach from one part of the body and migrate to another). BRAF mutations primarily affect the first of these functions, cell growth. When BRAF is mutated in a cell, the cell receives a continuous signal to grow and divide. This signal from BRAF also has a smaller effect of reducing the probability of cells dying by apoptosis, an effect promoting metastasis, and effects promoting angiogenesis. BRAF mutations are often found in benign growths. 172
Salem Health: Cancer Mutations of other genes are needed to destroy the remaining cell functions and make a growth malignant. For example, the destruction of the TP53 gene (also known as p53) will help the cancer overcome cell aging (which normally slows down the overgrowing cells) and apoptosis (which normally kills off some of the overgrowing cells). For comparison, TP53 mutations are rarely found in benign growths and are almost always found as secondary changes in cancers. Because BRAF mutations are found in benign and malignant growths, many people believe BRAF is an early change that eventually leads to malignant cancers. Cancers that seem to begin with BRAF mutations also seem to end up being among the most malignant. Even though BRAF is associated with the worst types of malignancies, the silver lining is that since BRAF mutations happen early, while the tumors are still benign, the BRAF mutation can serve as an early warning. BRAF mutation is not found in all cancer but only in cancers of certain tissues. Most of these tissues are what doctors call adenoid tissues. Specifically, BRAF mutation has been found in melanoma (skin), glioma (nerve), thyroid, ovarian, and colon cancer. Researchers have shown that 80 percent of the benign nevi (moles) studied carried the BRAF mutation and that 66 percent of malignant melanomas studied carried the BRAF mutation. In benign gliomas, BRAF mutation is rarely observed, but in malignant gliomas, the BRAF mutation was almost always observed. Testing and treatment: Standard tests of DNA can be done on blood or tumor tissue samples to detect the BRAF mutation. While these tests are very reliable, the knowledge of the BRAF gene mutation and the tests for it are new and are not yet widely available. BRAF mutation tests will help doctors determine the exact type of cancer, how dangerous it is, and what types of treatment to use. One drug in testing is BAY 43-9006. This drug seems to reverse the effect of BRAF mutation and stop the growth of cells. It also seems to kill the cancer cells by restoring normal cell death (apoptosis). Although only laboratory experiments have been done, some researchers expect that actual tests in people with cancers will show that the drug will not only stop the growth of the cancers but may kill the cancers entirely. History: The discovery of the BRAF mutation is a direct result of the Human Genome Project. In the 1990’s the Human Genome Project sequenced the human genome and described the complete set of about 30,000 human genes, the instructions for the body. In the 2000’s the Cancer Ge-
Salem Health: Cancer
Brain and central nervous system cancers
nome Project started examining all 30,000 genes in cancers to find broken genes. One result was the discovery of the BRAF gene mutation in 2002. Christopher Pung, B.S., C.L.Sp. (CG)
tumors of the cerebellum, and central neuroblastomas, which affect the brain cortex. The naming system for pediatric brain tumors is still evolving and remains controversial.
u
Risk factors: Chemicals such as vinyl chlorides, aromatic hydrocarbons, and N-nitroso compounds in cigarettes; ionizing radiation; electromagnetic fields; and viral infections have been suggested as possible environmental risk factors. Some brain cancers appear to be more common in people working with radiation and chemicals, such as employees of nuclear plants and oil refineries. However, none of these environmental factors have been conclusively shown to cause brain cancer. Genetic risk factors include inherited diseases such as tuberous sclerosis and von Hippel-Lindau disease.
For Further Information Begley, Sharon. “Science Journal: Nature’s Quirks Limit DNA-Based Drug Possibilities.” Pittsburg PostGazette, November 11, 2005. Davies, H., et al. “Mutations of the BRAF Gene in Human Cancer.” Nature 417 (2002): 949-954. Shaw, Gina. “BRAF Mutations Predict Tumor Response.” Drug Discovery and Development 8 (2005): 8. u
Other Resources
Atlas of Genetics and Cytogenetics in Oncology and Haematology BRAF http://atlasgeneticsoncology.org/Genes/ BRAFID828.html The Human Genome Melanoma and the BRAF Gene http://genome.wellcome.ac.uk/doc_WTD020812.html See also Genetics of cancer.
u Brain and central nervous
system cancers Category: Diseases, symptoms, and conditions Also known as: Brain tumors, central nervous system (CNS) tumors, gliomas, glioblastomas, astrocytomas, meningiomas, neuromas Related conditions: Seizures, psychiatric symptoms (including abnormal personality and behavioral characteristics), loss of memory and cognition Definition: Brain and central nervous system cancers are masses of abnormal cells (malignant tumors) in the brain and central nervous system that grow rapidly and can invade surrounding normal tissue. Brain tumors are named for both the type of cell from which they arose and their location in the brain. For example, schwannomas are named after the Schwann cells, astrocytomas after astrocytes, oligodendrogliomas after oligodendrocytes, meningiomas after the meninges or brain membranes, and pinealoblastomas after the pineal gland. Exceptions are medulloblastomas, which are undifferentiated neuroectodermal
Etiology and the disease process: The causes of brain and central nervous system cancers are still unproven. Environmental, genetic, medical, and lifestyle factors may all play a role in causing these cancers. Brain tumors can be primary or secondary. Primary tumors originate in the brain and are rarer than secondary brain tumors, accounting for around one-fourth of all brain tumors. Once they occur, primary brain tumors rarely metastasize to other tissues beyond the spinal cord. Examples of primary brain tumors are schwannomas, astrocytomas, medulloblastomas, meningiomas, and oligodendrogliomas. Secondary or metastatic tumors originate elsewhere in the body and migrate or metastasize to the brain. The types of cancer most likely to metastasize to the brain are breast cancer, lung cancer, melanoma, and colon cancer. Nasopharyngeal cancer can also metastasize to the brain via the cranial nerve or through openings in the bone at the base of the skull called foramina. Incidence: The annual incidence of primary invasive central nervous system tumors in the United States is 6.6 per 100,000 people, with an estimated 4.7 deaths per 100,000 people annually. Approximately 20,500 new cases of brain and central nervous system cancers occurred in the United States in 2007, as well as an estimated 12,740 deaths from these cancers. Brain tumors account for 85 to 90 percent of all primary central nervous system tumors. Primary brain tumors have a higher incidence in whites than in blacks and are more common in men than in women, with three out of five sufferers being men. Brain tumors usually arise in early or middle adult life and are most common in people older than sixty-five. However, brain cancer can occur at any age. Primary brain tumors are rarer than secondary brain tumors, with a ratio of 1 primary brain tumor to every 3 sec173
Brain and central nervous system cancers
Salem Health: Cancer
ondary brain tumors. Some experts put this ratio at closer to 1:10, attributing the increased detection of secondary tumors to more sensitive imaging methods. The most common primary brain tumors are astrocytomas, glioblastomas, meningiomas, and other mesenchymal tumors, which make up around 65 percent of all primary brain tumors. The most common primary spinal tumors are schwannomas, meningiomas, and ependymomas, accounting for 79 percent of primary spinal tumors. Secondary or metastatic brain tumors occur in 20 to 40 percent of brain cancer patients. About 80 percent of secondary tumors occur in the cerebral hemispheres, 15 percent in the cerebellum, and 5 percent in the brain stem. Multiple metastases to the brain are more common than solitary metastases, occurring in more than 70 percent of cases.
(including blurred vision, double vision, or loss of peripheral vision), loss of memory and cognition, personality or behavioral changes, abnormal breathing rates, dizziness, nausea or vomiting, loss of hearing, and hormonal disorders. In one study of brain tumors and seizures, seizures were observed in more than 38 percent of patients with primary brain tumors and in 20 percent of patients with cerebral metastases. Oligodendrogliomas are more likely than other types of central nervous system tumors to be associated with seizures. Screening and diagnosis: The first step of brain tumor screening involves a neurological exam to test vision, hearing, balance, coordination, and reflexes. If the neurological exam results warrant further testing, the doctor may order brain imaging scans, such as computed tomography (CT) and magnetic resonance imaging (MRI) scans, which produce pictures of the brain in which tumors can be distinguished by means of dyes or magnetic fields. Com-
Symptoms: Symptoms of brain tumors include persistent headaches that become more intense and frequent, seizures, problems walking and speaking, vision problems
Incidence of Brain and Central Nervous System Cancer per 100,000 People, by Gender 10 Men
9
Women
8.3 8 7 6
5.9
5
6.0
4.7
4.9 3.9
4
3.5
3.5 3.0
3
2.2 2 1 0 White
Hispanic
Black
Asian/Pacific Islander
American Indian/ Alaska Native
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 Note: Based on cases diagnosed in 2000-2004
174
Salem Health: Cancer puted tomography is better at detecting bone calcification and skull lesions. Magnetic resonance imaging is better for detecting soft-tissue and spinal cord tumors. Other tests include an angiogram, in which a dye is injected into the blood to highlight the blood vessels in and around the brain, X-ray scans of the head and skull to reveal changes to skull bones and calcium deposits associated with brain tumors, and positron emission tomography (PET), which identifies areas of abnormal brain metabolism. The discovery of genetic mutations (changes in specific genes) that are linked to different types of cancers has opened the door to future genetic screening for at-risk individuals. A genetic screen involves taking a blood sample and analyzing the deoxyribonucleic acid (DNA) in the sample for genetic mutations that are known to cause a specific type of cancer. When a tumor is detected on a brain scan, a biopsy is usually performed to make a diagnosis. A biopsy involves taking a sample of the tumor; this can be done in a separate procedure or during surgery to remove the tumor. The tumor can be biopsied by open craniotomy, in which the cranium or skull is opened to expose the brain, allowing a sample of the tumor to be surgically removed. Hard-toreach tumors can be sampled by means of a needle biopsy. A small hole, known as the “burr” hole, is drilled in the cranium, and tumor cells are extracted with a narrow-bore needle. The tumor sample is frozen and cut into very thin slices, which are then examined under a microscope. This allows the medical team to confirm the presence of a tumor and determine the specific type of tumor. Additional tests may also be performed to help pinpoint the tumor type. There is no standard method for staging brain tumors. Along with the tumor grade, the type of cell from which the tumor originated and the location in the central nervous system are used for classifying the tumor. Grade I tumors grow slowly and rarely spread to other tissues. The following types of brain tumors are classified as Grade I: pilocytic astrocytomas, Grade I meningiomas, and Grade I ependymomas. Grade II tumors typically grow slowly but may spread to other tissues. Grade II tumors include diffuse astrocytomas, Grade II meningiomas, oligodendrogliomas, Grade II ependymomas, oligoastrocytomas (made up of a mixture of oligodendrogliomal and astrocytomal cells), pinealcytomas, and craniopharyngiomas. Grade III tumors contain fast-growing cells that often spread to other tissues. Grade III tumors include anaplastic astrocytomas, anaplastic oligodendrogliomas, anaplastic ependymomas, anaplastic oligoastrocytomas, and pinealoblastomas. Grade IV tumors grow rapidly, spread aggressively, and contain cells that appear very different from normal cells.
Brain and central nervous system cancers Grade IV tumors include gliobastomas and medulloblastomas, which usually occur in children and adults aged twenty-one to forty. Treatment and therapy: The most common treatment for brain and central nervous system cancers involves surgery to remove as much of the tumor as possible without disrupting neurological function. Surgery usually does not result in the removal of all tumor tissue. In addition, some tumors are located deep in the brain and cannot be reached without considerable damage to the surrounding tissue. These tumors are sometimes diagnosed without conducting a biopsy and treated by nonsurgical means. Radiation treatment and chemotherapy can be used to remove cancer cells remaining after surgery and to treat deep-seated tumors that are not amenable to surgical removal. Radiation therapy is effective for a wider range of brain and spinal cord tumors than chemotherapy. Radiation can enhance the cure rate and prolong disease-free survival. A common type of radiation treatment is external beam radiation therapy (EBRT). Chemotherapy has been shown to prolong disease-free survival in patients with gliomas, medulloblastomas, and some germ-cell tumors. Chemotherapy includes the use of dexamethasone, mannitol, furosemide, and nitrosourea. Anticonvulsants are also used to treat cancer patients with seizures. The majority of brain tumors are accompanied by multiple metastases. These can be treated with a combination of surgery or radiosurgery and whole-brain radiation therapy (WBRT). Radiosurgery is useful for lesions that have a diameter smaller than 3 centimeters. Corticosteroids and anticonvulsants can also be used as needed. Chemotherapy is not as widely used for metastatic brain tumors but may be effective for brain metastases from chemosensitive primary tumors. New therapies that are currently being tested include the use of tyrosine kinase receptor inhibitors, farnesyl transferase inhibitors, viral-based gene therapy, and oncolytic viruses. Patients with tumors that do not respond well to the commonly used treatments can look into clinical trials using combinations of novel therapies with EBRT. Surgery to remove brain tumors can sometimes result in the damage of normal brain tissue. This can cause partial paralysis, changes in sensation, muscle weakness, and defects in thinking and language function. These patients may be referred for physical and speech therapy to regain muscle and language functions, respectively. Follow-up visits are an important part of patient care and usually occur every three to four months for the first two to three years after treatment, then once or twice a year after that. The doctor will discuss treatment side effects, review 175
Brain scan medical history, and conduct various tests to determine if the cancer has recurred or metastasized to other parts of the body. Prognosis, prevention, and outcomes: A cancer patient’s prognosis depends on age (whether younger or older than sixty), the number and location of tumors in the brain and spinal cord, the rate of tumor growth and metastasis, and the tumor’s response to treatment. The prognosis is better for brain metastases from breast cancer and worse for brain metastases from colon cancer. When doctors discuss survival rates, they are referring to the percentage of people with a specific type and stage of cancer who survive for a predetermined period of time after their diagnosis. A common statistic is the five-year survival rate. Doctors may talk about the percentage of people who are alive, the percentage who are symptom-free, or the percentage who are disease-free five years after diagnosis. These numbers are averages for large groups of people and do not predict the specific outcome for an individual patient. Because the causes of brain and central nervous system cancers are not well established, prevention strategies are still evolving. As with other cancers, quitting smoking, maintaining a healthy diet, and exercising probably have beneficial and preventive effects. A novel therapy that has been approved in Switzerland under the brand name DCVax-Brain involves vaccination with dendritic cells that recognize molecules on an individual patient’s tumor cells. When examining outcomes for brain cancer survivors, it is important to also consider their quality of life. A survivor’s quality of life has been directly linked to cognitive impairment, especially defects in speech and language. Ing-Wei Khor, Ph.D. u
For Further Information Connelly, J. M., and M. G. Malkin. “Environmental Risk Factors for Brain Tumors.” Current Neurology and Neuroscience Reports 7 (2007): 208-214. Hutter, A., et al. “Brain Neoplasms: Epidemiology, Diagnosis, and Prospects for Cost-Effective Imaging.” Neuroimaging Clinics of North America 13 (2003): 237-250. Ricci, P. E. “Imaging of Adult Brain Tumors.” Neuroimaging Clinics of North America 9 (1999): 651-669. Wen, P. Y., P. M. Black, and J. S. Loeffler. “Treatment of Metastatic Cancer.” In Cancer: Principles and Practice of Oncology, edited by V. T. DeVita, Jr., S. Hellman, and S. A. Rosenberg. 6th ed. Philadelphia: Lippincott Williams & Wilkins, 2001. 176
Salem Health: Cancer u
Other Resources
Cedars-Sinai Brain Tumors http://www.csmc.edu/5192.html MayoClinic.com Brain Tumor http://mayoclinic.com/health/brain-tumor/DS00281 National Cancer Institute Brain Tumor http://www.cancer.gov/cancertopics/types/brain Revolution Health Brain Cancer http://www.revolutionhealth.com/conditions/cancer/ brain-cancer/ WebMD http://www.webmd.com See also Acoustic neuromas; Astrocytomas; Ataxia telangiectasia (AT); Carcinomatous meningitis; Cell phones; Cognitive effects of cancer and chemotherapy; Craniotomy; Gliomas; Leptomeningeal carcinomas; Meningeal carcinomatosis; Meningiomas; Neuroblastomas; Neuroectodermal tumors; Neuroendocrine tumors; Neurofibromatosis type 1 (NF1); Neurologic oncology; Oligodendrogliomas; Orbit tumors; Pheochromocytomas; Primary central nervous system lymphomas; Schwannoma tumors; Spinal axis tumors; Spinal cord compression; Turcot syndrome; Von Hippel-Lindau (VHL) disease; Wilms’ tumor aniridia-genitourinary anomalies-mental retardation (WAGR) syndrome and cancer.
u Brain scan Category: Procedures Definition: Computed tomography (CT) scan and magnetic resonance imaging (MRI) are two widely used methods of scanning the brain to distinguish normal tissue from abnormal tissue (tumors or masses). The CT scanner uses X rays and a type of ionizing radiation (dye), to acquire images of bone and tissue. MRI uses nonionizing radio frequency signals to acquire its images and is best suited for noncalcified (soft) tissue. Both CT and MRI scanners generate multiple two-dimensional cross-sections, or “slices,” of tissue and produce three-dimensional reconstructions. For purposes of tumor detection and identification, MRI is generally superior. However, CT usually is more widely available, faster, and much less expensive,
Salem Health: Cancer
Brain scan
This series of MRI images, from left to right, show a brain tumor shrinking after radiation therapy, but with development of metastatic brain disease (far right). The scans were taken at the beginning of treatment and at six and fifteen months. (Custom Medical Stock Photo)
and it may be less likely to require the person to be sedated or anesthetized. If cancer is suspected, then the CT scan will provide X-ray images of the brain or other internal organs to detect masses or tumors. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. Acomputer combines the images by “stacking” them on top of each other to offer an exact three-dimensional rendering. MRI is a procedure using a magnet and radio waves to send a series of detailed images of the brain to a computer. A computer then produces cross-sectional or threedimensional images for evaluation. A substance called gadolinium may be injected into the patient through a vein. The gadolinium collects around the cancer cells so that they show up brighter in the picture. This procedure is also called nuclear magnetic resonance imaging (NMRI).
sensation throughout the body and a metal taste in the mouth. Only the head will be covered by the scanner, and those who experience claustrophobia generally do not have problems with a brain scan. After the procedure: Patients are not restricted after this procedure and may eat and drive as normal.
Why performed: Brain scans are ordered by physicians to offer the clearest information available about the brain. The method of scanning depends on the patient’s history and examination and the choice by the physician for diagnostic testing.
Risks: The MRI examination poses almost no risk to the average patient; however, if sedation is necessary, a nurse or technologist will monitor vital signs to avoid excessive sedation. The magnetic field is not harmful to the patient, but metal devices nearby can create malfunction in the MRI. If dye is injected, then there is a rare risk of mild allergic reaction. The CT scan poses a slight risk of cancer as a result of the exposure to radiation. Studies have shown this risk is equivalent to the amount of radiation to which an average person is exposed in three years from other, unavoidable sources. There is a risk to an unborn fetus; therefore CT scanning is not recommended for pregnant women. Nursing mothers must wait twenty-four hours after the dye is injected to return to nursing. There is always a slight chance of cancer from radiation exposure, but the benefit of an accurate diagnosis far outweighs the risk.
Patient preparation: If the brain scan involves injecting or ingesting a dye, then the patient may be asked to avoid eating or drinking four hours before the exam. All jewelry must be removed prior to the brain scan.
Results: The brain scan will be read by a neuroradiologist, and the results will be shared with the physician to discuss with the patient. Robert J. Amato, D.O.
Cancers diagnosed: Brain tumor, metastasized cancer
Steps of the procedure: The patient will be asked to lay down, placing the head in a stabilizer, and remain very still. If contrast (dye) is required, then it will be injected through the intravenous (IV) line that was placed by a radiology nurse or technologist prior to the exam. During the injection, it is normal for patients to experience a warm
u
For Further Information Buthiau, Didier, and David Khayat. CT and MRI in Oncology. New York: Springer-Verlag, 1998. Lee, Howard S., et al. Cranial and Spinal MRI and CT. 4th ed. New York: McGraw-Hill Professional, 1999. 177
BRCA1 and BRCA2 genes Wolbarst, Anthony Brinton. Looking Within: How X-Ray, CT, MRI, Ultrasound, and Other Medical Images Are Created, and How They Help Physicians Save Lives. Berkeley: University of California Press, 1999. See also Astrocytomas; Brain and central nervous system cancers; Computed tomography (CT) scan.
u BRCA1 and BRCA2 genes Category: Cancer biology Also known as: Breast cancer susceptibility genes; breast cancer 1, early onset; breast cancer 2, early onset Definition: BRCA stands for breast cancer susceptibility. BRCA1, the first breast cancer susceptibility gene, was identified and cloned in 1994. A second breast cancer susceptibility gene, BRCA2, was discovered soon after. Identification of BRCA1 and BRCA2 as breast cancer susceptibility genes has had a profound impact on understanding the disease. The immediate clinical use of their discovery for both diagnosis and accurate assessment of increased risk through screening has been one of the foremost success stories in the fight against cancer. Familial disease: Less than 5 percent of breast cancers are hereditary, but more than 90 percent of hereditary breast cancers are caused by mutations in either BRCA1 or BRCA2. Each year approximately 200,000 women in the United States are diagnosed with breast cancer, and about 5 to 10 percent of these women have an inherited mutant BRCA1 or BRCA2 gene. The mutations can be inherited from either the maternal or the paternal side of the family. Mutations in BRCA1 and BRCA2 increase a woman’s lifetime risk of not only breast cancer but also ovarian, colon, and Fallopian tube cancers. Women with an inherited alteration in one of these genes have an increased risk of developing these cancers before the menopause. Altered BRCA2 poses a greater risk in men than altered BRCA1. Men with altered BRCA2 are at a higher risk of breast cancer and prostate cancer. Alterations in the BRCA2 gene have also been associated with increased risks of lymphoma, melanoma, and cancers of the pancreas, gallbladder, bile duct, and stomach in both men and women. Risks and incidence: Estimates of lifetime risks suggest that approximately 12.9 percent of women in the general population will develop breast cancer, as compared with estimates of 78 percent of women with an altered BRCA1 or BRCA2 gene. The ovarian cancer risk is 49.4 percent in carriers versus 1.7 percent in the general population. 178
Salem Health: Cancer Among men, the breast cancer risk is 5.8 percent for carriers versus 0.01 percent in the general population. In carriers, risks for colon, pancreatic, and stomach cancers are also elevated twofold, threefold, and fourfold, respectively, with no increase in prostate cancer risk. Additionally, in BRCA1 mutation carriers, the lifetime risk of developing cancer of the breast can be as high as 85 percent and that of developing ovarian cancer as much as 42 to 63 percent. In BRCA2 carriers, the lifetime risk of developing breast cancer is as high as 86 percent and that of developing ovarian cancer about 27 percent. The likelihood that breast or ovarian cancer is linked with BRCA1 or BRCA2 mutations is highest in families with a history of multiple cases of breast and ovarian cancer, particularly involving a mother, sister, or daughter; diagnosis of breast cancer before the age of thirty-five; presence of male breast cancer in the family; two or more primary cancers such as breast and ovarian cancers or bilateral breast cancer (separate cancers in each breast) in an individual; other multiple cancers in the family, especially prostate cancer; and an Ashkenazi (central and eastern European Jewish) background. It is important to note that not every woman with this sort of background will carry a defective BRCA1 or BRCA2, and not every cancer that occurs in such families will be due to a BRCA1 or BRCA2 defect. Additionally not all women who carry a BRCA1 or BRCA2 mutation will develop breast or ovarian cancer. Mutations in BRCA1 account for breast or ovarian cancers in 45 percent of families with a history of breast cancer and up to 90 percent in families with a history of both breast and ovarian cancers. BRCA2 mutations account for breast cancer in about 35 percent of families with a history of breast cancer. Studies suggest that women who develop breast cancer before the age of fifty have a one in four chance of carrying a BRCA1 or BRCA2 mutation if they have any relative who also develops the disease before the age of fifty. There is a 50 percent chance that mutant carriers will transmit the mutated gene to their offspring. BRCA1-related breast cancer appears to be more aggressive than other types of breast cancer and has a poorer prognosis, and most BRCA1-related ovarian cancers are of the invasive type. Some characteristics of hereditary breast cancer, such as how it occurs at an earlier age, more often affects both breasts, and is associated with other cancers, make it clinically distinct from sporadic cancer. BRCA1 and BRCA2 were identified by linkage analysis of families with multiple cases of early-onset breast and ovarian cancer. BRCA1 is 5,592 kilobases long with 24 exons, and BRCA2 is twice as long with 10,254 kilobases and 27 exons. More than one hundred different alterations scattered throughout BRCA1 and BRCA2 have been iden-
Salem Health: Cancer tified. These alterations tend to be distinct, and in general, most families have a unique alteration. Mutations anywhere along either gene are associated with an increased risk of breast cancer. Some evidence suggests that mutations in the 5′ end of BRCA1 and mutations in exon 11 of BRCA2 might be associated with ovarian cancer. Alterations in certain regions of the BRCA2 gene are known to predispose individuals to a greater risk of ovarian cancer in women and prostrate cancer in men, as compared with alterations in other parts of the gene. This suggests differences in patterns of cancer between individuals with a BRCA1 mutation versus a BRCA2 mutation. Of the more than one hundred alterations identified in each gene (BRCA1 and BRCA2), three alterations have been identified in Ashkenazi Jewish families with a history of breast cancer. These alterations are 185deIAG and 5382insC (BRCA1) and 6174deIT (BRCA2). The estimated frequencies of the three alterations in the general Ashkenazi population are 1.0 percent, 0.1 percent, and 1.4 percent, respectively. Cellular function: BRCA1 and BRCA2 are tumorsuppressor genes, and the BRCA proteins are involved in a multitude of key cellular processes. Research has demonstrated the involvement of BRCA1 and BRCA2 proteins in complexes that activate repair of double-strand breaks and initiate homologous recombination, suggesting a key role of BRCA proteins in maintaining genome stability and integrity. In response to deoxyribonucleic acid (DNA) damage, BRCA1 is engaged in the transcriptional regulation of several genes such as P21 (CDKN1A) and GADD45, which activate cell-cycle check-point induced replication arrest to allow for repair. It is unclear why a defect in BRCA predisposes predominantly to cancer of the breast and ovary, even though the known functions of BRCA proteins are essential to all cell types. Whether estrogen, a known promoter of sporadic breast cancer, affects the risk of BRCA1- and BRCA2-related breast cancers is not clear. Given that factors that contribute to enhanced exposure to estrogen, such as early onset of menarche and late menopause, correlate with a higher incidence of breast cancer and that premenopausal oophorectomy (the surgical removal of the ovaries) exerts a preventive effect, an association is suggested between BRCA1 and BRCA2 and estrogen receptor alpha (ERα). Prevention: The best opportunity to reduce mortality is through early detection. Preventive mastectomy and preventive oophorectomy to reduce the risk of breast cancer and ovarian cancer respectively are possible options. Although oophorectomies are usually performed to reduce ovarian cancer risk, having an oophorectomy before meno-
BRCA1 and BRCA2 genes pause also reduces the risk of breast cancer. Removal of ovaries is associated with a decrease in the production of the hormones estrogen and progesterone, which play a major role in breast cancer progression. For a premenopausal woman with a BRCA mutation, oophorectomy reduces the risk of breast cancer by about 50 percent, and it reduces the risk of ovarian cancer by 80 percent, irrespective of the menopausal status. However, it is important to note that prophylactic surgery reduces but does not eliminate the risk of cancer and carries additional risks related to surgery. Behaviors that can reduce breast cancer risk include regular exercising, decreased alcohol consumption, early childbirth, and breast-feeding for more than twelve months—although effects of these on BRCA mutation carriers are yet unknown. Even though tamoxifen is known to reduce the risk of invasive breast cancer by 49 percent in patients with an increased risk of developing the disease, limited data are available regarding the use of tamoxifen for chemoprevention in women with BRCA1 and BRCA2 alterations. Existing data suggest that use of tamoxifen reduces the risk of breast cancer in BRCA carriers and is recommended for chemoprevention. Banalata Sen, Ph.D. u
For Further Information Bishop, D. T. “BRCA1 and BRCA2 and Breast Cancer Incidence: A Review.” Annals of Oncology 10, suppl. 6 (1999): S113-S119. Venkitaraman, A. R. “Cancer Susceptibility and the Functions of BRCA1 and BRCA2: AReview.” Cell 108, no. 2 (2002): 171-182.
u
Other Resources
Genetics Home Reference http://ghr.nlm.nih.gov HUGO Gene Nomenclature Committee Symbol Report: BRCA1 http://www.genenames.org/data/ hgnc_data.php?hgnc_id=1100 National Cancer Institute Genetics of Breast and Ovarian Cancer http://www.cancer.gov/cancertopics/pdq/genetics/breastand-ovarian National Human Genome Research Institute http://www.genome.gov See also Ashkenazi Jews and cancer; Breast cancer in men; Breast cancer in pregnant women; Breast cancers; 179
Breakthrough pain Carcinomatosis; Clinical breast exam (CBE); Ductal carcinoma in situ (DCIS); Estrogen-receptor-sensitive breast cancer; Family history and risk assessment; Genetic testing; Genetics of cancer; Hereditary cancer syndromes; Hormonal therapies; Invasive ductal carcinomas; Invasive lobular carcinomas; Lobular carcinoma in situ (LCIS); Medullary carcinoma of the breast; Molecular oncology; Mutagenesis and cancer; Oophorectomy; Ovarian cancers; Ovarian epithelial cancer; Pancreatic cancers; Risks for cancer; Salpingectomy and salpingo-oophorectomy; Tumor markers.
u Breakthrough pain Category: Diseases, symptoms, and conditions Also known as: Episodic or incident pain Related conditions: Breakthrough pain may be related to tumor progression or nerve compression as a result of cancer. It may also be a result of a treatment, including surgery, or a variety of painful disorders, such as arthritis. Definition: Breakthrough pain is a transient and intermittent flare of severe pain that “breaks through” analgesic medications. Risk factors: Anyone undergoing treatment for trauma, illness, and other painful conditions is at risk for breakthrough pain. Cancer patients—particularly those with advanced disease—are at high risk for breakthrough pain. Etiology and the disease process: Breakthrough pain generally is the result of whatever is causing a patient’s baseline persistent pain. Incidence: Approximately one-half to two-thirds of cancer patients and up to 86 percent of people taking painreducing medication for chronic pain experience breakthrough pain. The frequency of breakthrough pain varies among individuals; most patients with cancer-related pain have several episodes daily. Often, breakthrough pain flares up just before the patient is to take the next dose of pain medication; this is termed end-of-dose failure. Symptoms: The severity, duration, and cause of breakthrough cancer pain vary among patients. Typically, breakthrough pain happens fast. The average duration is approximately thirty minutes, but it may last from seconds to hours. Breakthrough pain is often unpredictable; it may occur spontaneously or it may be triggered by an activity, such as coughing or moving. It may manifest as an intensified or all-over dull sensation, or it may be a localized sharp pain. 180
Salem Health: Cancer Screening and diagnosis: There is no independently validated measurement available for the evaluation of breakthrough pain. Treatment and therapy: Breakthrough pain medications are generally short-acting and work rapidly to control sudden flares of pain. Breakthrough pain medications may be administered in several ways: orally, by injection, intravenously, under the tongue (sublingually), rectally, or transmucosally. Traditionally, opioid derivatives, such as morphine, administered intravenously, have been one of the fastest ways to alleviate breakthrough pain. A patientcontrolled analgesia device (PCA) allows for convenient intravenous administration of pain medication. One drug that specifically treats breakthrough pain is oral transmucosal fentanyl citrate. Fentanyl citrate dissolves rapidly (within five to ten minutes) via the mucous membranes. Cognitive techniques (including relaxation training, hypnosis, imagery, and distraction) and touch and music therapy may also help relieve breakthrough pain. Prognosis, prevention, and outcomes: Breakthrough pain medications are often called rescue medicines and are taken only at the time of an episode. It is important to take rescue medications at the earliest signs of breakthrough pain, as it is harder to control pain when it is allowed to build up. Anita Nagypál, Ph.D. See also Antinausea medications; Brief Pain Inventory (BPI); Pain management medications.
u Breast cancer in children and
adolescents Category: Diseases, symptoms, and conditions Also known as: Phyllodes tumors Related conditions: Adenocarcinoma Definition: Breast cancer is a malignant tumor that originates from breast cells. Most breast masses in children and adolescents are benign rather than cancerous in nature. One study noted fewer than fifty documented cases of breast cancer in girls between the ages of three and nineteen. Of these cases, juvenile secretory carcinoma was the most common and responsible for more than 80 percent of cases. The second most common form of breast cancer was intraductal carcinoma. Breast tumors called phyllodes tumors, although usually seen in women around forty-five years old, may occur
Salem Health: Cancer
Breast cancer in children and adolescents
Average Incidence of Breast Cancer, 1975-2000 Age Group 15-19 20-24 25-29
Incidence (per million people) 1.3 12.1 81.1
Source: Data from A. Bleyer, M. O’Leary, R. Barr, and L. A. G. Ries, eds., Cancer Epidemiology in Older Adolescents and Young Adults Fifteen to Twenty-Nine Years of Age, Including SEER Incidence and Survival: 1975-2000, NIH Pub. No. 06-5767 (Bethesda, Md.: National Cancer Institute, 2006)
in adolescents and have been reported in girls as young as ten years. These tumors may be benign, intermediate, or malignant. Another form of breast cancer in adolescents is primary breast carcinoma, which has been reported in girls between the ages of three and nineteen. However, in adolescents, most malignant breast masses are metastases from other cancers, such as Hodgkin disease, nonHodgkin lymphoma, primary hepatocellular carcinoma, neuroblastoma, and rhabdomyosarcoma. Risk factors: Risk factors for breast cancer in adolescents include having received chest-wall radiation and having a family history of breast cancer. If a child or adolescent receives radiation therapy to treat cancer of the chest area, the person’s risk for developing breast cancer later in life is significantly higher. The younger radiation was initiated, the higher the risk. This is especially the case when radiation is given to girls whose breasts are developing. Etiology and the disease process: Breast masses in children before and during puberty usually are breast buds. The development of breast buds in children is usually the first sign of puberty. The development of breast buds in children who are too young for puberty may indicate premature thelarche, or precocious puberty. Biopsy is warranted for cystic lesions that do not resolve with aspiration and for suspicious solid lesions. Some cancers start in glandular tissue that basically produces and secretes a substance. The ducts and lobules of the breast are glandular tissue, and the cancers starting in these areas are sometimes called adenocarcinomas. Incidence: Breast cancer in children and adolescents is rare. Generally, the lifetime probability of developing breast cancer is 1 in 6 overall, and 1 in 8 for invasive breast cancer. Globally, and in terms of all ages, breast cancer in-
cidence rates are highest in North America and northern Europe, and lowest in Asia and Africa. Symptoms: The most common finding with breast cancer in adolescents is a hard irregular mass and usually one that does not cause symptoms. As the cancer grows, symptoms may include a change of shape, size, and feel of the breast. Another symptom is bloody, yellow, or green, puslike drainage from the nipple. Advanced symptoms include bone or breast pain, swelling of the arm on the same side of the body as the breast with cancer, and weight loss. If metastasis occurs, other symptoms can include difficulty breathing, skin rash that is generalized, limb swelling, and back pain. Screening and diagnosis: Because a mass may not produce symptoms in the initial stages, all adolescents, especially girls with a family history of breast cancer or other malignancies, should have their breasts clinically examined regularly and should conduct monthly self-examination. Ultrasonography is the preferred imaging modality for breast masses in adolescents because of the increased density of the adolescent breast. Also the large amount of fibroglandular tissue makes mammography difficult to interpret. The accuracy of ultrasonography in differentiating solid from cystic lesions is 96 to 100 percent. Research suggests that an evaluation is warranted if no breast development occurs by the age of thirteen. The stage of breast cancer is based on tumor size; involvement of the skin, chest wall, or local lymph nodes; and whether the cancer has spread to other organs (metastasis). Stage I and Stage II are referred to as early stage or localized breast cancer. In Stage I the tumor size is less than 2 centimeters (cm) with no lymph node involvement. Stage II can exhibit lymph node involvement, but the nodes are small. The primary tumor size is larger than 2 cm but not larger than 5 cm. A tumor that is larger than 5 cm must be node-negative to be considered early stage. Stage III breast cancers are referred to as locally advanced breast cancer. In this stage, the tumors are large and greater than 5 cm across. There can be extensive axillary nodal involvement or nodal involvement of the soft tissues above or below the collarbone. A tumor is also designated Stage III if it extends to underlying muscles of the chest wall or the overlying skin. In Stage III, the breast may be undergoing the inflammatory process and appear red and swollen. Stage IV breast cancer, also known as metastatic breast cancer, consists of tumors that have spread to areas such as the brain, bones, skin, and even other organs. There may be any number of affected lymph nodes, and the primary tumor may be any size. 181
Breast cancer in men Treatment and therapy: The subsequent management of the adolescent with a breast mass depends on the type of mass. Surgical resection (excisional biopsy) may be necessary for cystic lesions that do not resolve with aspiration, when aspiration is not productive or not feasible, and for suspicious solid lesions. Although uncommon, more advanced forms of breast cancer have the potential to be treated similarly to the condition found in adults. Prognosis, prevention, and outcomes: The five-year survival rate refers to the number of patients who live at least five years after their cancer is found. According to the American Cancer Society (ACS), the five-year survival rates for persons with breast cancer that is appropriately treated are 100 percent for Stage I, 81 to 92 percent for Stage II, 54 to 67 percent for Stage III, and 20 percent for Stage IV. Jeffrey P. Larson, P.T., B.S., A.T.C. u For Further Information American Joint Committee on Cancer. AJCC Cancer Staging Manual. 5th ed. Philadelphia: Lippincott-Raven, 1997. Barry, Joanne. “Reaching Out to Educate.” Canadian Nurse 103, no. 8 (October, 2007): 34-35. Mandrell, B. N. “Secondary Breast Cancer in a Woman Treated for Hodgkin Lymphoma as a Child.” Oncology 21 (October, 2007): 27-29. Twombly, R. “Childhood Cancer Survivor Study Doubles to Examine Late Effects of New Treatments.” Journal of the National Cancer Institute 99, no. 21 (November 7, 2007): 1574-1576. u
Other Resources
National Cancer Institute Breast Cancer http://www.cancer.gov/cancertopics/types/breast UpToDate Overview of Breast Masses in Children and Adolescents http://patients.uptodate.com/topic.asp?file=adol_med/ 11491 See also Adenocarcinomas; Breast cancers; Breast selfexamination (BSE); Calcifications of the breast; Childhood cancers; Clinical breast exam (CBE); Cutaneous breast cancer; Phyllodes tumors; Young adult cancers.
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u Breast cancer in men Category: Diseases, symptoms, and conditions Also known as: Infiltrating or invasive ductal carcinoma, ductal carcinoma in situ, inflammatory breast cancer, Paget disease of the nipple Related conditions: Gynecomastia, fibroadenomas, papillomas Definition: Breast cancer occurs in men when malignant (cancerous) cells develop in the breast tissue of the male breast. The cancer can then spread into other tissues. Risk factors: Advanced age is a risk factor for men, just as it is for women. The median age of diagnosis for male breast cancer is sixty-eight. Men who have a close female relative with breast cancer are at risk and may be evaluated for the presence of a mutation in the BRCA2 gene. This mutation is responsible for 15 percent of breast cancers in men, and men with the mutation have a 6 percent lifetime risk for breast cancer. Other risks include radiation exposure (which may be occupational but is more often a result of treatment of other cancers) and liver disease, such as cirrhosis, which causes an increase in estrogen and a decrease in androgen hormones. Obesity and cigarette smoking may also play a role as risk factors. Many male breast cancers are estrogen-receptor-positive, which means that estrogen will increase the risk of development or accelerated growth of the cancer. Estrogen is given to some men to slow the growth of prostate cancer and is used by some men who are undergoing gender transformation. One risk specific to men for the development of breast cancer is Klinefelter syndrome, a genetic mutation involving at least one extra X chromosome, a condition that affects 1 in 850 men. These men have higher levels of estrogen and lower levels of androgens and therefore are at particular increased risk. Etiology and the disease process: There are a number of risk factors for male breast cancer, but none of the known causes can be eliminated. Most male breast cancers are invasive, infiltrating ductal carcinomas and are far more treatable in early localized stages. Therefore, efforts should be concentrated on early identification and treatment by increasing awareness of risk factors, heightening surveillance of those with nonmodifiable risks, and attempting to change those risks that can be modified. Incidence: Both men and women have breast tissue, and breast cancer occurs in men but is much rarer in men than in women, comprising only 1 percent of all cancers in men.
Salem Health: Cancer
Breast cancer in men
Stage at Diagnosis and Five-Year Relative Survival Rates for Invasive Male Breast Cancer, 1988-2001 Stage
Survival Rate (%) a
Localized Regionalb Distantc Unstaged
96.9 78.1 23.0 64.2
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007) a Cancer still confined to primary site b Cancer has spread to regional lymph nodes or directly beyond the primary site c Cancer has metastasized
The American Cancer Society states that in the United States in 2005 more than 1,500 cases of male breast cancer were diagnosed and almost 500 deaths occurred. Symptoms: Symptoms of breast cancer in men include breast lumps as well as nipple and skin changes. The cancer is most often diagnosed when a man goes to his doctor after finding a mass below the nipple in one breast. Nipple changes can include redness or patchy scaling of the skin, nipple retraction (pulling inward), and nipple discharge. Skin changes may include puckering and dimpling as well as redness and scaling; however, chest hair may obscure subtle skin changes, and men are not accustomed to examining their breasts in a way that would help them find early lumps. Even when men find early symptoms, they may be misinformed about male breast cancer or embarrassed and delay seeking medical care. Screening and diagnosis: Providing information that male breast cancer does occur and describing early symptoms may be the best screening tools to offer. Screening for male breast cancer is not common among primary care providers, but if a lump is detected or brought to the provider’s attention by the patient, the first step is a mammography done with spot compression or magnification and possibly ultrasound, followed by a biopsy. A biopsy is the only definitive way to diagnose breast cancer. Staging assesses the size, location, lymph node involvement, and degree of metastasis of the cancer, ranging from Stage 0, which is the earliest stage, to Stage IV, which is the most advanced.
Treatment and therapy: Treatment usually involves surgery to remove the breast tissue and often lymph nodes and some of the chest muscles as well. Sentinel lymph node biopsy can be used to attempt to avoid more radical removal of lymph nodes. Radiation therapy and chemotherapy may be employed. If the cancer is determined to be estrogen-receptorpositive, the antiestrogen drug tamoxifen can be used to slow the growth and reproduction of cells that require estrogen. Another drug used in treatment is megace, an antiandrogen drug that blocks the effects of androgen in the breast. Prognosis, prevention, and outcomes: Prognosis is similar for male and female breast cancer when cancers of the same stage are compared; however, male breast cancer often is not discovered as early as is female breast cancer. Early detection is especially important because men have less breast tissue than women, and therefore their cancers can more easily reach and invade the chest muscles. Age at diagnosis and general health influence outcomes. With advanced medical care, five-year survival rates now vary from close to 100 percent for cancers caught in Stage 0 to 25 percent for cancers that have progressed to Stage IV. Prevention efforts center on screening for risk factors that may heighten surveillance for disease and on patient education about early self-detection of changes in the male breast. Outcome also depends on prevention of recurrence, and increased screening as well as adjuvant chemotherapy may improve long term outcomes. Clair Kaplan, R.N., M.S.N., A.P.R.N. (WHNP), M.H.S., M.T. (ASCP) u
For Further Information Berek, J. S., and N. F. Hacker. Practical Gynecologic Oncology. Philadelphia: Lippincott Williams & Wilkins, 2005. DeVita, V. T., S. Hellman, and S. A. Rosenberg. Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2005. Estala, E. M. “Proposed Screening Recommendations for Male Breast Cancer.” The Nurse Practitioner 31, no. 2 (2006): 62-63.
u
Other Resources
American Cancer Society http://www.cancer.org National Cancer Institute Male Breast Cancer Treatment http://www.cancer.gov/cancertopics/pdq/treatment/ malebreast/ 183
Breast cancer in pregnant women See also Breast cancers; Breast self-examination (BSE); Clinical breast exam (CBE); Cutaneous breast cancer; Ductal carcinoma in situ (DCIS); Invasive ductal carcinomas.
u Breast cancer in pregnant
women Category: Diseases, symptoms, and conditions Also known as: Gestational breast cancer, lactational breast cancer, postpartum breast cancer
Salem Health: Cancer forty-four; of these women, only 10 percent will be pregnant at the time of diagnosis. Based on several analyses, the actual incidence of breast cancer during pregnancy has been estimated to fall between 1/3000 and 1/10,000 of all pregnant women. Breast cancer during pregnancy is second only to cervical cancer as the most common malignancy occurring during pregnancy. Of concern is that the incidence will most likely increase as women delay childbearing. In fact, women who have their first term pregnancy after the age of thirty have a twofold to threefold increased risk of breast cancer compared with women who have their first term pregnancy before the age of twenty.
Related conditions: Lactating adenoma, fibroadenoma, cystic disease, lobular hyperplasia, milk retention cyst (galactocele), abscess, lipoma, hamartoma, leukemia, lymphoma, sarcoma, neuroma, tuberculosis
Symptoms: Most often, women with breast cancer during pregnancy complain of a painless mass in the breast or a nipple discharge; a bloody nipple discharge is particularly concerning.
Definition: Gestational breast cancer is defined as breast cancer that occurs during pregnancy or up to one year thereafter.
Screening and diagnosis: All pregnant women should undergo a complete physical examination at the time they register for prenatal care, including a thorough breast examination. All new breast masses or nipple discharges should be evaluated promptly and not delayed until the pregnancy has been completed. The mean age at diagnosis of breast cancer during pregnancy is thirty-two to thirtyfour years. In most cases, the disease is advanced at the time of diagnosis. In general, the number of positive lymph nodes is greater, the tumors are larger, the steroid hormone status is more often negative, the number of cells synthesizing deoxyribonucleic acid (DNA) is greater, the number of mutations involving BRCA1 and BRCA2 is greater, and the tumor suppressor p53 is more often downregulated. Although the usefulness of mammography has been questioned in women less than thirty-five years of age because of higher breast density, mammography during pregnancy (in which breast density is increased) has been shown to be 90 percent sensitive in detecting malignancies. The irradiation exposure to the fetus is negligible and should not be a deterrent. Ultrasound, which carries no fetal irradiation risk, has been shown to be 100 percent sensitive in detecting a malignancy when the breast mass is palpable. The diagnosis rests, however, with pathologic confirmation, which can be obtained with a fine needle biopsy, a core needle biopsy, or an excisional biopsy. Staging is performed to determine if metastasis has occurred.
Risk factors: It is generally believed that breast cancer is years in the making; thus, pregnancy itself can be an aggravating risk factor for breast cancer because the physiologic changes that occur in the breast during pregnancy may mask an occult or nonpalpable mass. Further, there is often denial on the part of the physician or patient that breast cancer can occur during pregnancy, further aggravating the underlying risk. Moreover, the elevated levels of estrogen (hundredfold increase) and progesterone (thousandfold increase) during pregnancy may also stimulate cancer growth. Other traditional risk factors for breast cancer include a history of benign breast disease, menarche (onset of menstrual activity) before the age of twelve, drinking three or more alcohol-containing drinks daily, increased bone density, a sedentary lifestyle, nulliparity (no previous live births), first birth after the age of thirty, a firstdegree relative (mother or sister) with breast cancer, upper socioeconomic status, a history of endometrial or ovarian cancer, chest irradiation, increased breast density, a history of breast cancer, dietary fat intake (especially saturated fat), and obesity. Etiology and the disease process: Like all cancers, breast cancer arises when an oncogene (cancer-causing gene) is activated or the tumor-suppressor gene controlling the oncogene is silenced. Regardless of the precipitating risk factor, breast cancer appears to reflect the cumulative exposure to estrogen and progesterone. Incidence: Of all women diagnosed with breast cancer, only 12.7 percent will be between the ages of twenty and 184
Treatment and therapy: The management of breast cancer during pregnancy has the same goal as in patients who are not pregnant. Termination of pregnancy is not indicated. Surgery is generally delayed until the second trimester, and for nonmetastatic diseases, a modified radical
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Breast cancers
mastectomy is considered the standard conservative procedure. Similarly, even though all chemotherapeutic agents are category D (teratogenic), they have accumulated a favorable safety profile when used in the second and third trimesters. Fetal malformations range from 19 percent in the first trimester to 1.3 percent in the second and third trimesters based on nearly 100 pregnant women treated with 5-fluorouracil, doxorubicin, and cyclophosphamide (a standard chemotherapeutic regimen).
u Breast cancers
Prognosis, prevention, and outcomes: Women who are diagnosed with breast cancer during pregnancy are often diagnosed at a later stage, because breast changes during pregnancy, including increased breast size and changes in breast texture, make small, early-stage tumors harder to detect and diagnose. Roughly half of new cases are found in a late stage (III or IV), as compared with just over a quarter of cases that are diagnosed at Stage I and another quarter or so at Stage II. The five-year survival rate for women with negative lymph nodes is 82 percent; however, lymph node metastasis occurs in 65 percent of women with breast cancer during pregnancy. The overall survival for breast cancer during pregnancy is 70 percent. D. Scott Cunningham, M.D., Ph.D.
Definition: Breast cancer is the occurrence of a malignant tumor in the breast tissue. The most commonly diagnosed breast tumors are ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS). When discovered early, these tumors are easily treated. However, if gone undetected, the tumors can eventually metastasize, meaning that some of the cancer cells detach from the tumor and spread throughout the body, acting as “seeds” to trigger the further development of malignancy in distant body parts. Once metastatic breast cancer (MBC) forms, the cancer becomes much more difficult to treat.
u For Further Information Barnes, D. M., and L. A. Newman. “Pregnancy-Associated Breast Cancer: A Literature Review.” Surgical Clinics of North America 87 (2007): 417-430. Leslie, K. K., and C. A. Lange. “Breast Cancer and Pregnancy.” Obstetrics & Gynecology Clinics of North America 32 (2005): 547-558. u
Other Resources
National Breast Cancer Foundation http://www.nationalbreastcancer.org/about-breastcancer/ National Cancer Institute http://www.cancer.gov Susan G. Komen for the Cure http://cms.komen.org/komen/AboutBreastCancer/ index.htm See also Adenocarcinomas; Breast cancers; Breast selfexamination (BSE); Calcifications of the breast; Childbirth and cancer; Clinical breast exam (CBE); Cutaneous breast cancer; Duct ectasia; Ductal carcinoma in situ (DCIS); Ductal lavage; Ductogram; Estrogen-receptorsensitive breast cancer; Pregnancy and cancer.
Category: Diseases, symptoms, and conditions Also known as: Metastatic breast cancer (MBC), ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS) Related conditions: Intraductal papillomas, noncancerous adenomas (growths) of the breast tissue, cysts
Risk factors: Some risk factors have been established as very important for determining patients who would benefit from more careful preventative care and observation. However, the presence of one or more risk factors does not necessarily mean that the patient will actually develop a breast tumor. Conversely, up to 70 percent of women who develop breast cancer did not have any known risk factors before diagnosis. Women who previously had a breast tumor in one breast have a significantly increased risk of developing cancer in the other breast. The cancer in the second breast is considered unrelated and not a recurrence of the cancer in the first breast. Several factors are considered to moderately increase the risk of breast cancer in some women. As women age, they develop an increasing risk of developing breast cancer. For example, women between the ages of forty and forty-nine have a 1 in 68 risk of developing breast cancer; this risk nearly doubles to 1 in 37 for women between the ages of fifty and fifty-nine. Nearly half of women diagnosed with breast cancer are over sixty-five and postmenopausal. Mutations in two key genes, BRCA1 and BRCA2, have also been associated with an increased risk of developing breast cancer. These genes are considered tumor suppressors, and mutations can lead to their dysfunction. These mutations seem to be inherited, and having a direct family relative with breast cancer also increases the risk of developing breast cancer. This is most true for first-degree relatives, such as a mother, sister, or daughter. One first-degree relative with breast cancer can nearly double the risk for an individual to develop breast 185
Breast cancers cancer; two first-degree relatives with breast cancer causes the individual to be up to five times as likely to develop breast cancer. Other factors have been shown to only slightly increase the risk of developing breast cancer. These include obesity and increased alcohol intake. Further, women who began to menstruate early (prior to age twelve), who enter into menopause late (after age fifty-five), or who never have children have a small increase in the chance of developing breast cancer. This is thought to be due to the increased exposure these women have to estrogen, a hormone that can increase breast cancer development. Etiology and the disease process: One of the most commonly accepted models of breast cancer formation stems from the development of genetic aberrations in breast cells. Activated mutations in oncogenes, genes responsible for the growth and proliferation of cells, and inhibitory mutations in tumor-suppressor genes that negatively regulate cell growth play an instrumental role in cellular trans-
Salem Health: Cancer formation. Cell transformation is the process by which a normal cell changes into a tumorigenic cell, capable of growing into a malignant mass. A breast tumor begins when one or more tumorigenic cells form within the epithelial layer, the internal tissue lining of the breast. As the tumor grows, it spreads past the epithelium, invading into the deeper tissues of the breast. If left untreated, the breast tumor will eventually metastasize, as the tumor cells break away from the primary tumor and are dispersed throughout the body via the circulatory system. Breast cancers are primarily differentiated as hormonereceptor-positive or -negative. These receptors are the estrogen receptor (ER), progesterone receptor (PR), or both. The distinctions among these tumors are critical, as they are a major determinant in choosing the proper therapy. Both hormone receptors have a similar action: After either hormone binds to its respective receptor inside the cell, it subsequently transports into the nucleus, where it plays a major role in regulating gene expression. Incidence: Breast cancer is one of the most frequently diagnosed cancers in women in the United States, with an estimated more than 175,000 new cases per year. Breast cancer development seems to be affected by race, with a higher incidence occurring in white and African American women compared with Hispanic, American Indian, and Asian American women. Breast cancer is second only to lung cancer in inducing cancer-related deaths in women, but it is the primary cause of cancer-related mortality in younger women, ages twenty to fifty-nine. Since the early 1990’s, the incidence of breast cancer-related deaths has steadily decreased, a reduction most dramatically seen in younger white and African American women. The cause of this reduction is attributed to both improved anticancer therapy and earlier diagnostic abilities. The risk of a woman developing breast cancer at some point in her lifetime is nearly 1 in 8, or 13 percent. Although breast cancer most often occurs in women, it can rarely occur in men. Symptoms: Early breast cancer is usually free of symptoms. The first sign of breast cancer is most often a persistent lump in the breast. As the tumor develops, the individual may begin to experience other symptoms, including swelling of the armpit or breast and thickening of the breast tissue. Patients may also notice slight pain or tenderness in the breast. Changes in how the nipple looks is also frequently observed with breast cancer.
A mammogram showing a breast tumor. (©Visuals Unlimited/ Corbis)
186
Screening and diagnosis: Aclinical breast exam is a common method to detect lumps or abnormal changes in the breast tissue. If a lump is detected, the clinician will assess the characteristics of the lump. Lumps that are soft,
Salem Health: Cancer smooth, and round and move about easily are more likely to be benign, compared to hard, nonsymmetrical lumps that are tightly attached to the breast tissue, which are more likely to be cancerous. It is also recommended that women perform monthly breast self-examinations at home to detect changes between checkups. Subtle changes that may not register as a lump by touch can often be detected by mammograms, X-ray images taken of the breast. Further, many clinicians use mammograms to provide a more detailed look at lumps identified during an examination. Ultrasound and magnetic resonance imaging (MRI) can be used to directly image breast abnormalities. If a clinician feels that a certain breast abnormality warrants further investigation, a biopsy is performed to remove tissue that a pathologist can use to determine if any cancer is present. At the time of first diagnosis, most patients are diagnosed either with early, localized breast cancer or regional breast cancer. Only a small minority of patients receive a primary diagnosis of metastatic breast cancer (MBC). Recurrent breast cancer is a malignancy that has returned after previously being treated to the point of not being detected. Recurrence may occur locally in or near the breast or in distant parts of the body, such as the bone, liver, or lungs. Once a diagnosis is made, the stage of the breast cancer is determined. This is necessary for the physician to determine the extent of the disease and to prescribe the appropriate treatment. Stage 0 is described as in situ carcinoma. In situ carcinoma is noninvasive, meaning the cancer cells have not begun to spread beyond the epithelium, or tissue surface. The most common breast cancer of this stage is ductal carcinoma in situ (DCIS), in which cancerous cells develop within the milk ducts. Stage I is the earliest form of invasive breast cancer. At this point, the tumor is smaller than 2 centimeters (cm) in diameter and is confined to the breast. In Stage II, the tumor is either between 2 and 5 cm and has spread to the lymph nodes under the arm or is larger than 5 cm but has not spread outside the breast. Stage III is characterized by larger tumors that may have spread to lymph nodes and areas beyond the underarm, such as behind the breastbone or near the collarbone. Stage IV is the most advanced stage. At this point, the cancer is classified as distant metastatic cancer. Treatment and therapy: The main goals of breast cancer therapy are to eradicate the tumor and prevent its recurrence. Treatments can be categorized as either local or systemic, and the use of either or both is determined by the extent and stage of disease. Local therapies include surgery and radiation therapy. Surgery can be either minimal, such as a lumpectomy in which only the lump is removed, or
Breast cancers
Stage at Diagnosis and Five-Year Relative Survival Rates for Women with Breast Cancer, 1996-2004 Women Diagnosed (%)
Stage a
Localized Regionalb Distantc Unstaged
61 31 6 2
Survival Rate (%) 98.0 83.5 26.7 56.9
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 a Cancer still confined to primary site b Cancer has spread to regional lymph nodes or directly beyond the primary site c Cancer has metastasized
more drastic, such as a mastectomy in which the majority of the breast is removed. If the breast cancer has spread to local lymph nodes, these also may be removed at the time of surgery. Surgery is often used in conjunction with other therapies, including radiation therapy and systemic drug therapy. Once the breast cancer has metastasized and become MBC, surgery is not a viable therapeutic option. For MBC, systemic therapy is generally the standard treatment and consists of three main categories: chemotherapy, endocrine therapy, and biological therapy. The most effective chemotherapeutic agents for breast cancer are taxanes and anthracyclines, although other drug classes can be used. Despite the benefit these drugs can offer in lengthening patient survival, the accompanying toxic side effects can dramatically decrease the patient’s quality of life. Endocrine therapy is the standard of care for hormone-receptor-positive breast cancer. The most common type of endocrine therapy is the selective estrogen receptor modulator (SERM) tamoxifen, which can reduce the proliferative effect that estrogens have in the breast tumor cells. Although tamoxifen is generally tolerated better than chemotherapies, there is a high risk for developing resistance, after which the drug loses its benefit. The newest addition to the breast cancer therapy arsenal is targeted biological therapy. The prototypical example of this in breast cancer is trastuzumab, an antibody that recognizes and inhibits the human epidermal growth factor receptor (HER2) present on the surface of the breast cancer cell. HER2 is an effective breast cancer target because it is often overactivated in breast cancer, increasing the proliferative signaling downstream of its activation. 187
Breast implants Prognosis, prevention, and outcomes: The improvement of screening and diagnostic techniques has been instrumental in increasing the discovery of breast cancer early in development, when it is most easily treated. Additionally, the development of novel drugs and therapies has caused a significant increase in extending survival of breast cancer patients. Clinicians measure disease outcome by measuring survival rates; a disease-free survival of at least five years is generally considered to be a cure. Currently, the five-year survival rate for patients diagnosed with local breast cancer that has not spread beyond the breast is 98 percent. This survival rate is lowered to 83.5 percent in patients with regional metastasis. Patients with Stage IV metastatic breast cancer have a five-year survival rate of only 26.7 percent. Much effort has gone into determining methods of preventing breast cancer. Because many breast tumors depend on estrogen for growth and survival, decreasing unnecessary estrogen exposure may help prevent breast cancer. Some women with an especially high risk of breast cancer may elect to have an oophorectomy, surgery to remove both ovaries, the primary source of estrogen in premenopausal women. Additionally, regular exercise may reduce the amount of estrogen naturally produced by the body, decreasing the amount of estrogen to which the breast is exposed. An extreme preventative measure in women with a high risk for developing breast cancer is prophylactic mastectomy, a surgical procedure to remove the breast before any signs of cancer. Lisa M. Cockrell, B.S. u For Further Information Bowcock, Anne M, ed. Breast Cancer: Molecular Genetics, Pathogenesis, and Therapeutics. Totowa, N.J.: Humana Press, 1999. Craig, Jordan V., and Barrington J. A. Furr, eds. Hormone Therapy in Breast and Prostate Cancer. Totowa, N.J.: Humana Press, 1999. Grobstein, Ruth H. The Breast Cancer Book: What You Need to Know to Make Informed Decisions. New Haven, Conn.: Yale University Press, 2005. Kufe, Donald W., et al., eds. Holland Frei Cancer Medicine 7. 7th ed. Hamilton, Ont.: B. C. Decker, 2006. Manni, Andrea, ed. Endocrinology of Breast Cancer. Totowa, N.J.: Humana Press, 1999. u
Other Resources
American Cancer Society http://www.cancer.org National Breast Cancer Foundation http://www.nationalbreastcancer.org 188
Salem Health: Cancer National Cancer Institute Breast Cancer http://www.cancer.gov/cancertopics/types/breast Susan G. Komen for the Cure http://www.komen.org See also Accelerated partial breast irradiation (APBI); Adenocarcinomas; Aging and cancer; Antiestrogens; Antiperspirants and breast cancer; Birth control pills and cancer; Breast cancer in children and adolescents; Breast cancer in men; Breast cancer in pregnant women; Breast implants; Breast reconstruction; Breast ultrasound; Calcifications of the breast; Childbirth and cancer; Clinical breast exam (CBE); Cutaneous breast cancer; Diethylstilbestrol (DES); Duct ectasia; Ductal carcinoma in situ (DCIS); Ductal lavage; Ductogram; Estrogen-receptorsensitive breast cancer; Fertility drugs and cancer; Fibroadenomas; Fibrocystic breast changes; Genetic counseling; Genetic testing; Hormone receptor tests; Hormone replacement therapy (HRT); Invasive ductal carcinomas; Invasive lobular carcinomas; Lobular carcinoma in situ (LCIS); Lumpectomy; Lumps; Lymphadenectomy; Lymphangiography; Lymphangiosarcomas; Lymphedema; Mammography; Mastectomy; Medullary carcinoma of the breast; Metastasis; Microcalcifications; Needle localization; Obesity-associated cancers; Phyllodes tumors; Pregnancy and cancer; Premalignancies; Progesterone receptor assay; Tubular carcinomas; Wire localization.
u Breast implants Category: Procedures Also known as: Autologous breast implants, saline breast implants, saline-filled breast implants, silicone breast implants, silicone-filled breast implants Definition: Breast implants are used to reconstruct the natural appearance of one or both breasts following mastectomy for breast cancer. Breast implants may be composed of the patient’s own tissue taken from elsewhere on the body (autologous breast implants) or made of artificial substances (saline or silicone breast implants). Cancers treated: Breast cancer Why performed: Breast reconstruction is a choice for women following mastectomy. Mastectomy involves surgically removing one or both breasts for the treatment of breast cancer. Breast implants are used to replace breasts that have been removed, to create a symmetrical appear-
Salem Health: Cancer
Breast implants
Reconstructed breast Chest wall after mastectomy
Implant
Reconstruction of a breast following a total mastectomy. (©Visuals Unlimited/Corbis)
ance if only one breast was removed, or to replace the one breast that was removed and enhance the appearance of the remaining breast to improve symmetry. Breast implants are an option to wearing breast prosthetics (removable breast forms). Patient preparation: Breast implants come in a variety of shapes, sizes, and compositions. The plastic surgeon guides the patient in the selection process. Tissue expanders may or may not be used to stretch the skin in preparation for breast implant placement. In some cases, the tissue expander may be filled with saline and remain in the body, serving as the breast implant. There are two basic types of artificial implants, saline breast implants and silicone breast implants. Saline breast implants have a silicone outer shell and are filled with saline, a saltwater solution. Saline implants may be prefilled by the manufacturer or filled at the time of surgery and adjusted after surgery. Silicone breast implants have a silicone outer shell and are filled with silicone, a natural substance. Silicone breast implants may be prefilled with silicone by the manufacturer and nonadjustable, prefilled with silicone and allow
for saline insertion at the time of surgery, or prefilled with silicone and allow for saline insertion at the time of surgery and postsurgical adjustments. Saline implants were approved for use in the United States by the Food and Drug Administration (FDA) in 2000. Silicone implants were approved by the FDA in 2006. Both types of implants are not meant to last a lifetime, may need to be replaced, and have a risk of rupture. Saline implants are advantageous in that ruptures are readily identified because the breast size decreases and the saline solution is absorbed by the body. The size of saline implants can be adjusted easily. Some people believe, however, that saline implants do not look or feel as natural as silicone implants. Silicone implants have a texture similar to natural breast tissue. While silicone breast implants may look and feel more natural than saline implants, ruptures may not be as easily noticed with silicone breast implants. Following a rupture, the silicone remains near the implant and is not absorbed by the body. Autologous implants are made of tissue or a tissue flap that is taken from the patient, commonly the abdomen and buttocks. The tissue may contain fat, muscles, blood ves189
Breast reconstruction sels, and nerves. Autologous implants are a more specialized procedure involving microsurgery and take longer to heal, but they do not have the risk of rupture and do not need to be replaced over time. Some people believe that autologous implants produce the most natural results. Steps of the procedure: Breast implants may be inserted at the time of the mastectomy or at a later time in another surgery. Patients receiving radiation therapy following mastectomy may need to delay breast reconstruction. Breast implant procedures do not delay chemotherapy. Breast reconstruction surgery is performed with general anesthesia. Nipple reconstruction may take place following a breast implant procedure. After the procedure: Patients may spend one to six days in the hospital, depending on the procedure. Patients wear bandages and support garments while healing. Activities may be temporarily restricted, but most activities can be resumed in six to eight weeks. Artificial implants typically need to be replaced in time. Breast implants should not affect breastfeeding. Special mammography procedures may be needed, however. Breast implants only rarely obscure the detection of new cancer formation. Risks: The risks of artificial breast implants include rupture, leakage, rippling, infection, and capsular contraction (in which scar tissue surrounding the implants shrinks or hardens). Other risks include the general risks associated with surgery and anesthesia. Results: The optimal result is symmetrical, naturalappearing breasts. Mary Car-Blanchard, O.T.D., B.S.O.T. u
For Further Information Poeppl, N., et al. “Does the Surface Structure of Implants Have an Impact on the Formation of a Capsular Contracture?” Aesthetic Plastic Surgery 31, no. 2 (March/April, 2007): 133-139. “Silicone Gel-Filled Breast Implants Approved.” FDA Consumer 41, no. 1 (January/February, 2007). Stevens, W. G., et al. “A Comparison of Five Hundred Prefilled Textured Saline Breast Implants Versus Five Hundred Standard Textured Saline Breast Implants: Is There a Difference in Deflation Rates?” Plastic and Reconstruction Surgery 117, no. 7 (June, 2006): 21752181. Vázquez, G., and A. Pellón. “Polyurethane-Coated Silicone Gel Breast Implants Used for Eighteen Years.” Aesthetic Plastic Surgery 31, no. 4 (July/August, 2007): 330-336. 190
Salem Health: Cancer u
Other Resources
American Cancer Society http://www.cancer.org American Society of Plastic Surgeons http://www.plasticsurgery.org Breast Implant Safety.org http://www.breastimplantsafety.org See also Breast cancers; Breast reconstruction; Mastectomy; Self-image and body image; Sexuality and cancer.
u Breast reconstruction Category: Procedures Also known as: Breast implants; deep inferior epigastric perforator (DIEP) flap; free flap; gluteal flap; latissimus dorsi flap; pedicle flap; saline breast implants; silicone breast implants; transverse rectus abdominis muscle (TRAM) flap Definition: Breast reconstruction is a complex procedure performed by a plastic surgeon that restores the appearance of a breast after mastectomy to treat breast cancer. Cancers treated: Breast cancer Why performed: Breast reconstruction is performed to reconstruct the size and shape of the breast in a patient who has had a mastectomy. Most women who have had a mastectomy can have breast reconstruction, which may be done either at the time of mastectomy or at a later date. Breast reconstruction may improve the self-esteem and body image of a woman who has had a mastectomy. Patient preparation: A patient facing a mastectomy who is interested in breast reconstruction probably will be advised to consult with a plastic surgeon experienced in breast reconstruction prior to the mastectomy. Ideally, the breast surgeon and the plastic surgeon work together to develop the best surgical and breast reconstruction strategy for each patient, even if the reconstructive surgery will be done later. Two or more operations probably will be needed to achieve a satisfactory result. A patient will be given specific instructions prior to surgery. Since smoking can decrease a patient’s blood circulation, which is critical to the survival of transplanted tissue, a patient who is a smoker will be given instructions and tips to quit smoking prior to reconstruction procedures that involve the use of transplanted tissue. Steps of the procedure: There are two basic types of breast reconstruction, implant procedures and tissue flap
Salem Health: Cancer procedures. A combination of these procedures may also be used. Either type of procedure may be begun either at the same time as the mastectomy (immediate reconstruction) or at a later time (delayed reconstruction). Saline-filled implants are the most common type of implant used and consist of external silicone shells filled with sterile saline. The use of silicone gel-filled implants has decreased because of concerns of possible health risks if silicone leaks from the implant, although recent research has not found any health dangers associated with their use. Sometimes a one-stage procedure is possible, where the implant is placed behind the pectoral muscle in the chest in the first surgery. For most patients, a two-stage procedure is used in which a tissue expander, like a balloon, is implanted beneath the skin and chest muscle. Over a period of several months, the surgeon injects a saline solution at regular intervals to fill the expander and stretch the chest pocket. At the appropriate time, the expander is removed in a second operation and the permanent implant is put into place. Tissue flap procedures involve autologous tissue reconstruction and are the more surgically complex option
Breast reconstruction for breast reconstruction. Tissue from the abdomen or back (more commonly), or buttocks or thighs (less commonly), is used. Two types of methods, pedicle flap and free flap, are in use. In a pedicle flap procedure, some of the blood vessels feeding the tissue to be transferred are cut and some are kept intact. The tissue is tunneled beneath the skin to the chest area, where a new breast mound or pocket for an implant is created. In a free flap procedure, the flap of skin, fat, blood vessels, and muscle tissue is disconnected from its blood supply completely and removed from its original location, and intricate microsurgical techniques are used to reattach the tissue flap to new blood vessels near the chest. This procedure typically takes longer to complete than a pedicle flap procedure. Four main tissue flap procedures are performed: the TRAM (transverse rectus abdominis muscle) flap, the DIEP (deep inferior epigastric perforator) flap, the latissimus dorsi flap, and the gluteal flap. The TRAM flap procedure uses tissue and muscle from the lower abdominal wall, which may be transferred as a free flap or a pedicle flap. This procedure also results in a tightening of the lower abdomen, or a “tummy tuck.” Vari-
A transverse rectus abdominis muscle (TRAM) flap breast reconstruction. (Custom Medical Stock Photo)
191
Breast reconstruction ations on this procedure use different amounts of abdominal muscle. The use of less muscle for reconstruction may help the patient retain abdominal strength after surgery. The newer DIEP flap procedure uses skin, fat, and minimal abdominal muscle tissue, and it uses a free flap approach. Patients generally retain more abdominal strength with this type of breast reconstruction. The latissimus dorsi flap procedure transfers skin, fat, muscle, and blood vessels from the upper back as a pedicle flap, tunneling the tissue under the skin to the front of the chest. The amount of skin and other tissue used in this procedure is generally less than in a TRAM flap surgery, making it useful for reconstructing small and medium-sized breasts or for creating a pocket for a breast implant. The gluteal flap is a free flap procedure that uses skin, fat, blood vessels, and gluteal muscle tissue from the buttocks to create the breast shape. This procedure is an option for women who cannot use the abdominal site due to thinness or incisions, or for patient preference. Nipple and areola reconstruction is optional and, if done, is performed as a last step after the patient has healed from the first surgeries. The nipple is reconstructed using tissue from the breast itself or from another part of the patient’s body such as the inner thigh. The areola may be created by tattooing the skin to make it match the natural nipple and areola. Saving the nipple from the breast with cancer that is removed (called nipple saving or nipple banking) is sometimes done but is risky because the nipple tissue might contain cancer cells. After the procedure: A patient will likely feel tired and sore for a week or two after implant reconstruction, and longer, perhaps months, after tissue flap reconstruction. The patient will probably be discharged from the hospital with a surgical drain in place to allow excess fluids to drain from the surgical site. Stitches will be in place after the surgery, but they will most likely be absorbable sutures that will not have to be removed. Scars will fade over time but never go away entirely. It takes about six to eight weeks for the patient to return to normal, depending on the type of procedure performed. A patient will be advised to take it easy during this period and avoid overhead lifting and strenuous physical activity. Risks: Some risks of breast reconstructive surgery are bleeding, fluid collection, swelling and pain, excessive scar tissue, infection, the death of all or part of the flap, problems at the donor site, fatigue, changes in the affected arm, and the need for additional surgeries to correct problems. If an infection develops after the implant surgery, then the implant may need to be removed until the infection 192
Salem Health: Cancer clears. If an infection develops after flap surgery, then surgical cleaning of the wound may be necessary. Sometimes local complications occur with breast implants. The most common of these is capsular contracture, which can occur if the scar or capsule around the implant begins to tighten and squeeze down on the soft implant, making the breast feel hard. More surgery may be needed to remove the scar tissue, or the implant may need to be removed or replaced. Rarely, rupture of the implant may occur. Implants may not last a lifetime, so additional surgeries may be needed to replace them. Breast reconstruction has no known effect on the recurrence of breast cancer, and neither implant nor flap procedures decrease the likelihood of detection of a recurrence of breast cancer. Results: Breast reconstruction after a mastectomy can improve a woman’s appearance and self-confidence. Although the surgeon will try to create a breast shape that matches the other breast closely, a perfect match is not possible, and a reconstructed breast does not have natural sensations. In some cases, surgery on the other breast is performed to improve the match. Jill Ferguson, Ph.D. u
For Further Information Ahmed, S., et al. “Breast Reconstruction.” British Medical Journal 330 (2005): 943-948. Edlick, R. F., et al. “Advances in Breast Reconstruction After Mastectomy.” Journal of Long-Term Effects of Medical Implants 15 (2005): 197-207. Farhadi, J., et al. “Reconstruction of the Nipple-Areola Complex: An Update.” Journal of Plastic, Reconstructive & Aesthetic Surgery 59 (2006): 40-53. Fentiman, I. S., and H. Hamed. “Breast Reconstruction.” International Journal of Clinical Practice 60 (2006): 471-474. Piasecki, J. H., and K. A. Gutowski. “Breast Reconstruction.” Clinical Obstetics and Gynecology 49 (2006): 401-413. Serletti, J. M. “Breast Reconstruction with the TRAM Flap: Pedicled and Free.” Journal of Surgical Oncology 94 (2006): 532-537. Spear, S. L., and A. N. Mesbahi. “Implant-Based Reconstruction.” Clinics in Plastic Surgery 34 (2007): 63-73. u
Other Resources
American Cancer Society Breast Reconstruction After Mastectomy http://www.cancer.org/docroot/CRI/content/ CRI_2_6X_Breast_Reconstruction_After_ Mastectomy_5.asp
Salem Health: Cancer
Breast self-examination (BSE)
American Society of Plastic Surgeons Breast Reconstruction http://www.plasticsurgery.org/patients_consumers/ procedures/BreastReconstruction.cfm Breastcancer.org Reconstruction http://www.breastcancer.org/bey_tre_recon_idx.html Mayo Clinic Breast Reconstruction After Mastectomy http://www.mayoclinic.com/health/breastreconstruction/WO00083 See also Breast cancers; Breast implants; Mastectomy; Self-image and body image; Sexuality and cancer.
u Breast self-examination (BSE) Category: Procedures Definition: The National Breast Cancer Foundation recommends that all women age twenty and older conduct a breast self-examination (BSE) on a monthly basis, in addition to undergoing a clinical breast examination periodically, depending on age and state of health. Cancers diagnosed: Breast cancer Why performed: Breast self-examinations are performed by women on their own breasts to detect unusual swellings, lumps, thickenings, or other conditions that may suggest the possibility of a breast disorder, including breast cancer. It is believed that, if performed every month at the same time (in relation to the menstrual cycle), this examination will educate a woman about how her breasts feel normally and will alert her to any sudden changes, thereby facilitating early detection of a precancerous or cancerous mass. Patient preparation: It is recommended that the examination take place in the shower (where water smooths the skin and makes it easier to detect changes) or lying prone. Steps of the procedure: Using the left hand to examine the right breast (and vice versa), the woman should, with fingers flat, move gently over every part of the breast in a systematic fashion (vertically up to down or circularly from well beyond the exterial margins inward), starting well above the top margin of the breast and beyond each right and left margin as well. The examination should be conducted three times using light, medium, and heavy
A woman performs a breast self-examination. (PhotoDisc)
pressure. Women must also visually inspect their breasts in a mirror, raising arms overhead and looking at the breasts from all sides. Muscles should be both flexed and relaxed. Women should be particularly alert to any swellings, dimpling of the skin, “orange-peel” (peau d’orange) appearance, discoloration, changes in or discharges from the nipple, lumps no matter how small, or other unfamiliar signs. After the procedure: If a woman detects a change in how her breasts or nipples feel, then she should promptly schedule an appointment with her physician for follow-up tests. Risks: There are no risks in performing the examination, and generally such examinations cause no pain. Results: Women who perform a self-exam become familiar with their own breasts and are able to report abnormalities much earlier than is possible if they wait for an annual clinical examination or mammogram. Early detection of 193
Breast ultrasound precancerous or cancerous tissue greatly increases not only early treatment but also survival rates. Christina J. Moose, M.A. See also Breast cancer in pregnant women; Breast cancers; Calcifications of the breast; Clinical breast exam (CBE); Mammography; Nipple discharge; Palpation; Screening for cancer.
u Breast ultrasound Category: Procedures Also known as: Sonography, ultrasonography Definition: Breast ultrasound is the use of high-frequency sound waves to produce an image of the breast tissue. The sound waves used are in the range of 20,000 to 10,000,000 cycles per second and are inaudible to the human ear. They are bounced off of the breast tissue and are able to distinguish between solid tumors and fluid-filled cysts. The density and elasticity of tissues affect the velocity of the sound waves traveling through them. Tissues that are denser and less elastic slow the sound waves and appear as shaded areas on the screen image. Tissues that are less dense and more elastic do not interfere with the sound waves and appear as clear areas. The interpretation of the sound wave data is performed by a computer. An advantage of breast ultrasound is that it does not use radiation. Cancers diagnosed: Breast cancer Why performed: There are several reasons that breast ultrasounds are performed. After a questionable mammogram, a breast ultrasound may be used to further examine the breast tissue. Some breast conditions may look like a possible cancer on a mammogram but can be identified as benign on ultrasound. For example, breast cysts and some fibroadenomas appear as clear areas on a breast ultrasound, whereas a breast cancer would not. In women under the age of thirty-five, breast ultrasound may be the procedure of choice for screening for breast cancer because younger women have denser breast tissue, which makes it difficult to assess for abnormalities on mammography. Breast ultrasound may also be used to guide a needle biopsy, or needle localization. Ultrasound has proved effective at examining the breasts of women with breast implants. It is often able to illustrate whether the implant has ruptured or not. Mammography does not show fluid leaking from the implant. Patient preparation: No preparation of the patient is required. 194
Salem Health: Cancer Steps of the procedure: For a breast ultrasound, the patient puts on a hospital gown, which is open in the front, and then lies supine on a table. A pillow is placed under the shoulder of the breast to be scanned. The area to be scanned is uncovered. The patient’s arm is placed up over the head, resting on the examination table. The radiology technician or physician uses a transducer (an instrument to transmit and receive sound waves) to scan the breast tissue. A transducer looks like a small cell phone. A gel is used between the transducer and the patient to enhance the transmission of the sound waves for the scan. The transducer is moved slowly and lightly over the breast tissue. Usually, the breast lesion is viewed in several planes, so that its features can be defined. This is accomplished by changing the angle of the transducer in relation to the breast tissue. The images of the breast are printed for further examination. After the procedure: No additional patient care is required, so the patient can go home. Risks: There are no known risks of breast ultrasound for the patient. It appears that sound waves are safe for use on human beings. For the physician, however, there is the risk of making an incorrect diagnosis about the presence of breast cancer. Breast ultrasounds do not differentiate microcalcifications (mineral deposits) in the breast tissue. Microcalcifications that are clustered can be a first sign of a developing breast cancer. The accuracy of breast ultrasounds can vary with the skill of the technician. Once the ultrasound images have been printed, there is no way to determine the angle of the transducer, or to manipulate the images, as can be done with mammograms. Also, breast ultrasound is not as accurate at assessing the whole breast. It is most effective at assessing a small area of breast tissue. Results: The images of the breast ultrasound demonstrate the different breast tissues, with the ducts appearing darker than the adipose (fatty) tissue between the ducts. The breast ultrasound is most accurate at identifying breast cysts, which are fluid-filled. If on ultrasound an area of the breast appears particularly dense and opaque, then a breast cancer could be present. Breast ultrasound does not differentiate between benign tumors and malignant (cancerous) tumors or growths. As a result, a breast biopsy is required to identify the type of lesion. Christine M. Carroll, R.N., B.S.N., M.B.A. u
For Further Information Love, Susan M., and Karen Lindsay. Dr. Susan Love’s Breast Book. Rev. 4th ed. Cambridge, Mass.: Da Capo Press, 2005.
Salem Health: Cancer
Breslow’s staging
Pagana, Kathleen Deska, and Timothy J. Pagana. Mosby’s Manual of Diagnostic and Laboratory Tests. 3d ed. St. Louis: Mosby Elsevier, 2006.
progress, or stage, of the cancer and whether the cancer has spread. The stage helps oncologists choose the best treatment and determine the best prospects for recovery.
u
Patient preparation: No special preparation is needed for a skin biopsy.
Other Resources
American Cancer Society Mammograms and Other Breast Imaging Procedures http://www.cancer.org/docroot/CRI/content/ CRI_2_6X_Mammography_and_Other_Breast_ imaging_Procedures_5.asp Health A to Z Breast Ultrasound http://www.healthatoz/atoz/ency/ breast_ultrasound.jsp Imaginis Breast Cancer Diagnosis http://www.imaginis.com/breasthealth/ ultrasound_images.asp Yale Medical Group Breast Imaging at Yale http://www.yalemedicalgroup.org/news/dxrad/ ymg_breastimaging.html See also Breast cancer in children and adolescents; Breast cancer in men; Breast cancer in pregnant women; Breast cancers; Calcifications of the breast; Clinical breast exam (CBE); Imaging tests; Mammography; Microcalcifications; Needle biopsies; Premalignancies; Screening for cancer; Ultrasound tests.
u Breslow’s staging Category: Procedures Also known as: Breslow thickness, Breslow measurement, Breslow’s depth of invasiveness Definition: Breslow’s staging is a test to measure, in millimeters (mm), the vertical thickness (how far a tumor reaches into the skin) of a malignant melanoma tumor. The test was developed by Alexander Breslow (1928-1980), an American pathologist, in the 1970’s. Cancers diagnosed: Melanoma, the most deadly form of skin cancer Why performed: Once melanoma is confirmed by a skin biopsy, Breslow’s staging helps oncologists establish the
Steps of the procedure: A skin biopsy is usually done in the doctor’s office. A local anesthetic is injected into the area with a small needle. A sample of skin tissue is then removed for examination. After the procedure: The patient feels no pain and may go home. The skin sample is examined in a laboratory. If melanoma is confirmed, then the sample is subjected to Breslow’s staging to help determine prognosis and treatment. Risks: Small skin biopsies are generally safe and carry only a small risk of bleeding or infection. Sometimes a biopsy may leave a scar. Results: Early diagnosis is the most effective way of improving the cure rate for patients with melanoma. When laboratory tests confirm melanoma, Breslow’s staging classifies the progress of the cancer according to one of five stages. In the first stage, malignant melanoma cells are found only in the outer layer of skin and have not yet invaded the deeper layers or spread. Most patients with melanoma only in the outer layer of skin can be cured with surgery. The Breslow thickness of a melanoma tumor predicts the approximate five-year survival rate after the tumor is surgically removed.
• • • •
Smaller than 1 mm: 95-100 percent 1.0-2.0 mm: 80-96 percent 2.1-4.0 mm: 60-75 percent More than 4.0 mm: 50 percent
In the last stage, the melanoma could be any thickness but has spread to other parts of the body, most likely to the nearest lymph nodes. The majority of patients with melanoma that has spread to nearby lymph nodes cannot be cured with current treatments. The average survival of patients with melanoma that has spread to the lymph nodes is only 7.5 months. Only 5 to 10 percent of patients survive beyond five years. Wendell Anderson, B.A. See also Melanomas. 195
Brief Pain Inventory (BPI)
u Brief Pain Inventory (BPI)
Salem Health: Cancer See also Breakthrough pain; Pain management medications.
Category: Procedures Definition: The Brief Pain Inventory (BPI) is a questionnaire used to measure pain in cancer patients and other patients suffering from chronic pain. The BPI provides information on the intensity of pain (known as the sensory dimension) and the impact of pain on a patient’s daily routine (known as the reactive dimension). The BPI was developed in 1989 by Charles Cleeland, M.D., while with the Pain Research group at the University of Wisconsin. Cancers diagnosed or treated: All cancers that cause chronic or severe sporadic pain Why performed: The BPI is administered to determine cancer patients’ level of pain. Once the level of pain is determined, oncologists work to manage the painful symptoms of cancer and to make patients more comfortable. Pain management is especially important for terminal patients. Cancer pain appears when a tumor presses against organs, nerves, or bone. Treatments for cancer—such as chemotherapy, radiation therapy, and especially surgery— also can cause pain. The Veterans Administration and the Joint Commission on Accreditation of Health Care Organizations consider pain the fifth vital sign and require physicians to ask patients about their pain. Patient preparation: Taking the BPI requires no patient preparation. Steps of the procedure: The questionnaire for the BPI is usually filled out by the patient. In some cases, a doctor, nurse, or social worker helps by interviewing the patient and recording the answers. Filling out the short version of the BPI takes about five minutes, while the long version takes about ten minutes. After the procedure: After the patient completes the BPI, it is scored on a scale of 0-10 for both the severity and the impact dimensions of the pain. Risks: There are no inherent risks involved with the BPI. Its validity has been tested many times, and it has been translated into twenty-five languages. The only possible problem involved with the BPI is a patient’s inability or reluctance to report pain accurately. Results: The results of an individual patient’s BPI can be tabulated in a few minutes. The results help oncologists, nurses, and other caregivers develop a pain management plan for the cancer patient. Wendell Anderson, B.A. 196
u Brompton cocktail Category: Chemotherapy and other drugs Also known as: Brompton’s mixture, hospice mix Definition: Brompton cocktail is a palliative elixir containing morphine, cocaine, ethanol, and other ingredients to lessen or prevent the pain and distress associated with terminal illness, especially advanced cancer. It is no longer part of standard care. Cancers treated: Previously used for advanced, painful tumors in patients near death Delivery routes: Oral as a liquid How this substance works: Elixirs of morphine and cocaine were first described in 1896 as treatments for the pain associated with advanced cancer by the English surgeon Herbert Snow. A specific mixture was published under the auspices of the Royal Brompton Hospital in London in 1952; the ingredients included morphine hydrochloride, cocaine hydrochloride, alcohol, and chloroform water. Several different formulations calling for heroin (diacetylmorphine), cannabis, antiemetics, distilled spirits, and sedatives have been promoted over the years. Flavoring syrup is sometimes added. It was widely used in the early 1970’s, mostly in hospice care. Two of its main proponents were Cicely Saunders, founder of the modern hospice movement, and Elisabeth Kübler-Ross, a psychiatrist and authority on end-of-life care. The active ingredients are intended to provide a welcome combination of analgesia, disinhibition, and stimulation. Cough suppression was an important effect in patients with lung or airway malignancies (or end-stage tuberculosis). The mixture was promoted as more cost effective at treating intractable cancer pain than parenteral narcotics. Several significant liabilities have contributed to the disappearance of the Brompton cocktail from modern oncology practice. In 1979, controlled trials showed that oral morphine alone gave pain relief equivalent to the cocktail, that oral morphine and oral heroin were equally effective, and that oral cocaine had no effect on patients’ alertness or sociability. One study concluded that “the Brompton Cocktail is no more than a traditional British way of administering oral morphine to cancer patients in pain.” The potential for diversion and abuse was illustrated by a case report in which an individual obtained the mixture illicitly
Salem Health: Cancer and injected it in lieu of heroin. Each of the cocktail’s active ingredients has addictive and tolerization potential, making discontinuation difficult. Even though terminal cancer patients often require multiple drugs for symptom management, the convenience of an “all-in-one” mixture of drugs such as the Brompton cocktail is outweighed by the benefits obtained by monitoring and adjusting analgesics, antineoplastics, antiemetics, and psychoactive drugs individually. Side effects: The side effects include sedation, confusion, constipation, decreased breathing, tolerization, and addiction. John B. Welsh, M.D., Ph.D. See also Do-not-resuscitate (DNR) order; End-of-life care; Home health services; Hospice care; Pain management medications; Palliative treatment.
u Bronchial adenomas Category: Diseases, symptoms, and conditions Also known as: Bronchial gland tumors, mucous gland adenomas, bronchial carcinoid tumors, cylindromas Related conditions: Carcinoid syndrome Definition: A bronchial adenoma is a slow-growing tumor in the windpipe (trachea) or in the large air passages (bronchi) leading from the windpipe to the lungs. Risk factors: The cause and risk factors for bronchial adenomas are not known. Etiology and the disease process: A bronchial adenoma can be one of several types of tumors that begin in the mucous glands; the main types of tumors are carcinoids and adenoid cystic carcinoma (also called cylindroma). The tumors are usually small and slow growing and therefore may not be diagnosed for years. Symptoms of bronchial adenoma may be confused with those of bronchial asthma or chronic bronchitis. Incidence: Approximately 1 to 3 percent of pulmonary (relating to the lungs) tumors are bronchial adenomas. Bronchial adenomas can be found in individuals of all ages but usually are found in people between the ages of thirty and fifty; the incidence is equal for men and women. Symptoms: Some of the symptoms of bronchial adenomas are difficulty breathing, hoarseness, a persistent cough, coughing up blood (hemoptysis), wheezing sounds, or pneumonia that recurs or is slow to end.
Bronchoalveolar lung cancer Screening and diagnosis: A chest X ray, computed tomography (CT) scan, or magnetic resonance imaging (MRI) can be used to detect a tumor. Often physicians will use a bronchoscopy, a procedure in which a thin, flexible tube with a very small camera is used to look at the trachea and bronchi and to take a sample of cells (biopsy) for testing. This test can distinguish a bronchial adenoma from other types of tissue growths. Sometimes it may be necessary to insert a needle through the chest wall, between the ribs, to take the biopsy for determination of the type of tumor. Treatment and therapy: Treatment of bronchial adenoma is by surgical removal of the tumor. Surgery may be bronchoscopic surgery (during a bronchoscopy) if the tumor is small or open-lung surgery. There is a small chance of recurrence of a bronchial adenoma and a very small chance of metastases. Laser ablation (removal) of a bronchial adenoma may be done through a bronchoscope, especially for tumors that have recurred. Prognosis, prevention, and outcomes: Following removal of the tumor there is an excellent long-term prognosis for individuals with a bronchial adenoma. Vicki Miskovsky, B.S., R.D See also Adenocarcinomas; Adenoid cystic carcinoma (ACC); Bronchoalveolar lung cancer; Bronchography; Bronchoscopy; 1,4-Butanediol dimethanesulfonate; Carcinoid tumors and carcinoid syndrome; Coughing; Laryngeal cancer; Lung cancers; Pneumonia.
u Bronchoalveolar lung cancer Category: Diseases, symptoms, and conditions Also known as: Non-small-cell lung cancer (NSCLC), bronchioloalveolar lung cancer, lung adenocarcinoma Related conditions: Pleural effusion, pneumonia Definition: Bronchoalveolar lung cancer is a type of NSCLC that arises in the alveoli (air sacs of the lung). It can begin as either a single site or multiple sites, or spread rapidly as a pneumonic form. Bronchoalveolar lung cancer is less likely than other types of NSCLC to spread beyond the lungs. Risk factors: The most common cause of lung cancer is smoking cigarettes. Another major cause is exposure to secondhand smoke. Other risk factors include exposure to radon gas or asbestos, environmental pollution, tuberculosis, lung disease, and an inherited predisposition to lung cancer. 197
Bronchoalveolar lung cancer Etiology and the disease process: With bronchoalveolar lung cancer, cells in the alveoli begin to grow wildly. As they grow, they progress along the alveolar walls. Multiple sites may develop and then converge to consolidate some areas of the lungs. An obstructed area of the lung may become pneumonic. Incidence: NSCLCs account for about 75 percent of all lung cancers. Bronchoalveolar lung cancer makes up about 2 to 3 percent of this group. Although 10 percent of patients with lung cancer in the United States are nonsmokers, 25 to 30 percent of patients with bronchoalveolar lung cancer are nonsmokers. It is more common in women. Symptoms: The symptoms of bronchoalveolar cancer are coughing, shortness of breath, wheezing, chest pain, large amounts of watery sputum, and hemoptysis (coughing up blood). On physical examination, the lungs are dull to percussion (tapping on the chest wall), and breath sounds may be weak or absent on auscultation (listening with a stethoscope). If the tumor is pressing on a nerve, it can cause shoulder pain or hoarseness. Screening and diagnosis: Currently, there is no accurate, inexpensive screening test for bronchoalveolar lung cancer. Researchers are working to develop such a test by looking at a marker in the blood and also at breath analysis. To diagnose lung cancer, pulmonary function tests and a chest X ray may be performed. Chest X rays can demonstrate most lung cancers, except the very small. More sensitive tests are computed tomography (CT) scans, magnetic resonance imaging (MRI), and positron emission tomography (PET) scans. To differentiate between the types of lung cancer, a biopsy of the tumor must be performed. Bronchoscopy, thoracoscopy, or mediastinoscopy may be performed to examine pulmonary secretions and the lymph nodes of the lung. If the cancer exists on the periphery of the lung, it may be necessary to perform a needle biopsy through the chest wall. If none of these procedures is effective in determining the type of lung cancer, a surgical procedure called a thoracotomy (opening the chest) can be performed. The actual diagnosis of bronchoalveolar lung cancer is made by the pathologist, who examines the tumor cells under a microscope. The pathologist identifies the type of lung cancer and stages the cancer. All NSCLCs are staged in the same way, using a combination of numeric tumor grading and the TNM (tumor/lymph node/metastasis) stages. The stages are as follows: • Stage IA, T1 N0 M0: The tumor is less than 3 centimeters (cm) and there is no lymph node involvement or metastases. 198
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•
Stage IB, T2 N0 M0: The tumor is greater than 3 cm, but it has not spread beyond the lung. • Stage IIA, T1 N1 M0: The tumor is less than 3 cm, and there is spread to local lymph nodes. • Stage IIB, T2 N1 M0, or T3 N0 M0: Either the tumor is greater than 3 cm, or it has spread into the outside of the lungs, the chest cavity, or the pericardium (sac around the heart). • Stage IIIA, T 1-3 N2 M0, or T3 N1 M0: Either the cancer has spread to distant lymph nodes but has not metastasized, or the cancer has spread into adjacent tissues and muscles and has spread to local lymph nodes. • Stage IIIB, T4 N3 M0: Either the cancer has spread to nearby organs or it has spread to distant lymph nodes but has not metastasized. • Stage IV, M1: The cancer has metastasized to distant organs. Treatment and therapy: Treatment of lung cancer can include surgery, chemotherapy, and radiation. To remove a bronchoalveolar tumor, the surgeon can perform a wedge resection, a lobectomy, or a pneumonectomy. Chemotherapy for lung cancers is effective only 35 percent of the time. The most commonly used drugs are combinations of cisplatin (Platinol), carboplatin (Paraplatin), vinorelbine (Navelbine), vincristine (Oncovin), vinblastine (Velban), paclitaxel (Taxol), docetaxel (Taxotere), and gemcitabine (Gemzar). Newer chemotherapy drugs that interfere with cell growth and reproduction as well as angiogenesis (formation of new blood vessels) are being used. They are gefitinib (Iressa), erlotinib (Tarceva), and bevacizumab (Avastin). Radiation therapy for bronchoalveolar lung cancer is not effective as a cure, so it is reserved for treatment when surgery is not possible. Prognosis, prevention, and outcomes: Patients with lower stage cancers survive longer than those with highstage cancers. Research has shown that patients who have never smoked respond better to treatments for bronchoalveolar cancer. The best way to avoid lung cancer is by not smoking and by avoiding exposure to secondhand smoke. Christine M. Carroll, R.N., B.S.N., M.B.A. u
For Further Information Houlihan, Nancy G. Lung Cancer. Pittsburgh: Oncology Nursing Society, 2004. Hunt, Ian, Martin Muers, and Tom Treasure. ABC of Lung Cancer. Malden, Mass.: Blackwell, 2008. Roth, Jack A., James D. Cox, and Waun Ki Hong, eds. Lung Cancer. 3d ed. Malden, Mass.: Blackwell, 2008.
Salem Health: Cancer u
Other Resources
LungCancer.org http://www.lungcancer.org/ MayoClinic.com Lung Cancer http://www.mayoclinic.com/health/lung-cancer/ DS00038 National Cancer Institute Lung Cancer http://www.cancer.gov/cancertopics/types/lung See also Adenocarcinomas; Adenoid cystic carcinoma (ACC); Bronchial adenomas; Bronchography; Bronchoscopy; 1,4-Butanediol dimethanesulfonate; Carcinoid tumors and carcinoid syndrome; Coughing; Laryngeal cancer; Lung cancers; Pneumonia.
u Bronchography Category: Procedures Also known as: Bronchogram, laryngography Definition: Bronchography is a radiographic evaluation that examines the interior passageways of the larynx, trachea, and bronchi. Bronchography is used somewhat infrequently because of technological advances with computed tomography (CT) scans and bronchoscopy. Cancers diagnosed: Lung cancers Why performed: Bronchography is performed to examine structural or functional abnormalities of the lower respiratory tract. Abnormalities that are commonly investigated with bronchography include bronchiectisis, hemoptysis, chronic bronchitis, chronic pneumonia, and tumors. Patient preparation: The patient is asked to not eat or drink for several hours before the procedure. The patient may also be asked to perform thorough mouth hygiene before the procedure. Steps of the procedure: The patient is asked to remove all clothing, jewelry, and dentures; to dress in a gown; and to empty the bladder. Vital signs (such as blood pressure and respiratory rate) are taken. The patient is positioned on a table that can tilt in various directions. The patient may also be given a sedative. Next, numbing medication is injected into the back of the patient’s throat to prevent gagging. Finally, the physician passes the bronchoscope down the back of the throat into the trachea and bronchi. Contrast dye is released from the bronchoscope as it advances.
Bronchoscopy The dye forms a coating on the lining of the interiors of the bronchi, trachea, and larynx. The physician then takes several X rays from different positions, after which the bronchoscope is removed. After the procedure: The patient is moved to a recovery room and has vital signs monitored for several hours postprocedure. The patient will not be allowed to eat or drink until the gag reflex has returned. The patient may be asked to gently cough up any remaining contrast dye. Normal diet may be resumed after the procedure. The throat may feel sore after bronchography. A follow-up chest X ray is often performed twenty-four to forty-eight hours after the bronchography to verify the removal of the contrast dye from the airways. Risks: Risks of the procedure include infection or pneumonia and airway obstruction from the contrast dye in patients with emphysema or chronic obstructive pulmonary disease (COPD). Results: The contrast dye allows the physician to assess the likely presence or absence of respiratory system abnormalities, such as tumors, in the larynx, trachea, or bronchi. If abnormalities are detected, then the physician will either perform a confirmatory diagnostic procedure or devise a treatment plan based on the specific test results. Jeremy W. Dugosh, Ph.D. See also Adenocarcinomas; Adenoid cystic carcinoma (ACC); Bronchial adenomas; Bronchoalveolar lung cancer; Bronchoscopy; 1,4-Butanediol dimethanesulfonate; Carcinoid tumors and carcinoid syndrome; Coughing; Laryngeal cancer; Lung cancers; Pneumonia.
u Bronchoscopy Category: Procedures Also known as: Fiber-optic bronchoscopy Definition: Bronchoscopy uses a bronchoscope to allow a doctor to see, examine, and biopsy tissues in the respiratory tract and lungs. The procedure is used to check for cancer cells. A bronchoscope is a thin tube equipped with fiber optics or a miniature camera that produces images of the internal airways and lungs. Cancers diagnosed: Respiratory tract cancer, lung cancer Why performed: Bronchoscopy is a diagnostic procedure used to view the inside of the airways and lungs. Suspicious tissues are biopsied and examined in a laboratory in order to detect the presence of cancer cells. 199
Burkitt lymphoma
Salem Health: Cancer gen levels, and heart activity. Oxygen is delivered through a nasal cannula. The bronchoscope is inserted through the nose or mouth. The airways and lungs are inspected. A bronchoalveolar lavage may be performed, which involves inserting sterile fluid to remove mucus or cells for examination. A tissue biopsy is taken by clipping a sample of abnormal tissue. At the end of the procedure, the fluid and bronchoscope are removed. After the procedure: Patients may receive a chest X ray following the procedure to ensure that the lungs were not punctured. Patients should not eat or drink until the anesthesia wears off in order to prevent choking. Patients may be hoarse, experience fever, or cough up small amounts of blood. Risks: Bronchoscopy is considered a safe procedure. The primary risks are infection and bleeding. There is a slight risk of lung perforation, heart attack, irregular heartbeat, and low blood oxygen. Results: A healthy respiratory tract and lungs are free of swelling and abnormal growths. Suspicious growths are biopsied to determine whether cancer is present. Mary Car-Blanchard, O.T.D., B.S.O.T.
A physician uses a bronchoscope. (National Cancer Institute)
Patient preparation: Patients should stop taking aspirin or blood-thinning medication a week before the procedure. Brochoscopy uses local or general anesthesia. Patients receiving general anesthesia should not eat or drink after midnight prior to the day of the procedure. Bronchoscopy is usually an outpatient procedure, and patients should arrange to have someone else drive them home. Patients wear an examination gown, which is removed from the waist up during the procedure, and receive a sedative before the bronchoscopy begins. Steps of the procedure: Patients receive general or local anesthesia, depending on whether a rigid or a flexible bronchoscope is used. Local anesthesia is injected or sprayed into the throat. Patients receive medication to eliminate secretions and to prevent coughing or gagging. Monitors are placed to measure blood pressure, blood oxy200
See also Bronchial adenomas; Bronchoalveolar lung cancer; Bronchography; Carcinoid tumors and carcinoid syndrome; Computed tomography (CT) scan; Coughing; Endoscopy; Gastrointestinal cancers; Hemoptysis; Lambert-Eaton myasthenic syndrome (LEMS); Lung cancers; Mesothelioma; Otolaryngology; Pneumonia; Sputum cytology.
u Burkitt lymphoma Category: Diseases, symptoms, and conditions Also known as: B-cell lymphoma, small noncleaved cell lymphoma Related conditions: Non-Hodgkin lymphoma Definition: Burkitt lymphoma, first described by Denis Parsons Burkitt in 1956, is a type of non-Hodgkin lymphoma that develops from B lymphocytes, the cells that produce antibodies and fight infections. Risk factors: Most people who develop Burkitt lymphoma have no identifiable risk factors, but age, sex, ex-
Salem Health: Cancer
Burkitt lymphoma
posure to chemicals that damage deoxyribonucleic acid (DNA), infections such as the Epstein-Barr virus (EBV), and a weakened immune system may be factors leading to its development. Etiology and the disease process: In North America most cases of Burkitt lymphoma are sporadic and caused by a chromosomal rearrangement. Of these rearrangements, 90 percent involve a chromosomal exchange called a translocation between chromosomes 8 and 14. This translocation moves the MYC gene from its normal position on chromosome 8 to the vicinity of the gene producing immunoglobulin G (IgG) on chromosome 14. In 10 percent of Burkitt lymphoma cases, MYC has been translocated to the vicinity of antibody-producing genes on either chromosome 2 or chromosome 22. In its new chromosomal location, MYC is overactive and results in uncontrolled cell growth. The MYC gene encodes for a transcription factor that activates other genes. One gene that is activated is HMG-I/Y, whose product transforms normal B lymphocytes into rapidly growing tumor cells. Burkitt lymphoma is endemic in equatorial Africa and is associated with not only chromosomal translocations but also the Epstein-Barr virus (EBV), which also causes infectious mononucleosis and other cancers. About 30 percent of Burkitt lymphoma patients in the United States harbor EBV. In children the disease usually begins in the abdomen, develops rapidly, and metastasizes quickly. Abdominal swelling, fluid retention, and vomiting often occur. In adults the disease often begins with a painless enlargement of a lymph gland or abdominal swelling. Depending on the location of the affected lymph node, a variety of conditions may develop. Occasionally, Burkitt lymphoma affects the blood and may result in anemia, increased bleeding, and susceptibility to infections. The B cells may invade other tissues, causing a variety of symptoms. Because the cancer is one of the most rapidly growing human tumors, most cases are in either Stage III or Stage IV at the time of diagnosis. Incidence: Burkitt lymphoma is common in central Africa, where it accounts for as much as 50 percent of cancer deaths in children. The disease is relatively rare in the United States, but when it does occur, the average age at diagnosis is seven years, and the disease accounts for about 3 percent of the total cancer deaths in people under twenty years old. The disease is also three times as likely to occur in boys as in
girls and is more common in white children than children of other races. It is 1,000 times more likely to occur in acquired immunodeficiency syndrome (AIDS) patients. Symptoms: Although most cases in the United States develop in the abdomen, the first symptom is usually a painless swelling of an axillary, neck, or groin lymph node. The affected lymph node or nodes will grow rapidly and may form lumps. Depending on where the disease develops, other symptoms may occur. In Africa, where Burkitt lymphoma is endemic, the disease often affects the face and jaw, causing extensive swelling. Screening and diagnosis: Diagnosis is by biopsy of the affected tissue followed by histological examination. Spinal fluid analysis, blood cell and platelet counts, X rays, computed tomography (CT) scans, gallium scans, and positron emission tomography (PET) scans also can be
A child with a large facial tumor caused by Burkitt lymphoma. (Centers for Disease Control and Prevention)
201
1,3-Butadiene
Salem Health: Cancer
Relative Survival Rates for Burkitt Lymphoma, 1988-2001 Years
Survival Rate (%)
1 2 3 5 8 10
53.5 47.8 47.4 45.4 45.1 45.1
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007)
therapy, bone marrow transplants, and monoclonal antibodies also have been used to treat the disease. Prognosis, prevention, and outcomes: If the disease is relatively localized and has not spread, aggressive chemotherapy can cure up to 80 percent of the cases. If the central nervous system or the bone marrow has become involved, the effectiveness of treatment is significantly less. Charles L. Vigue, Ph.D. u
For Further Information Magrath, Ian, ed. The Non-Hodgkin’s Lymphomas. New York: Oxford University Press, 1997. Mauch, Peter, et al., eds. Non-Hodgkin’s Lymphomas. Philadelphia: Lippincott Williams & Wilkins, 2004.
u
used to diagnose the disease. The St. Jude’s Children’s Research Hospital system is commonly used to stage the disease in children. • Stage I: Lymphoma is localized to a single site. • Stage II: Lymphomas involve more than one site but are localized to one side of the body. • Stage III: Lymphomas involve multiple sites on both sides of the body but do not involve bone marrow or the nervous system. • Stage IV: Lymphomas involve the bone marrow or the nervous system. The Ann Arbor system is used for adults with the disease. • Stage I: Lymphoma is limited to one lymph node either above or below the diaphragm or is limited to one organ. • Stage II: Lymphomas are either in two or more lymph nodes on the same side of the diaphragm or are limited to one organ and the lymph nodes near that organ. • Stage III: Lymphomas have spread to lymph nodes on both sides of the diaphragm and may involve an organ. • Stage IV: Lymphomas have metastasized throughout one or more organs and may involve lymph nodes. Treatment and therapy: In children, Burkitt lymphoma is usually treated by aggressive and intense chemotherapy that may last for several months. The most common chemotherapeutic agent used is cyclophosphamide (Cytoxan), usually in combination with another chemotherapeutic agent. If large tumors are involved, radiation therapy may be indicated. In some cases surgery may be required to remove affected tissues. In adults Burkitt lymphoma is treated with chemotherapy involving a combination of chemotherapeutic agents. Radiation therapy is often used in combination with chemotherapy. Stem cell 202
Other Resources
Leukemia and Lymphoma Society http://www.leukemia-lymphoma.org/hm_lls Lymphoma Information Network Burkitt’s Lymphoma/Leukemia http://www.lymphomainfo.net/nhl/types/burkitts.html National Cancer Institute Non-Hodgkin Lymphoma http://www.cancer.gov/cancertopics/types/nonhodgkins-lymphoma See also Childhood cancers; Epstein-Barr virus; Genetics of cancer; Hepatitis C virus (HCV); Hodgkin disease; Infectious cancers; Lymphomas; Molecular oncology; MYC oncogene; Non-Hodgkin lymphoma; Oncogenic viruses; Proto-oncogenes and carcinogenesis; Viral oncology; Virus-related cancers; Young adult cancers.
u 1,3-Butadiene Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 2000 Also known as: Vinylethylene, bivinyl, buta-1,3-diene, α,γ-butadiene Related cancers: Leukemia, lymphosarcoma, reticulosarcoma, hematopoietic cancers Definition: 1,3-Butadiene is a hydrocarbon molecule made up of four atoms of carbon and six atoms of hydrogen. The first and last pairs of carbon atoms are held together by two chemical bonds or four electrons. The two and three carbons share a single pair of electrons. This atomic arrangement makes 1,3-butadiene highly flammable and extremely reactive.
Salem Health: Cancer Exposure routes: Inhalation, ingestion, dermal contact, exhaust from motor vehicles and cigarette smoke Where found: Industries involved in the synthesis of rubber-like materials, resins, and polymers At risk: Workers who deal with synthetic rubber, organic chemicals, and resins Etiology and symptoms of associated cancers: In all species studied, including humans, 1,3-butadiene has been shown to be oxidized to rings that involve two of the carbon atoms and one atom of oxygen. Such epoxides are chemically similar to the known carcinogen ethylene oxide. Tumor production in both rodents and humans involves reaction with deoxyribonucleic acid (DNA), producing genetic alterations in tumor-suppressor genes. History: The shortage of natural rubber in World War II caused an intense search for synthetic latex. It was determined that 1,3-butadiene reacts readily with other similar hydrocarbons to produce a wide variety of polymeric substances. An example is copolymerization with styrene, a molecule involving the carcinogen benzene. Uncertainty in early studies of 1,3-butadiene carcinogenicity resulted when conditions also involved benzene. More than 75 percent of 2 million metric tons of 1,3-butadiene produced in a typical year are consumed by the rubber industry; the compound is also involved in nylon synthesis. Studies of workers in synthetic rubber plants beginning in 1943 gave conflicting evidence concerning the carcinogenicity of 1,3-butadiene. Later animal studies with rats and mice exhibited a strong pattern of incremental risk for a variety of cancers. More carefully controlled studies of production workers in the early 1990’s documented 1,3butadiene’s carcinogenic nature. Extensive federal regulation of 1,3-butadiene exists. The U.S. Department of Transportation (DOT) lists the chemical as hazardous and requires special marking, labeling, and transporting precautions. The U.S. Environmental Protection Agency (EPA), acting under the Clean Air Act (1970), lists 1,3-butadiene as one of thirty-three hazardous air pollutants that present the greatest threat to public health and requires that as little as ten pounds of the substance must be reported. The Occupational Safety and Health Administration (OSHA) has set the permissible exposure limit at one part per million. K. Thomas Finley, Ph.D. See also Air pollution; Carcinogens, known; Carcinogens, reasonably anticipated.
1,4-Butanediol dimethanesulfonate
u 1,4-Butanediol
dimethanesulfonate Category: Carcinogens and suspected carcinogens; chemotherapy and other drugs RoC status: Known human carcinogen since 1985 Also known as: Myleran, busulfan Related cancers: In patients receiving busulfan for chronic myeloid leukemia (CML), cytological anomalies and cancers were observed at a variety of sites, including breast cancer, female genital cancers, and leukemia. Cancer patients given busulfan for bronchial cancer developed leukemia that was not dose related. Definition: Busulfan is a sulfonurea alkylating agent that contains reactive alkyl groups that readily combine with other molecules via cross-linking of deoxyribonucleic acid (DNA) strands in the nuclei of rapidly dividing cells, thereby destroying them. A prescription drug employed in chemotherapy of leukemias, especially CML, busulfan does not selectively harm cancer cells but kills normal cells as well, and it is considered to be mitogenic, carcinogenic, and leukemogenic. Locally it may cause blistering of the skin and damage to the eyes and respiratory tract. Systemic toxic effects include nausea and vomiting, reduction in both leukocytes and erythrocytes, and hemorrhage. Exposure routes: Intravenous (IV), oral/ingestion of tablets Where found: People may be exposed via chemotherapy (oral or IV) for treatment of various types of leukemia, especially CML, and before bone marrow transplants (used to treat CML), in combination with cyclophosphamide used as a conditioning regimen. At risk: There is a potential for occupational exposure in employees who formulate and package busulfan tablets, and for health care professionals who administer IV busulfan to patients. Etiology and symptoms of associated cancers: Busulfan may cause cellular dysplasias and cytologic abnormalities. Busulfan, which is both leukemogenic and carcinogenic, has been shown to cause cancer of the breast and female reproductive organs as well as leukemias in humans, though evidence is limited in animal studies. Related symptoms and signs vary by cancer. For leukemia, they in203
1,4-Butanediol dimethanesulfonate clude weakness, fever, bleeding gums, petechiae, swollen glands, and enlarged spleen or liver; for breast cancer, a new lump or mass in the breast; and, for endometrial cancer, postmenopausal, or irregular vaginal bleeding. History: Introduced in 1950, busulfan raised the median survival time for CML to approximately 3.5 to 4.5 years. However, because busulfan proved more efficient at destroying normal stem cells than CML cells, it has been largely supplanted by more specific and less toxic agents. Malignant tumors and acute leukemias have been reported in patients who were treated with busulfan; the World
204
Salem Health: Cancer Health Organization (WHO) found a cause-and-effect relationship between busulfan and secondary malignancies. The International Agency for Research on Cancer found four cases of acute leukemia among 243 patients treated with busulfan as adjuvant chemotherapy following surgical removal of bronchogenic carcinoma, suggesting that busulfan is leukemogenic. Cynthia Racer, M.A., M.P.H. See also Carcinogens, known; Carcinogens, reasonably anticipated; Chronic myeloid leukemia (CML).
Salem Health: Cancer
u CA 15-3 test Category: Procedures Also known as: Carbohydrate antigen 15-3, cancer antigen 15-3 Definition: CA 15-3 is a transmembrane glycoprotein (carbohydrate-containing protein) found in several tissue types. It is classified as a MUC1 member of the mucin family of proteins. This class of glycoproteins is thought to play a role in reducing cell-to-cell interaction and inhibition of tumor cell cytolysis. The core protein component is identical; the carbohydrate concentration (degree of glycosylation) is the component differentiating between tissue types. Serum/plasma levels are determined by immunoassay. Cancers diagnosed: CA 15-3 is not an organ-specific marker and has been found at elevated levels in ovarian, prostatic, and lung cancer. Additionally, increased CA 15-3 levels can be found concomitant with benign conditions such as breast or ovarian disease, endometriosis, pelvic inflammatory disease, hepatitis, pregnancy, and lactation. Why performed: Because CA 15-3 is not sensitive or specific enough to be used as a screening test, its primarily utility is as a tumor marker for monitoring response to therapy and recurrence in breast cancer patients. At least 70 percent of advanced breast cancer cases have tumors that shed CA 15-3. Blood levels typically are proportional to the tumor burden (mass), with higher levels of CA 15-3 indicative of the presence of a larger tumor. Patient preparation: No special patient preparation is required for accurate CA 15-3 analysis. Steps of the procedure: A blood sample is collected, typically by venipuncture. The collected serum (or plasma) is tested by immunoassay, which involves capturing the CA 15-3 present in the sample by means of monoclonal antiCA 15-3 antibodies. A second, detection (labeled) antibody is then introduced, which subsequently binds to the CA 15-3/anti-CA 15-3 complex. The addition of a substrate results in a detectable signal, the level of which is directly proportional to the amount of the CA 15-3 present in the sample. After the procedure: Pressure should be applied to the venipucture site in order to avoid the development of hematoma (a mass of clotted blood resulting from bleeding under the skin).
CA 19-9 test Risks: The risks of venipuncture are slight but include excessive bleeding, fainting, hematoma, and infection (always a slight risk any time the skin is broken). Results: Although each laboratory establishes reference intervals based on the local, normal population, a basic interpretive guideline would place normal at 0-31 units per milliliter (U/mL) and elevated at more than 31 U/mL. Pam Conboy, B.S. See also CA 19-9 test; CA 27-29 test; CA 125 test; Tumor markers.
u CA 19-9 test Category: Procedures Also known as: Carbohydrate antigen 19-9, cancer antigen 19-9 Definition: CA 19-9 is a glycolipid (carbohydratecontaining fat) characterized glycoprotein (carbohydratecontaining protein, or mucin). It is similar to the type A blood group protein, with additional sialic acid residues. CA 19-9 is found in normal fetal cells as well as in the pancreas, salivary ducts, gastric and colonic epithelium, pancreatic and gastric fluid, saliva, and meconium (first stool of a newborn). It is normally removed from circulation by the biliary system. Serum/plasma levels are determined by immunoassay. Cancers diagnosed or treated: CA 19-9 is elevated in patients with gastrointestinal tract carcinoma, including cancer of the pancreas, stomach, colon, and ovaries. Abnormally high values may also be detected in benign conditions such as acute pancreatitis, cirrhosis, cholecystitis, biliary obstruction, gastric ulcer, pulmonary disease, and chronic hepatitis C and in patients who smoke. Why performed: Because CA 19-9 is not sensitive or specific enough to be used as a screening test, its primarily utility is as a tumor marker for monitoring response to therapy and recurrence in pancreatic cancer patients. Levels are typically proportional to the tumor burden (mass), with higher levels of CA 19-9 indicative of the presence of a larger tumor. Very elevated levels, defined as more than 1,000 kilounits per liter (kU/L), are highly specific for pancreatic cancer and indicate very advanced disease. Patient preparation: No special patient preparation is required for accurate CA 19-9 analysis. 205
CA 27-29 test Steps of the procedure: A blood sample is collected, typically by venipuncture. The collected serum (or plasma) is tested by immunoassay, which involves capturing CA 19-9 present in the sample by means of monoclonal anti-CA19-9 antibodies. A second, detection (radiolabeled) antibody is then introduced, which subsequently binds to the CA 19-9/ anti-CA 19-9 complex. The addition of a substrate results in a detectable signal, the level of which is directly proportional to the amount of the CA19-9 present in the sample. After the procedure: Pressure should be applied to the venipucture site in order to avoid the development of a hematoma. Risks: The risks of venipuncture are slight but include excessive bleeding, fainting, hematoma, and infection (always a slight risk any time the skin is broken). Results: Although each laboratory establishes reference intervals based on the local, normal population, a basic interpretive guideline places normal at 0-40 kilounits per milliliter (kU/mL) and elevated at more than 40 kU/mL. Pam Conboy, B.S. See also Bile duct cancer; CA 15-3 test; CA 27-29 test; CA 125 test; Pancreatic cancers; Tumor markers.
u CA 27-29 test Category: Procedures Also known as: Carbohydrate antigen 27-29, cancer antigen 27-29 Definition: Similar to CA 15-3, CA 27-29 is a transmembrane glycoprotein (carbohydrate-containing protein, or mucin) found in several tissue types. This class of glycoproteins is thought to play a role in reducing cell-to-cell interaction and the inhibition of tumor cell cytolysis. The core protein component is identical; the carbohydrate concentration (degree of glycosylation) is the component differentiating between tissue types. Serum/plasma levels are determined by immunoassay. Cancers diagnosed: CA 27-29 is not an organ-specific marker and has been found at elevated levels in breast, ovarian, colon, stomach, kidney, lung, pancreas, uterus, and liver cancers. Additionally, increased CA 27-29 levels can be found concomitant with benign conditions such as first trimester pregnancy, endometriosis, ovarian cysts, and breast, kidney, and liver disease. Why performed: Because CA 27-29 is not sensitive or specific enough to be used as a screening test, its primary 206
Salem Health: Cancer utility is as a tumor marker for monitoring response to therapy and recurrence in previously treated Stage II and Stage III breast cancer patients. Blood levels are typically proportional to the tumor burden (mass), with higher levels of CA 15-3 indicative of the presence of a larger tumor. Physicians will typically order either CA 27-29 levels or CA 15-3 levels but not both, as they are considered essentially equivalent in diagnostic value. Patient preparation: No special patient preparation is required for accurate CA 27-29 analysis. Steps of the procedure: A blood sample is collected, typically by venipuncture. The collected serum (or plasma) is tested by immunoassay, which involves capturing CA 2729 present in the sample by means of monoclonal anti-CA 27-29 antibodies. A second, detection (labeled) antibody is then introduced, which subsequently binds to the CA 2729/anti-CA 27-29 complex. The addition of a substrate results in a detectable signal, the level of which is directly proportional to the amount of the CA 27-29 present in the sample. After the procedure: Pressure should be applied to the venipuncture site in order to avoid the development of a hematoma. Risks: The risks of venipuncture are slight but include excessive bleeding, fainting, hematoma, and infection (always a slight risk any time the skin is broken). Results: Although each laboratory establishes reference intervals based on the local, normal population, a basic interpretive guideline for CA 27-29 places normal at 0-32 units per milliliter (U/mL) and elevated at more than 32 U/mL. Pam Conboy, B.S. See also CA 15-3 test; CA 19-9 test; CA 125 test; Tumor markers.
u CA 125 test Category: Procedures Also known as: Cancer antigen 125, CA125, CA-125, CA125-II Definition: CA 125 is a mucinous glycoprotein that may be elevated in some cancer cells, particularly those associated with ovarian cancer. Cancers diagnosed: Ovarian cancer, uterine cancer, breast cancer, lung cancer
Salem Health: Cancer
Cachexia
Why performed: CA 125 serves as a biomarker or tumor marker to determine the presence of cancer. It is generated on the surface of cells and released into the bloodstream. Concentrations of CA 125 often are elevated in ovarian cancer patients.
u Cachexia
Patient preparation: No special preparation is necessary.
Related conditions: Anorexia
Steps of the procedure: To determine the level of CA 125 in a patient, blood is drawn from a vein, typically from the inside of an elbow or sometimes from the back of a hand. The site of extraction is first cleaned with an antiseptic. An elastic band is often applied around the upper arm to apply pressure and cause the vein to engorge with blood. After a needle is inserted into the selected vein, blood is collected in a syringe or an airtight vial. Once the blood is collected, the needle is removed and the puncture site is bandaged to stop any subsequent bleeding.
Definition: Cachexia is a complex syndrome in which changes in the way the body uses food—particularly fat and carbohydrates—lead to loss of muscle and fat. Anorexia (loss of appetite) is sometimes, but not always, associated with cachexia.
After the procedure: There may be throbbing or bruising around the extraction site. Risks: The risks involved in collecting blood to ascertain CA 125 levels include the possibility of excessive bleeding, fainting or light-headedness, blood accumulating under the skin (hematoma), and infection around the puncture site. There is always the possibility of multiple punctures being necessary to find a vein that will yield blood. Results: A CA 125 level greater than 35 units per milliliter (U/mL) of blood is considered to be elevated. In many cases, elevated levels are not an indication of cancer but instead can be attributed to other conditions, such as endometriosis and benign ovarian cysts. The lack of specificity is a key problem when using CA 125 as a cancer marker. In 79 percent of women tested with known ovarian cancers, CA 125 levels were elevated, while the other 21 percent showed no elevated CA 125 concentrations. The CA 125 test for ovarian cancer is most reliable in women who have gone through menopause. Tracking CA 125 levels periodically over time to determine the rate at which levels fluctuate is much more definitive than a single CA 125 test. Elevated CA 125 levels, particularly in postmenopausal women, indicate the need for further screening that may include ultrasonic imaging, computed tomography (CT) scans, and surgery. Alvin K. Benson, Ph.D. See also CA 15-3 test; CA 19-9 test; CA 27-29 test; Endometrial cancer; Fallopian tube cancer; Fertility drugs and cancer; Ovarian cancers; Ovarian cysts; Ovarian epithelial cancer; Proteomics and cancer research; Tumor markers; Uterine cancer.
Category: Diseases, symptoms, and conditions Also known as: Wasting syndrome, anorexia-cachexia syndrome
Risk factors: Certain cancers such as lung cancer or any cancer of the digestive tract—particularly of the esophagus, stomach, and pancreas—are more likely to be accompanied by cachexia. It is also common in advanced cancer, although infrequently it occurs in early cancers, sometimes even before diagnosis. Cachexia can also occur with acquired immunodeficiency syndrome (AIDS). Etiology and the disease process: In cancer-related cachexia, it is thought that the tumor releases chemicals that change food metabolism. Patients with cachexia tend to have poor appetites. Even with nutritional supplementation, the wasting cannot be reversed while the cancer remains. Incidence: When diagnosed, about 80 percent of patients with cancers in the upper gastrointestinal tract and 60 percent of patients with cancers of the lung have already lost considerable weight. More than 80 percent of patients who die from any cancer or from AIDS have cachexia. Patients with any solid tumor except breast cancer are generally more prone to cachexia, and it is also more common and more pronounced as the disease progresses in children and in the elderly. Symptoms: Cachexia is one of the most overwhelming symptoms of cancer, demolishing quality of life with numbing fatigue, loss of appetite or changes to taste, and severe weight loss of 10 percent or more of body weight. Screening and diagnosis: When a person experiences unexplained weight or appetite loss or fatigue, medical practitioners without more specific clues might perform such general screens as a complete blood count and a chest X ray. When the source of the problem is suspected, tests are more specific. With a known cancer, cachexia diagnosis is based on clinical history, substantial weight loss, and physical examination. The concentration of plasma albumin in blood will usually be low. Extensive diagnostics are not normally required. 207
Cadmium and cadmium compounds Treatment and therapy: The best course of action for cachexia is treatment of the underlying disease. After successful treatment, patients regain lost muscle and fat mass. Prognosis, prevention, and outcomes: Prognosis is very poor with cachexia in advanced disease. When cachexia occurs in the early stages of cancer, the cancer that causes it is often responsive to treatment, and successful treatment removes the source of changes to metabolism. Jackie Dial, Ph.D. See also Antinausea medications; Appetite loss; Nutrition and cancer treatment.
u Cadmium and cadmium
compounds Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 2000 Also known as: Cadmium chloride, cadmium sulfate, cadmium nitrate, cadmium oxide, cadmium sulfide, cadmium carbonate, greenockite, capsebon, cadmopur yellow Definition: Cadmium is a natural metal, usually occurring in combination with other elements rather than in its pure state. It is most frequently found in zinc deposits as cadmium sulfide. Commercial use of cadmium began at the end of the nineteenth century and became widespread by the middle of the twentieth century. The noncorrosive properties of cadmium led to its use in batteries, electroplating, and coating of other metals, such as steel. Workers are at risk for occupational exposure to cadmium through inhalation, but cadmium also may be released into the environment through these industrial processes. Additionally, cadmium is released into the environment from other sources, including forest fires, volcanos, weathering of rocks, and combustion of fossil fuels such as coal. Both industrial and natural releases of cadmium into the atmosphere put the general public at risk for exposure through contaminated water, air, and soil. Plants can absorb cadmium from contaminated soil, so the major exposure to cadmium in the general public is through the food supply. Tobacco plants are among those that absorb cadmium, so tobacco smoking is another source of exposure in the general public. Related cancers: Lung cancer, possibly prostate and kidney cancer Exposure routes: Inhalation and ingestion 208
Salem Health: Cancer Where found: Food (particularly grain cereal products, potatoes, and other vegetables), cigarette smoke, zinc and lead ores, electroplating and -coating, alloys, pigments (paint, glass, ceramics, porcelain, textiles, plastics, paper, and fireworks), stabilizers in plastics, nickel-cadmium batteries, smoke detectors, radiation detectors, and various electronics and laboratory equipment At risk: Workers who refine and smelt zinc and lead ores, workers in industries using thermal processes (iron production or welding cadmium-coated steel), and tobacco smokers Etiology and symptoms of associated cancers: Cadmium exposure can be acute or chronic. Acute toxicity through ingestion of cadmium may cause only short-term illness, but acute toxicity through inhalation can lead to severe damage to the lungs and even death. Chronic exposure to cadmium can cause damage to the lungs, kidneys, and sometimes bones. Studies have shown that inhalation of cadmium in the workplace is associated with lung cancer. Laboratory studies using cultured cells have shown that cadmium damages the dexoyribonucleic acid (DNA) of the cells and affects the cells’ ability to repair DNAdamage. These factors are likely to be the mechanism through which cadmium contributes to the formation of cancer in humans. Lung cancer can affect one lung or both. Lung cancer detection often occurs when the disease has progressed to late stages because symptoms may take years to appear. When symptoms do appear, they often are mistaken for other less serious conditions. Common signs and symptoms of lung cancer are persistent cough (not related to smoking); persistent pain in the chest, shoulder, or back; coughing up mucus or blood; recurrent respiratory infections; shortness of breath; fatigue; unexplained weight loss; and loss of appetite. Many of these symptoms may be attributed initially to other causes before lung cancer is eventually diagnosed. Lung cancer is the only cancer that has been confirmed to be associated with cadmium exposure. Studies from the 1960’s and later have had conflicting results regarding a connection between cadmium and prostate cancer. A number of studies have shown increases in the occurrence of prostate cancer in workers exposed to cadmium in nickel-cadmium battery plants and other industrial sites, but conflicting studies have indicated no increases or increases that were too small to be statistically significant. Cadmium has also been implicated in kidney cancer, with early studies showing a correlation between exposure and increases in kidney cancer. However, further studies have not confirmed this association.
Salem Health: Cancer History: Industrial use of cadmium became widespread in the middle of the twentieth century, and the toxic effects due to occupational exposure began to be recognized by the early 1950’s. Studies that examined workers who had been exposed to high levels of cadmium were used to examine the toxic effects, and by the 1960’s researchers were investigating cadmium’s potential carcinogenicity. Experimental animal studies also were conducted to research the toxicity and carcinogenicity of cadmium. Regarding the role cadmium played in the development of lung cancer, initial studies were inconclusive or conflicting. Confounding factors, such as workers who were also tobacco smokers or were exposed to additional heavy metals, contributed to the confusing results. Because of its toxic effects, many federal, state, and local agencies, including the Environmental Protection Agency (EPA), began to regulate cadmium in a variety of ways, including stipulation of allowable amounts in air and water. In 1992 the Occupational Safety and Health Administration (OSHA) ruled on permissible exposure limits (PELs) for workers exposed to airborne cadmium in the workplace. By 2000 sufficient studies reported that cadmium contributed to the development of lung cancer for it to be designated as a known human carcinogen by the U.S Department of Health and Human Services. Michelle L. Herdman, Ph.D. u For Further Information Klaassen, Curtis D., ed. Casarett and Doull’s Toxicology: The Basic Science of Poisons. New York: McGrawHill, 2001. Silvera, S. A. N., and T. E. Rohan. “Trace Elements and Cancer Risk: A Review of the Epidemiologic Evidence.” Cancer Causes Control 18 (2007): 7-27. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Eleventh Report on Carcinogens. Research Triangle Park, N.C.: Author, 2005. Waisberg, M., P. Joseph, B. Hale, and D. Beyersmann. “Molecular and Cellular Mechanisms of Cadmium Carcinogenesis.” Toxicology 192 (2003): 95-117. u
Other Resources
Agency for Toxic Substances and Disease Registry http://www.atsdr.cdc.gov U.S. Department of Labor Occupational Safety and Health Administration http://www.osha.gov
Caffeine U.S Environmental Protection Agency http://www.epa.gov See also Chewing tobacco; Coke oven emissions; Free radicals; Kidney cancer; Nickel compounds and metallic nickel; Soots; Urinary system cancers.
u Caffeine Category: Lifestyle and prevention; carcinogens and suspected carcinogens ATC code: N06BC01 Also known as: Trimethylxanthine, coffeine, theine, mateine, guaranine, methyltheobromine Definition: Sometimes considered the most widely used drug in the world, caffeine is an alkaloid stimulant found naturally in coffee, tea, cocoa, and many carbonated drinks. Caffeine is a secondary metabolite substance that plants manufacture as a pesticide against insects and other invertebrates. Humans use the naturally bitter caffeine as a stimulant. Coffee, tea, and cocoa have become extraordinarily popular in most cultures of the world. In the United States, for example, it is estimated that 80 percent of adults drink either coffee or tea and over 70 percent of adults and children consume soft drinks that contain caffeine. Different studies support different arguments that caffeine has a positive or negative correlation with cancer. Related cancers: Skin cancer, breast cancer, colon cancer, rectal cancer, bladder cancer, kidney cancer, ovarian cancer, pancreatic cancer Delivery routes: Caffeine is most often ingested as a stimulant in coffee, tea, cocoa, chocolate, soft drinks, and “energy drinks.” Caffeine tablets are also taken orally as a stimulant. Caffeine is also an ingredient in certain nonprescription drugs designed to address colds, flu, headache, and pain, as well as preparations that function as stimulants to allow users to stay awake. How this drug works: Caffeine acts as a stimulant because it inhibits neurotransmitters that normally act as depressants. Specifically, caffeine occupies the neuron’s receptor sites for adenosine, which is a neuron inhibitor. Instead of being blocked and inhibited, the neuron remains active, thereby increasing neuron activity. Despite numerous studies, the relationships between caffeine intake and cancer risk remain inconclusive at best and contradictory at worst. Some studies show an inverse relationship between caffeine intake and cancer risk, while 209
Caffeine other studies suggest that caffeine increases the risk of certain cancers. Links between caffeine and cancer risk are based on the suggestion that caffeine and some of its metabolites can cause changes in cell reproduction that might enhance growth and proliferation, thereby increasing the growth and spread of cancerous cells that develop. Alternatively, other studies have suggested that caffeine and a related molecule called theophylline can block production of an enzyme that is crucial for cell growth, thereby inhibiting tumor proliferation. Studies at Rutgers University demonstrated that hairless mice treated with caffeine showed much greater resistance to skin tumors than untreated mice, but the experiment has yet to be conducted on human volunteers. Possibly the greatest concern is about a possible relationship between caffeine consumption and breast cancer incidence, with some studies suggesting that a combination of caffeine and methylxanthines showed positive correlation to breast cancer and other diseases of the mammary glands. For example, caffeine and methylxanthines (also found in coffee and tea) are associated with increased severity of fibrocystic breast disease, which may lead to the development of breast cancer, but this finding is contradicted by other studies, leading the American Cancer Institute to announce that there is no evidence between breast cancer and caffeine intake at any level. Although numerous studies have suggested a causal re-
Salem Health: Cancer lationship between coffee intake and pancreatic cancer, none so far has provided conclusive support. The relationship between caffeine and cancer is complex and remains unproven; both the International Agency for Research on Cancer and the American Cancer Society have concluded that there is no evidence that caffeine is carcinogenic. This verdict is echoed by the World Health Organization (WHO) and the Food and Drug Administration (FDA).
Side effects: In the short term caffeine increases attention span and simultaneously decreases the feeling of tiredness and weariness. Caffeine intake in children may cause hyperactive behavior. Caffeine can offset some of the effects of alcohol, but performance and coordination remain unaffected. Caffeine also increases plasma levels of fatty acids, cortisol, and epinephrine. Negative effects of excessive caffeine consumption vary with age, diet, and exercise levels. Generally, higher caffeine intake may elevate blood levels of sugars and fats, increase blood pressure, irritate the lining of the stomach, and cause heartburn, irregular heartbeat, irritability, nervousness, anxiety, depression, insomnia, and the disruption of sleeping habits. Excessive caffeine intake has also been linked to stroke and heart attack. The relationship between caffeine intake and heart problems is of great concern. Recent studies by the Adventist Health Study group reported finding a 50 percent increase in risk of serious heart disease, including heart palpitations and cardiac arrhythmias, both of which can lead to heart attacks. Other studies, however, have failed to demonstrate any relationship between coronary heart disease, stroke, and caffeine intake. Some researchers have also suggested a relationship between caffeine doses and the severity and duration of premenopausal syndrome (PMS) in females among heavy consumers of coffee, tea, and other fluids containing caffeine. Other studies have linked higher-thannormal caffeine consumption with lowered rates of conception, birth defects, retarded fetal growth, reduced birth weight, spontaneous abortion, premature delivery, and stillbirth. There is some evidence that caffeine intake by males prior to mating may result in significant fetal growth retardation, but this too remains problematic A cup of cappuccino contains the alkaloid stimulant known as caffeine. (©Draganr/ and awaits further study. While none of Dreamstime.com)
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Salem Health: Cancer these claims is absolute, women are advised not to consume caffeine while pregnant or planning on becoming pregnant, since blood levels of caffeine can be transferred through the placenta and can be metabolized by a developing fetus. Finally, high caffeine intake reduces the absorption of dietary iron by 40 to 60 percent and reduces calcium intake while simultaneously increasing the rate of calcium loss, all of which may lead to serious calcium imbalance in blood and body fluid levels. Dwight G. Smith, Ph.D. u For Further Information Gilbert, S. G. A Small Dose of Toxicology: The Health Effects of Common Chemicals. Boca Raton, Fla.: CRC Press, 2004. Porta, M., et al. “Coffee Drinking: The Rationale for Treating It as a Potential Effect Modifier of Carcinogenic Exposures.” European Journal of Epidemiology 18, no. 4 (2003): 289-298. Rowley, R., M. Zorch, and D. B. Leeper. “Effect of Caffeine on Radiation-Induced Mitotic Delay: Delayed Expression of G2 Arrest.” Radiation Research 97, no. 1 (January, 1984): 178-185. Waldren, C. A., and I. Rasko. “Caffeine Enhancement of X-Ray Killing in Cultured Human and Rodent Cells.” Radiation Research 73, no. 1 (January, 1978): 95-110.
See also Benign prostatic hyperplasia (BPH); Clinical breast exam (CBE); Diarrhea; Esophagitis; Fatigue; Fibrocystic breast changes; Gastric polyps; Gastrointestinal complications of cancer treatment; Green tea; Hot flashes; Nutrition and cancer prevention; Side effects.
u Calcifications of the breast Category: Diseases, symptoms, and conditions Also known as: Microcalcifications, macrocalcifications Related conditions: Hyperplasia, precancer of the duct, fibroadenoma Definition: Calcifications are calcium deposits in breast tissue, not detectable by touch but visible on mammograms as white spots. Macrocalcifications are large deposits, not indicative of cancer. Microcalcifications appear as tiny white specks on mammograms. Scattered throughout a mammogram, they are usually not cause for concern. They may indicate possible precancer when they appear in irregular patterns or are concentrated in one area of the breast.
Calcifications of the breast Risk factors: Macrocalcifications and 80 percent of microcalcifications are harmless. Women in their childbearing years are prone to microcalcifications. Etiology and the disease process: Macrocalcifications are related to changes in the breast due to inflammation, injury, or aging. Microcalcifications may appear in areas of rapidly dividing cells and therefore can indicate precancer. Incidence: Macrocalcifications occur in about half of women over age fifty and in about 1 in 10 women under the age of fifty. Microcalcifications are usually evident in women only during their childbearing years. Symptoms: No symptoms are associated with calcifications of either kind. Screening and diagnosis: Calcifications are visible only on radiologic images. Macrocalcifications are harmless and require no further attention. Doctors may order special magnified mammographic views of microcalcifications in clusters or in odd patterns. Generally a biopsy is not needed at the first appearance of suspect patterns. Doctors typically have the patient repeat the mammogram three to six months later. If the repeat mammogram does not exhibit any obvious changes in the pattern or number of microcalcifications, a regular schedule of mammograms is adequate to monitor further changes. If microcalcifications appear particularly suspect on first appearance or if changes are noted in the repeat mammogram, a core needle biopsy or a surgical biopsy can be done to rule out precancer. Treatment and therapy: If a patient has microcalcifications removed for biopsy that prove to be precancerous, she should be followed closely with regular mammograms to identify any future occurrences. Prognosis, prevention, and outcomes: Macrocalcifications and the majority of microcalcifications (80 percent) have no relation to cancer. If a precancerous area is identified in microcalcifications, it can be removed completely many years before it has a chance to develop into actual cancer, and the patient’s prognosis is excellent. Any other suspect microcalcifications should be removed fully and analyzed. Patients should be closely followed for the occurrence of new microcalcifications. After menopause, microcalcifications generally no longer occur. Charlotte Crowder, M.P.H., ELS See also Breast ultrasound; Ductogram; Fibroadenomas; Hormone replacement therapy (HRT); Lobular carcinoma in situ (LCIS); Microcalcifications; Tubular carcinomas; Wire localization. 211
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u Calcium Category: Lifestyle and prevention Also known as: Calcium carbonate, calcium citrate, calcium phosphate Definition: Calcium is the most abundant mineral in the body. About 1 percent of calcium is found circulating in the blood, while the remaining 99 percent is stored in bones and teeth. Calcium must be obtained from the diet. It is found primarily in dairy products and is sold as a dietary supplement. Cancers treated or prevented: Colorectal cancer, breast cancer Delivery routes: Oral tablet How this substance works: Circulating levels of calcium help control metabolic events such as muscle contraction and nerve impulse transmission. In healthy people, the amount of calcium in the blood is kept within narrow limits by hormonal regulation. Calcium also helps to build strong bones and delay bone loss caused by aging (osteoporosis). The United States Office of Internal Medicine has established a maximum safe intake level for calcium of 2,500 milligrams per day for persons over one year of age. Animal studies and several human observational and research studies have found that increased intake of calcium is protective against the development of colorectal cancer. The reason for this protective effect is not understood, and not all studies have found calcium to be protective against colorectal cancer. In 2007, the Women’s Health Initiative study of more than 36,000 women aged fifty to seventy-nine found no effect of calcium on the development of colorectal cancer. More research must be done on the relationship between cancer and calcium in different age and gender groups before drawing any firm conclusions. Animal studies have also suggested that calcium may protect against breast cancer. In 2007, a peer-reviewed study of 10,500 premenopausal women found that when the intakes of calcium and vitamin D were simultaneously increased for an extended period, the risk of developing breast cancer was reduced by almost one-third. This effect was not seen in postmenopausal women. Clinical trials examining the relationship between cancer and calcium are under way; information is available at http://www .clinicaltrials.gov. Side effects: Complicating the situation with calcium is evidence that increasing calcium intake in men in amounts ranging from 600 to 2,000 milligrams or more per day may 212
Salem Health: Cancer increase the risk of developing prostate cancer. This is not, however, a consistent finding, and more rigorous studies need to be done. Many tumors that invade bone release stored calcium and cause the blood level of calcium to increase independent of dietary intake. This condition, called hypercalcemia, is the most common life-threatening metabolic disorder associated with cancer. Martiscia Davidson, A.M. See also Bone scan; Breast cancers; Caffeine; Calcifications of the breast; Cartilage supplements; Chemoprevention; Colon polyps; Colorectal cancer; Ductogram; Fiber; Gastrointestinal cancers; Hypercalcemia; Kidney cancer; Microcalcifications; Nutrition and cancer prevention; Polyps.
u Cancell Category: Complementary and alternative therapies; chemotherapy and other drugs Also known as: Entelev, Sheridan’s Formula, Jim’s Juice, Canctron, JS-114, JS-101, 126-F Definition: Cancell (previously known as Entelev) is a controversial and unapproved therapy developed in the late 1930’s. Cancell is a combination of chemicals that is thought to kill cancer cells by affecting their cellular respiration and/or electrical voltage. No clinical trials using Cancell have been published in peer-reviewed journals, and in 1989, the U.S. Food and Drug Administration (FDA) declared it illegal for manufacturers to sell and/or transport Cancell across state lines. Cancers treated or prevented: The manufacturers claim that Cancell can treat all types of cancer; however, it is not approved by the FDA. Delivery routes: Cancell is in liquid form and has been taken by mouth, inserted into the rectum, or applied to the skin (on the wrist or ball of the foot). How this substance works: Cancell (then known as Entelev) was first envisioned in the late 1930’s by the biochemist James V. Sheridan. In 1984, Edward J. Sopcak began making Cancell. Sheridan believed that Cancell affects cellular respiration, a chemical process that uses oxygen and provides energy to a cell. He further speculated that cells which do not require oxygen for respiration are “primitive” and that these primitive cells may be recognized, attacked, and killed by the body’s immune system or through other processes. Accordingly, Sheridan be-
Salem Health: Cancer lieved that Cancell could change cancer cells to a primitive state. Similarly, Sopcak thought that Cancell affected the vibrational frequency and energy of cancer cells, which may disrupt cancer proteins and change cancer cells to primitive cells. In either theory, the hypothesis is that Cancell makes cancer cells become primitive, which would allow the body to get rid of them. Cancell contains various ingredients, including the chemicals inositol, nitric acid, sodium sulfite, potassium hydroxide, sulfuric acid, and catechol. Laboratory studies conducted by the National Cancer Institute (NCI) found that Cancell could not be taken safely by humans at doses high enough to kill cancer cells. Therefore, the NCI concluded that Cancell did not show sufficient anticancer activity to merit continuing the studies. Furthermore, no studies of Cancell (in either animals or humans) have been published in peer-reviewed scientific journals. Side effects: The main side effects of Cancell include tiredness during the first few weeks of treatment, as well as nausea and diarrhea. Elizabeth A. Manning, Ph.D. See also Essiac; Laetrile; Mistletoe; PC-SPES; Sun’s soup.
u Cancer biology Category: Cancer biology Definition: The transformation of a normal cell into a cancerous one is a complicated process consisting of multiple steps and many changes to the cell and its normal control mechanisms. The fact that most human cancers develop later in life reflects the time required for these changes to occur. These changes include the activation of oncogenes, the inactivation of tumor-suppressor genes, and acquisition of a cell’s ability to become immortal, to invade new tissues at distant locations, and to induce the formation of new blood vessels. Characteristics of human cancers: Mutations that are present in the germ cells (egg and sperm) can be passed to the next generation. Mutations that occur in any other cells of the body, called somatic mutations, may affect the cell or tissue in which they occur, but they will not be passed to the next generation. Both germ-line and somatic mutations can cause cancer; it is estimated that approximately 10 percent of cancers are caused by germ-line, or inherited, mutations. Tumors can be either benign (those that remain localized and noninvasive), malignant (those that invade the
Cancer biology basement membrane and underlying tissue), or metastatic (those that shed cells that seed tumors in other locations of the body). Progressive degrees of abnormality are observed in benign, malignant, and metastatic tumors, suggesting that cancer develops in a stepwise process. Cancers can arise in almost all tissue types in the body, although approximately 80 percent of human cancers arise from epithelial cells—those cells that cover internal and external surfaces of the body, including the linings of internal organs and glands. The incidence of many types of cancer varies worldwide, and epidemiologic studies show that environment is the largest factor in variations in cancer incidence from country to country. Indeed, a number of environment and lifestyle elements, tobacco smoking being the most obvious, are known to be strongly correlated with the incidence of certain types of cancer. In 1975, it was shown that many chemicals that are capable of causing mutations in deoxyribonucleic acid (DNA) are also capable of causing cancer in laboratory animals. Later research showed, however, that not all chemicals that cause cancer also cause mutations. Therefore, other mechanisms besides DNA mutation must be involved in at least some cancers. Gene expression and signaling pathways: For the cells of an organism’s various tissues (lung and bone, for example) to display complex, tissue-specific characteristics, large groups of genes must be coordinately expressed while other genes must be repressed. Specialized proteins known as transcription factors are responsible for achieving this coordinated expression. Transcription factors bind to specific DNA sequences in the control region of each gene. The transcription of most genes is controlled by the binding of several distinct transcription factors in the gene’s control region. A single transcription factor can affect the expression of multiple genes that contain its binding sequence in their control regions. In cancer cells, a defective transcription factor may affect the expression of multiple genes, the end result of which is to create a cancer cell from a normal cell. Normal cells within tissues and within an organism communicate with each other in a regulated fashion through a multitude of chemical signals and pathways. Disruption of these normal signaling pathways is an important component of the formation of cancer. In normal cells, signals are transmitted through the various pathways in a number of ways: by a change in the level of activity of signaling molecules by noncovalent modifications, changes in the concentration of a signaling molecule inside a cell, or the direction of signaling molecules to particular locations within the cell. 213
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Salem Health: Cancer surface to which growth factors bind; signal transducers, proteins that make up the signaling pathways between the growth factor receptor and the cell nucleus; and transcription factors.
Tumor-suppressor genes: The class of tumorsuppressor genes includes a large number of genes whose protein products are involved in a multitude of normal cellular functions that in some way regulate a cell’s division and reduce the chance that the cell will become cancerous. Tumor-suppressor genes in cancer cells are often inactivated through mutation or other mechanisms. An inherited increased risk of developing a specific type of cancer in some families is often the result of the presence of a defective tumor-suppressor gene. It is the loss of function of tumor-suppressor genes that can lead to cancer, in contrast to oncogenes, which have gained functions or lost the ability to be controlled in their mutant form. The protein product of a particularly important tumor-suppressor gene, called TP53, causes cessation of cell division and even programmed cell death (apoptosis) in normal cells if the process of cell division malfunctions. In this way the cell’s well-being is monitored, protecting the organism from the effects of runaway division of wayward cells by activating the apoptotic pathway in such Colon cancer under the microscope. (©Micro Discovery/Corbis) cells. Apoptosis is an orderly process in which the DNA of a cell is degraded and the cell itself fragmented into smaller pieces that are taken up by Oncogenes: Normal cells contain a class of genes innearby white blood cells whose job is to clean up such devolved in the regulation of growth and division called bris. Loss of the ability to undergo apoptosis allows cancer proto-oncogenes. A proto-oncogene can mutate into a vercells to survive a variety of environmental stresses and sigsion that is permanently activated and causes uncontrolled naling imbalances. The TP53 gene in the DNA of cancer cell division, one of the hallmarks of a cancer cell. The cells often carries mutations that cause it to malfunction; transformation of a proto-oncogene into an oncogene may more than 90 percent of small-cell lung cancers and more involve a change to the structure of the protein itself or an than 50 percent of breast and colon cancers have been increase in its expression. Achange involving the structure shown to be associated with mutant forms of TP53. of the protein itself may require only very small changes; Normal cells throughout the body grow and divide to in some cases a single base pair mutation is sufficient. A generate two daughter cells in a highly organized and conchange involving an increase in expression often occurs trolled series of events called the cell cycle. A subclass of through increasing the number of copies of the gene in the tumor-suppressor genes controls cell-cycle events in norDNA. There are several ways that amplification of a gene mal cells. Control mechanisms at various steps of the cell can occur: by enhanced replication of a chromosome segcycle function to ensure that a preceding step is completed ment that carries its DNAor by the breaking away of such a before the next step can begin. These control mechanisms are inactivated in many types of cancer cells, allowing chromosome segment to form a small chromosome-like them to divide in an unregulated fashion. A particularly particle that is capable of replicating independently. important tumor-suppressor gene in this class is the retinoScientists have identified more than one hundred oncoblastoma (RB1) gene. The protein product for which the genes. They include growth factors, proteins that signal a RB1 gene codes, pRb, is affected in most if not all types of cell to divide; growth factor receptors, proteins on the cell 214
Salem Health: Cancer human cancer cells. Loss of normal regulation of the signaling pathway of which pRb is a component leads to unrestrained cell proliferation. Cell immortalization: The ability of a cell to divide indefinitely, called cell immortalization, appears to be a characteristic of all cancer cells. This ability has been shown to be related to the structures of the ends of chromosomes, called telomeres, which are composed of several thousand repeats of a six-base-pair sequence element. Every time a cell duplicates its DNA, the telomeres are shortened by fifty to one hundred base pairs, with the result that normal cellular DNA has the capacity for a finite number of replications. The ability to indefinitely maintain telomere length has been observed in virtually all types of cancer cells, the majority of which accomplish this by increasing the expression of the enzyme, telomerase, which is responsible for synthesizing telomeres. Angiogenesis: All cells depend on the availability of oxygen and nutrients for their growth and survival. Virtually all cells in a tissue must be located close to a capillary blood vessel that can deliver nutrients and take away metabolic waste products. For a cancer cell to progress to a macroscopic tumor, it must acquire the ability to induce the formation of new blood vessels, a process called angiogenesis. In normal cells, various negative and positive signaling pathways control the angiogenic process. Cancer cells appear to induce angiogenesis in a number of steps that change the balance of angiogenesis inducers and inhibitors during tumor development. Metastasis: Most types of human cancer will at some point undergo metastasis, the process whereby new tumors are seeded at distant sites from the primary tumor. Metastases are responsible for approximately 90 percent of all cancer deaths. Metastasis involves tumor cells leaving the primary tumor, invading adjacent tissues, and from there traveling to sites where they are able to settle and start the growth of new tumors. The primary route of metastasis is through the circulatory system, although metastatic cancer cells may also spread through lymph ducts to lymph nodes. Sometimes cancer cells traveling through the circulation form small obstructions that lodge in the arterioles and capillaries of various tissues. Complex interactions between the metastasizing cell and the microenvironment of the host tissue in which it lands govern the process of invasion into the tissue and colonization to form a metastasis in a process that is not well understood. Cancer cells that metastasize do not appear to have undergone major changes in their DNA compared with other cells in the original tumor. However, cancer cells that pos-
Cancer biology sess metastatic potential have alterations in several classes of proteins involved in the attachment of cells to their surroundings in a tissue, which render them less able to form such attachments. Cancer cells with metastatic potential may also have an increased ability to degrade proteins in their immediate environment. Metastasizing cells from various types of cancers tend to spread preferentially to some organs; for instance, prostate and breast cancers have a strong tendency to metastasize to the bone marrow, and colon cancer has a strong tendency to metastasize to the liver. The reason for this phenomenon is not well understood. Genomic instability: It has been estimated that multiple genetic changes, perhaps five to seven, are needed for the development of a full-fledged human cancer. A normal cell has numerous control and repair mechanisms that ensure the fidelity of DNA replication and, therefore, that the occurrence of mutations is rare. Malfunctioning of components of these control and repair mechanisms, such as TP53, leads to the observed chromosomal instability and variability of cancer cells. Genetic instability is pervasive in human cancer cells, which commonly exhibit various types of aberrantly structured chromosomes: the loss of entire chromosomes, the presence of extra copies of chromosomes, or the fusion of part of one chromosome with part of another. These chromosomal abnormalities disrupt normal DNA sequence and arrangement and probably help explain how precancerous cells acquire the necessary mutations to render them cancerous. Jill Ferguson, Ph.D. u
For Further Information Hanahan, D., and R. A. Weinberg. “The Hallmarks of Cancer.” Cell 100 (2000): 57-70. Karp, Gerald. Cell and Molecular Biology. 4th ed. New York: John Wiley, 2004. Weinberg, Robert A. The Biology of Cancer. New York: Garland Science, 2007.
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Other Resources
Emory University CancerQuest: Important Tumor Suppressors http://www.cancerquest.org/index.cfm?page=52 Inside Cancer http://www.insidecancer.org National Cancer Institute Cancer Topics http://www.cancer.gov/cancertopics 215
Cancer care team See also Angiogenesis; BRAF gene; BRCA1 and BRCA2 genes; Carcinogens, known; Carcinogens, reasonably anticipated; Cyclin-dependent kinase inhibitor-2A (CDKN2A); Cytokines; Epidemiology of cancer; Estrogen receptor downregulator (ERD); Genetics of cancer; Human chorionic gonadotropin (HCG); Immune response to cancer; Mitochondrial DNA mutations; MLH1 gene; MSH genes; Mutagenesis and cancer; MYC oncogene; Oncogenes; Placental alkaline phosphatase (PALP); PMS genes; Proteomics and cancer research; RB1 gene; RhoGD12 gene; SCLC1 gene; TP53 protein; Tumor necrosis factor (TNF); Tumor-suppressor genes.
u Cancer care team Category: Medical specialties Definition: The cancer care team consists of all the allied health professionals who are involved in a patient’s cancer diagnosis, treatment, and recovery or end-of-life planning. The team can include others who are not health professionals but are nonetheless an important part of the team. These can include spiritual leaders, social workers, and volunteers who provide assistance with transportation or housekeeping, as well as any other people who provide support or care for the individual with cancer. Subspecialties: There is a nearly infinite number of subspecialists who make up the cancer care team. The most important member of the cancer care team is the patient, because this person has the ultimate say in what services and treatment are received. A family member or friend who provides day-to-day care throughout the duration of the cancer treatment and afterward may have no medical training but is nonetheless an integral part of the cancer care team. In addition, the team contains those medical professionals attempting to treat the cancer, such as medical or surgical oncologists, and those whose main function is to help the patient live more fully or more comfortably, such as physical and occupational therapists, psychological counselors, and nutritionists. Also in the team are those whose primary function is to provide emotional support or generalized help for the patient and family, such as social workers, clergy members, and volunteers who provide transportation, help with meals, or simply companionship. Cancers treated: All types of cancer are treated by a cancer care team. The type of cancer the individual has and the planned treatment affect which professionals will be members of the team. The outcome of the cancer treatment 216
Salem Health: Cancer can also determine which professionals are part of the cancer care team. An individual diagnosed with a cancer that is in an early stage and is likely to go into remission probably will be involved with team members to help with the recovery process, such as occupational and physical therapists. An individual diagnosed with a cancer with a high mortality rate that has already spread significantly is likely to have a cancer care team that includes individuals trained in palliative care and end-of-life planning, such as hospice workers and financial planners. Training and certification: The training and certification required to be a member of the cancer care team depends on the role of the team member. A surgical oncologist requires an undergraduate degree, a medical degree, a long surgical residency, and additional surgical oncological training. Depending on the level of care nurses are allowed to provide, they may require various levels of training, including a master’s or doctoral degree. Psychological counselors or therapists usually are required to complete a master’s or doctoral level program. Assistants who are specialists in running certain types of machinery or equipment or assisting other health care professionals may have an associate degree or have completed a special certificate program. Some members of the cancer care team who assist with functions such as changing linens or retrieving necessary items may have received all of their training on the job. Services and procedures performed: The cancer care team sees the patient through the entirety of the cancer care process, from diagnosis and treatment to recovery or endof-life planning. The first member of the cancer care team that an individual usually sees is a general practice physician, gynecologist, dermatologist, or other doctor who determines that cancer is possibly present. At that point the member of the cancer care team who is seen next depends on the type of cancer suspected. A person might next see a radiological technologist who will take X rays or other images and submit them to the radiologist for reading. The person might instead see a technician who takes a biopsy sample of the lump if it is breast cancer that is suspected. If a biopsy or other sample is done, then the next member of the cancer care team may be the pathologist, who will do laboratory tests to determine whether cancer is present and, if so, which type of cells it contains. Once a diagnosis of cancer has been made, then the cancer care team expands dramatically. Often the team includes a case manager, who will coordinate all aspects of a patient’s care. The case manager may work with the patient’s primary physician, the primary oncologist, nurses,
Salem Health: Cancer pharmacists, and other professionals who are providing care to the patient. This way, one person knows everything that is going on and can help ensure that nothing is being missed or done unnecessarily. The case manager may even help with scheduling appointments and may be able to recommend people such as social workers to assist the patient. The team may also contain a social worker who is specially trained in helping cancer patients. The social worker can provide information about services available to the cancer patient and help with government paperwork and other issues that are often present during cancer care. The actual medical treatment for the cancer may be provided by a large number of oncologists with different specialties. Each of these oncologists works with a staff of medical professionals to help provide care. All these people are important members of the cancer care team, including any assistants or technicians who may help the patient get ready for procedures or teach them about proper selfcare for afterward. Although many members of the cancer care team are focused on trying to cure the cancer, other members of the
Cancer care team team are primarily interested in helping the patient maintain as good a standard of living and degree of independence as possible throughout the treatment and afterward. Physical and occupational therapists can help patients regain lost skills or mobility and help patients plan for the challenges of treatment, such as by teaching them energy conservation techniques to use while receiving chemotherapy treatments. A nutritionist can ensure that the patient gets all the required vitamins and nutrients during treatment and can help the patient work through issues such as weight loss or gain. If the cancer treatment is not successful, professionals can help patients and their families and friends with palliative care and end-of-life planning. These are important members of the cancer care team, even though trying to cure the cancer is not their goal. If the patient chooses hospice care, doctors and nurses who are specially trained in providing end-of-life care and comfort will become important members of the team. Financial planners, lawyers, and others can help the family ensure that all the cancer patient’s wishes will be carried out. Special bereavement
Many different health care professionals are part of the cancer care team. (Digital Stock)
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Cancer clusters counselors can also be part of the team to help the family make the most of the time that is left. Related specialties and subspecialties: There are many related specialties and subspecialties that provide support for the cancer care team. These include technicians who operate or service necessary machinery and equipment, technicians, schedulers and office staff, record keepers, and insurance liaisons. Helen Davidson, B.A. u For Further Information Corner, Jessica, and Christopher Bailey, eds. Cancer Nursing: Care in Context. Malden, Mass.: Blackwell, 2008. Hamilton, William, and Tim J. Peters. Cancer Diagnosis in Primary Care. New York: Churchill Livingstone/ Elsevier, 2007. Lyons, Lyman. Diagnosis and Treatment of Cancer. New York: Chelsea House, 2007. Nakamura, Robert M., et al., eds. Cancer Diagnostics: Current and Future Trends. Totowa, N.J.: Humana Press, 2004. u
Organizations and Professional Societies
American Society of Clinical Oncology http://www.asco.org 1900 Duke Street, Suite 200 Alexandria, VA 22314 Society of Surgical Oncology http://www.surgonc.org 85 West Algonquin Road, Suite 550 Arlington Heights, IL 60005 u
Other Resources
American Cancer Society http://www.cancer.org National Cancer Institute http://www.cancer.gov See also Cancer education; Caregivers and caregiving; Case management; Counseling for cancer patients and survivors; End-of-life care; Genetic counseling; Home health services; Hospice care; Living with cancer; Longdistance caregiving; Medical oncology; Oncology; Oncology clinical nurse specialist; Oncology social worker; Primary care physician; Psycho-oncology; Psychosocial aspects of cancer; Radiation oncology; Relationships; Second opinions; Support groups; Surgical oncology. 218
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u Cancer clusters Category: Social and personal issues Definition: A cancer cluster is a significantly higher than expected number of cases of cancer in a certain group, area, or time period. Identifying a possible cancer cluster: Cancer is a very common disease. The United States Centers for Disease Control and Prevention (CDC) estimate that about one in every three Americans will develop cancer at some point during his or her lifetime. With a disease as common as cancer, it is not unusual for two friends, coworkers, or neighbors to be diagnosed with the same kind of cancer or to be diagnosed at similar times. However, sometimes it may seem like more than just a normal coincidence. Sometimes it may seem as if many people in the same workplace, neighborhood, or family are being diagnosed with cancer. In these cases, a cancer cluster may exist. Many suspected cancer clusters are reported each year. According to the American Cancer Society, as of 2006 more than one thousand reports of suspected cancer clusters were being made to state health agencies every year. The vast majority of these suspected cancer clusters turn out not to be true cancer clusters after careful investigation and statistical analysis. For many of the clusters that are believed to be true cancer clusters, an underlying cancer agent is never satisfactorily identified. However, in some cases, a cancer cluster is identified and an environmental or other agent is found to be responsible. This is one way that substances can be identified as causing an increased risk of cancer. Just having a group of people who all seem to have been diagnosed with cancer at a similar time or who have a similar type of cancer is not enough to indicate that a true cancer cluster exists. A group of cancer cases is more likely to be a cancer cluster if one or more of certain factors exist. It is more likely to be a true cancer cluster if there is only one primary diagnosis of cancer involved and the cancer is an uncommon one. According to the American Cancer Society, it is estimated that more than 170,000 new cases of breast cancer were diagnosed in the United States in 2007. Therefore, if ten women in the same moderately sized town were diagnosed with breast cancer, it would be unlikely to indicate a cancer cluster, but if the same number of women were diagnosed with an extremely rare form of cancer, a cancer cluster might be more likely. If a very large number of cases of a common form of cancer occur, this may be a possible indication of a cancer cluster. Additionally, if cancer occurs in a particular group of people in whom it is not usually seen, such as breast can-
Salem Health: Cancer cer in men, or a type of cancer that usually develops in adults is diagnosed in children, it may be a sign of a possible cancer cluster. If a set of people who share a welldefined characteristic, such as all working in the same factory over the same period of time, are involved in the suspected cluster, it is generally more likely to be a true cancer cluster than if the suspected cancer cluster involves people who do not share a very specific common trait. Investigating a suspected cancer cluster: When a cancer cluster is suspected, it is usually reported to a state board of health or to a state cancer registry. Cancer registries collect information about cancer occurrences and cancer-related mortality statistics. Anyone can report a suspected cancer cluster; it does not have to be reported by a government employee or by a doctor or other health professional. Once a suspected cancer cluster has been reported, the state health department or other agency will collect information about the people in the suspected cluster. This will include information about the age and ethnic background of the people involved, the type or types of cancers, the places in which the individuals have lived and worked, the time period during which the cancers occurred, specific medical information about the cancers, and any other available information. The health agency will also try to gather information about what possible causes for the cancers exist, such as if there are any known or suspected carcinogens in the places in which the affected people work or live. They may also collect information about any other possible causes of the cancer, such as a history of smoking. After analyzing all the gathered information, experts at the health agency will decide if there is reason to suspect that a true cancer cluster exists. According to the American Cancer Society, four out of five of all reported possible cancer clusters are determined not to be true clusters based on preliminary information. This is because often what may seem like a large number of cases of cancer is still within reasonable expectations given the population and other variables. One of the ways that experts can determine whether it is possible that the group of cancers constitute a true cancer cluster is by doing statistical analysis to determine if the number of cancers is statistically significant. A group of cancers is statistically significant if it is more than the number of cancers that are expected to occur in the group by chance. In most cases, 5 percent is considered the benchmark to determine if something is statistically significant. This means that out of one hundred towns of the same size and population, for example, the number of cancers seen in the town in question would occur in five or fewer of the towns by chance alone. If it is determined that there may be a true cancer clus-
Cancer clusters ter, the state health agency, scientists, medical professionals, and sometimes federal agencies such as the CDC will begin to investigate in more depth. This may involve getting detailed medical records and histories, interviewing people in the area in question, and testing possible sources of carcinogens. It is usually a very time-consuming, manpower-draining, and money-intensive investigation. Once all the evidence has been gathered, experts try to determine if there is a true cancer cluster and what caused the cluster. Unfortunately, in many cases, it is never possible to determine a definite cause. This is because the factors that cause cancer are complex and interactive, and cancer may not be diagnosed for ten or more years after exposure to the believed carcinogen. Historic cancer clusters: Several well-known cancer clusters have been documented in the United States since the 1960’s. In some cases these clusters were linked to environmental toxins, such as toxic waste spills, and in other cases they have been linked to workplace-related exposures. Some cancer clusters have even helped identify substances that are carcinogenic that were not formerly known to be harmful. Possibly the most famous cancer cluster is the cluster in Hinkley, California, which was the basis for the film Erin Brockovich (2000). The cause believed to be at the root of the town’s problems was chromium-6 that had been dumped into unlined ponds by the Pacific Gas and Electric plant near the town. The chromuim-6 was believed to have leached out of the ponds and into the ground and drinking water of the residents of Hinkley. Another well-known cancer cluster was in Toms River, New Jersey. In Toms River, 118 children were found to have cancer between 1979 and 1995, far more than could be reasonably attributed to chance for that population. Investigations found that 4,500 barrels of toxic waste had been dumped at a landfill and much of the toxic waste had leached into the Toms River water supply. In the 1960’s, a very high number of cases of mesothelioma were found and were determined to have been caused by prolonged exposure to asbestos. At the time, asbestos was used frequently in consumer products and in shipbuilding. The discovery of the cancer cluster and the subsequent discovery of its cause led to a drastic change in the way asbestos is handled, its removal from schools and other public places, and the development of safe handling practices and alternative technologies. Without someone noticing and reporting the high incidence of mesothelioma, many more people might have been harmed by asbestos exposure. Helen Davidson, B.A. 219
Cancer education u For Further Information Carcinogens. Davenport, Iowa: Mangan Communications, 2007. Carney, Jan K. Public Health in Action: Practicing in the Real World. Sudbury, Mass.: Jones and Bartlett, 2006. Duffy, Jim. “Cancer Clusters.” Ecologist 37, no. 5 (June, 2007): 9-18. Greenberg, Michael R. Environmental Policy Analysis and Practice. New Brunswick, N.J.: Rutgers University Press, 2007. u
Other Resources
Centers for Disease Control and Prevention Cancer Clusters http://www.cdc.gov/nceh/clusters National Cancer Institute Cancer Clusters http://www.cancer.gov/cancertopics/factsheet/risk/ clusters See also African Americans and cancer; Africans and cancer; Ashkenazi Jews and cancer; Asian Americans and cancer; Ethnicity and cancer; Geography and cancer; Latinos/Hispanics and cancer; Mesothelioma; Native North Americans and cancer; Occupational exposures and cancer; Poverty and cancer; Statistics of cancer.
u Cancer education Category: Medical specialties Also known as: Health education, patient education, cancer study and teaching Definition: Cancer education involves the creation and distribution of information to teach health professionals by assisting their study and advancement of oncology procedures and enhancing their teaching of patients, the public, and peers. Cancer educators emphasize prevention, detection, and treatment methods to control cancers. Subspecialties: An interdisciplinary effort, cancer education encompasses diverse specialties, including oncology, nursing, pediatrics, dentistry, pharmacy, dietetics, genetic counseling, physical therapy, occupational therapy, psychology, physician assistance, and social work. Cancers treated: Cancer education addresses all known cancers, focusing on commonly occurring cancers, particularly breast, prostate, and colon cancers, which medical professionals frequently diagnose in patients. Interna220
Salem Health: Cancer tionally, medical, dental, and nursing schools educate students regarding cancers they will probably encounter in their residencies and practices. Graduate medical students obtain advanced cancer education according to specialties they pursue in their training and research. Training and certification: Cancer educators often receive basic training for educational procedures as part of health-related degrees they earn. The American Association for Cancer Education (AACE) offers workshops and clinics at its annual conferences, during which participants can acquire skills and learn developments in cancer education research and practices to earn credits and certificates acknowledging they participated in those educational experiences. The American Cancer Society (ACS) and Oncology Nursing Society present continuing education opportunities for cancer educators to complete specific training to learn methods and strategies for more effective cancer education services for patients and their caregivers. Services and procedures performed: Cancer education experts instruct medical professionals while they attend school and throughout their careers concerning methods to diagnose cancers in patients and to determine which treatments to recommend. Governments, academic institutions, and such groups as the American Cancer Society fund research to enhance educational opportunities for physicians and health professionals to provide suitable, up-to-date medical care for cancer patients. Professional and licensing organizations such as the American College of Surgeons offer resources in their educational departments. The American Association for Cancer Education and European Association for Cancer Education reinforce their members’ educational and teaching skills in medical and dental colleges, hospitals, and other forums by offering information in such specific areas of cancer education as oral oncology and palliative care and by encouraging continued training in cancer education. Those professional organizations collaboratively publish The Journal of Cancer Education, which contains news and articles evaluating cancer education techniques, communication, and research. Representatives of the American Association for Cancer Education survey cancer education taught at U.S. medical and dental schools to evaluate the curricula offered and offer insights regarding what cancer education should address in schools. Health professionals supply information to assist people in acquiring knowledge to prevent or mitigate cancer through informed decisions, early detection of symptoms, and the choice of effective treatments. Cancer educators inform both children and adults in their communities re-
Salem Health: Cancer garding cancer issues. Educators present cancer prevention information at schools and workplaces, advising healthy nutrition and behaviors to minimize risks associated with cancer. Cancer educators convey information concerning genetic testing for potentially inherited cancer vulnerabilities. Medical personnel realize cancer education counters misinformation and enables better medical care, helping adjust perceptions concerning cancer by explaining that many cancers are treatable, not terminal. Cancer educators create and distribute accessible information, assessing literacy and cultural factors to achieve effective communication. Educators evaluate attitudes regarding cancer in individual patients and their caregivers to determine the specific educational materials, ranging from pamphlets to videotapes and Internet resources, most likely to assist them. Cancer educators assist comprehension of information to ease physical and emotional aspects of cancer by explaining tests, procedures, medications, and side effects. Many hospitals and cancer centers maintain cancer education information in health libraries and learning centers with education personnel designated to administer those resources. Cancer groups, hospitals, and drug manufacturers publish educational material to assist cancer educators to learn about new treatments and pharmaceuticals. The American Cancer Society has pursued education through media, a Facts About Cancer pamphlet, lists of seven basic cancer symptoms, and educational guides devoted to specific cancers. The National Cancer Institute (NCI) contributes to cancer education by helping both health provider educators and people seeking cancer information. The institute published the Trainer’s Guide for Cancer Education (2005) and established a Cancer Information Service and an Office of Cancer Communications. The NCI Patient Education Branch created the Cancer Patient Education Network. The Wellness Community also provides cancer education resources. Elizabeth D. Schafer, Ph.D.
Candidiasis don. Patient Education in Health and Illness. 5th ed. Philadelphia: Lippincott Williams & Wilkins, 2005. Saca-Hazboun, Hanan. “Empowering Patients with Knowledge: An Update on Trends in Patient Education.” ONS Connect 22, no. 5 (May, 2007): 8-12. Varricchio, Claudette, et al., eds. A Cancer Source Book for Nurses. 8th ed. Sudbury, Mass.: Jones and Bartlett, 2004. Wilkes, Gail M., and Terri B. Ades. Patient Education Guide to Oncology Drugs. 2d ed. Sudbury, Mass.: Jones and Bartlett, 2004. u
Organizations and Professional Societies
American Association for Cancer Education http://www.aaceonline.com 620 Walnut Street 330 WARF Building Madison, WI 53726 European Association for Cancer Education http://www.eaceonline.com Academie Gezondheidzorg Saxion Hogescholen Postbus 70.000 7500 KB Enschede The Netherlands u
Other Resources
Cancer Patient Education Network http://www.cancerpatienteducation.org The Wellness Community http://www.thewellnesscommunity.org See also Cancer care team; Caregivers and caregiving; Case management; Clinical trials; Counseling for cancer patients and survivors; Family history and risk assessment; Genetic counseling; Primary care physician; Psychosocial aspects of cancer; Second opinions; Support groups.
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For Further Information Labus, James B., and Alison A. Lauber. Patient Education and Preventative Medicine. Philadelphia: W. B. Saunders, 2001. National Cancer Institute. Trainer’s Guide for Cancer Education. Bethesda, Md.: National Institutes of Health, National Cancer Institute, 2005. Osborne, Helen. Health Literacy from A to Z: Practical Ways to Communicate Your Health Message. Sudbury, Mass.: Jones and Bartlett, 2005. Rankin, Sally H., Karen Duffy Stallings, and Fran Lon-
u Candidiasis Category: Diseases, symptoms, and conditions Also known as: Thrush, yeast infection, fungal infection Related conditions: Fever, infections, and sepsis in cancer treatment Definition: Candida species are fungi that are found as part of the normal flora in humans and are also major hu221
Candidiasis
Salem Health: Cancer
pases) can alter protective mucous membranes, allowing penetration into the tissues beneath. The cell wall of Candida species is made up of beta-glucans, mannoproteins, and chitins (carbohydrates). Different growth conditions can result in changes in cell-wall components that drastically alter the morphology. Outside the body and on mucosal surfaces, Candida species exist as yeasts (round or oval, single-celled organisms). When tissues are invaded, the amount of cell-wall chitin is increased, and mycelia (long filaments) are formed rather than yeasts. This phenomenon is called dimorphism and may make the organism more challenging for the immune system. Formation of finger-like projections from yeast cells (pseudohyphae) seems to be imporCandidiasis in the mouth. (Custom Medical Stock Photo) tant in penetration into host cells. These and other candida virulence factors are man pathogens. The diseases caused by Candida species important contributors to disease causation, but it is the are termed candidiasis. impaired immune system of the host that usually tips the balance. Risk factors: Candida colonization increases after antibiotic (antibacterial) therapy, and the broader the spectrum Incidence: Autopsies of leukemia patients reveal dissemiof antibacterial therapy, the greater the growth. Cancer nated candidiasis involving major organs in 20 to 33 persurgery, particularly if it involves the gastrointestinal (incent of cases. Bloodstream invasion has been documented cluding oral) or female genital tract, can allow candida in more than 10 percent of patients with leukemia and present in the normal flora of these areas to enter into the about 1 percent of patients with lymphoma. The incidence previously protected underlying tissues. Cancer chemois lower in patients with solid tumors and in children. therapy can impair the immune system by decreasing the Symptoms: Symptoms can be quite varied, as many difproduction of white blood cells by the bone marrow. When ferent areas of the body and organs can be infected. Oral corticosteroids are used as part of the cancer chemotherdiscomfort and swallowing pain and difficulty may acapy, both neutrophil and lymphocyte function is impaired. company oral and esophageal candidiasis. Abdominal Radiation can damage mucous membranes and, in some pain can occur with stomach and intestinal ulcerations cases, the bone marrow as well. Vascular catheters used to caused by candida in cancer patients. Vaginal discharge administer cancer chemotherapy and other drugs are freand itching is often associated with candida vaginitis. quently ports of entry for candida. Urinary and gastroinEndophthalmitis can cause blurred vision. Infected petestinal catheters can also assist invading organisms. ripheral and central intravascular catheters may have minLeukemias, lymphomas, and bone marrow metastases can imal symptoms heralding the underlying suppurative result in diminished numbers of the normally functioning thrombophlebitis. However, the most common symptom neutrophils and lymphocytes essential to fight invading or sign of candidiasis, especially disseminated, is fever. organisms. Etiology and the disease process: Candida species are commensal organisms and are found as part of the normal human flora because of their ability to adhere to and persist on mucosal surfaces. It is only when this natural balance is upset that these opportunistic pathogens cause disease. Candidal organisms possess a number of virulence factors. Production of hydrolytic enzymes (proteinases and li222
Screening and diagnosis: The diagnosis of candidiasis may be presumptively made by physical examination of the cancer patient. Examination of the skin and oral cavity for plaques, ulcers, and erythema may be revealing. Candida endophthalmitis, resulting from bloodstream infection, is strongly suspected when characteristic cottonwool lesions are observed on ophthalmoscopic examina-
Salem Health: Cancer
Carcinoembryonic antigen antibody (CEA) test
tion of the retina. A new heart murmur may be the result of candida endocarditis associated with vascular catheter infection. Rales and decreased breath sounds may be present during candida pneumonia. Intraluminal urine seen in indwelling urinary catheters is frequently cloudy with white fluffy debris when urinary candida infection occurs. Intravascular catheter sites may reveal erythema, induration, or purulent drainage, but these signs can be subtle or absent in the neutropenic patient. Endoscopic examination can be helpful with gastrointestinal candidiasis, particularly esophagitis. Computed tomography (CT) and magnetic resonance imaging (MRI) scans of the abdomen can demonstrate abscesses. Blood tests for candida antigens, beta-glucan, and polymerase chain reaction (PCR) may provide a specific diagnosis. Microscopic examination of urine and tissue biopsies is also helpful. Culture of blood, urine, tissue biopsies, and the like provides specific diagnostic information, and the cultured Candida can be speciated and tested for susceptibility to antifungal agents.
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Treatment and therapy: The relatively nontoxic azole and echinocandin antifungals are most often used to treat candidiasis. Amphotericin B has long been standard therapy for invasive candidiasis, but the comparatively high toxicities have limited its use to refractory or resistant cases. If candida has been cultured, then fungal susceptibilities can be used to guide therapy. It is important to begin therapy as early as possible to achieve the best outcome, and this mandates that therapy be commenced in high-risk cancer patients before the availability of diagnostic studies if candidiasis is suspected. Adjunctive measures are also important. Vascular, gastrointestinal, or urinary catheters should be removed if possible. Immune function must be optimized. Colony-stimulating factors can increase neutrophil numbers in the neutropenic cancer patient.
See also Antifungal therapies; Fever; Gastrointestinal complications of cancer treatment; Taste alteration.
Prognosis, prevention, and outcomes: Disseminated candidiasis with candidemia in cancer patients has a crude mortality rate of 70 to 75 percent with an excess mortality rate of about 40 percent. Without treatment survival rates are less than 5 percent. Prevention is best accomplished by reducing the risk factors for infection. Removing catheters promptly, treating neutropenia, and using antibacterials only when absolutely necessary are all beneficial. Antifungal prophylaxis has been shown to reduce the incidence of candidiasis in cancer patients with neutropenia and also in patients for whom treatment has included bone marrow or solid organ transplantation. H. Bradford Hawley, M.D.
For Further Information Bodey, Gerald P., ed. Candidiasis. 2d ed. New York: Raven Press, 1993. Ostrosky-Zeichner, Luis, et al. “Deeply Invasive Candidiasis.” Infectious Disease Clinics of North America 16 (2002): 821-835. Pappas, Peter G., et al. “Guidelines for Treatment of Candidiasis.” Clinical Infectious Diseases 38 (2004): 161189.
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Other Resources
Centers for Disease Control and Prevention Candidiasis http://www.cdc.gov/nczved/dfbmd/disease_listing/ candidiasis_gi.html Mycology Online Candidiasis http://www.mycology.adelaide.edu.au/Mycoses/ Cutaneous/Candidiasis/
u Carcinoembryonic antigen
antibody (CEA) test Category: Procedures Also known as: Carcinoembryonic antigen antibody test Definition: Carcinoembryonic antigen antibody (CEA) tests are used primarily to monitor cancer patients to determine whether their disease is recurring and, if so, its stage and extent. CEAis a tumor marker, because anti-CEAantibodies bind to epitopes on carcinoembryonic antigens, allowing CEA quantification in body fluids (primarily serum) and CEA detection on cells or tissue sections by immunostaining. Cancers diagnosed: Primarily colorectal and gastrointestinal cancers, as well as cancers of the rectum, lung, breast, liver, pancreas, stomach, and ovaries Why performed: Anti-CEA antibodies are primarily used in the diagnosis of colorectal cancer; they are not recommended for cancer screening, but preoperative determination may assist in staging and surgical treatment planning. After treatment, anti-CEA antibodies may detect recurrence earlier than other techniques. Anti-CEA antibodies are also informative in lung, liver, breast, ovarian, stomach, and pancreatic cancers as they provide prognostic in223
Carcinogens, known formation. Anti-CEA antibodies can also be evaluated in urine (bladder cancer), bronchial lavage fluid (lung cancer), or cerebrospinal fluid (brain tumors) to improve diagnostic accuracy. Patient preparation: No preparation on the part of the patient is necessary. Steps of the procedure: The procedure involves a simple blood test and so consists only of the drawing of a blood sample from the patient. When anti-CEA antibodies are used for quantitative determination of CEA in body fluids, a typical solid-phase immunoassay protocol is used. This involves addition of the standards and samples to wells or beads with an adsorbed monoclonal anti-CEA antibody to “catch” and immobilize CEA by high-affinity binding to one of CEA’s epitopes. After incubation and washing steps, a second, enzyme-conjugated monoclonal antiCEA antibody against a different CEA epitope is added. CEA present in the specimen is “sandwiched” between the two different antibodies and serves to bind the enzyme to the well or bead. After washing, colorigenic substrate is added. The rate of color development indicates the activity of the antibody-conjugated enzyme, which is used to infer the CEA concentration in the sample by comparison with known standards. When anti-CEA antibodies are used to semiquantitatively visualize CEA in immunostaining procedures, the cells or tissues are typically fixed and embedded in paraffin, then sectioned onto glass slides for staining and conventional microscopy. Polyclonal anti-CEA antibodies may be chosen for immunostaining to improve sensitivity. After the procedure: No special care is needed other than to keep the area of the needlestick clean until it is healed, in order to avoid infection. Risks: No physical risks or side effects accompany a CEA test, although caution must be used in interpreting results. The CEA test itself poses no risk to the patient. Test results must not be interpreted in isolation to avoid overtreatment or undertreatment. Results: Standard levels have not been established for CEA tests and vary depending on the patient’s age and condition as well as testing methods. Anti-CEA-based assays of CEAin body fluids are difficult to interpret in isolation; serial measurements usually are inspected for recognizable patterns that indicate response to therapy, lack of response to therapy, or recurrence of disease. Because of heterogeneity among anti-CEA antibodies, the same reagents and methods should be used during longitudinal monitoring. In immunostaining procedures, many anti224
Salem Health: Cancer CEA antibodies recognize antigens shared by members of the CEA family of glycoproteins, resulting in extensive background staining. In particular, cells from the liver and gallbladder often react with anti-CEA antibodies because they contain biliary glycoprotein. Each test report should include a reference range and be interpreted by the consulting physician. In general, patients with early-stage, small tumors may have low, even normal, CEA levels; later-stage and metastatic disease may yield initially high CEA levels. A subsequent lower CEA level usually indicates reduced tumor activity, whereas a CEA level that rises over time may indicate tumor recurrence. John B. Welsh, M.D., Ph.D. See also Bile duct cancer; Colorectal cancer; Malignant tumors; Pathology; Placental alkaline phosphatase (PALP); Tumor markers.
u Carcinogens, known Category: Carcinogens and suspected carcinogens Definition: A carcinogen is any substance that causes cancer. A “known” human carcinogen is a chemical compound identified by the National Toxicology Program of the U.S. Department of Health and Human Services as displaying “sufficient evidence of carcinogenicity in humans [to indicate] a causal relationship between exposure to the agent, substance, or mixture and human cancer.” Chemicals and cancer: Certain chemicals are capable of causing cells in an organ of the body to grow uncontrollably. As early as a century ago, scientists knew of malignant growths produced by exposure to particular chemicals. The National Toxicology Program (NTP) produces a biennial Report on Carcinogens (RoC), which deals with carcinogenic compounds in humans, potential human exposure to these substances, and federal regulations of exposure limits to the chemicals. The introduction to the report defines a known carcinogen as a chemical for which there is sufficient evidence indicating a causal relationship between exposure and human cancer. Definitive data on carcinogenicity is difficult to obtain, because there often is a need for multiple exposures to the substance and a long induction period before a tumor appears. Genetics, lifestyle, and ethnic factors are also important in the development of certain tumors. The National Toxicology Program employs a variety of approaches but considers two-year studies in rodents to be its primary method of determining what substances are carcinogens.
Salem Health: Cancer
Carcinogens, known
Development of cancer: Cancers seem to develop in stages showing substantial overlap and not progressing uniformly. Much research on the initiation stage has been devoted to the study of changes in deoxyribonucleic acid (DNA). Many carcinogenic chemicals have been shown to cause mutations. Bonding to a strand of DNA produces a mutation that might be replicated before it can be repaired. Such an error might be passed along to future generations. Most such mutations do not affect the cell, but if a protein associated with growth is involved, it might create the potential for future rapid cell growth. It is also believed that reactions between potential carcinogens and DNA do not occur in a random process but rather in the production of genes. The way in which the promotion stage of cancer development proceeds is still obscure, but the nature of promoting substances provides clues. These compounds are believed to stimulate the production of multiple benign tumors. Their effect is reversible; with their withdrawal,
the tumor disappears. They are, however, not able to produce the cancer by themselves. At some point in the progression stage, another genetic change occurs that results in a selective growth advantage for the mutant cell. There are several ways in which such an event might take place: additional exposures to the original carcinogen, spontaneous mutation from replication enzymes, or changes in the genes caused by initiating mutations. The result is an irreversible change in the cell. The malignant conversion stage produces a distinct growth advantage for the affected cell. There is evidence from rodent studies that genetics is an important factor in these late-stage changes as well as in the early development of the cancer. Experiments reveal protein synthesis, amplification of gene creation, and further DNA reactions at this stage in the tumor cell. Testing for carcinogens: In testing to determine whether a substance is a carcinogen, scientists use animal testing
Known Human Carcinogens
• • • • • • • • • • • • • • • • • • • • • • • •
Aflatoxins Alcoholic beverage consumption 4-Aminobiphenyl Arsenic compounds, inorganic Asbestos Azathioprine Benzene Benzidine and dyes metabolized to benzidine Beryllium and beryllium compounds 1,3-Butadiene 1,4-Butanediol dimethylsulfonate (Myleran) Cadmium and cadmium compounds Chlorambucil 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (MeCCNU) bis(Chloromethyl) ether and technical-grade chloromethyl methyl ether Chromium hexavalent compounds Coal tars and coal tar pitches Coke oven emissions Cyclophosphamide Cyclosporin A Diethylstilbestrol Erionite Estrogens, steroidal Ethylene oxide
• • • • • • • • • • • • • • • • • • • • •
Hepatitis B virus Hepatitis C virus Human papillomaviruses: some genital-mucosal types Ionizing radiation: X radiation and gamma radiation, neutrons, radon, thorium dioxide Melphalan Methoxsalen with ultraviolet A therapy (PUVA) Mineral oils (untreated and mildly treated) Mustard gas 2-Naphthylamine Nickel compounds and metallic nickel Phenacetin and analgesic mixtures containing phenacetin Silica, crystalline (respirable size) Soots Strong inorganic acid mists containing sulfuric acid Tamoxifen 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) Thiotepa Tobacco-related exposures: environmental tobacco smoke, smokeless tobacco, tobacco smoking Ultraviolet radiation-related exposures: solar radiation, exposure to sunlamps or sunbeds, broad-spectrum ultraviolet (UV) radiation, ultraviolet A, B, and C radiation Vinyl chloride Wood dust
Source: U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Report on Carcinogens. 11th ed. (Research Triangle Park, N.C.: Author, 2005)
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Carcinogens, known
Salem Health: Cancer Extensive studies conducted by the National Toxicology Program and the International Agency for Research in Cancer (IARC) show that only one-third of suspected chemicals are actually carcinogenic. Approximately 96 percent of human cancer results from naturally occurring carcinogens. Intense study of such carcinogenic compounds shows that 95 percent involve only three types of chemicals: • Alkylating agents: Transfer small fragments (CH3) to DNA • Arylkylating agents: Transfer aromatic rings (C6H5) to DNA • Arylhydroxylamines: Transfer amines, containing NH2, to DNA. A common aspect of these materials is their ability to produce structures that have a deficiency of electrons. Such structures react rapidly with the electron-rich oxygen, sulfur, and nitrogen atoms of nucleic acids. K. Thomas Finley, Ph.D. u
Many carcinogens are alkylating agents, arylkylating agents, or arylhydroxylamines. (Pascal Goetgheluck/Photo Researchers, Inc.)
and also test for mutagens, relying on the fact that nearly all carcinogenic molecules also produce mutations. However, there are significant problems involved. A direct effort along this line involves seeking a lethal mutation involving the X chromosome, which determines the sex of the offspring. The realization that intermediate products from detoxification may be the cause of the initiation phase of cancer development has led to the development of tests involving bacteria and enzymes. These procedures greatly reduced cost (one-thousandth as much as mice) and time (two days compared with at least a year). It has become possible to test all new compounds for mutations and to conduct animal tests only on those showing positive results. All these approaches are actively being used by the National Toxicology Program. Achieving a balance: Although carcinogenic chemicals are of concern, it is important to recognize the actual risk. 226
For Further Information Perantoni, Alan O. “Carcinogenesis.” In The Biological Basis of Cancer, edited by Robert G. McKinnell et al. New York: Cambridge University Press, 1998. Ruddon, Raymond W. “Causes of Cancer.” In Cancer Biology. 4th ed. New York: Oxford University Press, 2007. Tomatis, Lorenzo, and James Huff. “Evolution of Research in Cancer Etiology.” In The Molecular Basis of Human Cancer, edited by William B. Coleman and Gregory T. Tsongalis. Totowa, N.J.: Humana Press, 2002. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Eleventh Report on Carcinogens. Research Triangle Park, N.C.: Author, 2005. Yuspa, Stuart H., and Peter G. Shields. “Etiology of Cancer: Chemical Factors.” In Cancer: Principles and Practice of Oncology, edited by Vincent T. DeVita, Jr., et al. 6th ed. Philadelphia: Lippincott Williams & Wilkins, 2001.
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Other Resources
American Cancer Society Known and Probable Carcinogens http://www.cancer.org/docroot/PED/content/ PED_1_3x_Known_and_Probable_Carcinogens.asp International Agency for Research on Cancer http://www.iarc.fr
Salem Health: Cancer National Toxicology Program http://ntp-server.niehs.nih.gov/index.cfm See also Acrylamides; Aflatoxins; Agent Orange; Air pollution; Alcohol, alcoholism, and cancer; 4-Aminobiphenyl; Arsenic compounds; Asbestos; Azathioprine; Bacteria as causes of cancer; Benzene; Benzidine and dyes metabolized to benzidine; Beryllium and beryllium compounds; Birth control pills and cancer; Bis(chloromethyl) ether and technical-grade chloromethyl methyl ether; Bisphenol A (BPA); 1,3-Butadiene; 1,4-Butanediol dimethanesulfonate; Cadmium and cadmium compounds; Caffeine; Carcinogens, reasonably anticipated; Cell phones; Chewing tobacco; Chlorambucil; 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (MeCCNU); Chromium hexavalent compounds; Cigarettes and cigars; Coal tars and coal tar pitches; Coke oven emissions; Cyclophosphamide; Cyclosporin A; Di(2-ethylhexyl) phthalate (DEHP); Diethanolamine (DEA); Diethylstilbestrol (DES); Dioxins; Electromagnetic radiation; Epstein-Barr virus; Erionite; Ethylene oxide; Fertility drugs and cancer; Formaldehyde; Free radicals; Hair dye; Helicobacter pylori; Hepatitis B virus (HBV); Hepatitis C virus (HCV); HER2/neu protein; Herpes simplex virus; Herpes zoster virus; HIV/AIDSrelated cancers; Hormone replacement therapy (HRT); Human growth factors and tumor growth; Human papillomavirus (HPV); Human T-cell leukemia virus (HTLV); Ionizing radiation; Melphalan; Mineral oils; Mustard gas; 2-Naphthylamine; Nickel compounds and metallic nickel; Oncogenes; Oncogenic viruses; Organochlorines (OCs); Pesticides and the food chain; Phenacetin; Plasticizers; Polycyclic aromatic hydrocarbons; Radon; Report on Carcinogens (RoC); Silica, crystalline; Simian virus 40; Soots; Sunlamps; Thiotepa; Ultraviolet radiation and related exposures; Vinyl chloride; Wood dust.
u Carcinogens, reasonably
anticipated Category: Carcinogens and suspected carcinogens Definition: Chemical compounds similar chemically to those that have shown carcinogenicity are labeled “reasonably anticipated carcinogens” by the National Toxicology Program of the U.S. Department of Health and Human Services. Describing cancer: Cancer has been studied intensely for a long time, yet its causes remain elusive and uncertain.
Carcinogens, reasonably anticipated There is much evidence that when certain chemical compounds are introduced to the human body, the probability of a tumor forming is increased. Scientists have used several methods to gather evidence about the carcinogenicity of a chemical before allowing general use. A central difficulty with methods of studying cancer is that a specific chemical, introduced by a particular route, does not always produce a tumor. Therefore carcinogenicity is defined in terms of the increased risk of producing a tumor. Because the primary interest of such studies is tumors produced in human beings, there is a species problem. It is very difficult to show that susceptibility to increased rates of tumor production in test animals predicts a similar outcome in humans. The National Toxicology Program (NTP) uses animal testing in its basic studies. Research conducted with bacteria also shows great promise. Such complications have resulted in the creation of a rather limited list of carcinogenic chemicals. It pays to take a conservative position in the field of public health, so there is a much longer list of suspected carcinogens. The National Toxicology Program issues a biennial Report on Carcinogens (RoC) in which compounds may be labeled “reasonably anticipated carcinogens” if they meet the following criteria: • There are limited studies in humans. • Sufficient animal studies exist. • Astructural relationship to a known carcinogen exists. Carcinogens and suspected carcinogens: Reports concerning chemicals linked to cancer make the public suspicious of all chemicals. Studies have shown that only onefourth to one-third of suspected molecules are actually cancer causing. More than 95 percent of carcinogenic chemicals belong to three general types of compounds. Chemists who work with organic compounds have always appreciated this relationship. A powerful tool in managing such compounds has been the structure-activity relationship. A given set of atoms, arranged in a particular pattern, will often lead to very similar chemical behavior. The chief cancer-causing molecules predominantly display one of the following chemical structural types: polycyclic aromatic hydrocarbons, aromatic amines, or alkylating agents. Polycyclic aromatic hydrocarbons: As their name suggests, polycylic aromatic hydrocarbons are composed only of atoms of the elements carbon and hydrogen, and the carbon atoms are linked together in a ring or cycle. The simplest chemical in this class is the known carcinogen benzene, which has a single ring of six carbon atoms. Mol227
Carcinogens, reasonably anticipated
Salem Health: Cancer
ecules of four or more benzene rings that are fused together by sharing two carbon atoms are quite common. Aromatic amines: As with the hydrocarbons, aromatic amines generally have the six-carbon atom ring, but they also have a nitrogen atom attached to that ring. The most common example is 2-naphthylamine. This compound has two benzene rings attached to each other and an ammonia-like nitrogen atom containing two hydrogen atoms attached to the second carbon atom. Alkylating agents: Although the first two categories of carcinogenic compounds are characterized by their struc-
ture, alkylating agents share a common chemical function. An alkyl group is a fragment of a molecule that is of high energy and therefore reacts rapidly. One of the most common is the methyl group composed of a single carbon atom and three hydrogen atoms. A methylating agent would be a molecule that can transfer such a reactive fragment during a chemical reaction. There are many compounds that can perform this function, but one of the most active subgroups is that of the nitrosamines, for example, Nnitrosodimethylamine. Like the aromatic amines, there is a nitrogen atom, but in place of the two hydrogen atoms, there are two methyl groups. The aromatic ring is replaced by a second nitrogen atom connected to an oxygen atom.
Reasonably Anticipated Human Carcinogens
• • • • • • • • • • • • • • • • • • • • • • • • • • • 228
Acetaldehyde 2-Acetylaminofluorene Acrylamide Acrylonitrile Adriamycin (doxorubicin hydrochloride) 2-Aminoanthraquinone o-Aminoazotoluene 1-Amino-2,4-dibromoanthraquinone 1-Amino-2-methylanthraquinone 2-Amino-3,4-dimethylimidazo [4,5-f]quinoline (MelQ) 2-Amino-3,8-dimethylimidazo [4,5-f]quinolaxine (MelQx) 2-Amino-3-methylimidazo [4,5-f]quinoline (IQ) 2-Amino-1-methyl6phenylimidazo[4,5-b]pyridine (PhlP) Amitrole o-Anisidine hydrochloride Azacitidine Benzotrichloride Bromodichloromethane 2,2-bis(Bromomethyl)-1,3propanediol (technical grade) Butylated hydroxyanisole (BHA) Carbon tetrachloride Ceramic fibers (respirable size) Chloramphenicol Chlorendic acid Chlorinated paraffins (C12, 60 percent chlorine) 1-(2-Chloroethyl)-3-cyclohexyl-1nitrosourea bis(Chloroethyl) nitrosourea
• • • • • • • • • • • • • • • • • • • • • • • • • •
Chloroform 3-Chloro-2-methylpropene 4-Chloro-o-phenylenediamine Chloroprene p-Chloro-o-toluidine and p-Chloroo-toluidine hydrochloride Chlorozotocin C.I. basic red 9 monohydrochloride Cisplatin Cobalt sulfate p-Cresidine Cupferron Dacarbazine Danthron (1,8-dihydroxyanthraquinone) 2,4-Diaminoanisole sulfate 2,4-Diaminotoluene Diazoaminobenzene 1,2-Dibromo-3-chloropropane 1,2-Dibromoethane (ethylene dibromide) 2,3-Dibromo-1-propanol tris(2,3-Dibromopropyl) phosphate 1,4-Dichlorobenzene 3,3′-Dichlorobenzidine and 3,3′-dichlorobenzidine dihydrochloride Dichlorodiphenyltrichloroethane (DDT) 1,2-Dichloroethane (ethylene dichloride) Dichloromethane (methylene chloride) 1,3-Dichloropropene (technical grade)
• • • • • • • • • • • • • • • • • • • • • • • • • • • • • • •
Diepoxybutane Diesel exhaust particulates Diethyl sulfate Diglycidyl resorcinol ether 3,3′-Dimethoxybenzidine and dyes metabolized to 3,3′-dimethoxybenzidine 4-Dimethylaminoazobenzene 3,3′-Dimethylbenzidine and dyes metabolized to 3,3′dimethylbenzidine Dimethylcarbamoyl chloride 1,1-Dimethylhydrazine Dimethyl sulfate Dimethylvinyl chloride 1,4-Dioxane Disperse blue 1 Epichlorohydrin Ethylene thiourea di(2-Ethylhexyl) phthalate Ethyl methanesulfonate Formaldehyde (gas) Furan Glass wool (respirable size) Glycidol Heterocyclic amines Hexachlorobenzene Hexachloroethane Hexamethylphosphoramide Hydrazine and hydrazine sulfate Hydrazobenzene Iron dextran complex Isoprene Kepone (chlordecone) Lead and lead compounds
Salem Health: Cancer
Carcinogens, reasonably anticipated
A summary of suspected carcinogens: Some common examples of probable carcinogens would include: • Dimethyl sulfate, which, like N-nitrosodimethylamine, has two methyl groups available to be transferred. The new compound has a sulfur atom and four oxygen atoms in place of the nitrogen and oxygen atoms of the carcinogen. • Benzo[a]pyrene has five benzene rings, all sharing two or more carbon atoms. • 2-Toluidine resembles 2-naphthylamine but has the second benzene ring replaced by a single methyl group. Bear in mind that while these compounds are suspected of being carcinogenic and proper safeguards are needed when they are used, there are many examples showing that
compounds with similar structure have very different, or no, carcinogenic properties. K. Thomas Finley, Ph.D. u
For Further Information Perantoni, Alan O. “Carcinogenesis.” In The Biological Basis of Cancer, edited by Robert G. McKinnell et al. New York: Cambridge University Press, 1998. Ruddon, Raymond W. “Causes of Cancer.” In Cancer Biology. 4th ed. New York: Oxford University Press, 2007. Tomatis, Lorenzo, and James Huff. “Evolution of Research in Cancer Etiology.” In The Molecular Basis of
Reasonably Anticipated Human Carcinogens (continued)
• • • • • • • • • • • • • • • • • • • • • • • • •
Lindane and other hexachlorocyclohexane isomers 2-Methylaziridine (propylenimine) 4,4′-Methylenebis(2-chloroaniline) 4,4′-Methylenebis (N,N-dimethyl)benzenamine 4,4′-Methylenedianiline and its dihydrochloride salt Methyleugenol Methyl methanesulfonate N-Methyl-N′-nitro-Nnitrosoguanidine Metronidazole Michler’s ketone (4,4′(dimethylamino)benzophenone) Mirex Naphthalene Nitrilotriacetic acid o-Nitroanisole Nitroarenes (1,6-dinitropyrene; 1,8-dinitropyrene; 6-nitrochrysene; 1-nitropyrene; 4-nitropyrene) Nitrobenzene Nitrofen (2,4-dichlorophenylp-nitrophenyl ether) Nitrogen mustard hydrochloride Nitromethane 2-Nitropropane N-Nitrosodi-n-butylamine N-Nitrosodiethanolamine N-Nitrosodiethylamine N-Nitrosodimethylamine N-Nitrosodi-n-propylamine
• • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • •
N-Nitroso-N-ethylurea 4-(N-Nitrosomethylamino)-1(3-pyridyl)-1-butanone N-Nitroso-N-methylurea N-Nitrosomethylvinylamine N-Nitrosomorpholine N-Nitrosonornicotine N-Nitrosopiperidine N-Nitrosopyrrolidine N-Nitrososarcosine Norethisterone Ochratoxin A 4,4′-Oxydianiline Oxymetholone Phenazopyridine hydrochloride Phenolphthalein Phenoxybenzamine hydrochloride Phenytoin Polybrominated biphenyls (PBBs) Polychlorinated biphenyls (PCBs) Polycyclic Aromatic Hydrocarbons Benz[a]anthracene Benzo[b]fluoranthene Benzo[j]fluoranthene Benzo[k]fluoranthene Benzo[a]pyrene Dibenz[a,h]acridine Dibenz[a,j]acridine Dibenz[a,h]anthracene 7H-Dibenzo[c,g]carbazole Dibenzo[a,e]pyrene Dibenzo[a,h]pyrene Dibenzo[a,i]pyrene
• • • • • • • • • • • • • • • • • • • • • • • • • • • • • • •
Dibenzo[a,l]pyrene Indeno[1,2,3-cd]pyrene 5-Methylchrysene Procarbazine hydrochloride Progesterone 1,3-Propane sultone β-Propiolactone Propylene oxide Propylthiouracil Reserpine Safrole Selenium sulfide Streptozotocin Styrene-7,8-oxide Sulfallate Tetrachloroethylene (perchloroethylene) Tetrafluoroethylene Tetranitromethane Thioacetamide 4,4′-Thiodianiline Thiourea Toluene diisocyanate o-Toluidine and o-toluidine hydrochloride Toxaphene Trichloroethylene 2,4,6-Trichlorophenol 1,2,3-Trichloropropane Urethane Vinyl bromide 4-Vinyl-1-cyclohexene diepoxide Vinyl fluoride
Source: U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Report on Carcinogens. 11th ed. (Research Triangle Park, N.C.: Author, 2005)
229
Carcinoid tumors and carcinoid syndrome Human Cancer, edited by William B. Coleman and Gregory T. Tsongalis. Totowa, N.J.: Humana Press, 2002. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Eleventh Report on Carcinogens. Research Triangle Park, N.C.: Author, 2005. Yuspa, Stuart H., and Peter G. Shields. “Etiology of Cancer: Chemical Factors.” In Cancer: Principles and Practice of Oncology, edited by Vincent T. DeVita, Jr., et al. 6th ed. Philadelphia: Lippincott Williams & Wilkins, 2001. u
Other Resources
American Cancer Society Known and Probable Carcinogens http://www.cancer.org/docroot/PED/content/ PED_1_3x_Known_and_Probable_Carcinogens.asp International Agency for Research on Cancer http://www.iarc.fr National Toxicology Program http://ntp-server.niehs.nih.gov See also Acrylamides; Aflatoxins; Agent Orange; Air pollution; Alcohol, alcoholism, and cancer; 4-Aminobiphenyl; Arsenic compounds; Asbestos; Azathioprine; Bacteria as causes of cancer; Benzene; Benzidine and dyes metabolized to benzidine; Beryllium and beryllium compounds; Birth control pills and cancer; Bis(chloromethyl) ether and technical-grade chloromethyl methyl ether; Bisphenol A (BPA); 1,3-Butadiene; 1,4-Butanediol dimethanesulfonate; Cadmium and cadmium compounds; Caffeine; Carcinogens, known; Cell phones; Chewing tobacco; Chlorambucil; 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (MeCCNU); Chromium hexavalent compounds; Cigarettes and cigars; Coal tars and coal tar pitches; Coke oven emissions; Cyclophosphamide; Cyclosporin A; Di(2-ethylhexyl) phthalate (DEHP); Diethanolamine (DEA); Diethylstilbestrol (DES); Dioxins; Electromagnetic radiation; Epstein-Barr virus; Erionite; Ethylene oxide; Fertility drugs and cancer; Formaldehyde; Free radicals; Hair dye; Helicobacter pylori; Hepatitis B virus (HBV); Hepatitis C virus (HCV); HER2/neu protein; Herpes simplex virus; Herpes zoster virus; HIV/AIDSrelated cancers; Hormone replacement therapy (HRT); Human growth factors and tumor growth; Human papillomavirus (HPV); Human T-cell leukemia virus (HTLV); Ionizing radiation; Melphalan; Mineral oils; Mustard gas; 2-Naphthylamine; Nickel compounds and metallic nickel; Oncogenes; Oncogenic viruses; Organochlorines (OCs); 230
Salem Health: Cancer Pesticides and the food chain; Phenacetin; Plasticizers; Polycyclic aromatic hydrocarbons; Radon; Report on Carcinogens (RoC); Silica, crystalline; Simian virus 40; Soots; Sunlamps; Thiotepa; Ultraviolet radiation and related exposures; Vinyl chloride; Wood dust.
u Carcinoid tumors and
carcinoid syndrome Category: Diseases, symptoms, and conditions Also known as: Gastrointestinal tract tumors, adenocarcinoid tumors Related conditions: Colon cancer, small bowel lymphoma Definition: A carcinoid tumor arises from hormoneproducing cells that line the small intestine, appendix, bronchi, colon, pancreas, ovaries, testes, bile ducts, gallbladder, stomach, and liver. Carcinoid syndrome is a group of symptoms caused by the release of hormones from a carcinoid tumor. Risk factors: No risk factors for carcinoid syndrome or carcinoid tumors have been identified, although they are thought to be related to a genetic mutation that is either inherited or spontaneous. Etiology and the disease process: Carcinoid tumors are slow-growing tumors that develop from enterochromaffin cells. These cells secrete hormones such as serotonin, histamine, prostaglandins, polypeptides, and tachykinins. Some 65 percent of carcinoid tumors occur in the gastrointestinal tract, and 25 percent are found in the lungs. The remaining 10 percent arise from other organs, or the primary site is unknown. Benign carcinoid tumors are small and have a low rate of recurrence. Malignant carcinoid tumors tend to be larger than 2 centimeters (cm) and are more likely to metastasize (spread to other organs). They also can invade adjacent tissue. The hormones secreted by gastrointestinal carcinoid tumors are broken down in the liver, so patients with these types of tumors do not experience carcinoid syndrome. However, if there are liver metastases, carcinoid syndrome can develop. Carcinoid tumors of the lungs, ovaries, and testes are more likely to cause carcinoid syndrome. Incidence: Research suggests a rate of from 1.5 to 8 cases per 100,000 people. Carcinoid syndrome is rare.
Salem Health: Cancer Symptoms: Large gastrointestinal tumors may cause abdominal pain, abdominal mass, bleeding, nausea and vomiting, obstruction, and diarrhea. Carcinoid tumors of the lungs cause coughing, chest pain, wheezing, blood-tinged sputum, and pneumonia. Lung carcinoid tumors cause the carcinoid syndrome about 20 percent of the time. The most common symptom of the carcinoid syndrome is facial flushing that can last from hours to days. Other common symptoms are diarrhea, abdominal pain, wheezing, valvular heart disease, sweating, rapid heart rate, weight gain, weakness, secondary diabetes, and increased body and facial hair. These symptoms are caused by the high levels of hormones released by the tumor. Screening and diagnosis: There is no routine screening for carcinoid tumors. Larger carcinoid tumors can be diagnosed by computed tomography (CT) scans or magnetic resonance imaging (MRI). If the CT scan shows abnormal lymph nodes or a liver tumor, a needle biopsy can be performed. Carcinoid tumors can also be found by somatostatin (a hormone) receptor scintography, a nuclear imaging scan. This scan uses indium 111 octreotide as a radioactive dye. Octreotide has an affinity for hormone-producing cells. This test is quite accurate, but it can miss very small tumors and tumors that do not have somatostatin receptors. Two other nuclear imaging procedures are used. They are positron emission tomography (PET) and metaiodobenzylguanidine (MIBG) scans. The PET scan picks up areas of the body with higher than normal metabolism. Like octreotide, MIBG is attracted to carcinoid tumors. The only way to verify that a tumor is a carcinoid tumor is to biopsy it. Biopsy may be done by endoscopy, bronchoscopy, or needle biopsy. Diagnosis of carcinoid syndrome can be done by performing a twenty-four hour urine test for 5-hydroxyindolacetic acid (5-HIAA). The normal rate of urinary excretion of 5-HIAA is 8 milligrams (mg). Persons with carcinoid syndrome can excrete between 100 and 2,000 mg of 5-HIAA. The staging for carcinoid tumors is based on the primary site. Treatment and therapy: If a carcinoid tumor is less than 2 centimeters (cm) in size, it can be removed by surgery. If the carcinoid tumor is larger than 2 cm, there are multiple tumors, or there are metastases, a cure is less likely. Surgery may be performed to ease the symptoms from the tumor or the carcinoid syndrome.
Carcinoid tumors and carcinoid syndrome Sometimes the goal of surgery is debulking (decreasing the size of the tumor). This is done to decrease symptoms of carcinoid syndrome or in preparation for chemotherapy or radiation therapy. Debulking can be performed by surgical resection, cryoablation (freezing), radiofrequency ablation (radiation), or hepatic artery embolization (blocking the blood supply to the liver). Chemotherapy may be used to treat carcinoid tumors. The chemotherapeutic drugs most frequently used are 5fluorouracil (Adrucil), cyclophosphamide (Cytoxan), streptozocin (Zanosar), and doxorubicin (Adriamycin). Interferon, an immune system stimulator, may be used with chemotherapy. Chemotherapy is effective in about 30 percent of cases, and its effects are short term. External radiation therapy can be administered to decrease tumor size and to decrease the symptoms that the patient is experiencing. Radiation is not effective against liver metastases. Medications can be used to treat carcinoid syndrome. Octreotide has been effective in reducing the size of some carcinoid tumors. Imodium, lomotil, ondansetran (Zofran), and cyproheptadine (Periactin) may eliminate the diarrhea. Tamoxifen (nolvadex), phenothiazides, gastric histamine receptor antagonists, phentolamine alpha blockers, and corticosteroids may decrease the flushing. Patients with carcinoid syndrome must take a niacin supplement and ingest adequate protein. Carcinoid tumors use nicotinic acid (a niacin breakdown product) and tryptophan to create serotonin and can deplete the body’s stores of niacin. Prognosis, prevention, and outcomes: With appropriate treatment, a person with carcinoid cancer or carcinoid syndrome can live for ten to fifteen years with a fairly good quality of life. There is no way to prevent carcinoid tumors. Christine M. Carroll, R.N., B.S.N., M.B.A. u
For Further Information Babovic-Vuksanovic, Dusica, et al. “Familiar Occurrence of Carcinoid Tumors and Association with Other Malignant Neoplasms.” Cancer Epidemiology Biomarkers and Prevention 8 (August, 1999): 715-719. Wilander, Erik, Monalill Lundqvist, and Kjell Öberg. Gastrointestinal Carcinoid Tumors. New York: Fischer, 1989. Zuetenhorst, Johanna M., and Babs G. Taal. “Metastatic Carcinoid Tumors: A Clinical Review.” The Oncologist 10, no. 2 (February, 2005): 123-131. 231
Carcinoma of unknown primary origin (CUP) u
Other Resources
American Cancer Society Detail Guide: Gastrointestinal Carcinoid Tumors http://www.cancer.org/docroot/CRI/ CRI_2_3x.asp?dt=14 Medicinenet Carcinoid Syndrome (Carcinoid Tumor) http://www.medicinenet.com/carcinoid_syndrome/ article.htm See also Achlorhydria; Antidiarrheal agents; Appendix cancer; Barium swallow; Bronchial adenomas; Duodenal carcinomas; Endocrine cancers; Gastric polyps; Gastrointestinal oncology; Grading of tumors; 5-Hydroxyindoleacetic acid (5HIAA) test; Imaging tests; Interferon; Neuroendocrine tumors; Nuclear medicine scan; Small intestine cancer; Stomach cancers; Surgical biopsies; Thymomas; Thymus cancer.
u Carcinoma of unknown
primary origin (CUP) Category: Diseases, symptoms, and conditions Related conditions: Skin cancer, lung cancer, prostate cancer, breast cancer, lung cancer, recurrent carcinoma Definition: Carcinoma of unknown primary origin (CUP) is an abnormal growth of cells, resulting in malignant (metastasized) cancer with no known origin. Carcinoma represents the most common cancers, including the common forms of skin, breast, prostate, lung, and colon cancer. Risk factors: Malignant transformation can be caused by exposure to toxic carcinogens such as such as radiation, tobacco smoke, and certain chemicals. Some viruses have been linked to cancer: Epstein-Barr virus and lymphoma, human papillomavirus and cervical cancer, hepatitis B virus and liver cancer, and Kaposi sarcoma-associated virus and Kaposi sarcoma. Additionally, many carcinomas are the result of a random genetic mutation, resulting in abnormally formed cells that can be cancerous. There are strong hereditary factors involved in carcinoma, so that having a family history of cancer can mean being predisposed to developing cancer. Etiology and the disease process: The origin of carcinoma is in the cells of the epithelium, which lines both the outside (skin) and the inside cavities and lumen of tissues and organs. In normal tissue, cells multiply to form new 232
Salem Health: Cancer cells, and the old or damaged cells self-destruct by apoptosis, or cell suicide. However, when cells undergo malignant transformation (genetic mutations that lead to cancer), they divide and grow at a rapid rate, and tumors form and grow. Tumors can grow quickly if the cells are dividing at a high rate, while slow-growing tumors result from slowly dividing cells. As more and more of these dividing cells accumulate, the normal tissue becomes diseased. The cancer can spread to other regions of the body. Incidence: Over 80 percent of all diagnosed cancers are a result of carcinoma. Of those, 2 to 4 percent are carcinomas of unknown origin, in that they have metastasized from an unknown location. Symptoms: Symptoms of carcinoma of unknown primary origin include local symptoms, metastasis symptoms, and systemic systems. Local symptoms include unusual bumps, nodes, cysts, or swelling; bleeding (usually found internally or in urine tests); and pain from compression of the tissues surrounding the area of a tumor growth. Metastasis symptoms include enlarged lymph nodes, neurological symptoms, an enlarged liver, and occasionally coughing or broken bones. Systemic symptoms refer to symptoms that affect the entire body, such as weight loss, excessive sweating, hormonal changes, or lack of iron in the bloodstream. Screening and diagnosis: Cancer is usually classified according to the tissue from which the cancerous cells originate, as well as the normal cell type they most resemble. Sometimes, however, although cancerous cells are present, their origin is unknown. Depending on symptoms present, a patient may undergo several tests including blood, urine, stool tests, and X rays. If carcinoma is suspected, the physician will usually order a biopsy to examine a small piece of the cancerous tissue under a microscope. Cancer is determined to be carcinoma of unknown primary origin when there is no evidence to determine the origin of the cancerous cells. By examining the pattern of spreading for the cancer, the physician may derive more information about where it originated. In cancers that appear above the diaphragm, lung cancer is usually the cause. Research has shown that over half of patients with carcinoma of unknown primary origin have cancer that originated in the lung or pancreas. According to the National Cancer Institute, physicians classify carcinoma of unknown primary origin into one of the following categories: • Poorly differentiated carcinomas: The cancer cells look very different from normal cells. • Metastatic melanoma to a single nodal site: Cancer of
Salem Health: Cancer the cells that color the skin (melanocytes) has spread to lymph nodes in only one part of the body. • Cancer in the cervical lymph nodes: Cancer is in the small, bean-shaped organs that make and store infectionfighting cells (lymph nodes) in the neck area. • Isolated axillary metastasis: Cancer has spread only to lymph nodes in the area of the armpits. • Inguinal node metastasis: Cancer has spread to lymph nodes in the groin area. • Multiple involvement: Cancer has spread to several different areas of the body. Treatment and therapy: Treatment of carcinoma of unknown primary origin depends on the suspected origin of the cancer, the microscopic analysis of the cancer cells, and other factors. Surgery is a common treatment for carcinoma of unknown primary origin; the cancer and a small portion of the healthy tissue surrounding it are removed. Various surgical procedures are used, depending on the location of the cancer. Radiation therapy is often used before surgery to shrink tumors or after surgery to kill remaining cancer cells; it can also be used as a therapy without surgery. Chemotherapy is a systemic treatment that uses drugs to kill cancerous cells. Once the drugs enter the body and travel through the bloodstream, they kill cancerous cells throughout the body. Drugs can be administered orally or by injection into the veins or muscles. Occasionally chemotherapy is administered after surgery has removed all cancer cells as a preventive measure to ensure that new cancer cells do not develop (adjuvant therapy). Hormone therapy has shown success in halting the production of hormones that assist in the growth of cancerous cells. Synthetic hormones or other drugs block the body’s natural hormones, or hormone-producing glands are removed by surgery. If carcinoma of unknown primary origin has been categorized, the treatment is more specific. If the cancer is classified as poorly differentiated cells or discovered within the abdomen, the most common treatment is chemotherapy. If the cancer is found in the neck area, treatment may include removal of the lymph nodes and tonsils, radiation therapy, or neck surgery. A lymph node dissection may be performed if the cancer has spread to the lymph nodes. When cancer is found in lymph nodes near the armpit, surgery is performed to remove the nodes and often the breast tissue, along with radiation and chemotherapy. If the cancer is found in the lymph nodes near the groin area, surgery is performed to remove the lymph nodes and some groin tissue. If the cancer is found in several areas of the body,
Carcinomas usually a systemic therapy such as chemotherapy or hormone therapy will be used to deliver treatment to the entire body. Prognosis, prevention, and outcomes: The prognosis for patients with carcinoma of unknown primary origin is poor. The average survival is approximately three to five months; 25 percent of patients survive one year, and only 10 percent of patients survive five years. Studies have shown that cancer found in the lymph nodes has a longer survival rate. Colonoscopies, mammograms, and prostate cancer screenings can lead to early detection and possibly longer survival times. Robert J. Amato, D.O. u
For Further Information Fizazi, Karim, ed. Carcinoma of an Unknown Primary Site. New York: Taylor & Francis, 2006. Icon Health. The Official Patient’s Sourcebook on Carcinoma of Unknown Primary: A Revised and Updated Directory for the Internet Age. San Diego, Calif.: Author, 2002.
u
Other Resources
American Cancer Society Detailed Guide: Cancer of Unknown Primary http://www.cancer.org/docroot/CRI/ CRI_2_3x.asp?rnav=cridg&dt=58 National Cancer Institute Cancer of Unknown Primary http://www.nci.nih.gov/cancertopics/types/ unknownprimary/ See also Breast cancers; Carcinogens, known; Carcinogens, reasonably anticipated; Carcinomas; Carcinosarcomas; Lung cancers; Metastasis; Prostate cancer; Skin cancers; Survival rates.
u Carcinomas Category: Diseases, symptoms, and conditions Also known as: Epithelial cell cancer Related conditions: Dysplasia, metaplasia Definition: Carcinoma refers to any type of cancer that arises from epithelial cells. Carcinomas are distinguished from cancers of connective tissue (sarcomas), from cancers of blood-forming cells (leukemias and lymphomas), and from germ-cell tumors (teratomas). Carcinomas aris233
Carcinomas ing from stratified squamous epithelium are termed squamous cell carcinomas; those arising from glandular epithelium are termed adenocarcinomas. Risk factors: Risk factors fall into two categories: environmental and hereditary. Environmental risk factors include exposure to carcinogenic chemicals or ionizing radiation, or infection with oncogenic viruses. Thousands of carcinogenic chemicals are known, and many are subject to strict regulations regarding exposure. Exposure to ionizing radiation, the most important source of which is the ultraviolet portion of sunlight, is another risk factor. Other important risk factors are inborn genetic variations that predispose individuals to particular cancers and immune system dysfunction.
Salem Health: Cancer gen (PSA) is used to screen men at risk for prostate cancer; those with high levels are then candidates for diagnostic biopsy. Diagnosis of carcinoma is usually done by pathologists based on microscopic examination of biopsied tissue. Features of carcinoma include cellular traits such as abnormally large nuclei, loss of multicellular organization, and disruption of the basement membrane. Staging of carcinoma is based on searches for malignant cells in adjacent structures and lymph nodes. Carcinoma staging uses the International Union Against Cancer (UICC) and American Joint Committee on Cancer (AJCC) system that describes the tumor itself, lymph node involvement, and metastatic lesions; however, other staging systems are also used, such as Dukes’ classification of colon cancer.
Symptoms: Symptoms of early carcinoma vary widely according to the epithelial cells affected and their growth pattern. Advanced or terminal carcinoma symptoms include cachexia, pain, fatigue, and depression.
Treatment and therapy: Treatment options for carcinoma include surgery, chemotherapy, radiotherapy, immunotherapy, monoclonal antibody therapy, and other, less common approaches. Treatment plans are made based on the disease grade and stage and the functional status of the patient. Surgical therapy (mechanical removal of the tumor) reliably reduces the tumor burden and offers complete resection as the best outcome. Examples include surgical removal of the breast (mastectomy) or prostate (prostatectomy). Chemotherapy (systemic administration of anticarcinoma drugs) can damage tumor cells anywhere in the body, usually by interfering with deoxyribonucleic acid (DNA) replication. Many chemotherapy regimens harm healthy tissue as a dose-limiting toxicity. Radiotherapy is the use of high-energy electromagnetic radiation (X rays or gamma rays) to damage or kill cancer cells; radiation can be delivered from the outside or by implantation of radioactive pellets (brachytherapy). Immunotherapy refers to attempts to attack carcinoma cells with the patient’s own immune cells. Monoclonal antibody therapy depends on knowledge of signal transduction pathways and uses antibodies to block or disrupt the malignant cells’ growth. An example includes the use of monoclonal antibodies against human epidermal growth factor receptor 2 (HER2) such as trastuzumab to interfere with signals generated by the HER2 receptor in breast cancer.
Screening and diagnosis: Carcinoma screening consists of careful inspection of epithelial cells at risk as well as blood tests for circulating tumor markers. Inspection for skin cancer may be as straightforward as looking for suspicious changes on the skin, whereas screening for cervical cancer involves scraping or brushing cells from the uterine cervix followed by staining and microscopic examination (a Pap smear). Blood tests can also be used to screen for carcinoma based on shedding of tumor-specific molecules into the circulation. A blood test for prostate-specific anti-
Prognosis, prevention, and outcomes: Although some types of carcinoma are quite deadly, many forms are indolent and manageable. Prognosis depends mostly on the type of carcinoma, the histologic grade, and the anatomic stage. Prevention efforts can reduce the incidence of carcinomas within populations and take the form of avoidance of or reduction of exposure to carcinogens. Examples include smoking-cessation campaigns to prevent some cases of lung cancer and promotion of sunscreen use to prevent some cases of melanoma. Individuals may further reduce
Etiology and the disease process: Epithelial cells are more prone to malignant transformation than other types of cells because they are routinely exposed to the outside environment. Therefore, carcinoma is far more prevalent than sarcoma, leukemia, or other forms of cancer. The etiology of carcinoma hinges on cellular alterations that confer several key traits on the cell: unregulated growth, stimulation of new blood vessel formation, tissue invasion, and metastatic potential. Infection by oncogenic viruses causes carcinoma by introduction of foreign genes into the cell; these oncogenic genes (oncogenes) can confer the attributes of malignancy to the infected cells. Gene disruption can cause carcinoma via abnormal activation of oncogenes or, alternatively, by abnormal inactivation of tumor-suppressor genes. Incidence: Carcinoma is by far the most prevalent form of cancer, accounting for more than 90 percent of new cancer cases and cancer deaths. In 2005, there were approximately 1.2 million new cases and 500,000 deaths from carcinoma in the United States.
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Salem Health: Cancer their risk of cancer by losing weight and being physically active. Outcomes continue to improve because of the integration of treatments and supportive care. John B. Welsh, M.D., Ph.D. u For Further Information Hanahan D., and R. A. Weinberg. “The Hallmarks of Cancer.” Cell 100 (2000): 57-70. Kufe, D. W., et al., eds. Holland Frei Cancer Medicine. 7th ed. Hamilton, Ont.: BC Decker, 2006. Ruddon, R. W. Cancer Biology. 4th ed. New York: Oxford University Press, 2007. Schottenfeld, D., and J. F. Fraumeni, Jr., eds. Cancer Epidemiology and Prevention. New York: Oxford University Press, 2006. Weinberg, R. A. The Biology of Cancer. New York: Garland Science, 2007. u
Other Resources
American Cancer Society http://www. cancer.org National Cancer Institute http://www.cancer.gov See also Adenocarcinomas; Adenoid cystic carcinoma (ACC); Adrenocortical cancer; Appendix cancer; Ascites; Basal cell carcinomas; Bile duct cancer; Birt-Hogg-Dubé syndrome (BHDS); Bladder cancer; Bowen disease; Breast cancer in men; Breast cancers; Bronchoalveolar lung cancer; Carcinoma of unknown primary origin (CUP); Carcinomatosis; Carcinomatous meningitis; Carcinosarcomas; Cervical cancer; Chordomas; Choriocarcinomas; Comedo carcinomas; Ductal carcinoma in situ (DCIS); Duodenal carcinomas; Endocrine cancers; Epidermoid cancers of mucous membranes; Ethnicity and cancer; Fallopian tube cancer; Gallbladder cancer; Granulosa cell tumors; Hereditary leiomyomatosis and renal cell cancer (HLRCC); Hereditary mixed polyposis syndrome; Hereditary non-VHL clear cell renal cell carcinomas; Hereditary papillary renal cell carcinomas; Invasive ductal carcinomas; Invasive lobular carcinomas; Leptomeningeal carcinomas; Liver cancers; Lobular carcinoma in situ (LCIS); Lung cancers; Medullary carcinoma of the breast; Meningeal carcinomatosis; Merkel cell carcinomas (MCC); Metastatic squamous neck cancer with occult primary; Mucinous carcinomas; Multiple endocrine neoplasia type 2 (MEN 2); Ovarian epithelial cancer; Pancreatic cancers; Parathyroid cancer; Penile cancer; Pituitary tumors; Prostate cancer; SCLC1 gene; Skin cancers; Small intestine cancer; Squamous cell carcinomas;
Carcinomatosis Stomach cancers; Teratocarcinomas; Thymus cancer; Transitional cell carcinomas; Trichilemmal carcinomas; Tubular carcinomas; Urethral cancer; Urinary system cancers; Uterine cancer; Vaginal cancer; Virus-related cancers; Vulvar cancer; Yolk sac carcinomas.
u Carcinomatosis Category: Diseases, symptoms, and conditions Also known as: Carcinosis Related condition: Metastasis Definition: Carcinomatosis is a condition in which a malignant tumor (or carcinoma), originating in the epithelial cells lining the internal and external surfaces or passageways that run through all organs, has spread via the bloodstream or lymphatic system through a process called metastasis. This is in contrast to carcinoma in situ, in which the cancer has not spread to neighboring tissues and involves only the cells where it originated. Although strictly speaking carcinomatosis should be used only for epithelial cancers, or carcinomas, it is sometimes employed to describe other types such as sarcomas—cancers of connective tissues such as bone, cartilage, or fat—that have spread widely throughout the body. Carcinomatosis is also used to describe a cancer in a relatively large region of the body. Risk factors: Cancer risk increases as a function of smoking; consuming a high-fat diet; being overweight or obese; unprotected exposure to the sun’s ultraviolet rays; increasing age; gender (often men have a higher risk); race (which race has an increased risk depends on the cancer); poverty and thus access to health care, screening, and early diagnosis; genetics (sometimes tied to ethnicity or religion); or environment (exposure to pollution, toxins, and ionizing radiation). However, every cancer has distinct risk factors. Etiology and the disease process: Just as every cancer has distinct risk factors, every cancer also has distinct, organ-specific causes. However, what is common among cancers is the out-of-control growth and accumulation of abnormal cancer cells. Carcinogens—substances that cause gene mutation—may be chemical, irradiative, viral, immunological, or hereditary. Incidence: In the United States the incidence of cancer among men is as follows: prostate, 33 percent; lung, 13 percent; colorectal, 10 percent; bladder, 7 percent; nonHodgkin lymphoma, 6 percent; and skin melanoma, 5 percent. Among women the rates were breast, 32 percent; 235
Carcinomatosis lung, 12 percent; colorectal, 11 percent; endometrial, 6 percent; and non-Hodgkin lymphoma, 4 percent. Symptoms: Most cancers develop from a single aberrant cell. This cell then proliferates to generate a clinically detectable tumor, which may be benign or malignant. In some cases, multiple primary tumors may occur; this may or may not be followed by metastasis. The symptoms may evidence the progression from normal cell through premalignant lesions to fully malignant cancers capable of moving to distant sites. Screening and diagnosis: Screening may be general through blood tests, X rays, computed tomography (CT scans), and endoscopy. However, for some cancers, there are specific screening tests. For example, for prostate cancer, screenings include digital rectal examinations to detect irregularities of the prostate gland and blood tests to detect levels of prostate specific antigen (PSA), but prostate biopsies are more definitive. Similarly, colonoscopies (colorectal examinations) help identify precancerous or cancerous polyps or tumors that may also be confirmed by biopsies, and Pap smears test for abnormal cells that might signal the start of cervical cancer. Most types of cancer are categorized in Stages I, II, III, and IV. These stages of cancer are based on the extent of spread and whether the cancer has moved to lymph nodes or other organs. Each stage classification is slightly different for every type of cancer, ranging from the least extensive spread (Stage I) to the most extensive (Stage IV), where the cancer has spread through the bloodstream beyond the primary site; that is, it has metastasized. The condition of carcinomatosis usually refers to cancers in Stage III or IV. Treatment and therapy: Treatment options include surgery, radiation therapy, chemotherapy, and hormone therapy. Radiation therapy uses X rays or other high-energy rays to kill cancer cells or shrink tumors. Radiation may be used alone, or before or after surgery. Chemotherapy uses drugs (singly or in combination) to kill cancer cells. Alternative therapies include dietary formulas, homeopathy, or hypnotherapy. Complementary therapies consist of such procedures as massage or even music, often to reduce the anxiety that often accompanies a cancer diagnosis. Prognosis, prevention, and outcomes: Thanks to the increasing numbers of diagnostic tools and treatment options, the prognosis for specific forms of cancer has improved even though predicting the outcome of any individual treatment is very difficult. As for prevention, avoidance of smoking drastically reduces the incidence of lung cancer, while reducing the 236
Salem Health: Cancer body mass index to below twenty-five cuts down the risk of colon, kidney, pancreatic, esophageal, uterine, and breast cancer. Reducing the intake of processed meats and to a lesser extent red meat diminishes the likelihood of colorectal cancer. Limiting direct exposure to the sun reduces malignant skin melanomas. Modifying not only lifestyle risk factors but also occupational factors such as avoiding the inhalation of asbestos fibers at the workplace also helps cancer prevention. The use of specific drugs may also be preventive, as is testing for such genes as BRCA1 and BRCA2, which cause breast cancer. Various forms of screening such as Pap smears, colonoscopies, and PSA tests have also been found to be effective preventive measures. As for outcomes, mortality rates for the most common forms of cancer among men were as follows: lung cancer, 31 percent; prostate, 10 percent; colorectal, 10 percent; pancreatic, 5 percent; and blood leukemia, 4 percent. Among women, the corresponding figures were lung, 27 percent; breast, 15 percent; colorectal, 10 percent; ovarian, 6 percent; and pancreatic, 6 percent. Peter B. Heller, Ph.D. u
For Further Information Eyre, Harmon J., et al., eds. Informed Decisions: The Complete Book of Cancer Diagnosis, Treatment, and Recovery. 2d ed. Atlanta, Ga.: American Cancer Society, 2002. “Facts About Cancer.” In American Medical Association Family Medical Guide. 4th ed. Hoboken, N.J.: John Wiley, 2004. Kleinsmith, L. J. Principles of Cancer Biology. San Francisco: Pearson Benjamin Cummings, 2006. Tannock, I. F., et al., eds. The Basic Science of Oncology. 4th ed. New York: McGraw Hill, 2005. Turkington, Carol A., and William LiPera, eds. The Encyclopedia of Cancer. New York: Facts on File, 2005.
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Other Resources
American Cancer Society http://www.cancer.org National Cancer Institute http://www.cancer.gov See also Appendix cancer; Ascites; Carcinomatous meningitis; Carcinosarcomas; Fallopian tube cancer; Gynecologic cancers; Hyperthermic perfusion; Leptomeningeal carcinomas; Lumbar puncture; Meningeal carcinomatosis.
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u Carcinomatous meningitis Category: Diseases, symptoms, and conditions Also known as: Meningeal carcinomatosis, leptomeningeal carcinomatosis, leptomeningeal metastasis Related conditions: Almost any type of cancer can be associated with this condition, but it is generally seen with melanoma and breast and lung cancers. Definition: Carcinomatous meningitis is the spread or infiltration of tumor cells from a primary central nervous system (CNS) source, such as a brain tumor, or from a distant or secondary source, such as a lung or breast tumor, via the blood to the subarachnoid space, where it spreads via the fluid covering the brain, called the cerebral spinal fluid (CSF), to involve the coverings of the brain, known as the leptomeninges. The leptomeninges are further subdivided into the pia mater and the arachnoid. The space between the two is called the subarachnoid space, and this space acts as the conduit for the spread of tumor cells as it contains the CSF fluid. Risk factors: In adults, primary brain tumors such as oligodendroglioma or secondary tumors, also called metastases, from lung, breast, melanoma, lymphoma, ovarian, or gastric cancer can spread to the brain surfaces. In children, primary brain tumors such as ependymoma, pineal tumors, meduloblastoma, germinoma, or glioblastoma can spread to the leptomeninges. Etiology and the disease process: The leptomeninges are the coverings of the brain. The leptomeninges can be further subdivided into the pia mater, a thin translucent sheet or membrane that adheres to the surfaces of the brain and spinal cord, and the arachnoid, a delicate weblike membrane between the dura and pia mater. The space between the two is called the subarachnoid space and is filled with fluid called cerebral spinal fluid, which nourishes the brain and cushions it. When tumor cells invade the subarachnoid space between the pia mater and the arachnoid, that invasion is called carcinomatous meningitis. Unlike other forms of meningitis, where the invading organism is a bacteria, fungus, or virus, the invaders in carcinomatous meningitis are cancer cells, and therefore it is not an infection. Tumor growth in carcinomatous meningitis is along the CSF and can involve the dura, pia-arachnoid, or rarely the spinal cord itself. In adults, tumor growth usually results from spread of a primary brain tumor (a cancer that starts in the brain) such as oligodendroglioma or of secondary cancers from lymphoma, melanoma, or lung, breast, or
Carcinomatous meningitis gastric tumors. A secondary cancer occurs when cancer cells leave the primary site (usually the breast in carcinomatous meningitis) and spread to another organ or different parts of the body (metastasize). These secondary cancer cells can stay inactive for many years, so even when a cancer appears to have been successfully treated, it can recur. No one knows what triggers the cancer cells to become active again. It is estimated that between 3 and 5 out of every 100 patients with cancer will develop carcinomatous meningitis, and it can occur with any type of cancer but most commonly occurs in breast cancer. Incidence: The incidence of carcinomatous meningitis is increasing because cancer patients are surviving longer. It is seen in about 3 to 5 percent of patients who have cancer. Symptoms: Patients usually complain of nonspecific symptoms such as headache or back pain, or focal neurologic deficits such as weakness in an extremity. Screening and diagnosis: Carcinomatous meningitis can be diagnosed by magnetic resonance imaging (MRI) or myelography together with computed tomography (CT). A cerebral spinal fluid (CSF) or spinal tap (also called a lumbar puncture), whereby a needle is inserted into the spinal fluid within the subarachnoid space and the CSF fluid is sampled, is the usual form of diagnosis, although CSF cytology is negative in 10 percent of cases. On noncontrast CT, there is obliteration of basal cisterns or sulci with hydrocephalus as an indirect sign. Contrast-enhanced MRI is more sensitive than CT and typically shows enhancement of the basilar cisterns or sulci with focal subarachnoid masses less common. It should be noted that up to 30 percent of confirmed cases of meningeal metastases will have a negative MRI. Treatment and therapy: This disease is difficult to cure, and the treatment aim is usually to ameliorate symptoms, usually by chemotherapy injected into the spinal fluid via lumbar puncture (intrathecal methotrexate) or by radiotherapy to the brain. Prognosis, prevention, and outcomes: Some patients respond to treatment; however, the prognosis is generally poor, with death occurring within one month if the disease is untreated. Treatment can extend median survival to three to six months. New treatment options involving new chemotherapy regimens are being tested. Debra B. Kessler, M.D., Ph.D. u
For Further Information Carpenter, Malcolm B. Core Text of Neuroanatomy. 2d ed. Baltimore: Williams & Wilkins, 1981. 237
Carcinosarcomas Grossman, Robert I., and David M. Yousem. Neuroradiology: The Requisites. St. Louis: Mosby-Year Book, 1994. Osborn, Anne G. Diagnostic Neuroradiology. St. Louis: Mosby-Year Book, 1994. Robbins Pathologic Basis of Disease. 5th ed. Philadelphia: W. B. Saunders, 1994. Watanabe, M., R. Tanaka, and N. Takeda. “Correlation of MRI and Clinical Features in Meningeal Carcinomatosis.” Neuroradiology 35 (1993): 512-515. u
Other Resources
American Cancer Society http://www.cancer.org National Cancer Institute http://www.cancer.gov See also Acoustic neuromas; Carcinosarcomas; Craniotomy; Infection and sepsis; Leptomeningeal carcinomas; Lumbar puncture; Meningeal carcinomatosis.
u Carcinosarcomas Category: Diseases, symptoms, and conditions Also known as: Mixed epithelial-stromal carcinomas, mixed epithelial-nonepithelial malignant tumors, collision tumors, malignant mixed mullerian tumors, sarcocarcinomas Related conditions: Carcinoma, carcinoma in situ, carcinoma of unknown primary, carcinomatosis, carcinomatous meningitis Definition: Carcinosarcomas are malignant tumors (abnormal masses of tissue that can invade and destroy local tissue and spread to other regions) that are a combination of carcinoma (cancer of epithelial tissue, which is skin or tissue that lines organs) and sarcoma (cancer of connective tissue, such as bone) that occur throughout the body. The stromal (connective tissue) component is usually high grade (contains abnormal cells that will most likely grow and spread quickly). The mesenchymal (the mass of tissue that develops mainly from the mesoderm, the middle layer of the trilaminar germ disc during development) component is classified into two groups: the homologous form composed of cell types that are normally found and the heterologous form composed of cell types that are not normally found.
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Salem Health: Cancer Risk factors: Tamoxifen (a nonsteroidal triphenylethyl compound), widely used as adjuvant therapy in the treatment of breast cancer, has been positively correlated with the development of uterine carcinosarcoma. Radiation and chemical exposure also have been associated with carcinosarcomas. Etiology and the disease process: The cause of carcinosarcomas is poorly defined. For malignant mixed mullerian tumors (carcinoma of the endometrium), based on histological staining preparations, the epithelial and stromal components are presumed to originate from the same cell. Incidence: Incidence depends on the type of carcinosarcoma. Uterine carcinosarcoma is estimated at 33.4 and 17.0 per million in black and white women respectively. Symptoms: Carcinosarcomas can occur anywhere in the body. They often produce no signs and symptoms in their early stages. They may grow and produce a lump or swell. A tumor may cause pain if it impinges on nerves or muscles. The tumor may cause blockage, bleeding, or other pathological features depending on the location. Screening and diagnosis: Carcinosarcomas, like many cancers, are staged according to their size and location, their spread to lymph nodes, their spread to other regions in the body, and their grade. Magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound are frequently used for diagnosis. Biopsies are conducted to determine the malignancy and the grade (aggressiveness) of the tumor. Treatment and therapy: Treatment options for carcinosarcomas, as with other cancers, depends on size, type, location, and stage. Prognosis, prevention, and outcomes: Prognosis and outcome are determined primarily by depth of invasion and stage. Rena C. Tabata, M.Sc. See also Carcinoma of unknown primary origin (CUP); Carcinomatosis; Carcinomatous meningitis; Meningeal carcinomatosis; Metastatic squamous neck cancer with occult primary; Uterine cancer.
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u Cardiomyopathy in cancer
patients Category: Diseases, symptoms, and conditions Also known as: Doxorubicin-induced cardiomyopathy, secondary cardiomyopathy, bleomycin-induced cardiomyopathy, radiation-induced cardiomyopathy Related conditions: Breast cancer, esophageal cancer, lymphoma, metastases from primary cancers Definition: Cardiomyopathy is a disease in which the heart muscle is abnormally enlarged, thickened, or stiffened, decreasing its ability to pump blood. According to the World Health Organization, cardiomyopathies can be divided into three types: dilated, restrictive, and hypertrophic, both primary (or idiopathic) and secondary. Cardiomyopathy in cancer patients involves the secondary type of cardiomyopathy, due to a specific cause, usually chemotherapeutic agents such as doxorubicin as well as radiation, which is often employed for lymphoma or cancer of the breast or esophagus. In addition, metastases to the heart muscle from a cancer found elsewhere in the body can result in a restrictive form of cardiomyopathy. Risk factors: Risk factors for cardiomyopathy in cancer patients include radiation and chemotherapy. Etiology and the disease process: Both doxorubicin and bleomycin cause a dilated type of cardiomyopathy in which both the left and right ventricles are enlarged. The drugs most frequently associated with cardiotoxicity are doxorubicin (Adriamycin) and daunorubicin, which are anthracyclines. The total dose of anthracyclines a person receives determines the probability of developing chronic cardiomyopathy. Other chemotherapeutic drugs that can cause dilated cardiomyopathy include mitoxantrone, interferon, aldesleukin, trastuzumab (a monoclonal antibody), bleomycin, cyclophosphamide, 5-fluorouracil, vincristine, vinblastine, busulfan, mitomycin C, cisplatin, amsacrine, paclitaxel, and docetaxel. In dilated cardiomyopathy due to chemotherapeutic agents, the left ventricle typically demonstrates global hypokinesis, whereas the right ventricle has a less severe abnormality of contractility. Because of the ventricular dilatation, both mitral and tricuspid regurgitation are common, and patients with this condition also exhibit reduced ejection fractions. Decreased cardiac output, decreased stroke volume, and decreased systolic function are seen as well. Mural thrombi may also be present due to akinesis of the cardiac apex. Radiation to the chest can cause a restrictive form of
Cardiomyopathy in cancer patients cardiomyopathy. In this condition the normal heart muscle is replaced by abnormal tissue. This abnormal tissue restricts the diastolic relaxation of the heart muscle so that the heart has normal ventricular size and contractility but aberrant diastolic relaxation leading to elevation of end diastolic pressures of the ventricles. Incidence: The incidence of congestive heart failure secondary to cardiomyopathy from epirubicin is 0.7 percent. Doxorubicin is more cardiotoxic than epirubicin, and the incidence of congestive heart failure ranges from 3 to 4 percent. Symptoms: In restrictive cardiomyopathy, the signs and symptoms are related to congestive failure and arrhythmias. In dilated cardiomyopathy due to chemotherapeutic agents, occasionally these agents will cause an acute cardiotoxic effect, with symptoms such as abnormal heart rhythms and electrocardiogram changes. Screening and diagnosis: Chest X ray demonstrates the paradox of a huge heart with clear lungs in dilated cardiomyopathy. In the restrictive form of cardiomyopathy, the chest X ray often shows a normal-size heart with pulmonary congestion. Because the resultant abnormal physiology of restrictive cardiomyopathy is similar to that of constrictive pericarditis, distinction between these two entities is difficult. Magnetic resonance imaging (MRI), like computed tomography (CT), demonstrates a pericardial thickness greater than 4 millimeters in all patients with constrictive pericarditis, but this is rarely seen in restrictive cardiomyopathy. In restrictive cardiomyopathy, the electrocardiogram shows low voltage in the late stages, and echocardiography shows decreased diastolic function with normal to
Some Common Symptoms of Cardiomyopathy
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Tiredness Weakness Abnormal heart rhythm (rapid or pounding) Heart murmur Swelling of legs, ankles, and feet Bloating of the abdomen Shortness of breath while at rest or after exercise Dizziness, fainting, or light-headedness during exercise
Source: National Heart, Lung, and Blood Institute
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Cardiopulmonary resuscitation (CPR)
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decreased ejection fractions. In dilated cardiomyopathy, echocardiography always demonstrates a decreased ejection fraction because of an enlarged left ventricle with global hypokinesis. Systolic function is normal in restrictive cardiomyopathy, whereas it is always decreased in dilated cardiomyopathy. The reverse is true with diastolic function, where it is normal in dilated cardiomyopathy but decreased in restrictive cardiomyopathy. Gated myocardial scintigraphy shows decreased left ventricular ejection fraction, shortened ventricular ejection time, and decreased rate of ejection in dilated cardiomyopathy. Because marked focal wall abnormalities are usually absent in dilated cardiomyopathy, this may help distinguish it from endstage coronary artery disease, which can manifest with focal-wall motion abnormalities.
u
Treatment and therapy: Nuclear medicine techniques have become important in monitoring left and right ventricular function in patients receiving chemotherapeutic agents that are cardiotoxic, including anthracyclines such as doxorubicin and daunorubicin. Gated myocardial scintigraphy is reproducible, allowing for serial assessment of ejection fractions and the selection of patients who may best tolerate the medication. Gated myocardial scintigraphy is especially important in monitoring patients to determine the onset of cardiac toxicity. Many clinicians allow the ejection fraction to fall to 0.45 in patients receiving doxorubicin before discontinuing therapy. Newer forms of anthracyclines called liposome encapsulates have been shown to be less toxic to the heart and still effective against cancer.
Category: Procedures Also known as: Basic life support
Prognosis, prevention, and outcomes: Lifestyle changes can reduce symptoms of heart failure from cardiomyopathy. Reducing salt and fluid intake and avoiding alcohol are beneficial as well as a judicious exercise plan to increase stamina without overtaxing a failing heart. Some patients whose cardiomyopathy progresses despite medication may be candidates for cardiac transplant. Debra B. Kessler, M.D., Ph.D. u
For Further Information Brandenberg, R. O., et al. “Report of the WHO/ISFC Task Force on Definition and Classification of Cardiomyopathies.” Circulation 64 (1981): 437A. Brant, William E., and Clyde A. Helms. Fundamentals of Diagnostic Radiology. Baltimore: Williams and Wilkins, 1994. Mettler, Fred A., and Milton J. Guiberteau. Essentials of Nuclear Medicine Imaging. 3d ed. Philadelphia: W. B. Saunders, 1991. 240
Other Resources
American Heart Association Cardiomyopathy http://www.americanheart.org/ presenter.jhtml?identifier=4468 The Cardiomyopathy Association http://www.cardiomyopathy.org/ See also Nuclear medicine scan; Radionuclide scan.
u Cardiopulmonary
resuscitation (CPR) Definition: Cardiopulmonary resuscitation (CPR) is an emergency procedure performed by health care providers and laypeople that maintains breathing and circulation after a person’s heartbeat and breathing cease. Cancers treated: Can be used to support those with cancer with an advance directive declaring a desire for life support Why performed: CPR is performed to maintain breathing and circulation and to prevent brain death when a person suffers cardiopulmonary arrest. Patient preparation: Before beginning CPR, the patient is placed on a flat firm surface in a face-up position. If the patient is found face down, then the patient must be logrolled into a face-up position. Steps of the procedure: The health care provider makes sure that the patient is unresponsive by tapping the patient on the shoulder and asking, “Are you all right?” The health care provider activates the emergency system, calls for a defibrillator, and begins CPR. The patient’s airway is opened using the head tilt-chin lift maneuver unless a head or neck injury is suspected. To perform this maneuver, the health care provider places one hand on the patient’s forehead and applies pressure firm enough to tilt the patient’s head back. Next, the health care provider places the fingertips of the other hand under the bony portion of the patient’s lower jaw near the chin and then lifts the chin. If a head or neck injury is suspected, then a jaw-thrust maneuver is performed. To perform this maneuver, the health care provider gets into position at the patient’s head, rests the thumbs (pointing toward the patient’s feet) on the patient’s lower jaw near the corners of
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Cardiopulmonary resuscitation (CPR)
A man receives CPR. (Digital Stock)
the mouth, and opens the airway by lifting the lower jaw with the fingertips. While keeping the airway open, the health care provider looks, listens, and feels for breathing. If no breathing is detected within ten seconds, then the health care provider gives two breaths (each over one second). Each breath should deliver enough volume to make the patient’s chest rise. If the patient has no response, then the health care provider checks to see whether the patient has a pulse. If a pulse is present, then the health care provider continues delivering eight to ten breaths per minute. If no pulse is detected, then the health care provider kneels (or stands, if the patient is in a bed) next to the patient’s chest and begins compressions. Chest compressions are begun by placing the heel of one hand on the sternum in the middle of the chest and then placing the heel of the second hand on top of the first. The sternum is depressed 1.5 to 2.0 inches (for an adult), and compressions are delivered at a ratio of thirty compressions to two breaths. Approximately one hundred compressions are delivered each minute. Cycles of thirty compressions and two breaths are delivered continuously until an automated external defibrillator (AED) or stan-
dard defibrillator arrives, the patient begins to move, or the advanced cardiac life support team arrives. When a defibrillator arrives, it is attached to the patient, and the patient’s heart rhythm is evaluated. If the heart rhythm is shockable, then the health care providers stand clear of the patient while a shock is delivered. If the patient’s rhythm returns to normal and the patient begins to move, then CPR is stopped. Ir the patient’s condition remains unchanged, then CPR is continued for five cycles immediately after the shock. The heart rhythm is checked again, and another shock is delivered if the rhythm is shockable. If the rhythm is not shockable, then CPR is resumed while advanced cardiac life support is administered. After the procedure: During advanced cardiac life support, an endotracheal tube is inserted through the patient’s nose or mouth and then advanced into the airway. This tube is used to administer oxygen directly into the patient’s lungs. The patient is attached to a portable continuous cardiac monitor, and a large intravenous (IV) catheter is inserted. The IV catheter is used to administer fluids and medications to help establish a normal heart rhythm and maintain blood pressure. 241
Caregivers and caregiving When the patient’s heart rhythm begins to stabilize, the patient is transferred to the intensive care unit (ICU). The respiratory therapist attaches the patient to a mechanical ventilator to assist the patient’s breathing. The ICU nurses attach the patient to a continuous cardiac monitor and an automatic blood pressure cuff so that they can closely monitor the patient’s heart rhythm and vital signs. The nurses also listen to the patient’s heart and lungs. A chest X ray is obtained to make sure that the endotracheal tube is in the proper location. A 12-lead electrocardiogram and blood samples are obtained to help determine the cause of cardiac arrest. When the cause is determined, an individualized treatment plan is developed. The length of stay in the ICU depends upon the patient’s condition and response to treatment. Risks: According to the American Heart Association, CPR can double a patient’s chance of survival if provided immediately after cardiac arrest. CPR is not without risk, however. It can cause sternal and rib fractures, pneumothorax (collection of air in the chest cavity), hemothorax (collection of blood in the chest cavity), injury to the heart and great vessels, organ laceration, or aspiration of stomach contents into the lungs. Results: Positive results of CPR are the return of spontaneous breathing and normal heart rhythm without signs of brain damage. When CPR is ineffective, death commonly results. Collette Bishop Hendler, R.N., M.S. u For Further Information American Heart Association. “2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.” Journal of the American Heart Association 112, no. 24 (December 13, 2005). BLS for Health Care Providers. Dallas: American Heart Association, 2006. Cardiovascular Care Made Incredibly Visual. Philadelphia: Lippincott Williams & Wilkins, 2007. Thygerson, A., et al. First Aid, CPR, and AED. 5th ed. Sudbury, Mass.: American College of Emergency Physicians/Jones & Bartlett, 2006. u
Other Resources
American Heart Association http://www.americanheart.org See also Advance directives; Do-not-resuscitate (DNR) order; End-of-life care; Living will. 242
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u Caregivers and caregiving Category: Social and personal issues Definition: Caregivers are people who are engaged in providing care to an ill person. There are two categories of caregivers, paid professionals and informal caregivers. Professional caregivers—home health aides, companions, and hospice workers—are trained to provide caregiving services. Informal caregivers, usually family and friends of the ill person, typically provide services without charge because of their relationship with the person. Statistics: According to the Family Caregiver Alliance, there are an estimated 44 million people in the United States who are engaged in caregiving for a family member. Three out of five informal caregivers are women. A majority of caregivers are middle-aged, and a quarter of all caregivers provide care for someone over the age of fifty. Half of all caregivers are employed full or part time and provide fewer than eight hours of care per week. The average caregiver spends four to five years in this role. Many informal caregivers provide care for a loved one living in close proximity; however, a number of caregivers fall into the long distance category, spending on average $392 a month on travel and out-of-pocket expenses as part of their caregiving duties. The role of the caregiver: There is no “typical” caregiver in terms of the support the person provides to an ill person. Some caregivers help with grocery shopping and laundry, others take a loved one to doctor visits and help change bandages, while still others provide long-distance support
Tips for Self-Care for Caregivers
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Recognize the signs of stress and learn to manage it. Take breaks from caregiving without feeling guilty. Seek help from others, whether relatives, friends, agencies, or professionals. Recognize your emotions and try to understand what they are telling you. Seek counseling or care if depression strikes you. Pay attention to your own health needs. Get enough sleep and eat a balanced diet. Engage in exercise on a regular basis. Keep the lines of communication flowing among you, the ill person, and the health care team. Identify specific problems and seek solutions.
Source: Family Caregiver Alliance
Salem Health: Cancer
Caregivers and caregiving
to someone by checking in with the individual on a regular basis and lending an ear. According to the American Cancer Society, for caregivers to give appropriate care, they need to take time to listen to the person requiring caregiving and ask what types of help that person may need on an ongoing basis. Open communication is vital. A caregiver may think the patient needs help with something that the person feels capable of handling. To keep conflict and frustration to a minimum, the caregiver and cancer patient must be willing to listen to each other’s needs and concerns. Both parties need to keep focused on their goal: to provide the About 44 million people in the United States are engaged in providing care for a family member. (Digital Stock) most appropriate care and make sure all needs are met. In addition to the important role a can provide services, long-distance caregivers can consult caregiver plays in the life of the patient, the caregiver is a local telephone book or do an Internet search. The type of also a vital part of the health care team. Caregivers can proprofessional caregiver hired will vary depending on a pavide important information on the patient’s health by obtient’s needs. It is also helpful for a long-distance caregiver serving health signs and symptoms while they help the pato make a list of the ill person’s local friends and contact tient. Typically, caregivers look for changes in mental and them to see if they would be willing to check in on the indiemotional function and any noticeable changes in the pavidual on occasion and help with tasks that must be done in tient’s condition. Caregivers should ask the medical properson. It may also be wise to set aside money on a regular viders how to keep records and how to perform any tasks basis to pay for those times when the caregiver may unex(such as bandage changing) that they are being asked to pectedly need to travel to the patient’s side. do. The American Red Cross offers caregiving courses onProfessional caregivers can perform a number of tasks line and in person that may help caregivers feel more comand go by different names, according to the National Assopetent in their new role. ciation for Homecare. For example, a home health aide can Caregivers need to take time to think about what tasks administer medical treatments, while a companion will sit must be done and determine what they realistically can and with the ill person and may help with light housekeeping want to provide for the ill person. They must determine but is not trained to perform medical duties. Regardless of what they will do themselves and what they will delegate the services the professional caregiver is providing, the to other family members or a hired professional, according main caregiver needs to ask questions to determine whom to the National Cancer Institute. No single person can do to hire. The content of these questions concerns how long everything, and a caregiver’s hardest decision may be dethe caregiver has been working in the field, what kind of termining what tasks must be delegated to others. There is training he or she received, and the professional’s fee and no reason that caregivers should feel guilty about not being work availability. In addition, the employer should check able to do everything alone. When caregivers ask friends the caregiver’s references. Payment for professional careor relatives to help they should not be offended if they are giving services is typically through a combination of selfrefused, as people may have other demands on their time pay and public and private entities. and other priorities. However, when people offer to help, caregivers should take them up on their offers. Those providing long-distance support need to deterCare for caregivers: Some challenges caregivers typimine in what ways the cancer patient needs help and then cally talk about include having less time for their personal find professional or informal caregivers to help with those lives and the difficulty of trying to balance their current responsibilities with their caregiving role. Other concerns needs. To find contact information for local agencies that 243
Caregivers and caregiving include financial strains and feeling physically, emotionally, and mentally distressed. It is important for caregivers to take time to take care of themselves. Many caregivers become so focused on helping someone else that they forget to make themselves a priority. Caregivers can temporarily put aside their needs to help someone else, but putting aside these needs for long periods of time is not wise and can be detrimental to their physical and emotional health. Studies show that informal caregivers are at a higher risk for physical, mental, and emotional illness. They have increased risk for cardiovascular disease, can have impaired immune systems, and may have increased blood pressure and insulin levels. In addition, caregivers are prone to depression, anxiety disorders, and feelings of guilt. Emotionally, caregivers can feel a sense of anger at themselves and the patient, be prone to irritability that leads to moodiness, and be unable to concentrate. To combat the potentially harmful effects of caregiving, it is important for caregivers to make time for themselves and maintain a routine that will be beneficial to their own health. For example, they should make time to exercise, eat well, and get enough sleep as well as to connect with friends and families, pursue their own interests, and do nice things for themselves. Caregivers should also find ways to deal with their emotions regarding their role. Many caregivers will face emotions that range from anger, grief, and guilt to anxiety, depression, and loneliness. These feelings are all normal, and having other caregivers with whom to share their experiences or just being able to vent their emotions is important. Caregiver support groups: Many caregivers find it easier to cope with their role by reaching out to others who share their experiences. From in-person support groups held at local community centers and hospitals to online chat rooms, there are a number of ways a caregiver can connect with other caregivers. Caregivers should try out various types of support groups to find the best option. There are also a number of books about caregiving that include stories by other caregivers. There is no reason caregivers should have to cope alone, as there are many opportunities for caregivers to connect with each other. Jennifer M. Hickin, B.S. u
For Further Information Barry, Michael S. The Art of Caregiving: How to Lend Support and Encouragement to Those with Cancer. Colorado Springs, Colo.: Life Journey, 2007. Capossela, Cappy, and Sheila Warnock. Share the Care: 244
Salem Health: Cancer How to Organize a Group to Care for Someone Who Is Seriously Ill. Rev. ed. New York: Simon and Schuster, 2004. Gilbar, Ora, and Hasida Ben-Zur. Cancer and the Family Caregiver: Distress and Coping. Springfield, Ill.: Charles C Thomas, 2002. Hennessey, Maya. If Only I’d Had This Caregiving Book. Bloomington, Ind.: AuthorHouse, 2006. Houts, Peter S., and Julia A. Bucher, eds. Caregiving: A Step by Step Resource for Caring for the Person with Cancer at Home. Rev. ed. Atlanta: American Cancer Society, 2003. Intner, Riki, and Roberta Cole. Caregiving from the Heart: Tales of Inspiration. San Francisco: Elders Academy Press, 2006. Kane, Jeff. How to Heal: A Guide for Caregivers. New York: Allworth Press, 2003. Mintz, Suzanne Gebben. Love, Honor, and Value: A Family Caregiver Speaks Out About the Choices and Challenges of Caregiving. Sterling, Va.: Capital Books, 2002. Perry, Angela, ed. The American Medical Association Guide to Home Caregiving. New York: J. Wiley & Sons, 2001. Rose, Susannah, and Richard Hara. One Hundred Questions and Answers About Caregiving for Family or Friends with Cancer. Sudbury, Mass.: Jones & Bartlett, 2004. u
Other Resources
American Cancer Society Caregiving: How to Care for a Loved One with Cancer—and Yourself http://www.cancer.org/docroot/MLT/content/ MLT_3_1x_Caregiving_—_How_to_Care_for_a_ Loved_One_With_Cancer_And_Yourself.asp CancerCare http://www.cancercare.org Family Caregiver Alliance http://www.caregiver.org National Alliance for Caregiving http://www.caregiving.org National Association for Home Care and Hospice http://www.nahc.org ARCH National Respite Network Respite Locator http://www.respitelocator.org
Salem Health: Cancer See also Advance directives; Aging and cancer; Aids and devices for cancer patients; Cognitive effects of cancer and chemotherapy; Counseling for cancer patients and survivors; Do-not-resuscitate (DNR) order; Elderly and cancer; End-of-life care; Financial issues; Grief and bereavement; Home health services; Hospice care; Informed consent; Karnofsky performance status (KPS); Living with cancer; Long-distance caregiving; Palliative treatment; Personality and cancer; Poverty and cancer; Prayer and cancer support; Psychosocial aspects of cancer; Relationships; Second opinions; Self-image and body image; Sexuality and cancer; Singlehood and cancer; Stress management; Support groups; Survivorship issues; Transitional care; Watchful waiting.
Carotenoids found in the thyroid, adrenal gland, breast, brain, and testes. Symptoms of these tumors can include rash, fever, and joint pain. Screening and diagnosis: Although no standard screening guidelines exist for Carney complex, it is recommended that people suspected of having the disease receive an echocardiogram and blood tests (particularly for prolactin, cortisol, and insulin-like growth factor 1, or IGF-1) once a year, as well as frequent skin, thyroid, and genital exams. If a diagnosis of Carney complex is made, patients should be referred to an oncologist, as there is an increased risk in the development of cancer in patients with Carney complex. Treatment and therapy: Treatment and therapy are based on the symptoms exhibited by the patient.
u Carney complex Category: Diseases, symptoms, and conditions Also known as: Nevi, atrial myxoma, myxoid neurofibroma, and ephelides (NAME) syndrome; lentigine, atrial myxoma, mucocutaneous myxoma, blue nevi (LAMB) syndrome Related conditions: Cushing syndrome, multiple thyroid nodules, benign tumors Definition: Discovered in 1985 by J. Alden Carney, Carney complex is a very rare, inherited genetic condition that can cause a variety of symptoms, ranging from skin pigmentation to tumor growth throughout the body. It primarily involves the endocrine system and, depending on the severity of its symptoms, can lead to cancer or heart failure. Risk factors: Because Carney complex is an inherited condition, risk factors include family members with Carney complex. Genetic testing or screening is advised for patients with family members who have been previously diagnosed with Carney complex. Etiology and the disease process: The genes PRKAR1A and CNC2 have been identified in causing Carney complex. It is thought that additional genes are also involved. Incidence: Carney complex is a rare condition with only 400 cases being documented worldwide. Symptoms: Onset of Carney complex usually begins in a person’s twenties, and symptoms can include spotted pigmentation of the skin on the eyes, lips, mouth, and genitals, as well as heart-related conditions, such as tumors in the chambers of the heart, which, while typically benign, can lead to stroke or heart failure. These tumors can also be
Prognosis, prevention, and outcomes: As Carney complex has been diagnosed in less than 400 people throughout the world, with approximately 50 to 75 percent of those cases due to genetic inheritance, prevention is limited to repetitive screening and genetic testing. The outcome of Carney complex is determined by the severity of the symptoms and the speed of diagnosis. Anna Perez, M.Sc. See also Adrenal gland cancers; Adrenocortical cancer; Cushing syndrome and cancer; Endocrine cancers; Genetic counseling; Genetic testing.
u Carotenoids Category: Lifestyle and prevention Also known as: Carotenes (alpha-carotene, betacarotene) Definition: Carotenoids are chemical substances found in yellow, orange, and red fruits as well as dark green, leafy vegetables. They are rich in antioxidants, and some studies suggest that inclusion of carotenoids in diets sharply reduces the risks of a variety of cancers. Other studies warn that they may actually promote cancer when taken in pill or capsule form, especially in smokers or former smokers. Cancers treated or prevented: May reduce risk of prostate, breast, lung, cervical, colon, stomach, rectal, ovarian, oral, pharyngeal, bladder, and other cancers Delivery routes: Oral in diet, tablet, or capsule How these compounds work: Carotenoids are chemicals produced by plants best known for their reddish and yellowish colors, as in the reds of a tomato or carrot. Carot245
Cartilage supplements enoids reduce the risk and incidence of cancer by acting as antioxidants, binding with and thereby reducing the amount of free radicals in the human body. Free radicals (which act as oxidants) are unstable molecules that lack a sufficient number of electrons. In their quest to become stable, they can wreak havoc on genetic material and proteins, disrupting cell molecules and chemical processes and making cells more susceptible to cancer. Antioxidants eliminate many of these cell-harming free radicals, in theory reducing the predisposition of cells to become cancerous. Studies have also suggested that carotenoids in the diet can inhibit cancer development by stimulating the manufacture of detoxifying enzymes and inhibiting the proliferation of cancer cells by the regulation of communication between cancer cells. The mechanism by which carotenoids may affect or prevent cancerous cells is unknown. Lycopene and betacarotene are the two most widely studied carotenoids, though there are at least six hundred known carotenoids in all. Researchers have shown in the laboratory that small concentrations of alpha- or beta-carotene severely hindered the growth and spread of neuroblastoma cells. The N-myc gene exists in all cells and codes for proteins that stimulate cell growth. Usually, this gene is dormant unless the cell becomes damaged or receives signals to activate cellular growth. Carotenoids inhibit this gene activity, causing a decrease in activation or complete inactivation of this gene in cancerous cells. Most—but not all—studies show an inverse relationship between serum levels of carotenoids and cancer incidence, but others show no affiliation and still others even show that high levels of certain carotenoids such as 3carotene may increase the risk of certain types of cancers. All, however, agree that the antioxidant role of carotenoids reduces the concentration of harmful oxidants, and many more studies are being conducted that may better control for lifestyle differences, age, gender, and genetic predisposition. It remains the consensus among researchers and physicians that regardless of the study outcomes, carotenoids are most likely beneficial and play some role in cancer prevention. Side effects: Although no specific side effects are known, consumption of large amounts of 3-carotene may increase the risk of lung cancer, especially in smokers. As stated in the Wellness Guide to Dietary Supplements (produced by the Berkeley Wellness Letter, available online at http:// www.wellnessletter.com/): Don’t assume that beta carotene or other antioxidants in supplement form are beneficial, or even harmless. Don’t
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Salem Health: Cancer take beta carotene pills, particularly if you’ve ever been a smoker. Beta carotene is plentiful in vegetables and fruits, and is safe and beneficial when consumed from such foods.
Dwight G. Smith, Ph.D. See also Antioxidants; Beta-carotene; Chemoprevention; Fruits; Nutrition and cancer prevention; Stomach cancers.
u Cartilage supplements Category: Complementary and alternative therapies; lifestyle and prevention; chemotherapy and other drugs Also known as: Shark cartilage, bovine cartilage Definition: Cartilage is a type of dense, semi-opaque, elastic connective tissue found in humans and animals that has no blood supply of its own. It consists of cells called chondrocytes in a matrix of collagen, protein, and sugar. Cartilage supplements, often promoted as a treatment for cancer, come from animal sources, particularly the heads and fins of sharks and the windpipes of cattle. Cancers treated or prevented: Lymphoma, breast cancer, colon cancer, lung cancer, prostate cancer, brain cancer Delivery routes: Administered orally via pills, powders, or liquids; also given as enemas, by topical application, or through intravenous and intramuscular injection How this substance works: The use of shark cartilage for cancer treatment is based on the process of angiogenesis, the development of new blood vessels. In the 1970’s, Dr. Judah Folkman noted that most tumors require a supply of nutrients and oxygen carried through blood in order to grow. It was found that shark cartilage has a protein that inhibited angiogenesis in the laboratory. Therefore, it was proposed that it could block the blood supply to tumors and literally “starve” them. William Lane, who holds a Ph.D., investigated this possibility and in 1993 published Sharks Do Not Get Cancer, which established shark cartilage as a leading alternative cancer therapy. Cases of tumors in sharks, however, have been documented. It has also been found that an active ingredient in shark cartilage is too large to be absorbed into the human bloodstream from the digestive tract. Dr. John Prudden in the 1950’s found that bovine cartilage contains complex molecules called mucopolysaccharides, which were thought to stimulate the immune system to fight off cancer and to block cell division and
Salem Health: Cancer growth. Although there has been much continuing research, results on the use of cartilage supplements have been mixed. Extensive clinical studies so far, however, conclude that none of the cartilage supplements offers any significant benefits for cancer patients. Side effects: Cartilage supplements contain high amounts of calcium. Taking them with thiazide diuretics, which raise calcium levels in the blood, may therefore result in dangerous calcium levels. Supplements not from reputable manufacturers may be contaminated. One case of shark cartilage-induced hepatitis has been noted. Large doses may cause nausea. Because cartilage supplements stop or hinder the development of new blood vessels, pregnant or breastfeeding women, children, and patients recovering from surgery or heart attack should not take them. Martha O. Loustaunau, Ph.D. See also Calcium; Complementary and alternative therapies; Integrative oncology; Nutrition and cancer prevention.
u Case management Category: Social and personal issues Also known as: Medical case management, disease management, care management, patient care management, care coordination, care planning Definition: In general terms, case management is a process that brings together the resources of disparate people and agencies to evaluate a person’s health needs and put together, implement, coordinate, and monitor a plan to address them. The process combines, as needed, the resources of patients and their families, health care professionals, social service agencies, community groups, employers, and insurance carriers to meet its goals. Goals of case management: The principal goal of case management is to help patients and their families navigate the complex and fragmented health care system by coordinating efforts among service providers to deliver timely, appropriate, and cost-effective care according to each individual’s needs. Health care has been increasingly moving toward a patient-centered model, in which the values, preferences, cultural traditions, family situations, and lifestyles of patients and their families are taken into consideration. Therefore, case management typically tries to involve patients and their families in prevention plans, treatment options, and financial decisions. It also aims to
Case management reduce health care costs for patients and service providers. By coordinating all the various functions of treating people for serious diseases such as cancer, efficiency is increased and cost is decreased. Case management also tries to improve the standards of care for patients. Many medical and government organizations—along with individual hospitals, clinics, and medical centers (including cancer centers)—have established case management guidelines. These guidelines, based on empirical research and numerous trials and observations, provide a system to help patients across what is known as the continuum of care. Clinical and ethical standards apply in all areas of care, from prevention of disease to end-of-life issues, and to all the components of case management. Case management components: Case management has developed a set of core components: screening and assessment, treatment, community involvement, arranging for nonmedical services, monitoring, and reassessment. These core components, along with sets of subcomponents, come together to create a specific care plan for each patient. For example, the case management components and subcomponents for the care plan of a seventy-five-year-old man with prostate cancer might include the following: • Screening and assessment: examinations by the patient’s primary care provider, referrals to an oncologist or urologist, testing to determine the nature of the disease, establishing a treatment plan based on the stage of the cancer, evaluating the patient’s financial status, creating the cancer care plan • Treatment: aggressive radiation therapy, five days a week for seven weeks at a cancer center • Community involvement: scheduling rides for the patient to and from the cancer center with volunteers from the local chapter of the American Cancer Society, introducing the patient and the patient’s family to a local support group, referring the patient to an oncology social worker • Arranging for nonmedical services: working with Medicare or Medicaid to pay for treatment • Monitoring: periodic checking to see that all components of the cancer care plan are functioning, and adjusting the plan if necessary • Reassessment: scheduled follow-up visits with doctors, the oncology social worker, and Medicare or Medicaid Managing all these components to create the cancer care plan is the job of the medical case manager. The medical case manager: Most medical case managers (MCMs) are registered nurses. The medical case manager may also be a staff member of a hospital or cancer center and is often hired by an employer or insurance carrier. The 247
Castleman disease role of the medical case manager includes, but is not limited to, the following: • Overseeing patients’ cancer care throughout diagnosis, treatment, and follow-up • Assessing patients’ health, nutrition, psychological, and care needs • Assessing patients’ financial needs • Educating patients on different cancer types, treatments and side effects, and possible outcomes to allow them to make informed decisions about their care • Helping patients communicate more effectively with their doctors • Linking patients with the appropriate community resources • Coordinating the efforts of the cancer care team The cancer care team: Each cancer patient’s needs are different. Meeting those needs requires a team of professionals with different expertise. Depending on the patient, the cancer care team may consist of the following individuals, all under the watchful eye of the medical case manager: • Oncology social worker: a professional trained in counseling and providing practical assistance in navigating the health care system • Psychiatrist or psychologist: to help the patient who has trouble coping psychologically with cancer • Nurses: providers of a wide range of help, from implementing the care plan to answering questions for the patient and family • Home health aide: a worker who helps cancer patients at home with daily living tasks • Rehabilitation specialists: physical, occupational, and speech therapists who help patients recover from the physical changes caused by cancer or cancer treatment • Oncology nutritionist: a specialist who advises on diet to help the patient cope with the consequences of cancer and side effects of treatment • Hospice workers: caregivers who focus on the special needs of patients with terminal cancer Wendell Anderson, B.A. u
For Further Information Cohen, E., and T. Cesta. Nursing Case Management: From Concept to Evaluation. 3d ed. St. Louis: Mosby, 2000. Fattoursso, D., and C. Quinn. A Case Manager’s Study Guide. 2d ed. Sudbury, Mass.: Jones and Bartlett, 2004. Mullahy, C. The Case Manager’s Handbook. Sudbury, Mass.: Jones and Bartlett, 2004. 248
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Other Resources
Case Management Society of America http://www.cmsa.org National Cancer Institute http://cancer.gov See also Cancer care team; Cancer education; Caregivers and caregiving; Counseling for cancer patients and survivors; Family history and risk assessment; Genetic counseling; Home health services; Hospice care; Karnofsky performance status (KPS); Living with cancer; Longdistance caregiving; Medical oncology; Oncology; Oncology clinical nurse specialist; Oncology social worker; Pharmacy oncology; Primary care physician; Psychooncology; Radiation oncology; Rehabilitation; Surgical oncology.
u Castleman disease Category: Diseases, symptoms, and conditions Also known as: Angiofollicular lymph node hyperplasia, angiomatous lymphoid, Castleman tumor, giant benign lymphoma, Castleman’s disease Related conditions: Angiocentric immunoproliferative lesion, lymphomatoid papulosis Definition: Castleman disease is a rare disorder of the lymphatic system that causes the growth of benign tumors. Two localized forms often appear in the mediastinum: hyaline-vascular, accounting for almost 90 percent of the cases, and plasma cell. The multicentric type involves several different areas of the body. Risk factors: Human immunodeficiency virus (HIV) infection is the only known risk factor. It is much more common in HIV patients, particularly in those who have developed acquired immunodeficiency syndrome (AIDS). Etiology and the disease process: The etiology of this disease remains unknown. Increased production of interleukin-6 (IL-6) in the lymph nodes may play a role in the development of the disease. Human herpesvirus 8 (HHV-8) also plays a role in the development of the multicentric type. Incidence: Although the number of patients diagnosed annually is unknown, Castleman disease is a very rare condition. Two leading cancer centers in the United States each see about two cases per year. The number of cases has
Salem Health: Cancer been rising over the past twenty years, however, as the incidence of HIV infection has increased. Symptoms: Most patients who have the hyaline-vascular type are asymptomatic. Those who have the plasma cell type may have excessive sweating, fatigue, fever, skin rash, or weight loss. Those who have the multicentric type may have a variety of symptoms depending on the areas affected—a common finding is enlarged liver or spleen. Screening and diagnosis: There is no screening method. Diagnosis is suggested by the appearance of benign lymphatic tumors on imaging studies and the presence of elevated IL-6 levels. Definitive diagnosis can be made only by removal or biopsy of the tumor for histologic examination. Treatment and therapy: Therapy is usually symptomatic. For localized types, the most common treatment is surgical removal of the tumor. Corticosteroids are used to treat specific symptoms associated with plasma cell and multicentric types, and the multicentric type is sometimes treated with chemotherapeutic agents. Prognosis, prevention, and outcomes: Prognosis for the localized types is good following complete surgical removal of the tumor. Prognosis is poor, however, for the multicentric type, with an overall mortality rate of 50 percent and median survival of twenty-six months. Jeremy W. Dugosh, Ph.D. See also Benign tumors; Cutaneous T-cell lymphoma (CTCL); Lymphomas; Mycosis fungoides.
u Cell phones Category: Carcinogens and suspected carcinogens Also known as: Cellular phones Related cancers: Gliomas, astrocytomas Definition: Cell phones are handheld electronic communication devices that send and receive wireless electromagnetic signals. Their ubiquitous use and proximity to the brain during use has prompted concerns over their long-term impact on human health, including their potential association with cancers. Exposure routes: Radiation that is strong enough to penetrate human tissue Where found: Electronic devices such as mobile or cellular phones, microwave ovens, and computer monitors that emit radiofrequency radiation
Cell phones At risk: Possibly people who are exposed to high levels of electromagnetic radiation, such as electric railway workers and those exposed to lower levels of radiation over many years Etiology and symptoms of associated cancers: Of the dozens of epidemiological studies published since the 1990’s on the harmful effects of cell phones, only a few have indicated a possible relationship between cell phone usage and cancer. The overwhelming scientific evidence supports the conclusion that cellular phones do not pose a health risk for the more than one billion users worldwide. The electromagnetic frequency range of cell phones is from about 850 to 1900 megahertz. Regulatory bodies in the United States do not recognize radiofrequency radiation emitted from a cell phone as a carcinogen. At high enough levels, radiofrequency energy can damage biological tissue through the application of heat. This energy is essentially what gets produced in a microwave oven when it cooks food. Since mobile or cellular phones emit very low levels of radiofrequency radiation, it had always been assumed that these small electronic devices do not pose a health risk. However, some scientists have argued that long-term exposure to even low intensities of radiation could promote the development and growth of tumors as well as contribute to other kinds of health problems. Because cell phones are placed right against the head, in close proximity to the radiofrequency waves being sent and received, researchers wondered if they would cause damage. Brain tumors, originating from different types of cells, have received the most attention, particularly tumors that have developed on the same side of the head that the individual most often uses when talking on the phone. Of the 47,000 new cases of brain tumors diagnosed each year in the United States alone, only a small number of cases can be understood in terms of what has caused the cancer to develop. Unfortunately, little is known about potential mechanisms that might cause brain cancers to develop in general. In terms of cell phone radiation as a possible cause of cancer, no hypothesis has been offered that adequately explains how low levels of radiofrequency energy emitted from cell phones could alter biological tissue or bring harm to the user. History: The incidence of brain tumors began rising in the 1990’s, and this increase cannot be fully explained by the improved diagnostic methods used to detect these tumors. One way to study possible external factors that might be responsible for the increase in tumors is to conduct an epidemiological study. Epidemiological studies look at the 249
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frequency of a health problem—such as cancer—in different groups of people. For example, those who have been diagnosed with a brain tumor are compared with a group who share similar characteristics except they do not have a brain tumor. Scientists can then explore how these two groups might differ in terms of frequency, duration, and exposure intensity of radiofrequency radiation from cellular phone usage. One weakness of this type of study is that it is not particularly well suited to determine cause-andeffect relationships. In 2002, Lennart Hardell from University Hospital, Orebro, Sweden, and his colleagues found an increase in malignant brain tumors associated with the use of analog, digital, and cordless phones. He also found that risks for astrocytomas increased over time and that risk of glioma went up for periods greater than ten years. There did not appear to be an increased risk for meningioma over a long period of time. In another study, Hardell came to the conclusion that there is no association between cell phones and salivary gland tumors. Although Hardell and colleagues have published data that support claims that cellular phone use is associated with brain cancer, dozens of other studies have found results to the contrary. Several studies conducted after 2002 have inCell phone radiation has been suggested as a source of brain cancer, cluded much larger numbers of people. Increasing but little scientific evidence supports this theory. (©Popa Sorin/Dreamstime.com) the number of participants can strengthen the research by making it easier for scientists to generalize the results to the overall population. In one of the the Risk for Malignant Brain Tumours.” International largest studies on the use of cell phones and risk for cancer Journal in Radiation Biology 78 (2002): 931-936. ever conducted, more than 420,000 Danish citizens were Schuz, J., et al. “Cellular Telephone Use and Cancer Risk: followed for up to twenty-one years. The researchers Update of a Nationwide Danish Cohort.” Journal of the found no evidence for risk of tumor development from the National Cancer Institute 98 (2006): 1707-1713. use of cell phones either in short-term use or in those who had been using cell phones for more than ten years. Overall, the vast majority of research supports the conu Other Resources clusion that cellular phones do not pose a threat for cancer International Commission for Electromagnetic development. No relationship has been reliably found Safety when variables such as the number of years used, the cuBenevento Resolution mulative hours of phone use, or the number of calls has http://www.icems.eu/benevento_resolution.htm been taken into consideration. Bryan C. Auday, Ph.D. u
For Further Information Connelly, Jennifer M., and Mark Malkin. “Environmental Risk Factors for Brain Tumors.” Current Neurology and Neuroscience Reports 7 (2007): 208-214. Hardell, L., M. Hansson, and M. Carlberg. “Case-Control Study on the Use of Cellular and Cordless Phones and 250
National Cancer Institute Cellular Telephone Use and Cancer: Questions and Answers http://www.cancer.gov/cancertopics/factsheet/Risk/ cellphones See also Electromagnetic radiation; Ultraviolet radiation and related exposures.
Salem Health: Cancer
u Cervical cancer Category: Diseases, symptoms, and conditions Also known as: Cervical squamous cell/ adenocarcinoma, cervical intraepithelial neoplasm (CIN) Related conditions: Squamous intraepithelial lesion (SIL), dysplasia, human papillomavirus (HPV) infection Definition: Cervical cancer is a slow-growing cancer of the female reproductive organs. The two primary types of cervical cancer are squamous cell carcinoma and adenocarcinoma. Classified by microscopic examination, squamous cell carcinoma accounts for 90 percent of diagnosed cases. The majority of the remaining cases are classified as adenocarcinoma, a cancer that develops from the mucus-producing gland cells in the endocervix. Additionally, a very small minority of cervical cancer cases demonstrate characteristics of both types and are therefore classified as adenosquamous or mixed carcinomas. Risk factors: The most significant risk factor for developing cervical cancer is infection with high-risk types of human papillomavirus (HPV). HPV is sexually transmitted, and certain sexual behaviors can increase the risk of infection: sex at an early age, multiple sexual partners (directly or indirectly through a partner who has multiple sexual partners), and sex with an uncircumcised partner. Although use of condoms does not eliminate the potential for HPV infection because any skin-to-skin contact can be sufficient to transmit the virus, condoms nonetheless do provide limited protection. Studies have identified the following additional risk factors: • Obesity/low-fiber diet • Smoking • Concomitant infection with another sexually transmitted disease such as human immunodeficiency virus (HIV), herpes simplex virus (HSV), or chlamydia • Long-term oral contraceptive use • Multiple full-term pregnancies • In utero exposure to diethylstilbestrol (DES, a hormone prescribed from 1940 to 1971 for some pregnant patients considered at high risk for miscarriage) • Family history of cervical cancer Etiology and the disease process: Human papillomavirus (HPV) is a group of more than one hundred distinct viruses, with approximately forty strains capable of infecting the genital tract. Researchers have classified fifteen HPV types as high risk for cancer development, with a nearly two-thirds prevalence of types 16 and 18 in cervical cancer samples. In the vast majority of cases, HPV infec-
Cervical cancer tion is spontaneously cleared by a healthy immune system. In a minority of cases, however, the virus can remain latent for years before eventually converting normal cervical cells to cancerous ones. Because only a small percentage of women infected with HPV progress to cervical cancer, lifestyle and immune system competence are believed to play a vital role in the progression of the disease. Incidence: Cancer of the cervix is second only to breast cancer in prevalence among women worldwide. Nearly 500,000 new cases are diagnosed each year, with a greater than 80 percent occurrence in developing countries. Age-standardized incidence rates fall in the 15 per 100,000 range for most first-world countries. In the United States, more than 11,000 new cases are diagnosed each year, with nearly 4,000 deaths annually. Symptoms: Early cervical cancer does not generally produce any distinguishable signs or symptoms. Abnormalities found in screening tests are the most common and effective method for detecting the presence of precancerous and cancerous cervical cells. As untreated disease progresses, symptoms may include unusual vaginal bleeding (after intercourse, between periods, postmenopausal); watery, bloody, and foul-smelling vaginal discharge; pelvic pain; or pain during intercourse. Screening and diagnosis: Extensive cervical screening programs designed to detect early, precancerous cervical changes are well established in most developed countries. Exfoliative cytology (Pap test) is the primary component of these programs, although molecular HPV deoxyribonucleic acid (DNA) testing is also commonly incorporated. Colposcopy is a second-level diagnostic procedure used as a follow-up to abnormal screening results. Named after the physician who developed the procedure (Papanikolaou), exfoliative cytology, or Pap test, is a screening procedure involving the collection and microscopic evaluation of cervical cells. During a routine pelvic examination, cervical cells are collected by broom, brush, spatula, or other means. These cells are either smeared directly onto a microscope slide (as in the traditional, “dry” Pap smear) or transferred into a liquid medium to concentrate the cells for subsequent transfer onto a slide. This new liquid-based cytology has demonstrated greater test sensitivity because more cells can be analyzed. The HPV DNA test is a molecular analysis of a cervical sample to determine the presence of HPV and its type. This test is used in conjunction with an abnormal Pap test as an additional diagnostic tool. A colposcopy is a pelvic examination in which a light source and binocular microscope are used to enable a di251
Cervical cancer
Salem Health: Cancer
Five-Year Survival Rates for Cervical Cancer, by Stage Stage
Survival Rate (%)
IA IB1 IB2 IIA/B IIIA/B IV
95+ 90 80-85 75-78 47-50 20-30
rect magnified inspection of the patient’s cervix, vagina, and vulva. Application of a weak acetic acid solution also serves to highlight any suspicious abnormalities. Following abnormal screening results, additional tests may be ordered to confirm diagnosis and determine how far the cancer has spread (staging): • Biopsy: Analysis of a small section of tissue collected from the cervix • Proctoscopy: Visual inspection of the rectum for the presence of cancer • Imaging (such as X ray, magnetic resonance imaging, computed tomography, positron emission tomography): Patient/organ appropriate imaging to inspect for cancer spread (metastasis) Cervical cancer is staged based on tumor size, invasive nature, and degree of metastasis (spread to lymph nodes/ organs). Cervical cancer is staged with the International Federation of Gynecology and Obstetrics (FIGO) system: • Stage 0: Carcinoma in situ; superficial cancer is detected in the cervical lining. • Stage I: Cancer has invaded the cervix but has not spread. • Stage IA: Microscopic amounts of cancer cells are present. • Stage IA1: Cancer invasion is less than 3 millimeters (mm) deep and less than 7 mm wide. • Stage IA2: Cancer invasion is between 3 and 5 mm deep and less than 7 mm wide. • Stage IB: Cancer is greater than 5 mm deep and greater than 7 mm wide. • Stage IB1: Cancer is visible but less than 4 centimeters (cm). • Stage IB2: Cancer is visible and greater than 4 cm. • Stage II: Cancer has spread beyond the cervix but is contained within the pelvis. • Stage IIA: Cancer has spread to the upper part of the vagina. 252
•
Stage IIB: Cancer has spread to the parametrial tissue (next to the cervix). • Stage III: Cancer has spread to the lower part of the vagina or the pelvic wall. • Stage IIIA: Cancer has spread to the lower third of the vagina. • Stage IIIB: Cancer has spread to the pelvic wall or blocks urine flow. • Stage IV: Cancer has spread to nearby organs. • Stage IVA: Cancer has spread to the bladder or rectum. • Stage IVB: Cancer has spread to more distant organs. Treatment and therapy: Treatment of cervical cancer largely depends on disease stage. The three treatment options are surgery, radiation, and chemotherapy. Surgical removal is used primarily for nonmetastatic lesions. Cryosurgery uses a metal probe cooled with liquid nitrogen to freeze cancerous cells. Laser surgery uses a laser to burn (vaporize) cancerous cells. In conization, a thin, heated wire (LEEP, or loop electrosurgical excision procedure) or surgical/laser knife (cold knife cone biopsy) removes the affected tissue. Rarely used as a sole treatment, conization aids in diagnosis before additional surgery or alternative treatment. In a hysterectomy, the degree of the removal of uterine tissue (simple vs. radical) depends on the stage and patient circumstances. Radiation employs high-energy X rays to kill cancer cells, either externally (external beam radiation) or internally via a radioactive capsule (brachytherapy). Chemotherapy uses anticancer drugs (such as cisplatin, paclitaxel, topotecan, ifosfamide, or fluorouracil) taken orally or intravenously to treat metastasized cancer. Prognosis, prevention, and outcomes: Early detection through effective screening programs offers a high probability for complete cancer eradication. Continued adherence to annual cervical screening and healthy habits is integral to continued remission. A new vaccine, Gardasil, approved by the Food and Drug Administration offers protection against the most dangerous, high-risk HPV types 16 and 18. It also protects against types 6 and 11, which cause genital warts. For greatest efficacy, the vaccine should be administered before the patient has become sexually active. The Federal Advisory Committee on Immunization Practices (ACIP) recommends vaccination for girls aged eleven and twelve. The committee also recommends that nonvaccinated women from age thirteen to twenty-six receive catchup vaccinations. Although the American Cancer Society (ASC) agrees with the initial vaccination protocol, it recommends catch-up vaccinations for young women aged
Salem Health: Cancer thirteen to eighteen only. ACS recommends that older women discuss the potential benefit of the vaccination with regard to their personal risk factors for previous exposure to HPV. Pam Conboy, B.S. u
For Further Information Devita, Vincent T., Jr., Samuel Hellman, and Steven A. Rosenberg, eds. Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2005. Saslow, D., et al. “American Cancer Society Guideline for Human Papillomavirus (HPV) Vaccine Use to Prevent Cervical Cancer and Its Precursors.” CA: A Cancer Journal for Clinicians 57 (2007): 7-28. Stewart, Bernard W., and Paul Kleihues, eds. World Cancer Report. Lyon, France: IARC Press, 2003. u
Other Resources
American Cancer Society http://www.cancer.org American College of Obstetricians and Gynecologists http://www.acog.org American Society for Colposcopy and Cervical Pathology http://www.asccp.org Gynecologic Cancer Foundation http://www.thegcf.org International Agency for Research on Cancer http://www.iarc.fr National Cancer Institute http://www.cancer.gov National Cervical Cancer Coalition http://www.nccc-online.org World Health Organization http://www.who.org See also Afterloading radiation therapy; Antiviral therapies; Benign tumors; Biological therapy; Birth control pills and cancer; Carcinomas; Carcinomatosis; Colposcopy; Conization; Diethylstilbestrol (DES); Endometrial cancer; Exenteration; Fertility drugs and cancer; Gynecologic cancers; Human papillomavirus (HPV); Hysterectomy; Hystero-oophorectomy; Infectious cancers; Loop electrosurgical excisional procedure (LEEP); Pap test; Pelvic examination; Pregnancy and cancer; Vaccines, preventive; Vaginal cancer; Virus-related cancers.
Chemoembolization
u Chemoembolization Category: Procedures Also known as: Transcatheter chemoembolization, transarterial chemoembolization (TACE) Definition: Chemoembolization is a method of treating cancer by introducing chemotherapy drugs directly into a tumor using a catheter placed in an artery that supplies blood flow to the tumor. Chemoembolization works by blocking the flow of healthy blood to the tumor, thereby shrinking the tumor. It is among the category of procedures known as minimally invasive treatments because it targets the tumor and spares healthy tissues. Cancers treated: Primary liver cancer (hepatoma); other cancers, such as colon cancer, that have spread (metastasized) to the liver. Individuals who have obstruction in vessels of the liver or have liver diseases such as cirrhosis are not usually eligible for chemoembolization. The use of chemoembolization also depends on the number and size of the tumors. Why performed: Chemoembolization is used primarily for cancer in the liver, whether the cancer is confined to the liver or has spread to the liver from another organ. It is sometimes used in combination with surgery, external radiation therapy, or other cancer treatments. In advanced cancers, chemoembolization is used as a palliative treatment (directed at providing comfort and quality-of-life care) to manage symptoms related to the cancer, such as pain or fluid buildup in organs. Chemoembolization offers advantages over traditional chemotherapy, since high doses of chemotherapy drugs can be given directly into the tumor rather than systemically. Also, since the blood supply to the tumor (which is needed for tumor growth) is blocked, the chemotherapy drugs can remain in direct contact with the tumor for a longer time than with traditional chemotherapy. The treatment can also be given more often, usually with fewer side effects since the drug is limited to distribution directly to the tumor area and is not circulating throughout the body. Chemoembolization is also more cost-effective than some other cancer treatments such as surgery or conventional radiation therapy. Patient preparation: A few days prior to the procedure, the patient has blood work to make ensure good liver and kidney functioning. Blood-clotting tests are also done to make sure the patient’s blood clots properly. The patient is usually seen by an interventional radiologist, a medical doctor who is specially trained in treatment and diagnostic procedures using catheters, probes, and im253
Chemoprevention age X-ray-guidance. The interventional radiologist will perform the chemoembolization procedure. The physician will also need to know if the patient is taking any bloodthinning medications such as aspirin or coumadin, since they can affect the procedure. The patient is usually admitted to the hospital on the day of the procedure. Steps of the procedure: An intravenous (IV) line is started in the patient for medication and to provide fluid to the patient throughout the procedure. Although a medication is given through the IV to help the patient to relax, the patient is essentially awake throughout the procedure. An interventional radiologist performs the procedure under angiography (a special X ray of the arteries and veins) so that the catheter can be placed in the correct vessel that supplies blood to the tumor. A local anesthetic is used to numb the femoral artery area in the groin, where a small incision is made through which the catheter will be inserted. The physician follows the catheter placement via a monitoring screen. Once the interventional radiologist has threaded the catheter through the artery branches supplying the tumor, the chemotherapy drug used to embolize or block the blood supply is injected through the catheter. The patient may feel a momentary pressure or burning sensation. After the procedure: After the chemoembolization, a pressure dressing is applied to the groin, and the patient must lie flat for approximately eight hours. Patients may experience pain in the tumor area or groin, and possibly some nausea and fever as a result of the procedure. Since these symptoms may last for up to a week, patients are given pain medications to control symptoms and antibiotics on discharge from the hospital. Usually a one- to twonight stay in the hospital is required so that the patient can be monitored. Most patients can resume normal activities within one to two weeks. A follow-up computed tomography (CT) scan or magnetic resonance imaging (MRI) is usually ordered by the interventional radiologist one month after chemoembolization in order to assess the continued effectiveness of the treatment on the tumor. Thereafter, a CT scan or MRI is usually done every three months. Risks: As with any invasive procedure, there are potential risks. Risks of the chemoembolization procedure include infection at the catheter insertion site or blood clots occurring in vessels other than the one supplying the tumor. Results: Chemoembolization is considered a treatment for liver cancer but should not be considered curative. Although it may be used to treat liver tumors and cause 254
Salem Health: Cancer shrinkage and symptom control, studies to date have not suggested chemoembolization as a cure or first-line treatment. Jo Gambosi, M.A., B.S.N. u
For Further Information Baert, A. L., C. Bartolozzi, and R. Lencioni. Liver Malignancies: Diagnostic and Interventional Radiology. New York: Springer, 2003. Kufe, Donald W., et al., eds. Holland Frei Cancer Medicine 7. 7th ed. Hamilton, Ont.: BC Decker, 2006. VanSonnenberg, Eric, William McMullen, and Luigi Solbiati. Tumor Ablation: Principles and Practice. New York: Springer, 2005. u
Other Resources
National Cancer Institute http://www.cancer.org Society of Interventional Radiology http://www.sirweb.org See also Arterial embolization; Embolization; Hereditary leiomyomatosis and renal cell cancer (HLRCC); Hereditary non-VHL clear cell renal cell carcinomas; Hereditary papillary renal cell carcinomas; Kidney cancer; Leiomyomas; Liver cancers; Urinary system cancers; Virusrelated cancers.
u Chemoprevention Category: Chemotherapy and other drugs; lifestyle and prevention Definition: Chemoprevention is a pharmacological approach to preventing the development of cancer using one or several natural or laboratory-made substances (such as drugs, vitamins, dietary supplements, or foods) that interfere with carcinogenesis (the transformation of normal living cells into cancer cells). Discussion: Cancer affects people of all ages in the United States. The incidence rates of some forms of cancer have declined over the past few years while those of others have increased. Many financial and human resources have been spent on the diagnosis and treatment of cancer, and much research has been done on its prevention. Most of this research has confirmed that certain lifestyle choices play a significant role in the development of cancer. In fact, an estimated two-thirds of all cancers could be eliminated through healthy lifestyle choices. Changes in diet could eliminate almost one-third of cancers. Exercise and diet
Salem Health: Cancer are primary ways that people can diminish their chances of developing cancer. Prevention research has increasingly focused on chemoprevention for persons at high risk for certain cancers. These studies are designed to evaluate the effectiveness and usefulness of substances that may serve as chemoprevention. Since the 1980’s the National Cancer Institute has identified more than four hundred agents that may have the ability to prevent cancer. The value of these compounds in human subjects is the focus of numerous clinical trials. How chemoprevention works: Research has focused on ways to arrest or even reverse the process of carcinogenesis (the transformation of normal living cells into abnormal or cancer cells). Studies show that certain substances have the ability to stop the formation of cancer tumors by one of two means: preventing mutations (genetic cellular changes) that often lead to cancer or stopping the duplication of damaged cells that can result in malignant tumors. Substances can interact at various points along the process of carcinogenesis: the beginning (initiation), middle (promotion), and end (progression). These substances may inactivate the cancer-causing agent, suppress tumor growth, induce useful enzymes, or act as antioxidants. Chemoprevention is the result of studies directed toward the prevention of cancer rather than its treatment. An optimal chemoprevention agent should be nontoxic, safe for long-term use, easy to administer, inexpensive, and effective. Chemoprevention compounds may be natural dietary products or synthetic compounds. Unlike chemotherapy, which kills normal healthy cells as well as cancer cells in people with active cancer, chemoprevention uses relatively harmless substances that may prevent cancer in people with no known malignancy but who are at increased risk for cancer development. Examples of chemoprevention: Breast cancer is a primary concern for women in the United States, with an average lifetime risk of 12.7 percent, or 1 in 8 women. Chemoprevention may be effective in preventing breast cancer in women who are at high risk or in preventing cancer in the second breast of women who have been diagnosed with breast cancer. Breast cancer prevention studies specifically target women who are cancer free but at high risk. The National Cancer Institute (NCI) funded the Breast Cancer Prevention Trial (BCPT), with recruitment of subjects from 1992 through 1997. This study used the antiestrogen drug tamoxifen and had promising results, with 49 percent fewer diagnoses of invasive and noninvasive cancer in the group that took the drug. However, both temporary and some long-term adverse side effects
Chemoprevention such as endometrial cancer, uterine sarcoma, pulmonary embolism, and deep vein thrombosis occurred. Another study of breast cancer prevention in high-risk women compared outcomes using the chemoprevention drugs tamoxifen and raloxifene. Still other National Cancer Institute clinical trials have begun to investigate the effectiveness of soy protein, soy isoflavones, grape seed extract, and green tea extract in preventing breast cancer. Another possible chemoprevention for breast cancer is indole 3-carbinol from broccoli. With the exception of skin cancer, prostate cancer is the most common cancer and is the second leading cause of cancer-related deaths in American men. The National Cancer Institute has several ongoing clinical trials assessing if certain antiandrogens and antiestrogens can prevent prostate cancer. One clinical trial used a drug called finasteride to reduce dihydrotestosterone (a metabolite of testosterone), associated with prostate cancer; results showed a reduction in the incidence of prostate cancer. However, there were side effects such as decreased libido (sexual drive), increased erectile dysfunction, and gynecomastia (excessive breast development in males). One study used pomegranate juice to slow or halt the increase in prostate specific antigen (PSA); an increase in PSA would indicate the prostate cancer had returned. Another study employed a dietary approach to reduce the intake of fat and increase the intake of fruit and vegetables. Supplementation with vitamin E, selenium, or lycopene and dietary substances such as tea, soy products, and indole-3-carbinol (in broccoli) may be chemoprotective, but these have not been proven effective at reducing the incidence of prostate cancer. Other subjects of clinical trials at the National Cancer Institute have included aspirin, fish oil, and lycopene (found in tomatoes, watermelon, and pink grapefruit). Colorectal cancer is the third most common cancer in the United States and also ranks third in cancer-related deaths. Increased consumption of fruits and vegetables seems to provide some protection against colorectal cancer. The National Cancer Institute has a commitment to develop and validate other possible ways to prevent colon cancer. One study involved the chemoprevention effect of calcium and vitamin D. Another study looked at consuming eicosapentaenoic acid (EPA), a highly purified form of omega-3 fatty acids that naturally occurs in fish. A third study focused on the use of selenium, a naturally occurring micronutrient found in dietary sources such as nuts (especially Brazil nuts), meat, eggs, and fish. Several investigations have begun examining the use of curcumin, part of a common spice used in Indian curries, for its antitumor and anti-inflammatory effects and its possible ability to prevent the intestinal inflammation associated with colon 255
Chemoprevention cancer. Another topic of investigation has been the adding of high-fiber foods or wheat cereal to the diet to prevent colon cancer. Drugs that have begun to be studied regarding chemoprevention of colorectal cancer include aspirin, calcium carbonate, and 1α 25-dihydroxy cholecalciferol (active vitamin D3). Cancer of the cervix (the organ that connects the vagina to the uterus) is a national concern. The National Cancer Institute estimated that in 2007 more than 11,000 cases would be diagnosed in the United States and more than 3,600 women would lose their lives to this cancer. Research has shown that persistent exposure to the human papillomavirus (HPV) is a primary key to cervical cancer development. In early 2007, the Journal of the American Medical Association (JAMA) reported that 26.8 percent of women in the United States between the ages of fourteen and fifty-nine tested positive for HPV. More than one hundred viruses are strains of HPV, and more than thirty of these are transmitted sexually. Some produce genital warts or benign tumors, and some place women at high risk for cervical cancer. In 2006, the United States Food and Drug Administration approved new vaccines that target the strains of HPV most commonly responsible for cervical cancer. One vaccine is effective against two high-risk HPVs that cause about 70 percent of cervical cancers. Vaccines given to young women before they become sexually active serve as chemoprevention for cervical cancer. Women may take the vaccines after they become sexually active, but they provide less protection because infection may already have occurred. As with all drugs, some side effects may occur. Chemoprevention is being viewed as a key to cancer prevention in various other cancers. Researchers have begun testing whether the use of nonsteroidal anti-inflammatory drugs (NSAIDs) may prevent oral cancers. Some studies show that black raspberry extract may prohibit cancer growth in the mouth, as might Bowman-Birk inhibitor (BBI), a substance found in soybeans. The prevention of liver cancer, which kills 14,000 people annually, may be possible using oltipraz, a compound with properties resembling the antioxidant properties of broccoli, cabbage, and other cruciferous vegetables. Though liver cancer accounts for only about 2 percent of all cancers, the incidence is rising, and chemoprevention could slow this rate. The use of vaccines for the hepatitis B virus may protect against liver cancer. Benefits and risks of chemoprevention: Some 1.4 million people are diagnosed annually with cancer in the United States. The goal of chemoprevention is to reduce the incidence of new cancers, which will improve the qual256
Salem Health: Cancer ity of life for many Americans and keep the workforce in place. In one study, cancer was associated with the highest loss of work days because of illness or impairment. The cost of cancer to the workers themselves and to their employers reinforces the need for measures and interventions such as chemoprevention to reduce the incidence of cancer. Chemoprevention targets only high-risk populations because chemoprevention medications are not seen as useful or applicable for the general public. However, changes in diet and in the choice of foods consumed may affect the incidence of certain cancers. Most authorities do not recommend taking vitamins and supplements but rather endorse eating a well-balanced diet that is low in fat and high in fruits and vegetables. This is commonsense cancer prevention. Successes are not seen quickly but rather may become visible over extended periods of time. In fact, one study, called the Alpha-Tocopherol, Beta-Carotene Lung Cancer Prevention Study, demonstrated an 18 percent increase in lung cancer in the beta-carotene group. Clearly, judicious use of supplements is warranted because negative outcomes as well as positive ones can occur. People who are considering a change in diet should check with their health care providers, as some vitamins and supplements can interact adversely with some prescription medications. Summary: The research involving chemoprevention is encouraging and warrants more study and research dollars. Studies show that simple changes in lifestyle and eating habits can make a sizable impact on the incidence of cancer in the United States. Chemoprevention may some day be able to prevent people at high risk from developing cancer and keep cancer away in those who are in remission. The already burdened health care system could use its limited resources in trying to prevent other chronic diseases. Chemoprevention may not be the answer, but maybe it can be an answer to cancer in the United States. Marylane Wade Koch, M.S.N., R.N. u
For Further Information Loop, Matthew J. Cracking the Cancer Code: The Secret to Transforming Your Health from Inside Out. New York: iUniverse, 2006. Runowicz, Carolyn D., and Sheldon H. Cherry. The Answer to Cancer. Emmaus, Pa.: Rodale Books: 2004. Sheridan, Stacey L., Russell P. Harris, and Steven H. Woolf. “A Suggested Approach from the U.S. Preventive Services Task Force, Shared Decision-Making Workgroup of the U.S. Preventive Services Task
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Chemotherapy
Force, Elsevier Science.” American Journal of Preventive Medicine 26, no. 1S (2003): 56-66. Sporn, Michael B., and Nanjoo Sun. “Prevention of Cancer.” Carcinogenesis 21, no. 3 (2000): 525-530. Varona, Verne. Nature’s Cancer Fighting Foods. New York: Penguin Putnam, 2001. u
Other Resources
Centers for Disease Control and Prevention HPV Vaccine Questions and Answers http://www.cdc.gov/std/HPV/STDFact-HPVvaccine.htm#hpvvac1 National Cancer Institute http://www.cancer.gov See also Antioxidants; Beta-carotene; Bioflavonoids; Calcium; Carotenoids; Cartilage supplements; Coenzyme Q10; Dietary supplements; Fiber; Folic acid; Garlic and allicin; Ginseng, panax; Glutamine; Green tea; Herbs as antioxidants; Indoles; Isoflavones; Lutein; Lycopene; Nutrition and cancer prevention; Omega-3 fatty acids; Phytoestrogens; Prevention; Resveratrol; Saw palmetto; Soy foods; Sun’s soup.
u Chemotherapy Category: Chemotherapy and other drugs Definition: Chemotherapy is the treatment of cancer with medications that have a certain toxic effect on cancer cells. Chemotherapy drugs are used to slow the growth of cancer cells, shrink tumors prior to other treatments such as surgery or radiation, or cure a specific cancer. • First-line or standard chemotherapy: Given to destroy cancerous cells before disease progression or recurrence; first-line chemotherapy has been determined, through research studies and clinical trials, to have the best probability of treating a certain type of cancer • Second-line chemotherapy: Given to destroy cancerous cells when the disease has not responded to firstline chemotherapy or has recurred after first-line chemotherapy • Adjuvant chemotherapy: Given to destroy cancerous cells that may remain after a known cancerous tumor has been surgically removed or after radiation therapy has been given • Consolidation or intensification chemotherapy: Given once a remission is achieved, with the goal of sustaining a remission.
Six drugs commonly used to treat cancer. (National Cancer Institute)
• •
Induction chemotherapy: Given to induce a remission Maintenance chemotherapy: Given in lower doses to help prolong a remission • Palliative chemotherapy: Given to ease the symptoms of cancer and improve a patient’s quality of life Cancers treated: All Subclasses of this group: Alkylating agents, anthracyclines, antimetabolites, corticosteroid hormones, mitotic inhibitors, nitrosoureas, topoisomerase inhibitors; some chemotherapy drugs do not fit into these classifications, including dactinomycin (Cosmegen), hydroxyurea (Droxia), L-asparaginase (Elspar), procarbazine (Matulane), and thalidomide (Thalomid) Delivery routes: Chemotherapy drugs are most commonly administered intravenously (through an IV) or orally (by mouth) as pills, capsules, or liquid. They may also be administered topically (applied to the skin) as creams or lotions or injected directly into a tumor (intratumorally or intralesionally), into the muscle (intramuscularly), or under the skin (subcutaneously). The administration method 257
Chemotherapy is dependent on the drug’s specific action, dose, and potential side effects. In some cases, two or more administration methods may be used at once. Intravenous chemotherapy medications may be infused through a peripheral central catheter (thin, flexible tube) inserted into a vein in the arm or hand; through a central venous catheter, also called a vascular access device; or through a port implanted into a large vein in the neck, chest, or arm. A central venous catheter is used to deliver chemotherapy when several drugs need to be administered at the same time, when continuous infusion chemotherapy is being given, or when long-term therapy is needed. A catheter may also be placed in an artery (intra-arterial), in the cerebrospinal fluid (intrathecal), in the chest (intrapleural), in the abdomen (intraperitoneal), or in the bladder (intravesical) to deliver the medication. A medication infusion pump is sometimes used with a catheter to deliver a preprogrammed dose of medication. Chemotherapy can be administered on an inpatient, outpatient, or at-home basis, depending on the specific drug and the type of cancer, its location, and its aggressiveness. Where chemotherapy is administered may be dependent upon the patient’s insurance requirements, as well as the physician’s and patient’s personal preferences. Chemotherapy drug dosages are based on a patient’s body weight in kilograms or a patient’s body surface area expressed in meters squared, which is calculated using the patient’s height and weight. Chemotherapy is given at regular intervals, or cycles, depending on the type and stage of cancer and how many chemotherapy drugs are being given at the same time. Rest periods between doses allow normal cells to recover from the effects of the medication. It is important for patients to receive the full recommended course of therapy to achieve the maximum therapeutic benefit. In some cases, the physician may adjust the course of treatment based on the incidence of certain side effects. Liposomal therapy is a newer chemotherapy delivery method in which liposomes (microscopic synthetic capsules) are used to deliver chemotherapy drugs. The coating on the liposome capsules allows the medication to remain in the circulation for a longer period of time, so that the drugs selectively target cancer cells and decrease side effects on healthy tissue. Some liposomal medications currently available include doxorubicin liposomal (Doxil) and daunorubicin liposomal (DaunoXome). How these drugs work: In the 1940’s, nitrogen mustard became the first chemotherapy agent used to treat cancer. The use of chemotherapy for cancer treatment was discovered accidentally during World War II when a group of soldiers exposed to sulfur mustard gas, a chemical warfare 258
Salem Health: Cancer agent, were later found to have very low white blood cell counts. Scientists hypothesized that this agent would have a similar effect on cancer. An IV injection of nitrogen mustard was given to several patients with advanced lymphomas and was successful in treating the cancer. More than one hundred types of chemotherapy drugs are now available, with many more being investigated. Chemotherapy is a systemic treatment; the medicines travel through the whole body and are not confined to one specific treatment area. Chemotherapy drugs therefore can reach cancer cells that may have traveled from the main tumor through the blood or lymph systems to other parts of the body. Chemotherapy drugs may be given alone or in combination with other drugs or treatments, such as radiation therapy or surgery. The chemical composition, action, and side effects of chemotherapy drugs vary. Chemotherapy drugs are classified according to how they affect cancer cells’ molecular context, cellular activities or processes, and specific phases of the cell cycle. Targeted cancer therapies block the growth and spread of cancerous cells by interfering with cancer cell development, growth, and division. Some targeted therapies interfere with the proteins that are involved in the process that signals normal cells to turn into cancerous cells. Targeted therapy is available with a few chemotherapy drugs, while many other targeted therapy medications are under investigation. Monoclonal antibodies are synthetic forms of protein that can help guide chemotherapy drugs directly into a tumor. Monoclonal antibodies are used only for certain types of cancer in which antigens and the respective antibodies have been identified, such as some types of breast cancer and lymphomas. Angiogenesis inhibitor drugs may prevent the growth of blood vessels that supply oxygen from surrounding tissue to cancerous cells or tumors, thereby starving the cells of oxygen. The type of chemotherapy prescribed is different for each patient and is based on the type of cancer, the stage of the disease, the patient’s age and overall health, the presence of coexisting medical conditions, and other cancer treatments that may have been given previously. Side effects: Because chemotherapy drugs are systemic, they target cancerous as well as normal tissue and can have toxic side effects, depending on the specific drug, its dosage, the duration of administration, and the patient’s physical condition. One of the most common side effects of chemotherapy is fatigue (tiredness), which may be the result of anemia (a (continued on page 260)
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Chemotherapy
Chemotherapy Drugs by Group Type
Drug Name
Trade Names
Alkylating agents
busulfan injection carboplatin chlorambucil cisplatin cyclophosphamide dacarbazine ifosfamide mechlorethamine (nitrogen mustard) melphalan hydrochloride thiotepa temozolomide
IV Busulfex, Myleran Paraplatin Leukeran Platinol AQ Cytoxan, Neosar DTIC-Dome Ifex, Mitoxana Mustargen Alkeran Thioplex Temodar
Anthracyclines, antitumor antibiotics
bevacizumab bleomycin daunorubicin doxorubicin epirubicin idarubicin mitoxantrone
Avastin Blenoxane Cerubidine Adriamycin, Doxil, Rubex Ellence Idamycin PFS Novantrone
Antimetabolites
5-fluorouracil capecitabine clofarabine injection cytarabine mercaptopurine methotrexate injection thioguanine
Adrucil Xeloda Clolar Cytosar-U Purinethol Rheumatrex Thioguanine Tabloid
Corticosteroid hormones
dexamethasone prednisone methylprednisolone sodium succinate
Decadron, Dexone, Solurex Prednisone Intensol, Sterapred Solu-Medrol
Mitotic inhibitors, plant alkaloids
docetaxel paclitaxel vinblastine vincristine vinorelbine
Taxotere Onxol, Taxol Velban Oncovin, Vincasar Navelbine
Nitrosoureas
carmustine fotemustine lomustine streptozocin
BiCNU Muphoran CeeNU, CCNU Zanosar
Topoisomerase inhibitors
etoposide injection irinotecan paclitaxel teniposide topotecan hydrochloride
Toposar, VePesid injection Camptosar Onxol Vumon Hycamtin
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Chemotherapy
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decrease in oxygen-carrying red blood cells) or the result of the increased energy required to recover from the effects of the chemotherapy drugs. Other factors contributing to fatigue include poor appetite, lack of sleep, and emotional stress. Depressed blood cell counts may increase the patient’s risk of infection and anemia. In addition, reduced platelets can cause easy bruising or bleeding including nosebleeds, bleeding gums, blood in the urine or stool, and unusually heavy menstrual flow. Other common side effects include nausea and vomiting, loss of appetite, diarrhea, and fluid retention. A registered dietitian can provide nutritional therapy to help the patient develop an eating plan that meets dietary requirements but reduces these side effects and helps make treatment more tolerable. In some cases, antinausea or antidiarrheal medications may be prescribed to help prevent these troublesome side effects. It is important for patients to ask their physicians first before taking overthe-counter remedies for these side effects, as they could interfere with the action of the chemotherapy drug. Since many chemotherapy drugs kill fast-growing cancer cells, they may also target fast-growing normal cells in the hair follicles, which can lead to alopecia (hair loss).
Some chemotherapy drugs may cause only hair thinning, while others may cause complete hair loss, including loss of body hair and eyebrows. Hair loss is temporary, and hair will regrow after the cancer treatments are completed. Emotional or mood changes, such as depression or anxiety, may occur. Patients should discuss their concerns about these side effects with their physician; support groups are available to help patients cope, and antidepressant medications can be prescribed when necessary. In some cases, chemotherapy can cause certain side effects that are painful, such as burning or pain in the fingers or toes. Pain medications may be prescribed to reduce pain associated with cancer treatment. Some chemotherapy drugs may lead to infertility (both amenorrhea in women and impaired spermatogenesis in men). In extreme cases, chemotherapy can lead to heart muscle damage (cardiotoxicity), which would mitigate the chemotherapy regimen. There are several lifestyle changes a patient can make to manage certain side effects, such as fatigue and mouth, gum, and throat problems. The National Cancer Institute offers a publication, Chemotherapy and You, that provides several techniques for managing side effects. The time it takes to recover from chemotherapy side ef-
Chemotherapy Drug Groups, Actions, and Cancers Treated Drug Class
Action
Cancers Treated
Alkylating agents
Directly damage the DNA of cancer cells to prevent the cells from reproducing
Chronic leukemias; non-Hodgkin lymphoma; Hodgkin disease; multiple myeloma; lung, breast, ovarian, and other cancers
Anthracyclines, antitumor antibiotics
Act by binding with DNA and preventing RNA synthesis, a key step in the creation of proteins
Breast, colorectal, lung, and other cancers
Antimetabolites
Interfere with the growth of DNA and RNA
Leukemias; breast tumors; ovarian, gastrointestinal, and other cancers
Corticosteroid hormones
Slow the growth of some cancers that depend on hormones
Lymphoma, leukemias, multiple myeloma, and other cancers
Mitotic inhibitors
Prevent cell division by interfering with tubulin, a protein that is the basic building block of the fibers responsible for cell multiplication
Myeloma; lymphoma; leukemia; breast, lung, and other cancers
Nitrosoureas
Interfere with the enzymes in cancer cells that are responsible for copying and repairing DNA
Brain tumors, non-Hodgkin lymphoma, Hodgkin disease, multiple myeloma, malignant melanoma, and other cancers
Topoisomerase inhibitors
Interfere with the action of topoisomerase enzymes, the enzymes that control the manipulation of the structure of DNA
Leukemias; lung, ovarian, gastrointestinal, and other cancers
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Salem Health: Cancer fects varies, depending on the patient’s physical condition and the type of chemotherapy drug, dosage, and how long the medication was taken. Chemotherapy side effects are usually short term and often go away once treatment is finished. Patients should ask their doctor about the risk of side effects, both short term and long term, and the risk of serious side effects. Angela M. Costello, B.S. u For Further Information Chabner, Bruce A., and Dan L. Longo, eds. Cancer Chemotherapy and Biotherapy: Principles and Practice. Philadelphia: Lippincott Williams & Wilkins, 2006. Fischer, David S., et al. The Cancer Chemotherapy Handbook. 6th ed. St. Louis: Mosby, 2003. National Cancer Institute. Chemotherapy and You. NIH Publication No. 07-7156. Bethesda, Md.: National Institutes of Health, U.S. Department of Health and Human Services, 2007. Also available at http://www .cancer.gov. Skeel, Roland T. Handbook of Cancer Chemotherapy. 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2007.
u
Other Resources
American Cancer Society http://www.cancer.org CancerCare http://www.cancercare.org Chemocare.org http://www.chemocare.org National Cancer Institute http://www.cancer.gov/ See also Alkylating agents in chemotherapy; Androgen drugs; Angiogenesis inhibitors; Antiandrogens; Antiestrogens; Antimetabolites in chemotherapy; Antineoplastics in chemotherapy; Antiviral therapies; Benzodiazepines; Biological therapy; Chlorambucil; Cyclophosphamide; Cyclosporin A; Cytokines; Drug resistance and multidrug resistance (MDR); Immunotherapy; Interferon; Interleukins; Matrix metalloproteinase inhibitors; Monoclonal antibodies; Plant alkaloids and terpenoids in chemotherapy; Proteasome inhibitors; Topoisomerase inhibitors; Tyrosine kinase inhibitors; Vaccines, therapeutic.
Chewing tobacco
u Chewing tobacco Category: Lifestyle and prevention; carcinogens and suspected carcinogens RoC status: Known human carcinogen since 2000 Also known as: Smokeless tobacco, chew, snuff, dip, plug tobacco Related cancers: Oral cancers and cancers of the esophagus, larynx, pharynx, stomach, and bladder Definition: Also called smokeless tobacco, these tobacco and tobacco-based products that are not smoked but chewed or otherwise used in the mouth, such as chew, snuff (both oral and inhaled), dip, and plug tobacco, cause or are associated with certain cancers and other disorders of the mouth. Exposure routes: Oral by chewing, sucking, and ingestion Where found: Sold in the form of snuff, chewing tobacco, and plug tobacco At risk: Users of smokeless tobacco Many individuals use tobacco by smoking it in the form of cigarettes or cigars, and in pipes. Other individuals use tobacco by simply chewing it. Some do not even chew it, but use it by keeping it inside their mouth, such as in a cheek or between the teeth and lower lip, and absorb it by sucking on it. The tobacco products release their chemicals, like nicotine, and these are absorbed into the body. Relative to cigarettes, three to four times as much nicotine is absorbed into the body per dose with smokeless tobacco. Additionally, because having these substances in the mouth will generate saliva, individuals who use them may frequently be spitting out the saliva and part of these products or their juices in the process of using them. Such products include chew, snuff, and dip. Chew is a form of shredded tobacco leaves. Snuff is processed tobacco that is fine-grained and smaller particles, similar to prepared spices or tea; it may even be powdery. It is so fine in some cases that users may inhale or sniff it, rather than use it orally. Dip is another term for snuff and refers to how individuals will use the material. For instance, they may dip their finger into a packet or pinch it to get the dose required to place in the mouth. Plug tobacco is similar to chew, but instead of having loose leaves, the tobacco is compressed into a hard plug that is placed in the mouth between the cheek and gums for use. All serve the same function—to dispense nicotine to the user—and all are classified under the general term of chewing tobaccos. 261
Chewing tobacco
Salem Health: Cancer
these products is worldwide. Approximately 90 percent of individuals with mouth cancers are tobacco users. In the United States, approximately 3 percent of adults, 8 percent of high school students, and 3 percent of middle school students are smokeless tobacco users. Many high school and middle school students learn about smokeless tobacco through its use by members of professional sports teams, such as baseball players and hockey players. Recent prevention efforts have focused on sports players who have endured problems related to oral cancers telling their stories and warning students about the risks to dissuade them from starting this habit. Relative to women, men are about two to ten times as likely to use smokeless Gum damage caused by chewing tobacco. (Science Source) tobacco, depending on the age group examined. In the United States, 9 perEtiology and symptoms of associated cancers: Many incent of smokeless tobacco users are American Indians and dividuals wrongly believe that because they are not smokAlaska natives, relative to 4 percent of whites, 2 percent of ing tobacco, they are skirting the normal cancer risks African Americans, 1 percent of Hispanics, and 0.6 perposed by tobacco in cigarettes. However, this is not true. In cent of Asian Americans. Oral cancers usually occur in infact, chewing tobacco also carries health and cancer risks. dividuals aged forty to sixty; however, they may occur at Smokeless tobacco contains at least twenty-eight known any age. Tobacco use combined with alcohol use can dracarcinogens. These cancer-causing agents form in the tomatically increase the risk of cancers related to smokeless bacco while it is growing, being processed, and being aged tobacco. Oral cancers account for only 2 to 4 percent of for use. They include substances such as acetylaldehyde, cancers diagnosed in the United States annually, but they arsenic, benzopyrene, cadmium, formaldehyde, hydrazine, have one of the lowest survival rates. and nitrosamines. Nitrosamines are some of the most danNancy A. Piotrowski, Ph.D. gerous carcinogens in smokeless tobacco. Oral cancers are commonly associated with such tou For Further Information bacco use and are somewhat of a function of the direct or Bellinir, Karen, ed. Tobacco Information for Teens: close contact of the substance with parts of the mouth, Health Tips About the Hazards of Using Cigarettes, such as the bones, cheeks, floor of the mouth, gums, roof Smokeless Tobacco, and Other Nicotine Products. Deof the mouth, and tongue. Further, users sometimes swaltroit: Omnigraphics, 2007. low juices from these products, causing them to travel Icon Health. Smokeless Tobacco: A Medical Dictionary, elsewhere into the body. As a result, smokeless tobacco Bibliography, and Annotated Research Guide to Interuse is associated with cancers of the esophagus, larynx, net References. San Diego, Calif.: Author, 2004. pharynx, stomach, and bladder. Often problems will show MacKay, Judith, and Michael P. Eriksen. The Tobacco Atup first as sores in the mouth that will not heal, difficulty las. Geneva: World Health Organization, 2002. swallowing or chewing, ear pain, voice changes, or sore Snell, Clete. Peddling Poison: The Tobacco Industry and throats that seem to persist. Another sign might be lesions Kids. Westport, Conn.: Praeger, 2005. or areas of discoloration, such as white patches or red sores Winter, John C. Tobacco Use by Native North Americans: on the gums, tongue, or cheeks. Exposed tooth roots may Sacred Smoke, Silent Killer. Norman: University of also begin to have problems. Oklahoma Press, 2000. History: Reports on health problems related to smokeless tobacco use date back to the eighteenth century. Use of 262
See also Head and neck cancers; Oral and oropharyngeal cancers; Throat cancer; Tobacco-related cancers.
Salem Health: Cancer
u Childbirth and cancer Category: Social and personal issues Definition: Childbirth is an extremely emotional experience that, although often filled with happiness, can also be extremely stressful. Childbirth during cancer treatment, or shortly thereafter, can add more stress for the new mother and her family, as well as causing feelings of fear, anxiety, and depression. Pregnancy during cancer treatment: Cancer treatment is an extremely stressful time for any woman, but pregnancy and childbirth during cancer treatment add many new concerns. Many of the commonly used cancer treatments, such as radiation therapy, are not appropriate for women who are pregnant. In many cases, a woman and her doctor may decide to postpone certain cancer treatments until after the baby is born. Labor may be induced a few weeks early so that cancer treatment can begin as soon as possible. Chemotherapy is not considered safe for women who are in their first trimester of pregnancy. However, some chemotherapy drugs may be appropriate for women who are in their second or third trimesters. Chemotherapy drugs reduce blood counts, so chemotherapy must be stopped for a few weeks before childbirth. This gives the mother’s body time to elevate blood counts back to normal levels and reduces the possibility of complications from childbirth such as infection and excessive bleeding. Childbirth after cancer: For many women who have had successfully treated cancer, pregnancy and childbirth do not pose any special risks. For some women, however, pregnancy and childbirth can be a risk to the mother’s health. If the cancer or cancer treatment caused damage to any of the systems that are affected or stressed by pregnancy or childbirth, such as the lungs or the cardiovascular system, pregnancy or childbirth may cause adverse health effects. Pregnancy and childbirth after cancer can also make it more difficult for the mother and her doctor to be vigilant in watching to make sure the cancer has not returned. Breast cancer, for example, is often much harder to detect in pregnant and nursing women because pregnancy and nursing cause the breasts to swell and become denser. This can disguise small lumps or changes in the breast that may indicate that breast cancer has returned. Mammograms are also harder to read accurately when a woman is pregnant or nursing because of the density of the breast tissue. Research: Research on childbirth and cancer is an active and growing field. It has many complexities and chal-
Childbirth and cancer lenges because of the number of physiological changes that occur during pregnancy and because of the number of different types of cancers and cancer treatments. It also poses special challenges because the health and wellbeing of the mother and developing baby are always of primary importance, so certain types of research cannot be undertaken. For example, it would be unethical to conduct studies on the effects of chemotherapy on the developing baby when the mother is in the first trimester because it is believed that chemotherapy would harm the developing baby. Research has not shown that there is any statistically significant link between childbirth and the recurrence of cancer. Women who have children after successful cancer treatment are believed to be at the same risk of recurrence as women who do not have children. Researchers have, however, begun to uncover a link between childbirth and the prognosis of a breast cancer diagnosis. Swedish researchers did a large study of women in Sweden diagnosed with breast cancer and found that women who were diagnosed shortly after their last childbirth had a worse prognosis than women diagnosed a very long time after their last childbirth. Follow-up research is being done to try to understand what mechanism may account for this and to determine if it may be true of other cancers as well. Emotional considerations: Cancer treatment is an extremely stressful event in anyone’s life, but for a woman who is expecting, it presents even more challenges. After spending days and weeks trying to eat healthy food, do the right amount of exercise, and do everything possible to ensure the best atmosphere for the baby’s development, it can be devastating to consider the implications of a cancer diagnosis and treatment plan. The woman’s cancer care team can help her sort through the various choices and help ensure that she makes the best choices possible both for herself and for her developing baby. Many women will have anxiety about issues such as what will happen to the baby if they are unable to care for it during their cancer treatment or what may happen if the cancer is difficult or impossible to treat. Counseling can help the mother-to-be work through her fears for the future, and many resources are available to help mothers care for their babies if they have to undergo treatments such as chemotherapy shortly after they give birth. Frank discussions with health care team members and the support of family and friends can help ease the difficulty of having a child during cancer treatment. Helen Davidson, B.A.
263
Childhood cancers u For Further Information Harpham, Wendy Schlessel. When a Parent Has Cancer: A Guide to Caring for Your Children. New York: Perennial Currents, 2004. McKay-Moffat, Stella, ed. Disability in Pregnancy and Childbirth. New York: Churchill Livingstone/Elsevier, 2008. Oktay, Kutluk, H., Lindsay Nohr Beck, and Joyce Dillon Reinecke. One Hundred Questions and Answers About Cancer and Fertility. Sudbury, Mass.: Jones and Bartlett, 2008. Pavlidis, N., and F. Peccatori. Cancer and Pregnancy. New York: Springer, 2007. u
Other Resources
American Cancer Society http://www.cancer.org National Cancer Institute http://www.cancer.gov See also Breast cancer in pregnant women; Endocrine cancers; Endometrial cancer; Fallopian tube cancer; Fertility drugs and cancer; Fertility issues; Gynecologic cancers; Gynecologic oncology; Infertility and cancer; Placental alkaline phosphatase (PALP); Pregnancy and cancer; Uterine cancer; Vaginal cancer.
u Childhood cancers Category: Diseases, symptoms, and conditions Also known as: Childhood neoplasms Related conditions: Leukemia, lymphoma, brain cancer, osteosarcoma Definition: Childhood cancers are cancers that occur in a person from infancy through age nineteen. The twelve major types of childhood cancers vary by type of histology, site of origin, race, sex, and age. They are leukemias, lymphomas, brain and spinal tumors, sympathetic nervous system tumors, retinoblastoma, kidney tumors, liver tumors, bone tumors, soft-tissue sarcomas, gonadal and germ-cell tumors, epithelial tumors, and other and unspecified malignant tumors. The most common types are leukemias and lymphomas. Risk factors: Childhood cancers result from noninherited mutations or changes in the genes of developing cells. Some risk factors have been associated with different types of childhood cancers such as acute lymphocytic leu264
Salem Health: Cancer kemia (ALL) and acute myelogenous leukemia (AML). If a child has an identical twin who was diagnosed with ALL or AML before the age of six, the child has a 20 to 25 percent greater risk of developing the illness. Nonidentical twins and other siblings of children with leukemia have two to four times the average risk of developing the illness. Children with Down syndrome, Klinefelter syndrome, or other genetic syndromes and those who have received drugs following organ transplants also are at greater risk of developing leukemia. Children who have received radiation therapy or chemotherapy for other types of cancer have an increased risk of developing leukemia within an eight-year period following treatment. Etiology and the disease process: In childhood leukemia, an abnormal amount of white blood cells, or leukocytes, is produced in the bone marrow; these cells invade the bloodstream and deplete the body’s ability to fight infection. As the disease progresses, it affects the body’s ability to produce red blood cells and platelets, resulting in anemia, bleeding disorders, and continued risk of infection from the overproduction of white blood cells. Lymphocytes are infection-fighting white blood cells that are made and stored in the lymph nodes (organs in the neck, groin, abdomen, chest, and armpits), spleen, thymus, tonsils, and bone marrow. In lymphoma, the white blood cells of the lymphatic system grow abnormally, producing cancerous cells called Reed-Sternberg cells. Although Hodgkin disease is most often seen in children aged fifteen or older, nodular lymphocyte predominance (LP) is more common in younger children, accounting for about onefifth of the incidence of most Hodgkin disease in children. Non-Hodgkin lymphoma (NHL) occurs more often in boys than girls and most often between the ages of two and ten. Unlike the non-Hodgkin lymphoma seen in adults, most cases of NHL in children are of the fast-growing, aggressive type (such as Burkitt lymphoma, non-Burkitt lymphoma, and lymphoblastic lymphoma). Another common type of childhood cancer, neuroblastomas (solid tumors), often begins in one of the adrenal glands above the kidneys; the tumors can also can arise in nerve tissues in the neck, abdomen, pelvis, or chest. While the cause of neuroblastomas is unknown, they are believed to arise from anomalies during the normal development of the adrenal glands. Incidence: Childhood cancer is the leading cause of death in the United States in children from infancy to fourteen years of age. However, childhood cancer is relatively rare; each year 1 to 2 children per 10,000 children in the United States will be diagnosed with cancer. Childhood cancer is estimated to occur at the rate of 17 per 100,000 children
Salem Health: Cancer
Childhood cancers
Yearly Incidence of Cancers Among Children and Adolescents Under Age Twenty, 1990-1995 Cancer Lymphoid leukemia Acute nonlymphocitic leukemia Hodgkin disease Non-Hodgkin lymphoma Central nervous system malignancies
Incidence per 1 Million Children 29.2 7.6 12.1 10.5 1.9
Source: L. A. G. Ries et al., eds., Cancer Incidence and Survival Among Children and Adolescents: United States SEER Program, 1975-1995, NIH Pub. No. 99-4649 (Bethesda, Md.: National Cancer Institute, SEER Program, 1999)
through the age of nineteen. Incidence is higher for boys than girls, and cancer rates are higher for children under five years of age and those between the ages of fifteen and nineteen. According to a National Cancer Institute (NCI) study from 1975 to 1995, the majority of cancers occurring in childhood were leukemias (25 to 30 percent). Of these, 60 percent were cases of acute lymphocytic leukemia (ALL), and 38 percent were acute myelogenous leukemia (AML). The next most common type was miscellaneous intracranial and intraspinal neoplasms (mostly solid, typically brain tumors involving the cerebellum or brain stem) at 16.7 percent, followed by lymphomas at 15.5 percent. Leukemias are the most common cancer in those under age five (and decrease proportionally in those over age five), and lymphomas are most common in those fifteen to nineteen years old. Hodgkin disease occurs at a rate of 12.6 per 1 million children, while non-Hodgkin lymphoma occurs at a rate of 10.5 per 1 million children. Other types of childhood cancer include Wilms’ tumor, affecting one or both kidneys and seen in children between two and three years of age; neuroblastoma, the most common form of solid tumor occurring outside the brain in children, often diagnosed by one year of age; retinoblastoma, or eye cancer; rhabdomyosarcoma, developing in cells that become mature voluntary muscle (the most common soft-tissue sarcoma seen in children); and primary bone cancer (osteosarcoma). Mortality for childhood cancers has declined significantly in the past thirty years, largely because of early detection and advances in treatment. However, the incidence of invasive cancer in children has increased slightly during the same period. The incidence of all types of invasive cancer in children has increased from 11.5 cases per 100,000 children in 1975 to 14.5 cases per 100,000 in 2004.
The reasons for this increase in incidence are unclear. However, the increase in the incidence of childhood brain tumors may be attributed to advances in early detection, as technologies such as magnetic resonance imaging (MRI) allow more accurate and differential diagnosing of tumors, and advances in neurosurgical techniques allow for biopsies of brain tumors. These advances in detection methods have resulted in an increase in discovery and diagnosis of malignant tumors.
Symptoms: The symptoms of childhood cancer vary by type, may mimic symptoms of other illnesses, and may include unexplained weight loss; headaches and vomiting; increased swelling or pain in bone, joints, back, or legs; a detectable lump or mass in the abdomen, pelvis, chest, armpit, or neck; unusual bleeding, bruising, or rash; recurring infections; sudden and persistent eye or vision changes; nausea or vomiting without nausea; a whitish color behind the pupil; tiredness or pallor; and recurring and persistent fevers. A child in the early stages of leukemia may not have these symptoms but may exhibit other changes in behavior, such as lacking the usual energy to engage in activities. A painless swelling of the lymph nodes, fever, and fatigue are often symptoms of both Hodgkin disease and non-Hodgkin lymphoma. The type of Hodgkin disease most often seen in young adults ages fifteen and older is associated with these symptoms: swollen lymph node in the neck, groin, or armpit; lethargy and weakness; facial swelling; night sweats; unexplained fever and weight loss; abdominal pain or swelling; difficulty breathing; and pain. Non-Hodgkin lymphoma may progress quickly in children, with many initially diagnosed at Stage III or IV, so these children may first complain of abdominal pain, fever, or constipation or decreased appetite originating from an abdominal mass. Neuroblastoma, or a cancer of the sympathetic nervous system, the most common type of cancer in infants, is usually seen as a lump or mass in the abdomen causing swelling, discomfort, pain, or a feeling of fullness. A neuroblastoma can also occur in the pelvis, neck, or eye. Often the neuroblastoma may spread to bone, causing pain, limping, weakness, numbness, or inability to walk. In about one-quarter of cases, the child may develop fever; less common symptoms include rapid heartbeat, flushed skin, sweating, irritability, high blood pressure, and diarrhea. 265
Childhood cancers Screening and diagnosis: There are no tests that screen for childhood cancers such as leukemia or lymphoma; however, there are standard tests for diagnosing. Typically, a parent notices a change in a child’s behavior and brings the child to the doctor, who will conduct a complete physical and examine the child for enlargement of the lymph nodes, liver, or spleen. If a blood cancer such as leukemia is suspected, the doctor will order a complete blood count (CBC) with differential. A fraction of patients with leukemia may have a normal blood test result when diagnosed. Suspicious cases must have a bone marrow test to confirm the diagnosis of leukemia. If Hodgkin disease or non-Hodgkin lymphoma is suspected, the doctor will do a thorough exam and order a CBC and a chest X ray. If the diagnosis of lymphoma is confirmed, the doctor may refer the child to a specialist, such as a pediatric hematologist or oncologist, for further diagnostic tests such as a biopsy of the tumor to differentially diagnose the type of lymphoma, a bone marrow aspirate, or an imaging test such as a computed tomography (CT) scan. Neuroblastomas are relatively rare, and screening for them in children with no symptoms is not believed to decrease mortality from the disease, so no screening test is conventionally used. Most neuroblastomas are detected within the first six months of life. Adoctor who suspects an
Salem Health: Cancer infant of having a neuroblastoma will order a urinalysis, which will reveal a higher-than-normal concentration of metabolites from the body’s breakdown of catecholamine neurotransmitters. If the physical exam and urine chemistry results indicate a neuroblastoma, the doctor will proceed to order other tests, such as an X ray, CT scan, abdominal ultrasound, CBC, blood test of liver and kidney function, bone scan, metaiodobenzylguanidine (MIBG) scan, and bone marrow aspiration. Staging is used to describe the disease at the time of diagnosis and to help the doctor determine the type of therapy, its course, and its prognosis. Leukemia, unlike other childhood cancers, is staged based on its presence and proliferation in organs other than its presence in the bone marrow and blood. Other factors in staging include sex, race, organ spread, types of leukemic cells, presence of abnormal chromosomes, and response to treatment within seven to fourteen days of inception. Staging to assess a child’s prognosis seems to be more important in children with ALL than in those with AML. Age and white blood cell count (WBCC) are important factors in staging ALL, with children younger than one and older than ten at highest risk (having a high white blood cell count of 50,000 cells per cubic millimeter). Lymphoma is staged based on the extent of the disease. Stage I lymphoma is limited to one primary area of the lymph node or organ, while Stage IV indicates the lymphoma has spread to one or more tissues or organs outside the lymphatic system. Neuroblastomas are staged I to IV-S, with Stage I being a tumor that is visible, is localized, and can be removed, and Stage IV being a cancer that has spread to distant lymph nodes or other parts of the body. In Stage IV-S, limited to a child under one year of age, the cancer has spread to skin, liver, or bone marrow but not to bone. Alternatively, neuroblastomas may be staged on the basis of low, intermediate, and high risk, depending on the features of the cancer cells, the age at which the child is diagnosed, and the stage of the disease.
The most common cancers in children are leukemias and lymphomas. (Digital Stock)
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Treatment and therapy: Childhood cancers are treated with surgery, chemotherapy, radiation therapy, or a combination of two or more therapies. Cancers in children, unlike those in many
Salem Health: Cancer adults, typically are fast growing and respond well to chemotherapy. Children are often treated in children’s cancer centers, which tend to offer new therapies and the latest treatment with clinical trials. The NCI recommends that children with cancer be treated by a multidisciplinary team consisting of a pediatric oncologist and other specialists and that all children be considered for clinical trials to test the effectiveness of existing treatments and evaluate the benefits and side effects of experimental treatments. The American Cancer Society (ACS) recommends that parents ask their pediatric cancer team about the potential side effects of treatment before the regimen begins. Side effects include hair loss, fatigue, risk of infection, easy bruising or bleeding, vomiting, diarrhea, bone marrow changes leading to anemia, lower white blood cell counts leading to reduced ability to fight infections, and a reduction in platelet production leading to easy bleeding and bruising. Treatment for the most common forms of cancer seen in children, acute lymphocytic leukemia (ALL) and acute myelogenous leukemia (AML), consists of three phases: induction, consolidation, and maintenance. Once the cancer is staged by risk group, induction therapy is designed to induce remission such that leukemic cells are no longer present in bone marrow, normal cells return, and blood counts return to normal. The monthlong treatment, often performed in the hospital, is intense because of the risk of serious infection, but more than 95 percent children with ALL who receive this treatment experience remission. Although the cancer is in remission, consolidation treatment lasting four to six months and maintenance therapy lasting at least two years are required to destroy all cancerous cells. These intravenous chemotherapies are coupled with intrathecal chemotherapy (drugs injected into the fluid surrounding the brain and spinal cord) to destroy cancer cells that may have spread to the central nervous system. In addition, radiation therapy may be directed at the brain or spinal cord if the leukemia was present in cerebrospinal fluid at the time of diagnosis; however, the side effects and long-term effects of radiation to the brain are such that this type of radiation therapy is avoided whenever possible. Low-risk ALL has the highest cure rate, 85 to 95 percent of all cases. The three main types of therapy for Hodgkin disease are radiation therapy to decrease tumors and destroy cancerous cells; chemotherapy or systemic drug therapy; and bone marrow and peripheral blood transplants, particularly for those whose disease recurs. The four types of nonHodgkin lymphoma seen in children (Burkitt, lymphoblastic, anaplastic large-cell lymphoma, and large B-cell lymphoma) may be localized in a swollen lymph node, but
Childhood cancers often the disease has spread to other organs at the time of diagnosis. Some neuroblastomas go away without treatment, while others commonly require surgery. Approximately half of the tumors spread to bone and bone marrow, requiring chemotherapy, radiation therapy, stem cell transplantation, or immunotherapy. The location of the tumor, age of the child, and diffusion of the tumor are factors in determining the recommended treatment. Prognosis, prevention, and outcomes: Overall, death rates have declined and five-year survival rates have increased for most types of childhood cancers. The increase in survival rates is attributable to new treatments resulting in cures or long-term remission for many children with cancer. Although the majority of cancers respond well to treatment, some will recur and require the child’s doctor to develop a new treatment plan. The most commonly reported longevity statistic is the five-year survival rate, or the percentage of children with cancer who live at least five years after diagnosis. This survival rate is 79 percent for all sites, 79 percent for leukemia, 95 percent for nonHodgkin lymphoma, and 66 percent for neuroblastoma. The survival rate for chronic lymphoblastic leukemia (CLL) has been reported to approach 90 percent. Children with cancer respond to chemotherapies and tolerate treatment better than adults do, making their prognosis bright. However, children who survive cancer may have long-term effects that require lifelong follow-up. These late or delayed effects can include hormonal disturbances in the endocrine system causing short stature, problems in puberty, thyroid or fertility disturbances, secondary learning difficulties, and other health consequences of the disease or treatment. Published data on long-term survivors of childhood cancers indicate that those most at risk of developing secondary sarcomas (cancers of connective or supportive tissue such as in bone, fat, or muscle) are children whose primary cancer was in soft tissue, bone, or renal tissue, or was Hodgkin disease. Because sarcomas can occur anywhere in the body and are more difficult to detect, long-term aggressive follow-up of childhood cancer patients is critical to their staying healthy. Susan H. Peterman, M.P.H. u
For Further Information Eiser, Christine. Children with Cancer: The Quality of Life. Mahwah, N.J.: Lawrence Erlbaum Associates, 2004. Fromer, Margot Joan. Surviving Childhood Cancer: A Guide for Families. Oakland, Calif.: New Harbinger, 1998. 267
Chlorambucil Keene, Nancy. Chemo, Craziness, and Comfort: My Book About Childhood Cancer. Washington, D.C.: Candlelighters, 2002. Langton, Helen. The Child with Cancer: Family-Centred Care in Practice. New York: Baillière Tindall, 2000. u
Other Resources
Candlelighters Childhood Cancer Foundation http://www.candlelighters.org The Leukemia and Lymphoma Society http://www.lls.org Memorial Sloan-Kettering Cancer Center http://www.mskcc.org See also Acute lymphocytic leukemia (ALL); Bone cancers; Breast cancer in children and adolescents; Craniopharyngiomas; Craniosynostosis; Cryptorchidism; DenysDrash syndrome and cancer; Ependymomas; Family history and risk assessment; Genetics of cancer; Hereditary polyposis syndromes; Hodgkin disease; Juvenile polyposis syndrome; Leukemias; Medulloblastomas; Nephroblastomas; Neuroblastomas; Non-Hodgkin lymphoma; Pediatric oncology and hematology; Peutz-Jeghers syndrome (PJS); Pheochromocytomas; Pineoblastomas; Pleuropulmonary blastomas; RB1 gene; Retinoblastomas; Rhabdomyosarcomas; Rothmund-Thomson syndrome; Spinal axis tumors; Spinal cord compression; Vaginal cancer; Von Hippel-Lindau (VHL) disease; Wilms’ tumor; Wilms’ tumor aniridia-genitourinary anomalies-mental retardation (WAGR) syndrome and cancer; Yolk sac carcinomas; Young adult cancers.
u Chlorambucil Category: Chemotherapy and other drugs; carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1981 Also known as: Leukeran, chloraminophene, Ambochlorin, Ecloril, Linfolysin Related cancers: Acute myeloid leukemia (AML), acute nonlymphocytic leukemia (ANLL) Exposure routes: Inhalation, ingestion, dermal contact Where found: Chemically synthesized; provided as treatment to people with cancer or autoimmune disorders as sugar-coated 2-milligram tablets 268
Salem Health: Cancer At risk: Patients receiving chlorambucil for treatment of cancer or autoimmune disorder; occupational exposure via skin contact or dust inhalation during pharmaceutical processing Definition: Chlorambucil is an alkylating agent of the nitrogen mustard class. As with other agents in this class, chlorambucil undergoes chemical activation to the aziridinium ion, which reacts with deoxyribonucleic acid (DNA) to form a covalent bond. This alkylation damages DNA and leaves it more prone to breakage. When taken up by rapidly dividing cells (such as cancer cells), damaged DNA is unable to repair itself quickly, leading to cell death. Etiology and symptoms of associated cancers: Acute myeloid (or nonlymphocytic) leukemia is a malignancy of blood in which myeloid precursor cells do not mature. These immature cells proliferate rapidly without normal maturation into granulocytes and monocytes. Early signs and symptoms are similar to those of influenza and include fever, weakness, fatigue, loss of appetite, and pain in the bones and joints. Infections, delayed healing of minor cuts, and unusual bruising or bleeding may occur. AML may occur at any age but typically occurs at about age sixty-five. Prognosis varies by age. Overall, 65 to 85 percent of patients achieve complete remission, with 20 to 40 percent achieving five-year survival. Children and adults older than the age of sixty are less likely to achieve complete remission. Alkylating agents such as chlorambucil increase the risk of acute myeloid leukemia, as does exposure to radiation and chemicals, such as benzene. History: Chlorambucil has been used in chemotherapy since the 1960’s, often for long durations. Although it is considered to be the least toxic nitrogen mustard derivative in use, sufficient evidence for carcinogenicity in animals and humans exists. Anecdotal evidence of carcinogenicity has been reported by the International Agency for Research on Cancer (IARC) since the early 1980’s. In most case reports, patients were also receiving radiotherapy or other potential carcinogens. A randomized trial inpolycythemia vera patients showed a thirteenfold increase in the incidence of AML in patients receiving chlorambucil. Risk of development of acute leukemia increased with dose and length of treatment. Karen M. Nagel, Ph.D. See also Antineoplastics in chemotherapy; Myelodysplastic syndromes; Waldenström macroglobulinemia (WM).
Salem Health: Cancer
u 1-(2-Chloroethyl)-3-(4-
methylcyclohexyl)-1nitrosourea (MeCCNU) Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1991 Also known as: Semustine Related cancers: Leukemia, preleukemia Definition: MeCCNU is used to treat various cancers, including some of the brain. A nitrosourea alkylating agent, MeCCNU contains alkyl groups that mainly react with the deoxyribonucleic acid (DNA) in the cell nuclei via a process called interstrand cross-linking. Local side effects of MeCCNU may include blistering of the skin as well as damage to the eyes and respiratory tract. Systemic toxic effects include nausea and vomiting, reduction in both leukocytes and erythrocytes, hemorrhagic tendencies, and nephrotoxicity. Busulfan and cyclophosphamide are among other alkylating agents used in cancer chemotherapy. Exposure routes: Oral (ingestion of capsules) Where found: 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)1-nitrosourea (MeCCNU) is an investigational drug. Patients may be exposed via oral adjuvant chemotherapy for various cancers, including those of the brain, lung, and digestive system. At risk: The National Institute for Occupational Safety and Health (NIOSH) conducted a survey from 1981 to 1983 and determined that approximately 229 workers were potentially exposed to MeCCNU. Etiology and symptoms of associated cancers: Though the exact mechanisms are unclear, it is believed that the most significant actions of alkylating agents are those that disturb cell growth, mitosis, and differentiation of rapidly dividing cells, providing the rationale for use in cancer therapy. However, because alkylating agents such as MeCCNU do not selectively kill cancer cells, they have a toxic effect on normal cells and are considered carcinogenic, mitogenic, and leukemogenic. Symptoms of leukemia may include weakness, fever, bleeding gums, petechiae (small red spots on the skin), lymphadenopathy (swollen glands), splenomegaly (enlarged spleen), and hepatomegaly (enlarged liver). History: Introduced in 1963 because of their lipophilicity and, therefore, ability to cross the blood-brain barrier, nitrosourea alkylating agents such as MeCCNU were designed to treat brain and meningeal cancer. However,
Cholecystectomy based on scientific data, MeCCNU has been shown to be carcinogenic in humans. In 1983 researcher J. D. Boice and colleagues found a twelvefold relative risk of leukemic disorders in 2,067 patients given adjuvant treatment with MeCCNU compared with those given other therapies. In 1987 the International Agency for Research on Cancer (IARC) demonstrated a significant dose-related response to MeCCNU with an adjusted relative risk of approximately fortyfold for patients who received the highest dose of MeCCNU. Also in 1987 the IARC concluded that there was evidence that MeCCNU was carcinogenic in experimental animals. In 1977 researcher J. H. Weisburger had found an increased incidence of tumors and leukemias in animals injected with MeCCNU. Cynthia Racer, M.A., M.P.H. See also Alkylating agents in chemotherapy; Chemotherapy.
u Cholecystectomy Category: Procedures Also known as: Open cholecystectomy, laparoscopic cholecystectomy Definition: Cholecystectomy refers to the surgical removal of the gallbladder. There are two approaches that may be used to remove the gallbladder. An open cholecystectomy involves making a single abdominal incision through which the gallbladder is extracted. This approach is used in complicated cases in which a more thorough exploration of the upper abdomen for cancer spread is anticipated. The minimally invasive laparoscopic cholecystectomy makes use of four abdominal incisions small enough to allow the insertion of a laparoscope and instruments (trocars). The gallbladder is extracted through one of the large ports. This approach is often reserved for uncomplicated gallbladder disease, although gallbladder cancer is found after removal in 1 percent of all patients undergoing liver and biliary tract surgery. Higher recurrence of gallbladder cancer is also reported with this method. Cancers treated: Gallbladder carcinoma, melanoma, metastatic carcinoma Why performed: Cholecystectomy is performed to remove the primary tumor and reduce the possibility of liver tissue invasion, regional lymph node infiltration, and distant spread (metastasis) of tumor cells. Although the main indication for performing a cholecystectomy is for definitive treatment of symptomatic gallbladder stone obstruc269
Cholecystectomy
Salem Health: Cancer
A laparoscopic cholecystectomy. (Custom Medical Stock Photo)
tion of the bile ducts (cholelithiasis), a gallbladder carcinoma is sometimes an incidental finding. Patient preparation: The patient first undergoes several laboratory and imaging tests in order to confirm clinical suspicions of gallbladder cancer based upon the patient’s medical history and physical examination. They include an ultrasound and a computed tomography (CT) scan of the abdomen in order to assess the size and spread of the cancer. A CT scan is particularly helpful in visualizing the liver and bile duct anatomy in relation to the cancer. Once the diagnosis is confirmed, preoperative patient preparation includes surgical risk assessment through a general physical examination, especially of the heart (electrocardiograph, or EKG) and lungs (chest X ray, pulmonary function tests), and temporary discontinuance of drugs that may complicate the patient’s recovery. Another consideration is ensuring that the patient has nothing by mouth at least eight hours before the procedure. Steps of the procedure: The patient is positioned, and the surgical site is sterilized. An incision is made near the border of the lower right ribcage, or a larger abdominal inci270
sion slightly to the right of the umbilicus. After the surgeon cuts through the skin and divides the abdominal muscles, the abdominal cavity is entered and the liver is identified. It is common to encounter some adhesions between the liver, gallbladder, and adjacent bowel; these adhesions are cut away. Once the liver and gallbladder are visualized, the gallbladder outlet (cystic duct), contained in a ligament connecting the liver to the duodenum, is exposed and slightly constricted by silk suture to prevent gallstones from passing. The adjacent gallbladder artery (cystic artery) and right hepatic artery are identified to avoid tying off the latter. The gallbladder is dissected away from the liver, starting from the bottom (fundus) and going toward the cystic duct. The cystic artery is reached, then subsequently tied off and cut. The junction between the cystic duct and the larger common bile duct is identified, and the cystic duct is tied off and cut 3 to 5 millimeters away from the common bile duct. An alternative, retrograde approach involves tying off and cutting the cystic duct and artery first before proceeding to dissect the gallbladder away from the liver.
Salem Health: Cancer In more extensive cancer spread, removal of the gallbladder also involves an extended resection (part of the liver and lymph nodes) or a radical resection of the gallbladder involving adjacent structures such as a margin of underlying liver, the common bile duct, the hepatoduodenal ligament, and nearby lymph nodes from the liver, stomach, bowel, and pancreas. Severe spread may even involve removal of a large section of the liver and affected organs. After the procedure: The patient is monitored in the postanesthesia care unit until fully awake and vital signs are stable. The patient may then be discharged to the surgical ward for postoperative monitoring for yellowing of the skin (jaundice), fever, and abdominal pain or enlargement, among other signs. Laboratory examinations and imaging studies are done if signs of deterioration are suspected. Once the patient is stable, ambulatory, urinating, and eating, the patient may be discharged after a few days. Risks: Some of risks of cholecystectomy are procedurerelated and thus preventable. The main risk involved in cholecystectomy is bleeding from small vessels that were not cauterized or ligated intraoperatively. Another risk is ligation of the common bile duct. Bowel injury may lead to bowel adhesions, leakage, fistulas, or inflammation of the abdominal cavity (peritonitis). Ligation of the right hepatic artery may also occur. Results: During the surgery, surgeons may find the gallbladder filled with an irregular mass or polyps, accompanied by mucus or gallstones. Tumors may extend outside the gallbladder and occasionally “replace” the gallbladder itself and encroach on surrounding structures in similar fashion. Microscopically, the cancerous cells resemble the secreting cells of the gallbladder wall (adenocarcinoma). Aldo C. Dumlao, M.D. u For Further Information Gislason, Stephen J. Food and Digestive Disorders: Irritable Bowel Syndrome, Crohn’s Disease, Celiac Disease, Ulcerative Colitis, Ulcers, Reflux, and Motility Disorders. Sechelt, B.C.: Environmed Research, 2003. Goldberg, Andrew, and Gerard Stansby. Surgical Talk: Revision in Surgery. River Edge, N.J.: Imperial College Press, 2005. Premkumar, Kalyani. Interactive Pathology for Massage Therapists. Baltimore: Lippincott Williams & Wilkins, 2000.
See also Gallbladder cancer; Hepatic arterial infusion (HAI); Nuclear medicine scan; Ultrasound tests.
Chordomas
u Chordomas Category: Diseases, symptoms, and conditions Also known as: Chordocarcinomas, chordoepitheliomas Related conditions: Sarcomas Definition: Chordomas are cancerous bone tumors that can occur anywhere along the spinal cord, most commonly at the base of the skull, at the base of the spine (sacrum), or in the tailbone (coccyx). Risk factors: There are no known risk factors. Bone injury, environment, diet, medications, and genetics do not appear to play a role in the development of chordomas. Etiology and the disease process: Chordomas develop in leftover pieces of cells from the notochord, a flexible, rodshaped structure that forms during early fetal development and precedes the spine. Incidence: Chordomas are rare. Most cases have been reported in persons age forty to seventy. Sacrum chordomas are more common in men; chordomas at the skull base are more common in women. Symptoms: Symptoms develop gradually and depend on the tumor site. Tumors near the skull base can cause headaches, face pain, and vision problems. Tumors in the lower spine and tailbone area may lead to leg weakness, leg or groin numbness, constipation, impotence, and bowel and bladder dysfunction. A tailbone chordoma may manifest with a noticeable mass. Chordomas in the upper part of the spine may cause hoarseness and swallowing problems. Screening and diagnosis: Most chordomas grow slowly and do not spread, and the gradual development of symptoms often results in a delayed diagnosis. Patients often have symptoms for more than a year before diagnosis. Computed tomography and magnetic resonance imaging can reveal bone destruction and tissue damage. Biopsy of the tumor confirms the diagnosis. Treatment and therapy: Surgery to remove the tumor and surrounding tissue is the best option but often difficult because of the tumor’s precarious positioning near the spinal cord and brain. Surgery often results in some type of nerve loss. For example, removing a chordoma from the tailbone can damage the nerves that control bladder and bowel function. Radiation therapy may be used along with surgery to ensure that all cancer cells are destroyed. Chemotherapy does not appear to be an effective treatment for chordomas. 271
Choriocarcinomas
Salem Health: Cancer
Duke University student Josh Sommer, right, who has a chordoma, is researching the disease with Duke oncologist Neil Spector. (AP/ Wide World Photos)
Prognosis, prevention, and outcomes: If cancer cells remain after treatment, a chordoma can recur and spread to other parts of the body, most commonly the lymph nodes, lungs, and liver. The recurrence rate is high. Survival rates depend on the location of the tumor. Persons with chordomas of the skull base tend to have the best prognosis. Overall, about 90 percent of persons with chordomas survive about five to ten years. Kelli Miller Stacy, ELS See also Bone cancers; Spinal axis tumors.
Definition: One of the most dangerous germ-cell cancers, choriocarcinoma is a quick-growing cancer that occurs in a woman’s uterus after a pregnancy, miscarriage, or spontaneous abortion. This cancer arises from trophoblastic cells of the placenta and mimics the development of normal placental tissue. The cancer is usually invasive (metastatic), growing so fast that the original tumor outgrows its blood supply and dies, leaving behind only a small scar. For unknown reasons, it metastasizes early to the lungs, liver, and brain. Risk factors: Pregnant women are at risk.
u Choriocarcinomas Category: Diseases, symptoms, and conditions Also known as: Chorioblastomas, trophoblastic tumors, chorioepitheliomas, gestational trophoblast neoplasia, gestational trophoblastic disease Related conditions: Invasive mole 272
Etiology and the disease process: Choriocarcinoma is an uncommon cancer that is associated with pregnancy. Choriocarcinomas result from genetic damage to a germ cell. The cancer forms in the trophoblast (placental) cells that surround the baby. About half of all choriocarcinomas arise from a hydatidiform mole, also known as a molar pregnancy, in which a nonviable embryo implants and rapidly grows within the mother’s uterus. Approximately one-quarter of choriocarcinomas occur after pregnancy
Salem Health: Cancer has resulted in the delivery of a normal child. The remainder of cases occur after any type of abortion, ectopic pregnancy, or genital tumor. Most choriocarcinomas form inside the reproductive organs, such as the testes or ovaries, especially in young adults. A few choriocarcinomas arise in sites outside the reproductive organs (extragonadal tumors); these are usually found in young adults and are more common in men. Incidence: In North America, choriocarcinoma occurs in approximately 1 in 30,000 to 40,000 pregnancies. Choriocarcinoma is more common in Asian Americans than African Americans, and least common in whites. Choriocarcinoma has been shown to occur following hydatidiform mole (50 percent), normal term pregnancy (25 percent), and spontaneous abortion (25 percent). Symptoms: The symptoms of a choriocarcinoma vary, depending on where the tumor originates and where it spreads. If the cancer is in the uterus, the most common symptom is bleeding. Cancers in the ovary often have only subtle signs such as widening of the waistline or pain. In the testes, choriocarcinomas can often be felt as small painless lumps. Choriocarcinomas that spread to other organs may reveal their presence as a result of the bleeding or complications from bleeding that occur in their presence. In the brain, this bleeding can cause a stroke. Additional symptoms may include irregular vaginal bleeding, uneven swelling of the uterus, persistently high human chorionic gonadotropin (HCG) levels, or localized pain. Screening and diagnosis: Most choriocarcinomas produce human chorionic gonadotropin, a hormone normally found only during pregnancy. The presence of HCG in the blood can help in diagnosing this cancer and monitoring the success of treatment. Choriocarcinomas are usually referred to a doctor who specializes in cancer treatment (an oncologist). To diagnose this tumor, the doctor will do a physical examination and examine the internal organs with X rays or ultrasounds. Choriocarcinomas may not be biopsied before being treated because they tend to bleed heavily. Choriocarcinomas can be detected using ultrasound, X rays, computed tomography (CT), magnetic resonance imaging (MRI) scans, or positron emission tomography (PET) scans. Treatment and therapy: After making the initial diagnosis, the oncologist will take a careful history and perform an examination to rule out metastasis (spread to other organs). Chemotherapy is the treatment of choice. Choriocarcinoma is one of the tumors that is most sensitive to chemotherapy. The cure rate, even for metastatic choriocarcinoma, is about 90 percent. Almost all patients
Choriocarcinomas without metastases can be cured; however, metastatic disease to the kidneys, liver, or brain can be fatal. The chemotherapy regimen is generally EMA-CO: etoposide, methotrexate, actinomycin D, cyclosphosphamide, and vincristine (Oncovin). A hysterectomy (surgical removal of the uterus) is rarely required; however, a hysterectomy may be offered to patients over forty years of age or those desiring sterilization. It may be required for those with severe infection and uncontrolled bleeding. Prognosis, prevention, and outcomes: No known means of prevention exists; however, early detection of the symptoms and prompt medical treatment can improve the odds of survival. Although careful monitoring after the removal of a hydatidiform mole or the termination of pregnancy may not prevent the development of choriocarcinoma, it is essential in early identification of the condition, which improves outcome. The prognosis for choriocarcinomas in the uterus is very good. Although these tumors have often spread throughout the body, chemotherapy results in a cure or remission in at least 85 to 90 percent of cases. Women who have had choriocarcinomas often go on to have normal pregnancies and deliveries. Choriocarcinomas in sites other than the uterus have a poorer prognosis. These tumors tend to spread quickly and do not always respond well to chemotherapy. Although treatment can be effective, the outcome usually depends on how widely the cancer is dispersed. Generally, the prognosis is worse if the cancer can be found in the liver or brain, if HCG levels are high, or if the original tumor developed outside the gonads. However, about two-thirds of women who initially have a poor outlook go into remission (a disease-free state). Thomas L. Brown, Ph.D. u
For Further Information Baker, Vicki V. “Gestational Trophoblastic Disease.” In Clinical Oncology, edited by Martin D. Abeloff et al. 2d ed. Philadelphia: Churchhill Livingstone, 2000. Berkowitz, Ross S., and Donald P. Goldstein. “Gestational Trophoblast Neoplasia.” In Practical Gynecologic Oncology, edited by Jonathan S. Berek and Neville F. Hacker. 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2004. Vinay, Kumar, Abul K. Abbas, and Nelson Fausto. Robbins and Cotran Pathological Basis of Disease. 7th ed. Philadelphia: Elsevier/Saunders, 2005.
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Other Resources
Eyes on the Prize.org http://www.eyesontheprize.org/index.shtml 273
Chromium hexavalent compounds My Molar Pregnancy.com http://www.geocities.com/thornfield8998/molar.html See also Germ-cell tumors; Gestational trophoblastic tumors (GTTs); Human chorionic gonadotropin (HCG); Hydatidiform mole; Pituitary tumors; Teratocarcinomas.
u Chromium hexavalent
compounds Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1980 Also known as: Hexavalent chromium, chromium 6, chromium (Vl), Cr (Vl) Related cancers: Lung cancer, and less commonly, cancer of the nose and nasal sinus cavities Definition: The term “hexavalent” describes how highly oxidized chromium becomes in a chemical compound and means that chromium has combined with six oxygen atoms. It is this fully oxygenated form that is associated with chromium’s greatest industrial use and most serious health concerns.
Salem Health: Cancer ation and perforation, bronchitis, asthma, pneumonia, decreased lung function, and cancers of the nose, sinuses, and lung. Even short-term exposure may manifest in fits of coughing, wheezing, and shortness of breath. Although the respiratory tract is the primary area of concern, injury to the kidneys, liver, teeth, eardrums, eyes, and skin is possible. Although genetic damage following hexavalent chromium exposure is clear, research has not yet described the exact cellular mechanism that results in cancer. History: Shortly after chromium, “the red mineral,” was found in Siberia toward the end of the eighteenth century, it became useful as a paint pigment and leather-tanning product. Although some of its health risks soon became apparent, it was not until 1980 that the U.S. government officially acknowledged its role as a carcinogen. In the twenty-first century, businesses using hexavalent chromium must establish the exposure rates of their workers. The Occupational Safety and Health Administration (OSHA) has mandated strict monitoring and eight-hour exposure limits to hexavalent chromium dust or fumes in targeted job sites. Richard S. Spira, D.V.M. See also Cancer clusters; Cigarettes and cigars; Lung cancers; Nasal cavity and paranasal sinus cancers.
Exposure routes: Primarily inhalation and to a lesser extent skin contact and water intake Where found: Chromate dyes of plastics, inks, and photographic processing compounds; anticorrosive agent in paints, electroplated metal, and welded stainless steel; and also in leather-tanning products, textile dyes, and wood preservatives At risk: Workers in daily contact with hexavalent chromium. There is also concern among people living near contaminated wastewater, people who breathe air polluted with chromium hexavalent compounds, and those who have skin contact with products containing these compounds. Hexavalent chromium became part of the American lexicon following the film Erin Brockovich (2000), a cautionary tale about a cancer cluster seemingly associated with industrial contamination of the local drinking water. In a 2001 report, the Environmental Protection Agency estimated that more than two thousand work sites released 7 million tons of chromium compounds into the environment. The health risk from this discharge is unknown. Etiology and symptoms of associated cancers: The respiratory tract is the most common site for hexavalent chromium damage. This damage may lead to septal ulcer274
u Chromosomes and cancer Category: Cancer biology Also known as: Chromosomal instability, CIN Definition: Cancer is usually conceived of as resulting from a series of mutations in two classes of genes: oncogenes and tumor suppressors. Cancer cells, however, typically exhibit broader changes to their chromosome structure that extend well beyond the deoxyribonucleic acid (DNA) base changes that accompany most mutations. These include changes in chromosome number as well as the deletion, duplication, inversion, and translocation of chromosomal segments. Chromosomal aberrations, however, have historically been more difficult to study than mutations, and no direct evidence of their role in carcinogenesis has been produced. Scientists continue to debate whether these chromosomal changes play a causal role in cancer or are simply an artifact of the mutations that lead to cancerous states. However, some consensus has been reached that mutations and chromosomal instability probably play complementary roles in the formation of cancer and that neither acts completely independent of the other.
Salem Health: Cancer
Chromosomes and cancer
factual role of aneuploidy in cancer includes that aneuploid cells have been found to be associated with certain precancerous lesions and therefore could not have been caused by the formation of a cancerous state, that there are specific chromosomal translocations that are diagnostic of certain forms of cancer (these are often referred to as marker chromosomes when used in this context), and that the degree of aneuploidy in a cancer cell often correlates with the severity of the disease and can even be predictive of clinical outcomes. Aneuploidy has also been suggested to be one of the reasons cancer cells are so well adapted for continuous growth in their particular environment. By displaying a nearly limitElectron micrograph of human chromosomes. (Biophoto Associates/Photo Researchers, Inc.) less number of phenotypes that result from changing the dosage of many different combinations of genes, those cells Etiology and symptoms of associated cancers: Most that are particularly well adapted will be selected for and cancer cells are aneuploid. “Aneuploidy” is the term used will propagate more cells like themselves. However, there to describe the gain or loss of a chromosome in a cell, remains no direct evidence that an aneuploid state causes whether it be an entire chromosome or just a portion of the cellular changes that lead to cancer. one. In the latter case, the gain or loss has also been deAnother chromosomal abnormality that is associated scribed as a DNA insertion, or duplication, respectively. with almost all cancer cells, but which was not evident iniUnlike single mutations, aneuploidy can affect the exprestially using conventional cytological techniques, is the sion of genes by the thousands as large numbers of genes presence of very short telomeres. Telomeres are arrays of have their expression effectively doubled or cut in half by repetitive DNA that are found on the ends of linear chrothe duplication or deletion, respectively, of a chromomosomes. These structures protect genomic DNA from somal segment. Such changes in a gene’s “dosage” may, in the shrinkage that occurs in chromosomes every time they turn, lead to an increased rate of cellular mutation, espeare replicated. DNA polymerase, the enzyme that is used cially if the affected genes are involved in the repair of to copy DNA, is unable to copy a complete linear molecule DNA damage. Aneuploidy and mutation can therefore be of DNA because of its use of a ribonucleic acid (RNA) “primer” to initiate its activity. Telomeres are therefore thought of as complementary processes, with one state ofdegraded each time a cell duplicates and divides, providten leading to the other. ing a distinct limit on the number of divisions any cell can An extreme form of aneuploidy is polyploidy, where undergo. Rapidly dividing cells, such as those associated the entire complement of chromosomes in a cell has been with cancer, quickly reach this limit and enter a stage duplicated, so that there are more than the usual two copies deemed cellular crisis. Most cells that reach this stage stop of each chromosome in the cell. Many solid tumors have dividing, and many die, but cancerous cells overcome this been shown to be made up of polyploid cells. Subtler limitation, called the Hayflick limit after American cell bichanges in gene expression can also result from two other ologist Leonard Hayflick, who first described this phechromosomal aberrations that are seen to occur in cancer nomenon in 1962. To do this, most cancer cells express an cells: inversion and translocation. Here, a chromosomal enzyme called telomerase, which adds DNA repeats to the segment is “flipped around” in a chromosome or is transends of the chromosomes and allows cells to continue diferred to a different chromosome. Although the genes on viding indefinitely. this segment are still present in the cell, they may be differShortened telomeres have been shown to be associated entially expressed, because precisely where a gene is lowith chromosomal instability. Telomeres in this shortened cated on a chromosome often affects its level of activity. state often fuse with one another or to other regions of Evidence that supports a causative rather than arti275
Chronic lymphocytic leukemia (CLL) double-stranded breaks within chromosomes to avoid further degradation. The number of such break sites in cancer cells is often increased because of mutations in the DNA enzymes used to repair such damage. Chromosomes that are fused end-to-end or to another chromosomal segment that contains a centromere are then further jumbled when their DNA is pulled apart during mitosis. The centromere is a region of DNA that typically makes up the center of a chromosome and is the area to which the mitotic spindle attaches when sister chromosomes are separated from one another. The chromosomal abnormalities associated with aneuploidy can result from such cycles of fusion followed by chromosomal breakage. History: The concept that cancer is essentially a chromosomal disease is not a new one. In 1902 Theodor Boveri, a German zoologist, proposed that changes in chromosome number were the cause of tumor formation. He used cytological techniques to view the chromosomes of a tumor cell using a microscope. This is not to say that his aneuploidy theory did not leave room to account for the contributions of changes to specific genes. As the concept of thegene began to take shape during the early twentieth century, Boveri formulated a theory of how aneuploidy caused cancer that incorporated an early notion of mutational changes. He proposed that abnormal mitoses could lead to a combination of “chromatin determinants” that, in turn, would lead to cancer. However, when oncogenes and tumor suppressors were discovered in the 1970’s and 1980’s, the concept of aneuploidy as the causative factor of cancer began to fall out of favor. The notion that the identification of specific mutations in a finite number of genes would lead to a full understanding of cancer was an appealing one. As more and more cancer-causing genes were identified, the goal of understanding cancer at a molecular level seemed attainable. However, as time progressed, the mutational theory failed to explain a number of observations, including that cancer is rare in newborns, something one would not predict if newborns inherited cancer-causing genes from their parents; that certain carcinogens are known to cause cancer without causing mutations; and that a long latency period is always present before cancer develops, even after exposure to fast-acting mutagens. The resurgence of the aneuploidy theory of cancer formation can also be linked to the development of new techniques in the 1990’s, such as microarrays, which allow the expression levels of many genes to be assayed at the same time. Using microarray analysis, cancers were seen to exhibit changes in hundreds, or even thousands, of genes— many more than could be accounted for by a purely 276
Salem Health: Cancer mutational model. As cancer research progresses, the role of both mutations as well as chromosomal aberrations will need to be taken into account to fully understand their contributions to carcinogenesis. James S. Godde, Ph.D. u
For Further Information Deusberg, P., R. Li, A. Fabarius, and R. Hehlmann. “The Chromosomal Basis of Cancer.” Cellular Onocology 27 (2005): 293-318. Maser, R. S., and R. A. DePinho. “Connecting Chromosomes, Crisis, and Cancer.” Science 297 (2002): 565569. Rajagopalan, H., and C. Lengauer. “Aneuploidy and Cancer.” Nature 432 (2004): 338-341. Richards, R. I. “Fragile and Unstable Chromosomes in Cancer: Causes and Consequences.” Trends in Genetics 17 (2001): 339-345. Weaver, B. A. A., and D. W. Cleveland. “Does Aneuploidy Cause Cancer?” Current Opinion in Cell Biology 18 (2006): 658-667.
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Other Resources
National Cancer Institute The Center of Excellence in Chromosome Biology http://ccr.cancer.gov/initiatives/CECB/ National Center for Biotechnology Information Cancer Chromosomes http://www.ncbi.nlm.nih.gov/sites/ entrez?db=cancerchromosomes See also Cancer biology; Childhood cancers; Cytogenetics; Family history and risk assessment; Gene therapy; Genetic testing; Genetics of cancer; Hereditary cancer syndromes; Mitochondrial DNA mutations; Oncogenes; Proto-oncogenes and carcinogenesis.
u Chronic lymphocytic leukemia
(CLL) Category: Diseases, symptoms, and conditions Also known as: Chronic lymphoid leukemia Related conditions: Acute lymphocytic leukemia, acute myeloid leukemia, chronic myeloid leukemia Definition: Chronic lymphocytic leukemia (CLL) is a cancer of the white blood cells. A lymphocyte is a type of white blood cell made in the bone marrow that helps fight
Salem Health: Cancer infection. For unknown reasons, the bone marrow begins to make lymphocytes that develop abnormally, causing this fast-growing type of cancer. In this disease name, “chronic” means that the disease does not progress as rapidly as acute lymphocytic leukemia. Risk factors: There are few risk factors for CLL. Past research has concluded that the risk of developing CLL is not affected by environmental factors. However, research is ongoing as to whether exposure to herbicides and insecticides increases the risk of CLL. About half the people who develop CLL have chromosomal abnormalities, such as deletions on a chromosome or an extra chromosome. People with close relatives who have CLL have a slightly increased risk of developing this disease. Risk increases with age; patients with CLL are rarely under the age of forty-five and are generally over the age of sixty. Men are more likely to develop CLL than women, and whites and those of Russian Jewish or Eastern European Jewish descent are more likely to develop it than those of other racial and ethnic backgrounds.
Chronic lymphocytic leukemia (CLL)
Incidence of Chronic Lymphocytic Leukemia per 100,000 People, by Gender 7 Women
Men 6
5.8
5 4.4 4
3
2.9
2.8 2.1
2 1.3 1
1.1 0.6
0 White
Black
Hispanic
Asian/Pacific Islander
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 Note: Based on cases diagnosed in 2000-2004
Etiology and the disease process: CLL starts in a single white blood cell (lymphocyte). These CLL cells begin to multiply and crowd out the normal white blood cells. The CLL cells accumulate in the bone marrow, but they do not stop normal blood cell production quite as much as some other types of leukemia. Slow-growing CLL may cause only minimal changes in the blood for years. Some patients begin to produce an antibody during the CLL disease process that works against their body’s own red blood cells and causes a severe type of anemia. In a small number of CLL patients, the disease changes and begins to act like a more aggressive type of lymphoma or leukemia. In a very small number of CLL patients, throughout the disease process, CLL begins to act like acute lymphocytic leukemia (ALL). Incidence: About 15,340 people in the United States were diagnosed with CLL in 2007. Most with CLL are more than fifty years old. Symptoms: Symptoms of CLL usually develop slowly. Patients may find out they have this type of slow-growing
cancer after getting blood tests for another condition. Symptoms may include anemia, bleeding easily, bone pain, bruising easily, fever, joint pain, loss of appetite, night sweats, pain or a feeling of fullness below the ribs, shortness of breath, swollen liver, swollen lymph nodes, swollen spleen, tiredness, unexplained or repeated infections, and weight loss. Screening and diagnosis: There is no screening test for CLL. Blood and bone marrow tests are necessary to diagnose CLL. These tests look for abnormal lymphocyte cells. A bone marrow aspirate test (using a long needle to take marrow out of the bone) and a bone marrow biopsy (surgical removal of some bone marrow) are two possible tests. The bone marrow aspirate test looks for abnormal cells in the bone marrow and can also be used for other types of analysis. A bone marrow biopsy can show how much disease is already in the bone marrow. The results of these tests help determine which type of drug therapy to use and how long treatment should last. Another test that may be performed, immunophenotyping, helps determine 277
Chronic lymphocytic leukemia (CLL)
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whether the increased lymphocytes in the blood are monoclonal (came from a single malignant cell). This can help distinguish CLL from other types of diseases that cause increased lymphocytes in the blood. Depending on where the cancer started and the results of testing, CLL may be categorized into B-cell CLL (the most common type), T-cell CLL (which generally behaves more like other T-cell cancers than like CLL), or NK-cell CLL. B-cell CLL may be divided into further subtypes based on whether genetic mutations have occurred. As these mutations may affect how rapidly the disease progresses, this further division may help doctors determine treatment and which patients will benefit from earlier treatment. These subdivisions may also give a general idea of the progression and outcome of the disease, such as what effect the disease will have on marrow and blood cell development and what other organs, such as kidneys, bowels, or liver, may be affected. Researchers are investigating whether these subdivisions of CLL are actually different types of cancer. Staging of CLL involves evaluating the number of CLL cells; whether the liver, lymph nodes, or spleen are enlarged; and whether the red blood cell or platelet counts are low. In the Rai system, used commonly in the United States, CLL is divided into five stages: • Stage 0: Large numbers of lymphocytes in the blood but no other symptoms • Stage I: Large numbers of lymphocytes in the blood and enlarged lymph nodes • Stage II: Large numbers of lymphocytes in the blood, enlarged liver or spleen, possibly enlarged lymph nodes • Stage III: Large numbers of lymphocytes in the blood, too few red blood cells (anemia), possibly enlarged lymph nodes, liver, or spleen • Stage IV: Large numbers of lymphocytes in the blood, too few platelets, possibly too few red blood cells, and possibly enlarged lymph nodes, liver, or spleen
lower, anemia becomes worse, the lymph nodes or spleen have enlarged, or symptoms have become bothersome to patients. Treatment involves slowing the growth of CLL cells, keeping patients well enough to carry out daily activities, and protecting patients from infections, because the abnormal white cells are not able to fight infection. CLL is usually treated with chemotherapy or monoclonal antibody therapy. Both these therapies involve the use of certain drugs or drug combinations to kill abnormal lymphocytes. A bone marrow or cord blood transplant may help some CLL patients. A transplant is a high-risk procedure, however, and probably will not be used unless a patient has a fast-growing type of CLL, is younger than fifty-five years of age, and has a close relative who is a good transplant match. Older patients or patients with slow-growing CLL are not good transplant candidates. CLL is not usually treated with radiation therapy. However, radiation may be used if a large mass of lymphocytes is blocking an important part of the body, such as the kidneys, stomach, intestines, or throat. In a small number of CLL patients, surgery to remove the spleen (splenectomy) can help relieve pressure if the spleen is filled with too many CLL cells. If patients with CLL have problems fighting infections, they may be treated with antibiotics. If infections become a chronic problem, patients may be treated with injections of a protein found in the blood that fights infections (immunoglobulin). Follow-up treatment for CLL involves regular doctor visits and continuing lab tests to make sure the CLL cells are not beginning to increase rapidly. These doctor visits also help find any side effects from treatment. Patients who have had CLL are at increased risk for developing some other cancers, such as lung, colon, or skin cancer, and patients should be screened for these conditions during follow-up visits.
Treatment and therapy: Patients diagnosed with CLL may not need treatment immediately. They may have good health for several years without any treatment at all. However, doctors will want to watch and wait—closely follow patients with CLL to ensure that the CLL is not getting worse. This allows patients to avoid the side effects of treatment until treatment is necessary. However, some patients will need treatment near the time of diagnosis because these patients have had the disease for some time and it is progressing or because they have a faster-growing type of CLL. Treatment may become necessary when the number of CLL cells rapidly becomes higher, the number of normal cells becomes
Prognosis, prevention, and outcomes: There is no cure for CLL and no known way of preventing the disease. However, many patients, especially those with slowgrowing forms of this disease, may live for many years in good health. Survival rates range from one year to more than twenty or thirty years depending on stage and form of disease. The five-year survival rate of CLL patients is greater than 70 percent. Marianne M. Madsen, M.S.
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For Further Information Caligaris-Cappio, F., and R. Dalla-Favera, eds. Chronic Lymphocytic Leukemia. New York: Springer, 2005.
Salem Health: Cancer Faguet, G. B. Chronic Lymphocytic Leukemia: Molecular Genetics, Biology, Diagnosis, and Management. Totowa, N.J.: Humana Press, 2003. Parker, James N., and Philip M. Parker, eds. The Official Patient’s Sourcebook on Chronic Lymphocytic Leukemia: A Revised and Updated Directory for the Internet Age. San Diego, Calif.: Icon Health, 2002. u
Other Resources
Chronic Lymphocytic Leukemia Foundation http://www.cllfoundation.org Leukemia and Lymphoma Society http://www.leukemia-lymphoma.org National Cancer Institute Chronic Lymphocytic Leukemia Treatment http://www.cancer.gov/cancertopics/pdq/treatment/ CLL See also Acute lymphocytic leukemia (ALL); Acute myelocytic leukemia (AML); Agent Orange; Blood cancers; Chronic myeloid leukemia (CML); Hairy cell leukemia; Hemolytic anemia; Immunoelectrophoresis (IEP); Leukemias; Lymphocytosis; Monoclonal antibodies; Richter syndrome; Side effects; Staging of cancer.
u Chronic myeloid leukemia
(CML) Category: Diseases, symptoms, and conditions Also known as: Chronic granulocytic leukemia, chronic myelocytic leukemia, chronic myelogenous leukemia Related conditions: Acute lymphocytic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myelomonocytic leukemia, chronic neutrophilic leukemia, juvenile myelomonocytic leukemia, other myeloproliferative disorders such as essential thrombocythemia, myelofibrosis, and polycythemia vera Definition: Chronic myeloid leukemia (CML) is one of the four types of leukemia, cancers of the white blood cells. Patients with CML have a growth of malignant bone marrow cells, and these bone marrow cells begin to accumulate in the blood. Usually, these patients have a chromosome abnormality called the BCR-ABL cancer gene. “Chronic” means this cancer is more slow growing than an acute type of cancer. “Myeloid” is the type of white blood cell that is affected.
Chronic myeloid leukemia (CML) Risk factors: About 95 percent of people with CML have a chromosome abnormality called the Philadelphia chromosome (named after the city where it was first documented). The Philadelphia chromosome occurs when a piece of chromosome 22 breaks off at a gene called BCR. If a piece of chromosome 9 breaks at a gene called ABL and switches with the break in chromosome 22, the BCR-ABL cancer gene forms. This gene somehow instructs cells to make a protein that leads to CML. This gene appears only in the cells that form blood and is not passed on to other family members. This switch in chromosomes may be affected by very high levels of radiation (such as in atomic bomb survivors) or high-dose radiation therapy for other kinds of cancers. However, most people with CML do not have these risk factors, and others who have these risk factors do not develop CML. Etiology and the disease process: Like all leukemias, CML begins with a change in a single cell. At diagnosis, patients may be feeling well. Usually, the body makes more white blood cells only when fighting an infection, and when the infection has passed, the number of white blood cells returns to normal. However, if this disease is not treated, the white blood cells begin to increase rapidly and start to circulate in the blood, causing swelling of the liver and spleen. The number of BCR-ABL cancer genes in the body increases. The disease may progress to a phase in which the patient has a low red blood cell count (anemia) and the platelets are not able to function properly. Eventually the ability of the white blood cells to fight infection is affected. Incidence: About 4,500 people in the United States were diagnosed with CML in 2007. Though children may have CML, it is very uncommon; only about 2 percent of CML patients are children. Most CML occurs in adults. It is slightly more common in men than women. The risk of getting this cancer increases with age; most patients are adults older than age sixty. Symptoms: Symptoms of CML usually develop slowly. Patients may find they have this type of cancer after getting blood tests for another condition. Symptoms may include anemia (low red blood cell count), bleeding easily, bone pain, bruising easily, fever, loss of appetite, night sweats, pain or a feeling of fullness below the ribs (especially in the upper left abdomen), paleness, shortness of breath, stomach pain, swollen liver, swollen spleen, tiredness, unexplained or repeated infections, weakness, and weight loss. Screening and diagnosis: There is no screening test for CML. Generally, CML can be diagnosed from an exami279
Chronic myeloid leukemia (CML) nation of the blood cells. However, bone marrow tests may be done to look for changes not seen in the blood. Cytogenetic tests (tests that analyze a cell’s chromosomes) may also be used to confirm the diagnosis by looking for the BCR-ABL cancer gene. The results of these tests help determine which type of drug therapy to use and how long treatment should last. CML has three phases that are determined by how many immature leukemia cells (blasts) are in the bone marrow and blood: • Chronic phase: Most patients, about 85 percent, are in this stage when their CML is diagnosed. During this time, the blood and bone marrow have less than 5 percent blasts. Red blood cells and platelets are affected; however, white blood cells are still fighting infection. This stage may last for years. • Accelerated phase: During this phase, there are more than 5 percent but less than 30 percent blasts in the blood and bone marrow. Patients may begin to feel ill. They may have anemia, the number of platelets in the blood may drop, and the white cells may either increase or decrease. The number of blast cells begins to increase, and the
Salem Health: Cancer spleen may swell. At this phase, the disease is progressing, and patients are likely to move into the next phase. • Blast crisis phase: In this phase, there are more than 30 percent blasts in the blood and bone marrow. Patients in this phase often have infections. They may also be short of breath or tired and have stomach pain, bone pain, or bleeding. The number of blast cells in the blood and bone marrow increases, and the number of red cells and platelets drops. At this phase, CML may begin to act more like an acute leukemia.
Treatment and therapy: Drugs or chemotherapy are usually used to achieve treatment goals for patients with CML. These goals include bringing the red blood cell and platelet counts back to normal and eliminating all the cells with the BCR-ABL gene. This treatment also helps shrink the spleen back to normal size. Treatment does not cure CML. However, patients usually achieve remission, during which they feel well and are able to return to normal activities. If treatment is stopped, the symptoms are likely to flare up again. This may also happen if a patient becomes resistant to the drug treatment. Another possible treatment for CML is to have white blood cells removed from the blood (leukapheresis). This Incidence of Chronic Myeloid Leukemia may help if a patient has a very high per 100,000 People, by Gender white blood cell count, so high that the white blood cells are interfering with 2.5 blood flow to parts of the body, such as Women Men the brain. Monitoring whether treatment is 2.0 2.0 1.9 working is important with this disease. Patients will continue to have blood tests to see if red blood cell, white blood 1.5 1.5 cell, and platelet counts are returning to 1.5 normal. A blood test or bone marrow bi1.2 opsy (surgically removing some bone 1.1 1.0 marrow) can show whether the BCR1.0 ABL gene count is decreasing. Cytoge0.8 netic tests such as fluorescent in situ hybridization (FISH) or polymerase chain 0.5 reaction (PCR) may be used to monitor the level of BCR-ABL genes. Other tests, such as computed tomography (CT) scans or ultrasounds, may be used to see 0.0 how this cancer is affecting other parts White Black Hispanic Asian/Pacific of the body, such as the spleen. Islander A bone marrow or cord blood transSource: Data from National Cancer Institute, Surveillance Epidemiology and End plant may help some CML patients. A Results, Cancer Stat Fact Sheets, 2008 Note: Based on cases diagnosed in 2000-2004 transplant is a high-risk procedure but is the only cure for CML. Whether a pa-
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Salem Health: Cancer tient is a good candidate for a bone marrow transplant depends on the patient’s age and overall health, how the patient is responding to treatment with drugs, and how well donor cells and patient cells match. Transplants are generally more successful in younger patients and in those patients who are still in the chronic phase. Prognosis, prevention, and outcomes: There is no known way to prevent CML, though promising drugs are being tested. A bone marrow transplant is currently the only cure for CML; however, many patients can control CML with drug therapy. Outcomes for this disease depend on many factors, including age, size of spleen, and blood cell counts. The median survival rate for CML is four to six years. However, when the disease has moved into the accelerated phase, survival is usually less than one year. When this disease has moved into the blast crisis phase, survival rates drop to only a few months. Marianne M. Madsen, M.S. u For Further Information Cortes, Jorge, and Michael Deininger, eds. Chronic Myeloid Leukemia. New York: Informa Healthcare, 2007. Lackriz, Barb. Adult Leukemia: A Comprehensive Guide for Patients and Families. Cambridge, Mass.: O’Reilly, 2001. Talpaz, Moshe, and Hagop M. Kantarjian, eds. Medical Management of Chronic Myelogenous Leukemia. New York: Dekker, 1998. u
Other Resources
CMLHelp.org http://www.cmlhelp.org Leukemia and Lymphoma Society http://www.leukemia-lymphoma.org National Cancer Institute Chronic Myelogenous Leukemia Treatment http://www.cancer.gov/cancertopics/pdq/treatment/ CML See also Acute lymphocytic leukemia (ALL); Acute myelocytic leukemia (AML); Biological therapy; Bone marrow transplantation (BMT); 1,4-Butanediol dimethanesulfonate; Chronic lymphocytic leukemia (CLL); Computed tomography (CT) scan; Genetics of cancer; Leukapharesis; Leukemias; Myeloproliferative disorders; Tyrosine kinase inhibitors.
Cigarettes and cigars
u Cigarettes and cigars Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 2000 Also known as: Smoking tobacco Definition: Cigarettes and cigars are made from dried tobacco leaves, to which manufacturers add hundreds of substances to enhance flavor and other properties. The primary difference between cigars and cigarettes is that cigars are wrapped in leaf tobacco or other substances that contain tobacco, whereas cigarettes are wrapped in paper or other substances that do not contain tobacco. Also, cigars typically do not have filters. According to the American Cancer Society, a single large cigar can contain as much tobacco as an entire pack of cigarettes. Tobacco and tobacco smoke contain more than 4,000 chemicals, of which as many as 250 are known to be toxic or carcinogenic. The composition of smoke varies depending on the product, tobacco blend, chemical additives, and other factors. Some of the toxic compounds found in tobacco smoke include ammonia, tar, cyanide, carbon monoxide, and the carcinogens benzene, aromatic amines, arsenic, and chromium. Sidestream (second-hand) smoke contains many of the same carcinogens as mainstream smoke, sometimes in higher concentrations. Because cigars contain more tobacco than cigarettes and usually burn longer, they give off more sidestream smoke with higher concentrations of carcinogens. Related cancers: Cancers of the lung, oral cavity, larynx, pharynx, esophagus, bladder, stomach Exposure routes: Inhalation is the primary route of exposure to the carcinogens found in cigarettes and cigars. Smoking tobacco produces mainstream smoke that is inhaled by the smoker. Secondhand exposure via sidestream smoke (also called secondhand smoke, passive smoke, or environmental tobacco smoke) can also occur. Cigarettes are the primary source of tobacco smoke exposure; cigars are less common. Direct exposure through the mouth, gums, and swallowed saliva can also occur during smoking. Where found: Legally sold in the form of cigarettes and cigars At risk: All users of smoking tobacco are at risk of developing cancer. As of 2007, approximately 21 percent of adults in the United States (45.3 million people) were smokers. In 2006, about 371 billion cigarettes were consumed. The use of tobacco products varies with gender, age, and racial and ethnic background. More men smoke (23.9 percent) than women (18.0 percent). Smoking is 281
Cigarettes and cigars much more common among adults ages eighteen to fortyfour (48.5 percent) and forty-five to sixty-four (21.9 percent) than among those over age sixty-five (8.6 percent). In addition, of high school students, 23 percent smoke cigarettes and 14 percent smoke cigars. Overall smoking rates are highest among American Indians and Alaska natives (32 percent), whites (21.9 percent), and blacks (21.5 percent). Each year, approximately 438,000 people in the United States die prematurely from smoking or sidestream smoke exposure; another 8.6 million suffer from smoking-related illnesses. Cancer was among the first diseases causally linked to smoking, and cigarette smoking is the primary cause of cancer mortality in the United States (responsible for at least 30 percent of all cancer deaths). It is the leading risk factor for lung cancer and causes approximately 90 percent of lung cancer deaths in men and almost 80 percent in women. Smoking light cigarettes or those with less tar does not substantially reduce lung cancer risk.
Salem Health: Cancer Inhalation of sidestream smoke also increases cancer risk. More than 126 million nonsmoking Americans, including children, are regularly exposed to secondhand smoke, and more than 3,000 nonsmoking Americans die of lung cancer each year, primarily because of exposure to sidestream smoke. Cigar smoking is a popular habit in the United States. Rates more than doubled in the 1990’s, and approximately 5.1 billion cigars were consumed in 2005. Cigar smoking is most common among men ages thirty-five to sixty-four who have higher incomes and educational backgrounds. Most new cigar users are teenagers and younger males (ages eighteen to twenty-four). In addition, in 2004, about 18 percent of students (grades six to twelve) smoked at least one cigar in the past thirty days. Etiology and symptoms of associated cancers: Toxic ingredients in cigarette smoke travel throughout the body, causing damage in several different ways. Some carcinogens in tobacco smoke produce substances called epoxides when they undergo oxidation (burning). These epoxides bind to and damage the deoxyribonucleic acid (DNA) in cells, causing them to grow abnormally or divide quickly and uncontrollably, resulting in tumor development. Although nicotine is not considered carcinogenic, it can inhibit cell death, thereby promoting tumor development. Symptoms vary with the type of cancer. History: Based on the findings of hundreds of scientific articles, the U.S. Surgeon General first reported a causal association between cigarette smoking and cancer in 1964. The health risks associated with sidestream smoke were first published by the Surgeon General in 1972. Cigarettes are subject to several state and federal regulations. The 1964 Surgeon General’s report led to laws requiring warning labels on tobacco products; however, those laws were only applied to cigars much later. Television advertising of cigarettes has been prohibited since 1971 and has since been expanded to include advertising on radio and other electronic media; these regulations do extend to cigar advertising. Cigarettes and cigars are also subject to taxes, which vary from state to state. In addition, it is currently illegal to sell tobacco products to minors, and in many states it is illegal for a minor to possess any form of tobacco. Many states also prohibit smoking in restaurants and in some public places. Jaime Stockslager Buss, M.S.P.H., ELS u
Cigarette smoking is the primary cause of cancer mortality in the United States; it is the cause of at least 30 percent of all cancer deaths. (PhotoDisc)
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For Further Information Brandt, A. M. The Cigarette Century: The Rise, Fall, and Deadly Persistence of the Product That Defined America. New York: Basic Books, 2007.
Salem Health: Cancer Lapointe, Martin M., ed. Adolescent Smoking and Health Research. New York: Nova Biomedical Books, 2008. U.S. Department of Health and Human Services. The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General. Washington, D.C.: Author, 2006. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Eleventh Report on Carcinogens. Research Triangle Park, N.C.: Author, 2005. Wesley, Merideth K., and Ingrid A. Sternbach, eds. Smoking and Women’s Health. New York: Nova Science, 2008. u
Other Resources
American Cancer Society Tobacco and Cancer http://www.cancer.org/docroot/PED/PED_10.asp American Lung Association What Is the Connection Between Tobacco Use and Lung Disease? http://www.lungusa.org/site/c.dvLUK9O0E/ b.4061173/apps/s/content.asp?ct=5328919 Centers for Disease Control and Prevention Smoking and Tobacco Use http://www.cdc.gov/tobacco See also Chewing tobacco; Lung cancers; Oral and oropharyngeal cancers; Smoking cessation; Tobacco-related cancers.
u Clinical breast exam (CBE) Category: Procedures Definition: A clinical breast exam (CBE) is a screening test for cancer and other breast conditions intended to detect palpable masses and other indications of possible malignancy at an early stage of progression. ACBE is done by a clinician (physician, nurse practitioner, or physician’s assistant). It includes the inspection and palpation of the axillary and supraclavicular lymph nodes and breasts for masses and tenderness, examination for skin changes of the breast, and evaluation for nipple discharge. Cancers diagnosed: Breast cancer, including cancer in the milk ducts or lobules and cancer that is invasive to surrounding breast tissue; less commonly, breast cancer may originate outside the ducts or lobules, as with inflammatory breast cancer and Paget disease of the breast.
Clinical breast exam (CBE) Why performed: Breast cancer is the most commonly diagnosed cancer in U.S. women. It is estimated that in the United States, one out of seven or eight women will develop breast cancer at some time in their lives, and early diagnosis is key to effective treatment. Breast cancer is the second leading cause of cancer death in U.S. women. In 2006, over 212,000 women in the United States were diagnosed with breast cancer. Positive findings on a clinical breast exam that may be indicative of cancer require further tests. A clinical breast examination can find cancers that are missed by mammography up to 10 percent of the time, and 5 percent of breast cancers are found by the clinical breast examination alone. Mammography is used for screening in women who are forty years and older and diagnostically in younger women who are symptomatic. Clinical breast examination has not been found to be valuable for screening younger women because of limitations posed by their denser breast tissue. Ultrasonography has been used along with clinical breast examination for screening of high-risk young women, as has magnetic resonance imaging (MRI), but this use of MRI is controversial because of its high cost. Patient preparation: Before conducting a breast examination, the clinician reviews the patient’s history and any concerns, including whether she performs breast selfexamination (BSE), any history of lumps or nipple discharge, any history of breast surgeries, and family history of breast cancer. Family medical history is most significant if a first-degree relative (or relatives) developed breast cancer while premenopausal. Some women may come for a CBE with a known high risk for breast cancer, including a diagnosis of high-risk status from genetic screening for the BRCA1 and BRCA2 genetic defects. Steps of the procedure: Before the CBE, the clinician informs the patient that many of the steps to be performed are the same ones that she can herself in a self-exam, as the best time to teach BSE is while performing an examination. Clinical breast examination begins with visual inspection of the breasts. Adequate lighting is important to distinguish subtle changes. Flexation of the pectoral muscles with the patient’s hands on her hips, followed by examination of the breasts as the patient lifts her hands high above her head, will help determine the presence of dimpling or retractions, inverted nipples, and other skin changes. Following visual examination, the lymph nodes should be palpated for any swelling, masses, or tenderness, including those above and below the clavicle and the axillary nodes. It is recommended that this be done while the patient is sitting. Following examination of the lymph nodes, 283
Clinical breast exam (CBE)
Salem Health: Cancer biopsy, mammography, and, for women younger than thirty-five years old, diagnostic breast ultrasound. Mammography can help to evaluate the need for follow-up, but accurate diagnosis of a mass requires biopsy. A biopsy may be done in the office as a needle biopsy (either fine-needle or core needle) or surgically as an excisional biopsy (lumpectomy) that is both diagnostic and may provide treatment. A fine-needle biopsy produces the fastest results, but a negative result for a needle biopsy is nondiagnostic, meaning that because of the high rate of false negatives, further surgical evaluation is needed. After the procedure: The clinician will reinforce the need for breast self-exam and, for negative examinations, discuss intervals for regular screening mammography and make referrals if necessary. If any positive findings occur, then the need for further testing is discussed. Many patients need help arranging for additional testing, and many clinician offices will assist with scheduling of appointments rather than leaving patients to coordinate care when they may be emotionally distraught by the possibility of a cancer diagnosis.
This breast exhibits the skin change known as peau d’orange, which looks like the surface of an orange with regularly spaced, shallow pitting. (©Scott Camazine/ Phototake—All rights reserved)
the patient lies supine with her arm high above her head to flatten out the breast tissue and facilitate examination. Palpation should include the full margins of the breast tissue, including the tail of Spence, the area of breast tissue that extends from the upper outer quadrant toward the axilla, which is the site where most malignancies develop. It is important that the entire breast margin be palpated with the flats of the fingers moving in dime-size circles in a systematic fashion so that no area is missed. Common areas that are missed in self and clinical breast exams include the tissue that extends up to the clavicle and the area directly underneath the nipple. Each area should be palpated using light, medium, and then firm pressure. A well-done clinical breast examination takes at least several minutes. Studies have documented increased success in finding lesions when a minimum of five minutes is spent doing an examination, although studies have also documented that many clinicians spend less than two minutes, an inadequate amount of time, examining the breasts. Patients who are not used to examinations that take longer may be anxious and require reassurance that this is being done in order to be thorough, not as a result of suspicious findings. When a new breast lump is detected in a patient who is premenopausal, she will often be counseled to wait through one menstrual cycle and then return to the clinic for evaluation. In many cases, the lumps are benign and will spontaneously resolve. If a lump persists, the patient is referred to a breast surgeon who will evaluate the lump using 284
Risks: Clinical breast examinations are associated with no direct physical risk. False negative results, however, can be misleading and delay diagnosis, while false positive results are very common and can result in invasive testing and significant emotional distress and anxiety as well as expense. Results: The results of a clinical breast examination may be negative (no findings), in which case no action other than continuation of regular clinical screening and breast self-examination is warranted. Findings that are positive may include a discrete mass, a thickened area, breast tenderness or pain, nipple discharge, and skin changes. Discrete masses may be fixed or mobile and tender or nontender, and they may be in the breast tissue itself or in the axillary lymph nodes. They are carefully described as to shape, size, and location in the breast, including depth. A thickened area of breast tissue may be detected bilaterally (in both breasts) or unilaterally (in one breast only). It will be evaluated further but is less likely than a discrete mass to be a cause for concern. Breast tenderness may be bilateral or unilateral. It may
Salem Health: Cancer be hormonal and vary over the course of a month, but if associated with skin changes it can be related to infection or possible malignancy. Breast tenderness is common with some hormonal contraception and with pregnancy. Episodic sharp breast pain has been found to be responsive, in many cases, to a decrease in caffeine intake. Nipple discharge may be bilateral or unilateral and may be clear, reddish or bloody, milky, or greenish. It may occur spontaneously or only with manual expression. It may or may not have an odor. History of recent pregnancy as well as some medications (in particular, many antipsychotics) may cause a bilateral, nonsticky milky discharge called galactorrhea. Bilateral discharge is usually benign. Secretions may be collected on a slide and examined under a microscope to help determine the need for further evaluation, including mammography, other imaging methodologies, and biopsy. Skin changes may include uneven fullness or flattening, asymmetry that was not previously present, rashes and discoloration, areas of warmth and redness, retraction or dimpling of the skin, inversion of the nipple, crusting and erosion or ulceration of the nipple and areola, and the skin change described as peau d’orange, which looks like the surface of an orange with regularly spaced, shallow pitting. Skin changes are particularly associated with inflammatory breast cancer, which may cause red and swollen skin and a peau d’orange appearance, and Paget disease, which may cause an eroded and/or retracted nipple. Nipple inversion is of clinical concern only if it has not been present previously. Clair Kaplan, R.N., M.S.N., A.P.R.N. (WHNP), M.H.S., M.T. (ASCP) u
For Further Information Fenton, J. J., et al. “Specificity of Clinical Breast Examination in Community Practice.” Society of General Internal Medicine 22 (January 9, 2007): 332-337. Grobstein, Ruth H. The Breast Cancer Book: What You Need to Know to Make Informed Decisions. New Haven, Conn.: Yale University Press, 2005. Knutson, D., and E. Steiner. “Screening for Breast Cancer: Current Recommendations and Future Directions.” American Family Physician 75, no. 11 (June 1, 2007): 1660-1666. McDonald, S., D. Saslow, and M. H. Alciati. “Performance and Reporting of Clinical Breast Examination: A Review of the Literature.” CA: A Cancer Journal for Clinicians 54 (2004): 345-361. Weiss, N. S. “Breast Cancer Mortality in Relation to Clinical Breast Examination and Breast Self-Evaluation.” Breast Journal 9, suppl. 2 (May/June, 2003): S86-S89.
Clinical trials u
Other Resources
American Cancer Society Detailed Guide: Breast Cancer—Can Breast Cancer Be Found Early? http://www.cancer.org/docroot/CRI/content/ CRI_2_4_3X_Can_breast_cancer_be_found_early_5 .asp?sitearea= Susan G. Komen Foundation http://cms.komen.org See also Breast cancer in children and adolescents; Breast cancer in men; Breast cancer in pregnant women; Breast cancers; Breast self-examination (BSE); Calcifications of the breast; Mammography; Needle biopsies; Nipple discharge; Palpation; Screening for cancer.
u Clinical trials Category: Medical specialties Also known as: Clinical studies, clinical research studies, clinical investigational studies Definition: According to the U.S. Food and Drug Administration (FDA), a clinical trial is the systematic investigation of the impact of materials (such as investigational drugs and medical devices) or methods (such as surgery and radiation) on a disease state, conducted according to a formal trial protocol. The main objective of a clinical trial is evaluating the safety and efficacy of new materials or new methods in humans before approving these materials or methods for commercial use. To ensure the safety of all involved, clinical trials are strictly regulated by the FDA. The trial design can be controlled or uncontrolled, randomized or nonrandomized, and nonblinded, singleblinded, or double-blinded. Controlled means that the group receiving the new treatment is compared with a control group, whose members can be receiving a placebo, a different dose, no treatment, or standard-of-care treatment, or be historical subjects. Randomized means that patients who are selected to take part in a specific trial are randomly assigned to either the treatment or the control group. Single-blinded means that only the investigator, not the patient, knows whether the patient is in the treatment or control group. Double-blinded means that neither the investigator nor the patient knows to which group the patient has been assigned. FDA-regulated clinical trials are prospective, meaning that clinical data are collected forward according to a trial plan, in contrast to retrospective studies, where clinical data are retrieved from existing 285
Clinical trials sources, such as medical charts. Controlled, randomized, double-blind trials have the strongest scientific value. Starting a clinical trial has to be approved by the FDA and the Institutional Review Board after thorough scientific and ethical review of the mandatory regulatory documents (namely, investigational new drug application or investigational device exemption) for the new drug or medical device submitted by the clinical trial sponsor, which is normally a pharmaceutical or medical device company. Also, conducting, monitoring, inspecting, recording, and analyzing a clinical trial must be based on national FDA regulations and the International Conference on Harmonisation’s Good Clinical Practice (ICH-GCP) guidelines to ensure proper ethical conduct of a clinical trial (such as voluntariness of participation). Participants in a clinical trial are either healthy subjects (also called probands) or subjects with a specific target disease (such as breast or prostate cancer) and the clinical trial team, consisting of the (principal) trial investigators, the trial coordinator, and other health care professionals. For any drug, multiple trials in three phases must be conducted. In phase I trials, normally healthy subjects are involved, and these trials mainly focus on the trial’s feasibility. In addition, pharmacokinetic and pharmacodynamic data on the new drug are collected, and the maximal tolerable dose is determined (therefore, phase I trials are also called dose-finding trials). Phase I trials are usually shortterm (two weeks or less) and limited to ten or fewer individuals. Phase II trials are conducted to confirm the effective dose and regimen of the investigational new drug and to provide early efficacy and safety information. These trials are usually short-term (two months or less) and include approximately fifty to three hundred subjects with the primary target disease. Phase III trials normally include patients with the primary disease but also allow for associated conditions. These trials are normally longer-term and involve one hundred to thousands of patients, depending on the target disease. The goals of these trials are to determine efficacy for the main indication (such as breast cancer), the rates of adverse events (side effects), and, for drugs, the optimal dose. Phase IV trials, also called postmarketing trials, are conducted according to the product label in a very large patient population after FDA approval of the new drug, medical device, or method. The goal of these trials is normally further therapy optimization. Cancers addressed: Clinical trials are offered for patients with many kinds of cancers to evaluate new treatment options or altered treatment options or new indications for existing cancer therapies. 286
Salem Health: Cancer Training and certification: The required qualification and obligations of a clinical investigator to conduct a clinical trial are outlined in the regulations of the Food and Drug Administration and the Good Clinical Practice (GCP) guidelines. According to these regulations and guidelines, the principal clinical investigator (PI) of a clinical trial must, for example, submit a detailed curriculum vitae showing that the person is qualified by training and experience to investigate a new drug or method. The person should have at least two years’ experience in conducting clinical trials. The PI is trained in detail about the new drug or method before the beginning of a clinical trial. This training is provided by the clinical trial sponsor, which is normally a pharmaceutical company developing the drug. The training includes reviewing the clinical investigator’s brochure, a document prepared by the trial sponsor and containing all known relevant information on the investigational product, including preclinical, pharmacokinetic, and pharmacodynamic data in animals and in humans as well as data from earlier clinical trials. The training also includes how to properly report potential side effects in the patients according to the regulatory requirements. In addition, the PI has to train the trial team (trial coordinator, coinvestigators, and others) on the investigational product, including its proper use or administration according to the trial protocol, which must be strictly followed. Services and procedures performed: Participants in a clinical trial can possibly benefit from being treated with an investigational new drug or method or a commercially available drug used for a new indication, particularly if standard treatments are not effective or do not exist for the patient’s disease. Patients do not have to pay for the new treatment, and their overall health is generally more closely and thoroughly monitored than in nontrial settings. However, the new treatment is not guaranteed to work, and patients’ health may deteriorate during or after completion of the clinical trial. Also, patients may be part of the control group and not receive the new drug. Before patients can be included in a clinical trial, the investigator has to make sure that they meet strict inclusion criteria that have been outlined in the clinical protocol. If a patient meets all inclusion criteria and none of the exclusion criteria, the person must be thoroughly informed about the trial, and all questions must be answered satisfactorily. The investigator has to make sure that the patient has understood all benefits and potential risks involved with the trial, as well as the procedures performed at each trial visit and the patient’s obligation to complete the trial visits and to comply with all instructions given by the
Salem Health: Cancer investigator. The patient must also understand the alternative treatment options. Then, if the patient is still willing to participate in the trial, the individual has to sign and date a patient consent form stating that participation in the clinical trial is voluntary and that the patient can withdraw at any time without compromising the standard care to which the patient is otherwise entitled. The patient consent form must have been previously approved by an investigational review board (IRB), an independent group of medical and nonmedical professionals whose goal is to ensure that the clinical trial is performed safely, with integrity, and with respect to the rights of the participating subjects. After signing the informed consent, patients will be screened to ensure they are eligible for the trial. Screening visits generally include taking an anamnesis (a case history), performing a physical exam and lab tests, and documenting all medications the patient is currently taking. After the screening visit, eligible patients are randomly assigned to either the treatment or the control group, if the design of the trial requires patient randomization. After performing the trial procedure, which can include, for example, taking a specific investigational new drug or undergoing a surgical procedure, the patient will be closely monitored during the subsequent, predefined follow-up visits. Depending on the protocol, the patient procedures during these visits may include another physical exam, lab tests, an electrocardiograph (ECG), filling out questionnaires, and the recording of all side effects that may have occurred since the last visit, whether they may be associated with the trial treatment or not. All patient data collected are documented on case report forms by the clinical trial personnel. If any serious side effects occur between trial visits, the patient must inform the trial personnel immediately, seek immediate medical help, or both. The investigator’s responsibility is to report immediately any serious side effects (those that are life-threatening, lead to hospitalization, or are fatal) to the trial sponsor, which will take all required actions. All patient personal data are encoded before transferring them to any third party so the patients’ identities are concealed. After completion of an individual trial, which can take weeks or years depending on the trial phase and design, the trial data are analyzed, typically by the trial sponsor. The outcome of the analysis may influence the design of the next trial phase. The trial results may be published in a scientific journal. In many cases, however, analyses are performed at predetermined times during a clinical trial, which may lead to continuation or discontinuation of the trial (for example, if the trial results show a significant benefit). Use of so-called open-label trials after phase III
Clinical trials trials is relatively common. They typically follow a doubleblind, randomized, placebo-controlled trial of a new drug, and patients may be invited to enroll because this kind of trial allows gathering of further data about safety and tolerability of the new drug or device in long-term, day-today use. Treatment schedules, drug treatment, and doses are known to both the investigator and the patient in these trials. To apply for marketing approval of a new drug (or medical device) that has been tested in clinical trials, the sponsor must prepare a new drug application (NDA) or a corresponding marketing application for the medical device for submission to the FDA. This document contains all information on preclinical and clinical trials, as well as other knowledge about the drug or device. The FDA’s review of a standard new drug application typically takes just over a year. Silke Haidekker, Ph.D. u
For Further Information Blichert-Toft, M., H. Mouridsen, and K. W. Andersen. “Clinical Trials.” International Seminars in Surgical Oncology 12 (1996): 32-38. Friedman, L. M., C. D. Furberg, and D. L. DeMets. Fundamentals of Clinical Trials. 3d ed. New York: Springer, 1998. Jenkins, V., and L. Fallowfield. “Reasons for Accepting or Declining to Participate in Randomized Clinical Trials for Cancer Therapy.” British Journal of Cancer 82 (2000): 1783-1788. Olver I., et al. “The Adequacy of Consent Forms for Informing Patients Entering Oncological Clinical Trials.” Annals of Oncology 6 (1995): 867-870. Thornton, H. “Clinical Trials: A Brave New Partnership.” Journal of Medical Ethics 20 (1994): 3-4. Verheggen, F., R. Jonkers, and G. Kok. “Patients’ Perceptions on Informed Consent and the Quality of Information Disclosure in Clinical Trials.” Patient Education and Counseling 29 (1996): 137-153.
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Organizations and Professional Societies
Association of Clinical Research Professionals http://www.acrpnet.org 500 Montgomery Street, Suite 800 Alexandria, VA 22314 Society of Clinical Research Associates http://www.socra.org 530 West Butler Avenue, Suite 109 Chalfont, PA 18914 287
Coal tars and coal tar pitches u
Other Resources
Abramson Cancer Center of the University of Pennsylvania Oncolink/Emerging Med Cancer Clinical Trials Matching Service http://www.oncolink.com/treatment/matching.cfm CenterWatch Clinical Trial Listings Service http://www.centerwatch.com International Conference on Harmonisation of Technical Requirement for Registration of Pharmaceuticals for Human Use http://www.ich.org/cache/compo/276-254-1.html National Cancer Institute Finding Clinical Trials http://www.cancer.gov/clinical_trials U.S. Food and Drug Administration http://www.fda.gov See also American Association for Cancer Research (AACR); American Cancer Society (ACS); American Institute for Cancer Research (AICR); Chemoprevention; Chemotherapy; Complementary and alternative therapies; Dana-Farber Cancer Institute; Dietary supplements; Duke Comprehensive Cancer Center; Fox Chase Cancer Center; Fred Hutchinson Cancer Research Center; Informed consent; Jonsson Comprehensive Cancer Center (JCCC); M. D. Anderson Cancer Center; Mayo Clinic Cancer Center; Medical oncology; Medicare and cancer; Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI); National Science Foundation (NSF); Prevent Cancer Foundation; Robert H. Lurie Cancer Center.
u Coal tars and coal tar pitches Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1980 Also known as: Coal tar pitch volatiles (CTPVs) Related cancers: Skin cancer, scrotal cancer, lung cancer, bladder cancer, kidney cancer, leukemia, digestive tract cancers including the esophagus, as well as cancers of the oral cavity and larynx Definition: Coal tar is a product of bituminous coal distillation and is composed mainly of aromatic hydrocarbons. 288
Salem Health: Cancer Coal tar pitch is the residue produced by the distillation or heat treatment of coal tar. Continued distillation of the coal tar yields a variety of products, including benzene, toluene, xylene, naphthalene, anthracene, acridine, benzopyrene, chrysene, pyrene, and phenanthrene. The many coal tar distillates are central to the synthesis of dyes, drugs, explosives, flavorings, perfumes, preservatives, synthetic resins, paints, and stains. The remaining pitch left after distillation finds uses in paving, roofing, waterproofing, and insulation materials. Exposure routes: Inhalation, ingestion, skin contact Where found: Pesticides, roofing materials, pipe coatings, enamels, plastics, dyestuffs, synthetic fibers, synthetic rubbers, varnishes, paints, electrodes, binders used in aluminum smelting, epoxy resins, denatured alcohol, carbon brushes, graphites, road-paving materials, naphthalene, pharmaceuticals, high-temperature-resistant materials At risk: Those at risk include workers exposed to coal tars or coal tar pitches. Additionally, patients using therapeutic levels of coal tar preparations may be at risk for skin cancer. Especially vulnerable are workers exposed to coal tar fumes found in coal gasification and coke production. Etiology and symptoms of associated cancers: Coal tars and coal tar pitches contain several carcinogens, which include such known offenders as benzene and naphthalene. The resulting cancers include skin cancer (notably scrotal cancer), digestive tract cancers, lung cancer, bladder and kidney cancers, and leukemia. The cancer type is often associated with the workers’ exposure. For example, millwrights and welders are prone to digestive tract cancers and leukemia, while workers exposed to tar distillates show an increased risk of bladder cancer, and rates of kidney cancer climb with exposure to petroleum or coal tar pitches. History: Since 1775, when scrotal cancer was first described in chimney sweeps, industrial exposure to coal tar has been targeted as an important carcinogen. From coal tar pitch volatiles at coke ovens to pharmaceuticals used in the home, the carcinogenic potential is fully recognized. Richard S. Spira, D.V.M. See also Air pollution; Carcinogens, known; Carcinogens, reasonably anticipated; Coke oven emissions; Melanomas; Photodynamic therapy (PDT); Polycyclic aromatic hydrocarbons.
Salem Health: Cancer
u Cobalt 60 radiation
Coenzyme Q10
Category: Procedures
shrink or eliminate a tumor, then success is determined by the presence or absence and size of the tumor. Robert Bockstiegel, B.S.
Definition: Cobalt 60 is a radioactive isotope that is used to provide radiation therapy during cancer treatment.
See also External beam radiation therapy (EBRT); Gamma Knife; Radiation oncology; Radiation therapies.
Cancers treated: Many cancers, including breast, bladder, oral, and brain cancers Why performed: Cobalt 60 radiation is used to shrink or destroy tumors or to kill residual cancer cells left after surgical removal of a tumor. Patient preparation: Patient preparation will vary depending on the type of radiation therapy being administered and the type and location of the cancer. Before therapy is begun, the doctor works with other members of the cancer care team to develop a plan that will provide the maximum dose of radiation to the tumor or cancerous area while creating as little harm as possible to healthy cells in the surrounding area. Steps of the procedure: Cobalt 60 radiation can be administered in many ways. One way is to use a machine to aim the beam of radiation at the desired area from outside the body. Cobalt 60 can also be administered internally. Small capsules containing cobalt 60 can be inserted into the desired area to release radiation at close range. A device known as a Gamma Knife is a machine that uses 201 separate, stationary beams of cobalt 60 radiation to treat cancers that occur in the brain. After the procedure: Aftercare varies depending on the type of therapy performed. For most uses of cobalt 60, no specific aftercare is required unless the patient experiences significant side effects. Risks: The risks of cobalt 60 radiation vary depending on the type of radiation treatment being done, the strength of the radiation dose, the length and frequency of treatment, and the area of the body being targeted. Side effects of cobalt 60 radiation can include fatigue and nausea. If the radiation is delivered from an external source, then the patient may experience skin redness, tenderness, peeling, or discoloration. If the radiation is delivered internally, then there may be soreness around the cite of the delivery device(s). Results: The way in which success is determined when cobalt 60 is administered depends on the goal of the treatment. If the goal was to eliminate residual cancer cells, such as after surgical tumor removal, then the treatment is usually considered a success if the cancer does not return for five or more years. If the goal of the procedure was to
u Coenzyme Q10 Category: Lifestyle and prevention; complementary and alternative therapies Also known as: Co Q 10, ubiquinone, vitamin Q 10 Definition: Coenzyme Q10 is a fat-soluble vitamin or vitamin-like substance sometimes used in cancer treatment and prevention. A vitamin is an organic compound needed in very small amounts for the body to function normally. Vitamins serve as coenzymes or precursors to coenzymes that are normally present in food or may sometimes be generated in the body. Coenzyme Q10 is produced in all bodily tissues and is present in tiny quantities in food. Coenzyme Q10 has been shown to significantly reduce the cardiotoxicity of cancer chemotherapy drugs such as Adriamycin (doxorubicin). Studies of coenzyme Q10 used as an adjuvant to boost therapeutic outcome following standard treatment for breast cancer showed good results in a small number of patients; the studies, however, were neither randomized nor controlled. Cancers treated or prevented: All, particularly breast cancer Delivery routes: Orally as a pill (capsule or tablet) or intravenously (IV injection), the latter in animal studies How this substance works: Coenzyme Q10 was first isolated from beef heart mitochondria (energy-producing structures in the cell) by Dr. Frederick Crane in 1957. A year later, Karl Folkers determined the exact structure of coenzyme Q10. Coenzymes are cofactors upon which the relatively large and complex enzymes absolutely depend in order to function. Coenzyme Q10 acts as a coenzyme for at least three mitochondrial enzymes in addition to enzymes in other areas of the cell. Mitochondrial enzymes are crucial for the production of high-energy adenosine triphosphate (ATP), upon which all cellular activities depend; coenzyme Q10 acts as a coenzyme for several of the key enzymatic energy-generating steps in the cell. It also serves as an antioxidant vital to its clinical effects. Studies in animals found that coenzyme Q10 boosts the immune system and may be helpful in fighting certain infections and cancer. Since some conventional cancer therapies 289
Cognitive effects of cancer and chemotherapy such as drugs and radiation therapy destroy cancer cells by producing free radicals, researchers are trying to find out whether coenzyme Q10 in conjunction with traditional cancer treatments may affect the outcome. Side effects: While no serious side effects have been reported with coenzyme Q10 usage, the most frequently reported side effects include insomnia, higher-than-usual levels of liver enzymes, upper abdomenal pain, sensitivity to light, irritability, headache, dizziness, heartburn, and extreme fatigue. It should be kept in mind that coenzyme Q10 is a dietary supplement; it has not been approved for use as a cancer treatment by the Food and Drug Administration (FDA) and is regulated not as a drug but as a food. Cynthia Racer, M.A., M.P.H. See also Anthraquinones; Antioxidants.
u Cognitive effects of cancer and
chemotherapy Category: Social and personal issues Definition: Cancerous brain tumors often lead to neurological problems such as difficulties with memory, attention span, speed of mental processing, and reasoning skills. Chemotherapy for all types of cancer also can cause deficits in normal, healthy cognitive functioning. The drugs used can interfere with mental processing and produce what some refer to as “chemobrain” or “chemofog,” but the problems typically subside shortly after the treatment is terminated. However, for some individuals, the difficulties will remain for months or even years after chemotherapy has ended. Diagnosing cognitive deficits: Cognitive functioning refers to a host of processes that are performed by the brain that allow people to adapt to their environment and make informed judgments. Cognitive skills refer to the ability to attend to and concentrate on one or more tasks at the same time, to initiate and plan future actions, to engage in verbal or written language, and to have the ability to learn and recall information. All of these skills help people cope in a complex world. When one or more of these processes are short-circuited, mild or even devastating consequences can ensue. People with cognitive problems are likely to find it difficult to return to work or school and to function as well as they did in the past. In more severe cases, people might find it difficult to fully manage their normal daily activities. Their ability to maintain social relationships, to man290
Salem Health: Cancer age a household, and to monitor their own self-care during treatment can be significantly diminished. Because healthy cognitive functioning is so important, any dysfunction regarding cognitive processes brought on by cancer directly or due to chemotherapy must be diagnosed, assessed, and followed closely. The preponderance of evidence reveals that chemotherapy in standard-dose ranges can bring on cognitive impairments in approximately 20 percent of cancer patients. If high-dose treatments are used, research has shown that there is a significantly greater likelihood that normal functioning will be adversely affected. Neuropsychological testing with instruments such as the Halstead-Reitan Neuropsychological Battery, the Mini-Mental Status Exam, and the Weschler Adult Intelligence Scale is commonly done to diagnose and assess cognitive problems. These tests are crucial not only for providing an initial benchmark regarding how well an individual is functioning but also for long-term tracking of cognitive performance during and after cancer treatment. Behavioral symptoms: Patients undergoing chemotherapy often report that their ability to think is clouded and that they feel as if their heads are in a fog. Their ability to think and process information efficiently seems slowed and compromised. Neurological and neuropsychological testing reveals that some chemotherapy patients will have difficulty concentrating or paying attention. For others, the primary cognitive deficits emerge in terms of memory processing. Although long-term memory appears to be spared, short-term memory, including the manipulation of concepts that are present in the immediate consciousness, can be severely affected. Problems with comprehension, combined with language difficulties, can make it very difficult for a person to engage in multitasking, an ability that is very important for adequate functioning in the workplace or in school. Almost any combination of cognitive symptoms can result in problems with decision making and reasoning. Fortunately, the cognitive symptoms experienced by most cancer patients are usually mild to moderate. Although the literature contains reports of severe cases of delirium (mental confusion) due in part to chemotherapy, these instances are rare. In addition, in the vast majority of people with deficits brought on by cancer-fighting drugs, particularly adults, the chemo-induced cognitive problems are usually transient. Young children undergoing chemotherapy are more susceptible to long-term cognitive deficits. This is most likely because their central nervous systems are still immature and the drugs are affecting the development of
Salem Health: Cancer critical brain structures that are involved in mental processing. Long-term consequences for young children include an increased risk for developing a learning disability or attention-deficit disability, a general lowering of the intelligence quotient, and overall lowering of academic success in school. Possible causes and mechanisms involved: Although numerous studies have been conducted on the effects of chemotherapy agents on cognitive functioning, relatively little is known about the specific mechanisms that create the deficits. It is known that most chemotherapy drugs do not easily cross the blood-brain barrier. This protective barrier controls the types of substances that can leave the blood supply and enter the central nervous system. Because most chemotherapy drugs have difficulty crossing the barrier, they appear to exert their effect on the brain by influencing multiple secondary mechanisms that ultimately produce cognitive impairments. Several chemotherapy agents have been implicated in a neurological impairment called leukoencephalopathy, which is characterized by profound changes in the brain’s white matter. This condition could be caused by drugs coming into contact with the brain’s glial cells, which form the protective myelin sheath that covers some neurons. If the drugs are toxic to the glial cells, resulting in cell death, this could lead to abnormal neural signaling and ultimately influence cognitive processing. Another possible mechanism could be chemotherapy-induced anemia, which has long been associated with poor mental functioning, as is the case with vascular dementia. When the brain is not getting enough oxygen, it can result in deficiencies in alertness, attention, concentration, and memory. Brain tumors can lead to deleterious effects on cognition through several mechanisms. First, as brain tumors begin to grow, they can displace healthy structures adjacent to the cancer and alter the functional properties of neurons. Typically, as the tumor grows, more and more healthy tissue will be displaced, leading to more cognitive deficits. One explanation for the problems that develop is that the tumor growth squeezes adjacent structures to the point that the brain tissue that makes up the structure is no longer able to function normally. If this squeezing occurs over a long period of time, it could result in massive cell destruction, leading to permanent cognitive impairment. Management and treatment: Usually, chemotherapyinduced cognitive deficits begin to subside shortly after treatment has ended. If the deficits do not go away, there are ways to manage the impairments. Neurocognitiveenhancing drugs can be prescribed to help counteract whatever mechanisms might be involved in maintain-
Cognitive effects of cancer and chemotherapy ing the cognitive deficiencies. Behavioral stimulants, such as methylphenidate, commonly used in children with attention-deficient disorder, have been found to increase alertness, concentration, and energy levels in adults who have suffered from cognitive problems brought on by chemotherapy. Another treatment alternative involves cognitive rehabilitation therapy. This form of therapy targets specific areas of need, such as multitasking, organizational skills, or short-term memory, and teaches patients to practice mental exercises that force them to use their brains in a way that strengthens these areas. In some instances, patients are able to develop new coping strategies that compensate for cognitive processes that have become compromised. Bryan C. Auday, Ph.D. u
For Further Information Corrigan, Patricia, Humberto Fagundes, and Alan P. Lyss. Chemotherapy and Radiation for Dummies. Hoboken, N.J.: John Wiley & Sons, 2005. Kelvin, Joanne F., and Leslie Tyson. One Hundred Questions and Answers About Cancer Symptoms and Cancer Treatment Side Effects. Sudbury, Mass.: Jones and Bartlett, 2005. Magee, Sherri, and Kathy Scalzo. Picking Up the Pieces: Moving Forward After Surviving Cancer. Piscataway, N.J.: Rutgers University Press, 2007. Perry, Michael C., and James E. Wooldridge. Companion Handbook to the Chemotherapy Source Book. 2d ed. Philadelphia: Lippincott Williams & Wilkins, 2004.
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Other Resources
Cancer Symptoms.org Cognitive Dysfunction http://www.cancersymptoms.org/ cognitivedysfunction Cancer.Net http://www.cancer.net/portal/site/patient National Cancer Institute http://www.cancer.gov See also Anxiety; Brain and central nervous system cancers; Depression; Elderly and cancer; Leukoencephalopathy; Living with cancer; Neurologic oncology; Omega-3 fatty acids; Opioids; Personality and cancer; Psychooncology; Psychosocial aspects of cancer. 291
Coke oven emissions
u Coke oven emissions Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1981 Also known as: 3,4- benzopyrene, benzanthracene, chrysene, phenanthrene, benzene, toluene, and xyglenes Related cancers: Respiratory cancers including tracheal, bronchial, and lung cancers as well as cancers of the skin, prostate, scrotum, large intestine, pancreas, bladder, and kidneys Definition: Coke oven emissions are produced when bituminous coals are heated in the absence of oxygen to produce coke, tars, and light oils. Roughly 60 percent of the coal is converted to coke; the remainder is emitted in the form of by-products including light oils and gases and vapors of methane, ethane, ethylene, propylene, formaldehyde, ammonia, nitrogen oxides, cadmium, arsenic, and carbon monoxide. Tar acids, naphthalene, creosote, and pyridine are also emitted as coke oven gas tar. These various gases and vapors fall under the category of coke oven emissions and are the source of concern as potential carcinogens. Exposure routes: Inhalation, dermal contact Where found: Coke oven emissions occur when coal is processed to produce coke, or when the coke is combusted as fuel for making steel and processing ores, and in the manufacturing of substances such as graphite products. At risk: Workers in coke oven plants that produce coke from coal, at coal tar plants, and in the aluminum, steel, graphite, electrical, and construction industries are especially at risk. Residents in the immediate vicinity of cokeproducing plants and coal tar industries are also at risk of higher-than-normal exposure to vapors and gases. Etiology and symptoms of associated cancers: Coke oven emissions are related to respiratory cancers that can develop from inhalation or ingestion of toxic substances. These cancers typically interfere with speaking and breathing and often affect taste and smell. Skin cancer may result from dermal contact with toxic substances and is characterized by a tumor on or just below the skin surface, which may become red and irritated. Cancers of the prostate, scrotum, pancreas, bladder, kidney, and large intestine can develop if toxic substances are ingested and pass through the blood or urinary system. They may affect urine flow, frequency, and strength or may disable ejaculation. Pancreatic, kidney, and intestinal cancer can cause extreme abdominal discomfort as well as hinder the digestion and blood-cleansing processes. 292
Salem Health: Cancer History: Coke, or pure carbon, is used as a fuel reductant in the manufacture or synthesis of steel, iron, calcium carbide, graphite, and electrodes. The chemicals given off as coke oven emissions can be used in making plastics, solvents, dyes, drugs, paints, roads, roofing, insulation, pesticides, and sealants. Coke production in the United States began to decrease around 1950 because of a seemingly strong relationship between exposure to coke oven emissions and cancer rates. A number of studies conducted in the United States, Japan, Sweden, and the United Kingdom have produced significant evidence linking coke oven emissions with increased cancer rates among coke oven workers, especially cancers of the skin, lungs, and prostate. One study with 15,818 cohorts showed that occupational exposure to coke oven emissions was associated with significant excess mortality from cancer of the respiratory system and of the prostate. Another study found higher rates of lung cancer among topside coke oven workers and among those working near the tops, or lids, of the ovens, where exposure rates were greatest. Additional studies have shown significant links between exposure to coke oven emissions and incidence rates of malignant skin tumors and kidney, large intestine, and pancreatic cancers. Because of the studies confirming the relationships between coke oven emissions and cancers, numerous safety regulations are in place, including limitations on exposure levels to coke oven emissions and the use of respirators and protective clothing for coke oven workers. Still, use of coke as a fuel remains high in certain industries. Regulations require that coke oven emissions be collected, but structural defects, including loose-fitting doors and lids on coke ovens and poor engineering controls, result in continued release of varying amounts of potentially carcinogenic coke oven gases and vapors. Dwight G. Smith, Ph.D. See also Air pollution; Benzene; Coal tars and coal tar pitches.
u Cold nodule Category: Diseases, symptoms, and conditions Also known as: Hypofunctioning thyroid nodule Related conditions: Thyroid cancer, Hashimoto or de Quervain’s thyroiditis Definition: A cold or hypofunctioning nodule is a focal area of decreased uptake of radiotracer on a nuclear medicine thyroid scan that may correlate with a thyroid nodule
Salem Health: Cancer
Colectomy
felt on routine physical examination of the thyroid gland performed by a doctor.
u Colectomy
Risk factors: The risk factors for a cold nodule are the same as those for thyroid cancer, including previous radiation to the neck area as therapy for acne or for enlarged tonsillar tissue, a family history of thyroid cancer, and exposure to radioiodine in childhood.
Category: Procedures Also known as: Colon resection, large bowel resection, large intestine surgery
Etiology and the disease process: About 80 to 90 percent of solitary thyroid nodules are hypofunctioning. Although malignant thyroid tumors do not concentrate radioisotopes well and can therefore manifest as cold thyroid nodules, only about 10 to 20 percent of cold thyroid nodules occurring in young patients and about 5 percent of cold nodules occurring in adult patients are malignant. The remainder consist of cysts, inflammatory nodules of either Hashimoto or de Quervain’s thyroiditis, hemorrhagic benign nodules, or degenerative nodules. Incidence: The annual incidence of cold thyroid nodules in the general population is 5.2 per 100,000 young people and 55.9 per 100,000 adults. Symptoms: Symptoms include enlargement of the thyroid gland or a palpable lump or nodule within the gland. Physical findings suggestive of a malignant nodule in the thyroid include lymphadenopathy in the neck, size of the nodule, fixation to adjacent structures, or tracheal deviation. Screening and diagnosis: A cold nodule on a nuclear medicine scan may be composed of solid or cystic material or a combination of both as shown by thyroid ultrasound. Ultrasound is not especially useful for differentiating benign from malignant nodules of the thyroid unless multiple tiny echogenic foci are seen throughout the nodule, suggestive of microcalcifications. However, it is useful in guiding fine needle aspiration of the nodule. Neither computed tomography (CT) nor magnetic resonance imaging (MRI) helps distinguish benign from malignant thyroid nodules unless there is cervical adenopathy or local invasion. Treatment and therapy: Biopsy of the nodule is usually recommended using fine needle aspiration under ultrasound guidance to obtain tissue for pathologic evaluation. If the pathology from the biopsy shows malignant cells, then surgical removal of the nodule is warranted. Prognosis, prevention, and outcomes: If the nodule is benign, the prognosis is excellent. If the nodule is found to contain cancerous cells, then the prognosis depends on the stage and type of thyroid cancer found at surgery. Debra B. Kessler, M.D., Ph.D. See also Thyroid nuclear medicine scan.
Definition: Colectomy is the surgical removal of part or all of the colon. Either the two remaining ends of the bowel are connected (anastomosis) or the lower end is sealed and the upper end is rerouted to a new opening (ostomy) in the abdomen, forming a stoma. The ostomy may be temporary or permanent. Cancers treated: Colon cancer Why performed: For patients at high risk for colon cancer, colectomy is performed to remove precancerous lesions or to prophylatically remove the entire colon, thereby preventing the disease. For patients with colon cancer, colectomy is performed to remove the diseased colon segment with a margin of healthy tissue and all draining lymph nodes, as well as other lesions and involved structures, thereby curing or controlling the disease. For patients with advanced colon cancer, colectomy is performed to manage obstructions, perforations, hemorrhages, or other symptoms. Patient preparation: Medical tests are completed to plan effective treatment and to evaluate the patient’s fitness for major surgery. If an ostomy is needed, then a specialist counsels the patient and helps choose the location for the stoma. For the colectomy, certain patient medications may need to be stopped, the patient’s bowel must be cleaned, and the patient’s stomach must be emptied. In an emergency, patient evaluation and preparation may be limited. If the patient’s colon is partially obstructed, then the obstruction is relieved before the colectomy. If the patient’s colon is completely obstructed, perforated, or bleeding profusely, then the bowel cannot be prepared, and emergency surgery (colectomy or an alternative) is performed once the patient is stabilized. Steps of the procedure: Colectomy is performed in an hospital. Before the surgery, sensors are placed to monitor the patient’s condition. An intravenous (IV) line is started, and an antibiotic is infused. General anesthetic is administered, and a breathing tube is placed. The patient is positioned, a urinary catheter is inserted, and the incision site is prepared. Colectomy has four steps: opening and evaluation, tissue removal, anastomosis or stoma formation, and inspection and closure. Details vary with the part(s) of the colon involved (ascending, transverse, descending, or sigmoid); 293
Coloanal anastomosis
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why the colectomy is needed (prevention, cure/control, or relief); and the surgical approach chosen (open or laparoscopic). In an emergency, these steps may be reordered or performed as separate procedures. To begin, the surgeon opens the abdomen with one large incision; four to five small incisions, when using a laparoscope; or a combination of these approaches. Within the abdomen, the surgeon looks for cancer and other abnormalities, then evaluates the colon segment to be removed. If the colon segment cannot be removed safely, then a bypass procedure is performed instead. If the colon segment is removable, then the colectomy continues. To remove tissue, first the major blood vessels to that colon segment are tied. The colon segment is freed from attachments. The mesentery for that colon segment is clamped and divided; the tied blood vessels are divided and sealed; and then that colon segment is divided and removed, as well as any adjacent tissues that are diseased. All tissues are taken to the laboratory for histopathologic evaluation. Either the remaining ends of the bowel are connected, forming an anastomosis (colo-colo, colo-rectal, or coloanal), or the lower end is sealed and the upper end is rerouted. When rerouting, first an ostomy opening is made in the abdomen. The upper end is passed through the ostomy opening; the bowel segment is sized to an appropriate length; and the edge of the cut end is folded back and stitched to the abdomen, forming a stoma. Finally, the inside of the abdomen is inspected and cleaned, and the incision is closed.
bleeding, perforation, abscess, fecal contamination, incisional hernia, bowel obstructions, and peritoneal seeding.
After the procedure: Anesthesia is stopped, and the breathing tube is removed. The urinary catheter and the IV line are kept. If an ostomy was needed, then a clear collection pouch (ostomy appliance) is fitted over the stoma. The patient is transferred to the recovery room and then to a hospital room. Medications are given to control pain and infection. The patient slowly progresses to a normal diet and learns to regulate bowel function. If an ostomy was needed, then it is monitored; once the stoma starts functioning, the patient learns to care for it and to empty and change pouches. At home, the patient follows the physician’s instructions about medications, activities, and diet. Additional treatment with radiation therapy, chemotherapy, or both may be recommended.
See also APC gene testing; Colorectal cancer; Colostomy; Gardner syndrome; Hereditary polyposis syndromes; Pancolitis; Turcot syndrome.
Risks: Colectomy is moderately safe, with low mortality, but it is riskier in emergencies. The risks relate to anesthesia, infection, and inadvertent damage to structures. Side effects are common, with the most frequent ones being urinary infection, wound infection, and problems related to anastomosis or ostomy. Less frequent side effects are 294
Results: Long-term outcome varies with patient-specific factors (such as life-threatening condition, disease stage, and overall health) and therapeutic combinations (such as type of radiation therapy, chemotherapy, or both after surgery). Curative removal is possible for many first-time patients, but otherwise recurrence rate is high. Five-year survival is excellent for patients with localized cancer but is poorer for patients with more advanced disease. Patricia Boone, Ph.D. u
For Further Information Levin, Bernard, et al., eds. American Cancer Society’s Complete Guide to Colorectal Cancer. Atlanta: American Cancer Society, 2006.
u
Other Resources
American Cancer Society Colon and Rectum Cancer Surgery http://www. cancer.org Patient Education Institute Colon Cancer Surgery: Interactive Tutorial http://www.nlm.nih.gov/medlineplus Society of American Gastrointestinal and Endoscopic Surgeons Laparoscopic Colon Resection http://www.sages.org
u Coloanal anastomosis Category: Procedures Also known as: Low anterior resection of the rectum; ileal pouch anal anastomosis Definition: Coloanal anastomosis is the surgical removal of a portion of a diseased rectum or the entire rectum and the attachment of the colon to the remaining rectum or to the anal muscle. This technique preserves anal function so that, in the long term, the process of eliminating stool remains nearly the same. Cancers treated: Rectal and colon cancer Why performed: Coloanal anastomosis is performed to treat colorectal cancer or severe dysplasia with inflamma-
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Coloanal anastomosis anal muscle. The surgeon also creates a temporary loop ileostomy during the first surgery to divert stool into an external colostomy bag outside the body to allow the bowel to heal. In some cases, the side of the colon is attached to the anus (side-to-end coloanal anastomosis), and a small pouch is created from a section of the colon (about 2 inches long) to store stool until it is eliminated. With the J-pouch coloanal anastomosis procedure, a larger, J-shaped pouch is created. About six to eight weeks after the first surgery, a second surgery is performed to reverse the loop ileostomy and restore anal function. Recent studies have suggested that there is no need for a temporary diverting stoma, so patients should discuss the surgical technique with their surgeon.
Coloanal anastomosis. (Custom Medical Stock Photo)
tory bowel diseases when other medical therapies have not been effective. It is also performed when a malignant stricture or fistula is suspected. Patient preparation: Before surgery, the patient’s medical status must be optimized by managing malnutrition, treating infection, and correcting anemia and dehydration. In some cases, total parenteral nutrition (tube feeding) may be required before surgery to rest the bowel and reduce symptoms that may be occurring as a result of eating solid foods. Tests before surgery may include biopsy, endoscopic evaluation, and radiography. Patients should receive thorough education regarding the risks, benefits, and expected outcomes of the proposed surgery. The health care team should discuss the patient’s expectations after surgery as well as the care of the temporary ostomy. One week before the procedure, patients must stop taking anticoagulants, as directed by the physician, to reduce the risk of increased bleeding during surgery. The patient uses a bowel preparation the day before surgery to cleanse the bowel. In many cases, antibiotics are given to reduce the risk of infection. The day before surgery, the patient follows a clear liquid diet and should not eat or drink anything after midnight the evening before surgery. Steps of the procedure: The procedure is usually performed in two stages. During the first surgery, the diseased portion of the rectum or the entire rectum is removed and the bowel is reconnected to the remaining rectum or the
After the procedure: Medications are given to manage pain, and an intravenous line delivers fluids and medications as needed. In some cases, nutrients are delivered intravenously until the patient is well enough to take foods orally. A urinary catheter removes urine and is removed about two to three days after surgery. Tubes may be in place to remove fluids and bloody drainage from the wound. Anal leakage is common after surgery and occurs as a result of the stress on the anal muscles during surgery. It may occur for several weeks and can be managed by wearing a cotton pad. The patient is not able to eat or drink until bowel function is restored, as indicated by the passage of liquid waste. Bowel function usually returns within twenty-four hours up to a few days after surgery. The patient gradually progresses to a clear liquid diet and advances to full liquids and soft, bland foods. The hospital stay is about five to seven days, depending on the patient’s recovery. The patient is encouraged to get out of bed and walk the day after surgery, and activity gradually progresses to several daily walks in the hall. Before going home, the patient receives instructions from an enterostomal therapy (ostomy) nurse who teaches the patient about caring for the temporary ostomy, obtaining ostomy supplies, and managing potential complications such as stomal blockage. The patient receives specific activity and dietary guidelines. A follow-up schedule is provided, and home care nursing services are scheduled as necessary. The patient can gradually return to regular activities, with a full return to normal activities within five to six weeks after being discharged from the hospital. Risks: The most frequent complication is pouchitis, an inflammation of the pouch characterized by increased stool frequency, urgency, incontinence, abdominal cramps and pain, and flulike symptoms. Other risks include wound infection, urinary tract infection, poor postoperative ano295
Colon polyps
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rectal function, stricture of the anastomosis, anal fistula or abscess, and reduced fertility. Results: Coloanal anastomosis surgery prevents the longterm need for a colostomy bag, maintains anal sensation, and improves continence after the rectum has been removed. Angela M. Costello, B.S.
Colon
u For Further Information Berndtsson, Ina, et al. “Long-Term Outcome After Ileal Pouch-Anal Anastomosis: Function and HealthRelated Quality of Life.” Diseases of the Colon & Rectum 50 (2007): 1545-1552. Heppell, Jacques. “Surgical Management of Inflammatory Bowel Disease.” UptoDate, January, 2008. Huh, Jung Wook, et al. “A Diverting Stoma Is Not Necessary When Performing a Handsewn Coloanal Anastomosis for Lower Rectal Cancer.” Diseases of the Colon & Rectum 50 (2007): 1040-1046. Kiran, R., and V. Fazio. “Inflammatory Bowel Disease: Surgical Management.” In Fecal and Urinary Diversions: Management Principles, edited by J. Colwell, M. Goldberg, and J. Carmel. St. Louis: Mosby, 2004. u
Polyps
Worms
Diverticular disease
Other Resources
American Society of Colon and Rectal Surgeons http://www.fascrs.org National Cancer Institute General Information About Rectal Cancer http://www.cancer.gov/cancertopics/pdq/treatment/ rectal/Patient National Digestive Diseases Information Clearinghouse (NDDIC) http://digestive.niddk.nih.gov/index.htm See also Colectomy; Colorectal cancer; Enterostomal therapy; Exenteration; Hereditary polyposis syndromes; Ileostomy; Stent therapy.
u Colon polyps Category: Diseases, symptoms, and conditions Also known as: Colorectal polyps Related conditions: Familial adenomatous polyposis (FAP), Gardner syndrome, colon cancer Definition: Colon polyps are extra clumps of tissue that grow inside the large intestine. Most polyps are benign, but some can turn into cancer. 296
Ulcerative colitis Crohn’s disease Polyps Bowel cancer Appendicitis
Ulcerative colitis
Polyps and other intestinal disorders.
Risk factors: People older than age fifty and those with a family or personal history of colon polyps or colon cancer are more likely to develop these growths. Ulcerative colitis and Crohn disease increase a person’s risk of polyps. Genetic mutations play a role in a small number of colon polyp cases. A high-fat diet, alcohol consumption, smoking, excess weight, and a lack of exercise have also been linked to an increased risk for colon polyps. Etiology and the disease process: Polyps are caused by abnormal cell growth. They may be smaller than a pebble or larger than a golf ball. Some are flat; others have a domelike shape. The larger the polyp, the more likely it will turn cancerous.
Salem Health: Cancer There are three types of colon polyps: adenomatous, hyperplastic, and inflammatory. Adenomatous polyps may turn into cancer if they grow larger than a quarter inch wide. Hyperplastic polyps are rarely cancerous. Inflammatory polyps may develop after a flare-up of inflammatory bowel disease. Incidence: Persons over age sixty with normal risk factors have a 1 in 4 chance of developing a polyp. Colon polyps afflict more men than women. Symptoms: There may be no symptoms. However, some polyps, particularly larger ones, can cause constipation or diarrhea, blood in the stool, rectal bleeding, or crampy abdominal pain. Screening and diagnosis: A doctor may feel a rectal polyp during a rectal exam, but a physical exam is usually normal. Other tests used to screen for polyps include barium enema, sigmoidoscopy, or colonoscopy. Cancer experts recommend that persons age fifty and older at normal risk be screened every ten years with a colonoscopy. Alternatively, screening with sigmoidoscopy or barium enema may be done every five years. People at increased risk for polyps may need screenings more often. Treatment and therapy: Polyps can be removed during a colonoscopy or sigmoidoscopy or surgically through the abdomen. A biopsy of the polyp determines if it is cancerous. Prognosis, prevention, and outcomes: A low-fat diet rich in fruits and vegetables and foods high in calcium and folate may reduce the risk of colon polyps. Other forms of prevention include regular exercise, losing excess weight, avoiding alcohol, and not smoking. Kelli Miller Stacy, ELS See also Adenomatous polyps; Cholecystectomy; Colonoscopy and virtual colonoscopy; Colorectal cancer; Colorectal cancer screening; Desmoid tumors; Duodenal carcinomas; Gastric polyps; Gastrointestinal cancers; Gastrointestinal oncology; Hereditary mixed polyposis syndrome; Hereditary polyposis syndromes; Juvenile polyposis syndrome; Polypectomy; Polyps; Rectal cancer; Sigmoidoscopy.
Colonoscopy and virtual colonoscopy
u Colonoscopy and virtual
colonoscopy Category: Procedures Also known as: Endoscopy, CT colonoscopy Definition: These procedures employ either a colonoscope (a flexible tube inserted into the colon with a light and camera at the tip) or computerized imaging to examine the large intestine for precancerous, cancerous, and other conditions. Cancers diagnosed: Cancers of the large intestine and rectum, precancerous adenomas, polyps Why performed: These procedures are intended for the prevention and early detection of colon cancer for people over the age of fifty, or earlier when indicated. They are also a necessary component in the management of inflammatory bowel diseases (Crohn disease and ulcerative colitis) or for individuals who have a family history of polyps or diseases of the large intestine. Many patients resist the procedure as a result of embarrassment and/or concern over the bowel preparation, which is the same for both traditional and virtual colonoscopy. Neither procedure replaces the need for yearly testing for blood in the feces with a fecal occult blood test (FOBT) or a fecal immunochemical test (FIT). There are several considerations in deciding on the appropriate procedure. Patients should discuss family history of any bowel disease, increasing age, existing medical problems, and other personal issues with a physician when deciding the most appropriate procedure. Both forms of colonoscopy are considered the most thorough and accurate in examining the entire large intestine, but there are differences in how they are performed and what happens if a test is abnormal. Patient preparation: Patients should not stop taking any medications (such as insulin, aspirin, or blood thinners) to prepare for a colonoscopy unless approved by their physicians. Three days before either procedure, the patient should stop eating a high-fiber diet or taking fiber supplements and iron-containing vitamins or iron tablets. The day before the procedure, all three meals should consist only of clear liquids, such as tea, broth, gelatin, clear juices, tea, or coffee. The doctor will provide bowel preparation information and laxatives, either tablets or liquid, to take the day before the procedure and possibly again four hours before the procedure. The large intestine must be completely empty and free of all fecal matter in order to clearly see any abnormal growths or changes in the wall of the intestine. The 297
Colonoscopy and virtual colonoscopy patient may not eat or drink anything after midnight before the procedure unless it is water to take approved medication. Steps of the procedure: Traditional colonoscopy is usually performed in an outpatient surgery suite. Patients are moderately sedated and given pain medication through an intravenous catheter. It is common for patients to sleep through the procedure, which can take thirty to sixty minutes. The patient lies on the left side, and a colonoscope is inserted through the anus and rectum. The doctor watches a video screen as the tube is guided through the large intestine. Examination includes visualization during slow withdrawal of the tube, as some growths can be hidden in folds in the intestine. The gastroenterologist is looking at the actual lining of the intestine—not a computerized image. The following can be done during this procedure: removal of polyps, sampling of abnormal tissue (biopsy), removal of small growths, stopping of small areas of bleeding, laser treatment of abnormal tissue or growths, and the introduction of certain medicines. Virtual colonoscopy is performed by a radiologist in a radiology suite. No sedation is necessary. The patient is
Salem Health: Cancer asked to lie on the back on a table. A thin tube is inserted into the rectum introducing air to inflate the large intestine for better visualization. The table passes through the scanner as three-dimensional computerized images of the large intestine are made and immediately viewed on a video screen. The patient is instructed to periodically hold the breath to be sure that the images taken are clear. The procedure is repeated with the patient lying on the stomach and is completed in ten to fifteen minutes. Identification of anything abnormal might require traditional colonoscopy. Repeat bowel preparation will be necessary if the procedure cannot be performed the same day. After the procedure: The patient will need to be driven home after traditional colonoscopy, as the sedation used during the procedure makes it unsafe to drive. It can take one to two hours after traditional colonoscopy for the patient to be alert enough to be driven home. There can be some abdominal cramping and feelings of gas. Normal activities can be resumed the following day. Virtual colonoscopy does not require medication, and patients are free to leave immediately after the procedure. Some cramping might occur following virtual colonoscopy because of the introduction of air during the procedure. Risks: Perforation and/or infection of the large intestine, while very uncommon, is a possible complication from traditional colonoscopy. The doctor will provide an information sheet that describes what is normal and not normal following colonoscopy. Symptoms that should indicate calling the doctor include bloody diarrhea, blood coming from the rectum, dizziness, fever, severe abdominal pain, and weakness. There is radiation exposure with virtual colonoscopy.
Colon cancer detected by colonoscopy. (Brian Evans/Photo Researchers, Inc.)
298
Results: Both procedures are considered the most thorough in examining the entire large intestine. Traditional colonoscopy is better at finding growths smaller than 10 millimeters and has the advantage of permitting biopsies of abnormal growths, removal of polyps, treatment of inflammation or disease, and laser treatment during the examination. Virtual colonoscopy is a much newer procedure and has been widely embraced by those who are fearful of traditional colonoscopy. Traditional colonoscopy is required following virtual colonoscopy if any abnormalities
Salem Health: Cancer are found. Some studies have found that certain abnormalities on virtual colonoscopy were normal when traditional colonoscopy followed. Studies continue comparing the benefits and drawbacks of each procedure. Janet R. Green, M.S.P.H. u For Further Information Cotterchio, M., et al. “Colorectal Screening Is Associated with Reduced Colorectal Cancer Risk: A Case-Control Study Within the Population-Based Ontario Familial Colorectal Cancer Registry.” Cancer Causes & Control 16, no. 7 (2005): 865-875. Waye, Jerome D., Douglas K. Rex, and Christopher B. Williams, eds. Colonoscopy: Principles and Practice. Malden, Mass.: Blackwell, 2003. Yee, Judy. Virtual Colonoscopy. Philadelphia: Lippincott Williams & Wilkins, 2008. u
Other Resources
American Cancer Society http://www.cancer.org Mayo Clinic http://www.mayoclinic.org National Cancer Institute http://www.cancer.gov See also Adenomatous polyps; Barium enema; Colon polyps; Colorectal cancer; Colorectal cancer screening; Crohn disease; Digital rectal exam (DRE); Diverticulosis and diverticulitis; Hereditary mixed polyposis syndrome; Hereditary polyposis syndromes; Inflammatory bowel disease; Juvenile polyposis syndrome; Laxatives; Polypectomy; Polyps; Rectal cancer.
u Colony-stimulating factors
(CSFs) Category: Chemotherapy and other drugs ATC code: BO3XA01-erythropoietin, BO3XA02darbepoetin alfa, LO3AA02-filgrastim, LO3AA03molgramostim, LO3AA09-sargramostim, LO3AA10lenograstim, LO3AA12-ancestim, LO3AA134pegfilgrastim Also known as: Hematopoietic growth factors Definition: Colony-stimulating factors (CSFs) are glycoproteins that stimulate the production of blood cells. Several recombinant CSFs have achieved widespread clinical use. Others have been identified but have not been as-
Colony-stimulating factors (CSFs) sessed in clinical trials or have not been approved for use by the Food and Drug Administration (FDA). Cancers treated: Colony-stimulating factors are not used to treat cancers per se. Rather, they are used as supportive care to increase red blood cell, white blood cell, and hematopoietic stem cell counts that are depleted during some forms of chemotherapy or radiation therapy. CSFs generally are administered only to patients with nonmyeloid malignancies and usually as primary prophylaxis to prevent febrile neutropenia or to allow dose intensity with specific chemotherapy regimens. CSFs are administered after chemotherapy or radiation therapy. They also may be used before bone marrow or stem cell transplantation to increase the number of cells available for transplant or after transplantation to assist in bone marrow recovery. Delivery routes: Because colony-stimulating factors are proteins and are subject to digestion and degradation in the stomach, they are administered either as intravenous (IV) infusions or subcutaneous injections, depending on the specific formulation used. Some CSFs are presented in prefilled syringes, allowing patients to inject themselves at home without the need to go to a hospital or doctor’s office. How these drugs work: Hematopoiesis, the formation of blood cells, is the process by which early hematopoietic stem cells in the bone marrow with potential for renewal, proliferation, and differentiation give rise to large numbers of mature cells through a series of intermediate cells. As the stem cells mature, they lose their ability to selfrenew and become specialized. Stem cells produce cells that belong to one of three lineages: erythroid cells (red blood cells), lymphoid cells (white blood cells, including T cells and B cells), and myeloid cells (white blood cells such as granulocytes and macrophages, and platelets or thrombocytes). The process of proliferation, differentiation, and maturation is complex, with many interacting steps, and is controlled by CSFs, alone or in combination. To date, more than twenty CSFs have been identified. They are active in very small amounts. Once CSFs were discovered in experimental models, the genes for them were identified and cloned. Many of the endogenous CSFs have been produced as recombinant human forms and have received marketing approval from the FDA. The recombinant human forms of CSFs can be used to replace or supplement the endogenous proteins after chemotherapy or radiation therapy or in the case of anemia caused by kidney failure or the anemia of chronic disease, which includes cancer. 299
Colorectal cancer Erythropoietin or epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp) increase the number of red blood cells by causing committed erythroid progenitor cells to proliferate and differentiate. Filgrastim (Neupogen) and pegfilgrastim (Neulasta) are granulocyte CSFs that increase the number of neutrophils, white blood cells specific to fighting infection. Another white cell factor, lenograstim (Granocyte), is available in Europe and other countries. The granulocyte CSFs increase the circulating half-life of neutrophils and enhance their ability to attack bacteria. Sargramostim (Leukine) is a granulocyte-macrophage CSF used to increase several types of white blood cells; molgramostim (Leucomax) is another version that is available in Europe. Granulocyte-macrophage CSFs are locally active and remain at the site of infection to recruit and activate neutrophils. Ancestim (Stemgen) is a CSF that promotes the development of stem cells, which can differentiate into the other types of blood cells; it is not available in the United States. Interleukin-11 (oprelvekin, Neumega; LO3AC02) is not a CSF but is used to increase platelet counts in patients with cancer who are receiving myelosuppressive chemotherapy. Side effects: All drugs and biologic products that are effective have side effects, and each type of CSF has side effects specific to it. Patients who are receiving CSFs should consult their health care professionals and the package insert for specific information concerning side effects. In general, however, the side effects from use of CSFs are much less intense than those from chemotherapy or radiation therapy. Common side effects are bone pain, flulike symptoms, fever, fatigue, and loss of appetite. MaryAnn Foote, M.S., Ph.D. u
For Further Information Armitage, J. O. “Emerging Applications of Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor.” Blood 92 (1998): 4491-4508. Molineux, G., M. A. Foote, and S. G. Elliott, eds. Erythropoietins and Erythropoiesis: Molecular, Cellular, Preclinical, and Clinical Biology. Basel, Switzerland: Birkhäuser Verlag, 2003. Morstyn, G., M. A. Foote, and G. J. Lieschke, eds. Hematopoietic Growth Factors in Oncology: Basic Science and Clinical Therapeutics. Totowa, N.J.: Humana Press, 2004. Welte, K., et al. “Filgrastim (r-metHuG-CSF): The First Ten Years.” Blood 88 (1996): 1907-1929. 300
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Other Resources
Epogen http://www.epogen.com Leukine http://www.leukine.com Neulasta http://www.neulasta.com Neupogen http://www.neupogen.com Procrit http://www.procrit.com See also Biological therapy; Bone marrow transplantation (BMT); Cytokines; 5Q minus syndrome; Gene therapy; Immunotherapy; Interleukins; Leukopenia; Myelofibrosis; Myeloproliferative disorders; Neutropenia; Soots; Stem cell transplantation; Thrombocytopenia; Umbilical cord blood transplantation.
u Colorectal cancer Category: Diseases, symptoms, and conditions Also known as: Colon cancer, rectal cancer, intestinal cancer Related conditions: Familial polyposis Definition: Colorectal cancer (CRC) is cancer of the colon, which is also called the large intestine, and the rectum. The cells of the colon and rectum become abnormal and lose the defining characteristics of normal intestinal cells and their ability to divide in a controlled way. These cells grow rapidly and form tumors. The large intestine includes the ascending colon, transverse colon, and sigmoid colon. The rectum and anus follow the sigmoid colon, where solid waste (feces or stool) exits the body. Carcinoma, a type of cancer derived from epithelial cells, is the most common cell type found in CRC. Epithelial cells normally line the digestive system, glands, and make up the top layers of skin. Intestinal epithelial cells vary somewhat from those in other parts of the body. Risk factors: Increasing age, a family history of colorectal cancer, familial polyposis, ulcerative colitis, and Crohn disease increase risk. A high-fat, low-fiber diet and inactivity can play a role, but the mechanism of this association is not known. Etiology and the disease process: Some changes take place in the colon before cancer develops. A small area of
Salem Health: Cancer
Colorectal cancer
Incidence of Colorectal Cancer per 100,000 People, by Gender 80 72.6
Men
Women
70 60.4
60 55.0
49.1
50
47.5
44.0
42.1
40
35.3
39.6
32.9
30 20 10 0 Black
White
Asian/Pacific Islander
Hispanic
American Indian/ Alaska Native
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 Note: Based on cases diagnosed in 2000-2004
precancerous cells will begin to form on the surface of the intestine. These cells can mutate into cancerous cells and will continue to grow in both directions—outward from the surface and inward though deeper layers of tissue that form the multiple layers of the intestinal wall. As the abnormal growth invades these layers, it can encroach on blood vessels and lymph nodes, from which cancer cells can travel to the liver or other organs. Liver metastases are common with advanced disease. The most common large intestine abnormality is noncancerous growths called polyps. Polyps grow into the intestine from its walls. Some polyps have a stalk. Polyps usually grow in the sigmoid colon and the rectum. Adenomatous polyps (derived from glandular tissue) are more likely to become malignant (cancerous). Approximately 25 percent of people with colon cancer have polyps somewhere else in the large intestine. Familial polyposis is a hereditary condition. There is a genetic predisposition to grow many—even one hundred or more—precancerous adenomatous polyps in the large intestine. Cases of colorectal cancer due to this condition appear before the age of forty, unlike colorectal cancers
due to other causes, which have a higher rate of incidence with advancing age. Polyps are removed unless there are so many of them that it is better to remove a section of the large intestine containing the polyps. Frequent examination of the large intestine is necessary to watch for new growth. The most extreme measure to prevent the growth of more polyps is the surgical removal of the rectum and anus. A surgical opening is made in the abdominal wall (ileostomy), where solid waste can be collected in a pouch. Incidence: Colorectal cancer is the third most common cancer for men and women in the United States and other Western countries. It is also the third leading cause of death. In 2007, there will be approximately 79,600 new cases of colon cancer in men and 75,000 cases in women. Approximately 26,000 men and women will die each year from this disease. From 2000 to 2004, the median age at diagnosis for colorectal cancer was seventy-one years. The median age at death was seventy-five years. Men, in general, have higher incidence rates per 100,000 people than women: Black men have the highest rate at 72.6 per 100,000; whites, 60.4; Asian/Pacific Is301
Colorectal cancer landers, 49.1; Hispanics, 47.5; and American Indian/ Alaska natives, 42.1. Among women, black women have the highest incidence rates at 55 per 100,000, followed by white women, 44.0; American Indian/Alaska natives, 39.6; Asian/Pacific Islanders, 35.3; and Hispanics, 32.9. Trends in colorectal cancer incidence for men and women from 1975 to 2004 show a decline for all races and ethnicities. Symptoms: There are no symptoms of early colorectal cancer. Screening is the most important component in prevention and early detection. Symptoms such as weight loss, constipation, blood in the stool, and liver disease indicate a more advanced stage of disease. Screening and diagnosis: There are several tests for screening and diagnosis. The type and frequency of testing depend on the patient’s age and medical history. A yearly fecal occult blood test/fecal immunochemical test (FOBT/ FIT) is recommended in people age fifty or older. A physician decides which additional test—double-contrast barium X ray, flexible sigmoidoscopy, or colonoscopy— should be given to each person, starting at age fifty and every five to ten years after for those without new symptoms. • Fecal occult blood test (FOBT): Three fecal samples taken at different times are placed on special cards that are
Salem Health: Cancer sent to the laboratory for testing. The presence of blood in the sample indicates that further testing is required. A positive FOBT does not necessarily mean cancer. Blood can come from hemorrhoids, a noncancerous polyp, or inflammatory bowel diseases such as Crohn disease or ulcerative colitis. • Fecal immunochemical test (FIT): A relatively new test, also known as an immunochemical fecal occult blood test (iFOBT), to detect blood in the feces. The advantage to this test is that the patient is not required to restrict certain foods and medications before collecting the sample. Also, early evidence indicates that the FIT might be more specific in detecting blood than the FOBT. • Double-contrast barium X ray: An X ray of the colon and rectum using barium for contrast. Growths, narrowing of the colon, and evidence of inflammation can be seen, as the barium outlines the large intestine. Biopsies and polyp removal are not possible with this procedure. • Flexible sigmoidoscopy: The sigmoidoscope is a flexible tube with a light and a tiny camera at the tip. The instrument is introduced into the rectum. Polyps, other growths, and evidence of inflammation can be seen in the lower one-third of the intestine and rectum. Biopsies (tiny samples of abnormal tissue) can be taken of tissue that appears abnormal. • Colonoscopy: The colonoscope is a flexible tube with a light and tiny camera at the tip. The patient is given “conscious sedation” and frequently sleeps though the procedure. The tube is introduced through the rectum and is passed into all three sections of the large intestine. Biopsies of abnormalities can be taken. The colonoscopy is the only test that visualizes the entire colon and allows for biopsy of abnormalities. If a biopsy is positive for cancer, further testing is required to see if the cancer has spread. The process is called staging. • Stage 0: Very early cancer is present on the innermost layer of the intestine. • Stage I: Cancer is in the inner layers of the colon. • Stage II: Cancer has spread through the muscle wall of the colon. • Stage III: Cancer has spread to the lymph nodes. • Stage IV: Cancer has spread to other organs.
Colon cancer. (David M. Martin, M.D./Photo Researchers, Inc.)
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Treatment and therapy: Treatment options vary according to disease stage and the age
Salem Health: Cancer and general health of the patient. The main treatment categories are surgery, chemotherapy, radiation therapy, and targeted therapy (specifically targeting cancer cells by stimulating the immune system). More than one of these treatments may be used. Many patients choose to get a second opinion, which allows them to have increased confidence in the treatment option that they have chosen with their physician or to explore other options. It is very important that colorectal cancer patients ask questions necessary to feel confident that they understand the disease and treatment. Patients are advised to take a trusted friend or family member to appointments and write down questions at home to ask their physician. Surgery is the primary treatment. The type of surgery depends on the stage of disease. Laparoscopic surgery, which involves a small incision in the abdomen, can remove some Stage 0 and Stage 1 tumors and cancerous polyps (polypectomy). Surgery in the early stages can be curative. Surgical procedures range from polypectomy, often performed during a colonoscopy, to resection (removal) of major sections of the large intestine or rectum. When resection is performed, up to one-third of the intestine is removed. The ends of each section are then attached (anastomosis) where there is healthy tissue on each side. Cancer of the rectum and anus may require colectomy, a process in which the surgeon removes part or all of the colon, brings a normal section of the large intestine through an opening in the abdomen, and attaches a bag to collect solid waste. Radiation therapy focuses high-energy beams directly into the tumor from outside the body, killing the cancer cells. Radiation usually follows surgery to remove a large mass or tumor. Radiation therapy is very precise and can be focused on small areas of tumor cells not seen during surgery. There are times when radiation is used before surgery to shrink a tumor and ease removal. Radiation for colon cancer is performed with a linear accelerator. Precision calculations determine the most direct path to the tumor cells while damaging the fewest normal cells. Treatment lasts only a few minutes per day and might continue for several weeks. Endocavitary radiation treatment for cancer of the rectum and anus is performed internally. A small, handheld device is introduced into the rectum, where the dose of radiation can more directly reach the cancer cells. Side effects from radiation include skin irritation, nausea, bladder irritation, bowel incontinence, diarrhea, rectal irritation, and fatigue. Sexual dysfunction can occur in men and women. Chemotherapy involves several strategies. It can be used after surgery when all evidence of cancer is gone, or it
Colorectal cancer can work to prevent a return of the cancer, which is called adjuvant chemotherapy. Drugs used to treat colorectal cancer include fluorouracil (5-FU), capecitabine (Xeloda), oxaliplatin (Eloxatin), and irinotecan (Camptosar). Systemic chemotherapy is the introduction into the body of toxic, cancer-fighting chemicals, which find cancer cells and kill them. Cancer cells divide more rapidly than normal cells. Chemotherapy drugs get inside the cancer cells more rapidly and kill them. A targeted variation is injecting chemotherapy drugs directly into an artery supplying blood to an organ (liver) that contains tumor cells. Side effects of chemotherapy are due to the toxicity of the drugs, which kill cancerous and noncancerous cells. Common side effects are severe diarrhea, low blood counts, nausea, and vomiting. Newer medications are available to control the nausea and vomiting. Targeted therapy exploits unique abnormalities of cancer cells other than just rapid cell division. Proteins called monoclonal antibodies selectively find the cancer cells and kill them. There are fewer side effects, possibly from less damage to normal cells. Targeted therapy is not without side effects or danger. Lung scarring, rashes, fatigue, infection, and allergic reactions are all realities with this therapy. Monoclonal antibody and target therapy drugs include bevacizumab (Avastin), cetuximab (Erbitux), and panitumumab (Vectibix). Prognosis, prevention, and outcomes: People who are aware of their family history for colorectal cancer or polyps are in a good position to lessen their chances for contracting colorectal cancer. High-fat, low-fiber diets are implicated in higher rates of CRC, but the mechanism is not known. People who eat lean meat, smaller portions of meat, and more vegetables and grains have lower rates of CRC. Physical activity also seems to be important. It is imperative that beginning at age fifty, yearly FOBT/FIT testing is performed and that colonoscopy, flexible sigmoidoscopy, or double-contrast barium X ray is also performed every five to ten years. The main reason people do not have these screening tests are concerns about the colon-cleansing procedure before testing, unease about taking fecal samples for the FOBT, and embarrassment. Excellent prognosis or cure is associated with early detection. Stages 0, I, II, and III are potentially curable. Colorectal cancer that has not spread (metastasized) or invaded the intestinal wall has a greater chance for cure. More than 90 percent of patients receiving treatment during the early stages will survive at least five years. Some 39 percent of colorectal cancer is found in the early stages. Stage IV cancer has spread to organs such as the liver, 303
Colorectal cancer screening ovaries, lungs, or peritoneum. Surgery is performed not to cure the cancer but to prevent the colon from becoming blocked by the tumor. Liver metastases have been successfully removed through surgery. There have been some cures from this procedure, but this stage of disease is difficult to cure. Multiple therapies are used with Stage IV disease and include targeted therapies, chemotherapy, freezing tumors, and radiation. Janet R. Green, M.S.P.H. u For Further Information Brown, Gina. Colorectal Cancer. New York: Cambridge University Press, 2007. Cassidy, Jim, Patrick Johnston, and Eric van Cutsem, eds. Colorectal Cancer. New York: Informa Healthcare, 2007. Holen, Kyle, and Ki Young Chung. Dx/Rx: Colorectal Cancer. Sudbury, Mass.: Jones and Bartlett, 2008. u
Other Resources
American Cancer Society http://www.cancer.org
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u Colorectal cancer screening Category: Procedures Also known as: Fecal occult blood test (FOBT), immunoassay, or immunochemical, fecal occult blood test (iFOBT), flexible sigmoidoscopy, doublecontrast barium X ray, colonoscopy, or virtual colonoscopy Definition: Colorectal cancer screening tests are performed to detect abnormalities in the large intestine and rectum. The tests vary in accuracy, ease of performance, and invasiveness. Cancers diagnosed: Colorectal cancers Why performed: Early-stage colorectal cancers do not cause symptoms. The treatment of polyps or precancerous lesions can prevent the development of cancer, and the early detection of colorectal cancer can result in a cure. Testing is also performed as surveillance for chronic inflammatory conditions such as Crohn disease, ulcerative colitis, and familial polyposis.
Susan Cohan Kasdas Colon Cancer Foundation http://www.coloncancerfoundation.org
Patient preparation: Preparation varies with the test being performed. FOBT and iFOBT do not require patient preparation. However, FOBT restricts the eating of red meat and the taking of aspirin, ibuprofen, or other nonsteroidal anti-inflammatory drugs (NSAIDs), except acetaminophen, for three days before the samples are taken. Flexible sigmoidoscopy, double-contrast barium X ray, and colonoscopy require that the colon be free of all fecal material so that the lining of the intestine can be visualized. This preparation necessitates taking strong laxatives the day and evening before the examination, eating a clear liquid diet the day before the examination, and not eating any food after midnight of the day of the examination. Some preparation protocols also call for a selfadministered enema prior to the procedure.
See also Adenomatous polyps; Anal cancer; APC gene testing; Bethesda criteria; Colon polyps; Crohn disease; Cyclooxygenase 2 (COX-2) inhibitors; Desmoid tumors; Diverticulosis and diverticulitis; DPC4 gene testing; Duodenal carcinomas; Enteritis; Enterostomal therapy; Epidermoid cancers of mucous membranes; Gardner syndrome; Gastric polyps; Gastrointestinal cancers; Hemorrhoids; Hereditary mixed polyposis syndrome; Hereditary polyposis syndromes; Inflammatory bowel disease; Juvenile polyposis syndrome; MLH1 gene; MSH genes; PeutzJeghers syndrome (PJS); PMS genes; Polyps; Rectal cancer.
Steps of the procedure: The fecal occult blood test (FOBT), a test for the presence of blood in the feces, is the simplest test for colorectal cancer and is performed by the patient at home. It is never normal to have blood in the feces, but the presence of blood does not mean cancer. Preparation begins three days prior to the collection of a fecal sample. Patients are instructed to avoid ingesting red meat, beets, other red foods or food containing red dye, aspirin, vitamin C, or iron tablets. The collection kit contains small wooden sticks to obtain stool samples and place on the cards provided. Two samples from different parts of the stool are placed on the card provided and allowed to dry
Centers for Disease Control and Prevention http://www.cdc.gov Colon Cancer Alliance http://www.ccalliance.org MayoClinic.com http://www.mayoclinic.com National Cancer Institute http://www.cancer.gov
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Salem Health: Cancer before the card is closed with a flip-over cover (similar to a matchbook). Two samples are required from three separate stool samples on three cards. The cards are then placed in a envelope enclosed with the collection kit and sent to the laboratory. This test is performed yearly beginning at age fifty. The newer immunoassay (or immunochemical) fecal occult blood test (iFOBT) also detects blood in the feces, but it does not require food or medication restriction prior to sample collection (hence minimizing inaccurate results from lack of proper preparation). Only a single sample is required. There is evidence that the iFOBT might be more accurate at specifically detecting human blood in the stool, but if the result is positive, then further testing is necessary. This test is performed yearly beginning at age fifty. The double-contrast barium enema is an X ray of the colon and rectum following the introduction of a barium contrast material. After the colon is completely emptied, a barium sulfate solution and air are introduced through the rectum so that the outline of the colon is clear. Following the exam, the patient expels the barium solution and might experience abdominal cramping for up to twenty-four hours. This test should be done every five years unless flexible sigmoidoscopy or colonoscopy is performed. Flexible sigmoidoscopy allows the visual examination of the rectum and lower third of the intestine with a flexible tube lighted at the end. The physician is able to see a polyp, inflammation of the intestinal walls, or other growths. Biopsies (tiny samples of abnormal tissue) can be taken for diagnosis. This test is quick and has few complications. No sedation is required. The doctor can view only the lower third of the colon, however, so polyps or precancerous lesions beyond this point cannot be seen. If signs of disease are detected, then further testing might be necessary. This test is performed every five years unless doublecontrast barium X ray or colonoscopy has been performed. The most invasive yet most thorough examination for colorectal cancer is colonoscopy. A colonoscope is a flexible tube with a light and a tiny camera at the tip. The patient is usually given “conscious sedation” and sleeps though the procedure. The tube is introduced through the rectum and is passed through the entire colon. Biopsies and removal of polyps are performed as indicated. Virtual colonoscopy uses computerized images to see the entire colon, but biopsies cannot be performed. After the procedure: Patients have no special instructions to follow after FOBT, iFOBT, virtual colonoscopy, or sigmoidoscopy. Following a colonoscopy, which requires thirty to sixty minutes, the patient will be monitored while waking. Because sedation has been administered,
Colorectal cancer screening the patient will need to be driven to and from the procedure. Doctors will not allow a patient to drive or go home alone. Patients are told to rest for the remainder of the day and can resume normal activities the next day. Sometimes gas (air used during the procedure to make it easier to view the colon) is expelled for several minutes or hours following a sigmoidoscopy or colonoscopy. Risks: The FOBT and iFOBT tests involve no risks, and risks for the double-contrast barium enema and flexible sigmoidoscopy, which require no sedation, are rare. The flexible sigmoidoscopy may, rarely, result in small tears in the colon or rectum. The risks of colonoscopy include bleeding, the possibility of tears in the colon or rectum, and perforation of the colon or rectum. However, these are rare complications. The test should be performed at age fifty and every ten years thereafter if no polyps or other signs of disease are detected. Results: A negative FOBT result means that no blood was found in the stool samples. A positive test means that blood was found in one or more samples, and further testing will be necessary to determine the source of bleeding. FOBT should be repeated yearly but will not detect polyps or tumors that are not bleeding. The double-contrast barium enema can miss some small polyps and cancers. Biopsy and polyp removal cannot be performed. Therefore, additional diagnostic procedures might be necessary. Because sigmoidoscopy examines only the lower third of the colon, polyps or precancerous lesions to that point will be detected and removed; if found, additional procedures (colonoscopy) will be needed. Lesions beyond the lower third of the colon cannot be detected by sigmoidoscopy. Colonoscopy and virtual colonoscopy are the most sensitive and thorough tests available, although some small polyps and precancerous growths still might be missed. Janet R. Green, M.S.P.H. u
For Further Information Cotterchio, M., et al. “Colorectal Screening Is Associated with Reduced Colorectal Cancer Risk: A Case-Control Study Within the Population-Based Ontario Familial Colorectal Cancer Registry.” Cancer Causes & Control 16, no. 7 (2005): 865-875. Imperiale, T. F., et al. “Fecal DNA Versus Fetal Occult Blood for Colorectal Cancer Screening in an AverageRisk Population.” New England Journal of Medicine 351, no. 26 (2004): 2704-2714. Segnan, N., et al. “Randomized Trial of Different Screen305
Colostomy ing Strategies for Colorectal Cancer: Patient Response and Detection Rates.” Journal of the National Cancer Institute 97, no. 5 (2005): 347-357. u
Other Resources
American Cancer Society http://www.cancer.org American College of Gastroenterology Colorectal Cancer Screening http://www.acg.gi.org/patients/gihealth/colon.asp National Cancer Institute Colorectal Cancer Screening: Questions and Answers http://www.cancer.gov/cancertopics/factsheet/ detection/colorectal-screening See also Barium enema; Colon polyps; Colonoscopy and virtual colonoscopy; Colorectal cancer; Digital rectal exam (DRE); Diverticulosis and diverticulitis; Endoscopy; Fecal occult blood test (FOBT); Hemorrhoids; Immunochemical fecal occult blood test (iFOBT); Polyps; Rectal cancer; Sigmoidoscopy.
u Colostomy Category: Procedures Also known as: Ostomy surgery Definition: Colostomy is the surgical rerouting of the colon through a new opening (ostomy) in the abdomen, forming a stoma. A colostomy is described by the part of the colon involved (ascending, transverse, descending, or sigmoid); the type of stoma constructed (end-type or looptype), and the type of ostomy (temporary or permanent). Cancers diagnosed or treated: Colon cancer, rectal cancer, advanced anal cancer Why performed: Colostomy is performed to reroute the waste in the colon, either as a temporary diversion or as a permanent new path for waste to leave the body. Temporary diversion may be needed so that newly connected tissues in the lower bowel can heal, to stage an operation for a patient who has a partial obstruction or is too frail to undergo extensive surgery, or in an emergency to relieve an obstructing tumor or to allow an infection to clear before removing diseased tissue. Later, the temporary ostomy may be reversed to restore normal bowel function. Permanent colostomy is needed when the anal sphincter is removed, when the rectum and part or all of the colon are removed and it is not possible or optimal to connect the 306
Salem Health: Cancer remaining ends, or when an obstructing tumor cannot be bypassed or an unremovable tumor is likely to obstruct. Patient preparation: A series of medical tests are completed to plan treatment and to evaluate the patient’s fitness for this surgery. A specialist (ostomy nurse or enterostomal therapist) counsels the patient and helps choose the location for the stoma. For the procedure, certain patient medications may need to be stopped, the patient’s bowel must be cleaned, and the patient’s stomach must be empty. In an emergency, patient evaluation and preparation may be limited. Steps of the procedure: Colostomy is performed in a hospital as part of or as the first stage of a larger operation. For the procedure, sensors are placed to monitor the patient’s condition. An intravenous (IV) line is started, and an antibiotic is infused. General anesthesia is administered, and a breathing tube is placed. The patient is positioned, a urinary catheter is inserted, and the incision sites are prepared. Most commonly, a colostomy constructs either an endtype or a loop-type stoma. Details for each procedure vary with the larger operation needed, the parts of the bowel involved, and the surgical approach chosen (open or laparoscopic). With an end-type stoma, this procedure temporarily or permanently connects the upper end of the colon to an opening on the abdomen. First, an ostomy opening is made in the abdomen. The colon is freed from attachments and divided. The upper end is passed through the ostomy opening, the colon segment is sized to an appropriate length, and the edge of the cut end is folded back and stitched to the abdomen, forming an end stoma. The lower end may be totally removed, permanently sealed, temporarily sealed, or temporarily formed into a mucous fistula by connecting it to a second abdominal opening. With loop-type stoma, this procedure temporarily opens a loop of colon onto the abdomen and constructs either one stoma (end-loop) or two stomas (double-barrel). First, an ostomy opening is made in the abdomen. A loop of colon is freed from attachments and is brought through the ostomy opening. Then, either an end-loop stoma or a doublebarrel stoma is constructed. To construct an end-loop stoma, the loop is divided. The lower end is sealed and anchored with one stitch near the ostomy opening, and the cut edge of the upper end is folded back and stitched to the abdomen, forming one stoma. To construct a doublebarrel stoma, the loop is slit lengthwise. A small bridge is placed underneath the loop, bisecting the slit and raising the middle of the loop. The edges of the split are stitched to the abdomen on both sides of the bridge, forming two stomas.
Salem Health: Cancer
Colostomy
After the procedure: After the surgery anesthesia is stopped, and the breathing tube is removed. The urinary catheter and the IV line are kept. A clear collection pouch is fitted over the stoma. The patient is transferred to the recovery room and then to a hospital room. Medications are given to control pain and infection. The ostomy is closely monitored; once it starts functioning, the patient learns how to care for the stoma, empty and change pouches, and manage bowel function. At home, the patient follows the physician’s instructions for medications, activities, and diet. Risks: Colostomy is relatively safe. Stomal side effects are very common, but most are not serious. Early side effects are irritation and leakage. Later side effects are hernia, prolapse, fistula, obstruction, ischemia, necrosis, re-
traction, separation, and narrowing. When an ostomy is temporary, overall risk includes that of reversing the colostomy. Results: After colostomy, waste previously collected in the rectum and pushed through the anus now flows through the ostomy into a flat plastic pouch (ostomy appliance) that fits securely over the stoma. Many types and sizes of ostomy appliances are available, depending on the type of colostomy and patient-specific factors. Some patients benefit from minor changes in diet and alterations in clothing. All patients can perform the same activities as before. In recent years, patients’ quality of life has greatly improved with advances in ostomy management and stomal care. Patricia Boone, Ph.D.
The Results of Colostomy
Abdominal wall
Front view
Stoma
Closed section of the colon Side view Colostomy is performed to reroute the waste in the colon, either as a temporary diversion or as a permanent new path for waste to leave the body.
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Colposcopy
Salem Health: Cancer
u For Further Information Levin, Bernard, et al., eds. American Cancer Society’s Complete Guide to Colorectal Cancer. Atlanta: American Cancer Society, 2006. u
Normal Squamous Epithelium Transformation Zone Columnar Epithelium
Other Resources
American Cancer Society Colostomy Guide http://www.cancer.org
Keratosis Saline
American Society of Colon and Rectal Surgeons Ostomy http://ascrs.affiniscape.com
Lesion
United Ostomy Associations of America http://www.uoaa.org
Saline
See also Colectomy; Coloanal anastomosis; Diverticulosis and diverticulitis; Enterostomal therapy; Exenteration; Gastrointestinal cancers; Hereditary polyposis syndromes; Self-image and body image.
Mosaic Pattern with Punctation
3% Acetic Acid
u Colposcopy Category: Procedures Also known as: Colposcopy-directed biopsy Definition: A colposcopy is a diagnostic procedure in which the cervix is examined using a microscope and any abnormal tissue is biopsied.
3% Acetic Acid
Normal and abnormal colposcopy results. (LifeART© 2008 Wolters Kluwer Health, Inc.-Lippincott Williams &Wilkins. All rights reserved.)
Cancers diagnosed: Cervical cancer or its precursor, cervical intraepithelial neoplasia (CIN) Why performed: Colposcopy is performed as a follow-up to an abnormal Pap smear. It is also performed on a patient exposed to diethylstilbestrol (DES), with repeated inflammation of the cervix or an abnormal-appearing cervix, or with repeated atypical squamous cells of undetermined significance (ASCUS). Patient preparation: Patients should avoid placing anything in the vagina before the exam—including medicines for yeast infections, douches, and spermicides—and should abstain from sexual intercourse. The physician will provide specific instructions. Some physicians advise patients to take an over-the-counter pain medication, such as ibuprofen. Steps of the procedure: Colposcopy is performed in the office and takes ten to fifteen minutes. The patient lies on 308
an exam table in the same position as for a Pap smear. A speculum is used to open the vagina and view the cervix. The physician stains the cervix with acetic acid and iodine using a cotton swab. The physician examines the cervix using a microscope placed about 30 centimeters from the vagina and notes variations in the normally smooth, pink appearance of the cervix, including areas of disordered growth of cells (dysplasia), abnormal patterns of blood vessel growth (punctation), and acetowhite areas (patches of tissue that are white after staining with acetic acid). Biopsies of abnormal areas are taken using biopsy forceps and sent to a laboratory for examination by a pathologist. After the procedure: The patient may feel mild cramps or pinching and may have dark-colored vaginal discharge after the procedure if biopsies are taken. The physician may recommend that the patient avoid activities such as sexual intercourse, treating for vaginal yeast infections, and douching after the exam.
Salem Health: Cancer
Complementary and alternative therapies
Risks: There is little risk associated with this procedure; however, heavy vaginal bleeding, foul-smelling discharge, or a high fever should be reported to the physician.
DCIS has dead cells (necrosis) that plug the center of the breast duct. It tends to grow fast and has a higher risk of invasive cancer than noncomedo DCIS.
Results: A normal cervix is smooth and pink with no unusual patterns of blood vessels, turns dark with iodine staining, and has only mild acetowhite areas. Abnormal cervical tissue is rough or “humped up,” intensely acetowhite, includes patterns of blood vessel growth described as “punctuation” or “mosaic,” and is iodine-negative (yellow). The biopsies are graded as CIN I, CIN II, or CIN III, or carcinoma in situ. CIN I findings often resolve themselves and are usually followed with additional colposcopy and Pap smears. CIN II, CIN III, or carcinoma in situ is usually treated. Michele Arduengo, Ph.D., ELS
Incidence: Ductal carcinoma in situ is becoming increasingly common, accounting for 22 to 45 percent of newly diagnosed cases of breast cancer. The comedo type represents about 40 percent of the cases and carries a poorer prognosis.
See also Cervical cancer; Conization; Endoscopy; Gynecologic oncology; Hysterectomy; Loop electrosurgical excisional procedure (LEEP); Pregnancy and cancer; Virusrelated cancers; Vulvar cancer.
u Comedo carcinomas Category: Diseases, symptoms, and conditions Also known as: Ductal carcinoma in situ (DCIS), high nuclear grade or poorly differentiated DCIS Related conditions: Spontaneous nipple discharge, Paget disease Definition: Comedo carcinoma is a type of ductal carcinoma in situ (very-early-stage breast cancer), which accounts for approximately 22 to 45 percent of all breast cancers diagnosed with mammography. Most cases appear after the age of fifty-five and may persist for years without a palpable abnormality. Ductal carcinoma in situ (DCIS) refers to a family of cancers that occur in the breast ducts. There are two categories of DCIS, noncomedo and comedo. The high grade or comedo type represents 40 percent of all DCIS and on pathologic evaluation appears as pluglike necrotic material that can be expressed from the ducts of the cut pathology specimen. On mammography, often a linear branching or casting pattern of microcalcifications is visible. Risk factors: Risk factors include increasing age, having few children and the first child after the age of thirty, obesity, a history of atypical hyperplasia or of breast carcinoma, and having a mother or sibling with breast cancer. Etiology and the disease process: In comedo carcinoma, cancer forms in the breast ducts. The comedo form of
Symptoms: Most patients are asymptomatic. Less commonly, DCIS appears as a mass with ill-defined or lobulated borders on a mammogram, which may or may not be associated with malignant microcalcifications. Screening and diagnosis: On a mammogram, comedo carcinoma manifests as clusters of pleomorphic (manyformed), ductally oriented microcalcifications. In the staging system used to classify cancer, DCIS is known as Stage 0 and is sometimes called precancer. It may also be referred to as tumor in situ (Tis), which means that the cancer is noninvasive. Treatment and therapy: The standard treatment is needle localization and lumpectomy with radiation or simple or modified mastectomy. Prognosis, prevention, and outcomes: Some 20 to 50 percent of women with comedo carcinoma develop invasive cancer five to ten years after initial diagnosis if the cancer is not removed surgically. Debra B. Kessler, M.D., Ph.D. See also Duct ectasia; Ductal carcinoma in situ (DCIS); Invasive ductal carcinomas.
u Complementary and
alternative therapies Category: Complementary and alternative therapies Also known as: Complementary and alternative medicine (CAM) Definition: Complementary and alternative medicine (CAM) is defined by the National Center for Complementary and Alternative Medicine (NCCAM) as a group of diverse medical and health care systems, products, and practices not presently considered part of conventional medicine. Differences between complementary and alternative medicine: Complementary medicine is used along with conventional medicine. Conventional medicine includes 309
Complementary and alternative therapies allopathic (medical doctor, M.D.) and osteopathic (doctor of osteopathy, D.O.) medicine. Allied conventional health professionals include nurses, respiratory therapists, and psychologists. Examples of complementary therapies include using aromatherapy or massage to lessen discomfort following surgery or chemotherapy. Alternative medicine is used instead of conventional medicine. Treating cancer with the compound containing amygdalin (trademark Laetrile) in place of undergoing surgery, radiation, or chemotherapy is an example of an alternative therapy. Little reliable evidence exists for Laetrile’s efficacy as a cancer drug, and the U.S. Food and Drug Administration has not approved the use of this compound for cancer treatment. The NCCAM, part of the National Institutes of Health (NIH), defines integrative medicine as a combination of mainstream medicine and those parts of complementary and alternative medicine that have high-quality scientific evidence of safety and effectiveness. The NIH has placed complementary and alternative medicine modalities into five major categories: alternative medical systems, biologically based therapies, manipulative and body-based methods, mind-body interventions, and energy therapies. These provide a useful framework for understanding many different therapeutic approaches to health care. Alternative medical systems: Alternative medical systems are complete care systems, much as conventional medicine is a complete system of theory and practice. These complete systems have central philosophies, such as the healing power of nature, and use therapies in line with these philosophies. These systems include traditional Chinese medicine and other medical systems formulated outside of Western culture, such as American Indian, Tibetan, and Indian (Ayurvedic) systems, as well as homeopathic and naturopathic medicine, formulated within Western culture. Although considered alternative medicine in the United States, traditional Chinese medicine and Ayurvedic medicine are part of the culture and heritage of China and India, respectively, and in these countries they have been practiced for millennia and coexist with conventional medicine. According to the NIH, scientific evidence supports the use of acupuncture, a technique from traditional Chinese medicine, to treat postoperative and chemotherapy-associated nausea and vomiting. Acupuncture may be useful as an adjunct for treating pain-related conditions and other maladies. Naturopathy is a healing system initiated in Europe. It views disease as alterations in the body’s natural healing 310
Salem Health: Cancer processes. Naturopaths believe that the body can heal itself if it is in a healthy environment. They take a holistic approach to the body, looking at the patient’s mind, body, and spirit, and use therapies such as nutrition and herbal medicine, physical medicine, hot/cold compresses, massage, lifestyle and psychological counseling, and detoxification. Scientific evidence does not support naturopathy’s claims. Homeopathy was founded by Samuel Christian Hahnemann in Germany about two hundred years ago. Hahnemann believed that effective remedies must contain substances that produce effects similar to those produced by the diseases they cured, and he called this the principle of similars. Conventional medicine uses a thought process not unlike this principle in vaccine development. Homeopathy emphasizes the careful examination of all aspects of an individual’s health, including mental and emotional states, as well as distinctive physical and personality characteristics. Homeopathy employs liquids or pills that have been diluted from the original substance to the point that sometimes no detectable trace of the original molecule may be found. The manufacturing process involves vigorous shaking between dilution steps, purportedly producing the vital essence of the substance. Homeopathy contends that the memory of the original molecule is retained after the homeopathic dilution process and that the end product is therapeutic even when the original molecule is thinned out of measurable existence. Scientific and clinical evidence of the efficacy of homeopathy is lacking. Biologically based therapies: Biologically based therapies use natural substances such as herbs, vitamins, foods, and other dietary supplements. These substances are formulated in many ways, including tablets, capsules, gel caps, powders, teas, oils, and syrups. Although the idea of a natural substance is very attractive to many consumers, natural products can have serious side effects. Some biologically based therapies, such the use of shark cartilage or Laetrile (a compound containing amygdalin) to treat cancer, lack scientific support, while others have some scientific studies that show their efficacy. Amygdalin is a chemical found in the pits of many fruits. In the presence of certain enzymes, Laetrile breaks down and produces cyanide, a known poison. In addition to lacking effectiveness, Laetrile creates many side effects, mostly related to cyanide poisoning, including cyanosis (bluish skin secondary to oxygen deprivation), uncoordinated walking, liver damage, low blood pressure, and droopy upper eyelids. The essential oils used in aromatherapy are extracted
Salem Health: Cancer from fragrant plants such as chamomile, lavender, lemon, and cedarwood. These oils are inhaled or applied to the skin. Although aromatherapy does not cure cancer, it can help patients with quality-of-life issues. Studies have shown that odors can improve mood, enhance perceptions of health, and reduce anxiety. Allergic reactions and dermatitis have been reported as side effects of aromatherapy. The seeds of milk thistle, a plant native to Europe but also found in North and South America, have been harvested for more than two thousand years for use primarily as a treatment for liver disease. Silymarin, the chemical compound identified as the active ingredient in milk thistle seeds, is a potent antioxidant. It has been shown to help in cases of chronic hepatitis and cirrhosis, and some laboratory studies have indicated that it may increase the ability of some chemotherapeutic agents to treat cancer and decrease the drugs’ toxicity. More research must be done before its true efficacy is known. Few side effects are reported regarding milk thistle. Dietary supplements include vitamins, minerals, herbs, amino acids, enzymes, and organ tissues. Although many people take these types of compounds for health reasons, these supplements are not regulated the same way as are over-the-counter and prescription medications. Prescription medications, in particular, must go through extensive testing and clinical trials and have proven efficacy before they are allowed on the market. Dietary supplements are regulated in a manner closer to the production of salt and pepper than that of prescription medication. Manufacturers of herbs, vitamins, minerals, and other biologically based dietary supplements follow manufacturing guidelines for the production of food. Medications require Food and Drug Administration approval before they can be placed on the market, whereas individual manufacturers of dietary supplements are responsible for the safe production of their products. The Federal Trade Commission monitors dietary supplements for accuracy in advertisement, whereas the Food and Drug Administration regulates the production of prescription medications. These differences in oversight are not usually evident to the consumer, but consumers should be aware that supplements are much different from medications. Manipulative and body-based methods: Body-based therapies are based on movement or manipulation of body parts. Chiropractic or osteopathic manipulation and massage therapy are examples of manipulative and body-based therapies. Rolfing, reflexology, Trager bodywork, Alexander and Bowen techniques, the Feldenkrais method, and many other techniques and therapies are included in this category. The NCCAM reports that appointments with
Complementary and alternative therapies chiropractors and massage therapists represent 50 percent of all visits to complementary and alternative health practitioners. These practices focus on the body’s structural elements, such as bones and joints. Circulatory and lymphatic systems are often emphasized in manipulative and bodybased practices. Some of these techniques were developed over the past two thousand years in traditional systems from China and India, whereas others, such as chiropractic and osteopathic manipulations, arose in the last 150 years. Although many practitioners are formally trained in anatomy and physiology, considerable variability exists in the education and approaches of these providers. For example, osteopaths and chiropractors use manipulations involving rapid movements, whereas massage therapists use techniques involving slower force applications. Manipulative and body-based modalities share some principles, including the body’s ability to heal itself, self-regulation by the human body, and the interdependence of parts of the human body. These characteristics, along with the laying on of hands, are attractive to some health care consumers seeking relief from various ailments. Studies have shown massage to be useful in the short-term relief of pain, anxiety, depression, fatigue, and stress in cancer patients, but there is no scientific support for claims that massage slows the growth or spread of cancer. Mind-body interventions: Mental, emotional, spiritual, and behavioral factors affect an individual’s health. Mindbody therapies focus on these powerful factors and on the interaction between mind, brain, body, and behavior. The therapies are generally based on respecting and enhancing the human capacity for self-care and individual knowledge. Techniques included in this category include hypnosis, meditation, visual imagery, biofeedback, yoga, tai chi, spirituality, support groups, and therapies tapping creative channels such as music, writing, art, or dance. Some of these therapies, such as patient support groups, have become part of integrated or even conventional medicine. Evidence exists that a number of the mind-body therapies have been shown to help strengthen the immune system and reduce pain, anxiety, stress, and depression, thus improving the quality of life for cancer patients. Energy therapies: Energy therapies use two major types of energy fields, biofield and bioelectromagnetic. Biofield therapies claim to manipulate energy fields surrounding and penetrating the body. These energy fields have not been adequately measured or scientifically proven. Some energy therapy techniques try to change biofields by ma311
Complete blood count (CBC)
Salem Health: Cancer
nipulating the body or applying pressure in, on, or through these biofields. Examples include Reiki and Therapeutic Touch. Bioelectromagnetic-based techniques involve using electromagnetic fields, including pulsed, magnetic, alternating-current, or direct-current fields in unconventional manners. Their efficacy for cancer has not been proved.
National Cancer Institute Complementary and Alternative Medicine http://www.cancer.gov/cancertopics/treatment/cam
Perspective and prospects: Conventional health care is disease oriented, tends toward specialty-based care, and is often used after an acute event (a major accident or illness). Allopathic and osteopathic (conventional) medicine becomes more specialty oriented as more scientific mechanisms for disease are discovered. Many people using complementary and alternative therapies are more concerned with maintaining health and optimizing defenses against disease. These people do not reject conventional health care but see conventional health care as an important part of their overall care plan, particularly for acute disease. Those who turn to complementary and alternative therapies after becoming ill typically want to optimize their chances for becoming well. Many therapies previously considered a part of complementary or alternative medicine—such as support groups for cancer patients, hypnosis for smoking cessation, aspirin for reducing inflammation, or digitalis for heart conditions—have become part of mainstream or integrative medicine. Science does not support all modalities of complementary and alternative medicine, but it supports some aspects. The NCCAM, part of the U.S. Department of Health and Human Services, conducts and funds scientific research into nonconventional medicine in an attempt to help medical professionals and the public understand which therapies have been shown to be safe and effective. Richard P. Capriccioso, M.D.
See also Anthraquinones; Antioxidants; Cancell; Carotenoids; Cartilage supplements; Coenzyme Q10; Curcumin; Delta-9-tetrahydrocannabinol; Dietary supplements; Electroporation therapy; Essiac; Ginseng, panax; Green tea; Herbs as antioxidants; Integrative oncology; Laetrile; Mistletoe; PC-SPES; Phenolics; Saw palmetto; Sun’s soup.
u For Further Information Keegan, L. Healing with Complementary and Alternative Therapies. Albany, N.Y.: Delmar, 2001. Peters, David, and Anne Woodham. Encyclopedia of Natural Healing. London: Dorling Kindersley, 2000. Zhang, Qunhao. “Complementary and Alternative Medicine in the United States.” Asia Pacific Biotech News 8, no. 23 (December 1, 2004): 1274-1277. u
Other Resources
MayoClinic.com Complementary and Alternative Medicine http://mayoclinic.com/health/alternative-medicine/ PN00001 312
National Center for Complementary and Alternative Medicine http://nccam.nih.gov
u Complete blood count (CBC) Category: Procedures Also known as: Hemogram Definition: A complete blood count (CBC) is a group of blood tests that provides information about red cells, white cells, and platelets. The tests included are white cell count (WBC); white cell differential (the percentage of each of the white cell types—neutrophils, lymphocytes, monocytes, eosinophils, and basophils); red cell count (RBC); hemoglobin (HGB); hematocrit (HCT); platelet count (PLT); mean corpuscular volume (MCV); mean corpuscular hemoglobin (MCH); mean corpuscular hemoglobin concentration (MCHC); mean platelet volume (MPV); and red cell distribution width (RDW). The test is performed using whole blood on an automated hematology analyzer. The HCT, MCH, and MCHC are calculated from the measured results of the RBC, HGB, and MCV. MPV is the average size of the platelets. RDW is a calculation based on the red cell indicating the variation in red cell size. A technologist may make a thin smear of the sample on a glass slide, stain it with special dyes, and examine the cells using a microscope. Cancers diagnosed: All Why performed: The CBC is a common screening test. It does not determine a specific type of cancer. The results may lead the physician to order other blood tests and imaging studies that determine the presence of cancer. Chemotherapy and radiation treatments may affect any or all of the tests that make up a CBC. Therefore, a CBC or any part of it is used to monitor treatment.
Salem Health: Cancer
Computed tomography (CT)-guided biopsy
A complete blood count is a common screening test that provides information about red cells, white cells, and platelets. (PhotoDisc)
Patient preparation: No special preparation is needed. Steps of the procedure: A small sample of blood is collected from a vein and placed in a tube. In children, blood may be obtained from a capillary in the heel or finger. After the procedure: A small gauze or cotton ball is applied at the site of needle insertion. The patient is asked to apply pressure. The person collecting the blood observes the site for bleeding and may apply a bandage. The bandage may usually be removed in thirty to sixty minutes. Risks: The risks of CBC include bleeding, bruising, hematoma (bleeding under the skin), fainting, light-headedness, or multiple needlesticks to obtain a sample. Results: Normal CBC levels vary by the patient’s sex and age and the analyzer used. Each laboratory establishes a set of normal ranges based on this information. The physician receives a report of the test results with the normal values. CBC results may be higher or lower than normal depending on the type of cancer, treatment, any bleeding, or infectious processes taking place. Wanda E. Clark, M.T. (ASCP)
See also Aleukemia; Bone cancers; Cachexia; Childhood cancers; Crohn disease; Embryonal cell cancer; Fanconi anemia; Germ-cell tumors; Hairy cell leukemia; Herpes zoster virus; Hodgkin disease; Lambert-Eaton myasthenic syndrome (LEMS); Leukapharesis; Leukemias; Lymphocytosis; Myelodysplastic syndromes; Myeloproliferative disorders; Nephrostomy; Neutropenia; Pneumonia.
u Computed tomography
(CT)-guided biopsy Category: Procedures Definition: A biopsy is needed when a mass has been found on physical examination or from an X ray, magnetic resonance image (MRI), or CT scan. In a CT-guided biopsy, a very thin needle is inserted into the mass while it is being visualized with the CT to withdraw fluid or tissue to be used to determine a diagnosis. CT-guided biopsy can allow a patient to avoid having to go to an operating room 313
Computed tomography (CT)-guided biopsy to have the biopsy completed. Many oncology patients are unable to tolerate an operation, so this procedure is a valuable diagnostic tool. Cancers diagnosed: CT-guided biopsy can be used to help diagnose many different masses located in various organs in the body, such as the lung, liver, kidney, and adrenal glands. Solid tumors are frequently biopsied to determine the type of tumor and how fast it is growing. This information will then be used by the oncologist to determine what type of chemotherapy to use and whether radiation would benefit the patient. Why performed: A biopsy is done to achieve a definitive diagnosis for tumors and masses. In order to ensure that proper treatment is given to the patient, the exact type of cancer must be determined. A mass in the kidney may be kidney cancer or another type of cancer that has spread to that organ. The biopsy can determine what type of cells are present and then what type of therapy would be best to treat that diagnosis. ACT-guided biopsy is done on masses located on internal organs or in deep tissue. Often these
Salem Health: Cancer masses cannot be felt on examination but are found through imaging. Patient preparation: This procedure can be done on both an inpatient and an outpatient basis. Preparation will depend on in what organ or area the mass is located. The patient may receive a sedative or pain medication before the procedure and may also be connected to a cardiac monitor to ensure that no cardiac abnormalities occur. The patient may be asked not to eat anything in the eight hours before the procedure. It is important to identify patients who have claustrophobia, as they may experience anxiety with the CT itself and need medication to decrease this anxiety. Patients may have their blood levels monitored to ensure that they have the ability to clot after a biopsy has been completed. Patients should give informed consent prior to having the biopsy done. Steps of the procedure: The procedure can take as little as twenty minutes to complete. The patient is positioned as comfortably as possible on the back, side, or abdomen to allow for proper access to the area requiring biopsy. The
A patient undergoes a CT scan. (Digital Stock)
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Salem Health: Cancer patient should remain in the same position during the whole procedure. A preliminary CT scan is performed to locate the site for needle insertion for the biopsy. Once this site is determined, the skin is properly cleaned and a numbing medication is injected. The biopsy needle is then inserted through the skin into the mass. Another CT is done to determine where the tip of the needle is resting. When the tip of the needle is in the correct location, then the biopsy, or sample, is taken and prepared for pathology. After the needle is removed, an additional CT is done to ensure that there are no air bubbles or bleeding. After the procedure: After completion of the procedure, the patient is monitored either in the hospital or the recovery room for a few hours and then discharged home. The patient may still be drowsy or dizzy from the medication and should not drive. Risks: CT-guided biopsies are not recommended for patients who have a bleeding disorder or thrombocytopenia. If the patient is or may be pregnant, then special precautions will need to be taken. Risks related to CT-guided biopsies are minimal and include bleeding and infections. It is not recommended that a needle biopsy be done on the spleen because of the tendency of that organ to bleed. There is also a 25 percent risk of a pneumothorax, or collapsed lung, when a biopsy of the lung has been done. Pneumothorax may also occur when biopsies of the liver or adrenal glands have been done. Results: A preliminary evaluation may be done by the physician prior to sending the sample to pathology. Not all physicians may do so. Many times the sample is sent straight to the pathologist for diagnosis and evaluation. The pathologist will be able to determine what the mass consists of and give a diagnosis so that treatment may begin. If the sample size was not sufficient or the pathologist is unable to determine a diagnosis, then a repeat biopsy may need to be done. Katrina Green, R.N., B.S.N., O.C.N. u For Further Information Cooper, Geoffrey M. The Cancer Book: A Guide to Understanding the Causes, Prevention, and Treatment of Cancer. Boston: Jones and Bartlett, 1993. Finn, William G., and LoAnn C. Peterson, eds. Hematopathology in Oncology. Boston: Kluwer Academic, 2004. Klag, Michael J., et al., eds. Johns Hopkins Family Health Book. New York: HarperCollins, 1999.
See also Computed tomography (CT) scan; Cordotomy; Dukes’ classification.
Computed tomography (CT) scan
u Computed tomography (CT)
scan Category: Procedures Also known as: Computed axial tomography (CAT) scan, abdominal CT, brain CT, chest CT, contrast CT scan, conventional CT, cranial CT, CT-guided biopsy, electron-beam CT scan, full body CT scan, helical CT scan, lumbosacral CT, multislice CT scan, orbit CT, pelvic CT, spiral CT, thoracic CT, 3D CT, virtual bronchoscopy, virtual colonography, virtual colonoscopy, virtual CT, virtual endoscopy, volumetric CT scan Definition: A computed tomography (CT) scan is a radiological imaging test used to create cross-sectional slice images of a portion of or the entire body. The slice images are stacked to create three-dimensional images. CT images provide more anatomical detail than X rays. Cancers diagnosed: Most Why performed: CT is a valuable tool for screening for cancer, locating tumors, performing guided biopsy, identifying cancer that has spread, staging cancer, planning and monitoring cancer treatment, and checking for cancer recurrence. CT can identify blood vessels that support a tumor, as well as the tumor’s shape, size, location, and volume. CT scans are used with procedures to diagnose cancer, such as needle-guided biopsies. They are used in cancer treatments, such as radiofrequency ablation and interstitial therapy. CT images are archived in computers or printed form. Images are printed on film or with laser imaging. They can be sent and viewed online within a facility and can be compared for changes over time. Conventional CT was developed in the early 1970’s. CT uses controlled amounts of thin, high-energy radiation beams. Images are taken from a variety of angles. A computer calculates information about the images and produces a slice image of a specific area of the body. CT can be taken of the entire body or a specific section. Dye is used to enhance images to show more detail and contrast. The contrast dye can be swallowed, received intravenously, or administered in an enema. CT has evolved to become faster and to use lower doses of radiation. Spiral or helical CT allows images to be collected quickly. The rapid process helps compensate for movements or breathing that otherwise can blur images. Additionally, spiral CT produces thinner slices of images that show even greater detail. A computer stacks the images to create three-dimensional, rotational pictures of a 315
Computed tomography (CT) scan tumor. Spiral CT is especially useful for imaging liver, lung, and pancreatic cancer. Recent technology allows doctors to use CT with endoscopy to create virtual endoscopy, virtual bronchoscopy, and virtual colonoscopy or CT colonography. The process uses a computer to create and manipulate threedimensional images to create a “fly-through” view of an organ, as seen on endoscopy. CT is used to guide surgeons precisely during procedures. CT is used with needle aspiration biopsy for tumors, such as for breast cancer biopsies. The CT guidance eliminates the need for invasive exploratory surgery. CT is used to guide certain radiation treatments. For example, interstitial therapy uses CT guidance to insert radioactive material into a tumor. CT is also used to create a three-dimensional image of a tumor to allow external beam radiation to precisely target the tissue and spare as much healthy tissue as possible. Patient preparation: CT scans may not be appropriate for some people. Patients should let their doctor know if they have diabetes or kidney disease or if they are pregnant. Some facilities conduct a pregnancy test on all women prior to scanning because the radiation can be dangerous to a developing fetus. Children, patients with movement disorders, or patients that are claustrophobic may receive a mild sedative prior to the test. In extreme situations, people may be sedated if they are not able to remain still while the images are taken. Some CT machines may not be used for people that weigh more than three hundred pounds because of size parameters of the machinery. About 5 percent of patients are allergic to contrast dye. Patients should let their doctor know if they are allergic or sensitive to contrast dye, iodine, or shellfish. CT scans are outpatient procedures performed at a hospital radiology department or freestanding radiology center. Patients will receive instructions prior to their procedure, which vary depending on which procedure is conducted. Patients may be instructed not to eat or drink for several hours before the CT. Some patients need to use an enema or laxatives. Patients may need to drink a liquid contrast agent before arriving at the clinic or upon arriving at the clinic. Patients wear an examination gown or robe for the procedure. They must remove metal objects that can interfere with the imaging process, such as jewelry, hearing aids, hair clips, glasses, or dentures. Steps of the procedure: Patients are led into the imaging room. A radiology technologist conducts the CT. Patients lie on a narrow table. The technologist may use positioning devices to help patients maintain specific postures for 316
Salem Health: Cancer the test. Head-stabilizing devices may be used for brain scans. Patients may be instructed to change positions throughout the procedure. During the CT scan, the radiologist technician steps into a room that is separated by a glass partition. The radiologist is in constant contact with the patient via a microphone and intercom system. The radiologist technician operates the CT machine. To take a CT, the table slides into the doughnut-shaped hole of the scanner. Patients must remain motionless while the images are taken. Patients are instructed to take a deep breath and hold it until they are told to exhale. The CT scanner has an X-ray component that emits beams at specific angles. The beams pass through the body and are detected by equipment on the opposite side. The equipment makes buzzing or clicking noises while the scanner is employed. Patients receiving a contrast material may have a CT scan first, receive the contrast material, and then receive a final CT scan. An intravenous (IV) line is inserted into the hand or forearm to deliver injected contrast material. Contrast material may be swallowed. An enema is also used to insert contrast material for gastrointestinal-related CT scans. The contrast material may make patients feel temporarily warm or flushed. The actual CT scan is short, but the preparation and positioning time makes the procedure last from about ten to thirty minutes. Spiral CTs are shorter in length. Patients are asked to wait until it is confirmed that the images are clear. Patients are observed for allergic reactions for a short time following the procedure. After the procedure: There are usually no aftercare procedures following CT. If the patient has received sedating medication, a friend or relative must drive the patient home. Risks: Patients may experience an allergic reaction to the contrast dye. The symptoms include hives, shortness of breath, nausea, wheezing, itching, or a bitter taste in the mouth. Severe allergic reaction or anaphylactic shock is a rare risk. Radiation from CT is higher than that of standard X rays. CT is not recommended for pregnant women; the risks to others are minimal. Results: CT images are read by a radiologist and conveyed to the ordering doctor. The doctor may view the images as well. CT images depict anatomical structures in black, white, and shades of gray. Air, soft tissue, hard tissue, fluids, and the contrast agent show details that otherwise cannot be seen. Abnormal results show different characteristics from what is expected, such as tumors,
Salem Health: Cancer
Conization
cysts, cancer metastasis, tumor density, tumor composition, enlarged lymph nodes, or atypical fluid accumulations. In some cases, CT can help differentiate between types of tumors. Mary Car-Blanchard, O.T.D., B.S.O.T. u For Further Information Applegate, K. “Pregnancy Screening of Adolescents and Women Before Radiologic Testing: Does Radiology Need a National Guideline?” Journal of American College of Radiology 4, no. 8 (August, 2007): 533-536. Ishikawa, S., et al. “Mass Screening of Multiple Abdominal Solid Organs Using Mobile Helical Computed Tomography Scanner: A Preliminary Report.” Asian Journal of Surgery 30, no. 2 (April, 2007): 118-121. Sone, S., et al. “Long-Term Follow-up Study of a PopulationBased 1996-1998 Mass Screening Programme for Lung Cancer Using Mobile Low-Dose Spiral Computed Tomography.” Lung Cancer, August 3, 2007.
See also Angiography; Bone scan; Brain scan; Bronchography; Computed tomography (CT)-guided biopsy; Cystography; Ductogram; Endoscopic retrograde cholangiopancreatography (ERCP); Gallium scan; Hysterography; Imaging tests; Lymphangiography; Magnetic resonance imaging (MRI); Mammography; Nuclear medicine scan; Percutaneous transhepatic cholangiography (PTHC); Positron emission tomography (PET); Radionuclide scan; Thermal imaging; Thyroid nuclear medicine scan; Urography; X-ray tests.
u Conization Category: Procedures Also known as: Cone biopsy, cold-knife conization, loop electrosurgical excision procedure (LEEP) Definition: Conization is the surgical excision of an en bloc section of the cervix to diagnose suspicious lesions that may be precancerous or overt cancer. Cancers diagnosed: Precancerous lesions, such as highgrade suspicious intraepithelial lesions (HGSIL) or cervical intraepithelial neoplasia II or III; cervical cancer Why performed: Conization of the cervix is performed when complete microscopic visualization (colposcopy) of all lesions is inadequate or inconclusive or reveals inconsistent results when compared to a Pap smear. Although a Pap smear and colposcopy detect 58 to 89 percent of all precancerous and cancerous lesions, conization can pro-
Cervical conization, showing the area to be excised. (LifeART© 2008 Wolters Kluwer Health, Inc.-Lippincott Williams & Wilkins. All rights reserved.)
vide a definite pathological diagnosis. Conization can also be therapeutic if the entire lesion is removed and frank involvement of other organs (vagina, uterus bladder, or rectum) is absent. Patient preparation: The patient undergoes preoperative evaluation, including blood workups to determine her fitness to undergo surgery and general anesthesia. Patients are instructed to take nothing by mouth the night before the procedure. Steps of the procedure: After the patient is anesthetized and prepared, the cervix is visualized. Local anesthesia is administered if the patient is not under general anesthesia. The cone base area is determined by applying Lugol’s solution. The uterine depth is determined prior to incising. Incision is done in a circular, centrally angled fashion. A suture at the twelve o’clock position of the specimen is placed. Curettage of the remaining ectocervix is done to detect any lesions above the cone tip. Cautery or ligation of any bleeding vessels and vaginal packing is done. After the procedure: The patient is monitored in the postanesthesia care unit until she is fully awake and ambulatory and her vital signs are stable. Once stable in unit, the 317
Continuous hyperthermic peritoneal perfusion (CHPP) patient may be discharged on the same day. Admission for overnight observation is warranted if the patient is unstable or other medical problems need to be managed. Risks: The most significant risk is miscarriage in women (10 percent) who intend to become pregnant after conization. Only specialists experienced in managing the potential complications should care for these patients. Other risks include excessive intraoperative or postoperative bleeding for as many as ten to fourteen days (30 percent), cervical narrowing as a result of scarring, perforation of adjacent organs, and infertility. Results: A benign histologic examination of the specimens may reveal increased but orderly normal cell growth within the lesion but no elements of disordered growth of abnormal cells. Histologic examination of the specimens that reveals disordered proliferation and abnormal cellular characteristics is suggestive of cervical cancer. Aldo C. Dumlao, M.D. See also Biopsy; Cervical cancer; Colposcopy; Endoscopy; Gynecologic cancers; Hysterectomy; Loop electrosurgical excisional procedure (LEEP); Pap test; Pregnancy and cancer; Vulvar cancer.
u Continuous hyperthermic
peritoneal perfusion (CHPP) Category: Procedures Also known as: Intraperitoneal hyperthermic perfusion, intraperitoneal hyperthermic chemotherapy Definition: Continuous hyperthermic peritoneal perfusion (CHPP) is a procedure that delivers highly heated fluid containing chemotherapeutic agents directly to the abdominal cavity, often during or immediately after abdominal surgery. Cancers treated: Primary mesothelioma; primary stomach cancers; recurrent or widely spread ovarian cancers; recurrent colon cancer; cancers in the lung, breast, or appendix that have spread Why performed: The benefits of CHPP are twofold. First, hyperthermia increases cancer cell sensitivity to other treatments (radiotherapy and chemotherapy) and increases the effectiveness of some chemotherapy (such as mitomycin-C) through improved pharmacokinetics. Second, regional administration allows for the direct treatment of errant cancer cells that remain after tumor excision while preserving noncancerous cells. 318
Salem Health: Cancer Patient preparation: Preparation is similar to that of any abdominal surgery. The patient’s bowel must be cleansed, and the patient must fast on the day of the procedure. Before surgery and CHPP, intravenous lines are inserted, and general anesthesia is administered. During surgery, the body temperature may be allowed to drop by 3 to 5 degrees Fahrenheit to accommodate impending hyperthermia. Steps of the procedure: The effectiveness of CHPP is related to the maintenance of a narrow temperature range for a prescribed time, so administration must be monitored closely. First, fluid-delivery tubing and thermometer probes are inserted into the abdominal cavity. Fluid is heated outside the body and is pumped in via catheter to bathe the area, usually at 106 to 108 degrees Fahrenheit, for forty-five minutes to two hours. Then, the fluids are removed with draining tubes. After the procedure: After CHPP, the patient’s incision is closed as with any abdominal surgery. Initial recovery in the intensive care unit (ICU) involves the evaluation of surgical recovery and may require temporary feeding tubes. Risks: Because surgery and CHPP are often performed together, it is difficult to separate their complications, which include bleeding, infection, and wound-healing problems. Although most normal tissue remains intact to 111 degrees Fahrenheit, the death of normal cells is possible with hyperthermia. Most adverse effects of CHPP are temporary and include local pain, local blood clots, and burns or blisters to the skin, muscles, and nerves. More seriously, damage to blood vessels or to the lungs and heart may occur. Results: Like systemic chemotherapy, the goal of CHPP is to destroy cancer cells in the peritoneal cavity. Unlike systemic therapy, CHPP aims to eradicate lingering cancer cells directly without affecting normal cells. Nicole M. Van Hoey, Pharm.D. See also Hyperthermic perfusion.
u Cordectomy Category: Procedures Also known as: Vertical hemilaryngectomy, partial laryngectomy Definition: A cordectomy is a surgical procedure for treating laryngeal cancer. It entails resection of an entire vocal cord, the surrounding soft tissue, and the inner lining of the thyroid cartilage. Cancers treated: Laryngeal (glottic) carcinoma
Salem Health: Cancer Why performed: In defining treatment protocols, the larynx is divided into three anatomical regions: supraglottis, glottis, and subglottis. The distribution of carcinoma among these regions is estimated at 40:59:1. Glottic carcinomas are the most common and readily detected because of the prompt development of symptoms (hoarseness, sore throat, and dysphagia). Early-stage glottic carcinoma can be treated effectively by a single modality, utilizing surgery or radiation. Radiation therapy will provide 85 percent local control for T1 (Stage 1) glottic cancer and local control in 65 percent of T2 (Stage 2) lesions. Vertical hemilaryngectomy (cordectomy) can achieve local control rates of 95 percent for T1 lesions and 80 percent for T2 lesions. Overall, surgery provides better local control, but the potential benefit of radiation therapy has been voice preservation. Patient preparation: A routine preoperative workup and assessment of anesthetic risks are required. Prior to any surgery for laryngeal cancer, physical examination of the larynx is accomplished with indirect mirror visualization or by direct laryngoscopy. Magnetic resonance imaging (MRI) scans are employed to evaluate tumor size, location, airway patency, and cartilage involvement. Steps of the procedure: With the patient under general anesthesia, surgical exposure is performed through a traditional transcervical incision. Exposure of the vocal cords is achieved through a laryngofissure approach (a midline incision through the thyroid cartilage). Carbon dioxide (CO2) laser cordectomy is now an alternative surgical option. Carried out as an endoscopic procedure, it can be performed on an outpatient basis. The single disadvantage with this procedure is the problem of evaluating free (healthy) tissue margins, especially on frozen section. After the procedure: With traditional cordectomy, the patient stays in the hospital for a few days so that vital signs, incision site, and respiratory status can be monitored. Patients undergoing laser cordectomy are required to stay only for observation (three to four hours) to detect any signs of airway obstruction. Postoperatively, an adult companion should remain with the patient for the first twenty-four hours. Risks: The specific risks of cordectomy involve speech problems, airway obstruction, and aspiration. General surgery risks include postoperative infection, scarring, and potential neurologic-vascular compromise to the operative area.
Cordotomy Results: The success of postoperative rehabilitation depends on anatomic and patient factors. The extent of the surgery, the type of reconstruction, and the utilization of radiation are important anatomical factors. Patient factors include motivation, dexterity, and access to speech therapy. John L. Zeller, M.D., Ph.D. See also Electrolarynx; Esophageal speech; Laryngeal cancer; Laryngeal nerve palsy; Laryngectomy; Throat cancer; Tracheostomy.
u Cordotomy Category: Procedures Also known as: Open or closed cordotomy, unilateral or bilateral cordotomy Definition: Cordotomy is a surgical procedure that disables selected sensory tracts contained within the spinal cord (interruption of the lateral spinothalamic tract). The procedure is commonly performed on patients experiencing severe pain as a result of cancer. Anterolateral cordotomy is effective in relieving unilateral, somatic pain while bilateral cordotomy may be required for visceral or bilateral limb pain. Cordotomy is usually done percutaneously (stereotactic technique) with fluoroscopic guidance while the patient is under local anesthesia. Open cordotomy is not recommended for patients with unstable medical conditions but may be required if percutaneous cordotomy is not feasible or a previous attempt has failed. Cancers treated: This surgical technique addresses the management of cancer pain that does not respond to oral analgesics. Why performed: Pain is experienced by up to 75 percent of patients with advanced cancer. Between 25 and 30 percent of these patients report the pain as severe or excruciating. Intraspinal procedures are the last of a long treatment continuum that includes the following: • systemic regimens utilizing medications and physical therapy • direct operations for spinal decompression or stabilization • psychological protocols • chemotherapy and/or radiation therapy • regional anesthetics and opioids The extensive number of available drugs has resulted in adequate control of discomfort from most malignant cancers. For a small number of cancer patients, however, re319
Cordotomy ferral for anesthetic or neurosurgical procedures for pain management is still needed. The optimal candidate for this operation should have unilateral, severe pain in the fifth cervical vertebra (C5) or lower dermatomes that is not treated adequately by less invasive methods. Cordotomy appears to be more effective in the treatment of intermittent shooting pains rather than distressing dysesthesias (burning, prickling pain, or aching). It is indicated for localized, not general, pain and is not usually indicated for pain in the upper torso because of the risk of respiratory complications. Patient preparation: The procedure is usually done on an outpatient basis. Patients are instructed not to eat or drink anything for five hours prior to the procedure. In cases where open surgery is required, patients should not eat or drink for twenty-four hours prior to the surgery. In both cases, someone should drive the patient to and from the procedure and stay with the patient for at least eighteen to twenty-four hours afterward. Steps of the procedure: The patient is placed in a supine position with the upper cervical spine in a horizontal position. The patient is given light intravenous sedation. Using local infiltration of anesthesia between the first and second cervical vertebrae, the physician introduces a cordotomy needle in the side of the neck on the side opposite that of the perceived pain. An image intensifier is used to define the point of the dural puncture. Once the needle has been introduced into the subarachnoid space of the spinal cord, a contrast medium is injected to visualize the surrounding anatomy. A special insulated electrode is inserted through the needle. With monitoring, the electrode is directed into the spinal cord. An electrical cable line is attached to the electrode, and the tip is stimulated with an electrical current. During each stimulation, the patient is closely questioned about sensory changes and motor twitching. In this setting, portions of the spinothalamic tract are destroyed to result in a desired level of analgesia. Disturbances in temperature sensation are usually seen as a result of these cordotomy lesions. The CT-guided cordotomy technique is similar to this traditional percutaneous method except that the cordotomy electrode needle is inserted with the patient in a computed tomography (CT) machine. In selected cases, an open cordotomy is needed. The patient is completely anesthetized, placed in a prone position, and undergoes a traditional surgical exposure. A laminotomy is performed at the level of the first and second thoracic vertebrae (T1 and T2), and the spinal cord is directly visualized. Placement of the electrode is accom320
Salem Health: Cancer plished with C-arm fluoroscopy, and disruption of the spinothalamic tract is electrically monitored. After the procedure: Postoperative care consists of observation for ipsilateral leg weakness, changes in bladder control, significant lower medication requirements, and possible respiratory depression. Hospitalization is usually for one or two days. Risks: The complication rate from unilateral cordotomy is low, with a mortality rate between 0.6 and 6.0 percent. Bowel incontinence and bladder dysfunction can be seen in 2 to 10 percent of patients. Although information relative to sexual function is difficult to obtain, reports of impotency are rare. Transient hypotension can occur in 2 to 8 percent of cases. Permanent muscle weakness with ataxia (difficulty in walking) can be a major concern in 1 to 6 percent of patients. Respiratory problems are mild and transient, but respiratory failure has been documented in 1 percent of patients. Postcordotomy dysesthetic syndromes (burning distress throughout the entire area that was made analgesic) can occur in 1 to 10 percent of patients. Their pathophysiologic mechanisms are unknown. Open surgical cordotomy seems to be less effective and certainly has a higher risk of complication than do percutaneous techniques. Results: Cordotomies are performed to treat cancer pain, often from lung or gastrointestinal malignancies. The procedure has been rarely employed in the treatment of lumbar radiculopathy or peripheral neuropathy. The target sites are the lower body as opposed to the upper body in about two-thirds of patients. In the hands of experienced surgeons, the spinothalamic tract can be located in 95 percent of patients. Adequate levels of pain relief are found in as high as 95 percent of patients on discharge from the hospital. At last follow-up, the success rate drops to 84 percent. Review of the literature realistically suggests longterm success rates of 50 to 75 percent. Repeat cordotomies may be necessary in 10 percent of patients. John L. Zeller, M.D., Ph.D. u
For Further Information Crul, B., L. Blok, and J. van Egmond. “The Present Role of Percutaneous Cervical Cordotomy for Treatment of Cancer Pain.” Journal of Headache Pain 6, no. 1 (February, 2005): 24-29. Giller, C. A. “The Neurosurgical Treatment of Pain.” Archives of Neurology 60 (2003): 1537-1540. Jones, B., et al. “Is There Still a Role for Open Cordotomy in Cancer Pain Management?” Journal of Pain and Symptom Management 25, no. 2 (2003): 179-184.
Salem Health: Cancer
Corticosteroids
Loeser, John D., ed. Bonica’s Management of Pain. 3d ed. Philadelphia: Lippincott Williams & Wilkins, 2001. Raj, P. Prithvi., ed. Pain Medicine: A Comprehensive Review. 2d ed. St. Louis: Mosby, 2003.
After the procedure: Either a suture (stitch) or Steri-Strip (adhesive paper) is applied to close the edges of the incision. A sterile dressing is applied over the biopsy site. The patient is monitored for one hour after the biopsy.
See also Infusion therapies; Pain management medications; Palliative treatment.
Risks: The risks of core needle biopsy are bleeding from the biopsy site, local nerve damage, infection, and, for lung biopsies, pneumothorax (collapse of a lung).
u Core needle biopsy Category: Procedures Also known as: Stereotactic (exact) biopsy, Mammotome biopsy, Advanced Breast Biopsy Instrument (ABBI) biopsy Definition: A core needle biopsy is a procedure in which a sample of a tumor is extracted by using a wide-gauge hollow needle, a Mammotome, or an ABBI. The Mammotome and the ABBI are used for breast biopsies only. A core needle can range in size from 0.25 to 1.0 centimeter in diameter. It has a spring-loaded device that suctions out the tissue sample. The Mammotome suctions in breast tissue and cuts it with a rotating blade. The ABBI extracts a cylinder of breast tissue about the size of the tumor. Cancers diagnosed: Breast, prostate, kidney, musculoskeletal, and skin cancers Why performed: Needle biopsies are performed to obtain tissue samples from a tumor that is suspected of being cancerous. Patient preparation: If a core needle biopsy is performed in a physician’s office, then ultrasonic guidance is used to localize the tumor, unless it is palpable. If it is palpable, no radiologic guidance is required. Needle biopsies that require the use of radiologic imaging to visualize the tumor or that are high risk are performed in an outpatient surgical center or hospital. The preparation for these procedures may include a physical examination, blood work, and possibly an electrocardiogram (EKG). The patient would need to fast for two to four hours before the procedure. Steps of the procedure: The patient is positioned so that the area to be biopsied is exposed. This area is then scrubbed and disinfected. A local anesthetic is injected into the area. If the tumor is not superficial, then a small incision (0.125-inch to 0.25-inch long) is made into the tissue above the tumor. The core needle is inserted through the incision, and several tissue samples are taken.
Results: The biopsied tissue is sent to a pathologist to be examined under a microscope. The surgeon receives a report that describes the size, shape, and activity of the cells and their nuclei and states whether the tumor is cancerous. Christine M. Carroll, R.N., B.S.N., M.B.A. See also Biopsy; Breast cancer in pregnant women; Calcifications of the breast; Clinical breast exam (CBE); Computed tomography (CT)-guided biopsy; Needle biopsies; Needle localization; Pleural biopsy; Progesterone receptor assay; Stereotactic needle biopsy.
u Corticosteroids Category: Chemotherapy and other drugs ATC code: H02-systemic, D07-dermatological, S02sensory organs, M01-musculoskeletal Definition: Corticosteroids are synthetic forms of the naturally occurring hormones produced by the cortex of the adrenal gland. Cancers treated: Brain cancer, lymphomas, leukemias, lung cancer, renal cancer, bone cancer Subclasses of this group: Systemic-short-acting, systemicintermediate-acting, systemic-long-acting, inhaled, topical, intranasal, ophthalmic, intra-articular (into a joint) Delivery routes: These drugs can be taken orally as tablets. There are solutions that may be administered intravenously. They can also be inhaled from metered dose or disk inhalers, instilled into the nostrils, applied to the skin, or dropped into the eyes. In addition, steroids may be injected into inflamed joints in the body. How these drugs work: Corticosteroids are used primarily to suppress the immune response of the body in instances when this response is causing troublesome symptoms and/or damaging the tissues of the body. They accomplish this by decreasing the activity of white blood cells and the production of the chemicals that are involved in the symptoms of inflammation. By decreasing inflammation, corticosteroids can often decrease the symptoms of cancer and chemotherapy. 321
Coughing
Salem Health: Cancer
Common Corticosteroids Drug
Brands
Subclass
Delivery Mode Cancers Treated
Beclomethasone
Vanceril, QVAR
Inhaled
Inhalation
Lung cancer
Betamethasone
Celestone
Long-acting
Oral, IV
Lymphomas; leukemia; multiple myeloma; gastrointestinal, ovarian, bone, liver, and renal cancers
Dexamethasone
Decadrol, Decadron
Long-acting
Oral, IV
Brain tumors
Fluticasone
Flovent
Inhaled
Inhalation
Lung cancer
Hydrocortisone
Solu-Cortef, Cortef, Hydrocortone
Short-acting
IV
Lymphomas; leukemia; multiple myeloma; gastrointestinal, ovarian, bone, liver, and renal cancers
Methylprednisolone Medrol, Solu-medrol
Intermediate-acting Oral, IV
Lymphomas; leukemia; multiple myeloma; gastrointestinal, ovarian, bone, liver, and renal cancers
Prednisolone
Delta-cortef, Hydeltrasol, Intermediate-acting Oral, IV Predacort, Prednisol
Lymphomas; leukemia; multiple myeloma; gastrointestinal, ovarian, bone, liver, and renal cancers
Prednisone
Deltasone
Intermediate-acting Oral
Lymphomas; leukemia; multiple myeloma; gastrointestinal, ovarian, bone, liver, and renal cancers
Triamcinolone
Azmacort
Inhaled
Lung cancer
Side effects: Systemic corticosteroids have many side effects, including increased appetite, weight gain, insomnia, mood swings, muscle weakness, increased growth of body hair, easy bruising, swollen face, acne, stomach irritation, restlessness, cataracts, glaucoma, and water retention. They can cause medical problems such as osteoporosis, worsening of diabetes, and high blood pressure, as well as psychiatric problems such as depression and anxiety. Because they depress the immune response, corticosteroids can increase a patient’s susceptibility to infections. Christine M. Carroll, R.N., B.S.N., M.B.A. See also Antinausea medications; Chemotherapy; Pain management medications.
u Coughing Category: Diseases, symptoms, and conditions Also known as: Hacking, barking, expectorating, hawking, whooping, tussis Related conditions: Asthma, pneumonia, lung cancer, melanoma, lymphomas, thyroid cancer, sarcomas, leuke322
Inhalation
mia, and cancer metastasis (spread of cancer) from primary locations such as the breast, kidney, colon, stomach, rectum, prostate, testis, and bones Definition: Coughing is the sudden and noisy expulsion of air from the chest in response to an irritation in the airway or respiratory tract. Coughing causes a repetitive contraction of the thorax. Etiology and the disease process: The purpose of coughing is to naturally clear the airway and throat of irritants or foreign bodies. Coughing is usually a reflex triggered by irritants that stimulate the cough receptors of the respiratory system. A cough starts with a deep breath and occurs when the diaphragm and chest muscles press on the lungs, forcing the air out through the throat. Coughing clears the airway or lungs of phlegm (sputum). Sometimes a dry cough occurs with postnasal drip, asthma, gastroesophageal reflux disease, or in response to medications such as beta-blockers for blood pressure or aspirin. Smoking is a common cause of coughing. Chronic or persistent coughing lasting two to three weeks with no obvious source usually indicates underlying disease. A cough that lasts months may indicate lung cancer or metastatic cancer.
Salem Health: Cancer Incidence: Coughing is a natural response to respiratory irritants, so almost everyone coughs at some time. When seen by a health care provider for a cough, nonsmokers with a normal chest X ray will receive a benign diagnosis about 93 percent of the time. However, one of the primary signs of lung cancer is persistent or chronic coughing over an extended time, often with bloody sputum. Over 90 percent of lung cancers start in the bronchi or large tubes that branch off the trachea (the airway that allows air to enter the lung). Lung cancer is the leading cause of cancer death in both women and men, causing an estimated 160,440 deaths in 2004. About 90 percent of lung cancer in men and 80 percent in women occurs in smokers. Coughing is often a symptom. Symptoms: Any persistent cough lasting over two weeks should be evaluated by a health care provider. Coughing up bloody or rust-colored mucus (hemoptysis) from the lungs may indicate metastasis of the primary cancer for a cancer patient. Lung cancer can result in narrowing of the bronchial tubes, causing wheezing and coughing. Screening and diagnosis: Several tests can be used to determine the cause of persistent coughing. A chest X ray is a noninvasive screening tool that takes a picture of the chest, heart, lungs, ribs, arteries, and diaphragm. A radiologist examines the X ray to determine if the patient has conditions such as infections from pneumonia or bronchitis, scarred lung tissue, collapsed lung, tuberculosis, lung cancer, or lung tumor. Acomputed tomography (CT) scan will show smaller tumors or nodules undetected by a screening X ray. Another diagnostic tool is the sputum specimen. The patient produces a deep cough and collects the mucus in a cup. Cultures are collected from the sputum and examined for bacteria or blood. A positive culture confirms abnormal results and indicates a disease is present. A bronchoscopy is a diagnostic procedure using a flexible or rigid tube put down the nose or throat into the lungs. The health care provider can extract samples of tissue (biopsy) or fluids and lung cells for further examination. This is usually an outpatient procedure. Lung cancer is diagnosed through this procedure and the accompanying biopsy examination. Treatment and therapy: Treatment for coughing depends on the underlying cause. Coughing is generally treated with medications such as cough suppressants and expectorants to loosen the mucus so that it can be expelled. Some cough medications are over the counter (OTC), while others such as codeine require a doctor’s prescription.
Coughing Surgery or chemotherapy may be indicated for a lung tumor. In secondary lung cancer, the malignancy has spread (metastasized) from a primary or distal site to the lungs; radiation therapy may alleviate the coughing by reducing the size of the cancer. If the irritation is coming from a blocked airway, laser therapy can sometimes burn the tumor out of the airway; a tube (stent) is inserted to relieve the pressure and hold the airway open. Prognosis, prevention, and outcomes: The prognosis for coughing depends on the underlying cause. Because research has confirmed that smoking can cause lung cancer, prevention translates into not smoking. If the coughing is benign or nonmalignant (not cancer related), coughing can be prevented by minimizing exposure to the offending cause. The outcome should be positive if the irritant is removed. Avoiding fumes and toxic chemicals as well as known allergens can decrease the incidence of coughing and possible lung cancer. If the coughing is related to lung cancer, treatment of the cancer may decrease the respiratory irritation from the cancer. Marylane Wade Koch, M.S.N., R.N. u
For Further Information Homsi, Jade, Declan Walsh, and Kristine A. Nelson. “Important Drugs for Cough in Advanced Cancer.” Supportive Care in Cancer 9, no. 8 (November, 2001). Meuser, T., et al. “Symptoms During Cancer Pain Treatment Following WHO Guidelines: A Longitudinal Follow-up Study of Symptom Prevalence, Severity, and Etiology.” Pain 93, no. 3 (September, 2001): 247257. Redington, Anthony E., and Alyn H. Morice, eds. Acute and Chronic Cough. Boca Raton, Fla.: Taylor and Francis, 2005. Roth, Jack A., James D. Cox, and Waun Ki Hong, eds. Lung Cancer. 3d ed. Malden, Mass.: Blackwell, 2005.
u
Other Resources
American Cancer Society http://www.cancer.org American Lung Association http://www.lungusa.org Lung Cancer Alliance http://www.alcase.org National Cancer Institute http://www.cancer.gov See also Bronchial adenomas; Bronchoalveolar lung cancer; Bronchoscopy; Hemoptysis; Lung cancers; Pneumonia; Smoking cessation; Sputum cytology. 323
Counseling for cancer patients and survivors
u Counseling for cancer patients
and survivors Category: Social and personal issues Definition: Counseling involves the services and service providers available to help people with cancer, those who have survived cancer, and their families cope with the physical and psychological effects of the illness, during and after medical treatment. Why counseling might be needed: Those diagnosed with cancer, and their families, face many complex issues at all stages of the illness. The experience of being diagnosed with, and treated for, cancer changes every aspect of life: The person suddenly is faced with combating a disease with an uncertain outcome. Patients must strive to cope with the physical aspects of cancer, including pain, fatigue, and treatment side effects, as well as psychological and emotional issues, such as fear, stress, anger, denial, change in physical appearance, loss, death, anxiety, and even guilt. Families and caregivers also experience intense emotional reactions. In addition, the person with cancer may need to address financial and legal issues, spiritual issues, and the practical aspects of living with cancer. Together, these emotional and practical concerns often are referred to as psychosocial issues. Thus, a person who has cancer (and his or her family members) may seek counseling for help with a specific issue or feeling (such as death), for support in working through the many emotions encountered throughout treatment, or simply to “talk through” the experience with someone else and to retain a sense of meaning in life. It is important for both the patient and family to understand that seeking help to address these issues can be beneficial and requires a great deal of courage. Emotional and psychological problems: Some patients might encounter psychological problems resulting from cancer treatment. Depression, for example, can be caused by some types of chemotherapy. In addition, patients inevitably experience emotional reactions to physical changes created by some types of cancer therapy, such as hair loss or weight changes. Sometimes, emotional or psychological problems can create physical reactions, such as a rapid heartbeat, tense muscles, or insomnia. Further emotional difficulty is created if a patient must face the disease and treatment without any emotional support. In contrast, other patients may be surrounded by family and friends but nevertheless feel isolated and lonely. The person’s “developmental stage” will affect how he or she feels about, and deals with, the emotions surround324
Salem Health: Cancer ing cancer. Children and teenagers, for example, experience different emotions from adults. In short, every patient experiences different emotions and reacts differently. These emotions, as well as an overwhelming feeling of helplessness and lack of control over life, may affect the person’s ability or motivation to seek medical or psychological treatment. The emotions themselves often feel very foreign to the person experiencing them, and this alone can introduce additional fear and anxiety. Reactions of family and caregivers: Family, friends, spouses, parents, and colleagues—indeed, everyone involved with the person who has cancer—is affected by it and responds in his or her own way. It is important that those involved understand that everyone’s reactions affect one another, including the patient. For instance, family members may experience fear and anxiety, just like the patient, but may keep it to themselves in an effort to “protect” the patient. Often, this lack of communication between caregivers and patient may be more damaging than helpful. It is equally important to address the emotions experienced by the family in order to benefit both the patient and family. Problems with practical issues: Many practical aspects of life may be affected by cancer. These include financial difficulties, as well as problems with employment, education, and obtaining health care services. Addressing these problems can help patients and families feel some sense of control in their lives, despite the uncertainty of cancer. Types of counselors and what they do: Many types of counselors and counseling services are available to help cancer patients and their families. Yet, there now is so much information available, it can be difficult to know where to begin to find help and what type of help different service providers can offer. • Medical staff involved in the patient’s care may help patients address some of the issues listed above. Yet, there are many people who are trained specifically to address the emotional, psychological, and practical issues that patients face. These service providers may be employed by hospitals, government agencies, or private organizations, or they may work in private practice. • Genetic counselors help people who are concerned about inherited forms of cancer and their family’s or their own risk for certain types of cancer. Training includes a master’s degree with work in medical genetics and counseling. Many genetic counselors also are certified by a professional board. • Medical social workers help patients find and access various services (such as financial advice or at-home care)
Salem Health: Cancer needed during and after treatment. Some social workers also may be trained to help patients and families address emotional issues. Training includes a bachelor’s degree and usually a master’s degree in social work (M.S.W.) and state licensure. • Mental health counselors work specifically with the emotional and psychological issues affecting patients and families. The counselor may work individually with the patient and/or with the patient’s family members. Some counselors specialize in working with illness-related issues. Training usually includes a master’s degree in psychology or a related area (M.S. or M.A.P.) and state licensure. • Nurse practitioners are registered nurses who have completed additional training (usually a master’s degree) in managing specific medical conditions, including cancer. The nurse usually provides medical services but also may advise patients on psychosocial issues. Often, nurses talk through issues with patients during medical checkups or treatments. • Oncology nurses are registered nurses (with advanced certification or a bachelor’s degree in nursing) who spe-
Counseling for cancer patients and survivors cialize in working with cancer patients. These nurses provide a broad range of medical services, which also may include addressing psychosocial issues. • Pastoral counselors address emotional and psychological issues affecting patients and families within the context of a specific religious orientation (usually Christian). Training includes a master’s degree in psychology or divinity (M.Div.), with further state licensure (often in marriage and family therapy) and certification by a professional board. • Psychologists are trained specifically to address emotional and psychological issues and to diagnose psychological problems (for example, major depressive disorder). Training includes a doctorate (Ph.D.) in psychology or related area with state licensure. • Psychotherapists are trained specifically to address emotional and psychological issues, through talking with the client. Psychotherapists often work with patients primarily to address aspects of meaning and emotion in the patient’s life, and work secondarily with specific psychological or behavioral symptoms. The psychotherapist is not licensed to prescribe medication but often works with
Counseling helps patients deal with changes associated with being diagnosed with and treated for cancer. (Digital Stock)
325
Cowden syndrome people who are taking medication for mental health problems. Training includes a master’s degree, usually in psychology (M.A.P.), and state licensure. • Psychiatrists usually focus specifically on psychiatric and/or psychological disorders that require medication and are caused by a physical process (for example, brain cancer that is creating behavioral difficulties). These providers are medical doctors (M.D.’s) who specialize in mental health. Some psychiatrists focus mainly on diagnosing conditions and prescribing medication, rather than on counseling. • Volunteers are key in many organizations, providing services such as support groups or telephone hotline services. Often, the sponsoring organization provides brief training for these volunteers, and in many cases the volunteers have had some personal involvement with cancer or with cancer patients. Types of counseling services: Counseling services can include individual sessions with the providers mentioned above; group sessions with other patients or family members, led by a mental health professional; support networks available by phone or by computer; and organized activities or classes led by volunteers or by trained professionals. Amy J. Neil, M.S., M.A.P. u
For Further Information Cousins, Norman. Anatomy of an Illness as Perceived by the Patient. New York: W. W. Norton, 1979. Fiore, Neil. The Road Back to Health: Coping with the Emotional Aspects of Cancer. Berkeley, Calif.: Celestial Arts, 1990. Granet, Roger. Surviving Cancer Emotionally: Learning How to Heal. New York: John Wiley & Sons, 2001. Holland, Jimmie, and Sheldon Lewis. The Human Side of Cancer. New York: HarperCollins, 2000. Siegel, Bernie. Love, Medicine, and Miracles. New York: Harper & Row, 1986. u
Other Resources
Salem Health: Cancer CancerCare http://www.cancercare.org National Cancer Institute http://www.cancer.gov Patient Advocate Foundation http://www.patientadvocate.org See also Anxiety; Cancer care team; Cancer education; Caregivers and caregiving; Case management; Elderly and cancer; End-of-life care; Family history and risk assessment; Financial issues; Genetic counseling; Grief and bereavement; Home health services; Hospice care; Informed consent; Karnofsky performance status (KPS); Living with cancer; Long-distance caregiving; Medicare and cancer; Oncology social worker; Overtreatment; Palliative treatment; Personality and cancer; Prayer and cancer support; Psycho-oncology; Psychosocial aspects of cancer; Relationships; Self-image and body image; Singlehood and cancer; Stress management; Support groups; Watchful waiting.
u Cowden syndrome Category: Diseases, symptoms, and conditions Also known as: Multiple hamartoma syndrome Related conditions: PTEN hamartoma tumor syndrome (PHTS), Lhermitte-Duclos disease Definition: Cowden syndrome is an inherited disorder characterized by the presence of multiple tumorlike growths, termed hamartomas. Although these hamartomas are generally benign, or noncancerous, individuals with hamartomas have a predisposition to the development of certain cancers. Risk factors: Cowden syndrome is inherited in an autosomal dominant pattern and therefore may be inherited from just one parent.
Association of Oncology Social Work http://www.aosw.org
Etiology and the disease process: Cowden syndrome is linked to mutations in the PTEN gene. PTEN is a tumorsuppressor gene, which normally functions to control cell growth and division. The mutations in PTEN may either be inherited or occur spontaneously. Approximately 80 percent of patients with Cowden syndrome have identified mutations in the PTEN gene. However, the cause of the condition in the other 20 percent of patients is unknown.
Cancer Hope Network http://www.cancerhopenetwork.org
Incidence: The exact incidence of Cowden syndrome is not known but is estimated at 1 in 200,000 individuals.
American Cancer Society http://www.cancer.org American Psychosocial Oncology Society http://www.apos-society.org
326
Salem Health: Cancer
Craniopharyngiomas
Symptoms: The major defining symptom of Cowden syndrome is the presence of multiple hamartomas. These growths are generally small and most often occur on the skin and on mucous membranes such as the inside of the nose and mouth. However, hamartomas may also occur on the inner lining of the intestines and within other parts of the body. Also, patients with Cowden syndrome often develop noncancerous breast and thyroid diseases. Another common symptom of Cowden syndrome is macrocephaly, or an enlargement of the patient’s head.
1 to 4 inches in size. They grow by expansion and can cause compression of structures such as the optic chiasm and nerves and the pituitary stalk and gland. The three subtypes are adamantinomatous or pediatric type, which is the classic and most common form of this tumor, having primarily a cystic composition, usually with a solid component; papillary or adult type, which has a more encapsulated, solid component that typically has no calcifications; and mixed type, which is composed of transitional features between the adamantinomatous and papillary variants.
Screening and diagnosis: Cowden syndrome is typically diagnosed through recognition of the extensive hamartomas. To help confirm a diagnosis, the PTEN gene can be sequenced to identify any mutations.
Risk factors: The cause of craniopharyngioma is not known, and there are no known environmental or infectious risk factors. More than 50 percent of people with craniopharyngiomas are younger than eighteen (adamantinomatous type), and most cases occur in children between the ages of five and ten. The second most common age range in which craniopharyngioma occurs is between forty and sixty years (papillary). Craniopharyngiomas do not appear to be more prevalent in a particular gender or ethnicity, nor do they appear to be inherited.
Treatment and therapy: The hamartomas and other symptoms related to Cowden syndrome are typically not treated; however, the main recommendation is for these patients to continue to be screened to watch for the early development of cancerous lesions. Prognosis, prevention, and outcomes: Because Cowden syndrome is often an inherited disorder, little can be done to prevent the disease. Patients with Cowden syndrome have a heightened risk of developing certain cancers. These include breast cancer, thyroid cancer, and uterine cancer. However, with routine screening, these tumors may be diagnosed in early stages and therefore often respond well to therapy. Lisa M. Cockrell, B.S. See also Family history and risk assessment; Thyroid cancer; Trichilemmal carcinomas.
u Craniopharyngiomas Category: Diseases, symptoms, and conditions Also known as: Rathke pouch tumors, adamantinomas Related conditions: Endocrinological and neurological dysfunctions Definition: A craniopharyngioma is a slow-growing, histologically benign tumor that has been found above and below the sella turcica (depression in the upper surface of the sphenoid bone) and in ectopic locations in the brain. Most craniopharyngiomas are found in the sella turcica and the area above it, home to the pituitary gland and hypothalamus. Although generally benign, craniopharyngiomas, like malignant tumors, can metastasize to areas outside the brain. When discovered, they typically range from
Etiology and the disease process: Although the etiology of craniopharyngiomas has not been determined with certainty, several theories exist as to their origin. One theory is that craniopharyngiomas are another form of a congenital tumor known as an epidermoid cyst. (Epidermoid cysts can arise anywhere in the body and are proven to be congenital.) Another theory suggests that they arise from embryonic dental or jaw tissue (dental anlage). A third theory, and the one that seems to be the most popular, purports that craniopharyngiomas are remnants of Rathke’s pouch (a depression in the roof of the developing mouth that gives rise to the anterior pituitary) and arise from squamous cell nests found at the junction of the pituitary stalk and the distal portion of the anterior pituitary. Craniopharyngioma appears as a single, large cyst or multiple cysts filled with a cloudy, proteinaceous, brownishyellow material that glitters because it contains floating cholesterol crystals. This kind of tumor most frequently arises in the pituitary stalk and projects into the hypothalamus. Craniopharyngioma causes symptoms in three different ways: first, as it grows it increases the pressure on the brain; second, as it enlarges it interferes with the normal function of the pituitary gland; and third, as it grows upward, it damages the optic nerve. Incidence: Craniopharyngioma is a rarely occurring, nonheritable cancer. According to the National Cancer Data Base, the overall incidence of craniopharyngioma in the United States is 0.13 per 100,000 persons per year. Craniopharyngiomas account for 1 to 3 percent of all 327
Craniopharyngiomas intracranial tumors and 4.2 percent of all childhood intracranial tumors. The incidence does not vary by sex or race. Approximately 340 cases of craniopharyngiomas occur annually in the United States, with 96 occurring in children between birth and fourteen years of age. Recurrences usually occur at the primary site. Ectopic and metastatic recurrences are extremely rare and have been reported after surgical removal. Recurrence rates can be as high as 20 percent. Symptoms: Symptoms frequently develop slowly and become obvious only after the tumor enlarges to about 1.5 inches in diameter. Craniopharyngiomas produce symptoms by compression of adjacent neural structures, leading to endocrine and visual problems; they obstruct cerebrospinal fluid pathways, causing hydrocephalus and increased intracranial pressure, which lead to headaches and nausea. The most common symptoms are headache (55 to 86 percent of patients), endocrine dysfunction (66 to 90 percent of patients), and visual disturbances (37 to 68 percent of patients). Headaches are slowly progressive, dull, continuous, and positional, becoming severe when endocrine symptoms become obvious. Endocrine dysfunction includes hypothyroidism, adrenal failure, and diabetes insipidus; young patients typically display growth failure and delayed puberty. Nearly three-quarters of patients suffer some sort of damage to the optic pathway. Other manifestations relate to the various connections of the hypothalamic-pituitary complex and surrounding structures. Tumors located in the thalamus and frontal lobes are often accompanied by corresponding endocrine, autonomic, and behavioral problems, such as hyperphagia and obesity, short-term memory deficits, psychomotor retardation, emotional immaturity, and lethargy. Screening and diagnosis: Computed tomography (CT) scanning and magnetic resonance imaging (MRI) are the screening methods of choice for craniopharyngioma. MRI, with or without administration of contrast enhancement, is generally preferred over CT scanning but may not be as readily available. Although CT can clearly demonstrate the characteristic calcifications and size of the tumor, MRI can demonstrate the size and extent of the tumor as well as any ventricular involvement. MRI results can confirm cystic features of the tumor. Various MRI sequences, such as fluid-attenuated inversion recovery (FLAIR), gradient echo, and diffusion-weighted imaging, can aid in making the correct diagnosis. The diagnostic workup for craniopharyngioma also includes complete endocrinological and neuroophthalmological evaluation with visual-field examination and neuro328
Salem Health: Cancer psychological assessment. The endocrinological tests will include serum electrolytes, serum and urine osmolality, thyroid studies, morning and evening cortisol levels, growth hormone levels, and luteinizing and follicle-stimulating hormone levels. Postoperatively, CT scanning is performed to establish a baseline from which follow-up scans will be judged. MRI is often performed to determine whether there is any residual tumor. Treatment and therapy: There is no medical therapy per se for craniopharyngioma. There is little debate that the standard treatment of this tumor is surgical excision followed by adjuvant radiotherapy; however, controversy does exist about the optimal degree of excision. Some physicians believe that complete resection is the best treatment and that every effort should be made to remove as much of the tumor as possible. Others advocate a planned partial tumor excision, leaving radiotherapy or radiosurgery to complete the removal. The controversy stems from the fact that nearly all craniopharyngiomas are located in eloquent areas of the brain; removal necessitates maneuvering around very delicate anatomical structures, which, if damaged during the course of tumor removal, could fail to perform normally, leaving the patient with severe deficits. Craniopharyngiomas tend to adhere to the structures and tissues that surround them, making them difficult to excise without disturbing or damaging these other entities. It is especially challenging to resect a craniopharyngioma that is adhering to the pituitary gland, the hypothalamus, or the optic chiasm and nerves. For example, damage to the pituitary gland, which controls the activity of many other endocrine glands, such as the thyroid, the ovaries, and the adrenal glands, can result in a cascade of endocrine-related disorders including hypothyroidism, obesity, diabetes, and, in children, failure to thrive. Damage to the hypothalamus, which controls the activity of the pituitary by releasing various hormones to regulate it, can result in a host of problems from interrupted circadian rhythm to impaired immune system function. Damage to the optic chiasm and optic nerves can cause visual disturbances ranging from mild hemianopsia (in which each eye is able to send images from only half its field of vision to the brain) to complete blindness. Because of these issues, treatment of craniopharyngioma is complex. The surgical approach used is dictated by the tumor’s location. If the predominant portion of the tumor is intrasellar, the approach is usually transsphenoidal (through the sphenoid bone). The transsphenoidal approach is less invasive than craniotomy (in which part of the skull is re-
Salem Health: Cancer moved to provide access to the brain) and therefore preferable. Craniotomy is necessary when the predominant component is suprasellar. Certain suprasellar masses may be approached through an extended transsphenoidal craniotomy. The pterional craniotomy is the standard approach to suprasellar lesions because it allows the surgeon to see the optic nerves and chiasm. A subfrontal approach is used for lesions that are anterior to the optic chiasm, but this may be difficult to determine preoperatively. Cyst aspiration combined with instillation of radioactive isotope phosphorus-32 is the alternative to traditional resection; however, a tumor with significant solid components is not likely to respond to this type of treatment. Prognosis, prevention, and outcomes: The survival rate for patients who undergo surgery for craniopharyngioma is estimated to be 86 percent at two years and 80 percent at five years postdiagnosis. Survival varies by age group, with excellent survival rates for patients younger than twenty years old and poorer survival rates for those older than sixty-five. Molecular and genetic studies focusing on the treatment and prevention of craniopharyngioma are ongoing. Keller Kaufman-Fox, B.A. u For Further Information Chakrabarti, I., A. P. Amar, W. Couldwell, and M. H. Weiss. “Long-Term Neurological, Visual, and Endocrine Outcomes Following Transnasal Resection of Craniopharyngioma.” Journal of Neurosurgery 102 (2005): 650-657. Chiou, S. M., et al. “Stereotactic Radiosurgery of Residual or Recurrent Craniopharyngioma, After Surgery, with or Without Radiation Therapy.” Neuro-oncology 3 (2001): 159-166. Garrè, M. L., and A. Cama. “Craniopharyngioma: Modern Concepts in Pathogenesis and Treatment.” Current Opinions in Pediatrics 19 (2007): 471-479. Merchant, T. E., et al. “Craniopharyngioma: The St. Jude Children’s Research Hospital Experience, 19842001.” International Journal of Radiation Oncology, Biology and Physics 53 (2002): 533-542. Rekate, Harold L. “Craniopharyngioma.” Journal of Neurosurgery (Pediatrics 4) 103 (2005): 297-298. u
Other Resources
MedlinePlus Craniopharyngioma http://www.nlm.nih.gov/medlineplus/ency/article/ 000345.htm
Craniosynostosis National Cancer Institute Childhood Craniopharyngioma http://www.cancer.gov/cancertopics/pdq/treatment/ childbrain/Patient/page10 See also Brain and central nervous system cancers.
u Craniosynostosis Category: Diseases, symptoms, and conditions Related conditions: Craniofacial syndromes Definition: Craniosynostosis is a process resulting in premature closure or fusion of the cranial sutures. The most common site is the sagittal suture, followed by the coronal, lambdoidal, and metopic. This condition results in an abnormally shaped skull and occurs with a male-to-female ratio of 3:1. Approximately 10 percent are familial, resulting from an autosomal dominate inheritance. Other cases are the result of chromosome deletions, duplications, translocations, breaks, missense, or splice-site abnormalities. Prenatal head constraint is hypothesized as a causative factor in some cases. In utero human development proceeds in a normal fashion, with abnormalities becoming apparent at birth or shortly thereafter. The phenotypic presentation is variable. More than one hundred syndromes have been associated with craniosynostosis. Risk factors: Primary cases of craniosynostosis, in the majority of cases, is the result of spontaneous genetic mutations, although it can also be transmitted genetically from a parent. Children with microcephaly (poor brain growth) are at risk of developing craniosynostosis. Normal brain growth pushes the cranial bones apart at the sutures, but with impaired brain growth, sutures may prematurely fuse. Etiology and the disease process: Mutations in fibroblast growth factor receptor (FGFR1, FGFR2, FGFR3), TWIST, and MSX2 genes are associated with craniosynostosis development. Fibroblast growth factor receptors affect animal growth, development, and homeostasis. They regulate cell growth, differentiation, migration, and survival. They exert direct influence on the formation of various tissues, organs, and blood vessels and are responsible for wound healing. FGFR mutations are directly associated with specific growth and development abnormalities, including the inability to control cell growth leading to tumor formation. Currently, four FGFR mutations have been identified. These mutations produce a variety of results. Germline 329
Craniosynostosis mutations cause skeletal dysplasia (hypochondroplasia, achondroplasia) and craniosynostosis syndromes (Apert, Beare-Stevenson, Crouzon, Pfeiffer, Jackson-Weiss), while somatic mutations cause a variety of cancers. Oncogenes and tumor-suppressor genes are located near recombination sites on chromosomes. Thus, when breaks, translocations, deletions, and amplifications occur in these regions, tumor-suppressor genes can be excluded or oncogenes can be amplified. These processes lead to the development of various cancers. FGFR mutations have been identified in endometrial, breast, gastric, colorectal, bladder (urothelial), cervical, endometrial, and glial tumors and multiple myeloma. In addition, FGFR mutations are implicated in the formation of benign skin lesions such as epidermal nevi and seborrheic keratoses. Saethre-Chotzen syndrome, an autosomal dominantly inherited form of craniosynostosis, is caused by the mutation of the transcription factor gene TWIST1. The protein encoded by this gene is a transcription factor that regulates metastasis and is overexpressed in Saethre-Chotzen syndrome. This abnormality is highly associated with early breast cancer development. An autosomal dominant MSX2 defect has been identified as the causative agent in Boston-type craniosynostosis. Incidence: Craniosynostosis occurs in 1 in 3,000 live births. The association with different syndromes varies from 1 in 25,000 to 1 in 150,000. Symptoms: Normally, bone growth in the skull occurs at its edges, where the initial skull bones are approximated by fibrous connective tissue. When premature fusion of approximated skull bones occurs, the skull assumes an abnormal shape. Palpation of the sutures, fontanels, and skull bones; measurement of the skull circumference; and observation of the skull shape are performed by the care provider during a physical examination of the individual. Premature suture closure may result in additional symptoms, such as increased intracranial pressure and developmental delay. The individual may exhibit bulging eyes, widespaced eyes, a beaked nose, low-set ears, and a small jaw. Certain syndromes may also be associated with hand and limb abnormalities. Screening and diagnosis: Detection is through physical examination and radiographic techniques including X rays and three-dimensional computed tomography (CT) scans. A CT scan not only can detect suture fusion but also can evaluate the brain for underlying structural abnormalities, thereby assisting the surgeon in planning corrective surgery. 330
Salem Health: Cancer Individuals with craniosynostosis are at risk for having an associated syndrome and for developing various cancers. Because of the high incidence of chromosomal defects, duplications, deletions, and substitutions associated with craniosynostosis, affected individuals are candidates for genetic counseling and chromosomal analysis. Early and consistent screening for cancer leads to diagnosis and treatment in earlier stages of the disease, making a cure more possible. Treatment and therapy: Surgery is performed to reopen closed sutures and provide a more normal-appearing skull. An open surgical technique is used with multiple suture fusions or if the surgery is performed after the first year of life. This method involves an ear-to-ear incision, removing, reshaping, replacing, and securing the affected bones. For a single fused suture or if surgery is done in the first few months of life, surgical instruments called endoscopes are inserted through small scalp incisions, and small pieces of bone are removed, releasing the suture fusion. These patients then wear a custom-molded helmet for several months. The helmet provides a template for normal skull growth and shape. For other cosmetic issues, the individual may require orthodontic and orthognathic (jaw) surgery to restore normal facial features. Prognosis, prevention, and outcomes: The prognosis for craniosynostosis is good and improves with early detection and treatment. The morbidity and mortality depend on associated defects as part of a syndrome. Currently, there is no method to prevent autosomal dominant transmission to offspring or to prevent new mutations. FGFR mutations produce a variety of results. Research is necessary to determine how mutations result in different consequences. If it can be determined how mutations affect outcomes, definitive targeted therapies can be developed. One such proposal is anti-FGFR therapy, designed to target the upregulated FGFR genes. Because of the associated risk for a variety of cancers, the individual will require ongoing evaluation and screening for carcinogenesis. Wanda Todd Bradshaw, R.N.C., M.S.N. u
For Further Information Cohen, M. Michael. “Malformations of the Craniofacial Region: Evolutionary, Embryonic, Genetic, and Clinical Perspectives. American Journal of Medical Genetics 115 (2002):245-268. Coumoul, Xavier, and Chu-Xia Deng. “Roles of FGF Receptors in Mammalian Development and Congenital Diseases.” Birth Defects Research 69 (2003): 286-304. Hansen, Ruth, et al. “Fibroblast Growth Factor Receptor 2,
Salem Health: Cancer
Craniotomy
Gain-of-Function Mutations, and Tumourigenesis: Investigating a Potential Link.” Journal of Pathology 207 (2005): 27-31. Ridgway, E. B. “Skull Deformities.” Pediatric Clinics of North America 5, no. 2 (2004): 359-387. u
Other Resources
Children’s Craniofacial Association http://www.ccakids.com March of Dimes Birth Defects Foundation http://www.marchofdimes.com National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/index.htm See also Craniotomy; Dry mouth; Mucosa-associated lymphoid tissue (MALT) lymphomas; Nasal cavity and paranasal sinus cancers.
u Craniotomy Category: Procedures Also known as: Brain surgery Definition: Craniotomy is a surgical procedure in which an incision is made into the skull to gain access to the brain. Cancers treated: Brain cancers, such as glioma, astrocytoma, medulloblastoma, and ependymoma Why performed: Craniotomy is performed for cerebral artery aneurysm clipping, arteriovenous malformation repair, increased intracranial pressure control, hematoma drainage, ventricular shunting, and abscess or tumor excision. Patient preparation: Before surgery, the patient undergoes a computed tomography (CT) scan or magnetic resonance imaging (MRI) of the brain to determine tumor location and size and to evaluate brain tissue swelling. Other routine studies are performed to check for abnormalities and establish a baseline for postoperative comparison. These studies include a chest X ray, an electrocardiogram (EKG), bleeding time, and blood tests to check kidney function, clotting times, white blood cell count, and electrolyte, hemoglobin, and oxygen levels. A blood sample is also drawn to check the patient’s blood type in case a transfusion is needed during surgery. The patient must not eat or drink for at least eight hours before surgery. An intravenous (IV) catheter is inserted for
A patient’s head is readied for a craniotomy. (Custom Medical Stock Photo)
fluids and medications. Depending on the tumor’s location, the patient may also receive a bolus dose of an antiseizure medication, such as phenytoin, to prevent seizure activity during and after surgery. An indwelling urinary catheter is also inserted so that urine output can be monitored closely during and after the procedure. Sequential compression devices are applied to the patient’s legs and worn during and after surgery to prevent blood clot formation. Steps of the procedure: Immediately before the procedure, an arterial catheter is inserted into the patient’s wrist to monitor blood pressure continuously during surgery. This catheter also permits blood sampling so that oxygen and electrolyte levels can be monitored. A central venous catheter may also be inserted to monitor the patient’s fluid status and to administer IV fluids and medications during surgery. After the patient is anesthetized, the neurosurgeon makes an incision into the skin and the skin is retracted. 331
Crohn disease Next, an incision is made into the muscle and the muscle is retracted. Special tools are used first to make holes in the skull bone and then to cut through the bone to make a bone flap. The bone flap is then separated from the protective layer that surrounds the brain and removed. It is kept moist during the procedure. Next, the neurosurgeon exposes the brain tissue and removes the tumor, if possible. Depending on the tumor location, a ventricular drain may be inserted to prevent hydrocephalus and monitor intracranial pressure. If a ventricular drain is not needed, then an intracranial pressure monitor sensor may be inserted. After the tumor is excised, the neurosurgeon ties off bleeding vessels and then replaces the bone flap and secures it using plates and screws. Next, the neurosurgeon closes the incision and covers it with a sterile dressing. This procedure typically takes several hours. After the procedure: The patient is transferred to the intensive care unit (ICU) and attached to a monitor that displays heart rhythm, blood pressure, oxygen saturation, central venous pressure, intracranial pressure, and cerebral perfusion pressure. These devices help the ICU nurses monitor the patient’s condition closely. The patient may have an endotracheal tube (breathing tube) connected to a mechanical ventilator to assist with breathing or may breathe independently with supplemental oxygen. A patient who is able to breathe without help from a ventilator will be encouraged to breathe deeply and use an incentive spirometer frequently to prevent pneumonia. The head of the patient’s bed is maintained at a prescribed elevation based upon the tumor’s location. Every two hours, nurses may gently roll the patient to prevent the development of pressure ulcers and pneumonia. If the patient’s neurologic status becomes unstable, however, then the patient may be unable to tolerate turning. Nurses closely monitor the patient’s vital signs, respiratory, and neurologic status to detect signs of increased intracranial pressure. If such signs are detected, then nurses administer diuretics, such as furosemide and mannitol, to decrease brain swelling. The patient will also receive a corticosteroid, such as dexamethasone, to combat inflammation. Medications such as codeine will also be administered to control pain. If a ventricular drain was inserted during the procedure, then the nurses will maintain the drain as ordered and closely monitor the type and amount of drainage. Nurses also monitor urine output frequently. A sudden increase in urine output without diuretic use may signal diabetes insipidus, a complication of craniotomy. During the immediate postoperative period, it is important to keep the patient’s environment calm and quiet to minimize anxiety and to avoid increasing intracranial 332
Salem Health: Cancer pressure. A drug-induced coma is sometimes necessary to control intracranial pressure that is unresponsive to other therapy; the need is rare, however, following brain tumor resection. When the patient’s condition is stabilized and ventricular drainage is minimal, the ventricular drain is removed and the patient’s activity level is increased. The length of hospital stay varies by the tumor location, extent of surgery, and the patient’s rate of recovery. Depending on the tumor’s extent and location, physical therapy, chemotherapy, or radiation therapy may be needed after surgical recovery. Risks: There are many risks associated with craniotomy, including increased intracranial pressure, surgical site infection, hydrocephalus, meningitis, intracerebral hemorrhage, air embolism, seizures, stroke, cranial nerve damage, syndrome of inappropriate antidiuretic hormone (SIADH), and diabetes insipidus. Results: Pathologic examination of the brain tumor specimen reveals the type of cancer. Collette Bishop Hendler, R.N., M.S. u
For Further Information Greenberg, Mark S. Handbook of Neurosurgery. 6th ed. New York: Theime Medical, 2006. Hickey, Joanne V. The Clinical Practice of Neurological and Neurosurgical Nursing. 5th ed. Philadelphia: Lippincott Williams & Wilkins, 2003. Surgical Care Made Incredibly Visual. Philadelphia: Lippincott Williams & Wilkins, 2007.
u
Other Resources
American Cancer Society http://www.cancer.org See also Astrocytomas; Brain and central nervous system cancers; Craniopharyngiomas; Neurologic oncology.
u Crohn disease Category: Diseases, symptoms, and conditions Also known as: Crohn’s disease, ileitis, ileocolitis, regional enteritis, enteritis Related conditions: Aphthous ulcers, episcleritis, scleroconjunctivitis, recurrent iritis, uveitis, erythema nodosum, pyoderma gangrenosum, spondyloarthropathy or spondyloarthritis-ankylosing spondylitis and sacroiliitis, peripheral arthritis, hypercoagulability, secondary amyloidosis,
Salem Health: Cancer primary sclerosing cholangitis, gallstones, perianal disease, malnutrition, malabsorption, osteoporosis, anemia, lymphoma, cholangiocarcinoma, adenocarcinoma of the gastrointestinal tract, colorectal cancer
Crohn disease Crohn Disease
Definition: Crohn disease is a chronic inflammatory condition of the gastrointestinal tract, anywhere from the mouth to the anus, but most commonly in the end of the small intestine called the ileum and in the adjoining large colon. Risk factors: Those with a family history of Crohn disease, a genetic predisposition, or a history of smoking are at greatest risk for this disease. Etiology and the disease process: Crohn disease (CD) belongs to the group of diseases known as inflammatory bowel disease (IBD), a generic term for diseases characterized by inflammation in the small and large bowels. Other IBDs are ulcerative colitis (UC) and indeterminate colitis (lymphocytic colitis and collagenous colitis). There are many theories about the etiology of Crohn disease, but the exact cause is unknown. It is known to run in families and be more common in certain ethnicities, suggesting a genetic predisposition. However, no specific reason or factor consistently explains the origin of the disease. The current belief relates Crohn disease to an inflammatory process. The human immune system protects people from harmful foreign substances (referred to as antigens) such as bacteria, viruses, and parasites. This protection is provided by cells and various proteins (such as antibodies) through an inflammatory reaction that is a response toward antigens or cell injuries. In Crohn disease, the immune system reacts abnormally against the affected part of the gastrointestinal tract and causes damage. This inappropriate inflammation leads to the clinical manifestations of Crohn disease. Studies have shown that the inflammation related to Crohn disease is multifactorial and may depend on genetic factors, immune reactions, and environmental cues. A region on the human chromosome 16 was found to possibly contain genes that are involved in the abnormal inflammatory response in Crohn disease. One such gene, known as NOD2/CARD15, was found to be more common in Crohn disease patients than in the general population. An abnormality in this gene causes a mutation in the gene product (protein) that ultimately weakens the immune system’s ability to recognize harmful bacteria. The immune reaction may be a response to antigens or to modified parts of the gastrointestinal tract associated with the inflammation. Antitumor necrosis factor-alpha (TNF-alpha) is a protein produced by the immune system that enhances the
Crohn disease is associated with colorectal cancer.
white blood cells’ ability to defend against infections and other foreign substances. TNF-alpha may be a cause of the inflammation associated with Crohn disease; it is abnormally elevated in Crohn disease, causing excessive inflammation and its adverse effects. IBDs (Crohn disease and ulcerative colitis) have similar symptoms, but they also have significant differences. Crohn disease can affect any part of the gastrointestinal tract, cause inflammation deeply penetrating through the tract linings (full thickness), and show radiographic results suggestive of Crohn disease. Ulcerative colitis affects the 333
Crohn disease colon and rectum; it can also cause a “backwash” ileitis in the junction of the small and large intestines. Ulcerative colitis inflammation is mainly in the superficial linings of the affected gastrointestinal tract. Tissue sampling further identifies the difference between Crohn disease and ulcerative colitis. Incidence: The incidence of Crohn disease is 7 new cases per 100,000 people per year, and the prevalence is 162 cases per 100,000 people per year. About 20 percent of Crohn disease cases run in families. Men and women are affected equally. Crohn disease is more common in people of European and Jewish heritage than those of other ethnicities. The onset of Crohn disease has two peaks: between the ages of fifteen and thirty and the ages of sixty and eighty. However, most patients are diagnosed before the age of thirty. Symptoms: The manifestations of Crohn disease are heterogeneous, including symptoms within the gastrointestinal tract and outside of it (extraintestinal). Constitutional symptoms of Crohn disease are fatigue, fever, loss of appetite, and weight loss. Most common gastrointestinal tract symptoms are prolonged diarrhea, with or without rectal bleeding, and abdominal pain (tenderness), usually in the lower right area, which can be mistaken for appendicitis. Malabsorption in the gastrointestinal tract can lead to malnutrition and weight loss, which is related to delayed development and poor growth in children. Mouth ulcers may manifest along with pain in the mouth and gums. Problems of the throat such as pain or difficulty with swallowing can occur if the esophagus is involved. Patients with Crohn disease may develop perianal diseases such as fissure in ano (fissures or tears in the lining of the anus) and fistula-in-ano (abnormal connection between the anal intestinal lining and another part of the body, such as the skin, bladder, vagina, or another part of the gastrointestinal tract). Fistulas are most common in the anal region; abscesses (pockets of pus) may be present as a complication. Blockage (obstruction) and perforation of the gastrointestinal tract may occur. Extraintestinal symptoms include eye disorders, skin problems, arthritis, and liver and gallbladder diseases. Screening and diagnosis: Screening is done through a comprehensive physical examination and a complete blood count to evaluate for anemia and infection. A stool test will be performed if there is gastrointestinal tract bleeding or infection. Special tests for antibodies, such as antineutrophil cytoplasmic antibodies and anti-Saccharomyces cerevisiae antibodies, may be used if the diagnosis of Crohn disease is uncertain. Radiographic studies can in334
Salem Health: Cancer clude upper and lower gastrointestinal series (barium enema). Upper or lower gastrointestinal endoscopy can identify the affected site, allow tissue sampling (biopsy), and confirm the diagnosis of Crohn disease. The severity of Crohn disease is diverse, and its activity is described as mild-moderate, moderate-severe, severe-fulminant, and remission. Treatment and therapy: Crohn disease has no cure; however, symptoms can be alleviated. Management of Crohn disease and its complications may include medications for treatment of symptoms such as antidiarrheal agents (loperamide and diphenoxylate), nutritional support, surgery, or a combination of these modalities. Medications for Crohn disease include antibiotics such as ciprofloxacin and metronidazole; anti-inflammatory drugs such as corticosteroids, sulfasalazine, and 5-aminosalicylate (5-ASA); immunomodulators that inhibit the immune response such as azathioprine, 6-mercaptopurine, and methotrexate; and biological therapies such as infliximab (Remicade) and adalimumab (Humira), which are antibodies that block TNF-alpha activity. All of these medications may have side effects ranging from nausea, vomiting, and headaches to infection susceptibility. The risks and benefits of medications are assessed and modifications implemented on an individual basis. Regular nutritional assessments are necessary to prevent malnutrition, which can result from malabsorption in the inflamed small and large bowels. Surgical intervention is needed in some cases, such as failure of medical treatment and complications such as obstruction, perforation, nonstop bleeding, abscess, and fistula. Prognosis, prevention, and outcomes: Crohn disease is a chronic medical condition. It can manifest in recurrent episodes of the active disease (flares) or remain in remission for variable time periods. Patients with Crohn disease are monitored closely for related conditions such as associated cancers. Regular cancer screening using colonoscopy is recommended for patients with Crohn disease because of its association with colorectal cancer. Miriam E. Schwartz, M.D., M.A., Ph.D., and Colm A. Ó’Moráin, M.A., M.D., M.Sc., D.Sc. u
For Further Information American Gastroenterological Association. Clinical Practice Committee. “Perianal Crohn’s Disease.” Gastroenterology 125, no. 5 (November, 2003): 1503-1507. Eyre, Harmon J., Dianne Partie Lange, and Lois B. Morris. Informed Decisions: The Complete Book of Cancer, Diagnosis, Treatment, and Recovery. 2d ed. Atlanta: American Cancer Society, 2002.
Salem Health: Cancer Hanauer, Stephen B., William Sandborn, and the Practice Parameters Committee of the American College of Gastroenterology. “Management of Crohn’s Disease in Adults.” American Journal of Gastroenterology 96, no. 3 (March, 2001): 635-643. Litin, Scott C., Jr., ed. Mayo Clinic Family Health Book. 3d ed. New York: HarperCollins, 2003. u
Other Resources
American Academy of Family Physicians http://familydoctor.org/online/famdocen/home/ common/digestive/disorders/252.html American College of Gastroenterology http://www.acg.gi.org American Gastroenterological Association http://www.gastro.org Crohn’s & Colitis Foundation of America http://www.ccfa.org/ Crohn’s and Me—Make the Connection http://www.crohnsandme.eu European Crohn’s and Colitis Organisation http://www.ecco-ibd.eu
Cruciferous vegetables
u Cruciferous vegetables Category: Lifestyle and prevention Also known as: Brassicaceae family, glucosinolates, isothiocyanates, indole-3-carbinol Definition: Cruciferous vegetables are edible plants from the Brassicaceae family that include broccoli, cauliflower, brussels sprouts, cabbage, arugula, watercress, bok choy, turnip and mustard greens, kale, kohlrabi, turnips, rutabagas, and radishes. Cruciferous vegetables contain a variety of healthful substances such as vitamin C, selenium, fiber, and sulfur-containing compounds called glucosinolates. The sulfur compounds give cruciferous vegetables their pungent taste and aroma. Cancers treated or prevented: Colorectal cancer, lung cancer, prostate cancer Delivery routes: Oral by diet How these compounds work: Cruciferous vegetables are rich sources of glucosinolate compounds, which may be the source of their cancer-fighting effects. When the vegetables are chopped or chewed, bioactive hydrolysis products of glucosinolates, such as isothiocyanates and indole-3carbinol, are formed. These compounds may help prevent certain cancers by eliminating dietary carcinogens from
European Federation of Crohn’s and Ulcerative Colitis Associations http://www.efcca.org Irish Society for Colitis and Crohn’s Disease http://www.iscc.ie MedlinePlus http://www.nlm.nih.gov/medlineplus/ crohnsdisease.html National Association for Colitis and Crohn’s Disease (UK) http://www.nacc.org.uk National Digestive Diseases Information Clearinghouse Crohn’s Disease http://digestive.niddk.nih.gov/ddiseases/pubs/crohns/ See also Bacteria as causes of cancer; Cholecystectomy; Colon polyps; Colonoscopy and virtual colonoscopy; Colorectal cancer; Colorectal cancer screening; Duodenal carcinomas; Enteritis; Gastrointestinal cancers; Ileostomy; Inflammatory bowel disease; Leiomyosarcomas; Pancolitis; Small intestine cancer.
Cruciferous vegetables such as broccoli are rich sources of glucosinolate compounds, which may be the source of their cancerfighting effects. (©Irochka/Dreamstime.com)
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Cryoablation the body or by preventing normal cells from becoming cancerous. Cooking or boiling cruciferous vegetables decreases the amount and bioavailability of glucosinolates, so raw vegetables provide much higher levels of the compounds than do cooked vegetables. Higher intakes of cruciferous vegetables have been linked to a lower risk of lung, prostate, and colorectal cancer in epidemiological studies. Current evidence is limited, however, and the effects are not consistent. In addition, it is not clear whether the beneficial effects of cruciferous vegetables come from the glucosinolate compounds or from other phytochemicals that act synergetically. Genetic variability may influence the effects of cruciferous vegetables on cancer risk. For example, individuals may vary in their capacity to absorb, metabolize, and eliminate glucosinolate compounds from the body. Thus, genetic differences that affect how long these compounds or their metabolites remain in the body may influence how protective they are against cancer. The National Cancer Institute recommends the daily consumption of five to nine servings of fruits and vegetables; human epidemiological studies suggest five weekly servings of cruciferous vegetables are beneficial. Side effects: Very high intakes of cruciferous vegetables may cause hypothyroidism. In addition, some of the isolated metabolites of glucosinolates in cruciferous vegetables, such as indole-3-carbinol, have produced mixed results in animal studies. For example, depending on when the compound is administered or the length of exposure, indole-3-carbinol can prevent or promote the development of cancer in animals. These studies highlight the disadvantages of isolating potentially beneficial compounds from food, as isolated compounds may produce unwanted effects, and the synergy of many compounds may be critical in cancer prevention. Linda Hart, M.S., M.A. See also Beta-carotene; Chemoprevention; Folic acid; Indoles; Lutein; Nutrition and cancer prevention; Polyps; Prevention; Stomach cancers; Thyroid cancer.
u Cryoablation Category: Procedures Also known as: Cryosurgery, targeted cryoablation therapy, ablation therapy Definition: Cryoablation is a minimally invasive method of treating tumors using extremely cold temperatures to destroy cancer cells or precancerous cells in a localized 336
Salem Health: Cancer area. Cryoablation uses liquid nitrogen, alcohol, or an argon gas-based system delivered through probes that are inserted through a small incision in the skin to freeze a particular area of the tumor and kill the cancerous tissue. Cancers diagnosed or treated: Prostate, kidney, skin, liver, lung, bone, soft-tissue, and pelvic cancers; also being studied for use in certain types of breast tumors and used for some heart rhythm disturbances Why performed: Cryoablation is often used when a tumor is not operable or removable because of the late stage of the cancer or its difficult location near major blood vessels or other organs not affected by the cancer. It may be used as a primary treatment for some cancers such as prostate cancer or as a palliative treatment for liver or other cancers to relieve pain and control cancer-related symptoms. Progress has been made in treating kidney cancers with cryoablation. Sometimes cryoablation is added to other traditional treatments (radiation therapy or chemotherapy) for cancer. Cryoablation is also used to remove precancerous lesions, such as precancerous moles. Patient preparation: Minimal preparation is needed for cryoablation. An intravenous (IV) line is started in the patient for sedation, and the patient’s blood work is checked. Some physicians may also prescribe an antibiotic as a preventive measure. Steps of the procedure: The procedure may take one to two hours. If the patient will have cryoablation during an operation as an added treatment for the tumor, then general anesthesia will be used and a hospital stay will be required. Most cryoablation procedures, however, can be done under local anesthesia and require only an overnight stay in the hospital. An interventional radiologist performs cryoablation using image guidance. A computed tomography (CT) scan, ultrasound, or magnetic resonance imaging (MRI) helps the interventional radiologist guide the probe (usually multiple probes) into the tumor and avoid damage to any healthy tissue surrounding the tumor. A local anesthetic is given in the area overlying the tumor where the probe will enter. The agent used (liquid nitrogen, alcohol, or argon gas) is then delivered through the probes to freeze the tissue. During freezing, an ice ball or crystals form inside and outside the cell spaces of the tumor tissue. The ice forming inside the cell space leads to cell death by injury to the cell membrane, structures within the cell, or both. Ice that forms outside the cell space, where freezing is slower, causes death by creating a rush of the fluid moving in the space outside the cell. This causes the cell to burst and re-
Salem Health: Cancer
Cryoablation
A doctor uses cryoablation to remove skin growths from a woman’s stomach. (Antonia Reeve/Photo Researchers, Inc.)
sults in cell death by a deprivation of oxygen to the cell and the cell membrane. After the procedure: The patient is monitored for a few hours and usually will have to stay overnight in the hospital. A drug such as ibuprofen may be given to relieve a patient’s discomfort from having to remain in one position during the procedure. Although there may be a few restrictions suggested by the physician, most patients can resume their daily activities within one or two days. Risks: Depending on the type of tumor, side effects from cryoablation vary. The most common minor side effects are pain or bruising at the site, fever, nausea, local infection, fatigue, and temporary low platelet count not requiring transfusion. Most resolve within a week. Major risks include freezing injury to organs near the tumor, fluid collection within the organ being treated, and puncture of the colon or other organs near the tumor that can result in major bleeding or infection.
For prostate cancer, impotence and loss of bladder control can be a major complication. A more recent cryoablation procedure for prostate cancer, called nerve-sparing cryoablation and focal prostate cryoablation, is being used to reduce the possibility of impotence and urinary incontinence. Results: The advantages of cryoablation are low complication rates, ability to destroy local tumor tissue with minimal discomfort to the patient, reduction in hospital stay, shortened patient recovery time, less scarring, and lower cost (compared to surgery). It is an especially useful treatment for cancers that are otherwise untreatable and can enhance an individual’s quality of life through better symptom control. For some cancers, such as lung and bone cancer, cryoablation is considered investigational, and health care insurance companies may not cover the procedure. Jo Gambosi, M.A., B.S.N. 337
Cryptorchidism u For Further Information Bahn, Duke, et al. “Focal Prostate Cryoablation: Initial Results Show Cancer Control and Potency Preservation.” Journal of Endourology 20, no. 9 (2006): 688692. Centeno, Arthur S., and Gary Onik. Prostate Cancer: A Patient’s Guide to Treatment. Omaha, Nebr.: Addicus, 2004. Chung, Leland. Prostate Cancer: Biology, Genetics, and New Therapeutics. Totowa, N.J.: Humana Press, 2001. VanSonnenberg, Eric, William McMullen, and Luigi Solbiati. Tumor Ablation: Principles and Practice. New York: Springer, 2005. u
Other Resources
American Cancer Society http://www.cancer.org Galil Medical Cryotherapy http://www.galil-medical.com/galil-medicalcryotherapy.html See also Adenoid cystic carcinoma (ACC); Basal cell carcinomas; Birt-Hogg-Dubé syndrome (BHDS); Carcinoid tumors and carcinoid syndrome; Cervical cancer; Dermatology oncology; Eyelid cancer; Hereditary leiomyomatosis and renal cell cancer (HLRCC); Kidney cancer; Radiofrequency ablation; Skin cancers; Surgical oncology.
u Cryptorchidism Category: Diseases, symptoms, and conditions Also known as: Undescended testicles, hidden testis, obscure testis, maldescended testis Related conditions: Reduced fertility, testicular cancer Definition: Cryptorchidism refers to a condition in which one or both testes are absent from the scrotum, having failed to descend into the scrotum before birth. It has been associated with development of testicular cancer later in life. Risk factors: There is a strong link between low birth weight and cryptorchidism. Additionally, premature infants can be born before descent of the testes takes place. Studies have shown that regular alcohol consumption during pregnancy is associated with a threefold increase in this abnormality. Those with cryptorchidism have between a four- and fortyfold greater risk of developing testicular cancer, most often in the third through fifth decades of life. 338
Salem Health: Cancer Etiology and the disease process: The testes remain high in the abdomen until the seventh month of gestation, when specific hormones initiate the movement of the testes from the abdomen into the two sides of the scrotum. The movement, controlled by hormones, occurs in two phases. The first phase involves movement across the abdomen to the entrance of the inguinal canal, and the second phase involves movement of the testes through the inguinal canal into the scrotum. Incidence: About 30 percent of premature and 3 percent of full-term infant boys are born with at least one undescended testis, making cryptorchidism the most common birth defect of male genitalia. However, most testes descend by the first year of life, making the true incidence of cryptorchidism around 1 percent overall. Symptoms: A manual exam of the scrotum determines if one or both testes are not present. For associated testicular cancer, a painless testicular mass is the most common symptom; a few young men may also experience diffuse testicular pain or swelling. Screening and diagnosis: Screening for cryptorchidism takes place immediately after birth as part of a routine physical exam. Diagnosis is generally confirmed by a manual exam, resulting in the determination of only one testicle (or none) in the scrotal sac. Treatment and therapy: A surgery known as orchiopexy is primarily performed in infancy for boys who have a testis still within the inguinal canal. When the undescended testis is in the inguinal canal, hormonal therapy is sometimes attempted and is occasionally successful. The most commonly used hormone therapy is human chorionic gonadotropin. A series of injections (ten injections over five weeks is common) is given, and the status of the testis or testes is reassessed at the end. The most common argument for orchiopexy as opposed to hormone treatment is to lower the risk of developing testicular cancer. For men with only one undescended testis, that risk is higher in the descended testis as well. Prognosis, prevention, and outcomes: The prognosis for correction of cryptorchidism is excellent. Currently there are no preventive measures for this disease, as it usually occurs during fetal development. Men who experienced cryptorchidism as infants, particularly if there is a family history of testicular cancer, have a 2.5- to 11-fold increased risk of developing testicular cancer and should be regularly screened starting at puberty. Boys typically are taught how to examine the testes and advised to report lumps or other abnormal characteris-
Salem Health: Cancer tics. Cancers (most commonly seminomas) caught early in this fashion are treatable. Semen and blood tests may begin in the late teenage years, and biopsy of the testes may be recommended in adults. Robert J. Amato, D.O. See also Spermatocytomas; Teratocarcinomas; Testicular cancer; Testicular self-examination (TSE); Yolk sac carcinomas.
u Culdoscopy Category: Procedures Also known as: Flexible culdoscopy Definition: A culdoscopy is a minimally invasive surgical procedure for visualizing the female pelvic organs through an endoscope (or culdoscope). The endoscope, a rigid viewing tube, is passed through the vagina into the cul-desac or retrouterine pouch (the pouch of Douglas), the part of the peritoneal cavity between the rectum and the uterus. The procedure can be used for the diagnosis of diseases such as cancer or the diagnosis of other conditions such as infertility or endometriosis. Cancers diagnosed: Cancer of the uterus, ovaries, or Fallopian tubes Why performed: Culdoscopy allows examination of the female pelvic organs and collection of a biopsy (tissue sample) for diagnosing cancer, with minimal discomfort for the patient. Patient preparation: The procedure is minimally invasive and is usually a hospital procedure with a short stay. Gas distension may be required for visualization but may not be necessary if the procedure is done in the knee-tochest position. Anesthesia required for the procedure may vary from local or regional to general anesthesia, depending on various factors. If a flexible tube is used, then the patient may stay awake during the procedure. The patient is informed of the risks involved, as well as the benefits of this type of diagnostic procedure. Steps of the procedure: The patient can be positioned in the knee-to-chest position or lying down (lithotomy) for this procedure. The endoscope, or culdoscope, is inserted into the female pelvic cavity via a small incision or puncture in the top of the posterior (back) vaginal wall. After the surgeon visualizes the pelvic cavity, a tissue sample may be taken and sent to the laboratory to determine the presence of cancer.
Curcumin After the procedure: The patient may be positioned on her abdomen to help expel any air used in the procedure. The patient is assessed and monitored for bleeding from the vagina. The patient should abstain from sexual intercourse, tampon use, or douches for at least two weeks or until cleared through her health care provider. Risks: Bowel injury and sepsis are possible risks of culdoscopy. Complications are estimated at 2 percent of patients and include bleeding at the puncture site, infection or peritonitis, or hypersensitivity or allergic reaction to the anesthetic used in the surgery. Results: Though culdoscopy is still useful as a diagnostic tool, many health care providers have replaced this procedure with a laparoscopy. Marylane Wade Koch, M.S.N., R.N. See also Endoscopy; Fallopian tube cancer; Gynecologic oncology; Pelvic examination; Uterine cancer; Vaginal cancer.
u Curcumin Category: Complementary and alternative therapies Also known as: Diferuloylmethane Definition: Curcumin is the active principle of turmeric, which is used as a common food additive in Asian cooking. It has been used for many centuries in ancient Chinese and Ayurvedic medical treatments. Curcumin has been selected, along with other promising diet-derived compounds, for testing as a chemopreventive agent for cancer targets in the NCI Chemoprevention Drug Development Program in the United States. Cancers treated or prevented: Supplemental treatment for chemical carcinogenesis caused by pesticides, breast cancer, metastatic melanoma, and lymphoma Delivery routes: Oral by capsule How this substance works: Curcumin is the active component of turmeric, a common spice found in the kitchen cabinets of Asia. Turmeric is a yellow powder obtained from the dried rhizomes of a flowering plant belonging to the ginger family. Curcumin is present in turmeric along with related yellow compounds called curcuminoids. It belongs to a chemical family of compounds known as polyphenols, which are antioxidants that destroy harmful tissue-damaging substances called free radicals. Curcumin has been reported to possess a wide range of medicinal properties, including the ability to inhibit can339
Cushing syndrome and cancer cerous tumors in the breast, colon, and skin in mice, rats, guinea pigs, and hamsters. Curcumin is being investigated for the prevention of colon cancer in a phase I clinical trial at the University of Michigan sponsored by the National Cancer Institute (NCI). One study reported that it reverses the negative effects of Taxol (paclitaxel), a breast cancer drug that can cause breast cancer cells to spread. Additionally, it is being tested against multiple myeloma and advanced pancreatic cancer. Based on experimental findings, curcumin has also been postulated to enhance detoxification of carcinogens such as DDT and dioxin by blocking their access to cells. The proposed hypothesis of the way curcumin inhibits cancerous cell growth is through its ability to block certain kinds of growth factors that are activated by chemical messengers called cytokines and kinases present in the cancer cells, sending signals to the cells to multiply. The structure of curcumin enables it to inhibit multiple kinases, thereby blocking the signals to the cells and effectively stopping the growth of certain types of cancer cells. Side effects: Ingesting large quantities of curcumin can cause ulcers. Curcumin, when used in conjunction with anticoagulants and thrombolytic agents, could enhance their activity and increase the risk of bleeding. Lalitha Krishnan, Ph.D. See also Antioxidants; Chemoprevention; Herbs as antioxidants.
u Cushing syndrome and cancer
Salem Health: Cancer the inflammatory response, balances the activity of insulin, and regulates the metabolism of proteins, sugars, and fats. It also helps the body respond to stress and is found in high levels in women in their last three months of pregnancy, highly trained athletes, and people suffering from depression. Cortisol secretion by the adrenal glands is tightly regulated. A peptide hormone called corticotropin-releasing hormone (CRH) is released into the bloodstream by a portion of the brain called the hypothalamus. CRH signals to the anterior lobe of the pituitary gland, which lies just below the hypothalamus, to release a protein hormone called adrenocorticotropin (ACTH). Circulating ACTH signals to the adrenal cortex cells to release cortisol. Normal blood cortisol levels shut off CRH and ACTH release by the hypothalamus and anterior lobe of the pituitary gland, respectively. Perturbation of this negative feedback control loop can abnormally increase blood cortisol levels. Particular tumors of the anterior lobe of the pituitary (pituitary adenomas) that secrete increased amounts of ACTH cause most cases of Cushing syndrome (Cushing disease). Tumors outside the pituitary also can secrete increased amounts of ACTH (ectopic ACTH syndrome). Lung tumors cause more than half these cases. Sometimes adrenal gland tumors can cause Cushing syndrome. Adrenocortical carcinomas cause high blood cortisol levels and rapid onset of symptoms. Incidence: The majority of Cushing syndrome cases are due to exogenous glucocorticoids. The annual incidence of endogenous Cushing syndrome is estimated at 10 to 15 cases per 1 million individuals.
Risk factors: People who take exogenous steroids, like arthritics or organ transplant patients, and families that show an inherited tendency to develop endocrine gland tumors are at risk of developing Cushing syndrome.
Symptoms: Symptoms of Cushing syndrome include rapid weight gain concentrated around the face (moon face) and trunk; excessive sweating; thinning of the skin that causes easy bruising, poor healing, and stretch marks; muscle weakness, particularly in the shoulders and hips; excessive hair growth in women; and fat pad deposition on the back of the neck and collar bone (buffalo hump). Excess cortisol also causes insomnia, infertility, and psychological disturbances that range from euphoria to psychosis and also commonly include depression, anxiety, and panic attacks. Complications include bone loss and osteoporosis, high blood pressure, kidney stones, type II diabetes, and unusual infections as a result of suppression of the immune system.
Etiology and the disease process: The adrenal glands lie on top of the kidneys, and the hormone cortisol is made by the outer layer (cortex) of the adrenal glands. Cortisol maintains blood sugar levels and blood pressure, reduces
Screening and diagnosis: The urinary free cortisol (UFC) test determines free cortisol concentrations in the urine over a twenty-four-hour period. Urinary cortisol concentrations higher than three to four times the normal level
Category: Diseases, symptoms, and conditions Also known as: Cushing’s syndrome, hypercortisolism, hyperadrenocorticism Related conditions: Polycystic ovary syndrome, pseudoCushing’s syndrome Definition: Cushing syndrome is an endocrine disorder that results from prolonged exposure of the body to high levels of the hormone cortisol.
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Salem Health: Cancer (50 to 100 micrograms a day) are highly suggestive for Cushing syndrome. However, measuring cortisol in saliva at nighttime has become more popular. High salivary cortisol levels are also indicative of Cushing syndrome. The dexamethasone suppression test determines the location of the abnormality. Dexamethasone mimics the physiological effects of cortisol, inhibiting ACTH release by the anterior lobe of the pituitary gland and decreasing cortisol production. If an ectopic source of cortisol production exists, then dexamethasone administration should not decrease blood or urine cortisol levels. Low-dose and high-dose dexamethasone tests are combined, and if there is no change in cortisol levels before and after dexamethasone administration for either test, an adrenal or ectopic ACTH-producing tumor is indicated. No change for the low-dose test and normal suppression in the high-dose test indicate a pituitary tumor. The CRH stimulation test further distinguishes between pituitary and ectopic ACTHproducing tumors. After an injection of CRH, patients with pituitary adenomas usually experience a rise in blood levels of ACTH and cortisol, but those with ectopic ACTH syndrome and cortisol-secreting adrenal tumors show no such response. If the endocrine tests are positive for Cushing syndrome, computed tomography scans of the chest and abdomen or magnetic resonance imaging of the pituitary gland can detect tumors of the adrenal glands or pituitary gland that might be producing excessive cortisol or ACTH. Treatment and therapy: Reducing the use of corticosteroid drugs can ameliorate the symptoms of exogenous Cushing syndrome. In the case of endogenous Cushing syndrome, surgery is recommended for tumors producing ACTH or cortisol. Radiation therapy is sometimes required to completely extirpate the tumor. Drugs that reduce cortisol production such as ketoconazole (Nizoral), mitotane (Lysodren), or metyrapone (Metopirone) can normalize cortisol blood levels and are given before surgery for those who are quite ill or to those for whom surgery and radiation were not completely successful. Prognosis, prevention, and outcomes: If left untreated, Cushing syndrome is lethal, but with treatment, most patients experience some relief of symptoms and cortisol normalization. Michael A. Buratovich, Ph.D. u
For Further Information Blevins, Lewis, S., ed. Cushing’s Syndrome. New York: Springer, 2002. Gaillard, Rolf C., ed. The ACTH Axis: Pathogenesis, Diagnosis, and Treatment. New York: Springer, 2003.
Cutaneous breast cancer Parker, James N., and Philip M. Parker, eds. The Official Patient’s Sourcebook on Cushing’s Syndrome: A Revised and Updated Directory for the Internet Age. San Diego, Calif.: Icon Health, 2002. Walsh, Mary. Cushing’s Syndrome, A Patient Guide: One Woman’s Journey. Rye, N.Y.: New Mill Press, 2001. Zuckerman, Eugenia, and Julie R. Ingelfinger. Coping with Prednisone (and Other Cortisone-Related Medicines): It May Work Miracles, but How Do You Handle the Side Effects? 2d ed. New York: St. Martin’s Griffin, 2007. u
Other Resources
MedlinePlus Cushing Syndrome http://www.nlm.nih.gov/medlineplus/ency/article/ 000410.htm National Endocrine and Metabolic Diseases Information Services Cushing’s Syndrome http://www.endocrine.niddk.nih.gov/pubs/cushings/ cushings.htm See also Adrenal gland cancers; Adrenocortical cancer; Carney complex; Endocrine cancers; Hepatomegaly; Hormonal therapies; Neuroendocrine tumors; Paraneoplastic syndromes; Pituitary tumors; Urinanalysis.
u Cutaneous breast cancer Category: Diseases, symptoms, and conditions Related conditions: Inflammatory breast cancer (IBC), melanoma of the breast, Paget disease of the breast Definition: Cutaneous breast cancer is the metastatic spread of a primary breast cancer to the skin. The most common site of skin metastases is to the affected breast, but it may also metastasize to the axilla, back, scalp, face, neck, extremities, around the ear, and above the clavicle. Risk factors: Although cutaneous cancer can occur with many types of cancer, it is most common with breast cancer and is associated with a history of breast cancer. It is not known why some breast cancers metastasize to the skin. Etiology and the disease process: Cutaneous breast cancer develops when the cancer cells invade the bloodstream or lymphatic system. For cutaneous cancer to develop, the 341
Cutaneous T-cell lymphoma (CTCL) cancer cells must evade the body’s immune defenses and then settle on the skin, where they invade the tissue. Incidence: Cutaneous breast cancer is relatively rare. It is estimated that from 0.7 to 10.4 percent of breast cancer patients will develop skin metastases. Symptoms: The symptoms of cutaneous breast cancer are changes in the skin, most commonly over the site of the primary breast cancer or on the mastectomy incision. There are several types of cutaneous lesions that can develop. The most common are reddened nodules (lumps) and papules (pimple-like lesions). There may also be purple papules, nodules, and plaques (flat, raised patches). Sometimes only a reddened, raised patch develops. The patch appears inflamed and has a defined margin. The last type is a large, purple plaque that has infiltrated the tissue. Screening and diagnosis: There is no screening in particular for cutaneous breast cancer. A diagnosis of cutaneous breast cancer is verified by skin biopsy. Cutaneous breast cancer is not staged as a separate entity because it is a sign of metastases of breast cancer and indicates Stage III or IV breast cancer. Treatment and therapy: Cutaneous breast cancer may be surgically excised, treated with photodynamic therapy, or cryotherapy (freezing). Systemic chemotherapy may be administered, or a topical cream called imiquimod 5 percent (Aldara) may be applied. Treatment is performed to improve the patient’s quality of life. Prognosis, prevention, and outcomes: Because it is a sign of advanced breast cancer, the presence of cutaneous breast cancer is indicative of a poor prognosis. There is no way to prevent it. Christine M. Carroll, R.N., B.S.N., M.B.A. See also Breast cancer in men; Clinical breast exam (CBE); Comedo carcinomas; Ductal carcinoma in situ (DCIS); Invasive ductal carcinomas; Nipple discharge.
u Cutaneous T-cell lymphoma
(CTCL) Category: Diseases, symptoms, and conditions Also known as: Anaplastic large-cell lymphoma, cutaneous anaplastic large-cell lymphoma, granulomatous slack skin, lymphomatoid papulosis, lymphoproliferative disorder, pagetoid reticulosis, reticulum cell sarcoma of the skin, Woringer-Kolopp disease 342
Salem Health: Cancer Related conditions: Adult T-cell leukemia and lymphoma, follicular mucinosis, mycosis fungoides, nonHodgkin lymphoma, peripheral T-cell lymphoma, Sézary syndrome Definition: Cutaneous T-cell lymphoma (CTCL) is a type of non-Hodgkin lymphoma that mainly affects the skin. It is an uncontrolled growth of T cells, a type of white blood cell. “Cutaneous” means that this disease affects the skin. Sézary syndrome is a type of CTCL in which the skin, lymph nodes, and blood are all affected. Mycosis fungoides is another kind of CTCL in which only the skin and lymph nodes are affected. Risk factors: What causes CTCL is not known. Usually people with lymphomas have some type of gene mutation; however, if there is an exact mutation associated with this type of cancer, it is still unknown. In some patients, this disease may be associated with a preexisting allergic condition or a viral infection. Currently, researchers are investigating whether there is a connection between this disease and viruses and whether environmental factors have any association with this disease. Etiology and the disease process: Most types of nonHodgkin lymphoma do not affect the skin. However, CTCL is different in that it mostly affects skin cells. This disease often starts with a rash that itches, sometimes to the point of interrupting sleep, or very dry skin. It may progress to red, scaly patches on the skin, called plaques, that spread to larger areas of skin. The skin may also have tumors that may become infected or turn into bloody sores. This disease may progress to the lymph nodes and, in advanced cases, can spread to the spleen, liver, and intestines. In some cases, this type of lymphoma may begin to act like a more aggressive Hodgkin lymphoma. Incidence: CTCL is quite rare. In the United States, only about 1,500 new cases of CTCL are diagnosed each year. People between the ages of forty and sixty are most likely to get this type of cancer, and children rarely have it. Men are twice as likely as women to develop CTCL, and it is slightly more common in African Americans than in those of other racial backgrounds. Symptoms: Symptoms of CTCL include a rash; red, scaly, itchy skin; and skin tumors. Screening and diagnosis: A physical examination is helpful in diagnosing CTCL. However, since CTCL’s effect on the skin is similar to that of many other conditions, a diagnosis of CTCL involves a biopsy of the affected skin. This skin is then examined under a microscope to determine if T cells are growing abnormally. Diagnosis may
Salem Health: Cancer also involve blood tests to determine if the cancer has spread to the blood system. Computed tomography (CT) or magnetic resonance imaging (MRI) scans may be used to look at lymph nodes to determine if the disease has spread to them. One type of staging of CTCL involves three stages; however, the disease does not always progress through these stages. • Pretumor stage: Small raised patches appear on the skin, usually on the breast or buttocks, though they may appear anywhere. These patches may resemble eczema. Most patients never progress beyond this stage. • Plaque stage: Red patches appear on the skin, and sometimes there is no hair growth in these patches. These irregularly shaped patches, called plaques, may appear anywhere on the body but are usually on the face or buttocks or in the skin folds. • Tumor stage: Tumors, or raised lumps, begin to appear on the skin. These tumors and the plaques may become ulcers (bleeding sores). Sometimes the lymph nodes are affected at this stage, and occasionally, the cancer affects internal organs such as the spleen, liver, or lungs at this stage. This disease may also be called Sézary syndrome, especially if it progresses to the point of having many abnormal lymphocytes in the blood. Sometimes in Sézary syndrome, the entire skin is red, thick, swollen, and itchy. Non-Hodgkin lymphomas are often graded into low grade (slow growing) or high grade (fast growing). CTCL is a low-grade non-Hodgkin lymphoma. Another type of staging of the disease, associated particularly with Sézary syndrome, is as follows: • Stage I: Only parts of the skin are affected with a red, scaly rash. There are no tumors, and lymph nodes are normal. • Stage II: The lymph nodes are normal or enlarged but have no cancerous cells, and the skin has red, scaly rash but no tumors, or the lymph nodes are normal or enlarged but do not contain cancerous cells, and the skin has tumors. • Stage III: Most of the skin is affected by the red, scaly rash, but the lymph nodes, either normal or enlarged, do not contain cancerous cells. • Stage IV: In addition to the skin rash, either cancer cells are in the lymph nodes or cancer cells have spread to other organs.
Cutaneous T-cell lymphoma (CTCL) If only small areas of the skin are affected, the disease can be treated by radiotherapy or electronic beam radiation. High-energy rays are directed at the affected skin, killing the abnormal lymphocytes while minimizing the damage to the healthy cells. This treatment is most effective during the early stages of the disease. It may also be used on the entire body if the cancer has not spread below the outer layer of the skin. Another type of topical therapy is UVB (ultraviolet light B) therapy. The patient’s skin is exposed to UVB, which can help slow down the growth of skin cells. CTCL can also be treated by a type of chemotherapy in which drugs are applied directly to the skin using a cream, gel, or ointment. If the cancer becomes much worse or is not responding to other types of therapy, conventional chemotherapy, where drugs are injected into the bloodstream, may also be used. Photochemotherapy, a combination therapy, may be used if the cancer affects a large area of skin. A patient takes certain drugs that make the skin very sensitive to a type of ultraviolet light called ultraviolet light A. After the drugs have had time to affect the tumors, the skin is exposed to ultraviolet light A, which kills the tumors in the skin. Researchers are investigating oral drugs and immunotherapy (therapy that uses the body’s own immune system to fight the disease) that may be useful for CTCL patients. Prognosis, prevention, and outcomes: CTCL may stay only in the skin for several years, and many patients can lead normal lives for quite some time while controlling the disease with treatment. Outcomes for CTCL depend on the type of disease the patient has, how quickly the disease is progressing, and how well the patient is responding to therapy. Prognosis for patients with mycosis fungoides is usually good, as this type of CTCL usually affects only the skin, and patients are generally diagnosed early in the disease process. These patients have a median survival rate of more than twelve years. Those with Sézary syndrome generally have a more limited prognosis with a median survival of five years as this disease extends into the blood system. Patients whose internal organs are affected have a median survival of two to four years. Marianne M. Madsen, M.S. u
Treatment and therapy: Treatments for CTCL involve treating the skin either topically (on the surface), systemically (through the blood), or a combination of both. Treatment may control the disease, but if a patient does not continue treatment, the disease may recur.
For Further Information Greer, John P., et al., eds. Wintrobe’s Clinical Hematology. 11th ed. Philadelphia: Lippincott Williams & Wilkins, 2004. Souhami, Robert, et al., eds. Oxford Textbook of Oncology. 2d ed. New York: Oxford University Press, 2002. 343
Cyclin-dependent kinase inhibitor-2A (CDKN2A) Zackheim, Herschel, ed. Cutaneous T-cell Lymphoma: Mycosis Fungoides and Sézary Syndrome. Boca Raton, Fla.: CRC Press, 2005. u
Other Resources
Cutaneous Lymphoma Foundation http://www.clfoundation.org Leukemia and Lymphoma Society http://www.leukemia-lymphoma.org Lymphoma Information Network http://www.lymphomainfo.net See also Mycosis fungoides; Sézary syndrome.
u Cyclin-dependent kinase
inhibitor-2A (CDKN2A) Category: Cancer biology Also known as: CDKN2, CDK4 inhibitor, multiple tumor suppressor 1 (MTS1), TP16, p16INK4a, p14ARF Definition: Cyclin-dependent kinase inhibitor-2A (CDKN2A) is a tumor-suppressor gene located on chromosome 9p21. The gene’s role: As a tumor-suppressor gene, CDKN2A plays a major role in regulating cell division. The loss of function of a tumor-suppressor gene is a key event in the multistep process that transforms a normal cell into a cancer cell. In normal cells, the proteins that arise from these genes play a role in regulating cell growth and proliferation. A loss of function of these genes by mutation results in uncontrolled cell growth that leads to cancer. The chromosomal region where CDKN2A is located is often mutated in cancer cells. The CDKN2A gene locus on chromosome 9p21 codes for two proteins, p16INK4a and p14ARF, both of which inhibit the cell cycle. Cyclin-dependent kinases (CDKs) have two subunits: a kinase subunit (cdk) and a cyclin that activates the kinase. Regulating the function of CDKs is another group of proteins known as the cyclin kinase inhibitors. The protein coded for by CDKN2A belongs to the cyclindependent kinase inhibitor family of proteins. It binds to CDKs and acts as an inhibitor of cell division. Disruption of the function of the CDKN2A gene, therefore, has major consequences on the normal functioning of a cell. Cancer and the gene: Unlike other tumor-suppressor genes that are inactivated by point mutations, inactivation 344
Salem Health: Cancer of CDKN2A occurs through homozygous deletions, mutations, or promoter methylation. Mutations in the CDKN2A gene are known to occur in patients with multiple primary myelomas. Inactivation of CDKN2A has also been reported in numerous primary tumors, including bladder carcinoma, glioma, mesothelioma, gastrinomas, T-cell acute lymphoblastic leukemia, melanoma, prostate adenocarcinoma, and renal cell carcinoma. Some gene alterations that have been observed in different cancers related with alteration in the structure or function of CDKN2A include hypermethylation of CDKN2A in gastrinomas, germ-line mutation in CDKN2A in pancreatic cancer and melanoma, and inactivation of CDKN2A in sporadic pancreatic cancers. An increased risk of melanoma and pancreatic cancer exists in individuals with CDKN2A mutations. Clinical observations such as detection of germ-line mutations in CDKN2A in melanoma-prone families, increased risk of pancreatic cancer among melanoma-prone families with CDKN2A mutations, and zero occurrence of pancreatic cancer in melanoma-prone families without the CDKN2A germ-line mutation suggest a link between CDKN2A mutations and occurrence of melanoma and pancreatic cancer. Families with co-occurrence of pancreatic cancer and melanoma should participate in clinical screening programs for CDKN2A mutations. This would enable identification of high-risk family members and a more improved individual risk assessment for better outcomes for CDKN2A mutation carriers. Banalata Sen, Ph.D. See also BRCA1 and BRCA2 genes; Hereditary cancer syndromes; MYC oncogene; TP53 protein.
u Cyclooxygenase 2 (COX-2)
inhibitors Category: Chemotherapy and other drugs ATC code: 101XX, M01AH Definition: Cyclooxygenase 2 (COX-2) inhibitors are a type of nonsteroidal anti-inflammatory drug (NSAID) that inhibits the COX-2 enzyme, which is involved in inflammation and cancer. Cancers treated: Primarily colorectal cancers, such as familial adenomatous polyposis (FAP); others under investigation, including breast, head and neck, lung, and pancreatic cancers
Salem Health: Cancer Delivery routes: These drugs are administered orally as either capsules or tablets and can be taken on an at-home basis.
Cyclophosphamide
Cyclooxygenase 2 (COX-2) Inhibitors Drug
Brand
Delivery Mode
Cancers Treated
Celecoxib
Celebrex
Oral
Familial adenomatous polyposis (FAP); others under investigation
How these drugs work: The COX Rofecoxib Vioxx Oral None (removed from market in enzymes catalyze the production of 09/2004) hormones called prostaglandins, which Valdecoxib Bextra Oral None (removed from market in stimulate cells to produce inflamma05/2005) tory responses. COX-1 is always expressed and is found in many tissues. Its inhibition can reduce inflammation but may also cause serious gastrointestinal side effects. In contrast, COX-2 is expressed only u Cyclophosphamide in response to stimulation signals and is present in a limited number of tissues. COX-2 is overexpressed, however, Category: Carcinogens and suspected carcinogens; in several cancers, correlating with poorer overall surchemotherapy and other drugs vival. Therefore, COX-2 inhibitors are being investigated RoC status: Known human carcinogen since 1980 for the treatment and prevention of cancer. Also known as: Cytoxan, Neosar COX-2 contributes to tumor growth by enhancing tumor cell proliferation and survival, inhibiting the body’s Related cancers: Bladder cancer, myeloproliferative and immune response to cancer, and inducing the development lymphoproliferative malignancies (leukemias) of new blood vessels that feed a tumor and help it spread to Definition: Cyclophosphamide is a highly toxic, antiother parts of the body. Because the active sites of the cancer drug that belongs to a family of drugs known as COX enzymes differ, COX-2 inhibitors can form tight alkylating agents. It is a derivative of nitrogen mustard. complexes with COX-2 that dissociate slowly, thereby blocking enzyme activity. These inhibitors only loosely Exposure routes: Orally or by intravenous injection as and reversibly bind to COX-1, however, with no effect on part of medical treatment. Skin contact or dust inhalation its activity. Blocking only COX-2 may reduce tumor is possible during the manufacturing process and in hancell growth and survival and improve immune responses dling of the drug during preparation and administration. against tumor cells without the risk of severe gastrointestinal complications as seen with COX-1 inhibition. Where found: Cyclophosphamide is used in the treatment of various cancers, including lymphoma and leukemia, in Side effects: The major side effects of COX-2 inhibitors bone marrow transplant as part of a peripheral stem cell are cardiovascular, such as increased risks of blood clots, mobilization or preparative regimen, as an immune supheart attack, stroke, and high blood pressure. This has led pressive agent following bone marrow or solid organ to two drugs, Vioxx (rofecoxib) and Bextra (valdecoxib), transplant, and to treat autoimmune disorders such as being removed from the market by the Food and Drug Adrheumatoid arthritis. ministration (FDA). COX-2 inhibitors may also cause indigestion, stomach bleeding, ulcers, and perforation of the At risk: People who have been previously treated with stomach or intestines. Long-term administration may recyclophosphamide alone or in association with other chesult in kidney toxicity and (rarely) liver toxicity. Allergic motherapy drugs; health professionals (nurses, pharmaskin rashes may also occur with celecoxib (Celebrex). cists, physicians) who handle the drug during preparation, Elizabeth A. Manning, Ph.D. administration, and cleanup; and workers involved in the See also Angiogenesis; Bone pain; Desmoid tumors; Hereditary polyposis syndromes; Nonsteroidal anti-inflammatory drugs (NSAIDs); Pain management medications; Premalignancies.
manufacturing process. An estimated 500,000 patients are treated with cyclophosphamide annually. The general population is not considered to be at risk. Etiology and symptoms of associated cancers: Cyclophosphamide is used to treat cancer, but studies show that it can cause a secondary cancer as a long-term side effect. 345
Cyclosporin A It is a cytotoxic drug that affects the growth of cancer cells by interfering with the deoxyribonucleic acid (DNA) within the cells. Normal, noncancerous cells are affected as well, causing side effects that may include inflammation and bleeding from the bladder (hemorrhagic cystitis), bone marrow suppression, nausea and vomiting, and hair loss (alopecia). It is the damage to cellular DNA that can lead to a secondary cancer months or years after treatment with cyclophosphamide. Patients who experience hemorrhagic cystitis during treatment with cyclophosphamide have been shown to be at a higher risk of bladder cancer after treatment. Signs and symptoms of bladder cancer include blood in the urine (hematuria), pelvic pain, pain during urination, and a frequent urge to urinate. Patients who are treated with cyclophosphamide for primary myeloproliferative or lymphoproliferative malignancies (leukemia) are at a higher risk for a secondary hematologic malignancy (leukemia) as a long-term side effect of treatment. The symptoms of secondary acute leukemia include recurrent infections, bone and joint pain, swollen lymph nodes, and shortness of breath. History: Cyclophosphamide was first synthesized in 1958. The first clinical trials were published at the end of the 1950’s. It has been in widespread use as a chemotherapeutic agent since the 1960’s. Melanie Hawkins, B.S.N., R.N., O.C.N. See also Adrenal gland cancers; Bladder cancer; Burkitt lymphoma; Carcinoid tumors and carcinoid syndrome; Estrogen-receptor-sensitive breast cancer; Myeloproliferative disorders; Nasal cavity and paranasal sinus cancers.
u Cyclosporin A Category: Chemotherapy and other drugs; carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1998 Also known as: Cyclosporin, ciclosporin, cyclosporine, CsA, CYA, Sandimmune, Neoral, Restasis, Gengraf, Cicloral Related cancers: Lymphoma, skin cancer Definition: Cyclosporin A is a drug approved by the U.S. Food and Drug Administration, now marketed as an immunomodulator. It is a short polypeptide with eleven amino acids, eight of which form a ring. Exposure routes: Oral, intravenous, or topical administration 346
Salem Health: Cancer Where found: Commercially available in pharmacies At risk: People given the drug for therapeutic immunosuppression Etiology and symptoms of associated cancers: Cyclosporin A modifies the immune response by inhibiting calcineurin in lympocytes (primarily T cells); calcineurin is then unable to normally activate transcription of interleukin-2. It also inhibits release of the important proapoptotic factor cytochrome C from mitochondria. Although not important in modulating the immune response, the deficit of cytochrome C may slow or prevent normal apoptosis and act as a pro-survival factor for malignant cells. Another mechanism by which cyclosporin A promotes cancer progression is independent of immune cell inhibition; this direct carcinogenicity involves activation of transforming growth factor beta (TGF-β). Tumors in transplant recipients may arise from the recipient’s cells or from cells brought in with the transplanted organ, whereby premalignant donor cells are no longer subject to the surveillance of an intact immune system. Symptoms of lymphoma include fatigue, enlarged and painful lymph glands, and elevated white blood cell counts. Skin cancer is usually detected by visual inspection. In some patients, tumors become apparent within a few weeks of treatment initiation, and in some cases discontinuation of the drug is followed by tumor remission. History: As part of a drug discovery effort, soil samples from Norway were tested and found to have immunosuppressive activity in the early 1970’s; the active component was found to be a small peptide produced by the fungus Tolypocladium inflatum Gams. The drug was first administered to prevent transplanted organ rejection in 1980 and was approved for this indication in 1983. Transplant recipients were soon found through registry data to have a threefold to fivefold increased risk of cancer compared with the general population, with more aggressive malignancies and overall poorer prognosis. Despite the increased risk of cancer, cyclosporin A has since been approved for other indications, including prevention of graftversus-host disease (GVHD), psoriasis, rheumatoid arthritis, nephrotic syndrome, and keratoconjunctivitis sicca (dry eyes). The drug continues to be widely used, and efforts to minimize post-transplant malignancies continue. John B. Welsh, M.D., Ph.D. See also Aplastic anemia; Edema; Fibroadenomas; Graftversus-host disease (GVHD); Myasthenia gravis; Pancolitis; Paraneoplastic syndromes; Sjögren syndrome.
Salem Health: Cancer
u Cystography Category: Procedures Definition: Cystography is a procedure in which dye is injected into the bladder and X rays are taken to examine the organ. Cancers diagnosed: Cancers of the bladder and urinary system, prostate cancer Why performed: Cystography is performed to allow doctors to get a detailed picture of the bladder to check for problems such as cancerous growths. Patient preparation: Before the procedure, the patient may be asked to refrain from eating solid food for a period of time. The patient may be asked not to drink any fluids or may be asked to drink an increased amount of fluids, depending on the type and purpose of the procedure. Steps of the procedure: The patient is asked to urinate to empty the bladder as the first step of the procedure. Then a catheter is inserted into the bladder. Through the catheter, a contrast dye is injected into the bladder, until the bladder is full. The patient will experience the feeling of a need to urinate as a result of the fullness of the bladder. Once the dye has been injected, X rays are taken of the bladder. If the patient is male, then a lead shield will be used to protect the testes from the X-radiation. The patient may be asked to move into several different positions to allow for different views of the bladder. Once all the X rays needed have been taken, the catheter is removed and the patient is allowed to expel the dye. After the procedure: After the procedure, the patient may be advised to drink a large amount of clear fluids for a few days to help flush the dye out of the bladder. Because of the dye, the patient’s urine may be an unusual color. Risks: Some risks are associated with cystography. There is a small risk of infection because of the insertion of the catheter, as well as a small risk of allergic reaction to the injected dye. This procedure is generally not advised for women who are pregnant because exposure to X-radiation can harm the fetus. Results: The cystography will provide the health care team with detailed pictures of the patient’s bladder to use in evaluating the presence of cancerous growths and other bladder problems. Patients generally do not experience any long-term side effects from the procedure. Robert Bockstiegel, B.S.
Cystoscopy See also Bladder cancer; Cystoscopy; Prostate cancer; Transitional cell carcinomas; Urethral cancer; Urinary system cancers; Urography; Urologic oncology; Urostomy.
u Cystoscopy Category: Procedures Also known as: Cystourethroscopy Definition: During urination, urine moves from the bladder, through the urethra tube, and to the outside of the body. Cystoscopy uses a cystoscope (a thin tube with a miniature camera and light) to allow a doctor to see, examine, and biopsy abnormal tissues inside the urethra and bladder. This procedure is used to check for possible cancer cells. Cancers diagnosed: Bladder and urethral cancer; followup for renal pelvis and ureter cancer Why performed: Cystoscopy is primarily a diagnostic procedure used to view the inside of the bladder and urethra. Suspicious tissues are biopsied with a clipper on the end of the cystoscope. The tissue samples are examined in a laboratory for the presence of cancer cells. Patient preparation: Cystoscopy is performed with general or local anesthesia. Patients receiving general anesthesia should not eat or drink after midnight prior to the day of the procedure. Patients may be asked to provide a urine sample prior to the cystoscopy. The urine sample is tested for the presence of infection. Patients will wear an examination gown for the procedure. Steps of the procedure: The patient is usually positioned on the back with the knees spread. The lower body is covered with a sheet. The opening of the urethra is cleansed, and a pain-relieving medication is applied. The cystoscope is inserted through the urethral opening and into the bladder. Sterile fluid travels through the cystoscope into the bladder to expand the folds in the bladder and provide the doctor with a good view of the bladder lining. A biopsy is taken of any abnormal-looking tissue. The procedure is short, usually lasting only a few minutes, after which time the fluid and cystoscope are removed. The patient can empty the bladder when the cystoscopy is complete. After the procedure: Patients may experience a burning sensation while urinating or blood in their urine for about twenty-four hours after the procedure. Antibiotics may be prescribed. Patients should drink plenty of water. 347
Cytogenetics
Salem Health: Cancer breakage of chromosomes is used to diagnose cancers. Many cancers are defined by cytogenetic test results. Subspecialties: Oncology cytogenetics, reproductive cytogenetics, molecular cytogenetics Cancers treated: All
A doctor uses a cytoscope to examine a patient. (©Yoav Levy/ Phototake—All rights reserved)
Risks: There is a slight risk of bladder perforation during the procedure or infection following the procedure. Men should contact their doctors immediately if testicular swelling occurs. Results: A healthy bladder wall appears smooth. Suspicious growths are biopsied to determine whether cancer is present. Mary Car-Blanchard, O.T.D., B.S.O.T. See also Bladder cancer; Cystography; Hematuria; Renal pelvis tumors; Transitional cell carcinomas; Urinary system cancers; Urography; Urologic oncology; Urostomy.
u Cytogenetics Category: Medical specialties Also known as: Chromosome analysis, karyotyping Definition: Cytogenetics is the study of chromosomes as seen under the microscope. Observation of gain, loss, or 348
Training and certification: Technologists perform cytogenetic analysis under the direction of laboratory directors and technical supervisors. Laboratory directors and technical supervisors are medical doctors or scientists with doctoral degrees experienced in cytogenetics and certified by the American Board of Medical Genetics; in addition, they may be required to pass state board examinations. Supervisors and technologists are certified by the National Credentialing Agency (NCA). NCA certification is not required to practice in the United States. California, Florida, and New York require professional licensing for cytogeneticists to practice. The licenses very closely follow the requirements of the NCA certification. NCA certification as a clinical laboratory specialist in cytogenetics, or CLSp (CG), is available to those who have appropriate educational backgrounds, including a bachelor’s degree, specialized training in cytogenetics, one year of experience in a cytogenetics laboratory, and satisfactory completion of an exam. Supervisors must take an additional exam to qualify as supervisors. NCA certification must be maintained through continuing education. Those with a bachelor’s degree may participate in training programs available at cytogenetics laboratories before applying for NCA certification. College-based programs also exist at Kennesaw State University, the University of Connecticut, the University of Texas M. D. Anderson Cancer Center, Northern Michigan University, Texas Tech University, the University of Kansas, and the University of Texas, San Antonio. Services and procedures performed: In cytogenetic analysis, cells are collected from a patient and then grown in cell culture. The cells are chemically treated so that the chromosomes are visible. The cells are grown in culture media that support the growth of that particular cell type. A chemical that stops cells during cell division is used to arrest the dividing cells at the metaphase stage, when the chromosomes are most condensed. Depending on the specimen type, the chromosomes may be grown on or dropped onto microscope slides. The resulting slides are then stained using various special techniques. The staining results in a unique banding pattern for each of the chromosomes. This allows the identification of the chromosomes and enables cytogeneticists to identify
Salem Health: Cancer
Cytogenetics
abnormal chromosomes. Multiple cells are analyzed by the technicians. The entire process—from collecting the sample at the physician’s office or hospital to processing, analysis, and reporting the results to the physician—varies depending on the tissue type. The cell growth can take a few days to more than a week. The results are given in the form of a photograph of the chromosomes (a karyotype) and a written report. The karyotype shows the chromosomes aligned and paired by their numerical classification. After the metaphase cells are karyotyped, it is much easier to compare the bands and to identify abnormalities. Typical abnormal results include the loss of a chromosome, the gain of additional chromosomes, the loss of part of a chromosome, inversions (when a middle piece of one chromosome is turned upside down), and translocations (when two or more chromosomes break and exchange parts). One or many changes may happen in any one tumor cell, and the cancer can be complicated by having many different, related cancer cell lines that are mutating and changing continuously. The changes can include loss or gain of different abnormal chromosomes and structural abnormalities. Doctors can interpret the kinds of cancer and the severity based on the results of cytogenetic tests. After successful treatment, subsequent cytogenetic testing should show normal chromosomes.
somes can be “probed” with tiny pieces of fluorescently labeled DNA. DNA will attach to other DNA of the same kind (complementary sequences). For example, a fluorescent probe for the TP53 cancer oncogene (also known as p53) may be used to identify the presence or absence of the TP53 gene on a patient sample. If the TP53 gene is present, the probe will attach. A fluorescent microscope will reveal a visible signal in the location of the TP53 gene. An abnormal specimen would be lacking that signal, indicating a deletion of the TP53 gene. Christopher Pung, B.S., C.L.Sp. (CG)
Related specialties and subspecialties: In addition to studying cancer, cytogeneticists can identify birth defects such as Down syndrome, in which an extra chromosome 21 can be observed. This use of chromosome analysis is referred to as reproductive cytogenetics. Amniocentesis specimens are most commonly used in reproductive cytogenetics. Beginning in the 1990’s, a new branch of cytogenetics, molecular cytogenetics, began to develop. Deoxyribonucleic acid (DNA) based tests are being applied to samples processed by cytogeneticists. Molecular cytogenetics is rapidly becoming its own specialty as new tests are being developed in conjunction with the growing understanding of the molecular basis of chromosome abnormalities. Most molecular cytogenetic tests are being performed with the fluorescence in situ hybridization (FISH) technique, which uses the complementary nature of DNA to answer specific questions about particular regions of the DNA. FISH can be used to identify abnormalities that may be too small to be seen using conventional cytogenetic methods. Microscope slides prepared to analyze chromo-
National Credentialing Agency http://www.nca-info.org P.O. Box 15945-289 Lenexa, KS 66285
u
For Further Information Harper, Peter S. First Years of Human Chromosomes: The Beginnings of Human Cytogenetics. Bloxham, England: Scion, 2006. Heim, Sverre, and Felix Mitelman. Cancer Cytogenetics. 2d ed. New York: Wiley-Liss, 1995. Mark, Hon Fong L., ed. Medical Cytogenetics. Boca Raton, Fla.: CRC Press, 2000.
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Organizations and Professional Societies
Association of Genetic Technologists http://www.agt-info.org P.O. Box 15945-288 Lenexa, KS 66285
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Other Resources
Mountain States Genetic Foundation Molecular Cytogenetics (FISH) http://mostgene.org/gd/gdvol13c.htm NCI-Frederick Comparative Molecular Cytogenetics Core Facility http://www.ncifcrf.gov/research/cytogenetics/ default.asp See also Blood cancers; Chromosomes and cancer; Chronic myeloid leukemia (CML); Genetics of cancer; Klinefelter syndrome and cancer; Leukemias; Myelodysplastic syndromes; Myeloproliferative disorders; Neuroblastomas; Nijmegen breakage syndrome; Pathology.
349
Cytokines
u Cytokines Category: Cancer biology; chemotherapy and other drugs ATC code: LO3-LO3AX Also known as: Lymphokines, monokines, interleukins and interferons, tumor necrosis factors, chemokines, granulocyte colony-stimulating factor Definition: Cytokines are a class of (mainly water-soluble) proteins or glycoproteins produced by white blood cells (immune system cells). Cytokines carry chemical messages between cells and are of particular importance in both the innate and the adaptive immune response. Immune cell activity can be stimulated or inhibited, or can stimulate or inhibit the activity of other cells. There are many cytokine subclasses. Cytokines are produced naturally by immune cells in the body and can also be produced in the laboratory.
Salem Health: Cancer syndrome, low blood pressure, high cardiac output. liver toxicity, renal toxicity, pulmonary edema, fever, chills, gastric acidity, and infection. Most of the toxic side effects can be reversed. Fever and chills are treated with acetominophen and antibiotics are used for infection. Cytokine storm is a syndrome that can occur with the overstimulation of cytokines and can result in severe adverse effects and death. Janet R. Green, M.S.P.H. See also Anthraquinones; Appetite loss; Bacillus Calmette Guérin (BCG); Beryllium and beryllium compounds; Biological therapy; Exercise and cancer; Fever; Gene therapy; Human growth factors and tumor growth; Immune response to cancer; Immunotherapy; Interferon; Interleukins; Tumor necrosis factor (TNF); Vaccines, therapeutic.
Cancers treated: Renal cell carcinoma, melanoma, lymphoma, Kaposi sarcoma, chronic myelogenous leukemia, and hairy cell leukemia; being studied as a treatment for breast cancer and other solid tumors
u Cytology
Delivery route: Subcutaneous or intravenous (IV) injection
Definition: Cytology is the microscopic study of the structure of cells. A cytotechnologist examines cells collected from patients. The purpose is for detection (screening) or diagnosis of cancer, precancerous states, or other diseases.
How these agents work: Cytokines are unique in that they bind to individual cell receptors. They can regulate several parts of the immune system by stimulating the production of cellular molecules that can attach themselves to the surface of tumor cells and have antitumor activity. Other cytokines suppress the activity of cells and thus inhibit their action. Cytokines do not have one mechanism of action, and many aspects of their cellular signaling are being actively researched. They are being investigated for their ability to kill tumor cells and for their potential to act as vaccines or adjuvant stimulants against the development of cancer cells by presensitizing the immune system to kill cancer cells if they develop. Immunotherapy is still being aggressively studied for mechanisms of action, stimulation, and suppression, and it is believed that it will work in conjunction with other therapies rather than alone. The attractiveness of immunotherapy is the specificity of attacking only cancer cells and not harming normal cells, finding small numbers of cancer cells not identified though other treatment modalities, and using the existing immune system to treat cancer. Side effects: Common side effects of cytokine treatment include nausea, vomiting, acute toxicity, capillary leak 350
Category: Medical specialties Also known as: Cytotechnology, cytopathology
Subspecialties: Molecular diagnostics, immunocytochemistry Cancers diagnosed: Primarily cancers of the cervix, uterus, lungs, breast, and urinary tract Training and certification: Cytotechnologists must obtain a baccalaureate degree from an accredited college or university. This includes a twelve-month cytotechnology program accredited by the American Medical Association’s Commission on Accreditation of Allied Health Education Programs (CAAHEP). Students must take classes in biology, chemistry, mathematics, and statistics and must meet general education requirements. Their clinical training may be in a hospital or university. Students learn how to collect and prepare samples for examination, how to use a microscope, how to recognize normal cells, and how to recognize changes in the cells that indicate the presence of disease. After completing course work, students take the American Society for Clinical Pathology (ASCP) Board of Registry (BOR) national certification exam for cytotechnology. If they pass the exam, students receive a certificate
Salem Health: Cancer
Cytology
and can use the initials CT (ASCP) after their name. Some states require state licensure of cytologists. These states are California, Florida, Hawaii, Louisiana, Montana, New York, Rhode Island, Tennessee, and West Virginia. Georgia and Nevada require state certification. Once certified, cytotechnologists must maintain competency through continuing education. The credits earned enable the cytotechnologist to renew certification every three years. In addition, cytotechnologists performing gynecological testing must pass an annual proficiency test. A cytotechnologist may go on to earn certification as a specialist in cytotechnology. A combination of education and work experience in an accredited laboratory under the
supervision of a certified pathologist qualifies the cytotechnologist to take the specialist exam. Cytotechnologists may obtain CT certification and work five years, earn a master’s degree and work four years, or earn a doctorate and work three years. Upon passing the exam, the cytotechnologist is certified as a specialist in cytotechnology and has the right to use the designation SCT (ASCP). Services and procedures performed: Cytologists work in the laboratory, where patients do not usually see them. However, the work they perform and the decisions they make play a major role in the diagnosis and treatment of cancer.
The Methods of Cytology
Cytologists use microscopes to examine cells and fluids obtained through biopsy and separated by centrifugation.
351
Cytology The majority of work performed by cytotechnologists is the screening test for cervical cancer, called a Pap test or smear. Physicians or other health care providers collect the samples by using a small spatula or brush to scrape cells from the cervix. The cells are either spread on a glass slide and a fixative sprayed on the sample, or are placed in a liquid preservative and sent to the cytology laboratory. Relevant patient clinical information is also sent with the sample. The cytotechnologist or an assistant assigns the sample a number. The samples are registered by number in a logbook or computer program. Samples collected in liquid are filtered and the cells are spread evenly on a glass slide. The cytotechnologist or an assistant places the slides in a series of solutions that stain the nuclei and cytoplasm of the cells. A cover slip is placed on the slide and permanently bound to the slide with mounting media. The cytotechnologist works in a quiet environment. Using a microscope, the cytotechnologist examines the slide using a low-power (ten-power, or ×10) objective and a ×10, ×12, or ×10 wide field ocular. The cytotechnologist systematically examines the slide by starting in one corner and going back and forth in a horizontal or vertical direction to ensure that the entire sample is observed. The cytotechnologist looks at the cell structure, including the nucleus (center of the cell) and the cytoplasm that surrounds the nucleus. Changes in the nucleus or cytoplasm may indicate the presence of cancer or precancerous conditions. If unusual cells are noted, a high-power (×40) objective is used to see more detail. These cells are then marked using one of several marking systems. Along with determining if the cells are normal or abnormal, the cytologist determines if there are adequate cells present. If the preparations are adequate and all cells are normal, the cytologist reports the results. All samples with unusual cells are further examined by a pathologist for final reporting of screening results or diagnosis. If the preparations contain an inadequate number of cells, the cytologist will contact the health care provider to collect another sample. Some labs may use an automated imaging system to examine the slides. However, a cytotechnologist must still examine samples that have abnormal findings on the automated system. The cytologist also prepares slides from body fluids such as urine, cerebrospinal fluid, and effusions. Effusions are abnormal accumulations of fluid and may be peritoneal (ascites or abdominal fluid), pleural fluid (fluid surrounding the lungs), or pericardial fluid (fluid surrounding the heart). The fluids are centrifuged to prepare a concentration of cells. The excess fluid is removed, and the cytologist makes a thin preparation of the cells on a glass slide. 352
Salem Health: Cancer The slide is then stained and examined under the microscope. The cytologist may assist radiologists, endocrinologists, or other physicians collecting cellular samples from patients by a technique called fine needle aspiration. The cytologist may examine the material microscopically to determine if an adequate sample was taken before the patient leaves the exam room. The cytologist prepares the slides and stains and examines them in the same manner that the Pap smears are examined for the presence or absence of cancer cells. Related specialties and subspecialties: Cytologists work not only independently but also as part of a team. In a screening or diagnostic cytology laboratory, cytologists always work with a pathologist. Pathologists are medical doctors with specialized training in the examination of tissues, cells, and body fluids. In addition to a medical degree, pathologists complete a three- to four-year residency program. The pathologist examines not only abnormal cytology smears but also tissue samples removed during surgery, directs the clinical laboratory, may perform autopsies, and consults with other physicians. Cytology labs must have a system to obtain both surgical samples and clinical confirmation of cytology results for comparison. Because of this close relationship between cytology and surgical specimens, cytologists also work with histotechnologists (histotologists). Histotechnologists prepare slides from surgical samples for the pathologist to examine under the microscope. A histotechnologist has a baccalaureate degree plus one year of histology laboratory training under the direction of a pathologist. In smaller laboratories, cytotechnologists and histotechnologists may share some functions, such as logging in samples, staining slides, and filing reports. Clinical laboratory scientists (CLS’s) work in the clinical laboratory. They perform cell counts and chemical and microbiology tests on the same types of fluids that the cytology lab may receive. When CLS’s see abnormal cells in a fluid, they check to see if cytology has been ordered. If not, the smear and remaining fluid as well as a copy of the results are sent to the cytology lab for further study. In large laboratories, an assistant under a cytotechnologist’s supervision may perform repetitive work such as assigning sample numbers, recording samples in a logbook, entering data into a computer, staining and adding the cover slip, and filing reports and slides. Cytotechnologists, particularly in specialty or research laboratories, may also work with molecular diagnostics and immunocytochemistry techniques. Wanda E. Clark, M.T. (ASCP)
Salem Health: Cancer u For Further Information Abeloff, Martin D., et al. Clinical Oncology. 3d ed. Philadelphia: Churchill Livingstone/Elsevier, 2004. American Medical Association. Health Professions Career and Educational Directory 2007-2008. 35th ed. Chicago: AMA Press, 2007. Cibus, Edmund S., and Barbara S. Ducatman. Cytology: Diagnostic Principles and Clinical Correlates. 2d ed. Philadelphia: Saunders, 2003. Keebler, Catherine M., and Theresa M. Somrak. The Manual of Cytotechnology. 7th ed. Chicago: ASCP Press, 1997. Koss, Leonard G., and Myron R. Melamed. Koss’ Diagnostic Cytology and Its Histopathologic Bases. 5th ed. Philadelphia: Lippincott/Williams and Wilkins, 2006. Rushing, Lynda, and Nancy Joste. Abnormal Pap Smears: What Every Woman Needs to Know. Amherst, N.Y.: Prometheus Books, 2001. Swanson, Barbara M. Careers in Health Care. New York: McGraw Hill Professional, 2005. u
Cytology American Society for Cytotechnology http://www.asct.com 1500 Sunday Drive, Suite 102 Raleigh, NC 27607 American Society of Cytopathology http://www.cytopathology.org 400 West 9th Street, Suite 201 Wilmington, DE 19801 u
Other Resources
American Cancer Society Testing Biopsy and Cytology Specimens for Cancer http://www.cancer.org/docroot/PED/content/ PED_2_3X_Testing_Biopsy_and_Cytology_ Specimens_for_Cancer.asp?sitearea=PED Papanicolaou Society of Cytopathology http://www.papsociety.org See also Cytogenetics; Hematologic oncology; Molecular oncology; Pathology; Sputum cytology.
Organizations and Professional Societies
American Society for Clinical Pathology http://www.ascp.org 33 West Monroe, Suite 1600 Chicago, IL 60603
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Dana-Farber Cancer Institute
u Dana-Farber Cancer Institute Category: Organizations Definition: The Dana-Farber Cancer Institute, a regional center for basic and clinical cancer research located in Boston, Massachusetts, is a Harvard Medical Schoolaffiliated institution. The institute, along with Massachusetts General Hospital and Brigham and Women’s Hospital (the Data-Farber/Harvard Cancer Center) and Children’s Hospital Boston, work together to provide comprehensive cancer care and treatment. Founding and history: In 1947 Sidney Farber, a Harvard Medical School graduate of the class of 1928, founded the Children’s Cancer Research Foundation. Farber, a pathologist at Children’s Hospital in Boston, was interested in finding a cure for leukemia. He conducted early chemotherapy studies with children who were seriously ill with leukemia and in 1948 published promising results in the New England Journal of Medicine. Funding for Farber’s research came from a charitable organization (the Variety Club of New England) made up of entertainers who wanted to support a local scientist. In 1948 “Jimmy,” a young patient of Farber, was introduced on Truth or Consequences, a popular radio program, and as a result of his appearance on the show, many contributions were made to support Farber’s research. The Variety Club’s patronage project was renamed the Jimmy Fund, a charitable organization for children’s cancer research. The scope of the research foundation was widened in 1969 to include cancer research and treatment for patients of all ages, and the name of the institution was changed to the Sidney Farber Cancer Center (and later modified slightly to the Sidney Farber Cancer Institute) in honor of Farber, who died in 1973. An industrialist, Charles A. Dana, supported the Children’s Cancer Research Foundation with major grants beginning in 1962, and the institution was renamed the Dana-Farber Cancer Institute in 1983 to reflect his generous support. Farber was a pioneer of the concept of total care, believing that all patient and family services, such as clinical care, nutrition counseling, and social work, should be provided in one place. Further, he believed that decisions about the care of a patient should be made by a team consisting of everyone involved in taking care of that patient. Through the years, the Farber family, including siblings, children, and grandchildren of Sidney Farber, have been involved with the Sidney Farber Cancer Institute in roles such as members of the Board of Governors or in initiating new programs. 354
Salem Health: Cancer Current facilities: The Dana-Farber Cancer Institute (DFCI), along with Brigham and Women’s Hospital and Massachusetts General Hospital, provide adult cancer treatment. All three institutions are affiliated with Harvard Medical School, and the program is one of thirty-nine centers nationwide designated by the National Cancer Institute as a comprehensive cancer care center. In 1996, the DFCI, Brigham and Women’s and Massachusetts General formed the Dana-Farber/Partners CancerCare system, and it is the largest such system in the United States. Adult patient care is provided at two locations: the Massachusetts General Hospital Cancer Center and the Dana-Farber/ Brigham and Women’s Cancer Center. Treatment of pediatric cancer patients is provided through a collaboration of the Dana-Farber Cancer Institute and Children’s Hospital Boston. Children’s Hospital is the pediatric teaching hospital for Harvard Medical School. Pediatric outpatient treatment is provided at the Dana-Farber Cancer Center, and pediatric inpatients are treated at Children’s Hospital. There are twelve cancer treatment programs for adults: breast cancer, endocrine cancer, gastrointestinal cancer, genitourinary cancer, gynecological cancer, head and neck cancer, hematologic malignancies, hematology, melanoma, neurologic cancer, sarcoma, and thoracic oncology. Pediatric programs and specialty services include bone and soft-tissue tumors, brain tumors, histiocytosis, Hodgkin disease, kidney tumors, leukemia, neuroblastoma, non-Hodgkin lymphoma, stem cell transplantation, and a pediatric advanced care team. The Dana Farber/Children’s Hospital Cancer Center recognizes the need to address potential late effects of pediatric cancers and has several childhood cancer survivor programs for long-term follow-up of patients. The Dana-Farber Cancer Institute is involved in a wide range of community outreach programs and has a mission to reach underserved and minority groups. Research: Research at Dana-Farber began in 1947 with Farber’s research on chemotherapy for children with cancer and continues today under the Dana-Farber/Harvard Cancer Center (DF/HCC). The DF/HCC comprises the Dana-Farber Cancer Institute, Harvard Medical School, Beth Israel Deaconess Medical Center, Brigham and Women’s Hospital, Children’s Hospital Boston, Massachusetts General Hospital, and Harvard School of Public Health. In 2000 the designation of the DFCI as a comprehensive cancer care center was redefined to include the DF/HCC. Research at the DF/HCC is carried out at eighteen core facilities by hundreds of researchers; the collaborative research programs have made significant contribu-
Salem Health: Cancer tions in areas such as basic cancer cell biology, genetic epidemiology, tumor immunology, and clinical/translational cancer research.
Delta-9-tetrahydrocannabinol pot, reefer, sinsemilla, weed; there are also many names signifying different growing regions and qualities of marijuana
Specialization: The bone marrow transplantation program is one of the nation’s oldest programs of its kind. The Pediatric Brain Tumor Program is the largest such program in the eastern region of the United States. The Quality of Life Clinic at DFCI provides comprehensive follow-up for adult survivors of pediatric cancers. Dana-Farber is a member of the Multiple Myeloma Research Consortium. Vicki Miskovsky, B.S., R.D.
Definition: Delta-9-tetrahydrocannabinol (THC), the psychoactive substance that is the active ingredient in the plant Cannabis sativa (marijuana), is debated as a viable medical treatment. Cancer patients use substances containing THC and its synthetic and derivative forms to relieve nausea and vomiting. Patients with human acquired immunodeficiency syndrome (AIDS) also use these substances to combat weight loss.
u
Delivery routes: Drugs such as Marinol capsules and Cesamet pills are taken orally. Dried forms of marijuana, including buds of flowers and leaves, pieces of leaves, seeds, and stems, are smoked in marijuana cigarettes or pipes; burned and vaporized using other means; or ingested in foods such as baked cookies. Cannabis sativa also may be used to produce the drug hashish, or hash, a resinous substance typically found in either block or oil form. Hash can be smoked or consumed orally. Oral forms are often used to mitigate nausea, which may accompany all forms of cancer and the chemotherapeutic drugs used to treat them. Non-oral forms (such as smoking) may be contraindicated for some types of cancer, such as lung cancers. Use also may be contraindicated in the presence of other medical and psychiatric conditions.
For Further Information Dollinger, M., et al. Everyone’s Guide to Cancer Therapy: How Cancer Is Diagnosed, Treated, and Managed Day to Day. 4th ed. Kansas City, Mo.: Andre McMell, 2002. Eyre, Harmon, and Dianne Partie Lange, eds. Informed Decisions: The Complete Book of Cancer Diagnosis, Treatment, and Recovery. 2d ed. Atlanta: American Cancer Society, 2002. Wisnia, Saul. The Jimmy Fund of Dana-Farber Cancer Institute. Charleston, S.C.: Arcadia, 2002. u
Other Resources
Dana-Farber/Brigham and Women’s Cancer Center http://www.cancercare.harvard.edu Dana-Farber Cancer Institute http://www.dfci.harvard.edu See also American Association for Cancer Research (AACR); American Cancer Society (ACS); American Institute for Cancer Research (AICR); Duke Comprehensive Cancer Center; Fox Chase Cancer Center; Fred Hutchinson Cancer Research Center; Jonsson Comprehensive Cancer Center (JCCC); M. D. Anderson Cancer Center; Mayo Clinic Cancer Center; Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI); National Science Foundation (NSF); Prevent Cancer Foundation; Robert H. Lurie Cancer Center.
u Delta-9-tetrahydrocannabinol Category: Complementary and alternative therapies; chemotherapy and other drugs Also known as: THC, dronabinol (Marinol), nabilone (Cesamet), Cannabis sativa, medical marijuana; slang terms include bud, ganja, grass, hemp, herb,
How this compound works: The human body has a cannabinoid system including receptors called CB1 and CB2 receptors. CB1 receptors are located in the central nervous system and peripherally. To date, there is a presumption that CB2 receptors are located in peripheral areas of the body only. Both CB1 and CB2 receptors are involved in nausea and vomiting, interacting with other neurotransmitters affecting both the central nervous system (CNS) and gastrointestinal system. Products containing THC, its derivatives, and synthetic forms are understood to affect the cannabinoid system as a whole and via these CB1 and CB2 receptors. Cannabis sativa is a plant whose history spans centuries across diverse cultures. The plant itself has many purposes, so its worldwide presence is understandable. It has been used for its spiritual and religious ceremonies in some cultures, for its medicinal purposes in others, and as a recreational drug in others. In some cultures, it is an illicit substance or highly controlled or regulated, depending on its form. In the United States, marijuana is the most widely used illicit drug. Effects may be substantially different de355
Delta-9-tetrahydrocannabinol pending on the presence of other substances used at the same time (whether they are legal, illicit, or medicinal) and the presence of physical or mental illnesses. For many years, marijuana use was thought to be associated with cancers, particularly those of the head, neck, and lungs, such as those commonly associated with tobacco products. Contemporary scientific reviews (Reena Mehra et al., 2006) and studies (Mia Hashibe et al., 2007) suggest, however, that such assertions are more cautionary and tentative. In fact, no studies have shown a definitive link between long-term marijuana use and cancer. As with other smoking, however, it is associated with increased respiratory infections and other physical changes. In addition, risks associated with secondhand smoke are still suspect. Marijuana and tobacco contain many of the same carcinogens. Therefore, caution is recommended regarding any marijuana use. Hashibe and colleagues point out that the current findings regarding marijuana and health deserve continued study. For instance, scientists need better methods to estimate dosages of marijuana smoked. Such methods would provide a way to allow scientists to more formally evaluate dose-response issues. This is problematic for epidemiologic and naturalistic studies of marijuana use because marijuana is a street drug. The quality of street drugs is not set at a known standard and does not have a certain amount of active ingredients per amount of the drug. There is also a need for studies of the effects of marijuana over longer periods to ensure that observation periods have been long enough to see long-term health impacts. For instance, studies evaluating longitudinal effects over a lifetime, or substantial portion of a lifetime, and potentially accounting for dose effects and method of administration will have benefit. Side effects: Short-term effects may vary by user but include things such as changes in sensory experiences, increases in appetite, relaxation, increased feelings of pleasure, decreases in feelings of nausea, memory and learning difficulties, panic, anxiety, coordination problems, and impaired problem solving. Long-term effects may include
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Salem Health: Cancer problems related to addiction, such as abuse or dependence, motivational problems, daily cough, phlegm problems, respiratory problems, and impact to the immune system. It is noteworthy that these effects are what would be observed in normal users—that is, individuals without other significant physical or mental health problems who are not using any other substances. In individuals with other characteristics, such as other physical or psychiatric problems, the effects might differ in important ways. Nancy A. Piotrowski, Ph.D. u
For Further Information Earleywine, Mitch. Understanding Marijuana: A New Look at the Scientific Evidence. New York: Oxford University Press, 2002. Faupel, Charles, Alan M. Horowitz, and Gregory Weaver, eds. The Sociology of American Drug Use. New York: McGraw-Hill, 2004. Grotenhermen, Franjo, and Ethan Russo, eds. Cannabis and Cannabinoids: Pharmacology, Toxicology, and Therapeutic Potential. Binghamton, N.Y.: Haworth Press, 2002. Hashibe, Mia, et al. “Marijuana Use and the Risk of Lung and Upper Aerodigestive Tract Cancers: Results of a Population-Based Case-Control Study.” Cancer, Epidemiology, Biomarkers, & Prevention 15, no. 10 (2006): 1829-1834. Mehra, Reena, et al. “The Association Between Marijuana Smoking and Lung Cancer: A Systematic Review.” Archives of Internal Medicine 166 (July 10, 2006): 13591367. Rosen, Winifred, and Andrew T. Weil. From Chocolate to Morphine: Everything You Need to Know About MindAltering Drugs. Rev. ed. Boston: Houghton Mifflin, 2004. Russo, Ethan B., and Franjo Frotenhermen, eds. Handbook of Cannabis Therapeutics: From Bench to Bedside. Binghamton, N.Y.: Haworth Press, 2006. See also Antinausea medications; Medical marijuana; Nausea and vomiting.
Salem Health: Cancer
u Denys-Drash syndrome and
cancer Category: Diseases, symptoms, and conditions Also known as: DDS Related conditions: Wilms’ tumor (WT), Frasier syndrome, WAGR syndrome Definition: Denys-Drash syndrome is a rare disorder that usually causes kidney failure by the age of three, malformed sex organs, and often Wilms’ tumor. It is caused by a WT1 gene mutation and was named for two pediatricians, Pierre Denys and Allan Drash, who initially described this condition. Risk factors: The primary risk factor is having a relative with a WT1-related disorder. Etiology and the disease process: Denys-Drash syndrome originates with the mutation of the WT1 gene’s chromosome 11, band p13. Children with Denys-Drash syndrome are usually born with kidney disease, which becomes apparent several weeks after birth through eighteen months. Malignant Wilms’ tumor growth in one or two kidneys occurs in approximately 90 percent of DenysDrash patients. Cancer occasionally extends from the kidneys into the livers, lungs, and lymph nodes. Incidence: The precise number of Denys-Drash syndrome cases is uncertain, with an estimated 160 cases from the late 1960’s through the early twenty-first century. U.S. physicians diagnose approximately 500 children annually with Wilms’ tumors, which represent 95 percent of kidney cancers affecting children and 6 percent of pediatric cancers. Symptoms: Denys-Drash syndrome patients often exhibit symptoms commonly associated with kidney disorders and Wilms’ tumors, including swollen abdomens, elevated blood pressure, and bloody urine. Both male and female Denys-Drash syndrome patients have abnormal external or internal genitalia. Screening and diagnosis: Physicians test young children born with genitalia irregularities for Denys-Drash syndrome. Chromosome analysis verifies WT1 gene mutations. During infancy, biopsies and blood tests detect problems with kidneys. Computed tomography (CT) scanning, magnetic resonance imaging (MRI), or ultrasounds of abdomens locate tumors. Pediatricians apply the National Wilms’ Tumor Study Group (NWTS) staging system’s five stages to determine effective treatments.
Depression Treatment and therapy: Medical strategies to combat Denys-Drash syndrome primarily consist of surgery, radiation, or chemotherapy, either separately or combined to impede growth and eliminate malignancies. Some DenysDrash syndrome patients undergo kidney transplantation and dialysis. Additional pharmaceutical and dietary therapies reduce blood pressure and aid kidney functioning. Prognosis, prevention, and outcomes: Denys-Drash syndrome patients often develop infections, circulatory problems, and additional cancers that exacerbate their condition. Preventive options include replacing kidneys with healthy transplants and routine screening for malignancies. Kidney failure causes the death of approximately two-thirds of Denys-Drash syndrome patients by age three. In contrast, approximately 90 percent of patients treated solely for Wilms’ tumor survive. Elizabeth D. Schafer, Ph.D. See also Nephroblastomas; Wilms’ tumor; Wilms’ tumor aniridia-genitourinary anomalies-mental retardation (WAGR) syndrome and cancer.
u Depression Category: Diseases, symptoms, and conditions; social and personal issues Also known as: Major depression, major depressive disorder, reactive depression, adjustment disorder with depressed features, depression with psychotic features, first episode depression, chronic depression, depression in remission Related conditions: Anxiety disorder, mood disorder, substance abuse, seasonal affective disorder, borderline personality disorder, schizoaffective disorder Definition: Depression is a common emotional state that can be conceptualized along a continuum ranging from transient, nonclinical periods of low mood and sadness that remit quickly on their own, to a serious, life-threatening, clinical disorder requiring aggressive psychiatric intervention. Depression can lead to significant impairment of an individual’s ability to function and is a leading cause of disability worldwide. Clinical depression often occurs with cancer because of its chronic and life-threatening nature, but it is not considered typical or expected, which is counter to a common yet erroneous belief that depression and cancer “understandably” go hand in hand. Depression nonetheless is one 357
Depression
Salem Health: Cancer
is based on a complex interaction of factors. These include genetic predisposition to aberrant neurochemical states that precede or result from • The type of cancer, its stage, and prognosis an inadequate stress response combined with a Whether they are newly diagnosed, in treatment, in remission, or • experiencing a recurrence distorted, negatively biased cognitive style or • How well developed their coping strategies are worldview that is learned and reinforced early • Their support group, including friends and family in life. This multidimensional framework indi• Their age cates need for a combined psychopharmaco• The availability of treatment logic and psychotherapeutic treatment approach • Their beliefs about why they got cancer that is well supported in the medical literature. Clinical depression can present as a single epiSource: National Cancer Institute sode, be chronic and unremitting, or occur over time with periods of remissions and exacerbations. of the most common psychiatric complications in cancer A crisis framework is often used to describe the occurpatients. rence of depression in the context of cancer. The acute crisis response (ACR) typically occurs at transitions in the Risk factors: Depression is most common among cancer disease trajectory (diagnosis, treatment initiation, recurpatients with advanced disease and with symptoms and rence, treatment failure, disease progression). The ACR is discomfort that are not treated or inadequately treated. It characterized by symptoms of anxiety and depression that commonly coexists with anxiety and is common in indiusually resolve within a short time period. Time frames are viduals with substance abuse problems and other chronic variable, but the ACR usually resolves when individuals physical and mental disorders. Most cancer patients maniknow what to expect in terms of treatment, receive reasfest transient symptoms of depression that are responsive surance that discomfort can be controlled, and mobilize to support, reassurance, and information about what to exusual coping strategies and support systems. When symppect regarding the course, treatment, and prognosis of toms worsen rather than resolve over time or coping mechtheir disease. Others experience unremitting or recurrent anisms are insufficient, treatment for depression must be depression requiring aggressive monitoring and intervenconsidered regardless of whether diagnostic criteria for a tion. The following list depicts risk factors that favor the clinical diagnosis are met. development of clinically significant depression within the context of a cancer diagnosis: Incidence: Prevelance rates vary and depend on the population studied, site and stage of disease, and method used • Family history of depression to measure depression. Prevalence rates among cancer pa• Past history of depression, depression treatment, psychiatric hospitalization, or significant psychiatric/persontients range from 5 percent (lower than general population ality disorder rates) to 90 percent. In general, studies that use established diagnostic criteria report rates of depression of about 25 • History of unusual, eccentric behavior percent. Rates of depression are highest among patients • Confusion (may be indicative of an organically based depression) with advanced cancer and in studies in which stringent diagnostic guidelines are not used. • Maladaptive coping style • Dysfunctional family coping or complex family issues Symptoms: Symptoms of depression in cancer popula• Limited social support tions include the following: • Financial problems including lack of insurance • Persistent sad mood • Multiple roles, obligations, and stressors • Loss of interest or pleasure in typically pleasurable ac• Advanced cancer tivities • Treatment resulting in disfigurement or loss of function Feelings of guilt, worthlessness, helplessness • • Presence of dependent children Crying, not easily comforted • • Inadequate symptoms management Frequent thoughts of death or suicide • • Treatment that has a depressionogenic effect (certain Trouble concentrating, indecisiveness • chemotherapies, steroids, narcotics) • Appetite change Etiology and the disease process: Simplistically stated, • Diminished energy that may be mixed with restlessness the etiology of clinical depression, cancer related or not, and anxiety
Factors Affecting How People Adjust to Cancer
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• •
Fatigue, loss of energy Insomnia or hypersomnia Diagnosis of cancer-related depression relies heavily on the presence of affective symptoms (the first five symptoms in the list). Neurovegetative symptoms (the last five symptoms in the list) that characterize depression in physically healthy individuals are not good predictors of depression in cancer patients because cancer and its treatment produce similar symptoms. Additional behaviors suggestive of depression include refusal, indecisiveness, or noncompliance with treatment; persistent anxiety and sadness, unresponsive to usual support; unremitting fear associated with procedures; excessive crying, hopelessness that does not diminish over time; an abrupt change in mood or behavior; eccentric behavior or confusion; and excessive guilt or self-blame for illness. Screening and diagnosis: A formal diagnosis of depression is based on fulfillment of criteria outlined in the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders: DSM-IV-TR (2000). The diagnostic subtypes of depression include major depressive disorder (severe depression that lasts for more than two weeks and is particularly amenable to pharmacologic treatment), adjustment disorder with depressed features (depression that occurs in response to a clearly defined event or stressor), dysthymia (chronic, low-level depression that pervades an individual’s personality and daily life), and bipolar disorder (a genetically determined severe form of depression that may or may not alternate between depressive lows and manic highs and is responsive to mood-stabilizing, pharmacologic agents). Major depression and adjustment disorder are common diagnoses among individuals with cancer. Dysthymia and bipolar disorder usually precede a cancer diagnosis or occur for the first time following cancer diagnosis in those genetically predisposed. Depressive symptoms not severe enough or of sufficient duration to achieve diagnostic status are the most common type of depressive phenomena in individuals with cancer. Because a formal diagnosis is not present, these symptoms are often ignored despite a common, negative impact. More research on the simultaneous occurrence of cancer and depression is needed, including symptom profiles, clinical treatment trials, and related outcomes. A number of tests screen for depression, but they have not been consistently incorporated into clinical care. Nonpsychiatric providers fail to diagnose and treat depression in as many as 50 percent of cancer patients with depressive disorders. Obstacles to recognizing depression
Depression include inadequate provider knowledge of diagnostic criteria, competing treatment priorities in oncology settings, time limitations in busy offices, concern about the stigma associated with a psychiatric diagnosis, limited reimbursement, and uncertainty about the value of screening mechanisms for case identification. In general, regardless of whether screening measures are used, if symptoms do not remit in a reasonable time frame, evaluation of depressive symptoms by a psychiatric specialist should be sought. Treatment and therapy: Psychosocial interventions can exert an important effect on the overall adjustment of patients and their families to cancer and its treatment. Factors contributing to the diagnosis of depression should influence the treatment approach. Treatments include psychopharmacologic treatment, individual psychotherapy, group therapy, family therapy, marital therapy, or some combination of these. Antidepressant medication should be chosen on the basis of diagnostic subtype, treatment response, and side effect profile. Bipolar disorder is usually treated with a mood stabilizer, requiring careful monitoring and adjustment, especially during active treatment, as therapeutic blood levels are narrow and can shift dramatically in response to electrolyte and metabolic changes. Major depression is commonly treated with one of several classes of antidepressant medication, commonly a selective serotonin reuptake inhibitor (SSRI) or a a selective serotonin and norepinepherine reuptake inhibitor (SSNRI). Dosages are typically lower than required in healthy individuals and can positively affect other symptoms that the patient might be experiencing, such as pain and anxiety. In the oncology setting, a multimodal treatment approach is most effective in treating depression and can have a positive impact on a range of psychosocial and medical outcomes. Prognosis, prevention, and outcomes: Left untreated, depression can produce a range of negative outcomes from diminished quality of life to noncompliance with treatment to diminished survival. Depression can be prevented in some individuals by providing preemptive counseling, education, support, and information about resources. Early recognition and treatment offer the best hope for rapid remission. Modern therapies are effective in treating depression even among cancer patients who are in progressive and terminal stages of illness. Treatment can vastly improve quality of life and diminish suffering; thus routine screening and treatment should be a universal aspect of comprehensive cancer care . Jeannie V. Pasacreta, Ph.D., A.P.R.N. 359
Dermatofibrosarcoma protuberans (DFSP) u For Further Information Akechi, Tatsuo, et al. “Major Depression, Adjustment Disorders, and Post-traumatic Stress Disorder in Terminally Ill Cancer Patients: Associated and Predictive Factors.” Journal of Clinical Oncology 22, no. 10 (May 15, 2004): 1957-1965. Carr, D., et al. Management of Cancer Symptoms: Pain, Depression, and Fatigue. Evidence Report/Technology Assessment 61. AHRQ Publication No. 02-E032. Rockville, Md.: Agency for Healthcare Research and Quality, 2002. Fleishman, S. “Treatment of Symptom Clusters: Pain, Depression, and Fatigue.” Journal of the National Cancer Institute: Monographs 2004, no. 32 (2004): 119-123. Lloyd-Williams M. “Screening for Depression in Palliative Care Patients: A Review.” European Journal of Cancer Care 10 (2001): 31ff. Parker, P. A., W. F. Baile, C. de Moor, and L. Cohen. “Psychosocial and Demographic Predictors of Quality of Life in a Large Sample of Cancer Patients.” Psychooncology 12, no. 2 (2003): 183-193. Patrick, D. L., et al. “National Institutes of Health State-ofthe-Science Conference Statement: Symptom Management in Cancer: Pain, Depression, and Fatigue, July 1517, 2002.” Journal of the National Cancer Institute 95 (2003): 1110ff. u
Other Resources
Abramson Cancer Center of the University of Pennsylvania Oncolink http://www.oncolink.org/resources American Psychosocial Oncology Society http://www.apos-society.org Cancer Care http://www.cancercare.org National Institute of Mental Health Depression http://www.nimh.nih.gov/health/topics/depression/ index.shtml Substance Abuse and Mental Health Services Administration http://www.samhsa.gov See also Anxiety; Appetite loss; Benzodiazepines; Elderly and cancer; End-of-life care; Exercise and cancer; Fatigue; Grief and bereavement; Hormonal therapies; Integrative oncology; Living with cancer; Medical marijuana; Opioids; Pain management medications; Palliative treat360
Salem Health: Cancer ment; Personality and cancer; Psycho-oncology; Psychosocial aspects of cancer; Self-image and body image; Survivorship issues.
u Dermatofibrosarcoma
protuberans (DFSP) Category: Diseases, symptoms, and conditions Also known as: Bednar tumor, familial dermatofibrosarcoma protuberans, fibrosarcomatous tumors with attenuated dermal surfaces, fibrosarcomatous progression, fibrosarcoma of the skin, metastatic dermatofibrosarcoma protuberans, progressive and recurring dermatofibroma Related conditions: Dermatofibroma, epidermal inclusion cyst, fibrosarcoma, giant cell fibroblastoma, fibrous histiosytoma, keloid and hypertrophic scar, lymphoma, malignant melanoma, metastatic carcinoma of the skin, morphea Definition: Dermatofibrosarcoma protuberans (DFSP) is a rare type of skin cancer that affects the inner layer of the skin (dermis). “Derma” means that it affects the skin. “Protuberans” means that it sticks out (protrudes) above the skin. Risk factors: There is no known cause of DFSP. In a minority of patients, about 10 percent, some type of trauma, such as a burn, scar, or injection site, has occurred at the site where the disease develops. Laboratory studies seem to show that a type of chromosome mutation tends to help the previous skin damage evolve into this type of cancer. In this chromosome mutation, material from chromosomes 17 and 22 somehow combine to form another chromosome or switch material from one chromosome to another. However, many people with this chromosome mutation do not develop DFSP, and many who have DFSP do not have this chromosome mutation. Etiology and the disease process: DFSP is a very slowgrowing cancer. It usually starts as a small, hardly noticeable lump on the skin, which may remain that way for several years. It may then get larger and develop into a sore, or plaque, that is irregularly shaped, can vary in color (it may be red-brown, red-blue, or simply a bit darker than the surrounding skin), and bulges out. This lump may be tender or bleed, or it may be painless. This type of cancer most often occurs on the body, arms, or legs. It very rarely occurs on the neck or head. Rarely, DFSP may appear as a thickened area of skin or
Salem Health: Cancer a soft depressed area of skin. This type of DFSP may go unnoticed for quite some time, until it has grown big enough for a patient to notice, and so may have spread far underneath the skin. This type of DFSP is difficult to diagnose as it looks very similar to other skin diseases. DFSP does not generally spread beyond the original tumor site. However, the tumors are very aggressive in that they move out underneath healthy skin. The tumor may be much larger under the surface than it appears to be from the top of the skin. This makes DFSP a difficult cancer to completely eliminate because the distance the tumor has spread underneath the top layer of skin may make it difficult to remove the entire tumor, and cells that are left behind tend to grow into another tumor. In rare cases, this cancer may spread to lymph nodes or into the bloodstream, where it may spread to the lungs, heart, brain, or bones. Incidence: This type of cancer is relatively rare, having a rate of about 4 new cases per 1 million people each year. DFSP occurs slightly more often in men than in women. Though it may occur in persons of any race, blacks develop this cancer at almost twice the rate whites do. An uncommon variant called Bednar tumor occurs mostly in
Dermatofibrosarcoma protuberans (DFSP) black patients. This cancer occurs most often in people between the ages of twenty and fifty. It is very rarely found in newborns, children, or the elderly (those over eighty years old). Symptoms: DFSP appears as a small, red-brown or redblue tumor on the skin that may develop into a larger, irregularly shaped lump. This lump may feel rubbery or firm. It is attached under the skin so it does not move around when touched. Usually, the lump is not painful. It may develop into a patch of several lumps or nodules. Screening and diagnosis: There is no screening test or staging system for DFSP. Because the appearance of the skin in a patient with DFSP can be similar to that of a patient with many other conditions, a diagnosis involves a biopsy of the affected skin. This skin is examined under a microscope to determine if cells are growing abnormally. There is no blood test available for determining whether a patient has DFSP. Usually, imaging tests such as computed tomography (CT) or magnetic resonance imaging (MRI) are not used in diagnosis unless the tumors are suspected to have spread into the lymph system or into other body areas.
Dermatofibrosarcoma protuberans on a patient’s back. (©ISM/Phototake—All rights reserved)
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Dermatology oncology Treatment and therapy: Surgery is generally the first line of treatment for this type of cancer. Usually, the tumor itself and a large amount of skin around it must be removed to ensure that the entire tumor, growing under the skin where it cannot be seen, is removed. This type of surgery is called wide excision. Mohs micrographic surgery (MMS) is often used because this type of surgery allows a surgeon to view the edges of the skin through a microscope during surgery. While removing the tissue around the edges of the tumor, the surgeon can keep checking to make sure the skin around the tumor site has no more cancerous cells. Once no more cancerous cells are present in the tissue at the edges of the surgery site, the surgeon can stop removing skin. This can help ensure removal of the entire tumor. When surgery is used to remove DFSP tumors, the surgical site is often large. Depending on the amount of skin removed, a patient may need skin grafts to close the surgery site. The tumors often have ragged edges and unusual shapes, making removal of the entire tumor difficult. As a result, DFSP has a high rate of recurrence. Any cancerous cells left behind tend to grow into another tumor. If the cancer is large or its removal would cause serious cosmetic damage, such as a scar on the face or in another exposed area, radiation therapy may be used. In radiation therapy, the skin is exposed to high-energy rays that destroy the cancerous cells while doing as little damage as possible to the surrounding healthy tissues. Radiation therapy may also be used as a follow-up to surgery. Chemotherapy is rarely used with DFSP, as it has proven to be relatively ineffective. Researchers are developing oral medications and molecular-level therapies to treat this type of cancer. Oral medications may be able to target the specific cancerous cells and kill them while causing few, if any, side effects to the rest of the body. Molecular-level therapies use the body’s own natural defenses to target and kill cancerous cells. Prognosis, prevention, and outcomes: This type of cancer usually does not spread, but it has a high rate of recurrence: In about 20 percent of DFSP patients, the cancer returns in the same place. Usually, this is because the first occurrence of the cancer was not completely removed. Because of this high rate of recurrence, it is important that patients continue to receive follow-up care. Recurrence usually happens within three years, and patients should be seen regularly during that period to assess any tumor sites to ensure that cancerous cells left behind during surgery have not begun to grow. If the cancer has spread into the lymph nodes or bloodstream, as it does in only about 3 percent of cases, the prog362
Salem Health: Cancer nosis is much worse than if the cancer has been contained to tumors in the skin, with death usually occurring within two years. Prognosis is even worse with the variation of this cancer called fibrosarcomatous progression, because this variation is a much more aggressive type of cancer. Older patients (over fifty years old) are more likely to have a poorer outcome than those who are younger. Marianne M. Madsen, M.S. u
For Further Information Agnew, Karen L., Barbara A. Gilchrist, and Christopher B. Bunker. Skin Cancer. Oxford, England: Health Press, 2005. Du Vivier, Anthony, and Phillip H. McKee. Atlas of Clinical Dermatology. 3d ed. Edinburgh: Churchill Livingston, 2002. Hunter, John, John Savin, and Mark Dahl. Clinical Dermatology. 3d ed. Malden, Mass.: Blackwell, 2002.
u
Other Resources
DermNet NZ http://www.dermnetnz.org/lesions/dfsp.html Skin Cancer Foundation http://www.skincancer.org See also Fibrosarcomas, soft-tissue; Sarcomas, soft-tissue.
u Dermatology oncology Category: Medical specialties Also known as: Dermatological oncology, dermatologic oncology, cutaneous oncology Definition: Dermatologic oncology is the medical specialty dealing with the diagnosis and treatment of skin cancers. Dermatologic oncologists may provide services and treatment in an office or hospital setting. They receive special education after medical school in dermatology, then additional training specific to oncology diagnosis, procedures, and surgeries. Often dermatologic oncologists can treat skin cancers, but for cancers that have spread to the lymph nodes or other areas of the body, they will enlist the assistance of other specialized medical professionals, such as medical or surgical oncologists. Subspecialties: Although there are no formal subspecialties in dermatologic oncology, many dermatologic oncologists specialize in particular types of cancer or treatments. Some dermatologic oncologists may specialize in rarer forms of skin cancer or in skin cancers that have
Salem Health: Cancer
Dermatology oncology
A doctor administers local anesthesia before removing a skin lesion from a man’s face. (©Pulse Picture Library/CMP Images/ Phototake—All rights reserved)
significantly metastasized. Others may have special training in a particular treatment or procedure and may focus their practice on it. Some dermatologic oncologists may concentrate on performing clinical research into experimental techniques or procedures and writing articles for journals. Cancers treated: Dermatologic oncologists diagnose and treat the three main types of skin cancers: basal cell carcinoma, squamous cell carcinoma, and melanoma. Basal cell carcinoma very rarely spreads beyond the skin and can most often be treated by in the office or on an outpatient basis. Squamous cell carcinoma also only rarely spreads to other areas of the body, although it does have a somewhat higher incidence of spreading than basal cell carcinoma. It too can usually be treated in the office or on an outpatient basis. Melanomas are the most common cause of death from skin cancer. This type of skin cancer is very treatable if found early, but if diagnosed later, it can be aggressive and
has a high incidence of spreading to the lymph nodes and other parts of the body. If found early, melanoma can usually be treated successfully in the office or on an outpatient basis. If melanoma has spread over a large portion of the skin or to other organs, dermatologic oncologists will work with other health care professionals such as medical and surgical oncologists, radiologists, and chemotherapists to treat the cancer. Dermatologic oncologists also treat rare forms of skin cancer such as Kaposi sarcoma, which develops in the skin’s blood vessels, and sebaceous gland carcinoma, which originates in the skin’s oil glands. Training and certification: Dermatologic oncologists must complete a residency in dermatology after successfully completing medical school. Residencies are generally at least four years in duration. After completion of the residency, doctors may take an American Board of Dermatology exam for board certification in general dermatology. The next step is usually a fellowship in derma363
Dermatology oncology tologic oncology. There is no specific board certification for dermatologic oncology. Dermatologic oncologists are taught to diagnose skin cancers and to perform simple treatments in the office setting or on an outpatient basis as well as more complex treatments. They usually receive training in working with other allied health professionals such as medical and surgical oncologists to deal with metastasized skin cancers. They are often trained to conduct clinical research. Services and procedures performed: Dermatologic oncologists provide a wide variety of diagnostic and treatment procedures. They usually begin with a visual inspection of the area believed to be cancerous. This checkup may be occasioned by concern expressed by a patient or because of a referral from a primary physician. If the dermatologic oncologist believes cancer is a possbility, the area will be biopsied. Biopsies generally fall into two categories, excisional and incisional. Excisional biopsies remove the entire lesion suspected of being cancerous as well as a small amount of healthy skin surrounding the lesion. The incisional biopsy is most frequently used when a lesion is very large and removal of the entire lesion is impractical. Biopsies are usually performed in the office or on an outpatient basis. The samples gathered are treated and examined under a microscope, often in the office by the dermatologic oncologist. However, the sample may be sent out to a dermapathologist if the diagnosis is not clear or the doctor lacks the necessary facilities. Once the lesion has been diagnosed as cancerous, dermatologic oncologists create a plan of treatment. They start by determining how deep the cancer has spread and if it has spread beyond the skin. If it has spread to the lymph nodes or other parts of the body, the dermatologic oncologist will work closely with other oncology professionals to provide treatment. If the cancer is diagnosed early and has not spread, it can usually be treated through surgery. An incision is made around the lesion, and the lesion is removed. For basal cell carcinoma and squamous cell carcinoma that are still small, this is often all that is needed. Malignant melanoma may be removed in this way, but noncancerous skin around the lesion is usually removed as well to ensure that all the cancer has been removed. Small lesions can be removed using cryosurgery, a technique in which the lesion is frozen off with liquid nitrogen, or electrodesiccation and curettage, during which the lesion is burned off with an electrified needle. Another treatment option, often used for larger lesions, is Mohs micrographic surgery. The dermatologic oncol364
Salem Health: Cancer ogist slowly removes small layers of tissue. The tissue is quickly examined to determine if it is cancerous, and if it is, another small layer of tissue is removed. This continues until a noncancerous layer of tissue has been removed. Related specialties and subspecialties: Many different health professionals may work with dermatologic oncologists. Assistants may help prepare patients, perform simple procedures, and do basic laboratory work. These assistants may also play a key role in helping patients understand their diagnosis and communicating information about preoperative and postoperative care. Dermatologic oncologists may send biopsies to a dermapathologist, a dermatologist who has received additional training in the diagnosis of dermatologic diseases and conditions. A dermapathologist will perform laboratory analysis on a submitted sample to determine if cancer is present, and if so, what type of cancer it is. If cancer is diagnosed and is believed or found to have spread to lymph nodes or other areas of the body, many health professionals will join the dermatologic oncologist in helping develop and carry out a plan of treatment for the patient. The health care team will include specialists in the area to which which the cancer has spread and will often involve a surgical or a medical oncologist, a radiologist, a chemotherapist, oncology nurses, and various other oncology experts. If the treatment for the cancer, or the cancer itself, is significantly disfiguring, a plastic surgeon may be involved. Helen Davidson, B.A. u
For Further Information Egan, Tracie. Skin Cancer: Current and Emerging Trends in Detection and Treatment. New York: Rosen, 2006. Frankel, David H., ed. Field Guide to Clinical Dermatology. Philadelphia: Lippincott Williams & Wilkins, 2006. Harmey, Judith H., ed. VEGF and Cancer. New York: Kluwer Academic/Plenum, 2004. Kaufman, Howard L. The Melanoma Book: A Complete Guide to Prevention and Treatment. New York: Gotham Books, 2005. McClay, Edward F. One Hundred Questions and Answers About Melanoma and Other Skin Cancers. Sudbury, Mass.: Jones and Bartlett, 2004.
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Organizations and Professional Societies
American Academy of Dermatology http://www.aad.org P.O. Box 4014 Schaumburg, IL 60618-4014
Salem Health: Cancer American Board of Dermatology http://www.abderm.org Henry Ford Health System 1 Ford Place Detroit, Michigan 48202-3450 u
Other Resources
American Cancer Society http://www.cancer.org Skin Cancer Foundation http://www.skincancer.org See also Basal cell carcinomas; Bowen disease; Choriocarcinomas; Eyelid cancer; Hand-foot syndrome (HFS); Kaposi sarcoma; Keratosis; Lip cancers; Melanomas; Merkel cell carcinomas (MCC); Moles; Skin cancers; Squamous cell carcinomas; Sunlamps; Ultraviolet radiation and related exposures; Xeroderma pigmentosa.
u Desmoid tumors Category: Diseases, symptoms, and conditions Also known as: Aggressive fibromatosis Related conditions: Familial adenomatous polyposis (FAP), Gardner syndrome Definition: Desmoid tumors are tumors of the tissue surrounding muscle that may develop anywhere in the body, but often in the abdomen. Risk factors: Familial adenomatous polyposis (FAP), an inherited syndrome in which thousands of polyps are found in the colon, is a risk factor as well as surgical trauma, pregnancy and childbirth, and exposure to high levels of hormones. Etiology and the disease process: In many cases the cause of desmoid tumors is not known; however, they may be related to trauma (especially surgical trauma) or to hormones. There is a known genetic association between desmoid tumors and familial adenomatous polyposis. Incidence: Desmoid tumors are uncommon, with an approximate annual incidence of 2 to 4 cases per 1 million people. Desmoid tumors are more frequent in women than in men. The tumors are usually found in individuals between the ages of ten and forty. Individuals with familial adenomatous polyposis have a 4 to 20 percent chance of developing a desmoid tumor.
Desmoplastic small round cell tumor (DSRCT) Symptoms: A desmoid tumor is usually a painless mass; it may be felt as a lump. Pain may develop if nerves, muscles, or organs are affected by the growing tumor. Tumors in the abdomen can cause abdominal pain, a change in bowel habits, or rectal bleeding. Screening and diagnosis: Ultrasound imaging is used initially to examine soft-tissue tumors. A computed tomography (CT) scan or magnetic resonance imaging (MRI) may be used subsequently. The diagnosis of desmoid tumor is made by biopsy. Treatment and therapy: Surgery to remove the tumor is the best treatment, but radiation or drug therapy may also be used either alone (if the tumor is inoperable) or in combination with surgery. Drug therapy may range from aspirin or COX-2 inhibitors (including celecoxib) to hormonal therapy (such as tamoxifen, toremifene, raloxifene, or progesterone). Low-dose chemotherapy for one year or highdose chemotherapy for a shorter period may be used when other therapies have failed or when the tumor is fast growing or causes symptoms. If there are no symptoms, watchful waiting (observation without treatment) could be appropriate. Prognosis, prevention, and outcomes: Desmoid tumors are benign and very rarely spread from the site of the original tumor. However, they are locally aggressive and local recurrence rates can be as high as 70 percent. Recurrence is monitored by repeat MRI. Individuals with desmoid tumors should be tested for mutations of the APC gene. Vicki Miskovsky, B.S., R.D. See also Fibrosarcomas, soft-tissue; Gardner syndrome; Hereditary polyposis syndromes.
u Desmoplastic small round cell
tumor (DSRCT) Category: Diseases, symptoms, and conditions Also known as: Desmoplastic sarcoma, desmoplastic cancer Related conditions: Solid tumor, testicular cancer, ovarian cancer Definition: A desmoplastic small round cell tumor (DSRCT) is a rare but highly aggressive tumor usually appearing in the abdomen and surrounding lymph nodes. Risk factors: There are no known risk factors that have been identified as specific for the DSRCT. 365
Developing nations and cancer Etiology and the disease process: The tumors in DSCRT appear to arise from early developmental cells in childhood. The cell of origin for this tumor is unknown. The tumor shows characteristics of epithelial, mesenchymal, and neural differentiation. The tumor can metastasize through lymph nodes or the bloodstream primarily into areas of the abdomen including the spleen, diaphragm, liver, and intestines. Other sites include the lungs, central nervous system, bones, uterus, bladder, genitals, abdominal cavity, and the brain. Incidence: DSCRT is extremely rare, usually occurring in men in their twenties. Symptoms: The most common symptoms include abdominal pain, abdominal mass, and gastrointestinal obstruction. Screening and diagnosis: Patients are often misdiagnosed at onset of symptoms, and the rapid growth of the tumor cells can lead to an advanced stage (in which the cancer has spread to lymph nodes and other organs) before being diagnosed. Confirmation of DSCRT is usually done by biopsy. Identification of a genetic abnormality in chromosomes 11 and 22 has been useful in confirming the diagnosis of the tumor. Treatment and therapy: Because the tumors involve a large portion of the abdomen, surgery is rarely an option. Patients have some success with high doses of chemotherapy and radiation therapy. Prognosis, prevention, and outcomes: The prognosis of patients diagnosed with desmoplastic round cell tumors is very poor, with fewer than 20 percent surviving more than two to three years. Research has shown that a genetic abnormality called translocation is apparent in chromosomes 11 and 22, and scientists continue to study the pathogenesis of this tumor and various chemical agents to find which are most effective against the tumor. Robert J. Amato, D.O. u
For Further Information Johanson, Paula. Frequently Asked Questions About Testicular Cancer. New York: Rosen, 2008. Kurth, Karl H., Gerald H. Mickisch, and Fritz H. Schröder. Renal, Bladder, Prostate, and Testicular Cancer: An Update. New York: Parthenon, 2001. Parker, James N., and Philip M. Parker, eds. The Official Patient’s Sourcebook on Testicular Cancer: A Revised and Updated Directory for the Internet Age. San Diego, Calif.: Icon Health Publications, 2002. See also Fibrosarcomas, soft-tissue. 366
Salem Health: Cancer
u Developing nations and cancer Category: Social and personal issues Definitions: Cancer describes a group of more than one hundred diseases that are a result of abnormal cells that grow unchecked in the body. These cells can spread, or metastasize, to other sites of the body when the cancer is aggressive or goes untreated. Metastases are the major cause of cancer death. Least developed or developing countries—sometimes referred to as Third World countries—are those countries with low incomes and significant poverty, few industries, minimal health care, and poor living conditions for the population. In these countries, cancer treatment, which requires sophisticated drugs and equipment, is rarely available, as resources are instead directed to survival, sanitation, nutrition, and other basic needs. Impact of cancer: The United Nations has created a human development index that measures the gross domestic product of a country, life expectancy, per capita income, literacy levels and other factors, and also allows each government to categorize itself as least developed, a failed state, developing, newly industrialized, emerging, or developed. Most African, some Central and South American, and some Asian countries are considered to be developing or least developed. Newly industrialized countries, such as South Africa, China, and India, are facing cancer care issues similar to those in developing countries, but they have growing resources to address the health needs of their populations. Because cancer is a disease that affects not only the patients but also their families and communities, the economic burden is significant and includes the cost of care as well as the impact of lost earnings. Other issues are the lack of government regulation of public health and industrial issues that increase the risk for cancer among the population. Incidence, death, and survival statistics: According to the World Health Organization, 12 million cases of cancer are diagnosed annually worldwide, with almost 8 million people dying of the disease. Of all deaths in the world, 12 percent are due to cancer, more than twice the number of deaths from acquired immunodeficiency syndrome (AIDS). Of the cancer deaths that occur each year, almost three out of four were in low- and middle-income countries. Mortality from cancer is generally due to lung, stomach, liver, colon, and breast cancers, which account for almost 5 million of the 8 million deaths annually. As cancer prevention, screening, and treatment im-
Salem Health: Cancer prove in developed countries, these countries are likely to experience a decline in cancer incidence, while incidence rates in developing nations are likely to continue to grow. In addition, because cancer is a disease of the aging, as the populations of developing countries live longer, experts predict that the incidence rates of cancer will increase in these countries. A study by the American Cancer Society reported that China has 20 percent of the world’s cancer cases, followed by the United States at about 15 percent. Globally, the cancers with the highest mortality rates for men (from highest to lowest) are lung, stomach, liver, colorectal, and prostate. For women, the leading causes of cancer death in descending order are breast, lung, stomach, colorectal, and cervical cancer. In least developed or developing countries, the survival rates for cancer are dismal. Cancer patients are usually diagnosed at a late stage of disease with complications that make cures almost impossible. Up to 90 percent of patients in less developed or developing countries have advanced cancer and incurable clinical complications when diagnosed. Risk factors: Tobacco use is the most important risk factor related to cancer development. Use of all forms of tobacco—cigarettes, cigars, pipes, and smokeless tobacco—contributes to lung, larynx, esophageal, stomach, bladder, mouth, and other cancers. As per capita income grows, the use of commercial tobacco products often increases with it. Other behavioral risk factors include excessive alcohol use, which contributes to breast, esophageal, liver, and other cancers according to the World Health Organization; nutritional deficiencies, such as a lack of fruits and vegetables in the diet; obesity; and unprotected exposure to ultraviolet (UV) light from the sun. Infectious agent and viruses, sometimes the result of unsafe sex practices, contribute to the development of cancer. Cervical cancer, caused by human papillomaviruses (HPV), and Kaposi sarcoma, caused by the human immunodeficiency virus (HIV), are prevalent in Africa. Air pollution and food contaminated with chemicals and mycotoxins are environmental factors that can contribute to the development of cancer. Agriculture is a common field of employment in developing countries, and the chemicals used can raise the workers’ risk of cancer. Mining and other nonregulated industries may also expose workers to risks. Because of fewer government regulations, chemicals banned as hazardous in developed countries are often used in developing countries. Reducing the global cancer burden: Up to 40 percent of cancers can be prevented by controlling risk factors and
Developing nations and cancer promoting a healthy lifestyle, while recognizing the economic constraints of the population. The single most important factor in reducing the global cancer burden is to stop tobacco use. Education that takes into consideration economic issues and culture is the key to cancer control. The World Health Organization and the United Nations outlined recommendations for cancer control programs worldwide, identifying the critical parts of any program to be prevention, early detection, prompt treatment, and appropriate care. For patients diagnosed with advanced cancers, appropriate care should be provided when there is a chance of cure or prolonged survival with an acceptable quality of life. For advanced cancers with no chance of cure, pain relief and palliative care for patients, along with support for families, are important as part of any program. The problem with any cancer control plan is that it requires a level of health care knowledge and sophistication to implement. However, when developing countries are struggling to provide sanitary living conditions and sufficient food for their populations, their priorities may not include cancer control. Infant mortality, communicable diseases, tuberculosis, HIV/AIDS, and malaria compete for scarce health care resources. Improving global cancer care: Public and private donations to organizations dealing with health problems in developing countries are at an all-time high. Governments, individuals, and humanitarian groups are raising billions of dollars to improve health care in developing countries. The International Finance Corporation of the World Bank has a public-private partnership initiative aimed at developing countries to enlist health care entrepreneurs to provide health-related services such as hospitals, dialysis centers, and cancer centers. Both the World Health Organization and the United Nations are involved in health care efforts worldwide. However, the minimal infrastructure to support the money that is being spent is often lacking. Most developing countries have few, if any, hospitals; not enough doctors, nurses, and other health care workers; and little government support and regulation to support a sustained health care effort. The most important step in improving global cancer care is to develop a strategy to use available money to develop a health care infrastructure that allows ongoing diagnosis, treatment, and care of disease. The focus for cancer programs should be education and lifestyle change, because 40 percent of cancers can be prevented. Early detection of cancer with appropriate treatment in developing countries would lead to reduced mortality worldwide. Immunizations, use of the HPV vaccine, and resources such as radiation therapy and chemotherapy 367
Di(2-ethylhexyl) phthalate (DEHP) need to be made available. Pain control and symptom management should be a priority. Cancer is a complex disease, but there is hope that survival and improved quality of life can occur if an effort is made to improve existing resources in developing countries. Patricia Stanfill Edens, R.N., Ph.D., FACHE u For Further Information MacDonald, T. H. Third World Health: Hostage to First World Health. Abingdon, England: Radcliffe, 2005. Ramanakumar, A. V. “Need for Epidemiological Evidence from the Developing World to Know the CancerRelated Risk Factors.” Journal of Cancer Research and Therapeutics 3 (2007): 29-33. Stewart, B. W., and P. Kleihues, eds. World Cancer Report. Geneva: World Health Organization, International Agency for Research on Cancer, 2003. u
Other Resources
International Union Against Cancer http://www.uicc.org United Nations http://www.un.org World Health Organization Cancer http://www.who.int/topics/cancer/en/ See also Africans and cancer; Air pollution; Financial issues; Fruits; Geography and cancer; HIV/AIDS-related cancers; Human papillomavirus (HPV); Nutrition and cancer prevention; Poverty and cancer; Risks for cancer; Statistics of cancer; Survival rates; Vaccines, preventive; Vaccines, therapeutic; Virus-related cancers.
u Di(2-ethylhexyl) phthalate
(DEHP) Category: Carcinogens and suspected carcinogens RoC status: Reasonably anticipated human carcinogen since 1983; under review for removal from the Twelfth Report on Carcinogens (RoC) Also known as: Diethylhexyl phthalate, bis(2-ethylhexyl) phthalate Related cancers: DEHP does not seem to cause cancer in humans. The mechanism by which cancers are induced in experimental animals by prolonged high doses of DEHP is not relevant to humans. 368
Salem Health: Cancer Definition: DEHP is a water-insoluble organic compound, a widely used phthalate with the molecular formula of C 24H38P4. It is used as a plasticizer mainly in the plastic polyvinyl chloride (PVC) for flexibility and softness of the final product. Exposure routes: Inhalation, ingestion, dermal contact, and medical procedures such as intravenous (IV) drug administation and blood transfusion Where found: DEHP is mainly used in plastic products such as children’s toys, vinyl upholstery, raincoats, and food packaging. Because DEHP is not chemically attached to the plastic, it can leach out. DEHP release is found in IV bags, blood bags, dialysis bags, medical tubing products, atmosphere, soil, and water. Some manufacturers have begun not to use DEHP in their products. At risk: DEHP may cause toxicity in humans. Because of its minimum exposure to humans, however, it does not present a general risk to human health. Newborns and infants are particularly at risk for toxicity in the hospital setting. Thus, the risk of developmental and reproductive abnormalities is greater among this subpopulation. Etiology and symptoms of associated cancers: The hepatocarcinogenicity (potential to cause liver cancer) of DEHP in rats has been proven. DEHP-induced peroxisome proliferation in rats is a phenomenon in which peroxisomes in hepatocytes (liver cells) are increased in number. Peroxisomes, also called microbodies, are intracellular respiratory organelles like mitochondria. Peroxisome proliferation protects the cell from increased oxidation. Failure to do so results in carcinogenesis—cell replication and tumor formation. No such peroxisomal route of carcinogenesis and thus no form of cancer due to DEHP have been demonstrated in humans. It may be because there are fundamental differences in metabolism between rats and humans; also, prolonged exposure of higher doses of DEHP in humans is unlikely. History: Plasticized PVC was invented in 1926. DEHP was implicated in animal hepatocarcinogesis in 1982, which was followed by classification of DEHP as an anticipated human carcinogen. DEHP’s possible removal from the twelfth Report on Carcinogens is based on the experts’ conclusion that the chemical cannot be reasonably anticipated to cause cancer in humans. It is important to note, however, that human carcinogenicity data remain incomplete. Arun S. Dabholkar, Ph.D. See also Plasticizers.
Salem Health: Cancer
u Diarrhea Category: Diseases, symptoms, and conditions Also known as: Dysentery, intestinal flu Related conditions: Colorectal cancer, gastrointestinal disease Definition: Diarrhea is the passage of frequent loose or liquid stools. Diarrhea is usually characterized by the passage of loose stools more than three to four times in one day. Risk factors: Diarrhea may occur as a result of cancer treatment, such as chemotherapy or other cancer medications; radiation therapy to the pelvis, rectum, or abdomen; or surgery. Diarrhea may be the result of an underlying condition, including central nervous system disorders, bowel obstruction, diverticulitis (outpouchings of the colon), and hernia. Diarrhea may be a sign of gastric cancer, colon cancer, rectal cancer, bowel cancer, and other cancers, and it also may occur on the growth or spread of these types of cancer. Lactose intolerance and certain medications, such as antibiotics, can increase the risk of diarrhea. Anxiety about cancer or cancer treatment also can contribute to the development of diarrhea. Etiology and the disease process: Chemotherapy and radiation therapy can cause changes in the function of the intestines, including increased or decreased peristalsis (the wavelike contraction of the muscles to propel the contents of the intestines through the digestive tract). An increase in peristalsis can cause stool to move faster through the intestines, leading to diarrhea or cramping. Chemotherapy also can change the normal bacteria in the intestines, causing diarrhea. Dehydration is a concern for patients who have diarrhea. Dehydration occurs when more fluid is lost than is taken in, and the body does not have enough water and other fluids to carry out its normal functions. Signs of mild dehydration include dry mouth, weakness, dizziness, and fatigue. Signs of severe dehydration require immediate medical attention and include extreme thirst; irritability and confusion; very dry mouth, skin, and mucous membranes; decreased urination; low blood pressure; rapid heartbeat; and fever. Incidence: Diarrhea is very common among patients undergoing cancer treatments, particularly those receiving certain chemotherapy drugs as well as radiation to the stomach or abdomen. The National Cancer Institute reports that 25 percent of patients experience severe diarrhea.
Diarrhea Symptoms: Symptoms of diarrhea include the passage of frequent loose or liquid stools more than three times in one day. Other symptoms that accompany diarrhea include urgency to have a bowel movement, bloating, and nausea. Symptoms range from moderate to severe, and vary among patients. Symptoms can impede cancer treatment, resulting in a delay, dose reduction, or discontinuation of therapy. Changes in stool frequency, consistency, volume, or the presence of blood, mucus, or pus in the stool may indicate an underlying disease. If diarrhea occurs more than six times a day, or does not resolve within twenty-four hours after taking prescribed antidiarrheal medications, the patient should call the prescribing physician. Screening and diagnosis: A thorough review of the patient’s medical history and a physical exam are performed, and stool tests can be performed to identify blood and bacterial, fungal, parasitic, or viral pathogens. Diagnostic tests may include upper endoscopy, upper gastrointestinal series (barium swallow), abdominal X rays, sigmoidoscopy, and colonoscopy. Treatment and therapy: Symptom management is critical to avoid an interruption in the delivery of cancer treatment. Aregistered dietitian can provide nutritional therapy to help the patient develop an eating plan that meets dietary requirements while reducing side effects, helping to make treatment more tolerable. In some cases, antidiarrheal medications are prescribed. First-line treatment includes loperamide and diphenoxylate/atropine. Secondline treatment for persistent, chronic diarrhea includes octreotide subcutaneous injections. It is important for patients to ask their physician first before self-treating diarrhea and related symptoms, as some over-the-counter remedies could interfere with cancer treatment. Conservative techniques to manage diarrhea include the following: • Increasing fluid intake to prevent dehydration • Eating bland foods in small amounts • Following a clear liquid diet of juices and broth until symptoms subside • Avoiding spicy, high-fat, and sugary foods • Eating small, frequent meals • Eating slowly and chewing food completely before swallowing • Taking medication with food, unless advised otherwise • Avoiding high-fiber foods and dairy products • Avoiding caffeine and alcoholic beverages • Including high-potassium foods, as advised by the doctor 369
Dietary supplements In addition to these recommendations, relaxation techniques such as deep breathing and guided imagery may help. Patients should follow their physician’s specific guidelines for managing treatment side effects and should call the doctor when symptoms are severe or persist for more than twenty-four hours. When necessary, nutritional supplements also may be recommended to ensure sufficient caloric and nutrient intake. Prognosis, prevention, and outcomes: Diarrhea can be effectively managed with conservative treatments and medications and is generally relieved when cancer treatments are completed. There usually are no long-term effects of gastrointestinal symptoms that are properly managed, according to the American Cancer Society. Hospitalization is recommended for patients with severe dehydration or diarrhea that results in the inability to maintain adequate hydration or nutrition and for patients with chronic diarrhea that does not resolve within twentyfour hours after taking prescribed antidiarrheal medications. Left untreated, chronic diarrhea can cause significant morbidity and mortality because of nutritional deficiencies, and fluid and electrolyte imbalances may lead to potentially life-threatening dehydration or impaired kidney function. Although cancer treatments can result in diarrhea that may be temporarily unpleasant to the patient, the potential side effects, if adequately managed under a physician’s care, should be measured against the cancer-fighting benefits of a particular treatment. Angela M. Costello, B.S. u For Further Information Field, Michael, ed. Diarrheal Diseases. New York: Elsevier, 1991. Kogut, Valerie, and Sandra Luthringer. Nutritional Issues in Cancer Care. Philadelphia: Oncology Nursing Society, 2005. Scott-Brown, Martin, Roy A. J. Spence, and Patrick G. Johnston, eds. Emergencies in Oncology. New York: Oxford University Press, 2007. u
Other Resources
American Cancer Society http://www.cancer.org American College of Gastroenterology http://acg.gi.org National Cancer Institute http://www.cancer.gov 370
Salem Health: Cancer National Institute of Diabetes and Digestive and Kidney Diseases National Digestive Diseases Clearinghouse http://digestive.niddk.nih.gov/index.htm See also Adrenal gland cancers; Angiogenesis inhibitors; Anthraquinones; Antidiarrheal agents; Antinausea medications; Chemotherapy; Crohn disease; Diverticulosis and diverticulitis; Gastrointestinal cancers; Gastrointestinal complications of cancer treatment; Inflammatory bowel disease; Laxatives; Rectal cancer; Side effects; Symptoms and cancer; Weight loss.
u Dietary supplements Category: Complementary and alternative therapies; lifestyle and prevention Definition: Dietary supplements are a broad category of materials that are defined by the U.S. Food and Drug Administration (FDA) as substances consumed in addition to a person’s normal diet. Subclasses of this group are vitamins, minerals, botanicals, amino acids, enzymes, and certain animal-derived products. Cancers treated or prevented: Dietary supplements are often taken, in an adjuvant mode, to help fight many types of cancer, although their effectiveness is rarely proven. Perhaps even more often, supplements are taken for cancer prevention or to boost the immune system. Delivery routes: Oral in the form of tablets, caplets, capsules, powders, and liquids such as extracts and teas. How these agents work: In the United States in 2007, dietary supplements were estimated to be a $22 billion industry. Supplements range from familiar multivitamin tablets to unusual substances such as snake venom. Some dietary supplements (such as vitamins and minerals) have accepted roles in conventional medicine as well as complementary and alternative uses. Other dietary supplements, including most botanicals, are used almost exclusively in complementary and alternative medicine. Complementary medicine supplements traditional Western medical care, while alternative medicine seeks to replace traditional Western medical care. Some dietary supplements, especially vitamins and minerals, are embraced by traditional Western medicine and play an important role in maintaining health, especially among individuals with cancer or other diseases that affect the body’s metabolism. Thirteen different vitamins are essential to human health. The body cannot make these
Salem Health: Cancer
Dietary supplements
compounds; they must be obtained either from food or In relation to cancer, people generally take dietary supfrom dietary supplements. The fat-soluble vitamins are plements for four reasons: to prevent a particular type of vitamins A, D, E, and K. The water-soluble vitamins are cancer; to meet the needs for a particular substance that vitamins B1 (thiamine), B2 (riboflavin), B3 (niacin), B5 they cannot acquire from diet because of their cancer (vita(pantothenic acid), B6 (pyridoxine), B7 (biotin or vitamin min supplements); to boost the immune system and help it H), B9 (folate or folic acid), B12 (cobalamin), and vitamin fight their cancer (ginseng); and to reduce specific sympC. Vitamins are generally safe when taken in amounts less toms associated with their cancer (ginger for nausea). The than the upper safe limit set by the U.S. Institute of MediAmerican Cancer Society cautions individuals with cancine. Megadosing, or taking large quantities of vitamins, cer to choose dietary supplements with care and with the can cause serious health complications, especially with the knowledge and advice of their physician. Much misinforfat-soluble vitamins, which build up in the body. Minerals mation and many unproved anecdotal claims about dietary are inorganic compounds found in the earth that are necessupplements and cancer exist on the Internet and in some sary in small amounts for human health. Like vitamins, fad medicine books. many minerals are safe and effective unless taken in Although millions of Americans use dietary supplemegadoses. ments daily, the safety and effectiveness of these products Botanicals (herbs) are dietary supplements derived varies depending on the type of supplement, the purity of from plants. Botanicals have been used for centuries in trathe manufacturing process, the dosage, the health of the inditional Chinese medicine, Ayurvedic or traditional Individual, and the way in which the supplement interacts dian medicine, pre-nineteenth century Western medicine, with other supplements and drugs. In the United States, diand homeopathy. The National Center for Complemenetary supplements are regulated under the 1994 Dietary tary and Alternative Medicine (NCCAM) conducts rigorSupplement Health and Education Act (DSHEA). This act ous investigations and clinical trials of many botanicals. regulates supplements as foods rather than as pharmaceuCommon botanicals that are claimed to treat cancer or tical drugs. Under the act, dietary supplement manufacturcancer symptoms include apricot pit, foxglove, ginseng, ers do not need to prove that their products are either safe green tea, and reishi mushroom. These claims have not or effective before they are marketed. This contrasts with been proved to the satisfaction of Western medicine. both over-the-counter and prescription drugs, which canAmino acids are molecules that are the building blocks not be sold until extensive testing (clinical trials) proves of proteins. Humans require twenty amino acids, twelve them to be both safe and effective in treating specific conof which the body can produce for itself. The rest must be ditions. obtained through diet or supplementation. Enzymes are proteins made in the body that regulate metabolic reactions. Prescription enzymes and amino acids are used in Western medicine when they replace compounds that the body is unable to make because of genetic defects. These substances are also sold as dietary supplements, some of which claim to treat cancer. Most traditional physicians do not accept these claims. Animal-based supplements include products such as fish oil, bee pollen, and bear bile. Many of these products are used in alternative medicine and claim to prevent or treat disease. Practitioners of Western medicine generally acknowledge the benefits of some dietary supplements, such as vitamins, Although millions of Americans use dietary supplements daily, such as these made from minerals, and fish oils, but question freeze-dried grape seeds, the safety and effectiveness of these products varies. (AP/ extreme claims. Wide World Photos) 371
Dietary supplements DSHEA limits the health claims that can be made for dietary supplements. Supplements cannot legally claim to treat or cure a particular disease. They are, however, allowed to make general claims, such as “helps build strong bones” or “helps lower cholesterol.” Any structure or function claims made for dietary supplements must have on the label the exact words, “This statement has not been evaluated by the FDA. This product is not intended to diagnose, treat, cure, or prevent any disease.” The packaging does not have to contain any warnings about potential side effects. Additional FDA regulations have been added since the original 1994 law. By the end of 2007, all supplement manufacturers were required to report consumer complaints, including complaints of adverse reactions, ineffectiveness, and contaminated products, to the FDA. Before 2007, there was no requirement to inform the FDA of any problems reported by consumers. In addition, in June, 2007, new FDA regulations established stronger good manufacturing practices for dietary supplements that required manufacturers to test for the identity, purity, strength, and composition of their products. These regulations were intended to help consumers determine exactly what is in the supplement and to certify that it is free from contamination by bacteria, fungi, glass, pesticides, heavy metals, and nonapproved additives. The new manufacturing regulations resulted from findings by independent laboratories and the FDA of many contaminated supplements, as well as those that contained material other that what was listed on the label or that contained less or none of the labeled ingredients. These regulations were scheduled to be phased in gradually and to apply to all supplements sold in the United States by 2010. Manufacturers are still not required to make any statements on the packaging about potential side effects, nor are they required to prove that a supplement is safe or effective. Side effects: The side effects of many dietary supplements have not been studied and are unknown. Megadosing with supplements that are generally safe at lower doses, however, may cause the supplement (if fat-soluble) to build up in the body and interfere with the absorption or metabolism of other supplements or pharmaceutical drugs. Botanicals may also change the way in which other drugs or supplements act in the body by speeding up or inhibiting their actions. In addition, many natural plant substances (such as foxglove, hemlock, or ephedra) can be dangerous or lifethreatening. According to the American Association of Poison Control Centers, twenty-seven U.S. deaths were 372
Salem Health: Cancer caused by dietary supplements in 2005, although some experts believe that the unreported number may be much higher. Finally, dependence on dietary supplements to treat cancer or any serious disease may deprive the individual of effective traditional drugs and medical care that can save or prolong life. Individuals interested in taking dietary supplements as part of their cancer treatment regimen should research information carefully and discuss their findings with their oncologist before beginning a supplement. Martiscia Davidson, A.M. u
For Further Information Alschuler, Lise, and Karolyn A. Gazella. Alternative Medicine Magazine’s Definitive Guide to Cancer: An Integrated Approach to Prevention, Treatment, and Healing. Berkeley, Calif.: Celestial Arts, 2007. Davis, W. Martin. Consumer’s Guide to Dietary Supplements and Alternative Medicines. Binghamton, N.Y.: Pharmaceutical Products Press, 2006. Micozzi, Marc S., ed. Complementary and Integrative Medicine in Cancer Care and Prevention: Foundation and Evidence-Based Interventions. New York: Springer, 2007. Quillin, Patrick. Beating Cancer with Nutrition. 4th ed. Tulsa, Okla.: Nutrition Times Press, 2005.
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Other Resources
American Cancer Society How to Know What Is Safe: Choosing and Using Dietary Supplements http://www.cancer.org/docroot/ETO/content/ ETO_5_3x_How_to_Know_What_Is_Safe_ Choosing_and_Using_Dietary_Supplements.asp MedlinePlus Dietary Supplements http://www.nlm.nih.gov/medlineplus/ dietarysupplements.html National Cancer Institute Office of Cancer Complementary and Alternative Medicine http://www.cancer.gov/cam/ National Institutes of Health Office of Dietary Supplements Dietary Supplements: Background Information http://dietary-supplements.info.nih.gov/factsheets/ dietarysupplements
Salem Health: Cancer U.S. Food and Drug Administration Dietary Supplements Overview http://www.cfsan.fda.gov/~dms/supplmnt.html See also Antioxidants; Artificial sweeteners; Beta-carotene; Bioflavonoids; Caffeine; Calcium; Carotenoids; Cartilage supplements; Chemoprevention; Chewing tobacco; Coenzyme Q10; Cruciferous vegetables; Fiber; Folic acid; Fruits; Garlic and allicin; Ginseng, panax; Glutamine; Green tea; Herbs as antioxidants; Indoles; Isoflavones; Lutein; Lycopene; Macrobiotic diet; Nutrition and cancer prevention; Nutrition and cancer treatment; Omega-3 fatty acids; PC-SPES; Phytoestrogens; Resveratrol; Saw palmetto; Soy foods; Sun’s soup; Wine and cancer.
u Diethanolamine (DEA) Category: Carcinogens and suspected carcinogens Also known as: Diethylolamine, 2,2 dihydroxydiethylamine, diolamine, bis-2hydroxyethylamine, iminodiethanol Related cancers: Liver and kidney cancer in mice Definition: Diethanolamine (DEA) is a secondary amine in a class of organic compounds known as ethanolamines, which combine the properties of amines and alcohols. A high-production chemical, DEA is a component of metalworking fluids, pesticides, antifreeze, pharmaceuticals, and personal care products. Its fatty acid derivatives, including cocamide DEA, lauramide DEA, and oleamide DEA, are emulsifiers or foaming agents. Exposure routes: Principally through dermal contact, inhalation of vapor and aerosols, ingestion Where found: Intermediates in agricultural and photographic chemicals, personal care products (such as lotions, creams, shampoos, and hair dyes), textile processing, pharmaceuticals, metalworking fluids, industrial gas treatments At risk: Workers in diethanolamine manufacturing facilities, metal industry workers exposed to lubricating liquids, consumers of personal care products and of some tobacco products Etiology and symptoms of associated cancers: Diethanolamine increases the risk of liver cancers (hepatocellular adenoma or carcinoma) and kidney cancers (renal tubule adenoma) in mice. The cancer risk to humans has not been firmly established by adequate epidemiological studies. DEA does not damage the genetic material; rather,
Diethylstilbestrol (DES) it perturbs cellular processes by causing a deficiency of choline, an essential nutrient in mammals. Choline depletion is known to induce changes in deoxyribonucleic acid (DNA) methylation, stimulate DNA synthesis, generate free radicals, and enhance susceptibility to oxidative damage—all events linked to tumorigenesis. Because rodents are more sensitive to choline deficiency than are humans, the relevance of the mouse tumor findings to humans is unclear. DEA’s potential carcinogenicity may stem from its ability to interact with nitrites. As contaminants or preservatives in commercial formulations, nitrites react with DEA to form nitrosodiethanolamine (NDELA), a carcinogen that induces tumors of the liver, nasal cavity, and kidney in laboratory animals. The National Toxicology Program has listed nitrosodiethanolamine as reasonably anticipated to be a human carcinogen. History: The industrial synthesis of ethanolamines depends on the wide-scale production of the primary reactant, ethylene oxide, discovered in 1859 by the French chemist Charles Adolphe Wurtz. In 1999 at the completion of a two-year carcinogenesis study, the National Toxicology Program reported that dermal applications of DEA or cocamide DEA induced liver and kidney cancers in mice. As early as 1979 the U.S. Food and Drug Administration urged the cosmetics industry to remove DEAderived nitrosamines from its products, but it has not strictly enforced the policy. In contrast, the European Union has enacted legislation to reduce DEA and nitrosodiethanolamine from cosmetics and toiletries. Anna Binda, Ph.D. See also 4-Aminobiphenyl; Antiperspirants and breast cancer; Carcinogens, reasonably anticipated.
u Diethylstilbestrol (DES) Category: Carcinogens and suspected carcinogens; chemotherapy and other drugs RoC status: Known human carcinogen since 1980 Also known as: Stilbestrol Related cancers: Breast, cervical, prostate, and vaginal cancers Definition: Diethylstilbestrol (DES) is a synthetic form of the hormone estrogen. Exposure routes: Patients are exposed to DES when it is used in medical therapies and in clinical trials for the treatment of prostate and breast cancer. It is typically adminis373
Digital rectal exam (DRE)
Salem Health: Cancer
tered orally or intravenously. Potential exposure by inhalation can occur to workers who are involved in the formulation and manufacturing of diethylstilbestrol. Where found: DES is found at sites where it is manufactured, packaged, and supplied. It can be found at medical facilities where it is prepared and administered during cancer clinical trials and treatments. During the 1970’s, it was found in cattle and sheep that were injected with diethylstilbestrol to promote their growth. At risk: Patients who are treated with DES for prostate and breast cancers are at high risk. Workers at locations where diethylstilbestrol is manufactured, packaged, and supplied for cancer clinical trials are at risk for contamination. Health care professionals who prepare and administer DES for cancer therapy risk contamination, as do workers in labs where diethylstilbestrol is used in biochemical research. Etiology and symptoms of associated cancers: DES behaves as a hormonal therapy. By acting as a chemical messenger in the body, it helps control the activity of cells and organs. When administered to pregnant women to help prevent miscarriages or premature deliveries, DES can cause clear-cell adenocarcinoma (CCA) of the vagina and cervix in the mother and in daughters exposed before birth. In sons exposed before birth, DES can increase the risk of testicular cancer. Since DES reduces the level of testosterone in the body, it helps slow down the growth of prostate cancer cells. Side effects of diethylstilbestrol chemotherapy include breast tenderness, lowering of sex drive, tiredness, nausea, and weight gain. History: DES was first synthesized in 1938 at the University of Oxford. It was the first synthetic estrogen. In 1941 diethylstilbestrol was found to be effective in the treatment of gonorrheal vaginitis, menopausal symptoms, and metastatic prostate cancer. Between the 1940’s and the 1980’s, it was used as estrogen-replacement therapy in estrogendeficient women. After epidemiological studies of women linked DES to vaginal and cervical cancers, the U.S. Food and Drug Administration (FDA) advised in 1971 that it no longer be given to pregnant women. To a large extent, tamoxifen has replaced the use of DES in breast cancer treatments, as has leuprolide in the treatment of prostate cancer. Alvin K. Benson, Ph.D. 374
See also Bisphenol A (BPA); Cervical cancer; Colposcopy; Gynecologic cancers; PC-SPES; Pregnancy and cancer; Testicular cancer; Vaginal cancer.
u Digital rectal exam (DRE) Category: Procedures Also known as: Rectal exam, prostate exam Definition: In this procedure, a gloved, lubricated finger is inserted into the rectum to check for abnormalities in the rectal wall. For men, the size and shape of the prostate gland can also be checked for any abnormalities. Cancers diagnosed: Prostate cancer, rectal cancer, colon cancer Why performed: A digital rectal exam (DRE) is a simple procedure used to screen for rectal, prostate, and colon cancers. This procedure allows the physician to check for any abnormal thickness or lumps in the rectal wall. For men, the physician can also check the prostate gland for any unusual characteristics, such as an increase in size or nodules and lumps, since it is located next to the rectum. The benefit of the DRE as a screening tool for prostate cancer is that it can reach a part of the prostate gland where most cancers generally begin. The American Cancer Society recommends that men over age fifty get a DRE annually. High-risk men, defined as those with a
A gloved hand palpates the prostate gland. (LifeART© 2008 Wolters Kluwer Health, Inc.-Lippincott Williams &Wilkins. All rights reserved.)
Salem Health: Cancer family history of prostate cancer or African Americans, should receive DREs yearly beginning at age forty-five. For women, this procedure is usually performed as part of an annual exam. Patient preparation: No special preparation is needed for this procedure. Steps of the procedure: A gloved, lubricated finger is inserted into the rectum. There may be slight discomfort during the exam, but this is a quick procedure that generally takes only a few minutes. A stool sample called a fecal occult blood test may also be taken to check for the presence of blood. This test is done to screen for colon cancer. After the procedure: There are no special instructions, and patients can return to normal activities after the procedure is completed. Risks: No risks are associated with this exam. Results: If abnormalities are detected during the procedure, then the physician will recommend additional screening tests, such as a colonoscopy or sigmoidoscopy, which are used to screen for colon cancer. If a problem is suspected with the prostate gland, then a prostate-specific antigen (PSA) blood test, an ultrasound, or possibly a biopsy of the prostate gland may be suggested to screen for prostate cancer. Vonne Sieve, M.A. See also Anal cancer; Anoscopy; Benign prostatic hyperplasia (BPH); Carcinomatosis; Colonoscopy; Diverticulosis and diverticulitis; Endorectal ultrasound; Prostate cancer; Prostate-specific antigen (PSA) test; Screening for cancer; Sigmoidoscopy; Urologic oncology.
u Dilation and curettage (D&C) Category: Procedures Also known as: Uterine scraping Definition: Dilation and curettage (D&C) is used to surgically remove sections of the lining of the uterus and suspicious growths in the uterus in an examination for cancer cells. The lining of the uterus is called the endometrium. “Dilation” refers to manually opening the cervix to access the uterus. “Curettage” refers to using a curette, a surgical instrument, to gently scrape sections of the endometrium away from the uterus. Cancers diagnosed: Uterine cancer (uterine sarcoma), endometrial cancer (endometrial carcinoma), precancer-
Dilation and curettage (D&C) ous cellular changes that can lead to cancer (endometrial hyperplasia), precancerous growths that can change to cancer (endometrial polyps) Why performed: D&C is performed to diagnose uterine cancer, endometrial cancer, or precancerous cells in the uterus. A D&C obtains tissue specimens for analysis by a pathologist. A D&C may be used if cancer is suspected or if a biopsy is suggestive of cancer but not conclusive. A small tissue sample is obtained in a biopsy, and a larger representation of the uterine tissues is collected with a D&C. Additionally, the tissue specimens may be tested for estrogen and progesterine receptor cells. Increases in these hormones are associated with an increased risk of uterine and endometrial cancer. Patient preparation: A D&C is a short outpatient procedure performed at a hospital’s surgery department or an outpatient surgical center. General anesthesia is usually used, so the patient is not awake. Patients should not eat or drink past midnight prior to the day of the procedure or for seven hours before the D&C. In some cases, spinal or epideral blocks may be used instead of general anesthesia. On the day of the procedure, the patient provides a urine sample and dons an examination gown. Steps of the procedure: The patient lies on her back on a surgical table. The patient’s knees are spread and her feet are placed in stirrups. The patient’s vital signs are monitored, and anesthesia is administered. The vaginal area and urethra are cleansed. A catheter tube may be inserted into the urethra to collect urine during the procedure. A speculum is inserted into the vagina to separate the vaginal walls. The cervix and vagina are cleansed. Metal devices are used to dilate the cervical opening to allow the doctor to access the uterus. A curette is an instrument used to remove the lining of the uterus in sections. It has a long narrow handle with a metal loop at the end. The curette is inserted through the vagina and cervix and into the uterus. The doctor uses the curette to gently scrape the lining of the uterus. The tissue specimens are prepared and sent to a pathologist for examination for cancer cells. When the D&C is complete, the dilating device, speculum, and catheter are removed. The patient is monitored in a postsurgical recovery area until she is alert and is provided with a sanitary napkin to protect her clothing from blood. The patient should not drive and needs to receive a ride home from another person. After the procedure: Patients may experience menstruallike cramps or backache and are prescribed pain medication. Bleeding and the passing of small blood clots may oc375
Dioxins cur for a few days following the procedure. Light vaginal bleeding or staining may continue for several weeks. Patients should wear sanitary napkins but should not use tampons. Patients are encouraged to rest for a few days following the surgery and should not participate in sexual intercourse during this time. Risks: A D&C is considered a low-risk procedure. The risks include those of general anesthesia as well as uterine perforation, cervical laceration, and endometrium scarring. Patients should contact their doctors if they experience heavy bleeding, increased pain, problems breathing, or fever and other signs of infection. Results: A pathologist examines the tissue specimens for cancerous or precancerous cells. The pathologist’s report is conveyed to the doctor. Mary Car-Blanchard, O.T.D., B.S.O.T. u For Further Information Engelsen, I. B., et al. “Pathologic Expression of p53 or p16 in Preoperative Curettage Specimens Identifies HighRisk Endometrial Carcinomas.” American Journal of Obstetrics and Gynecology 195, no. 4 (October, 2006): 979-986. Larson, D. M., et al. “Comparison of D&C and Office Endometrial Biopsy in Predicting Final Histopathologic Grade in Endometrial Cancer.” Obstetrics and Gynecology 86, no. 1 (July, 1995): 38-42. Merisio, C., et al. “Endometrial Cancer in Patients with Preoperative Diagnosis of Atypical Endometrial Hyperplasia.” European Journal of Obstetrics & Gynecology and Reproductive Biology 122, no. 1 (September 1, 2005): 107-111. Papaefthimiou, M., et al. “The Role of Liquid-Based Cytology Associated with Curettage in the Investigation of Endometrial Lesions from Postmenopausal Women.” Cytopathology 16, no. 1 (February, 2005): 32-39. Saygili, H. “Histopathologic Correlation of Dilatation and Curettage and Hysterectomy Specimens in Patients with Postmenopausal Bleeding.” European Journal of Gynaecological Oncology 27, no. 2 (2006): 182-184. Wang, X., et al. “Comparison of D&C and Hysterectomy Pathologic Findings in Endometrial Cancer Patients.” Archives of Gynecology and Obstetrics 272, no. 2 (July, 2005): 136-141.
See also Colposcopy; Conization; Cryoablation; Endometrial cancer; Gestational trophoblastic tumors (GTTs); Giant cell tumors (GCTs); Gynecologic cancers; Hysterectomy; Pap test; Uterine cancer. 376
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u Dioxins Category: Carcinogens and suspected carcinogens RoC status: Under the heading “2,3,7,8tetrachlorodibenzo-p-dioxin (TCDD),” known human carcinogen since 2001 Also known as: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); polychlorinated dibenzo-p-dioxin (PCDD) Related cancers: All cancers, including lung cancer and non-Hodgkin lymphoma Definition: Dioxins are polychlorinated dibenzo-p-dioxins (two benzene rings bridged with two atoms of oxygen). The one in which carbons 2, 3, 7, and 8 are chlorinated is called 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD is the deadliest synthetic chemical—so much so that its toxicity is used as a benchmark by which to rate the toxicity of other chemicals through a value called a “toxic equivalency factor” (TEF). Exposure routes: All species are exposed to dioxins through inhalation or ingestion via air, water, and food. In humans, the major source of TCDD is diet. Out of an average 120 picograms per day in food, 38 are from meat, 24 from dairy foods, 18 from milk, 13 from chicken and pork each, 8 from fish, 4 from eggs, and 2 from air. Where found: TCDD and other dioxins are not commercial products but are formed as by-products during both organochlorine manufacturing and waste combustion and incineration operations. Dioxins contaminate the atmosphere through incineration and waste disposal; the land through manufacturing, agricultural herbicides, and incineration; and the water through effluent discharges, especially from pulp and paper plants. Residues of TCDD, because of its thermo- and bio-stability, are widely distributed in the air, soil, water, sediments, biota (flora and fauna of a region), and human food. Because it has very low solubility in water and a very high partition coefficient, it accumulates in fat, becomes concentrated in aquatic biota, and is ecomagnified through the food chain. Freshwater biota hold the highest amount of TCDD, which may also be bound to organics in sediments. At risk: People at greatest risk for exposure to TCDD and other dioxins are those living near contaminated sites or eating contaminated foods, such as waste-incineration workers, firefighters, workers in chemical research facilities, those working in the production and use of pentachlorophenol and other chlorinated compounds, and those associated with chlorophenoxy herbicide production, use, and disposal.
Salem Health: Cancer
Dioxins
Etiology and symptoms of associated cancers: TCDD has extreme potency for chronic biological effects. There is a general commonality among animal species in some of the effects of TCDD, while other effects are speciesspecific. For example, birth defects and lowering of male sex hormones (testicular atrophy) have been reported in several bird and mammalian species. Chronic toxicity of TCDD increases with the duration of exposure. TCDD is regarded a both a teratogen (an agent of developmental malformations) and carcinogen (an agent of malignancy). It affects both the reproductive system (causing low sperm counts, lowering of testosterone, and testicular atrophy, among other effects) and developmental stages (leading to malformations in newborns). In humans, birth defects, termination of pregnancy, decreased fertility (lower sperm count and testosterone and testicular atrophy), endometriosis, diabetes, learning disorders, skin and lung effects, and cancer are commonly recognized. The half-life of TCDD in humans varies from thirty days to ten years. Men cannot degrade TCDD, while women can transfer it to a fetus via the placenta and to a newborn via breast milk. TCDD causes neurobehavioral deficits and lowering of testosterone in neonates due to their exposure in utero. The U.S. federal government, for example, has had to issue warnings about the consumption of TCDD-tainted Lake Michigan fish by women who are pregnant or want to become pregnant and by children and young adults. The carcinogenic effects of TCDD are evident in the increased rate of both benign and malignant tumors seen in those who experience significant exposures to the chemical. By binding to the “Ah receptor”—a protein ubiquitous in human and other vertebrate animal tissues that plays a major role in gene transcription—TCDD activates biological responses that can lead to carcinogenic activity. Because the chemical accumulates in fat over long periods of exposure, this carcinogenic activity increases with time, even with low chronic exposures.
to an overall increased risk for all cancers combined, an increased risk for lung cancer, and an increased risk for nonHodgkin lymphoma. The U.S. government has therefore classified TCDD as a known human carcinogen since 2001. TCDD was present in herbicides widely used in the 1960’s and 1970’s, including Agent Orange, used during the Vietnam War. Although TCDD no longer is used in these agents, it continues to occur as a by-product of paper and pulp bleaching (which is why some people, for example, prefer to use unbleached coffee filters and paper towels); in the incineration of municipal and hospital waste; in the production of metals; and in the combustion of both wood and fossil fuels. M. A. Q. Khan, M.D., Ph.D.
History: First listed as a reasonably anticipated carcinogen in the National Toxicology Program’s Second Annual Report on Carcinogens (1981), from the U.S. Department of Health and Human Services, TCDD underwent several subsequent studies. Some of these considered cancers in human populations occupationally exposed to TCDD, while others examined what took place at the molecular and cellular levels in human and animal tissue exposed to TCDD. The data from studies conducted through 1996 were evaluated by the International Agency for Research on Cancer (IARC), whose results were published in 1997. The IARC concluded that exposure to TCDD was linked
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For Further Information Colborn, T., D. Dumanoski, and J. P. Myers. Our Stolen Future. New York: Dutton Press, 1995. Committee on EPA’s Exposure and Human Health Reassessment of TCDD and Related Compounds. Board on Environmental Studies and Toxicology. Division on Earth and Life Studies. National Research Council of the National Academies. Health Risks from Dioxin and Related Compounds: Evaluation of the EPA Reassessment. Washington, D.C.: National Academies Press, 2006. Khan, M. A. Q., and R. H. Stanton. Toxicology of Halogenated Hydrocarbons. New York: Pergamon Press, 1980. U.S. Department of Health and Human Services. Public Health Service. National Toxicology Program. Eleventh Report on Carcinogens. Research Triangle Park, N.C.: Author, 2005. U.S. Environmental Protection Agency. Office of Research and Development. Office of Health and Environmental Assessment. Health Assessment Document for 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and Related Compounds. Washington, D.C.: Author, 1994. Other Resources
National Academy of Sciences http://www.nasonline.org National Cancer Institute http://www.cancer.gov National Toxicology Program http://ntp.niehs.nih.gov See also Agent Orange; Bile duct cancer; Curcumin; Organochlorines (OCs); Pesticides and the food chain; Sarcomas, soft-tissue; Vinyl chloride. 377
Disseminated intravascular coagulation (DIC)
u Disseminated intravascular
coagulation (DIC) Category: Diseases, symptoms, and conditions Also known as: Consumptive coagulopathy Related conditions: Bleeding, thrombosis Definition: Disseminated intravascular coagulation (DIC) is a condition that prevents the body from regulating blood clotting. Small blood clots develop throughout the body, and substances needed for clotting become depleted. This systemic coagulation and resulting inability to form clots can lead to organ failure and hemorrhage (excessive bleeding). DIC can be chronic and develop over time, or arise acutely and require emergency intervention. Risk factors: The clotting cascade associated with DIC can be brought on by a number of health problems: infection, severe trauma, cancer, complications during pregnancy and childbirth, and some types of snakebite. Patients with solid tumor cancers and acute leukemias have an increased risk. Chronic DIC may be induced or aggravated by various stimuli, including radiation therapy and chemotherapy. Acute DIC is usually associated with infections. Etiology and the disease process: DIC occurs when an overabundance of clotting factors are released into the bloodstream in response to tissue damage. Widespread clotting occurs within the microvasculature throughout the body. The excessive clotting can damage organs and, paradoxically, “uses up” clotting factors and platelets (clotting cells) such that the blood can no longer clot normally. Incidence: Some 10 to 15 percent of patients with metastatic cancer show evidence of DIC, and it is present in approximately 15 percent of patients with acute leukemia. Symptoms: Acute DIC symptoms include bleeding, sudden bruising, shortness of breath, and low urine output from kidney damage. Chronic DIC may produce no symptoms at all or only minimal bleeding or clotting. Screening and diagnosis: No single test is used to diagnose DIC. Blood tests include a D-dimer test (test for a certain breakdown product of blood clots), prothrombin time (measure of blood-clotting tendency), fibrinogen level (level of a protein needed for blood to clot), and complete blood count. The physician will look at the patient’s clinical symptoms (bleeding, bruising, and so on) along with available blood tests to make a diagnosis. 378
Salem Health: Cancer Treatment and therapy: Treatment for DIC involves treatment for the underlying cause. Supportive care with platelets and clotting factors will be used to stop excessive bleeding. Transfusions of blood cells may be necessary to replace blood that has been lost. In some cases, heparin (a blood thinner) may be used to stop the cascade of clotting events. Prognosis, prevention, and outcomes: Prognosis will be primarily determined by the underlying condition that led to DIC and the severity of the DIC itself. For patients with sepsis and severe trauma, the presence of DIC may increase the risk of death by 1.5 to 2 times. Melanie Hawkins, B.S.N., R.N., O.C.N. See also Acute lymphocytic leukemia (ALL); Acute myelocytic leukemia (AML); Leukemias; Mesothelioma; Paraneoplastic syndromes.
u Diverticulosis and
diverticulitis Category: Diseases, symptoms, and conditions Also known as: Diverticular disease Related conditions: Perforated bowel, bowel obstruction, chronic constipation, peritonitis, gastrointestinal bleeding, colon cancer Definition: Diverticulosis is a condition in which an outpouching occurs in an area of the colon. This area of outpouching is known as a diverticulum. Occasionally a diverticulum becomes infected or inflamed, leading to a condition known as diverticulitis. Risk factors: Risk factors include a low intake of dietary fiber and chronic constipation. Etiology and the disease process: Inadequate intake of dietary fiber is thought to contribute to the development of diverticulitis. When fiber is lacking in the diet, there is less residue in the fecal matter. Reduced residue narrows the bowel lumen, increasing intraluminal pressure during defecation. A diverticulum results when high intraluminal pressure is exerted on an area of weakness in the gastrointestinal wall, where blood vessels enter. High pressure causes layers of the wall in the area of weakness to herniate through the muscular wall, forming a diverticulum. Fecal material, undigested food, and bacteria collect in the diverticulum, forming a hard mass that diminishes blood flow to the diverticulum. The diverticulum becomes
Salem Health: Cancer
Diverticulosis and diverticulitis
Colon
Diverticuli
Diverticulitis, a condition in which outpouchings on the colon wall become inflamed, is a risk factor for cancer.
inflamed and infected, causing fever and lower abdominal pain. If this condition is left untreated, an abscess may develop and the intestinal wall may perforate. Incidence: According to the National Institutes of Health, diverticular disease affects about 2.5 million people in the United States. Of those individuals, more than 600,000 require hospitalization annually for treatment of the disease. About 20 percent of those diagnosed with diverticulosis will develop diverticulitis at some point in their lives. Symptoms: Diverticulosis typically produces no symptoms. Symptoms occur when a diverticulum becomes inflamed or infected and diverticulitis develops. When diverticulitis is mild, symptoms include moderate pain in the left lower abdomen and low-grade fever. The inflammation may also cause irritability and spasticity of the adjoining abdominal wall, producing diarrhea. In acute diverticulitis, severe cramping pain suddenly occurs in the
left lower abdomen. Anorexia, nausea, constipation, fever, weakness, and abdominal distension may also occur. When an abscess occurs and the bowel perforates, abdominal pain becomes severe and abdominal rigidity develops. High fever, chills, low blood pressure, increased heart rate, decreased level of consciousness, diarrhea, and diminished urine output also occur. Without immediate treatment, death may occur. Screening and diagnosis: Because diverticulosis does not produce symptoms, it is commonly discovered during testing for another disorder. It is also commonly found during colonoscopy for routine colon cancer screening. When symptoms prompt a visit to a health care provider, diverticulitis is diagnosed through physical examination and diagnostic testing. The health care provider will begin by taking a medical history, asking questions about the onset and severity of symptoms, bowel habits, dietary intake, and medications. The health care provider may also perform a digital rectal examination to check for a mass or blockage. A small stool sample may be obtained to check for occult blood (blood that is not visible to the eye). The health care provider may also order a blood test, known as a complete blood count, to check for signs of infection and bleeding. Blood cultures may be ordered to determine whether the infection has spread to the blood. An abdominal computed tomography scan, commonly referred to as an abdominal CT scan, may be performed to detect diverticulitis and can reveal an abscess. A barium enema may also be performed. An abdominal X ray may show free air under the diaphragm, indicating that perforation has occurred. When acute diverticulitis subsides, the health care provider may order a colonoscopy to determine the extent of disease and to rule out other disorders. Diverticulitis may be a risk factor for contracting certain types of cancer, and it can make cancers of the colon more difficult to properly diagnose. Treatment and therapy: Treatment for diverticular disease depends on the severity of disease. Diverticulosis is commonly treated with a high-fiber diet. Increasing fiber in the diet softens stools and decreases the pressure within the colon so that fecal material moves through freely. Twenty to thirty-five grams of fiber should be consumed each day. A psyllium dietary fiber supplement may also be recommended. Fluid intake should also be increased to two liters per day, if other medical conditions allow. Exercise also helps increase the rate of stool passage. Mild diverticulitis may be treated with a liquid diet to rest the bowel until symptoms subside, followed by a highfiber diet. Antibiotics such as metronidazole, ciprofloxacin, levofloxacin, or co-trimoxazole may be prescribed 379
Do-not-resuscitate (DNR) order for seven to ten days. A mild analgesic such as acetaminophen may also be recommended. If discomfort is caused by spasm, an antispasmodic such as oxyphencyclimine may be prescribed. Severe diverticulitis may require hospitalization for administration of intravenous antibiotics and fluids. If the infection does not subside with antibiotic therapy, surgical intervention may be necessary. Emergency surgery may also be necessary if a fistula or perforation occurs. Surgery involves removing a portion of the colon and clearing the abdominal cavity. Because infection is present, the colon cannot be reconnected until the infection is cleared. Therefore the surgeon must create a temporary colostomy. A second surgery is required to reconnect the colon after the infection is gone. Prognosis, prevention, and outcomes: With early recognition and treatment, prognosis is good. According to the National Institutes of Health, approximately 3,300 deaths occurred as a result of diverticular disease in 2002. Collette Bishop Hendler, R.N., M.S. u For Further Information Black, P. and C. Hyde. Diverticular Disease. Hoboken, N.J.: John Wiley & Sons, 2005. Kruis, W., et al. Diverticular Disease: Emerging Evidence in a Common Condition. Norwell, Mass.: Springer and Falk Foundation, 2006. Munden, Julie, et al. Pathophysiology Made Incredibly Easy! 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2008. u
Other Resources
MedlinePlus Diverticulosis http://www.nlm.nih.gov/medlineplus/tutorials/ diverticulosis/htm/index.htm National Digestive Diseases Information Clearinghouse Diverticulosis and Diverticulitis http://digestive.niddk.nih.gov/ddiseases/pubs/ diverticulosis/ See also Antidiarrheal agents; Colonoscopy and virtual colonoscopy; Colorectal cancer; Colorectal cancer screening; Crohn disease; Cruciferous vegetables; Diarrhea; Enterostomal therapy; Fecal occult blood test (FOBT); Fiber; Gastrointestinal cancers; Gastrointestinal complications of cancer treatment; Hemorrhoids; Immunochemical fecal occult blood test (iFOBT); Inflammatory bowel disease; Laxatives; Nuclear medicine scan; Nutrition and cancer 380
Salem Health: Cancer prevention; Obesity-associated cancers; Pancolitis; Sigmoidoscopy; Small intestine cancer; Upper gastrointestinal (GI) series.
u Do-not-resuscitate (DNR)
order Category: Social and personal issues Also known as: AND (allow natural death), no code Definition: A do-not-resuscitate (DNR) order permits natural death for a patient who has an irreversible, terminal condition, such as advanced cancer, and receives care by health professionals at home or in a medical facility. Purpose: The purpose of the order is to allow a cancer patient to experience a natural death while under the care of medical personnel. The order is enacted only when the patient stops breathing or the heart stops beating because of the terminal illness. Even with a DNR, a natural death may not be allowed if heart or respiratory failure is caused by an unrelated event such as a car accident. Health care professionals providing care to patients without DNR orders, regardless of the severity of disease, are legally required to provide cardiopulmonary resuscitation (CPR) and perform medical interventions at the time of death. These efforts must not only be initiated but also be continued until they are deemed futile by the physician or a designated professional. The extraordinary measures performed by health care professionals in the event of respiratory or heart failure include CPR and placing the patient on life support. These procedures are invasive and often considered painful. Appropriately performed CPR can cause broken bones and punctured organs even in generally healthy individuals, such as accident victims. Such injuries are more likely to occur in frail individuals who are near death. Life support may consist of intravenous (IV) drugs that cause the heart to continue to beat. Without the medications, the heart will stop and death will be irreversible in a few minutes, even with aggressive treatment. Mechanical ventilation (a breathing machine) is another form of life support. A tube is inserted into the patient’s throat and is attached to a mechanical ventilator. If the patient needs the ventilator for a long period of time, a tracheostomy (a surgical opening in the neck) will be created to attach to the machine. The ventilator causes artificial breathing. Without the machine, the patient would be unable to breathe, and life would not be sustained. Life support requires that an individual has continuous care, often in a medical facility.
Salem Health: Cancer
Down syndrome and leukemia
Procedure: In the United States, an adult who receives health care services and wants to be allowed to die a natural death must consult with a physician before a DNR order is written. The majority of individuals with DNR orders have a terminal illness such as advanced or aggressive cancer. Electing to die a natural death allows the individual to have some control in the death process. Most individuals report they would prefer to die in their own home rather than in a hospital or nursing home. Terminally ill patients may be able to stay at home if nursing or other care is provided. If they want to die naturally at home, a DNR is needed. These patients may be transferred to the hospital if a higher level of care is needed. The DNR order must be provided to ambulance personnel transporting the patient to prevent unnecessary interventions in the event of respiratory or cardiac failure on the way to the hospital. The first step in obtaining a DNR order is for cancer patients to discuss the issue with their medical provider. The best time to discuss these issues is before death is imminent. This allows for a less emotional and more rational discussion of the situation. Any adult who is mentally competent and his or her physician can determine if a DNR order is appropriate. If the patient is not competent to discuss the issue, family members may approach the physician. If the patient (or family if the patient is not competent) and physician are in agreement, the physician can write the DNR order. If the patient disagrees with the physician’s recommendations, he or she may select another health care provider or the physician may ask for a medical ethics consultation. The consultation is provided by a professional in medical ethics who is not involved in the direct care of the patient.
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Medical care: Many cancer patients and their families are afraid of having a DNR order. There is concern that inadequate medical care may be provided to those who have a DNR order. However, these orders do not interfere with routine medical care. Care of the patient changes only in its focus, not in its provision. Pain management, comfort, and end-of-life issues become the priority rather than disease management. The patient may have extensive health care needs, such as personal grooming, bathing, and feeding. These activities are continued. A DNR order prohibits only extraordinary measures that would prevent death or prolong life unnecessarily. For the DNR order to be active, a copy of the order must be submitted when entering home health care, hospice, or any other medical facility. If the order is not present and respiratory or cardiac failure occurs, cardiopulmonary resuscitation is medically obligated. A DNR order can be revoked by a patient at any time. Amy Bull, D.S.N., A.P.N.
Related conditions: Transient leukemia (TL), transient myeloproliferative disorder, transient abnormal myelopoiesis
For Further Information Gott, Peter H. Live Longer, Live Better: Taking Care of Your Health After Fifty. Sanger, Calif.: Quill Driver Books, 2004. Kiernan, Stephen P. Last Rights: Rescuing the End of Life from the Medical System. New York: St. Martin’s Press, 2006. Mayo Clinic. Mayo Clinic Family Health Book. 3d ed. New York: HarperCollins, 2003.
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Other Resources
American Cancer Society Advance Directives http://www.cancer.org/docroot/MIT/mit_3_1_1.asp National Cancer Institute End-of-Life Decisions http://www.cancer.gov/cancertopics/pdq/ supportivecare/transitionalcare/HealthProfessional/ page9 See also Advance directives; Counseling for cancer patients and survivors; Elderly and cancer; End-of-life care; Grief and bereavement; Hospice care; Informed consent; Living will; Palliative treatment; Relationships; Stress management; Survivorship issues; Transitional care.
u Down syndrome and leukemia Category: Diseases, symptoms, and conditions Also known as: Trisomy 21 and cancer of white blood cells
Definition: In Down syndrome the individual has three copies of chromosome 21 instead of two. Those with Down syndrome have a significant risk of developing certain forms of leukemia. Leukemia is a blood cancer in which cancerous changes take place in marrow cells that form lyphocytes (white blood cells). Risk factors: Children with Down syndrome have a ten to twenty times greater risk of developing leukemia. They develop acute lympholastic leukemia and two types of megakaryoblastic leukemia: transient leukemia (TL) and acute megakaryoblastic leukemia (AMKL). Down children have a five hundred times greater risk of developing AMKL than other children. Some 10 percent of newborns with Down syndrome develop TL. 381
DPC4 gene testing Etiology and the disease process: In TL and AMKL, blasts (immature blood cells) accumulate in blood and bone marrow, and white blood cell differentiation is abnormal. TL in the newborn goes into remission within a few months. Of those who had TL, 20 to 30 percent will develop AMKL later in life. Although the relationship between Down syndrome and increased risk for leukemia is not understood, it has been observed that as well as having trisomy for chromosome 21, children who develop TL have mutations in the transcription factor GATA1, which plays an important role in the normal development of red blood cells, megakaryocytic, and basophilic cell lines. The GATA1 gene (also known as a hematopoietic growth factor) is on the X chromosome. It is thought that additional mutations must occur for AMKL to develop. Incidence: The incidence of Down syndrome is 1 in 800, and 1 in 95 Down syndrome children will develop leukemia, compared with 1 in 2,000 children in general. Symptoms: As with other leukemias, the symptoms associated with Down syndrome leukemias include fatigue, skin pallor, bruising, bleeding, difficulty in wound healing, enlarged lymph nodes, and joint pain. Screening and diagnosis: Analysis of the blood is done in children with Down syndrome to test for signs of leukemia. In TL in Down syndrome, analysis of blood and bone marrow shows variable numbers of blasts. The acute leukemia cell produces nonfunctional leukemia cells that crowd out normal cells. Treatment and therapy: Children with Down syndrome and leukemia are typically treated with chemotherapy. Blasts of Down syndrome TL are sensitive to low doses of cytosine arabinoside. Children with Down syndrome and leukemia are more sensitive than other children to some drugs used in chemotherapy, such as methotrexate, so Down syndrome children must be carefully monitored for drug toxicity. Prognosis, prevention, and outcomes: Down syndrome TL neonates have a 15 percent risk of developing a potentially fatal liver disease and an increased risk of developing cardiopulmonary failure and spleen necrosis. Though Down syndrome children are at an increased risk of developing leukemias, they have a reduced risk of developing solid tumors. Susan J. Karcher, Ph.D. See also Acute lymphocytic leukemia (ALL); Acute myelocytic leukemia (AML); Blood cancers; Childhood cancers; Cytogenetics; Genetic testing; Myelodysplastic syndromes; Ultrasound tests. 382
Salem Health: Cancer
u DPC4 gene testing Category: Procedures Also known as: SMAD4, MADH4 Definition: The DPC4 gene product maintains normal cell growth rates. Mutations in DPC4 lead to uncontrolled cell growth and, ultimately, to many cancers, especially those of the gastrointestinal tract and pancreas. Inherited mutations in DPC4 are one cause of juvenile polyposis syndrome (JPS), an inherited condition that results in a predisposition to colorectal cancer. Cancers diagnosed: Juvenile polyposis syndrome, familial colon cancer Why performed: Approximately 20 percent of individuals afflicted with JPS, a condition in which numerous polyps form in the colon, bear mutations in the DPC4 gene. Other cases may be caused by mutations in BMPR1A or other genes. Although polyps resulting from JPS are initially benign, a small proportion may develop into carcinomas. Genetic testing is performed to confirm a diagnosis of patients exhibiting symptoms of JPS and to characterize the DPC4 mutation causing the disease. Because JPS is an inherited disorder, genetic testing is also often done in previously undiagnosed relatives of JPS patients to determine whether prophylactic treatment is required. Testing is performed at or before age fifteen, the time at which routine screening by colonoscopy is recommended. Patient preparation: Patients considering genetic testing may meet with a genetic counselor to discuss the benefits and risks of the test and the significance of negative, positive, and inconclusive tests. Material required for genetic testing is obtained from a blood sample or from cheek cells obtained by mouthwash. No special preparation is required. Steps of the procedure: Samples are sent to a clinical laboratory that offers DPC4 screening. Deoxyribonucleic acid (DNA) is isolated from the blood sample, and the DNA that encodes DPC4 is amplified by polymerase chain reaction (PCR) and sequenced using standard methods. After the procedure: The patient will consult with a physician and/or genetic counselor to discuss the implications of the test results. Risks: Complications from drawing blood are rare but may include excessive bleeding, hematoma, or infection. Because the information obtained from DPC4 screening
Salem Health: Cancer may have significant psychological effects, it is important that patients be offered genetic counseling. Results: Sequence analysis allows clinicians to identify the specific DNA mutation(s) present in a JPS patient. Once this mutation has been identified, close relatives can be screened to determine if they share the mutation that causes JPS. Routine colonoscopy and polypectomy, beginning at age fifteen, is recommended for those bearing mutations in DPC4. Kyle J. McQuade, Ph.D. See also Colorectal cancer; Colorectal cancer screening; Family history and risk assessment; Genetic counseling; Genetic testing; Hereditary cancer syndromes; Hereditary mixed polyposis syndrome; Hereditary polyposis syndromes; Juvenile polyposis syndrome.
u Drug resistance and
multidrug resistance (MDR) Category: Chemotherapy and other drugs Definition: Drug resistance is the loss of effectiveness of a drug used to kill or weaken cancer cells. It may be intrinsic (active in the cancer cell before treatment) or acquired (developed after treatment). Multidrug resistance (MDR) is the adaptation of cancer cells to withstand a large number of structurally and functionally unrelated drugs designed to kill cancer cells. Development of resistance: Drug resistance and MDR are major causes of treatment failure in cancer patients. When exposed to chemotherapeutic drugs, the cancer cell activates processes or synthesizes molecules that can inactivate or eliminate the drugs. Cancer cells have many alternative pathways at their disposal to overcome the toxic effects of chemotherapeutic drugs. Most of these mechanisms have origins in the normal cell. The oncologist recognizes the phenomenon of MDR and has developed treatment programs to delay its onset. Chemotherapy can consist of treatment with single drugs or multiple drugs. Chemotherapy is commonly combined with radiation or surgery. Research is ongoing to develop drugs that specifically target MDR when it develops. Anticancer drugs have to overcome many challenges before they can accomplish their mission. Tumors are rapidly growing and have a poorly developed vascular system. The cancer cells have difficulty in receiving adequate oxygen and nutrients and therefore adapt to a hypoxic (lowoxygen) environment. This hypoxic environment can cause
Drug resistance and multidrug resistance (MDR) cancer cells to become resistant to drugs. Drugs have difficulty navigating the poor tumor vascular system to reach the cells. The drugs must be able to pass the cell membrane, navigate the cytoplasm, and reach the nucleus, where most drugs exert their effects. They must accumulate in high concentrations in their active form and must sustain these concentrations long enough to kill the cancer cell. Drugs against MDR proteins: A major research focus is to develop drugs that counteract MDR proteins. The MDR proteins, known as drug efflux pumps, transport drugs out of cancer cells. These proteins belong to a family of proteins called the adenosine triphosphate (ATP) binding cassette proteins (ABCs). The ABC proteins are overexpressed (increase greatly) when exposed to chemotherapeutic drugs. These proteins reside in the cell membrane and consist of an embedded portion that forms a pore for transport of drugs and an internal portion that binds to the ATP molecule. When the ATP molecule is broken down, energy is released to drive the process. P-glycoprotein is the main MDR protein that has been studied, and it remains of primary interest. Intensive research has developed first-, second-, and third-generation inhibitors to this protein, with each generation improving on the previous generation. Researchers have begun development of inhibitors that act by binding to the ABC protein and inhibiting its activity. The drugs have diverse chemical structures and origins. Multidrug resistance-associated protein (MRP1) is also a major target of drug research. Six additional MRP proteins with structural similarities to MRP1 have been identified. Several other MDR proteins have been identified as well, including breast cancer resistant protein, mitoxantrone resistant protein, and others less well characterized. Cellular changes associated with MDR: MDR is commonly associated with changes in the intracellular distribution of the chemotherapeutic drug. Most cancer therapies target deoxyribonucleic acid (DNA) or nuclear enzymes. When MDR develops, there is a redistribution of drug from the nucleus into cellular vesicles such as the Golgi apparatus, endosomes, and lysosomes. The drugs are then transported toward the plasma membrane and excreted from the cell by the process of exocytosis. This process of elimination is considered passive and is different from the MDR efflux pumps, which require energy input to proceed. The expression of MDR pumps is also associated with altered drug distribution within cancer cells. Most chemotherapeutic drugs are mildly alkaline and have no charge. MDR cells have a more acidic pH inside subcellular vesicles than that of drug-sensitive cells. When drugs diffuse into the vesicles of MDR cells, they become 383
Drug resistance and multidrug resistance (MDR) protonated and take on a charge. The drugs are then trapped in the vesicles and cannot reach the nucleus to exert their effect. They can then be excreted from the cell by the process of exocytosis. Glutathione and its associated enzyme, glutathiononeS-transferase (GST), are commonly found in the body and serve as a natural detoxification mechanism. GST can increase in the presence of a chemotherapeutic drug in the cancer cell. GST then catalyzes the binding of glutathione to the drug. The drug then becomes more water soluble, less toxic to the cell, and more readily excreted. Research is under way to develop drugs that inhibit GST and thus restore the cancer cell’s sensitivity to the drug. Drugs that inhibit topoisomerase enzymes: The topoisomerase enzymes control the process of unwinding the DNA double helix during transcription or replication of the DNA molecule. This process is essential during cell division. Because cancer cells are rapidly dividing, topoisomerase inhibitor drugs are attractive treatments against a variety of cancers. To function, the drug must form a three-way complex with DNAand the enzyme. Conditions in the cell that interfere with this formation will lead to resistance. Mutations in the topoisomerase enzymes also cause resistance. Most topoisomerase inhibitors that have been the subject of clinical trials are derivatives of the plant extract camptothecin, although a semisynthetic derivative has also been developed. Drugs that inhibit DNA synthesis: Rapidly dividing cancer cells have a great need for DNA synthesis, so anticancer drugs such as methotrexate and 5-fluorouracil have been used to block pathways to its synthesis. Methotrexate inhibits the enzyme dihydrofolate reductase, while 5-fluorouracil blocks the enzyme thymidylate synthase. Both of these enzymes are required for the synthesis of nucleotides, the building blocks of DNA. Methotrexate was introduced in the mid-twentieth century for the treatment of acute lymphoblastic anemia, but resistance occurs rapidly. Resistance to the drugs can be due to increased production of the target enzymes, defective transport of the drugs, or increased excretion by efflux pumps. A number of chloroethyl- and methyl-nitrosourea therapeutic drugs attack the guanine unit of DNA in cancer cells to exert their toxic effect. The cancer cell acquires resistance to the drug by activating the enzyme O6-alkylguanine DNA alkyltransferase (AGT) to repair the damage. O6-benzylguanine inhibits the action of AGT and is used in the clinic in combination with nitrosourea drugs to reverse the resistance. Toxicity problems can occur when these drugs are used at levels needed to attain maximum effectiveness. 384
Salem Health: Cancer Protein kinase C is an enzyme that occupies a key role in the transfer of growth factor signals that result in DNA synthesis and cell division. This enzyme directly affects the expression of several proteins involved in drug resistance. These activities make protein kinase C an attractive target for therapeutic drugs. Drugs that stimulate apoptosis: Most cancer drugs act by stimulating the process of apoptosis (programmed cell death). The susceptibility of a cancer cell to apoptosis depends on the balance between pro- and antiapoptotic proteins in the cell. When the TP53 protein (the primary proapoptotic protein) discovers genetic damage to the DNA molecule, it summons other proteins to halt cell division, and if necessary, to initiate apoptosis. Most cancers show mutations in the TP53 gene, so that instead of helping to destroy cancer cells, they can even promote cancer. Antiapoptotic proteins, particularly the Bcl-2 family, become more active during chemotherapy, leading to resistance to apoptosis. Drugs that stimulate ceramide synthesis: Ceramide is the basic unit of sphingomyelin, a lipid structural element of cell membranes. Various stress stimuli, including radiation and chemotherapy, result in the formation of ceramide through the breakdown of sphingomyelin, or through synthesis from other molecules. Ceramide then acts as a second messenger relaying a signal to initiate apoptosis or other biological processes. MDR can result in a reduction in ceramide concentration through conversion to an inactive molecule. This reduces the effectiveness of chemotherapy, since many chemotherapeutic drugs exert their effect through apoptosis. Drugs are under development that increase ceramide levels in tumor cells by promoting ceramide synthesis or by blocking the conversion of ceramide to inactive compounds. Side effects: Depending on the chemotherapeutic drug administered, a variety of side effects can occur. These can include nausea and vomiting, diarrhea and vomiting, anemia, malnutrition, memory loss, depression of the immune system, and toxicity to certain body organs. David A. Olle, M.S. u
For Further Information Bredel, Markus. “Anticancer Drug Resistance in Primary Human Brain Tumors.” Brain Research Reviews 35 (2001): 161-204. Liscovitch, Mordechai, and Yaakov Lavie. “Cancer Multidrug Resistance: A Review of Recent Drug Discovery Research.” I Drugs 5, no. 4 (April, 2002): 349-355. Simon, Sanford M., and Melvin Schindler. “Cell Biologi-
Salem Health: Cancer cal Mechanisms of Multidrug Resistance in Tumors.” Proceedings of the National Academy of Sciences 91 (1994): 3497-3504. u
Other Resources
Chemocare.com http://www.chemocare.com National Cancer Institute Helping Yourself During Chemotherapy http://www.cancer.gov/cancertopics/helpingyourself-during-chemotherapy See also Alkylating agents in chemotherapy; Androgen drugs; Angiogenesis inhibitors; Antiandrogens; Antiestrogens; Antimetabolites in chemotherapy; Antineoplastics in chemotherapy; Biological therapy; Chemotherapy; Immunotherapy; Matrix metalloproteinase inhibitors; Plant alkaloids and terpenoids in chemotherapy; Proteasome inhibitors; Topoisomerase inhibitors; Tyrosine kinase inhibitors.
u Dry mouth Category: Diseases, symptoms, and conditions Also known as: Xerostomia, Sjögren syndrome, cotton mouth (slang), oral dryness, aptyalism, asialia, stomatitis sicca, Zagari disease
Dry mouth systemic lupus erythematosus (SLE), increased progesterone levels, and decreased estrogen levels. Other factors that amplify dry mouth include smoking tobacco or marijuana, hormone imbalances, mouth breathing, dry air environment, drinking strong citrus juices, vitamin or mineral deficiencies, anxiety and stress, alcohol consumption, high fevers, stones or tumors in the salivary ducts, hyperventilation, nasal obstruction, vomiting or diarrhea, and excessive sweating. Etiology and the disease process: Saliva contains enzymes that help break down and rinse away food particles and liquids. It also neutralizes acids and sugars in the mouth. Inadequate lubrication causes a dry mouth environment. When a person loses the ability to produce the normal amount of saliva, plaque and bacteria build up and adhere to the teeth, causing rapid, extensive decay and serious oral infections. Oral infections have the potential to interfere with planned cancer treatment therapies. Incidence: In general, dry mouth issues are more frequent in men; however, they also are more common in women during menopause and postmenopause. Dry mouth syndrome increases with the number of medications taken by an individual. Dry mouth can also be caused by an autoimmune disease called Sjögren syndrome. Approximately 4 million people are diagnosed each year with Sjögren syndrome. Approximately one-third to one-half of all cancer patients develop dry mouth complications because of radiation therapy, chemotherapy, and medication treatments.
Related conditions: Tooth decay, canker sores and mouth sores, geographic tongue, gum sensitivity, gingivitis, halitosis (bad breath), dysphagia (difficulty swallowing), dry eyes, nasal dryness, nosebleeds Definition: Dry mouth is an insufficient amount of saliva and moisture that would otherwise naturally lubricate and rinse the oral cavity. Risk factors: Many medications (prescription and over the counter) can cause dry mouth: antihistamines, antidepressants, antianxiety drugs, antihypertensive drugs, decongestants, sinus medications, pain medications, asthma and allergy medications, diuretics, and Parkinson’s medications. Chemotherapy or radiation treatments (particularly radiation therapy to the head and neck regions) also can cause this condition. Diseases and disorders that increase the risk of dry mouth include Parkinson’s disease, thyroid disorders, cancer, diabetes, human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS), Sjögren syndrome, stroke,
Dry mouth in Sjögren syndrome. (Custom Medical Stock Photo)
385
Duct ectasia Symptoms: Symptoms include a dry or fissured tongue, a dry oral cavity, chapped or cracked lips, difficulty swallowing, increased risk of tooth decay, increased chance of mouth sores, bad breath (halitosis), increased gum sensitivity, gingivitis, bleeding gums, a burning sensation in the mouth, a dry throat, dry eyes, and increased oral infections. Screening and diagnosis: The patient is the first to notice symptoms. Friends and relatives often hear the lack of saliva within the patient’s speech and notice an unpleasant mouth odor. Dentists often note the dryness during dental exams and discover an increase in the number of cavities. Treatment and therapy: Patients should drink plenty of liquids during meals and sip on water between meals to help rinse away food particles, make it easier to swallow, and neutralize any oral debris. Sipping on soda all day or sucking on sugary hard candies in an effort to alleviate dry mouth should be avoided. Instead, patients may eat sugarfree candy or chew sugarless gum to help stimulate their natural salivary secretions. They should also eat healthy foods including those with natural oils such as peanuts, peanut butter, and fish. Patients should avoid coffee and tea that have sugar or creamers added. They should stop smoking, avoid all tobacco products, and stop drinking alcohol. Patients should brush twice daily, floss after snacks and meals, and use alcohol-free fluoride mouth rinses. Some patients may need hormone replacement therapy (HRT) or vitamin supplements. They may also use artificial saliva substitutes or fluoride gels such as PreviDent, Biotene, or PerioGard. Prognosis, prevention, and outcomes: Dry mouth can be a temporary or permanent situation depending on its cause. Radiation therapy can permanently damage salivary glands, and chemotherapy can cause saliva to become thick. Patients may reduce dry mouth symptoms by changing their medications; however, they should check with their doctor before changing or discontinuing any medications. Using water rinses, saliva substitutes, and fluoride rinses without alcohol will help alleviate dry mouth symptoms, strengthen teeth, and fight future tooth decay. Serious oral infections and extensive decay may result in loss of teeth and difficulty wearing dentures. Maintaining excellent oral hygiene is a challenge with dry mouth issues. More frequent dental exams and cleanings are necessary to check for decay. By avoiding the triggers that provoke dry mouth and using the recommended treatments, dry mouth may be manageable. Suzette Buhr, R.T.R., C.D.A. 386
Salem Health: Cancer u
For Further Information American Dental Association. ADA Guide to Dental Therapeutics. 4th ed. Chicago: Author, 2006. Litin, Scott C., Jr., ed. Mayo Clinic Family Health Book. 3d ed. New York: HarperResource, 2003. National Institutes of Health. Dry Mouth. NIH Publication 99-3179. Bethesda, Md.: Author, 1999. Shafer, William G., Maynard K. Hine, and Barnet M. Levy. A Textbook of Oral Pathology. 4th ed. Philadelphia: W. B. Saunders, 1983. Waal, Isaac van der. Diseases of the Salivary Glands Including Dry Mouth and Sjögren’s Syndrome: Diagnosis and Treatment. New York: Springer-Verlag, 1997. u
Other Resources
American Cancer Society http://www.cancer.org American Dental Association http://www.ada.org National Institutes of Health National Institute of Dental and Craniofacial Research http://www.nidcr.nih.gov/HealthInformation/ DiseasesAndConditions/DryMouthXerostomia/ DryMouth.htm What Causes Dry Mouth? http://www.drymouth.info/consumer/ whatcausesDM.asp See also Aids and devices for cancer patients; Antidiarrheal agents; Antinausea medications; Appetite loss; Diarrhea; End-of-life care; Endoscopic retrograde cholangiopancreatography (ERCP); Graft-versus-host disease (GVHD); Hysterectomy; Lambert-Eaton myasthenic syndrome (LEMS); Mucositis; Opioids; Radiation therapies; Sjögren syndrome; Smoking cessation; Taste alteration; Weight loss.
u Duct ectasia Category: Diseases, symptoms, and conditions Also known as: Plasma cell mastitis, mastitis obliterans, comedomastitis, secretory disease of the breast Related conditions: Periductal mastitis Definition: Duct ectasia is a benign condition in which the mammary milk ducts (small tubes that carry breast milk to the nipple) fill with fluid and become plugged and inflamed.
Salem Health: Cancer Risk factors: Duct ectasia is more common in women with a history of periductal mastitis (infection of the breast ducts), cigarette smoking, an inverted nipple, and more than one pregnancy. The hormonal changes that occur with aging increase a woman’s risk of developing duct ectasia, as does a lack of vitamin A. Etiology and the disease process: Duct ectasia appears to start with an inflammatory process (the body’s response to irritation or injury), similar to an infection. A duct fills with fluid from the blood plasma, the lymph system, and the circulatory system. Lipids (fatty substances) and dead cells block the fluid from draining and lead to a buildup of the fluid in the duct. This causes the duct to dilate and become hardened. Incidence: Duct ectasia typically develops in women who are in their forties or fifties and are in perimenopause or menopause. Symptoms: Duct ectasia may appear as a lump in the breast or as an infection, marked by redness, swelling, pain, hardness, and fever. There may be a nipple discharge that is tan, white, greenish, or black. Sometimes, the nipple is inverted. Screening and diagnosis: Duct ectasia is diagnosed by physician examination of the nipple discharge, breast selfexamination, mammography, or breast ultrasound. Although the symptoms usually provide the necessary information for diagnosing duct ectasia, in some instances it may be necessary to biopsy the affected area of the breast. Treatment and therapy: The treatment for duct ectasia usually involves medication. The patient is given an antibiotic based on the culture and sensitivity of the nipple discharge. Warm, moist compresses are applied to the affected breast area three to four times a day for ten to fifteen minutes. The patient should wear a supportive bra and sleep on the unaffected side. In rare instances, it is necessary to incise (surgically open) and drain the infected duct. Prognosis, prevention, and outcomes: There is no method for preventing duct ectasia. Because duct ectasia is a benign problem, recovery is generally complete. Some women do have multiple incidences of duct ectasia. This condition does not increase a woman’s risk of developing breast cancer. Christine M. Carroll, R.N., B.S.N., M.B.A. See also Breast cancer in pregnant women; Comedo carcinomas; Ductal carcinoma in situ (DCIS); Lumps; Nipple discharge; Ultrasound tests.
Ductal carcinoma in situ (DCIS)
u Ductal carcinoma in situ
(DCIS) Category: Diseases, symptoms, and conditions Also known as: Stage 0 breast cancer Related conditions: Breast cancer, Paget disease of the nipple Definition: Ductal carcinoma in situ (DCIS) is a noninvasive form of breast cancer occurring in the ducts that are responsible for secreting milk. It is the most common type of noninvasive breast cancer, and because it is nonmetastatic, most patients survive their disease. Risk factors: Reproductive risk factors include women who never had a full-term pregnancy, had their first pregnancy after age thirty, started menstruation early, or had a late menopause. The use of oral contraceptives and postmenopausal estrogen-progestin replacement therapy (more than five years) has been shown to increase the risk of breast cancer. Having a family history of early-onset or bilateral disease and carrying the breast cancer susceptibility gene BRCA1 or BRCA2 increase the risks as well. Breast cancer risk increases with age, with most cases occurring in women over the age of sixty. The following are factors that reduce the risk of breast cancer: physical activity (exercise), multiple pregnancies, breast-feeding, and early removal of both ovaries. Etiology and the disease process: Not all DCIS lesions become invasive breast cancer, but most invasive lesions are preceded by DCIS. Most of the genetic changes present in invasive breast cancer are already present in DCIS, suggesting that if left untreated, these tumors would indeed become invasive. Incidence: The National Cancer Institute estimates that 12.7 percent of women born today will be diagnosed with breast cancer at some time in their lives. DCIS is the most common type of breast cancer, representing 21 percent of all newly diagnosed cases and as many as 30 to 50 percent of new breast cancers diagnosed by mammography. In 2005, there were estimated to be more than 60,000 new cases of DCIS in the United States. The use of mammography has greatly increased the detection and diagnosis of DCIS, leading to an increased rate of survival for those women whose lesions are detected early. Symptoms: Most breast cancers do not cause any pain, making them hard to detect. However, any change in the size or shape of the breast, change in the look or feel of the breast or nipple, or any lump or thickening in or near the 387
Ductal carcinoma in situ (DCIS) breast or underarm area may be a symptom of breast cancer. Other more obvious changes include nipple discharge, tenderness, an inverted nipple, and ridges in or pitting of the breast (when the skin looks like that of an orange). Screening and diagnosis: Because this disease can remain symptomless, monthly self-examination of the breasts after the age of twenty, yearly checkups, and regular mammographies after the age of forty are crucial to early detection. Most of the new cases of DCIS detected by mammography are not detectable by examination alone. Once DCIS is detected, tissue is sampled using fine needle aspiration (FNA) biopsy or core needle biopsy. According to the standard staging system, DCIS is a Stage 0 breast cancer. Pathologic analysis will determine the classification of the tumor, its size and margins, and if the tumor is hormone dependent. These criteria are then further classified as follows: • Grade I (low grade): Non-high grade without necrosis (the tumor cells look similar to normal cells, and the tumor may be solid, cribiform, or papillary) • Grade II (medium grade): Non-high grade with necrosis • Grade III (high grade): Very quickly growing tumor with the cells in the center of the duct becoming starved from the blood supply; described as “comedo” Treatment and therapy: Treatment will vary from case to case depending on the size and grade of the tumor and whether there is a family history of breast cancer. Typically, once diagnosis is confirmed, a lumpectomy is performed to remove the entire area of the DCIS and a marginal area of normal breast tissue around it. This is followed by radiation to the whole breast to kill cancer cells outside the surgical margin and to reduce the risk of the cancer coming back. In some cases a mastectomy, in which the entire breast is removed, may be recommended if the DCIS covers a very large area or multiple areas of the breast, or if the patient has a family history of breast cancer or a known gene abnormality (BRCA1 or BRCA2). Because this type of cancer has not invaded into the normal tissue, chemotherapy is not needed for DCIS. If the tumor tests positive for hormone receptors, hormonal therapy (tamoxifen and aromatase inhibitors) can be used to lower the risk of recurrence. Prognosis, prevention, and outcomes: Because DCIS is a precancerous or preinvasive lesion, the prognosis is very good. Less than 1 percent will die from this disease. It is possible that an invasive focus not found at the time of diagnosis will later develop into metastatic disease, but the likelihood is small. About 40 to 50 percent of local recur388
Salem Health: Cancer rences are invasive and 10 to 20 percent of patients will develop metastases and die from their disease. The more aggressive the therapy, the lower the rate of mortality. Additional treatment, including surgery, radiation therapy, antiestrogen therapy, or a combination of these, will reduce the chances of recurrence of the disease. Terry J. Shackleford, Ph.D. u
For Further Information Hunt, Kelly K., Geoffrey L. Robb, Eric A. Strom, and Naoto T. Ueno. Breast Cancer. M. D. Anderson Cancer Care Series. New York: Springer, 2001. Link, John. Breast Cancer Survival Manual: A Step-byStep Guide for the Woman with Newly Diagnosed Breast Cancer. 4th ed. New York: Holt, 2007. “The Picture Problem: Mammography, Air Power, and the Limits of Looking.” The New Yorker, December 13, 2004. http://www.gladwell.com/2004/2004_12_13_a_ picture.html. Roses, Daniel F. Breast Cancer. Philadelphia: Elsevier, 2005. Shockney, Lille D. Navigating Breast Cancer: A Guide for the Newly Diagnosed. Sudbury, Mass.: Jones & Bartlett, 2006.
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Other Resources
American Cancer Society http://www.cancer.org Breastcancer.org http://www.breastcancer.org National Cancer Institute Breast Cancer http://www.cancer.gov/cancertopics/types/breast Susan G. Komen for the Cure http://www.komen.org University of Texas, M. D. Anderson Cancer Center Breast Cancer http://www.mdanderson.org/diseases/breastcancer/ See also Breast cancer in children and adolescents; Breast cancer in men; Breast cancers; Comedo carcinomas; Ductal lavage; Ductogram; Invasive ductal carcinomas; Lobular carcinoma in situ (LCIS); Medullary carcinoma of the breast; Mucinous carcinomas; Progesterone receptor assay; Tubular carcinomas.
Salem Health: Cancer
u Ductal lavage Category: Procedures Definition: Ductal lavage is a minimally invasive method used to detect gradual changes in breast cells that could indicate a precancerous or cancerous condition. It has been dubbed the “breast Pap smear.” The idea dates back to the 1950’s, when Dr. George Papanicolaou (1883-1962), the inventor of the Pap smear to detect cervical cancer, first theorized that nipple fluid could be analyzed for precancerous changes.
Ductogram recommend that the procedure be done along with clinical breast examination and an imaging study, such as mammography. Kelli Miller Stacy, ELS See also Breast cancer in children and adolescents; Breast cancer in men; Breast cancers; Comedo carcinomas; Ductal carcinoma in situ (DCIS); Ductogram; Invasive ductal carcinomas; Lobular carcinoma in situ (LCIS); Medullary carcinoma of the breast; Microcalcifications; Mucinous carcinomas; Progesterone receptor assay; Tubular carcinomas.
Cancers diagnosed: Ductal carcinoma in situ (DCIS) Why performed: According to the American Cancer Society, more than 95 percent of breast cancers originate in the cells lining the milk ducts. Ductal lavage can identify atypical or abnormal changes in breast cells that may fuel cancer development in the future. The test is used to assess women at high risk of breast cancer. It is not intended as a screening tool for breast cancer, nor is it a replacement for mammography. Patient preparation: No preparation is needed. Steps of the procedure: A numbing cream is applied to the nipple area. The woman is asked to massage the breast area gently with both hands to help move fluid toward the nipple. A suction device placed over the nipple siphons tiny amounts of fluid from the milk ducts, which helps detect the natural duct openings. Once they are identified, a slender, hollow tube called a catheter is inserted into each duct that produced fluid. Saline flows through the catheter, rinsing out the duct and washing out cells. (Lavage is a French word that means “wash” or “rinse.”) The fluid containing the cells is then analyzed under a microscope. After the procedure: The procedure does not usually cause any discomfort. Some women may have a temporary feeling of pressure, tingling, or fullness afterward. No special follow-up care is needed. Risks: The risks of ductal lavage are rare but may include damage to a milk duct and infection at the site of the catheter insertion. Signs of infection include breast redness, warmth, severe tenderness, and/or persistent fever. Results: A normal result means that no abnormal cells were detected. In some cases, analysis of the milk duct cells may reveal atypical changes but cannot pinpoint their exact origin in the breast. Not every woman with atypical breast cell changes will develop breast cancer. Experts
u Ductogram Category: Procedures Also known as: Mammary ductogram, galactogram, galactography, ductogalactography Definition: A ductogram is an imaging procedure that uses a radio-opaque contrast dye to enhance mammography pictures. A ductogram is used to help identify if cancer is present in the duct of the nipple, which transport breast milk in lactating women. Cancers diagnosed: Breast cancer, ductal carcinoma in situ (DCIS) Why performed: A ductogram is used to help determine the source of abnormal nipple discharge and the location of possible cancer. Cancer may cause abnormal nipple discharge. DCIS begins as cancer in the cells that line the ducts. The cancer may remain contained in the nipple or may spread to other parts of the breast. Standard mammography may show small areas of microcalcifications, calcium collections that can be a sign of DCIS. A ductogram creates even better pictures of the suspicious area. Patient preparation: The patient should not use deodorant or powder on the day of the ductogram. The patient should not express discharge from the nipple before the procedure but should let her doctor know if she does not experience nipple discharge on the day of the procedure. In such cases, the ductogram may need to be rescheduled. The patient should inform her doctor if she is pregnant so that a protective drape will be placed over the abdomen during the procedure. A ductogram is performed at the radiology department of a hospital or an outpatient radiology center. It is an outpatient procedure that lasts from thirty minutes to an hour. The patient disrobes from the waist up and wears an examination gown for the procedure. 389
Duke Comprehensive Cancer Center
Salem Health: Cancer
A doctor injects a contrast medium into the breast of a female patient. (©BSIP/Phototake—All rights reserved)
Steps of the procedure: The breast and nipple are cleansed before the procedure. The nipple is sterilized with alcohol. The radiologist identifies which duct is producing abnormal discharge by applying pressure to the nipple to elicit discharge. Local anesthesia may be applied before a blunt-tipped cannula, a small needlelike device, is inserted into the duct. A syringe attached to the cannula delivers the radiopaque contrast dye. The cannula is removed, and mammography images are taken. After the procedure: A bandage is placed over the nipple. Patients should drink plenty of fluids to help eliminate the dye from the body. Risks: A ductogram is a low-risk procedure, but pain, infection, or bleeding may occur. Results: A healthy nipple does not reveal abnormalities. Any abnormalities, such as possible cancer, are highlighted on ductogram images. Mary Car-Blanchard, O.T.D., B.S.O.T. See also Breast cancer in children and adolescents; Breast cancer in men; Breast cancer in pregnant women; Comedo 390
carcinomas; Duct ectasia; Ductal carcinoma in situ (DCIS); Ductal lavage; Invasive ductal carcinomas; Invasive lobular carcinomas; Lobular carcinoma in situ (LCIS); Nipple discharge.
u Duke Comprehensive Cancer
Center Category: Organizations Definition: The Duke Comprehensive Cancer Center in Durham, North Carolina, is one of thirty-nine cancer centers that have been designated as comprehensive cancer centers by the National Cancer Institute. U.S. News & World Report has ranked the center in the top ten cancer hospitals in the United States and named it the top cancer facility in the South. The center serves patients not only from North Carolina but also from throughout the nation and the world. More than 25,000 new patients are seen every year at the center.
Salem Health: Cancer Facilities: Established in 1972, the Duke Comprehensive Cancer Center is a part of a large teaching hospital. Many of the physicians and nursing staff are well known for their research and expertise. In 2006, the hospital treated 9,000 inpatients and 175,000 outpatients. Programs and areas of strength include breast and ovarian oncology, the Preston Robert Tisch Brain Tumor Center at Duke, stem cell transplantation, esophageal and lung cancer, melanoma, the Cancer Patient Support Program, and the Oncology Recreation Therapy Program. The center treats children and young adults through the Division of Pediatric Hematology-Oncology at Duke University Medical Center, and the center’s Hereditary Cancer Clinic focuses on genetic cancers. Specializations: The Duke Comprehensive Cancer Center treats a large variety of both primary and metastatic cancers, including head and neck cancers, digestive cancers, respiratory cancers, bone and soft tissue cancers, melanoma and other skin cancers, breast cancer, genitourinary cancers (both male and female), brain and central nervous system cancers, endocrine cancers, lymphomas, myeloma, and leukemia. Oncology services are linked with hematology, surgery, neurology, orthopedics, and women’s health clinics. The center serves cancer patients from diagnosis to treatment and through survivorship. It also provides patients and their families with numerous resources, including a large network of oncologists. Oncologists are located not only on the Duke Hospital campus but also throughout the network, which extends up into Virginia and as far south as Florida. On the main campus, patients are seen in various specialty clinics: a hematology oncology clinic, a surgical oncology clinic, a brain tumor center, and an adult bone marrow clinic. The patients visit the clinics from the beginning of diagnosis well into remission. Also on the main campus is the Oncology Treatment Room, which serves outpatient chemotherapy patients and has a pheresis division. The center’s cutting-edge radiation oncology department provides the latest and best equipment for cancer patients. The center has three inpatient units that care for patients who are not able to receive their therapy on an outpatient basis. The Duke Center for Fertility provides an invaluable resource in addressing fertility issues surrounding cancer treatment. With improved therapies, cancer patients are surviving longer, and some wish to have children after treatment. The Center for Integrative Medicine offers support of the cancer patient as a whole person. Integrative medicine
Duke Comprehensive Cancer Center takes into consideration not only a patient’s diagnosis and treatment but also the individual’s diet, exercise, and mental well-being. The patient’s well-being is, in fact, an important aspect of all care provided by the center. It offers support groups and special programs to guide patients through their treatment and help them adjust to survivorship. Programs include chemotherapy classes, wig and turban programs, and the Look Good, Feel Good program. Duke also provides a cancer treatment library to help patients and family learn more about the disease. Research: The center conducts research on a regular basis, including small and large clinical trials. All oncology departments are involved with some aspect of cancer research, which covers areas such as vaccines, immunotherapies, chemotherapies, and stem cell research. The center also participates in the Duke Tumor Registry, a statewide program to improve the detection and treatment of cancer. The registry gathers information relating to cancer prevention, diagnosis, and treatment. Katrina Green, R.N., B.S.N., O.C.N. u
For Further Information Laszlo, John, and Francis A. Neelson. The Doctor’s Doctor: A Biography of Eugene A. Stead, Jr., MD. Durham, N.C.: Carolina Academic Press, 2006. National Cancer Institute, Division of Cancer Research Resources and Centers. The Cancer Centers Program. Washington, D.C.: U.S. Department of Health, Education, and Welfare, Public Health Service, National Institutes of Health, 1974.
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Other Resources
Duke Comprehensive Cancer Center http://www.cancer.duke.edu Duke Health System http://www.dukehealth.com National Comprehensive Cancer Network Duke Comprehensive Cancer Center http://www.nccn.org/members/profiles/duke.asp See also American Association for Cancer Research (AACR); American Cancer Society (ACS); American Institute for Cancer Research (AICR); Dana-Farber Cancer Institute; Fox Chase Cancer Center; Fred Hutchinson Cancer Research Center; Jonsson Comprehensive Cancer Center (JCCC); M. D. Anderson Cancer Center; Mayo Clinic 391
Dukes’ classification
Salem Health: Cancer
Cancer Center; Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI); National Science Foundation (NSF); Prevent Cancer Foundation; Robert H. Lurie Cancer Center.
u Dukes’ classification Category: Procedures Definition: Dr. Cuthbert E. Dukes (1890-1977) was a pathologist who developed the classification for operable colon or rectal cancer. He began his studies at St. Mark’s Hospital in 1922 and published the Dukes’ classification in 1932. Through many years of examining the various clinical stages and prognoses of patients diagnosed with rectal cancer, he was able to develop a pathological classification system that reflected the prognosis based on three categories: A, B, and C. Dukes’ classification has been modified to include B1 and B2 as well as C1 and C2. Dr. Vernon Astler and Dr. Fredrick Coller later modified Dukes’ classification to include a fourth stage, D.
Dukes’ Stages Stage
Description
A B1 B2 C1 C2 D
Confined to the lining of the colon Into the thin muscle right below the lining Through the thin muscle right below the lining Limited to bowel wall, with lymph nodes affected Through the bowel wall, with lymph nodes affected Distant spread of cancer or inoperable cancer
Steps of the procedure: The patient will be positioned for comfort. If in the operating room, then the patient will be given general anesthesia. If a sample is to be taken by CTguided biopsy or colonoscopy, then the patient may be given medications to cause sleepiness and block any pain. Once the patient is positioned and medication is given, the entrance site for the biopsy is cleansed with an appropriate solution. The physician will obtain the biopsy and then place the sample either in a vial with a preservative or on a slide for viewing. The samples will then be sent to the pathologist so that diagnosis and classification can be done. After the procedure: The patient will be monitored after the procedure for signs of bleeding or pain for a couple of hours. A patient who has completely awakened from the medication-induced sleep and is able to tolerate fluids is able to be driven home by a friend or Five-Year family member.
Survival Rate (%)
Cancers diagnosed: Colorectal cancers Why performed: Patients diagnosed with cancer of the colon or rectum will have treatment and therapy guided by the Dukes’ classification system. Patients who have been classified as Stage A may receive more aggressive treatment; those patients classified as Stage D may receive only palliative treatment. Patient preparation: Dukes’ classification is used for a patient who has had a biopsy of the tumor. The biopsy may be obtained surgically or through colonoscopy or a CTguided biopsy. The patient will have nothing to eat or drink for at least eight hours before any of these proce392
dures. If the cancer is in the lower gastrointestinal (GI) tract, then the patient will have to complete a bowel prep, which includes drinking a liquid to cause the stool in the GI tract to be evacuated. If the biopsy will be taken surgically, then the patient may have the skin shaved at the incision site.
97 80 80 65 35 5
Risks: Infections, pain, and bleeding are all risks of obtaining a biopsy for Dukes’ classification.
Results: Dukes’ classification is based on the pathology of the cancer. A patient will have a biopsy of the disease site and the pathologist will be able to stage the disease based on the defined classification stage. A better prognosis, or five-year survival rate, is directly related to the stage of the disease of the patient. Stage A indicates minimal disease and a high five-year survival rate. Stages B and C indicate that the disease has progressed into the surrounding tissue and the survival rate is decreased. Stage D indicates that the disease has spread, or metastasized, to another site. Stage D is directly related to a poor prognosis or poor chance of fiveyear survival rate. Katrina Green, R.N., B.S.N., O.C.N. See also ABCD; Breslow’s staging; Carcinomas; Gleason grading system; Grading of tumors; Staging of cancer; TNM staging.
Salem Health: Cancer
u Duodenal carcinomas Category: Diseases, symptoms, and conditions Also known as: Small intestine cancer Related conditions: Crohn disease, celiac disease, colon polyps Definition: Duodenal carcinoma is a cancer of the duodenum, the first (upper) part of the small intestine. Risk factors: Risk factors include Crohn disease, celiac disease, familial adenomatous polyposis (FAP), exposure to radiation, smoking, alcohol consumption, and a diet high in fats or high in salted, pickled, or smoked foods. Etiology and the disease process: Genetic disposition, environmental exposures, and lifestyle are all potential root causes of duodenal carcinoma. The duodenum is the first part of the small bowel that is exposed to ingested
Duodenal carcinomas chemicals that may be carcinogenic and to pancreatic biliary juices that may also be carcinogens. There are five types of small intestine cancers (adenocarcinoma, sarcoma, carcinoid tumors, gastrointestinal stromal tumors, and lymphoma). The most common type of duoendal carcinoma is adenocarcinoma. Incidence: Duodenal carcinoma is a relatively rare cancer that makes up less than 1 percent of gastrointestinal cancers. Symptoms: The symptoms of duodenal carcinoma may include abdominal pain, weight loss, bloating, cramping, blood in stools, and less commonly anemia and jaundice. Screening and diagnosis: There may be a considerable amount of time between the identification of nonspecific symptoms (such as abdominal pain and bloating) and the diagnosis of duodenal carcinoma. A physical exam, medical history, X rays of the abdomen, abdominal ultrasound, a barium contrast study, and an upper gastrointestinal series may be used in the diagnosis. Small intestine adenocarcinomas are staged beginning with adenocarcinoma in situ, Stage I (the cancer has invaded the connective tissue or muscular layer of the bowel), Stage II, Stage III (the cancer has spread to regional lymph nodes), and Stage IV (the cancer has spread to distant organs). Treatment and therapy: Surgery is the usual treatment, but surgical removal of a duodenal tumor can be difficult because of the area in which it is located. Surgery to bypass the area of the tumor (connecting the stomach to an area of the intestine beyond the mass) is sometimes necessary. Chemotherapy and radiation therapy are sometimes used to try to shrink the cancer or if the cancer has spread. Prognosis, prevention, and outcomes: Individuals with duodenal carcinoma should be monitored after treatment for signs and symptoms of recurrence and should have abdominal computed tomography (CT) scans every six months. Vicki Miskovsky, B.S., R.D. See also Cholecystectomy; Gallbladder cancer; Gastric polyps; Gastrinomas; Gastrointestinal cancers; Gastrointestinal oncology; Multiple endocrine neoplasia type 1 (MEN 1); Pancreatitis; Percutaneous transhepatic cholangiography (PTHC); Small intestine cancer; Upper gastrointestinal (GI) endoscopy; Upper gastrointestinal (GI) series; Zollinger-Ellison syndrome.
A tumor on the wall of the duodenum. (©MedicalRF.com/Corbis)
393
Dysplastic nevus syndrome
u Dysplastic nevus syndrome Category: Diseases, symptoms, and conditions Also known as: Atypical mole syndrome, dysplastic mole, Clark’s nevus Related conditions: Malignant melanoma, familial atypical mole and melanoma (FAMM) syndrome Definition: Dysplastic nevus syndrome is a skin condition characterized by the presence of numerous atypical nevi, or moles. Risk factors: White men and women with light-colored hair and freckled skin are believed to be at high risk for dysplastic nevi, especially with excessive sun exposure. Dysplastic nevi are strongly linked to melanoma: The presence of the former may signify an increased risk for developing the latter. Individuals with a family history of dysplastic nevi, with numerous dysplastic nevi on their bodies, and with at least two family members diagnosed with melanoma, are almost certain to develop melanoma. This is called familial atypical mole and melanoma (FAMM) syndrome. Etiology and the disease process: Dysplastic nevi are abnormally growing moles. Whether ultraviolet exposure plays a significant role in their development is still a subject for debate. Dysplastic nevi are, however, associated with frequent and severe sunburns, a family history of dysplastic nevi, and weakened immunity (for example, due to cancer chemotherapy). Incidence: In the United States, dysplastic nevi are present in 2 to 5 percent of the white population. In other countries, such as Australia, New Zealand, Germany, and Sweden, dysplastic nevi are clinically diagnosed in as much as
394
Salem Health: Cancer 18 percent of the adult white population. This condition rarely occurs in individuals of Middle Eastern, black, or Asian descent. No gender predilection exists; the condition may start manifesting as early as childhood. Symptoms: Unlike common moles, atypical nevi are asymmetrical; have uneven shades of tan, brown, red, or pink; have irregular borders; and are greater than 5 millimeters in diameter. Atypical moles are frequently found on the back, chest, abdomen, scalp, arms, or legs, but they can sometimes arise on unexposed areas such as the breasts or buttocks. Screening and diagnosis: A thorough examination of the patient’s skin surface and a detailed family history are important in screening for dysplastic nevi. An excisional biopsy and histological analysis of the tissue sample will differentiate between dysplastic nevi and malignant melanoma. Treatment and therapy: There is no definitive treatment for dysplastic nevi. Surgical removal of dysplastic moles does not guarantee against the development of melanoma. Prognosis, prevention, and outcomes: Individuals with dysplastic nevi syndrome should avoid prolonged sun exposure without sunscreen protection. Regular skin examinations will help monitor for any suspicious changes in dysplastic nevi. Ophelia Panganiban, B.S. See also Carney complex; Choriocarcinomas; Craniosynostosis; Gestational trophoblastic tumors (GTTs); Hereditary cancer syndromes; Human chorionic gonadotropin (HCG); Hydatidiform mole; Melanomas; Moles; Sjögren syndrome; Skin cancers.
Salem Health: Cancer
u Edema Category: Diseases, symptoms, and conditions Also known as: Lymphedema, fluid retention Related conditions: Cancers of the breast, colon, ovary, uterus, and testicles Definition: Edema, known as fluid retention, results from the accumulation of fluid in certain tissues, leading to swelling. In lymphedema, lymph (a fluid containing a high amount of lymphocytes, or white blood cells) accumulates in tissues because the excess fluid and proteins cannot be returned into the circulation. Edema can result in decreased mobility of the affected limb, as well as pain, risk of infection, and poorer quality of life. Risk factors: The main risk factor for edema is surgery for breast and other cancers in which removal of the primary tumor may lead to removal of nearby lymph nodes. Etiology and the disease process: Cancer-related edema either is caused directly by the cancer or is a result of treatment. In some cases, cancer cells may build up in the neighboring lymph nodes, blocking the flow of the lymphatic fluid. Cancer patients may also have poor nutritional intake, in part because of loss of appetite and metabolic disorders, and their bodies may not have sufficient amounts of protein to function normally. If the kidneys are impaired, they will not be able to properly rid the body of salt through the urine. This leads to an increased amount of salt in the body, causing water to be retained and leading to edema. Edema can also be the result of the drugs that cancer patients receive. Chemotherapy drugs associated with an increased risk of edema include cyclosporine, docetaxel, gemcitabine, imatinib, and thalidomide. Additional anticancer agents known to cause edema include corticosteroids, anabolic steroids, progestins, and nonsteroidal anti-inflammatory agents. In addition, some treatments may directly affect the lymphatic system. For example, in breast cancer patients, the neighboring axillary lymph nodes may be affected either by targeted radiation therapy or surgical removal (known as node dissection). Disrupting the lymphatic system is a cause of lymphedema. Incidence: Edema in the arm is a common side effect in breast cancer patients, especially if they have received radiation therapy or had a lymph node removed. The reported incidence depends on the type of breast cancer therapy administered and the time since treatment. Based on an analysis of multiple studies in which women received a variety of surgical procedures and adjuvant therapies, it is
Edema estimated that approximately 1 in 4 women may develop arm edema after treatment for breast cancer. Moreover, the frequency of lymphedema rises over time since treatment. Symptoms: The symptom of edema is swelling of the limbs. Screening and diagnosis: Edema may be diagnosed by measuring limbs; a difference of more than 2 centimeters between the circumference of the normal and affected limbs would indicate edema. Bioelectrical impedance (to quantify the fluid accumulation) and lymphoscintigraphy (to visualize the lymphatic system) may also be used. Treatment and therapy: Treatment for edema can be broken down into three categories: diet, supportive therapy, and pharmacological therapy. Reducing the amount of dietary salt consumed may help to manage edema. Patients should avoid foods that are high in salt or sodium, including canned soups, canned or processed meats, prepared mixes and foods (including frozen dinners and fast foods), snack foods (pretzels, potato chips, olives, cheeses, pickles), and high-salt seasonings (bouillon cubes, seasoned salts, soy sauce, Worcestershire sauce, and premixed spice packets). Supportive therapies are also important in treating edema. Elevating affected limbs above the heart may help reduce swelling. Other strategies include wearing elastic compression stockings or sleeves, which help to return the excess fluid into the circulation. Massage, compression pumps, and specialized physical therapy and exercise regimens may also be effective. Less frequently used methods include electrically stimulated lymphatic drainage (such as uniform or sequential compression with either pneumatic or hydrostatic pressure devices) and surgery (such as surgical excision of the affected area, insertion of a lymphatic-venous shunt, or liposuction). Diuretics are a commonly prescribed medication to reduce edema, since they inhibit the ability of the kidneys to reabsorb and retain salt, leading to the elimination of more salt and water in the urine. Loop diuretics, named because they target the loop of Henle within the kidney tubules, include furosemide (Lasix), torsemide (Demedex), and butethamide (Bumex). Thiazide diuretics may also be used, but they may cause potassium to be excreted in the urine. Potassium-sparing diuretics include spironolactone (Aldactone), triamterene (Dyrenium), and amiloride (Midamor). Elizabeth A. Manning, Ph.D. 395
Elderly and cancer u For Further Information Bourgeois, P., O. Leduc, and A. Leduc. “Imaging Techniques in the Management and Prevention of Posttherapeutic Upper Limb Edemas.” Cancer 83 (December 15, 1998): 2805-2813. Cohen, S. R., D. K. Payne, and R. S. Tunkel. “Lymphedema: Strategies for Management.” Cancer 92 (August 15, 2001): 980-987. Erickson, V. S., et al. “Arm Edema in Breast Cancer Patients.” Journal of the National Cancer Institute 93, no. 2 (January 17, 2001): 96-111. Mortimer, P. S. “The Pathophysiology of Lymphedema.” Cancer 83 (1998): 2798-2802. Petrek, J. A., P. I. Pressman, and R. A. Smith. “Lymphedema: Current Issues in Research and Management.” CA: A Cancer Journal for Clinicians 50, no. 5 (September/October, 2000): 292-307. u
Other Resources
Huntsman Cancer Institute Edema http://www.hci.utah.edu/patientdocs/hci/ drug_side_effects/edema.html MedicineNet.com Edema http://www.medicinenet.com/edema/article.htm National Cancer Institute Lymphedema http://www.cancer.gov/cancertopics/pdq/ supportivecare/lymphedema/healthprofessional See also Beckwith-Wiedemann syndrome (BWS); Lymphangiosarcomas; Lymphedema; Magnetic resonance imaging (MRI); Mastectomy; Nephroblastomas; Rhabdomyosarcomas.
u Elderly and cancer Category: Social and personal issues Definition: The risk of cancer increases with age. The National Cancer Institute (NCI) reports that 60 percent of new cases of cancer are diagnosed in those over the age of sixty-five. No definitive answer is found among the various theories for the increased risk. Possible connections include a reduced ability of the immune system to fight disease, increased vulnerability to toxic substances that alter deoxyribonucleic acid (DNA), and the cumulative effect of exposure to carcinogens over time. Managing can396
Salem Health: Cancer cer as a chronic disease, with attention to long-term survivor needs, helps this age group maintain a good quality of life. The physical, psychological, emotional, spiritual, social, and financial aspects of living with cancer require multiple tools and resources for individuals and caregivers coping with a malignant condition. Description of the population: In 2005, there were 36.8 million people aged sixty-five or older, representing 12.4 percent of the United States population. This was an increase of 3.2 million, or 9.4 percent, from 1995. The population under the age of sixty-five increased 13.3 percent during this same time period. However, the group aged forty-five to sixty-four increased by 40 percent, illustrating the exponential growth of the elderly population that will continue. There were 21.4 million older women compared with 15.4 million older men in 2005, a ratio of 139 women for every 100 men. This ratio increases with age because women live longer than men. The population as a whole is living longer. The group of people age eighty-five and up was forty-two times larger in 2005 than that same age group in 1900. According to the U.S. Census Bureau, the elderly population is expected to more than double by 2050, representing 1 out of every 5 people in the United States. Numbers will continue to grow as life expectancy improves and as advances in science are made that lead to improved treatments for cancer and higher survival rates. The elderly population is vulnerable to depression and a cancer diagnosis may worsen it. The loss of a spouse and deaths of friends create feelings of isolation and despair. They may face pressure to leave a long established residence or need to enter an assisted living facility or nursing home. Financial burdens from living on a fixed income and dwindling resources is another stressor. Visual and auditory deficits strain communication and may necessitate giving up hallmarks of independence such as driving. Coping skills are taxed with advancing age, especially when a person is faced with a new diagnosis of cancer or a recurrence after a period of remission. Medicare reimbursement for cancer treatments and supportive medications is driven by policy changes and may become insufficient over time. Homelessness among the elderly is not uncommon and may prevent early diagnosis of cancer from lack of health care access. Incidence, death, and survival statistics: The probability of developing an invasive cancer at the age of seventy or older is 1 out of 3 for men and 1 out of 4 for women. From ages sixty to sixty-nine, it is 1 in 6 for men and 1 in 9 for women. The elderly are ten times more likely to get cancer and fifteen times more likely to die from cancer than people under the age of sixty-five, according to the
Salem Health: Cancer
Elderly and cancer
Cancer is more common among those aged sixty-five and over, possibly because of a weaker immune system, increased vulnerability to substances that alter DNA, free-radical cell damage with time, and the cumulative effect of carcinogen exposure. (Digital Stock)
NCI. Some 70 percent of deaths from cancer occur in this age group. Reasons for increased mortality may be affected by less aggressive treatment, a delay in diagnosis and start of treatment, a personal choice to decline treatment, and the impact of other health problems on the cancer. Cancers linked to aging and common in the elderly include bladder, breast, colon, lung, pancreas, prostate, rectal, stomach, and acute myelogenous leukemia (AML), a cancer of the blood. Approximately one-third of nonHodgkin lymphomas are diagnosed in individuals over seventy years old. The average age for developing colorectal cancer is seventy-one according to the NCI. Risk and prevention: People aged fifty-five and older account for approximately 75 percent of cancer diagnoses. The majority of breast cancers occur after age fifty, with the highest incidence in those between the ages of seventyfive and seventy-nine. For women with ovarian cancer, survival is twice as likely in those under the age of sixty-
five as in those sixty-five and older. The majority of people with lung cancer are at least seventy years old at diagnosis. Older patients diagnosed with AML are less likely to achieve remission after treatment than younger ones. When elderly people think that their symptoms are related to aging, they may ignore the signs and delay consultation with a physician. The prevention of cancer in the elderly is much the same as in people of any age. Eating a low-fat, high-fiber diet; exercising; avoiding excessive use of alcohol; and limiting exposure to chemicals and radiation are ways to help reduce the risk of cancer. Cancer screening should continue throughout the life span, although there is disagreement among experts about screening frequency and situations in which it is reasonable to discontinue screening for certain cancers. Treatment considerations: Age is not the only factor used to decide whether aggressive treatment should be pursued. The functional status of older patients indicates 397
Elderly and cancer their ability to tolerate and respond to therapy. Treatment options may be limited by existing health problems such as hypertension and heart disease, which reduce tolerance to therapies. Drugs and chemotherapy agents may interact with medications taken for other conditions. Cognitive impairment caused by dementia or slowing mental processes compounds the side effects of medications such as opioids for pain, which cause somnolence. The normal effects of aging may alter or slow the way the body metabolizes drugs, increasing toxicities from treatment or reducing efficacy. Bias and stereotypes regarding the elderly may impede full recovery after treatment. For example, sexuality does not necessarily diminish in the elderly, but because many assume the loss of libido, subsequent problems with intimacy after treatment may not be adequately assessed. Another assumption is that a cancer diagnosis is less devastating for an older person than for someone younger because the older person is closer to the end of life. However, the majority of older adults are active and independent, with the potential to enjoy years of life despite cancer. Autonomy is preserved when the elderly learn everything possible about their diagnosis and prognosis, use providers trained in geriatrics, and obtain second opinions before choosing among treatments that include chemotherapy, radiation, immunotherapy, investigational agents, watchful waiting, palliative care, and hospice care. Perspective and prospects: Scientific data are used to determine appropriate treatment for a particular cancer and are based on the stage of the cancer, its potential for growth, and the order of administration when more than one therapy or regimen is employed. More clinical trials, with a design that accommodates participation of older people, are needed to enhance knowledge about cancer in the elderly and identify the best interventions for this age group. Cancer survivors benefit from a comprehensive plan that facilitates a return to a functional state after treatment. The education and training of health care providers in the specialty of geriatrics promotes the well-being and longevity of this population. Individuals of advanced age who live with cancer understand the unique challenges better than anyone and, as proponents of change, accelerate the gains in cancer management and treatment. Selfadvocacy by the elderly is made easier by availability of cancer resources in communities and on the Internet. For example, online cancer support groups provide an alternative for those who are homebound, and pharmaceutical companies have programs that furnish medication at no cost or at a discount. Linda August Vrooman, R.N., B.S.N., O.C.N. 398
Salem Health: Cancer u
For Further Information Beers, Mark H., and Robert Berkow. Merck Manual of Geriatrics. Rahway, N.J.: Merck Sharp & Dohme Research Laboratories, 2000. Hunter, Carrie P., Karen A. Johnson, and Hyman B. Muss. Cancer in the Elderly. New York: Marcel Dekker, 2000. Lichtman, M., et al. “International Society of Geriatric Oncology Chemotherapy Taskforce: Evaluation of Chemotherapy in Older Patients—An Analysis of the Medical Literature.” Journal of Clinical Oncology 25, no. 14 (May 10, 2007): 1832-1843.
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Other Resources
Administration on Aging Statistics on the Aging Population http://www.aoa.gov/prof/Statistics/statistics.asp Association of Cancer Online Resources http://www.acor.org Cancer Survival Toolbox Pain and the Elderly http://www.canceradvocacy.org/resources/ treatment-issues/pain/elderly.html Caring Connections http://www.caringinfo.org Federal and State Agencies for Seniors http://www.usa.gov/Topics/Seniors/ FederalState.shtml Foundation for Health in Aging http://www.healthinaging.org/public_education/ eldercare Gerontological Society of America http://www.geron.org National Institute on Aging http://www.nia.nih.gov See also Aging and cancer; Counseling for cancer patients and survivors; End-of-life care; Free radicals; Genetics of cancer; Home health services; Hospice care; Living with cancer; Long-distance caregiving; Medicare and cancer; Nutrition and cancer prevention; Occupational therapy; Overtreatment; Pain management medications; Palliative treatment; Psycho-oncology; Self-image and body image; Side effects; Social Security Disability Insurance (SSDI); Stress management; Support groups; Survival rates; Symptoms and cancer; Watchful waiting.
Salem Health: Cancer
Electromagnetic radiation
u Electrolarynx
u Electromagnetic radiation
Category: Social and personal issues Also known as: Artificial or mechanical larynx, AE or EL, throat back
Category: Carcinogens and suspected carcinogens RoC status: Solar radiation, exposure to sunlamps or sunbeds, known human carcinogens since 2000; broad-spectrum ultraviolet radiation (UVR), known human carcinogen since 2002; ultraviolet A, B, and C (UVA, UVB, UVC), reasonably anticipated human carcinogens since 2002; X radiation, gamma radiation, known human carcinogens since 2004 Also known as: EM radiation, EMR
Definition: The electrolarynx is an electronic device that allows a person with laryngeal cancer to communicate after having the larynx or voice box surgically removed. Communication after a laryngectomy: Laryngeal cancer can affect various places in the voice box, or larynx. One treatment is partial or total surgical removal of the larynx (laryngectomy). This leaves the patient without the capacity for speech and voice communication. Written communication is effective but may prove frustrating for patients. One option available for these patients is the electrolarynx, an electromechanical medical device used to make vibration to produce sound that the patient can form into words with the tongue, lips, teeth, and cheeks. Types of electrolarynx devices: Basically two devices for speech are available after loss of the voice to cancer. One is the battery-powered machine that is placed against the patient’s throat. The patient pushes a button and the device transmits vibrations that can be formed into words. In the second type, a small tube in the mouth receives vibrations directly into the mouth, with words made in a similar way. Charges for an electrolarynx can vary from $200 to $800, depending on the brand, model, and accessories. Both private insurance and Medicare may cover all or part of the costs. Some states provide these free of charge; these states include California, Georgia, Massachusetts, Kansas, North Carolina, South Carolina, and Texas. Enhancing communication: The patient using an electrolarynx can make communication easier by controlling the environment. When the patient talks to someone, it helps for both people to look at each other and remain in the same room or area, as part of successful communication is visual. Choosing an area without distracting background noise such as a television also helps. The patient can also use nonverbal communication, such as nodding or shaking the head, and can exaggerate consonants and prolong vowels to produce intelligible speech. Carrying a pen and paper as a backup may ease frustration. Marylane Wade Koch, M.S.N., R.N. See also Cordectomy; Esophageal speech; Laryngeal cancer; Laryngeal nerve palsy; Laryngectomy; Throat cancer; Tracheostomy.
Related cancers: Skin cancers, especially melanoma; leukemia Definition: Electromagnetic radiation is a form of energy, composed of individual oscillating photons. The amount of energy carried by each photon is proportional to its frequency. The collection of all possible frequencies of electromagnetic radiation is called the electromagnetic spectrum; this is subdivided (from highest to lowest frequency) into gamma rays, X rays, ultraviolet (UV) light, visible light, infrared light, microwaves, and radio waves. Alternatively, electromagnetic radiation can be divided into ionizing and nonionizing frequencies based on its ability to disrupt electrons. Exposure routes: Unshielded incident radiation Where found: Electromagnetic radiation is pervasive, and life would not be possible without it. Sunlight is the most important source of ultraviolet and visible light. Many devices also emit electromagnetic radiation. At risk: Individuals with occupational or volitional exposure to ionizing electromagnetic radiation Etiology and symptoms of associated cancers: When electromagnetic radiation interacts with matter, some of the photons’ energy alters the structure or increases the kinetic energy of atoms. Structural alterations include ionization (loss of electrons) and breakage of covalent bonds. Deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and proteins are all susceptible to damage by radiation. The skin is the primary carcinogenic target, and UVcaused skin cancers occur mostly on sun-exposed areas. Shorter wavelength electromagnetic radiation such as X rays and gamma rays penetrate the skin and can cause leukemia, lung cancer, and bone cancer. The interaction of electromagnetic radiation with DNA results in abnormal dimerization of adjacent pyrimidine bases, damage to individual bases, strand breakage, and cross-linkages between DNA and adjacent proteins. Such DNA damage contributes to cancer formation through the release of cy399
Electroporation therapy
Salem Health: Cancer
In this experiment, rats are exposed to electromagnetic fields to determine if they cause cancer. (Mauro Fermariello/Photo Researchers, Inc.)
tokines, induction of latent viruses, or mutations that cause functional changes in encoded protein molecules. History: The biological effects of electromagnetic radiation in the form of sunlight have been known since antiquity. The understanding of visible light as part of a continuous spectrum was advanced with the discovery of radio waves in 1887 by Heinrich Hertz and of X rays in 1895 by Wilhelm Conrad Röntgen. One of the first publications on the carcinogenicity of sunlight appeared in 1907, and a causal relationship was demonstrated by study in a 1928 publication that involved induction of skin cancer in mice by exposure to ultraviolet light. Cancers were linked to penetrating electromagnetic radiation (X rays and gamma rays) shortly after the isolation and characterization of radioactive isotopes in the 1800’s. John B. Welsh, M.D., Ph.D. See also Cell phones; Occupational exposures and cancer; Risks for cancer; Skin cancers; Sunlamps; Sunscreens; Ultraviolet radiation and related exposures; X-ray tests. 400
u Electroporation therapy Category: Procedures; complementary and alternative therapies Also known as: EPT Definition: Electroporation therapy is a process that uses high-intensity electrical currents that increase the permeability of cell membranes and enhance the ability of cytotoxic drugs, vaccines, and genes to enter into tumor cells. Cancers treated: Squamous cell carcinoma, basal cell carcinoma, melanoma, head and neck cancers, cutaneous and subcutaneous tumors, Kaposi sarcoma Delivery routes: Electrical pulses are delivered directly into tumors using special devices called electroporators or applicators. Description: Many potentially effective anticancer drugs are limited by their ability to permeate the cell membranes and gain entry into tumor cells. The lipid bilayers of cell
Salem Health: Cancer membranes possess unique physical and biochemical properties that prevent easy entry of exogenous materials. The principle of electroporation therapy is to increase permeability of the cell membranes by pulses of intense electric current, leading to formation of transient pores in the cell membrane. Pores aid in easy uptake of cytotoxic drugs and increase the intracellular drug concentration, thereby increasing their chances of direct action on tumor cells. An electroporator consists of a circular array of six electrode needles (as three pairs) that deliver pulses directly inside tumors and create an electric field through potential differences generated between these electrodes. Effective electroporation depends on strength and duration of the applied electric field. Optimization is required for each type of tissue and the kind of molecule being delivered (for example drug vs. deoxyribonucleic acid, or DNA). Application of short pulses of electric field results in the transient formation of pores on the cell membrane. Pores close shortly after the application of electric field is terminated, resulting in almost an entrapment of drugs or other molecules. Electroporation therapy results in enhanced killing of cancer cells and early necrosis of tumors. Clinical trials on squamous cell carcinoma patients that incorporated a treatment regimen with the drug bleomycin (a cytotoxic drug derived from the bacterium Streptomyces verticillus) followed by electroporation, demonstrated complete remission in a significant proportion of patients and partial remission in others. Combination therapy with bleomycin and electroporation was more effective than either treatment alone. Bleomycin in combination with electroporation dramatically enhanced the percentage of cells killed. Among the multitudes of drugs tested in combination with electroporation, bleomycin has been proven to be the most effective. Combined therapy also increases the duration of drug retention and decreases the dose of drug needed for effective treatment. Side effects: Minimal side effects have been observed with electroporation therapy. Some electric shocks can be experienced after administration of electric pulses. Geetha Yadav, Ph.D. See also Basal cell carcinomas; Electrosurgery; Kaposi sarcoma; Melanomas; Skin cancers; Squamous cell carcinomas.
Electrosurgery
u Electrosurgery Category: Procedures Also known as: Electrofulguration, fulguration, medical diathermy, surgical diathermy Definition: Electrosurgery is the use of electric current to cut, kill tumor cells, or cauterize. Cancers treated: A variety of cancers, especially those of the skin and mouth Why performed: Surgeons have many options for removing cancerous growths or tumors. The most traditional method is to use a sharp metal scalpel to cut around the tumor and remove it. This is frequently the method in which surgeons were originally trained and with which they have the most experience. It also is often the most cost effective. There is often significant bleeding during and after this type of procedure, however, and research scientists are always trying to identify new ways to better serve patients. One way that has been developed involves the use of a laser, while another is electrosurgery. Electrosurgery uses an instrument that gives off high-frequency alternating electrical current that heats up cells and allows surgeons to cut with a reduced amount of bleeding. The same equipment can also be used for electrocautery to stop bleeding. Patient preparation: The required patient preparation depends on the type of electrosurgery being done, as well as on the extent of the procedure. In many cases, the patient will be instructed to prepare in a way similar to preparations for other types of surgeries. This can include avoiding food and liquids for a specified period of time and may involve taking antibiotics to help prevent infection. Patients will generally be specially screened to ensure that they are good candidates for electrosurgery. Individuals with pacemakers or other devices may not be appropriate candidates because of the use of electrical current that flows through the patient’s body during the procedure. Steps of the procedure: Electrosurgery is performed by a surgeon who has had extensive specialized training in using electrosurgical equipment and performing related procedures. The procedure is done using a special generator that takes regular electric current and converts it to electrical current that alternates at a frequency slightly lower than that of AM radio stations. This is done because the electrical current in normal use would result in damage to the patient, including possible nerve or muscle damage and even electrocution. Electrical current of the frequency 401
Embolization used by electrosurgical devices is usually considered safe for most individuals, except for those with pacemakers or other implanted devices. The surgeon uses a special instrument through which the electrical current flows. The surgeon has a number of choices of voltage and frequency, which can be used to achieve various effects, and will usually start with the lowest possible power and increase it until the desired effect is achieved. The tip of the surgical instrument remains cool, but the energy is transferred to the surrounding cells. At low levels, this can cause water to leave the cells and the cells to dehydrate and shrivel. At higher levels, the water inside the cells actually heats enough to boil, but so quickly that it does not have time to escape the cell and the cell actually ruptures. The surgeon can use this instrument to make very thin and precise cuts, to heat tumors to destroy them, or to cauterize cells to stop bleeding, depending on the goal of the procedure. After the procedure: After electrosurgery, the patient will generally be taken to a recovery room if the procedure was performed under general anesthesia. If there is a wound at an incision site, then it will need to be cleaned and cared for regularly until healing is complete. In many cases, electrosurgery is not the only cancer treatment option being used in a patient’s comprehensive cancer care plan. If electrosurgery is used to remove a cancerous growth, then radiation therapy or chemotherapy may still be necessary to kill any cancer cells that remain after the majority are removed surgically. Risks: Many of the risks associated with electrosurgery are the same or similar to those associated with traditional surgical methods. There is a risk of significant blood loss, pain, swelling, and infection. With electrosurgery, there is also some risk of damage to healthy tissues surrounding the cancerous tissue. Because electrosurgery is usually performed under general anesthesia, there are also the risks associated with anesthesia, such as negative cardiovascular events or allergic reaction. There is some risk of severe burning at a site other than the site of the electrosurgery. Often, smoke is produced during electrosurgery that can be a risk not only to the patient but also to the surgery team if the room is not effectively ventilated. Results: Results from electrosurgery can vary greatly depending on the type of procedure performed, the area on which the procedure was performed, and other factors. In general, it is believed that electrosurgery can be an effective method for removing tumors or for destroying cancerous growths with less blood loss than traditional surgical methods. For some applications, however, there is concern 402
Salem Health: Cancer that electrosurgical techniques may lead to a higher rate of recurrence than other available techniques. Helen Davidson, B.A. u
For Further Information Dietel, M., ed. Targeted Therapies in Cancer. New York: Springer, 2007. Egan, Tracie. Skin Cancer: Current and Emerging Trends in Detection and Treatment. New York: Rosen Publishing Group, 2006. Lyons, Lyman. Diagnosis and Treatment of Cancer. New York: Chelsea House, 2007. Nathan, David G. The Cancer Treatment Revolution: How Smart Drugs and Other New Therapies Are Renewing Our Hope and Changing the Face of Medicine. Hoboken, N.J.: John Wiley & Sons, 2007. See also Electroporation therapy; Skin cancers; Urinary system cancers.
u Embolization Category: Procedures Also known as: Vascular embolotherapy; transcatheter embolization; vascular occlusion Definition: Embolization introduces an agent into the bloodstream to occlude or block a blood vessel that supplies a tumor or organ. This procedure is minimally invasive and can be an alternative to surgery. Cancers treated: Hepatic (liver) cancer and hepatic metastases; colorectal, pancreatic, and renal (kidney) cancers Why performed: The purpose of embolization is to shrink a tumor or slow its growth, to redirect blood flow, or to control bleeding. For example, preoperative embolization can reduce blood loss in a subsequent operation, such as liver resection (surgical removal of part of the liver) or nephrectomy (removal of a kidney). Occlusion of blood vessels of the liver to shrink hepatic metastases (cancer that has spread from other parts of the body) is an alternative to surgery when an existing condition, such as cirrhosis, precludes resection. Embolization can be combined with chemotherapy in a procedure called chemoembolization. It involves introducing a chemotherapeutic drug at the tumor site to enhance local concentration of the drug, thereby avoiding systemic side effects. The blood vessel supplying the tumor is then occluded with an embolic agent. In addition, embolization is an alternative to fibroidectomy (removal of uterine fibroids).
Salem Health: Cancer Patient preparation: A physician may order diagnostic images based on ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), or X rays to assess the involved organ or site and size of a tumor. In addition, diagnostic tests may be ordered to evaluate the patient’s blood and liver and kidney function. Prior to the embolization procedure, the patient is asked about the use of drugs and herbal supplements and about any allergies, such as to contrast media used in imaging. The night before the procedure, the patient may need to abstain from food and liquid for several hours. Steps of the procedure: A radiologist or other specially trained physician performs the procedure in an interventional suite or, perhaps, in an operating room. A nurse or anesthesiologist sedates the patient and, in some cases, administers general anesthesia. A small incision is made to insert a catheter through the skin into a blood vessel, such as the femoral artery of the leg. The physician threads the catheter through the blood vessel toward the organ or tumor site. A contrast medium or dye is injected into the blood so that angiographic images of the blood vessels can guide the radiologist’s progressive threading of the catheter. Sometimes the doctor replaces the initial catheter with a smaller one to move into smaller, branching blood vessels. When the site is reached, the physician introduces or injects an embolic agent via the catheter and then observes the resulting obstruction of blood flow on a video monitor. Embolic agents can be temporary or permanent. They include metallic coils, gelatin sponge particles or foam, polyvinyl alcohol foam granules, acrylic polymer microspheres, and liquid adhesive (glue). If additional blood vessels need to be embolized, then the physician repeats the process. Embolization can take about thirty minutes to complete, but it may take several hours. At the end of the procedure, the catheter is withdrawn and pressure is applied to the initial incision. After the procedure: The patient rests horizontally for several hours and usually stays one or more nights in the hospital, mainly for pain control. Some patients experience postembolization syndrome (pain, fever, nausea, vomiting, and fatigue) for a few days or weeks. These symptoms are more likely after embolization of a solid tumor. Many patients resume normal activity within a week. The physician may order follow-up imaging studies to assess the effects of embolization. Sometimes the patient undergoes an operation after the procedure. Risks: The risks associated with embolization are small when compared to surgery. A few patients, however, may be allergic to the contrast material used for angiography
Embryonal cell cancer during the procedure. In general, the use of catheters can bruise or damage blood vessels and can introduce infection. If the embolus (plug) occludes the wrong blood vessel, then an unintended interruption of blood flow can damage normal tissue. Results: Successful embolization alleviates the patient’s symptoms and may extend survival time. In some cases, diverting blood deliberately causes hypertrophy (increase in size) of part of the liver, thereby enabling surgery on what was previously an unresectable liver. If embolization is meant to reduce the size of a bulky tumor, then the associated pain becomes more manageable. Tanja Bekhuis, Ph.D. u
For Further Information Cahill, Bridget A. “Management of Patients Who Have Undergone Hepatic Artery Chemoembolization.” Clinical Journal of Oncology Nursing 9, no. 1 (2005): 69-75. “Interventional Radiology for the Cancer Patient.” In Cancer Medicine, edited by Donald W. Kufe et al. 6th ed. Hamilton, Ont.: BC Decker, 2003. Also available online at http://www.ncbi.nlm.nih.gov/books.
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Other Resources
RadiologyInfo http://www.radiologyinfo.org Society of Interventional Radiology Http://www.sirweb.org Web MD Embolization: Vascular Lesions http://www.emedicine.com See also Arterial embolization; Carcinoid tumors and carcinoid syndrome; Chemoembolization; Hemoptysis; Hereditary leiomyomatosis and renal cell cancer (HLRCC); Hereditary non-VHL clear cell renal cell carcinomas; Hereditary papillary renal cell carcinomas; Kidney cancer; Leiomyomas; Liver cancers; Urinary system cancers; Virus-related cancers.
u Embryonal cell cancer Category: Diseases, symptoms, and conditions Also known as: Embryonal cancer Related conditions: Testicular cancer, germ-cell tumor Definition: Embryonal cell cancer is a malignant germcell tumor that occurs most often in the testes and accounts 403
End-of-life care for about 40 percent of testicular tumors. Under the microscope, these tumors may resemble tissues of early embryos. This type of tumor can grow rapidly and spread outside the testicle. Risk factors: Birth defects such as male infants with undescended testis (chryptorchidism) can lead to embryonal cancer. Etiology and the disease process: Embryonic cells grow in the embryo, and some develop into germ cells that make up the reproductive system in men and women. These embryonic germ cells follow a midline path through the body after development and descend into the pelvis as ovarian cells or into the scrotal sac as testicular cells. Embryonal cell cancer results when the reproductive germ cell develops abnormally into cancerous cells. Differing from the other types of testicular cancers, embryonal carcinoma can have several of the properties of an abnormally developed fetus. Incidence: Embryonal cell cancer is very rare, accounting for approximately 40 percent of all testicular tumors, which occur in less than 1 percent of the male population. Embryonal carcinomas are usually seen in men age twentyfive to thirty-five but have also affected youths in their late teens. The chances of an embryonal carcinoma spreading from one testicle to the other are less than 1 percent. Embryonal carcinoma in the ovaries of females is extremely rare and usually occurs before the age of thirty. Symptoms: Patients with embryonal cell cancer usually have a tumor, swelling, or mass that can be felt or seen, or an abnormal shape, or irregularity in, testicular size. Screening and diagnosis: Diagnostic procedures for embryonal cell cancer may include biopsy of the tumor; blood tests, including testing for tumor markers and a complete blood count (CBC) to determine the size, number, and maturity of different blood cells within the blood; and multiple imaging studies such as computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, and X ray. Treatment and therapy: Specific treatment for germ-cell tumors is determined by the patient’s age, overall health, medical history, and the extent of the disease. Surgery is generally performed to remove the malignant cells, and patients may undergo chemotherapy or radiation to reduce the risk of recurrence of cancerous cells. Prognosis, prevention, and outcomes: With all testicular cancers, strategies employing surgery, chemotherapy, or radiation therapy (either alone or in combination) have 404
Salem Health: Cancer created cure rates approaching 100 percent for low-stage or early disease and more than 85 percent for more advanced tumors. Early detection by performing monthly testicular self-exams can greatly improve the chances of curing the cancer. Robert J. Amato, D.O. See also Beckwith-Wiedemann syndrome (BWS); Cryptorchidism; Germ-cell tumors; Kidney cancer; Rhabdomyosarcomas; Teratocarcinomas; Testicular cancer; Testicular self-examination; Yolk sac carcinomas.
u End-of-life care Category: Social and personal issues Also known as: Palliative care, supportive care, hospice care Definition: End-of-life care is palliative or supportive care given to terminally ill patients whose treatment goals have switched from curing cancer or extending life to achieving the best possible quality of life. Goals: Palliative care is patient- and family-centered care focused on achieving quality of life through the management of pain and other distressing symptoms. It also addresses intellectual, emotional, social, spiritual, and existential needs of patients and their families, while facilitating patient autonomy and control over care. Many cancer centers are integrating palliative care with lifeprolonging treatments as a part of comprehensive cancer care. Over the course of treatment for a potentially fatal illness such as cancer, goals are constantly evaluated based on the response of the disease. When a disease progresses despite treatment and no further treatment is available or if a person decides that the burden of treatment outweighs the benefit, palliative care becomes the main focus of care. The goals of end-of-life palliative care are set by patients in consultation with their families and health care providers. The treatment plan is based on the goals and is shaped by the patient’s definition of quality of life, treatment preferences concerning the type of care and the care setting, and physical and emotional condition. Aspects of care: An end-of-life palliative care plan is developed with the health care provider in consultation with family or in some cases a palliative care consultant. Symptom management and patient function are constantly assessed so that appropriate interventions can be made. When deciding on a course of treatment, care can be cate-
Salem Health: Cancer gorized as that which should be given, care that is optional, and care that should not be given because the patient or medical proxy refuses, it is not aligned with the patient’s goals, or it presents a burden of treatment that outweighs the benefits. There are many physical symptoms that are the focus of end-of-life palliative care: pain, fatigue, difficulty breathing, loss of appetite and weight, dry mouth, bedsores, depression, confusion or delirium, and vomiting, constipation, or diarrhea. Of these symptoms, pain, fatigue, and difficulty breathing are among the most common and distressing in people dying of cancer. Pain, as a direct result of the cancer or treatments, is treated with opioid and other pain medications, given orally or through a skin patch, rectal suppositories, injections, or patient-controlled analgesic devices in which a pump injects medication intravenously, subcutaneously, or into the spine. Around-the-clock dosing is recommended for chronic pain, while intermittent pain is treated as needed. Pain is often inadequately treated because of poor communication between patients and health care providers, fears of adverse side effects and addiction, and the health care provider’s lack of knowledge or experience in managing pain. Fatigue that cannot be relieved by rest is caused by the disease, treatment, medications, psychiatric comorbidities, difficulty breathing, infection, nutritional or chemical imbalances, sleep disturbances, or uncontrolled pain. It profoundly affects a person’s quality of life. Treatment of fatigue primarily involves addressing the cause, some drug therapies, and having the patient engage in exercise. Difficulty breathing, or dyspnea, can be caused by heart and lung conditions or infections, anemia, anxiety, malnutrition, or urinary retention or constipation. Treatment involves medical intervention when appropriate and focusing on comfort, which can include the provision of oxygen, having the patient sit up, moving the air around a room, relaxation techniques, and discontinuation of intravenous fluids to reduce the amount of fluid in the lungs. Some patients in the later stages of dying elect to use a ventilator or to take opioid pain medications or sedatives to ease the distress. In addition to management of physical symptoms, endof-life care provides psychological and psychiatric care to patients and families to provide support, to assist in making difficult decisions, and to help with depression, grief, life completion, or life closure issues. Education concerning the prognosis and the dying process provides autonomy over care and helps prepare patients and families. Information is often provided concerning patients’ legal rights to receive relief from pain and suffering, to make
End-of-life care their own health care choices, to document those choices through advance directives, and to have those choices enforced by a medical proxy if their decision-making capacity becomes impaired. Financial planning may also be provided with respect to facilitating insurance coverage of services or accessing community resources to provide or pay for services. Patients’ religious, spiritual, and cultural needs are assessed so that care can be delivered in the most respectful and effective manner possible. End-of-life care can be provided in the home, hospital on an inpatient or outpatient basis, nursing homes, or longterm care facilities. Since the 1970’s, the most developed and available form of end-of-life palliative care has been hospice care, provided in freestanding hospice centers or off-site in the community. People are typically eligible for hospice care if their doctors estimate they have six months or less to live and they have refused or exhausted all treatment options. Imminent death: Special end-of-life care provisions are made when a person is actively dying or death is imminent. These provisions include focus on comfort care;
End-of-life care focuses on achieving comfort for the patient through the management of pain and other symptoms. (Digital Stock)
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Endocrine cancers discontinuation of diagnostic tests or monitoring, especially unnecessary needle sticks; ensuring access to pain medications if the oral route is not available; relieving dry mouth and lips; repositioning for comfort; ensuring patient privacy; and facilitating the family’s desire for round-the-clock presence and uninterrupted time together. Education of patients and family members on the signs and symptoms of the stages of death will help ease their anxieties and fear and assist in decision making. Patients and families also often benefit from psychological or religious support. Patients or families may be faced with difficult decisions, which ideally should be discussed ahead of time. These include withdrawing or withholding medical interventions such as nonoral feeding, artificial hydration, mechanical ventilation, medications other than those for pain, dialysis, and cardiopulmonary resuscitation (CPR). Patients and families may also have to decide if termination sedation is appropriate. Sedation is indicated when a patient is removed from a ventilator and is expected to die shortly thereafter or for control of refractory symptoms that cannot be controlled despite aggressive efforts. Legal and ethical considerations: The federal Patient Self-Determination Act of 1990 gives patients the rights to participate in and direct their own health care. State law protects these rights through advance directives, which legally document a patient’s health care choices and designate a medical proxy who is authorized to make decisions if the patient loses decision-making capacity or is deemed incompetent by a court of law. Decision-making capacity is determined by physicians based on a patient’s ability to receive and evaluate information; communicate wishes; understand the risks, benefits, and alternatives to treatment; and make consistent and logical decisions, regardless of whether the person agrees with the physicians. If there are no advance directives and the patient loses decision-making capacity and has not designated a medical proxy, the health care provider must make the medical decisions. The intent of treatment dictates whether it is ethical. If the intent of treatment is desirable and helpful to a patient, then adverse effects, such as dying, are acceptable in endof-life palliative care; however, it is unethical to take measures solely to hasten death. There is no ethical or legal mandate to continue medical interventions if it is against the wishes of a patient with decision-making capacity or of a legally designated medical proxy or if the health care provider determines the burden of medical intervention outweighs the benefits. The decision to withdraw or withhold medical intervention is not euthanasia or assisted sui406
Salem Health: Cancer cide. Medical interventions are distinguished from pain relief and from ordinary care that can be given by a layperson, which should be given to ensure quality of life. Amanda McQuade, Ph.D. u
For Further Information Lynn, Joanne, and Joan Harrold. Handbook for Mortals: Guidance for People Facing Serious Illness. New York: Oxford University Press, 1999. Shannon, Joyce Brennfleck, ed. Death and Dying Sourcebook: Basic Consumer Health Information for the Layperson About End-of-Life Care and Related Ethical and Legal Issues. 2d ed. Detroit: Omnigraphics, 2006. Young, Carolyn, Cyndie Koopsen, and Daniel Farb. End of Life Care Issues Guidebook: A Guide for Healthcare Providers and the Public on the Care of the Dying. Los Angeles: University of Health Care, 2005. u
Other Resources
End of Life/Palliative Education Resource Center http://www.eperc.mcw.edu National Comprehensive Cancer Network http://www.nccn.org National Hospice and Palliative Care Organization http://www.nhpco.org Promoting Excellence in End-of-Life Care http://www.promotingexcellence.org See also Advance directives; Brompton cocktail; Do-notresuscitate (DNR) order; Elderly and cancer; Grief and bereavement; Home health services; Hospice care; Living will; Medicare and cancer; Pain management medications; Palliative treatment; Support groups.
u Endocrine cancers Category: Diseases, symptoms, and conditions Related conditions: Prolactinoma, acromegaly, gigantism, pituitary adenoma, thyroid cancer (papillary, medullary, follicular, C-cell, anaplastic), parathyroid adenoma, parathyroid carcinoma, pheochromocytoma, insulinoma, glucagonoma, somatostatinoma, multiple endocrine neoplasia (MEN) type 1 (Wermer syndrome), MEN type 2A (Sipple syndrome), MEN type 2B, carcinoid tumor, islet cell tumor, Cushing disease Definition: Endocrine cancers are a group of benign and malignant growths that originate from the tissues of the endocrine glands. The endocrine glands are responsible
Salem Health: Cancer for regulating a number of bodily functions, including cellular metabolism, growth, development of male and female primary and secondary sex characteristics, the menstrual cycle, water and sodium balance, calcium distribution, and blood pressure. A number of functions also relate to reactions to stressors, which include the fight-orflight response and immune system modulation. The endocrine system is related functionally to the nervous system in that it maintains the long-term equilibrium of vital organ systems. Complex feedback loops at the pituitary (secondary) or hypothalamic (tertiary) level as well as physiologic demands normally regulate hormone secretion. The hypothalamus-anterior pituitary axis regulates several glands, including the adrenal cortex, thyroid gland, and reproductive system. The hypothalamus-posterior pituitary axis directly regulates physiologic functions such as breast milk ejection and uterine contraction, and stimulates water retention in the kidneys. The autonomic axis regulates body functions in response to stress and injury and includes the adrenal medulla, the juxtoglomerular apparatus in the kidney, and the alpha and beta islet cells in the pancreas. The parathyroid gland does not belong to any axis. Endocrine cancers can alter this equilibrium, leading to potentially life-threatening conditions in extremis. Risk factors: The risk factors for developing an endocrine cancer depend on the cellular origin of the cancer and the stimulus that promotes cancer cell proliferation, and they can generally be classified as environmental or hereditary. Environmental risk factors may include exposure to radiation as in the case of thyroid cancers. Although spontaneous cases do arise, such as in cases of parathyroid adenomas and insulinomas, other endocrine cancers arise as part of a distinct clinical syndrome with multiple endocrine gland involvement. The most prominent risk factor for the development of hereditary endocrine tumors is a genetic predisposition. The MEN syndromes are autosomal dominant, with a 50 percent probability of offspring inheriting the disease. Etiology and the disease process: The transformation of a normal endocrine cell into a cancerous cell is often caused by a single or a number of additive unrepaired gene alterations that prevent uncontrolled cellular division and programmed cell death. These cancer cell transformations do not differ much from the transformation of cells in other organs and have common etiologic agents such as the tumor-suppressor gene TP53. However, specific tumorsuppressor gene mutations are responsible for the genesis of certain endocrine cancers. MEN 1 originates from either a mutation within the embryonic crest cell or inactivation of the tumor-suppressor gene MEN1, located on the
Endocrine cancers long arm of chromosome 11 (11q13). MEN 2A, 2B, and familial medullary thyroid carcinoma originate from a mutation in the RET proto-oncogene, located on the long arm of chromosome 10 (10q11.2). MEN1 tumor-suppressor gene mutations, along with changes in the RET protooncogene, have also been implicated in sporadic medullary thyroid carcinoma cases. Papillary thyroid cancer genesis has been attributed to mutations in the PTC and TRK-A genes, in conjunction with the RET proto-oncogene and RAS oncogene, respectively. Endocrine cancers may be functional or nonfunctional. Functional endocrine cancers are so named because the hormone secretions from the cancer cells have the same effect on the same target organs as do hormones from normal endocrine cells. These cancer cell hormones may be structurally identical or slightly altered. Functional endocrine cancers do not respond in a normal fashion to the inhibitory feedback mechanisms in normal endocrine cells. Although some cancers lack receptors that decrease or halt hormone secretion, other cancers may be stimulated by their own secretions in a way that resembles the inhibitory mechanisms of some endocrine glands. Nonfunctional endocrine cancers do not secrete hormones or hormonelike molecules. They may be derived from hormonesecreting cells but are more often derived from stromal tissue (tissue surrounding supporting tissue). They may nonetheless interfere with normal gland function by compressing or infiltrating surrounding tissue. Incidence: According to the American Cancer Society, about 25,520 new cases of endocrine cancer were reported in 2004, or less than 1 in 10,000 people. By affected organ, thyroid cancers are the most common of all endocrine cancers, followed by pituitary gland cancers. Specific data regarding the rarer cancers are sparse. Some endocrine cancers such as thyroid cancer tend to appear in individuals older than fifty years. Symptoms: Symptoms of endocrine cancer are generally related to both the indirect effects of malignancy—such as fever, malaise, anorexia, weight loss, or paraneoplastic syndrome—and the direct and gland-specific effects of the tumor. The specific symptoms of endocrine cancers are classically related to the endocrine gland axis from which they originate, wherein serum measurements of the hormones causing symptoms directly or indirectly follows. For example, a tumor in the thyroid gland causing symptoms of increased cellular metabolism (sweating, irritability, palpitations, irregular heartbeats, heat intolerance) may be confirmed by measurements of both thyroidstimulating hormone (TSH) and thyroid hormone. Alternately, a TSH tumor would be suspected in a patient who 407
Endocrine cancers
Salem Health: Cancer
Stage at Diagnosis and Five-Year Relative Survival Rates for Thyroid Cancer, 1996-2004 Stage Localizeda Regionalb Distantc Unstaged
Cases Diagnosed (%) Survival Rate (%) 59 34 5 3
99.7 96.9 56.0 89.3
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 a Cancer still confined to primary site b Cancer has spread to regional lymph nodes or directly beyond the primary site c Cancer has metastasized
exhibits hyperthyroid symptoms but has a normal thyroid gland, being mindful of the loss of the inhibitory feedback mechanism in these tumors. Other endocrine cancers may require a combination of laboratory tests relating to their functional status in addition to hormone levels. For example, a simple parathyroid gland tumor secreting parathyroid hormone-like substances may manifest in a patient with recurrent kidney stones and heart rhythm disturbances from a high serum calcium with a correspondingly low phosphorus level because of bone demineralization. Symptom overlap is more often present because of the different possible locations of a tumor along the hypothalamic-pituitary-target organ axis, requiring an exhaustive diagnostic workup. For instance, an anterior pituitary tumor such as a prolactinoma may have the symptoms of milk production and cessation of menses in a nonpregnant woman. Similarly, a gonadotropic hormone-secreting tumor or gonadotropin-releasing hormone (GnRH) tumor in the hypothalamus may also halt the menstrual cycle. Endocrine cancers can also manifest by compressing or infiltrating adjacent tissue and structures, altering their function. An example is anterior pituitary tumors, which may initially manifest as a partial blindness termed bilateral hemianopsia (involving the right and left visual fields of the right and left eyes, respectively) in which right and left optic nerve fibers are compressed as they cross below the anterior pituitary. The specific pituitary cells may be nonfunctional or secrete excess hormones that can affect the axis accordingly. Posterior pituitary tumors may also manifest in this fashion. Other cancers may remain undetected or grow to large sizes (as with ovarian cancers). 408
The hereditary multiple endocrine neoplasia (MEN) syndromes consist of two main variants, MEN 1 and MEN 2. MEN 1 has pituitary, parathyroid, and pancreas involvement. MEN 2A manifests as medullary thyroid cancer (MTC), pheochromocytoma, an adrenal medulla tumor, and parathyroid hyperplasia (overproliferation). MEN 2B is essentially type 2A without parathyroid involvement and with the addition of mucosal neuromas and gut ganglioneuromas (nerve cell tumors) with a Marfanoid body habitus (long limbs and fingers, flexible joints, lens dislodgement, and mitral valve prolapse). Isolated MTC may also be familial and is less aggressive compared with MEN-associated MTC. Screening and diagnosis: As clinical symptoms and signs of endocrine cancers can vary widely from textbookstyle presentations, diagnosis is generally oriented toward confirming clinical suspicions through routine laboratory tests and tests measuring hormone levels. Although interpretation of some tests—such as thyroid function tests and a twenty-four-hour urine collection for catecholamine metabolites of epinephrine and norepinephrine (metanephrine, vanillylmandelic acid, or VMA) for a suspected pheochromocytoma—may be straightforward, other tests approach diagnosis by process of elimination. Tests that require such multiple steps include the dexamethasone suppression test and the progesterone challenge test. The dexamethasone suppression test involves a screening of a twenty-four-hour urine collection for cortisol as well as evaluation of the anterior pituitary (Cushing syndrome) and adrenal cortex hormone levels in response to low and high doses of dexamethasone. The progesterone challenge is similar in that it assesses the onset of bleeding with administration of suppressing doses of estrogen and progesterone to assess the presence of an androgen-secreting tumor, among other, nontumor-related diseases. These tests may also be used to assess baseline glandular functioning. Tumor markers such as cancer antigen 125 (CA 125) for ovarian cancer are rarely used alone to confirm diagnoses, although they can be used to monitor for disease recurrence. Visualization of a suspected cancer is carried out as much as possible. Imaging studies provide information for determining whether surgery is possible. If surgery is a plausible option, imaging studies provide surgeons with a means by which to plan their approach. Conventional imaging studies include computed tomography (CT) and magnetic resonance imaging (MRI). Organ-specific studies such as thyroid scans or OctreoScans for islet cell tumors rely on tumor uptake of radiolabeled substances to disclose their location. Thyroid scans also help determine
Salem Health: Cancer the presence of hormone activity, which is absent in most thyroid cancers. Occasionally, local or distal spread of tumors may occur, in which case more comprehensive imaging studies of probable areas of spread, such as the chest, abdomen, pelvis, or head, are conducted. A biopsy of tumors with high-yield procedures such as fine needle aspiration of thyroid nodules or masses can greatly aid in planning future treatment. Occasionally, this may be done during an operation through frozen section, in which a tumor specimen is frozen and thinly sliced for microscopic evaluation by a pathologist. Formal, regular screening is not usually done because of the rareness of these cancers but may be conducted when patients have a family history of multiple endocrine gland involvement. Although tumors that are hereditary have a clear genetic etiology, routine genetic testing such as that for RET is reserved for patients with medullary thyroid cancer. Treatment and therapy: Treatment of endocrine cancers generally consists of surgical removal of the lesions alongside chemotherapy or radiotherapy. Medical therapies are often limited but nonetheless essential in reducing complications. These include ensuring the control of other diseases and correcting blood pressure and fluid and electrolyte derangements, particularly in patients in whom the thyroid, parathyroid, pancreatic islet cells, and adrenal glands are involved. The surgical approach for endocrine cancers usually conforms to the relevant local anatomy while achieving optimal visualization even if the surgical field may be quite limited. For instance, a transsphenoidal approach to the pituitary gland involves making a surgical “window” through the posterior aspect of the mouth, as opposed to thyroid surgery at the base of the neck. Spread to neighboring structures may entail lymph node sampling conforming to the lymph drainage within the area of the tumors in addition to removal of secondary sites of spread wherever possible. Chemotherapy and radiotherapy are instituted for most endocrine cancers to eliminate remaining tumor cells not removed by surgery and thus decrease the chance for recurrence. Prognosis, prevention, and outcomes: The 2004 ratio of deaths to incidence in the United States from endocrine cancers irrespective of cause was estimated at 9.6 percent. Total deaths from endocrine cancers from the same year were estimated at 2,440. Most endocrine cancers have high five-year survival rates approaching 95 percent or more. Thyroid cancers in particular have high five-year survival rates, around 96 percent if detected early. As with all other cancers, this may drop to 5 percent in advanced disease involving more malignant variants (medullary,
Endocrinology oncology follicular, anaplastic). Cancers that are detected late, such as ovarian or adrenal cancers, have correspondingly lower survival rates of 50 percent and 40 percent, respectively. Complications from surgery include bleeding, marked reduction or total loss of endocrine gland function, or interruption of hypothalamic-pituitary axis equilibrium. Hormone replacement therapy may eventually be lifelong, particularly in thyroid and pituitary gland cancers. Preventive measures include proper radiation shielding of neck and genital areas. Aldo C. Dumlao, M.D. u
For Further Information Braverman, Lewis E. Diseases of the Thyroid. 2d ed. Totowa, N.J.: Humana Press, 2003. Clark, Orlo H. Endocrine Tumors. Hamilton, Ont.: BC Decker, 2003. Kelloff, Gary, Ernest T. Hawk, and Caroline C. Sigman. Cancer Chemoprevention. Totowa, N.J.: Humana Press, 2005.
u
Other Resources
American Cancer Society http://www.cancer.org Cancer Index Endocrine Malignancies http://www.cancerindex.org/clinks2e.htm Stanford Cancer Center Endocrine Cancers http://cancer.stanford.edu/endocrine/ See also Adrenal gland cancers; Adrenocortical cancer; Endocrinology oncology; Endometrial cancer; Fertility drugs and cancer; Gynecologic cancers; Gynecologic oncology; Hormonal therapies; Human growth factors and tumor growth; Multiple endocrine neoplasia type 1 (MEN 1); Multiple endocrine neoplasia type 2 (MEN 2); Neuroendocrine tumors; Pancreatic cancers; Parathyroid cancer; Pituitary tumors; Thyroid cancer.
u Endocrinology oncology Category: Medical specialties Also known as: Endocrine oncology Definition: Endocrinology oncology is the treatment of cancers affecting the endocrine organs, which are organs that produce hormones. Endocrine organs include the thyroid, adrenal glands, endocrine pancreas, and pituitary gland. 409
Endocrinology oncology Cancers treated: Thyroid tumors (including papillary, follicular, medullary, anaplastic, and mixed papillary/ follicular tumors); parathyroid tumors; adrenal tumors (including pheochromocytoma and incidentally discovered adrenal masses); tumors of the endocrine pancreas (for example, insulinoma, gastrinoma, glucagonoma); tumors of the pituitary gland Training and certification: Most doctors who treat patients with endocrine cancers are not specifically trained through endocrinology oncology residencies and fellowships. Instead, they may have completed surgical residencies, either in general surgery or in oncology or endocrine surgery. The average length of a surgical residency is five years. They may also be trained in internal medicine (a
Glands of the Endocrine System
Salem Health: Cancer three-year residency), followed by specialized residency training in oncology or endocrinology (hormone and metabolic diseases), which usually takes another three years. In addition to postgraduate clinical training, residents and fellows may elect to participate in endocrine research. Research grants are available from organizations such as the American Association of Endocrine Surgery and the American Thyroid Association to support research in the areas of diagnosis, prevention, and treatment of endocrine disease, as well as in the underlying molecular, cellular, and physiologic disease mechanisms. These residency and fellowship programs are accredited by the Accreditation Council for Graduate Medical Education. In addition, physicians are usually certified by an American Board of Medical Specialties (ABMS) Member Board, and they continually receive accredited education to update their knowledge and skills and maintain their certification. There are relatively few endocrine specialists, compared with specialists in other fields. For example, a study conducted by the American Association of Endocrine Surgeons discovered that a small number of high-volume endocrine surgeons perform 24 percent of all endocrine surgeries. The number of specialized endocrine surgeons is projected to increase in the coming years, based on the growing number of endocrine cases and the increasing number of endocrine fellowships. Services and procedures performed: The major endocrine tumors treated are those of the thyroid, parathyroid, and adrenal glands. Thyroid cancers usually grow from nodules within the thyroid. Less than 1 percent of thyroid nodules are cancerous. The oncology team, led by an endocrinologist/oncologist/surgeon, is involved in biopsying, staging, and treating endocrine tumors. Thyroid tumors are usually diagnosed by needle biopsy of a thyroid nodule (this can be guided by ultrasound) or by biopsy of the excised nodule. The biopsy sample is examined under the microscope and, based on its cellular appearance, classified as papillary, follicular, medullary, anaplastic, or a mixed type. The next step is staging, based on the
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Salem Health: Cancer characteristics of the primary tumor and the degree of metastasis. The primary tumor is examined for size and extent of invasion of surrounding tissues. The presence, number, and location of metastases in the lymph nodes and in other organs are determined. Tumors may be well differentiated or poorly differentiated, similar to tumors affecting other organs. In general, thyroid tumors that are poorly differentiated are associated with a worse prognosis. However, this is not always the case, because a patient’s prognosis also depends on other factors, such as age and health status. Anaplastic tumors, making up 1 to 2 percent of thyroid tumors, are the most aggressive type of thyroid tumor. They are poorly differentiated and are almost always fatal within twelve months of a diagnosis. Some thyroid tumors can be treated by surgical removal of the affected parts of the thyroid; this procedure is called a hemithyroidectomy and is mainly used for lowrisk papillary thyroid tumors that are localized in one lobe of the thyroid gland (the degree of risk is calculated based on several factors known to affect prognosis). Sometimes almost the whole thyroid is removed (near-total thyroidectomy) to decrease the risk of cancer spread to the recurrent laryngeal nerve or parathyroid glands. If the primary tumor is more than 1 centimeter in diameter or if metastases are present, the entire thyroid needs to be removed (total thyroidectomy). Surgeons have started to use minimally invasive endoscopic thyroidectomy techniques with smaller neck incisions for patients with low-risk, welldifferentiated tumors. Although these techniques are gaining popularity, some controversy persists about the selection of patient candidates for this treatment. Surgical removal of the tumor is often followed by treatment with radioactive iodine. Most thyroid cancer cells retain their ability to absorb iodine; radioactive iodine is taken up by any remaining cancer cells, specifically destroying them. Other cells in the body lack the ability to absorb iodine and remain unharmed. After radioactive iodine treatment, patients are given thyroid hormone pills to replenish thyroid hormone levels. For the diagnosis of adrenal tumors, computed tomography (CT) and magnetic resonance imaging (MRI) techniques are frequently employed. Some adrenal tumors require angiography (study of the tumor blood supply) to determine if the tumor is affecting the blood supply to surrounding organs. Pheochromocytomas are rare tumors (annual incidence in the United States is 800) arising from cells in the adrenal medulla. These tumors secrete catecholamines that can cause hypertension, and raised levels of free catecholamines in the urine form the basis of the diagnostic test for pheochromocytoma. The typical treat-
Endocrinology oncology ment is surgical resection of tumors. Unresectable, recurrent, or metastatic pheochromocytoma has a five-year survival rate of less than 50 percent. Parathyroid tumors occur in the parathyroid glands, which produce parathyroid hormones. These tumors are most commonly adenomas and rarely carcinomas. Surgery is the typical treatment. Endocrine pancreatic tumors occur in the endocrine pancreas, which constitutes less than 5 percent of the pancreas and consists of pancreatic islet cells that produce hormones such as insulin, glucagon, and somatostatin. Surgical resection is the standard treatment for endocrine pancreatic tumors. Related specialties and subspecialties: The team that cares for endocrine oncology patients typically consists of the endocrinologist/oncologist/surgeon, radiologists, and oncology nurses. Radiologists specialize in techniques that are used to image tumors, including X ray, computed tomography (CT), ultrasound, and magnetic resonance imaging (MRI). The radiologists work closely with the other members of the team, using various techniques to diagnose tumors in endocrine organs. Once a tumor is found, radiologists help design and execute treatment plans, including highprecision external-beam radiation therapy for pituitary tumors and postsurgical treatment of thyroid and parathyroid tumors with radioactive iodine. Oncology nurses are involved in administering therapies to the patient, monitoring their progress, and managing any adverse effects the patient may experience while on therapy. Oncology nurses also help manage patients’ expectations of treatment efficacy and adverse effects, starting at treatment initiation, to ensure a high level of adherence to the therapy. Oncology nurses are typically registered nurses (RNs) who have undergone additional training, such as acquiring a master’s degree in nursing, and have attained certification in oncology. These certifications include oncology certified nurse (OCN), certified pediatric oncology nurse (CPON), advanced oncology certified clinical nurse (AOCN), advanced oncology certified clinical nurse specialist (AOCNS), and advanced oncology certified nurse practitioner (AOCNP) credentials. Oncology nurses maintain their certifications by periodically participating in continuing nursing education in their specialized field. Nurses are certified through nurses associations in the state where they work; these associations are accredited by the American Nurses Credentialing Center arm of the American Nurses Association. Ing-Wei Khor, Ph.D. 411
Endometrial cancer u For Further Information Brunt, L. M. “Endoscopic Parathyroid and Thyroid Surgery.” In Current Review of Minimally Invasive Surgery, edited by D. C. Brooks. Philadelphia: Current Medicine, 1998. Patel, K. N., and A. R. Shaha. “Poorly Differentiated and Anaplastic Thyroid Cancer.” Cancer Control 13, no. 2 (2006): 119-128. Sosa, J. A., et al. “The Maturation of a Specialty: Workforce Projections for Endocrine Surgery.” Surgery 142 (2007): 876-883. u
Organizations and Professional Societies
American Association of Clinical Endocrinologists http://www.aace.com 245 Riverside Avenue, Suite 200 Jacksonville, FL 32202 American Board of Medical Specialties http://www.abms.org 1007 Church Street, Suite 404 Evanston, IL 60201 American Association of Endocrine Surgeons http://www.endocrinesurgery.org 3550 Terrace Street Pittsburgh, PA 15261 The Endocrine Society http://www.endo-society.org 8401 Connecticut Ave, Suite 900 Chevy Chase, MD 20815 u
Other Resources
American Thyroid Association http://www.thyroid.org/index.html National Cancer Institute Pheochromocytoma Treatment http://www.cancer.gov/cancertopics/pdq/treatment/ pheochromocytoma/healthprofessional See also Adrenal gland cancers; Adrenocortical cancer; Endocrine cancers; Endometrial cancer; Fertility drugs and cancer; Gynecologic cancers; Gynecologic oncology; Hormonal therapies; Human growth factors and tumor growth; Multiple endocrine neoplasia type 1 (MEN 1); Multiple endocrine neoplasia type 2 (MEN 2); Neuroendocrine tumors; Pancreatic cancers; Parathyroid cancer; Pituitary tumors; Thyroid cancer. 412
Salem Health: Cancer
u Endometrial cancer Category: Diseases, symptoms, and conditions Also known as: Uterine corpus cancer, uterine cancer Related conditions: Obesity, hypertension, polycystic ovary syndrome, endometrial hyperplasia Definition: Endometrial cancer is cancer of the endometrial cells that line the uterus, which is the female organ in which the fetus develops. Estrogen, a female hormone, is a primary growth signal for the endometrium (lining of the uterus). When endometrial cells are exposed to increased levels of estrogen for long periods of time and when they acquire certain genetic mutations, they can become cancerous. Risk factors: Certain demographic characteristics—being over the age of fifty, being white, and never having been pregnant—can contribute to the risk of endometrial cancer. Long-term exposure to estrogen may also affect the incidence of endometrial cancer. Estrogen exposure can be in the form of hormone replacement therapy (commonly used to control menopause-related symptoms) or tamoxifen (an estrogen-like drug used to prevent or treat breast cancer). Increased exposure to estrogen can also occur in women who began menstruation early (before the age of twelve) or reached menopause late (after the age of fifty). Because estrogen can be produced in fatty tissue, being overweight can increase the risk of endometrial cancer. Furthermore, obesity-related conditions, such as type 2 diabetes and high blood pressure, may increase the risk. Finally, many diseases may also be associated with an elevated risk of endometrial cancer, including endometrial hyperplasia (a noncancerous condition characterized by overgrowth of the endometrium), a history of breast or ovarian cancer, and hereditary nonpolyposis colorectal cancer (a disease caused by mutations in deoxyribonucleic acid, or DNA, repair genes). Etiology and the disease process: Within the female reproductive system, the ovaries are responsible for producing the hormones estrogen and progesterone. The levels of these hormones fluctuate each month, allowing the endometrium to thicken (because of endometrial cell growth) at the beginning of the monthly menstruation cycle in preparation for an egg to be fertilized and implanted within the uterus. At the end of the monthly cycle, the endometrium is shed if pregnancy does not occur. Because estrogen is responsible for stimulating the growth of endometrial cells, too much estrogen may lead to too much cell growth. Genetic changes may also contribute to the transformation of normal cells into cancerous cells. Endometrial can-
Salem Health: Cancer cer can be divided into type 1 and type 2 carcinomas based on their relationship with estrogen and how the cells look under a microscope. Type 1 carcinoma, which accounts for 70 to 80 percent of all endometrial cancer cases, is estrogen dependent and associated with the inactivation of PTEN (a tumor-suppressor gene) and mutations in DNA repair genes, KRAS (a gene that encodes a proto-oncogene), and beta-catenin (a protein). In the less prevalent (but more aggressive) type 2 carcinoma, which follows an estrogenindependent pathway, major genetic changes within endometrial cells include mutations in TP53 (another tumorsuppressor gene) and overexpression of human epidermal growth factor receptor 2/neu (HER2/neu). When cells have tumor-suppressor genes and DNA repair genes that are not functional, they lose the ability to regulate growth and cell division, as well as the ability to fix additional mutations that may arise. Expressing excess growth factor receptors also means that cells may grow and divide more quickly and may not respond when cellular signals try to stop proliferation. Incidence: In women, endometrial cancer is the fourth most common cancer (after breast, lung, and colon cancers). Some 95 percent of uterine cancers are endometrial; the other 5 percent are due to cancerous muscle or myometrial cells within the uterus. The American Cancer Society estimated that in 2007 more than 39,000 new cases would arise and about 7,400 people would die from endometrial cancer in the United States. Symptoms: The most common symptoms in endometrial cancer are pelvic pain and vaginal bleeding between menstrual periods or after menopause. Screening and diagnosis: Screening tests such as a pelvic exam, a Pap smear (to check for cervical cancer), and a transvaginal ultrasound (to determine if the endometrium is too thick) may be performed. Blood tests can look for lower red blood cell counts (possibly indicating loss of blood from the uterus) and for raised levels of cancer antigen 125 (CA 125, a protein that is associated with tumors of the endometrium and ovaries). To make a diagnosis, a tissue sample from the uterine lining should be removed and analyzed under the microscope. Tissue samples can be obtained either by a biopsy or by dilation and curettage (D&C). AD&C is a more invasive procedure for obtaining endometrial tissue and may be done if the biopsy did not obtain a large enough sample or if the biopsy was positive for cancer and a confirmation is needed. Endometrial cancer is staged using the International
Endometrial cancer Federation of Gynecology and Obstetrics (FIGO) cancer staging system, as follows: • Stage I: The tumor is only in the uterus. • Stage II: The cancer has spread from the body of the uterus to the cervix. • Stage III: The cancer has spread outside the uterus but not outside the pelvis (and not to the bladder or rectum). Lymph nodes in the pelvis may contain cancer cells. • Stage IV: The cancer has spread into the bladder or rectum, or it has spread beyond the pelvis to other parts of the body. Treatment and therapy: Women with endometrial cancer may undergo surgical removal of the uterus, in a procedure known as a hysterectomy. Often, the uterus is removed along with the Fallopian tubes and ovaries as well as neighboring lymph nodes to ensure that all of the cancerous cells have been removed. Although this is the standard treatment for women already in menopause and no longer fertile, women of childbearing age need to consider the outcome of this surgery as they will lose the ability to have a child. For Stage I endometrial cancer, surgery to remove the uterus has been shown to be 90 percent effective. Radiation therapy, where high-dose X rays are used to kill cancer cells, may be used after surgery to prevent the formation of or treat existing cancer cells outside the uterus. Radiation may also be used in place of surgery if women refuse a hysterectomy or if a tumor is growing rapidly, associated closely with muscle cells in the uterus, or is highly vascularized (with lots of blood vessels infiltrat-
Age at Death for Uterine Cancer, 2001-2005 Age Group
Percentage Diagnosed
Under 20 20-34 35-44 45-54 55-64 65-74 75-84 85 and older
0.0 0.4 2.2 8.1 18.4 26.4 28.7 15.9
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 Note: The median age of death from 2001 to 2005 was seventy-three, with an age-adjusted death rate of 4.1 per 100,000 women per year.
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Endometrial hyperplasia ing the tumor). Radiation therapy can be delivered either conventionally (the standard external X ray) or as brachytherapy (internal radiation to target only the inner lining of the uterus). Although brachytherapy has fewer side effects than conventional radiation therapy, its effects are only local, so it cannot be used if the cancer has spread outside the uterus. Hormone therapy is often used when cancer has spread outside the uterus. Synthetic progestin, which is a form of progesterone, is used to inhibit the growth of cancerous endometrial cells. Although this therapy may be associated with higher risks of recurrence than surgical removal of the uterus, this option is attractive to women who still want to have children or who were diagnosed in a very early stage. Chemotherapy may also be used to kill cancer cells that have spread beyond the uterus. Prognosis, prevention, and outcomes: To prevent endometrial cancer (both initial and recurrent cases), taking hormones with progesterone may help slow or inhibit the growth of endometrial cells. Women may undergo hormone therapy with progestin or take birth control pills. Women who take birth control pills have a reduced risk of endometrial cancer for up to ten years after discontinuing oral contraceptives. As with other cancers, living a healthy lifestyle is important in reducing the risk of cancer. This includes maintaining a healthy weight (as obesity is a risk factor for developing endometrial cancer) and exercising regularly. For endometrial cancer, the five-year survival rates for women receiving the proper treatment are approximately 75 to 95 percent for women diagnosed at Stage I, 50 percent for Stage II, 30 percent for Stage III, and less than 5 percent for Stage IV. In a study analyzing recurrence rates across sixteen studies, the overall risk of recurrence was 13 percent, and this was even less in low-risk patients who were diagnosed with Stage I or II cancers or who did not have associated diseases known to increase the risk of endometrial cancer. This study also showed that about 70 percent of recurrences were accompanied by symptoms, and 68 to 100 percent of these recurrences occurred within about a threeyear span after the follow-up visit. Elizabeth A. Manning, Ph.D.
Salem Health: Cancer view.” Gynecologic Oncology 101, no. 3 (June, 2006): 520-529. Liu, F. S. “Molecular Carcinogenesis of Endometrial Cancer.” Taiwanese Journal of Obstetrics and Gynecology 46, no. 1 (March, 2007): 26-32. Robertson G. “Screening for Endometrial Cancer.” Medical Journal of Australia 178, no. 12 (June 16, 2003): 657-659. Sherman, M. E. “Theories of Endometrial Carcinogenesis: A Multidisciplinary Approach.” Modern Pathology 13, no. 3 (March, 2000): 295-308. u
Other Resources
MayoClinic.com Endometrial Cancer http://www.mayoclinic.com/health/endometrialcancer/DS00306/DSECTION=1 National Cancer Institute Endometrial Cancer http://www.cancer.gov/cancertopics/types/ endometrial See also Antiestrogens; 1,4-Butanediol dimethanesulfonate; CA 125 test; Chemoprevention; Colposcopy; Computed tomography (CT) scan; Conization; Dilation and curettage (D&C); Endometrial hyperplasia; Endoscopy; Family history and risk assessment; Geography and cancer; Ginseng, panax; Gynecologic cancers; Herbs as antioxidants; Hormonal therapies; Hormone replacement therapy (HRT); Hysterectomy; Hysterography; Hysterooophorectomy; Hysteroscopy; Isoflavones; Leiomyomas; Leiomyosarcomas; Mitochondrial DNA mutations; MLH1 gene; MSH genes; Nutrition and cancer prevention; Obesity-associated cancers; Pap test; Transvaginal ultrasound; Uterine cancer.
u Endometrial hyperplasia Category: Diseases, symptoms, and conditions Also known as: EH, endometrial neoplasia, endometrial intraepithelial neoplasia Related conditions: Endometrial cancer
u
For Further Information Canavan, T. P., and N. R. Doshi. “Endometrial Cancer.” American Family Physician 59, no. 11 (June, 1999): 3069-3077. Fung-Kee-Fung, M., et al. “Follow-Up After Primary Therapy for Endometrial Cancer: A Systematic Re414
Definition: Endometrial hyperplasia is the abnormal proliferation of the cells that comprise the inner cell lining of the uterus (endometrium). The endometrium is the tissue layer in which a fertilized ovum implants itself and divides. It consists of glands and surrounding supportive tissue (stroma) and is rich in blood, from which the develop-
Salem Health: Cancer ing embryo derives oxygen and nutrients through the placenta. Risk factors: Risk factors for endometrial hyperplasia are related to lifetime exposure to excess estrogen and include estrogen therapy without progesterone, tamoxifen therapy, late menopause, no history of childbirth, infertility or failure to ovulate, obesity, and obesity-related diseases (diabetes, hypertension). A known hereditary nonpolyposis colon cancer (HNPCC) genetic mutation carrier or a woman with a strong family history of colon cancer is at high risk not only for hyperplasia but for cancer as well. Etiology and the disease process: Endometrial hyperplasia is primarily caused by estrogen stimulation of the endometrial glands. These glands then proceed to multiply and enlarge. Abnormal endometrial hyperplasia may eventually arise from normal cyclic estrogen stimulation. However, there may be sources of excess estrogen independent of the menstrual cycle involved in abnormal endometrial proliferation, such as granulosa cell tumors, polycystic ovary syndrome (PCOS), tamoxifen therapy, or use of estrogen-containing birth control pills. Estrogen stimulation alone results in an unstable endometrial bed, which is prone to breakdown and bleeding. Over time, excessive endometrial stimulation and rapid cell division increase the chance of cell mutations that ultimately predispose the woman to cancer. Incidence: In women with documented abnormal uterine bleeding, 20 percent was caused by endometrial hyperplasia. The incidence may be as high as 25 percent in postmenopausal women on estrogen hormone replacement therapy (HRT); 36 to 49 percent in nonmenstruating, nonovulating women whose condition is the result of PCOS or other undetermined cause; and close to 50 percent in hypertensives and diabetics, although concomitant obesity as a source of excess estrogen formation may account for this according to other studies. Symptoms: Abnormal uterine bleeding is the main symptom associated with endometrial hyperplasia. The bleeding, compared with the woman’s normal menstrual cycle, may be characterized as excessive in amount, duration, frequency, or a combination of these. Painless spotting or bleeding from the vagina in a postmenopausal woman is the most common symptom reported in endometrial cancer. In premenopausal women, heavy menstrual bleeding can be confused with physiologic hyperplasia that occurs during the menstrual cycle. Bleeding between periods may also raise the suspicion of endometrial hyperplasia, although extrauterine masses producing excess estrogen or intrauterine masses such as polyps or fibroids bleeding
Endometrial hyperplasia into the uterine cavity must also be considered. Symptoms accompanying long-standing significant blood loss include fatigue due to anemia. On examination of the pelvis, an enlarged uterus in a nonpregnant or postmenopausal woman may also suggest hyperplasia. This may or may not be accompanied by abnormal findings in the ovaries, Fallopian tubes, and supporting ligaments. Screening and diagnosis: The American Cancer Society currently has no screening recommendations for endometrial hyperplasia. Further testing is carried out in patients who exhibit a high clinical suspicion for endometrial cancer, particularly postmenopausal women over forty years of age. These tests include an endometrial biopsy and an optional pelvic ultrasound when a mass is detected on physical examination. An adequate endometrial biopsy is the standard by which the endometrium is evaluated for cellular characteristics suggestive of precancer. Diagnosis of endometrial hyperplasia and type are dependent on microscopic examination of the biopsy sample. The biopsy sample, containing glands and tissue surrounding these glands (stroma), is examined and classified according to the proportion of glands to stroma, morphology of the glands, and cellular characteristics suggestive of precancer (cellular atypia). Simple, enlarged glands seen within a larger proportion of stroma pose about a 1 percent risk of progression to endometrial cancer. More complex glands possessing more cellular outpouchings than the previous type and a paucity of stroma pose a 3 to 5 percent risk. Simple and complex type glands with atypical cell characteristics (darkstaining cells with large nuclei and little cytoplasm) pose an 8 to 10 percent and 25 to 30 percent risk, respectively. Treatment and therapy: The type of treatment depends on the classification of the hyperplasia irrespective of atypia and, in premenopausal women, the desire to bear children after treatment. Cyclic progestin therapy is used for premenopausal women with no atypical cell findings on biopsy or for those with atypical findings who still wish to bear children. Treatment takes place over three to six months using progesterone contraceptives that can be taken by mouth, such as megestrol acetate and medroxyprogesterone acetate. Intramuscular medroxyprogesterone acetate and levonorgestrel via an intrauterine device (IUD) may also be used for three months and five years, respectively. Follow-up with endometrial biopsies is done every six months to check for recurrence. Discontinuation of progestin depends on the absence of symptoms and a normal biopsy. A total hysterectomy is the recommended course of action in premenopausal women who no longer desire to 415
Endorectal ultrasound bear children or are no longer of childbearing age, and in postmenopausal women with findings of atypia on endometrial biopsy. Prognosis, prevention, and outcomes: A substantial number of patients diagnosed with endometrial hyperplasia with and without atypical cells found on biopsy spontaneously regress (50 percent and 80 percent, respectively). However, treatment as described above should be strongly considered. Aldo C. Dumlao, M.D. u
For Further Information Boston Women’s Health Book Collective. Our Bodies, Ourselves: Menopause. New York: Simon & Schuster, 2006. Goodwin, Scott C., Michael S. Broder, and David Drum. What Your Doctor May Not Tell You About Fibroids: New Techniques and Therapies—Including Breakthrough Alternatives to Hysterectomy. New York: Warner Books, 2003. Rosenthal, Sara M. The Gynecological Sourcebook. 4th ed. New York: McGraw-Hill, 2003. u
Other Resources
American College of Obstetricians and Gynecolgists Endometrial Hyperplasia http://www.medem.com/MedLB/ article_detaillb.cfm?article_ID= ZZZ7Z2GWQMC&sub_cat=9 National Cancer Institute What You Need to Know About Cancer of the Uterus http://www.nci.nih.gov/cancertopics/wyntk/uterus/ page3
Salem Health: Cancer ities (such as fiber-optic or electronic and two- or threedimensional), and configuration (that is, the ultrasound transducer is either mounted on or passed through an endoscope). Cancers diagnosed: Rectal cancer Why performed: ERUS may be performed either as a diagnostic procedure to determine tumor boundaries and to assess spread into lymph nodes and pelvic organs or as a surveillance procedure to detect local recurrence. Patient preparation: A few days before the procedure, the patient may need to stop certain medications, such as aspirin products and blood thinners. The day before the procedure, the patient cleans the rectum, as with an enema. Steps of the procedure: ERUS is scheduled in a physician’s office or other outpatient setting. The patient wears a gown and lies on the side. The patient is awake; if needed, sedation or local anesthetic can be given. First, the physician performs a digital rectal exam. Then, the ultrasound transducer is inserted through the anus into the rectum, and a latex balloon (or alternative for a latex-sensitive patient) covering the ultrasound transducer is inflated. The ultrasound transducer is turned on, sending pulses of sound waves through the balloon into the rectal wall and adjacent tissues. As each pulse of sound waves hits different tissues, some sound waves bounce back and become a gray-scale image on a video monitor. The physician views the images as the ultrasound transducer is moved through the rectum. Tumor dimensions and lymph node sizes are measured. Abnormal tissues are sampled (biopsied) with a fine needle; all tissue samples are taken to the laboratory for cytologic evaluation.
See also Dilation and curettage (D&C); Endometrial cancer; Granulosa cell tumors.
After the procedure: The patient leaves and resumes normal activities, unless sedation or local anesthetic was needed. In the latter case, the patient will need to be driven home by a friend or family member.
u Endorectal ultrasound
Risks: ERUS is relatively safe, with a small risk of these side effects: perforation, bleeding, and infection.
Category: Procedures Also known as: Endorectal echoscopy, endorectal ultrasonography, rectal endosonography, transrectal ultrasound Definition: Endorectal ultrasound (ERUS) is the insertion of an ultrasound transducer through the anus to construct detailed images of the rectal wall and adjacent tissues. ERUS instruments vary in insertion tube design (such as size, flexibility, and view), ultrasound technology (such as frequency, orientation, and scanning), imaging capabil416
Results: ERUS images are interpreted with criteria developed by Ulrich Hildebrandt and Gernot Feifel in 1985. Boundaries of the tumor in the rectal wall are accurately determined from the thickness and continuity of each layer of the rectal wall. Lymph nodes and pelvic organs are assessed for size, shape, and irregularities. Because cancerous and inflamed tissues look similar in ERUS images, however, cytologic evaluation must verify that abnormalities in lymph nodes or pelvic organs are cancerous. Patricia Boone, Ph.D.
Salem Health: Cancer See also Anal cancer; Colonoscopy and virtual colonoscopy; Colorectal cancer screening; Prostate cancer; Prostate-specific antigen (PSA) test; Rectal cancer; Sigmoidoscopy; Transrectal ultrasound.
u Endoscopic retrograde
cholangiopancreatography (ERCP) Category: Procedures Definition: Endoscopic retrograde cholangiopancreatography (ERCP) is the X-ray study of the bile and pancreatic ducts using contrast dye injected in the ducts from a tube with a tiny camera at the end (endoscope) inserted down the patient’s throat and through the stomach to the duodenum.
Endoscopy complications, the patient may be allowed to return home. Some patients report a sore throat for several days and should eat a soft diet for the next twenty-four hours. Risks: The risk of complications for ERCP is minor (less than 5 percent) and includes pancreatitis, bleeding, and perforation of the esophagus, stomach, or small intestine. Pain, fever, and chills may indicate an infection. Patients may react to the anesthetic or dye with nausea, hives, blurred vision, dry mouth, retention of urine, or a burning or flushed feeling. Results: Normal findings show the biliary and pancreatic ducts are of normal size with no obstructions. Abnormal results include narrowing or inflammation of the ducts. Marcia Pinneau, R.N. See also Bile duct cancer; Endoscopy; Gallbladder cancer; Hepatomegaly; Pancreatic cancers.
Cancers diagnosed: Pancreatic cancer, bile duct cancer, gallbladder cancer
u Endoscopy
Why performed: ERCP permits a doctor to check for swelling or tumors in the ducts that pass digestive fluids from the gallbladder and pancreas to the stomach, to perform a biopsy, and to remove minor obstructions in the ducts. It may be recommended for patients with a familial history of pancreatic cancer, but it is not used as a routine screening tool for those with an average risk for cancer.
Category: Procedures Also known as: Brochoscopy, capsule endoscopy, colonoscopy, colposcopy, cystoscopy, cystourethroscopy, endoscopic retrograde cholangiopancreatography (ERCP), endoscopic ultrasound (EUS), enteroscopy, esophagogastroduodenoscopy (EGD), flexible bronchoscopy, flexible sigmoidoscopy, gastroscopy, hysteroscopy, laparoscopy, laryngoscopy, lower endoscopy, mediastinoscopy, panendoscopy, peritoneal endoscopy, pleuroscopy, proctosigmoidscopy, sigmoidoscopy, thorascopy, upper endoscopy, virtual endoscopy
Patient preparation: This procedure is done in an X-ray room. Patients must take nothing by mouth for eight hours prior to the procedure. The doctor may restrict medications such as aspirin, which may increase the risk of bleeding. Patients should report any allergy or sensitivity to anesthetics, dyes, or other medications. Steps of the procedure: The patient receives a sedative for relaxation and a local anesthetic in the throat to suppress the gag reflex. The doctor helps the patient swallow the endoscope and threads it through the esophagus and stomach into the duodenum, where the common bile duct enters the small intestine. The tube is narrow and flexible and does not interfere with breathing. With the end at the common bile duct, the doctor injects a radiopaque dye and takes an X ray. After removing a biopsy specimen, the doctor removes the tube. The procedure usually takes less than an hour. After the procedure: To prevent choking, the patient is not given anything to eat or drink until the anesthetic has worn off. After several hours of observation to rule out any
Definition: Endoscopy is a procedure that involves inserting a thin tube with a viewing instrument inside the body to examine the internal anatomy. There are many types of endoscopes, depending on the purpose of the procedure and the part of the body being examined. Endoscopes may be equipped with lights, fiber optics, ultrasound, lasers, or surgical instruments. Endoscopes may be inserted into the body through small incisions or through natural openings, such as the mouth, vagina, anus, or urethra. Common types of endoscopes include bronchoscopes, colonoscopes, colposcopes, cystoscopes, esophagogastroduodenoscopes, hysteroscopes, laparoscopes, laryngoscopes, mediastinoscopes, sigmoidoscopes, and thoracoscopes. Cancers diagnosed or treated: Anal cancer, bile duct cancer, bladder cancer, cancer of unknown origin, carcinoid 417
Endoscopy
Salem Health: Cancer Endoscopy and Its Uses
cancer, cervical cancer, colon cancer, colorectal cancer, endometrial cancer, esophageal cancer, gallbladder cancer, laryngeal and hypolaryngeal cancer, liver cancer, lung cancer, cancer of the nasal cavity and parasinuses, metastasized cancer, oral cavity and oropharynngeal cancer, ovarian cancer, pancreatic cancer, prostate cancer, small intestine cancer, stomach cancer, vaginal cancer, uterine cancer 418
Why performed: Endoscopies are medical procedures used to screen, diagnose, biopsy, stage, treat, and palliatively treat cancer. Endoscopy is used to screen for certain cancers, allowing early detection and treatment. It is used to provide more detailed information about suspicious tissues seen on imaging scans, which then can be biopsied or removed. Endoscopy is used to determine how far cancer has spread to help in staging. In advanced
Salem Health: Cancer cancer, surgical endoscopy is used for palliative care. Endoscopes are used in minimally invasive or “keyhole” surgeries. Capsule endoscopy is a newer technology in which a miniature camera and light source are contained in a capsule, which is swallowed. The capsule creates images of the intestine that cannot be reached with standard endoscopy. Virtual endoscopy is another newer technology that uses endoscopy and computed tomography (CT) scans to create three-dimensional images. Patient preparation: Preparation depends on the type of endoscopy that is being performed. Generally, upper endoscopies use sedation and local or general anesthesia and require fasting. Lower endoscopies use sedation and local or general anesthesia and require fasting, a liquid diet, laxative use, or an enema. Laparoscopic procedures require fasting and general anesthesia. Some endoscopic procedures may use local anesthesia and may not require fasting. Patients receive specific instructions prior to the procedures. Many types of endoscopies are performed as outpatient procedures at hospitals or surgical centers. Some procedures may require a short stay in the hospital. Steps of the procedure: The steps of the procedure depend on the type of endoscopy being performed. An upper endoscopy involves the use of a plastic mouthpiece to keep the mouth open. The well-lubricated endoscope is placed in the mouth and swallowed by the patient. The doctor gently guides the endoscope through the esophagus, stomach, and small intestine by viewing images on a monitor. A lower endoscopy involves placing a well-lubricated endoscope through the anus and into the rectum and/or colon. The procedure is guided by visual images on a screen. Laparoscopic endoscopy involves inserting the endoscope through a small incision. Air may be inserted to expand the body cavity to create a better view. Surgery may be performed with endoscopy. Surgical instruments may be used to take a biopsy. Lasers or surgical instruments may be used to remove small cancerous or precancerous growths. After the procedure: The patient is observed in the recovery area until alert. Patients receiving outpatient procedures may need another person to drive them home. Some procedures may require a short inpatient stay. Depending on the type of endoscopy, patients may experience discomfort and minimal bleeding. They will receive specific care instructions related to their procedures. Risks: The risks of endoscopy include pain, bleeding, infection, organ or tissue perforation, and those associated with general anesthesia.
Endoscopy Results: Healthy tissues are free of atypical or abnormal growths. Suspicious tissues may be biopsied during the endoscopy or with a separate procedure. Biopsied tissues or suspicious growths that are removed are tested for the presence of cancerous and precancerous cells. Mary Car-Blanchard, O.T.D., B.S.O.T. u
For Further Information Ersoy, O., B. Sivri, and Y. Bayraktar. “How Helpful Is Capsule Endoscopy to Surgeons?” World Journal of Gastroenterology 13, no. 27 (July 21, 2007): 36713676. Faigel, Douglas O., and David R. Cave, eds. Capsule Endoscopy. Philadelphia: Saunders Elsevier, 2008. Ginsberg, Gregory, et al. Clinical Gastrointestinal Endoscopy. Philadelphia: Elsevier Saunders, 2005. Hara, A. K., et al. “Imaging of Small Bowel Disease: Comparison of Capsule Endoscopy, Standard Endoscopy, Barium Examination, and CT.” Radiographics 25, no. 3 (May/June, 2005): 697-711. Hartmann, D., et al. “Capsule Endoscopy: Technical Impact, Benefits, and Limitations.” Langenbecks Archives of Surgery 389, no. 3 (June, 2004): 225-233. Pennazio, M. “Capsule Endoscopy: Where Are We After Six Years of Clinical Use?” Digestive and Liver Disease 38, no. 12 (December, 2006): 867-878. Sterman, Daniel, et al. Thoracic Endoscopy: Advances in Interventional Pulmonology. Malden, Mass.: Blackwell, 2006. Wilcox, C. Mel, Miguel Muñoz-Navas, and Joseph J. Y. Sung. Atlas of Clinical Gastrointestinal Endoscopy. 2d ed. Philadelphia: Saunders Elsevier, 2007.
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Other Resources
American Cancer Society http://www.cancer.org American Society for Gastrointestinal Endoscopy http://www.asge.org Society of International Gastroenterological Nurses and Endoscopy Associates http://www.signea.org See also Anoscopy; Bronchoscopy; Colonoscopy and virtual colonoscopy; Colposcopy; Culdoscopy; Cystoscopy; Endoscopic retrograde cholangiopancreatography (ERCP); Gonioscopy; Hysteroscopy; Laparoscopy and laparoscopic surgery; Laryngoscopy; Mediastinoscopy; Sigmoidoscopy; Thoracoscopy; Upper gastrointestinal (GI) endoscopy. 419
Endotheliomas
u Endotheliomas Category: Diseases, symptoms, and conditions Also known as: Hemangioendotheliomas, hemangiosarcomas, angiosarcomas, hemangiomas, meningiomas Related conditions: Soft-tissue sarcoma, benign tumors Definition: Endothelioma is a general term used to describe malignant or benign neoplasms of endothelial tissue (the cells that line blood vessels or lymphatic channels). These tumors can arise in any part of the body and often are referred to by terms specific to their location. For example, meningioma or dural endothelioma is a type of benign brain tumor, hepatic angiosarcoma or hemangioendothelioma is a type of liver cancer, and hemangioma is a tumor that often develops on or just under the skin. All fall under the somewhat broader heading of soft-tissue sarcomas. Risk factors: There are no readily identifiable risk factors particular to malignant endothelioma (angiosarcoma), although several risk factors associated with soft-tissue sarcomas in general have been identified. These include exposure to chlorophenols in wood preservatives and phenoxyacetic acid in herbicides, exposure to ionizing radiation, and very rare genetic predispositions in some families. Infantile hemangiomas do not appear to have a hereditary origin, and no known food, medication, or activity during pregnancy has been identified as a risk factor. Etiology and the disease process: The etiology of malignant endothelioma is obscure, although tumors have been known to develop as complications from a preexisting condition. Lymphedema resulting from radical mastectomy may trigger the development of angiosarcoma, and radiation-induced angiosarcomas have developed many years following successful radiotherapy for visceral carcinomas and Hodgkin disease. Environmental carcinogens such as vinyl chloride and thorium dioxide have been shown to induce hepatic hemangioendothelioma. Once initiated in the lining of the blood vessels, the tumor spreads rapidly and builds its own blood vessel network. The causes of infant and neonatal benign hemangioma are also unknown, although some studies have implicated the process of estrogen signaling in hemangioma proliferation. Other studies suggest that an interaction between fetal skin and the maternal placenta may trigger the tumor formation. Incidence: Less than 1 percent of newly diagnosed cancers are soft-tissue sarcomas. Of these, only about 2 percent are classified as hemangiosarcomas or angiosarco420
Salem Health: Cancer mas. The annual incidence of soft-tissue sarcomas in the United States is approximately 2 to 3 cases per 1 million people. Hemangiomas, on the other hand, are the most common benign childhood tumors, occurring in approximately 4 to 10 percent of white children (although they are much less prevalent in children of other races). They are common in twin pregnancies, and the incidence may be as high as 25 percent in premature infants weighing less than 1,000 grams. Female children are three to five times more likely to be affected than male children. Symptoms: Symptoms vary greatly depending on tumor location. Soft-tissue sarcomas of the extremities usually present as painless swellings that grow at a moderately rapid pace. Abdominal and thoracic endotheliomas may grow to large masses before detection. Neurologic symptoms may result from the compression of lumbar or pelvic nerves, and in the case of liver, heart, or bowel tumors, organ function may be compromised as the tumors grow. Up to one-third of patients may present with anemia or other evidence of recent hemorrhage, including gastrointestinal bleeding, hemothorax, or persistent hematoma. Infantile hemangiomas present a more predictable growth pattern. Although occasionally present at birth, most arise during the first few weeks after birth and grow rapidly over the next several months. This is followed by a gradual shrinking, which may occur over a period of one to seven years. Regression appears to be complete in 50 percent of children by the age of five and in essentially all children by the age of twelve. Screening and diagnosis: Diagnosis of malignant endothelioma in most cases is based on surgical biopsy and direct histological examination of tumor tissue. The characteristic network of blood vessels usually provides an unambiguous identification. Screening tests for industrial workers exposed to vinyl chloride are available, but screening programs for people exposed to other environmental carcinogens are not generally available because of the rarity of this type of cancer. Staging of these tumors generally follows the guidelines established by the American Joint Committee on Cancer. These stages are based on the size of the tumor (T), the degree of spread to regional lymph nodes (N), and spread to distant lymph nodes and organs (metastasis, M) as well as its grade. Treatment and therapy: Treatment of malignant endothelioma varies considerably depending on tumor location, although surgical removal with wide margins (2 centimeters, or cm) is recommended whenever possible. However, surgery may be inadvisable for a massive tumor or one extending into vital structures. In these cases and some-
Salem Health: Cancer
Enteritis
times following successful surgery, chemotherapy, radiation therapy, or both are often recommended. Most infantile hemangiomas disappear without treatment, often leaving no visible marks or scars. Occasionally in the case of large affected areas, cosmetic surgery may be indicated. Oral corticosteroids may be prescribed, and small raised lesions may be treated by the direct injection of corticosteroids. In cases of incomplete resolution or for flat, superficial lesions in cosmetically significant areas, pulsed dye laser therapy can be useful.
u Enteritis
Prognosis, prevention, and outcomes: Malignant endotheliomas, like most soft-tissue sarcomas, are clinically aggressive, often difficult to treat, and have a high rate of local recurrence and metastasis. The prognosis is poor, with reported five-year survival rates generally less than 20 percent. Jeffrey A. Knight, Ph.D.
Risk factors: In cancer patients, enteritis is caused by radiation therapy to the abdomen, pelvic area, or rectum. Radiation therapy is given either to treat an inoperable tumor or as an adjunct to surgery or chemotherapy. The likelihood of developing radiation enteritis depends on multiple factors, including: • where the radiation was targeted • strength and frequency of radiation treatment • tumor size • amount of bowel (large or small intestine) exposed to radiation • whether radiation therapy is given at the same time as chemotherapy • presence of radioactive implants to target tumors • patient health and nutritional status Generally, the higher the dose and frequency of radiation and the larger the amount of intestine exposed, the more likely the individual is to develop radiation enteritis. Patients who have diabetes, high blood pressure, poor nutritional status, or conditions that interfere with blood flow to the intestines are more likely to develop radiation enteritis.
u For Further Information DeVita, Vincent T., Jr., Samuel Hellman, and Steven A. Rosenberg, eds. Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2004. Weinberg, Robert A. The Biology of Cancer. New York: Garland Science, 2007. Weiss, Sharon W., and John R. Goldblum. Enzinger and Weiss Soft-Tissue Tumors. 4th ed. St. Louis: Mosby, 2001. u
Other Resources
Angiosarcoma Support Organization http://www.angiosarcoma.org/ Liddy Shriver Sarcoma Initiative http://liddyshriversarcomainitiative.org MayoClinic.com Angiosarcoma http://www.mayoclinic.com/health/angiosarcoma/ AN00841 National Cancer Institute Soft Tissue Sarcoma http://www.cancer.gov/cancertopics/types/ soft-tissue-sarcoma/ See also Angiosarcomas; Ewing sarcoma; Fibrosarcomas, soft-tissue; Hemangiosarcomas; Meningiomas; Sarcomas, soft-tissue; TNM staging.
Category: Diseases, symptoms, and conditions Also known as: Radiation enteritis Related conditions: Crohn disease, irritable bowel syndrome Definition: Enteritis is an inflammation of the small or large intestine or both. Enteritis can be acute (short term) or chronic (long lasting).
Etiology and the disease process: Enteritis is an inflammation of the bowel. In noncancer patients, acute enteritis most often occurs because the individual has consumed food or water contaminated with bacteria or viruses that irritate the intestine. Chronic enteritis occurs from gastrointestinal disorders such as Crohn disease. Radiation enteritis is a specific type of enteritis that occurs as the result of radiation therapy during cancer treatment. Radiation is used to kill rapidly dividing cancer cells. However, it also kills normal cells, especially those that divide frequently. The cells lining both the large and small intestine tend to divide often and can be substantially damaged by exposure to radiation necessary to treat cancer occurring in the abdomen and pelvis. As the cells lining the wall of the intestine are damaged, the digestive function is disrupted, and water and nutrients are no longer efficiently absorbed. In acute radiation enteritis, the changes to the cells are reversible and the con421
Enterostomal therapy dition usually clears up a month or two after radiation therapy stops. In chronic radiation enteritis, the cellular damage continues. Symptoms usually improve for a time, but recur between six and eighteen months after radiation therapy has been completed. Damage to the intestinal lining in chronic radiation enteritis is permanent, and symptoms are difficult to control. Incidence: There is controversy over how many people develop radiation enteritis. Some studies have found that almost all patients exposed to abdominal radiation develop some acute symptoms, while other studies have recorded rates of about 35 percent. This variation is probably due to different techniques and doses used at different cancer centers. Of those people who develop acute symptoms, between 5 and 15 percent develop chronic problems. Symptoms: Many symptoms of acute and chronic radiation enteritis are similar. They include crampy abdominal pain, nausea, vomiting, watery or bloody diarrhea, mucous discharge, and bleeding from the rectum. Individuals with chronic enteritis also lose weight, have vitamin deficiencies, and pass loose, fatty or greasy stools. Occasionally with chronic enteritis, the intestine may become obstructed or a perforation (hole) may develop. Screening and diagnosis: For acute radiation enteritis, diagnosis is made on the basis of symptoms appearing shortly after radiation therapy has begun. For chronic radiation enteritis, observation of symptoms and a patient history are used for diagnosis. In chronic enteritis, tests are done to rule out a return of the tumor or other conditions that could cause similar symptoms. Treatment and therapy: Radiation enteritis is treated by managing the symptoms. Dietary changes include avoiding spicy, fatty, and high-fiber foods, alcohol, and milk products, because the intestine often loses the ability to make the enzyme lactase, which is needed to digest milk. Diarrhea is treated with antidiarrheal medicines such as bismuth subsalicylate (Kaopectate), diphenoxylate and atropine (Lomotil), anhydrous morphine (Paregoric), or loperamide (Imodium). Fluid intake is increased to compensate for fluids lost with diarrhea. Antispasmodics may also be given to slow contractions in the bowel. Nutritional counseling is important, especially in chronic enteritis, because the bowel loses the ability to absorb nutrients. Nutritional supplements and digestive aids are often given. Surgery to remove the damaged portion of the bowel in chronic enteritis is controversial. Prognosis, prevention, and outcomes: Symptoms of acute radiation enteritis usually continue two to three 422
Salem Health: Cancer weeks after radiation therapy has finished. Within a few months, symptoms usually disappear completely, and the cells lining the intestine return to normal. In chronic radiation enteritis, the cells lining the intestinal wall are permanently damaged, and symptoms continue indefinitely, although treatment may help to control them. Nutritional counseling and modified diet can help reduce some symptoms of the disorder. Martiscia Davidson, A.M. u
For Further Information Dodd, Marilyn J. Managing the Side Effects of Chemotherapy and Radiation. 2d ed. San Francisco: Regents University of California School of Nursing, 2001. Keane, Maureen, and Daniella Chace. What to Eat if You Have Cancer. 2d ed. New York: McGraw-Hill, 2007. Smith, Tom. Coping with Bowel Cancer. London: Sheldon Press, 2006. Staritz, M., et al., eds. Side Effects of Cancer Chemotherapy on the Gastrointestinal Tract. Boston: Kluwer Academic, 2003.
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Other Resources
MedlinePlus Radiation Enteritis http://www.nlm.nih.gov/medlineplus/ency/article/ 000300.htm National Cancer Institute Gastrointestinal Complications http://www.cancer.gov/cancertopics/pdq/ supportivecare/gastrointestinalcomplications/patient See also Colorectal cancer; Crohn disease; Gastrointestinal cancers; Gastrointestinal complications of cancer treatment; Inflammatory bowel disease; Small intestine cancer.
u Enterostomal therapy Category: Procedures Also known as: Stomal therapy, stoma care, ostomy care Definition: Enterostomal therapy is the acute care and rehabilitative treatment of patients who have had an ostomy procedure. Cancers treated: Colorectal cancer, familial adenomatous polyposis, bladder cancer Why performed: Enterostomal therapy teaches patients how to care for abdominal stomas (surgically constructed
Salem Health: Cancer connections between the intestines and the skin). It also includes care for urinary or fecal incontinence and treatment of chronic wounds or pressure ulcers. A colostomy is a surgically created opening of the colon (large intestine) to divert stool, and an ileostomy is a surgically created opening of the ileum (end of the small intestine) to divert stool. Bypassing or removing part of the intestine or rectum may be necessary in the treatment of colorectal cancer, diverticulitis, or inflammatory bowel disease, especially when there is a blockage. The remaining end of the intestine is brought through the abdominal wall where wastes are excreted through a stoma and collected outside the body in an external pouching system adhered to the skin. The location of the stoma on the abdomen is dependent on where the ostomy was created. In some ileostomy procedures, an internal pouch (called an ileoanal reservoir, ileoanal anastomosis, or “J” pouch), is constructed from the remaining end of the small intestine and connected to the anus to allow normal stool passage via the anal sphincter muscles. Sometimes, a colostomy or ileostomy is temporary, allowing the newly constructed gastrointestinal system to heal when part of these organs have been removed or resected. A urostomy is a surgical procedure that diverts urine away from the bladder. The ileum or cecum (beginning of the large intestine) is surgically removed and reconstructed into a conduit created for the passage of urine from the kidneys through a stoma in the abdominal wall. The urine is collected outside the body in an external pouching system. A urostomy may be necessary in the treatment of bladder cancer. In some cases when the urinary sphincter muscle does not need to be removed, a “replacement bladder,” called an orthotopic neobladder, can be constructed from a section of the intestines and connected to the urethra to allow normal urination. Patient preparation: Tests performed before ostomy surgery may include X rays, ultrasound, colonoscopy or sigmoidoscopy, blood tests, urine tests, and an electrocardiogram (ECG). Complete bowel cleansing is required beforehand, and the patient will receive specific bowel preparation guidelines. The patient will also receive medication and dietary guidelines, which include following a clear fluid diet. Depending on the type of procedure to be performed, additional tests or patient preparations may be required. Steps of the procedure: The steps required for enterostomal therapy vary greatly, depending on the type of ostomy that the patient has had. In general, steps include gathering supplies; examining the stoma and condition of
Enterostomal therapy the surrounding skin daily and reporting abnormalities to the health care team; cleansing the skin; irrigating the stoma with water either daily or every other day; applying barriers, borders, or pastes to the skin around the stoma and applying the pouch; emptying the pouch when it is one-third full; and changing the pouch as prescribed (every one to three days). After the procedure: Patients who have had an ostomy wear an external pouching system to collect stool or urine because they cannot control the passage of stool, gas, or urine through the stoma. The pouching system also protects the skin around the stoma. There are a wide variety of pouching systems, and an enterostomal therapy nurse will work with the patient to select a system that meets the patient’s preferences and lifestyle. The stoma is usually swollen and large, but it will reduce in size once it has fully healed, within six to eight weeks after surgery. A nurse will teach the patient how to care for the stoma and skin around the stoma, change the ostomy bag, perform the irrigation procedure, and manage problems or emergencies. The patient will be required to demonstrate these activities independently before being discharged from the hospital. The patient will also receive resources for purchasing ostomy supplies. The patient does not have feeling in the stoma, but abdominal pain, cramping, bloating, and discomfort are common for a few weeks after the procedure. Pain medication is prescribed as needed. The patient is usually discharged in three to five days after the procedure, depending on the rate of recovery. Home care enterostomal therapy nursing services will be offered to aid recovery. Regular activities can usually be resumed within six to eight weeks. After surgery, patients often have concerns about resuming regular activities, returning to work, and engaging in sexual activity. The nurse will discuss these concerns with the patient and can provide referrals to community support resources and other medical specialists as needed. Risks: As with all surgeries, there are risks associated with ostomy procedures. Complications are rare but may include bleeding, need for further surgery, infection, or scarring. The health care team will discuss the potential risks of the procedure with the patient and his or her family or caregiver. Results: An ostomy can be a lifesaving surgery, improving symptoms and allowing a patient to enjoy a full range of activities. Angela M. Costello, B.S. 423
Eosinophilic leukemia
Salem Health: Cancer
u For Further Information Aronovitch, Sharon. “Changing a Bowel Diversion Ostomy Appliance: Pouching a Stoma.” In Delmar’s Fundamental and Advanced Nursing Skills. 2d ed. New York: Delmar Learning, 2004.
cell lineage. The abnormality generally begins in the early blast (immature) cell stage and results in an uncontrolled proliferation of the cells. Eosinophilic leukemias involve the specific white cell known as an eosinophil, a bilobed white cell that stains with the dye eosin.
u
Incidence: Eosinophilic leukemia is considered a subcategory of chronic myelogenous leukemias, a group of diseases with an annual incidence of 1 to 2 cases per 100,000 people. The specific number categorized as hypereosinophilic syndrome is not determined, due to its rarity.
Other Resources
Canadian Association for Enterostomal Therapy A Guide to Living with a Colostomy http://www.caet.ca/booklet_colostomy1.htm. International Ostomy Association http://www.ostomyinternational.org National Association for Continence http://www.nafc.org United Ostomy Association, Inc. http://www.uoa.org United Ostomy Associations of America http://www.uoaa.org Wound, Ostomy and Continence Nurses Society http://www.wocn.org/patients See also Abdominoperineal resection (APR); Colectomy; Coloanal anastomosis; Colorectal cancer; Colostomy; Diverticulosis and diverticulitis; Gastrointestinal cancers; Gastrointestinal complications of cancer treatment; Ileostomy; Urostomy.
u Eosinophilic leukemia Category: Diseases, symptoms, and conditions Also known as: Primary eosinophilia, hypereosinophilic syndrome (HES) Related conditions: Myelogenous leukemias Definition: Eosinophilic leukemia is a malignancy of blood-forming cells in which eosinophils (a type of white blood cell) are the prominent neoplastic leukocytes. Risk factors: Some forms have a genetic basis originating with chromosomal abnormalities (FIP1L1-PDGFRA fusion gene). However, most cases are idiopathic (of unknown origin). Etiology and the disease process: Leukemias are neoplastic lymphoproliferative diseases that involve bone marrow cells. The specific type of leukemia depends on which particular cell, usually in the leukocyte/white blood 424
Symptoms: Symptoms are often general, categorized as “flulike” symptoms. These include an unexplained fever, swollen lymph nodes, and unexplained fatigue. Screening and diagnosis: Screening is generally not carried out for leukemias. The extent of chromosomal abnormalities is occasionally used to determine prognosis. Diagnosis is based on the microscopic observation of immature or abnormal leukocytes, in particular, early-stage eosinophils, using either blood samples or bone marrow biopsies. Treatment and therapy: Treatment is based on the extent or stage of the disease and may involve a variety of procedures. The treatment of choice begins with chemotherapy involving the use of antiproliferative drugs such as vincristine or cyclophosphamide either orally or intravenously. Most chemotherapeutic drugs produce side effects such as nausea or a lowering of the blood count. Steroids are sometimes included with treatment as a means to reduce such effects. Other methods of treatment include surgery—removal of the spleen, a site of neoplastic cell production or accumulation—and radiation therapy. Radiation therapy has proven most useful as a palliative treatment rather than one that effects a “cure.” Biological therapy, the use of interferon-alpha, as a means to stimulate an immune response against the neoplasm may also be included in treatment. Prognosis, prevention, and outcomes: Since the genetic basis for eosinophilic leukemia is unknown, there is no known means of prevention. Prognosis depends on the effectiveness of treatment, the maturation stage of precursor cells, and the extent of neoplastic cell infiltration into other organs. Survival may be measured in months, or in some cases remission may last for decades. Richard Adler, Ph.D. See also Leukemias; Myeloproliferative disorders.
Salem Health: Cancer
u Ependymomas Category: Diseases, symptoms, and conditions Related conditions: Glial tumors and gliomas Definition: An ependymoma is a central nervous system cancer that arises from the ependymal cells that line the fluid-containing ventricles and central canal of the brain and spinal cord, respectively. Ependymomas are a type of glial cell tumor and are collectively derived from the cells that provide support and nourishment to neural cells. Ependymomas account for 3 percent of all glial cell tumors and 6 to 9 percent of all primary central nervous system tumors. Risk factors: The most salient risk factor relates to a genetically mediated transformation of normal ependymal cells into tumor cells. A history of neurofibromatosis type 2 is associated with the development of spinal ependymomas. Neurofibromatosis type 2, an autosomal dominant syndrome, is caused by a mutation in the NF2 gene manifesting with skin lesions (café-au-lait spots) and bilateral hearing loss from acoustic nerve tumor growth. Familial occurrences of isolated ependymomas have also been documented. Etiology and the disease process: Ependymomas originate from the transformation of an ependymal cell. Although no single aberration has been implicated, involvement of chromosome 22 has been most commonly implicated, the same chromosome that bears the NF2 tumor-suppressor gene (22q12). Changes seen in genetic studies include translocation (removal and subsequent reattachment of a chromosomal segment to another chromosome), deletion of the long arm (22q), or monosomy (absence of one half of a chromosome pair). One family study has narrowed down this region (22pter-22q11.2), suggesting that a tumor-suppressor gene may be responsible. Other aberrations in several other chromosomes were noted in other studies. Incidence: Ependymomas have two incidence peaks: in early childhood and in adulthood. The mean age of ependymoma occurrence in childhood is at five years, peaking again during adulthood at a mean age of thirty-four. However, a substantial number of ependymomas in children, 30 percent of all childhood cases, manifest before age three. By location, ependymomas in the brain are seen more commonly in children (90 percent of cases), while spinal (intramedullary) tumors are more commonly seen in adults (60 percent of cases).
Ependymomas Symptoms: Obstruction of the flow of cerebrospinal fluid (CSF) within the fourth ventricle, with resulting pressure buildup and tissue compression, usually occurs. Brain stem involvement may be seen as irritability or lethargy. Cerebellar symptoms denoting involvement may be seen as frequent loss of balance and dizziness. Occasional cerebrum involvement may manifest as personality and behavioral changes or one-sided body weakness or paralysis. Symptoms of increased pressure include nausea, vomiting, morning headache, and vision changes. Physical examination findings may include papilledema (swelling of both optic nerves), limb incoordination with voluntary movements, cranial nerve VI to X compression signs such as eye movement (nystagmus, lateral gaze weakness or paralysis), facial movement, speech and swallowing abnormalities, and increase in head circumference in babies less than two years of age. Spinal cord manifestations roughly correspond with the affected nerve root level, ranging from pain to sensory deficits, weakness, paralysis, loss of reflexes, and muscle wasting. Screening and diagnosis: There are no routine screening tests available for ependymomas. Clinical history, physical examination, and neuroimaging tests such as magnetic resonance imaging (MRI) or computed tomography (CT) can suggest an ependymoma. These tumors are seen as intraventricular or intramedullary masses that closely match or are darker in contrast to surrounding tissue. Clues that may aid in distinguishing a tumor from normal tissue include cystic formations, calcifications, hemorrhage, or necrosis. The final diagnosis of the type of ependymoma is mainly pathological, when a tissue sample is examined microscopically and classified according to the World Health Organization classification for ependymal tumors. Grade I includes subependymomas and myxopapillary ependymomas; grade II includes cellular, papillary, and clear-cell ependymomas, and grade III ependymomas are of the anaplastic (malignant) variety. Treatment and therapy: Treatment of ependymomas includes surgical removal, radiation therapy, and chemotherapy. The most important factor in a good prognosis is surgical removal, in which a gross total resection is done irrespective of tumor location, removing the entire primary tumor. Postoperative radiotherapy and chemotherapy—a regimen of cisplatin, etoposide, carboplatin, vincristine, and mechlorethamine or of ifosfamide, carboplatin, and etoposide (ICE)—are carried out to prevent recurrence. Radiotherapy is preferred over chemotherapy except in malignant cases. Restoration of normal cerebrospinal fluid circulation through the ventricles and central canal is a secondary objective if assessment of cerebrospinal fluid 425
Epidemiology of cancer shows poor outflow postoperatively. This may be achieved with the addition of a device diverting excess cerebrospinal fluid to the abdominal cavity (ventriculoperitoneal shunt). Prognosis, prevention, and outcomes: The overall fiveyear survival rate for all ependymoma patients is 50 percent. Children have a much lower five-year survival rate (14 percent) when compared with adults (76 percent) because of where children’s tumors are typically located. Prognosis depends on several predictors, the most significant being the extent of tumor resection. Five-year survival rates approach 70 percent in gross total resection as opposed to 30 to 40 percent in partial resection irrespective of tumor grade. Other factors include amount of remaining tumor, tumor grade, age, infratentorial location, local spread to the brain stem, metastases, and rate of recovery. Complications associated with surgery in posterior fossa (cerebellar) resections include cerebellar mutism (speech deficits or absence with cerebellar deficits) and long-term neurologic deficits. Aldo C. Dumlao, M.D. u For Further Information Dempsey, Sharon. My Brain Tumour Adventures: The Story of a Little Boy Coping with a Brain Tumour. London: Jessica Kingsley, 2003. Parker, James N., and Philip M. Parker, eds. The Official Patient’s Sourcebook on Adult Brain Tumors: A Revised and Updated Directory for the Internet Age. San Diego, Calif.: Icon Health, 2002. _______. The Official Patient’s Sourcebook on Childhood Ependymoma: A Revised and Updated Directory for the Internet Age. San Diego, Calif.: Icon Health, 2002. u
Other Resources
Cancer Backup Ependymoma http://www.cancerbackup.org.uk/Cancertype/Brain/ Typesofbraintumour/Ependymoma National Cancer Institute Childhood Ependymoma Treatment http://www.cancer.gov/cancertopics/pdq/treatment/ childependymoma/patient/ See also Brain and central nervous system cancers; Carcinomatous meningitis; Craniotomy; Gliomas; Simian virus 40; Spinal axis tumors. 426
Salem Health: Cancer
u Epidemiology of cancer Category: Cancer biology Definition: Cancer epidemiology is the study of the distribution, determinants, and frequency of malignant disease in specific populations. Three broad objectives related to the use and importance of epidemiologic cancer research are to identify factors related to the etiology of specific cancers; to use cancer-risk data to formulate theories regarding cancer prevention and control; and to educate a diverse public regarding the prevention and control of cancer. These strategies attempt to match educational and dissemination methods to population needs with attention to cancer risk, literacy, trust of medical professionals, and palatability of information, factors known to vary widely across population subgroups. Three types of epidemiologic research apply to the field of cancer. Descriptive epidemiology focuses on the trends and frequency of cancer in specific populations. Analytic epidemiology identifies causes and predisposing risk factors associated with the development of specific cancers. Clinical epidemiology delineates screening programs and evaluates outcomes for the range of prevention strategies implemented. Descriptive epidemiology: In 1995 the American Cancer Society estimated 1,252,000 new cancer cases and 547,000 cancer deaths in the United States. Cancer incidence and mortality rates are higher among men than women. Furthermore, African Americans have a higher cancer mortality rate than whites, which has been a source of discussion and controversy. Some argue that inherent genetic factors account for the discrepancy, whereas others attribute the difference to an overrepresentation of poverty among African Americans and superior health care received by affluent versus impoverished groups. The leading cancers in the United States are lung, breast, prostate, colorectal, and ovary, accounting for about 61 percent of cancer diagnoses. Americans over the age of sixty-five have a tenfold greater risk of developing cancer than do younger Americans. Despite an increase in overall cancer mortality rate between 1950 and 1990, mortality rates for all cancers combined have declined substantially for individuals under age forty-five. They have increased in people over age fifty-five, with that increase primarily related to lung cancer deaths. Many reports identify a decline in cancer mortality of about 14 percent since 1950, although these reports exclude deaths from lung cancer. These data seem biased and problematic, as smoking is the primary etiologic factor in lung cancer diagnoses and a leading public health issue. Excluding lung cancer from
Salem Health: Cancer cancer death statistics implies that if lifestyle issues and behaviors relate to etiology, science is not responsible or interested in research to develop effective prevention and treatment strategies. This denies the role of social, political, and economic factors in promoting increasingly prevalent maladaptive behaviors among vulnerable members of society and is an area worthy of aggressive debate and action in terms of research funding. U.S. Cancer Statistics: 2004 Incidence and Mortality marks the sixth time that the Centers for Disease Control (CDC), the National Program of Cancer Registries (NPCR), and the National Cancer Institute’s (NCI’s) Surveillance, Epidemiology, and End Results (SEER) Program have combined their data sources to produce a collaborative set of federal cancer incidence statistics (newly diagnosed cases) for a single year. Mortality statistics from the CDC’s National Vital Statistics System are also included and report 2003 cancer deaths both nationally and by state. The report was produced in collaboration with the North American Association of Central Cancer Registries. Analytic epidemiology: The goal of analytic cancer epidemiology is to identify the factors that predispose individuals to a cancer diagnosis and to quantify risk. Cancer risk factors include environmental exposures, genetic susceptibility, and immunosuppressive state and may be secondary to a history of malignancy, viral infection, or medical therapy. These risk factors can account for various aspects of carcinogenesis and assume varied degrees of causal primacy. Clinical epidemiology: Epidemiologic research plays an important role in the development of cancer-screening modalities and prevention strategies. Cancer prevention focuses on decreasing incidence by lowering risk through changes in lifestyle patterns and behavior. Primary prevention attempts to stop the development of cancer. Secondary prevention aims to improve cure rates by cancer screening and early diagnosis and treatment. Cancer screening involves testing to detect early-stage cancer in asymptomatic individuals. Ideally, screening tests should be easy to administer, noninvasive, and inexpensive. To be beneficial, early detection should alter prognosis and improve survival. Emerging data and discovery: New data are rapidly emerging that are changing cancer screening and prevention practices. Although these changes are quite positive, the proliferation of data can create confusion among health consumers and avenues to receive reliable information are needed.
Epidemiology of cancer For example, the human papillomavirus (HPV), types 16 and 18, has been causally related to cervical intraepithelial neoplasia. A history of genital warts is linked to human papillomavirus types 6 and 11 and may explain the increased risk associated with multiple sexual partners. Other sexually transmitted viruses, such as herpes simplex virus 2, may interact as etiologic factors. The vaccine Gardasil protects against four HPV types, which together cause 70 percent of cervical cancers and 90 percent of genital warts. Ideally, girls and young women should get the vaccine before they are sexually active because the vaccine is most effective in those who have not yet acquired any of the four HPV types covered by the vaccine. Girls and women who have not been infected with any of those four HPV types will get the full benefits of the vaccine; those who are sexually active may also benefit from the vaccine, although they may get less benefit from the vaccine if they may have already acquired one or more of the HPV types covered. One would assume that the worldwide annual rate of 300,000 deaths from cervical cancer could easily be reduced by application of the vaccine—but this new technology raises questions and obstacles to care, along with offering care: First, there is no test available to tell if a woman has had any or all of these four HPV types. Second, the need to vaccinate women before they become sexually active raises ethical issues, particularly among populations that fear the vaccine will send a message condoning teenage sexual activity. Other issues revolve around who should advertise and promote the vaccine, how it should be promoted in developing nations, and whether parents who resist vaccination should be held liable for their children’s sexual health. These and a host of other issues demonstrate how medical advances complicate cancer epidemiology as well as offering hope. Sociocultural issues: A sensitive issue regarding cancer screening relates to the fact that cancer prevention and control efforts center on the development of strategies to benefit the general population rather than individual lives. As new knowledge and technologies have proliferated at unprecedented rates, many ethical questions—such as fair and equitable allocation of health resources across diverse populations, the priority of individual needs versus those of the social aggregate, and the unfair distribution of resources to privileged groups—have come under considerable scrutiny. Some of these issues have become especially poignant as genetic technologies have identified specific ethnic factors to enhance the risk for certain cancers. The incidence increases fiftyfold in whites and thirtyfold in African Americans between the ages of fifty and 427
Epidemiology of cancer eighty-five. African Americans have the highest incidence of prostate cancer in the world, whereas Japanese have one of the lowest rates. Japanese who migrate to Hawaii develop a risk for prostate cancer higher than that of Japanese who remain in their home country, but only half that of American whites. African American men tend to have metastatic disease at diagnosis—indeed, 40 percent more often than whites do. The overall survival rate for African American men is 10 percent lower than that for white men, even when they are diagnosed at the same stage of disease. Endometrial carcinoma is the most common gynecologic malignancy. Its incidence is highest among white women, whereas its mortality rates are higher among African American women. For the past two decades, the incidence rates have been declining, except among African American women over fifty years old. Cultural, psychosocial, and demographic factors may discourage the use of genetic testing services among individuals who could benefit from them or, conversely, may promote use when testing has the potential to create more harm than benefit. To develop effective cancer detection and prevention programs, therefore, it is essential to consider cultural, demographic, and psychosocial issues that may foster or hinder utilization. Consumer lead advocacy groups have taken a grassroots approach to soliciting research dollars to fund basic and clinical research programs. That fact alone may skew inquiry toward those cultural, ethnic, and socioeconomic subgroups who value and can interpret results of medical research and who have sufficient personal resources to advocate on their own behalf. Lack of interest in genetic testing has been associated with less education, minority status, lower socioeconomic status, and less performance of other health-promoting behaviors. Culture plays a central role in determining health beliefs, attitudes, and behavior, but few health care providers realize that health is a cultural concept defined differently across cultures. Many are unaware that the health care system is culturally designed and administered largely according to mainstream values. In genetics, cultural consideration is particularly important. Although knowledge that certain diseases run in families spans all societies, beliefs about causation of familial diseases vary considerably. Cultural attitudes toward disease also differ among ethnic populations. Moreover, culture comes into play in providerclient interaction and communication, which are both key components of genetic counseling. People from cultures that expect authority figures to be directive may find nondirective genetic counseling confusing and bewildering. Between 1970 and 1990, the minority population grew at a rate about three times that of the total population. The U.S. Census Bureau projects that minorities will ac428
Salem Health: Cancer count for about one-third of the U.S. population by the year 2010. Given these trends, attention to ethnocultural barriers is paramount in achieving universal access to genetic services. Although cultural competency is not a licensing requirement for health professionals, it is vital in view of the sensitive nature of the issues to be discussed and the need for privacy and confidentiality of information exchanged. The professional genetics community includes few minorities, despite demographic trends—further limiting the access of minorities to culturally sensitive and relevant genetic services. This lack of input from minority communities also limits the shaping of public policy and planning of genetic research and counseling in ways meaningful to ethnic minorities. For individuals to benefit from genetic services, those services must be available, culturally appropriate, accessible, and affordable. Unless such issues are addressed, any attempt to broaden access to genetic services will be limited and perhaps even hazardous to a less informed population. Few primary care providers are ready to take on these new tasks. They need education in understanding not only the scientific advances in genetics but also their ethical, legal, cultural, and psychosocial implications. Inadequate appropriations to develop the needed service infrastructure have resulted in an inadequate number of genetic specialists, primary care providers, and public health providers prepared to incorporate genetics into practice. Among primary care providers, inadequate preparation in genetics is compounded by the severe time constraints imposed on virtually all service providers and by a lack of reimbursement for cognitive services. Most consumers also have low scientific literacy and know little about basic genetics or genetic testing. Without a degree of genetics literacy and an understanding of the limitations and risks involved including insurance and employment discrimination, psychological trauma, intrafamilial conflict, and social stigmatization, people cannot make truly informed decisions. Chemoprevention: A relatively new approach to cancer prevention is through chemoprevention (as opposed to chemotherapy, or drug treatment, following a cancer diagnosis). Cancer chemoprevention is defined as the reversal of carcinogenesis in the premalignant phase. The observation that retinoids, acting as modulators of cell differentiation, are effective in suppressing oral carcinogenesis and, therefore, in preventing second primary tumors in squamous cell carcinoma of the head and neck has led to the evaluation of these agents as chemopreventive therapy for tumors of the upper aerodigestive tract in high-risk
Salem Health: Cancer populations. Studies of adjuvant hormonal therapy with tamoxifen for breast cancer have shown a 50 percent reduction of contralateral disease, which led to a national tamoxifen chemoprevention trial to evaluate risk reduction for primary breast cancer in women at high risk. With the development of new molecular techniques, chemoprevention trials will be aided by the identification of markers for premalignant lesions. Prognosis for cancer epidemiology: Decision making regarding genetic susceptibility testing, health surveillance, chemoprevention and preventative surgery are being quickly added to the realm of health care options without adequate knowledge among professionals and the public regarding the meaning and practical relevance of this information. Psychosocial, cultural, and economic factors may affect the study, dissemination, and utilization of genetic discoveries to create service barriers and widen the gap between the haves and have nots among health care consumers. Genetic information is received against a backdrop of deeply held personal beliefs. The influence of culture on health beliefs and actions is enormous, and the role that culture, ethnicity, and religion play in formulating an individual’s motivation toward health-seeking behaviors must be addressed in all educational and clinical activities. Jeannie V. Pasacreta, Ph.D., A.P.R.N. u
For Further Information Centers for Disease Control. U.S. Cancer Statistics: 2004 Incidence and Mortality. Washington, D.C.: Author, 2004. Dennis, Leslie K., and Deborah Dawson. “Meta-analysis of Measures of Sexual Activity and Prostate Cancer.” Epidemiology 13, no. 1 (January, 2002): 72-79. Gandini, S., H. Merzenich, C. Robertson, and P. Boyle. “Meta-analysis of Studies on Breast Cancer Risk and Diet: The Role of Fruit and Vegetable Consumption and the Intake of Associated Micronutrients.” European Journal of Cancer 36 (March, 1990). Green, Lawrence W., and Marshall W. Kreuter. Health Promotion Planning: An Educational and Ecological Approach. 3d ed. Mountain View, Calif.: Mayfield, 1999. Little, Jullian. Epidemiology of Childhood Cancer. IARC Scientific Publications 149. Lyon, France: International Agency for Research on Cancer, 1999. Moolgavkar, S., et al., eds. Quantitative Estimation and Prediction of Human Cancer Risks. IARC Scientific Publications 131. Lyon, France: International Agency for Research on Cancer.
Epidermoid cancers of mucous membranes u
Other Resources
Centers for Disease Control and Prevention National Program of Cancer Registries http://www.cdc.gov/cancer/npcr National Cancer Institute Cancer Clusters http://www.cancer.gov/cancertopics/factsheet/risk/ clusters North American Association of Central Cancer Registries http://www.naaccr.org See also African Americans and cancer; Africans and cancer; Ashkenazi Jews and cancer; Asian Americans and cancer; Cancer clusters; Childhood cancers; Elderly and cancer; Ethnicity and cancer; Family history and risk assessment; Geography and cancer; Latinos/Hispanics and cancer; Native North Americans and cancer; Occupational exposures and cancer; Poverty and cancer; Singlehood and cancer; Statistics of cancer; Survival rates; Young adult cancers.
u Epidermoid cancers of
mucous membranes Category: Diseases, symptoms, and conditions Related conditions: Squamous cell carcinoma, skin cancers, head and neck cancers, nasopharyngeal cancer, laryngeal cancer, nasal cavity and paranasal sinus cancers, oral and oropharyngeal cancers, gastrointestinal cancers, urinary system cancers Definition: Epidermoid cancers of mucous membranes are squamous cell malignancies in tissues in which glands produce mucosal fluids to protect epithelial cells and assist various physiological functions. These membranes line the interiors of body cavities, organs, and structures that connect either directly or indirectly to external skin openings. Some references to epidermoid cancers of mucous membranes limit them to head and neck cancers. Since the mid-nineteenth century, medical literature has mentioned epidermoid cancers in other mucous membranes, which are extensive throughout the torso, including respiratory, gastrointestinal, and genitourinary tracts. Risk factors: Nicotine exposure increases people’s risk for developing epidermoid malignancies in mucous membranes in the mouth, larynx, and pharynx. Alcohol consumption exacerbates epidermoid cancer risks. Oncology 429
Epidermoid cancers of mucous membranes experts have associated epidermoid cancers of mucous membranes with such carcinogens as asbestos and industrial by-products, including sawdust. Medical professionals have connected these cancers to diets containing large amounts of salt and preservatives, which can damage mucous membranes. They have also tied these cancers to periodontitis and the Epstein-Barr virus. Some researchers hypothesize that the human papillomavirus (HPV) might cause epidermoid cancer in mucous membranes. Investigators have studied how pemphigoid, an autoimmune condition causing blistering of mucous membranes, possibly affects patients’ vulnerability to cancer. Etiology and the disease process: Epidermoid carcinomas form in squamous cells both in external skin tissues and internal membrane tissues in organs and cavities. Squamous cell carcinomas develop in the outer epithelial layer of membranes when routine cell division and replacement and sometimes epithelial cell production of keratin proteins deviate and extra abnormal cells and keratin accumulate. Malignant squamous cells typically first appear as lesions known as erythroplasia if they are red or brown and leukoplakia if they are white. Tumors grow and spread into other epithelial layers. For example, epidermoid tumors in lungs begin in respiratory passage membranes, then extend to adjacent organs or lymph nodes. Incidence: Squamous cell carcinomas associated with external skin cancers, with an estimated 400,000 diagnoses in the United States yearly, occur more frequently than they develop in mucous membranes. Statistics for each type of mucous membrane affected by epidermoid cancers vary. More than 90 percent of various head and neck cancers consist of squamous cell carcinomas. Some 30 percent of non-small-cell lung cancer cases diagnosed involve squamous cell carcinomas. Men are more susceptible than women to developing epidermoid cancers in mucous membranes. These malignancies tend to occur after the age of fifty. Symptoms: Many patients locate lumps in their neck or detect lesions on their lips or inside their mouth. These oral sores as well as others in mucous membrane tissues do not undergo the normal healing processes. Epidermoid cancers in mucous membranes may cause sore throats and affect how people chew, swallow, and speak. Swollen or numb sinus, jaw, or neck areas; impaired hearing; respiration difficulties; and altered sensory abilities are other symptoms. Some patients experience problems with how dentures fit. 430
Salem Health: Cancer Screening and diagnosis: Health professionals, including dentists, screen patients for potential membrane cancers and collect tissue or fluid samples for laboratory testing. Diagnostic procedures include computerized imaging and scanning, endosonography, and other tests. Physicians differentiate epidermoid carcinomas in mucous membranes from keratin cysts and mucosal melanomas. Oncologists stage most epidermoid cancers of mucous membranes with the TNM (tumor/lymph node/metastasis) system, devising designations that expand the four basic stages to describe lymph node impact more precisely in terms of tumor size, extent of metastasis, and location relative to nodes. Various types of mucous membrane epidermoid cancers have specific staging criteria, such as which vocal cord is affected. Treatment and therapy: Many physicians use radiation, chemotherapy, and surgical treatment to remove tumors, lymph nodes, or affected organs. Radiation and chemotherapy without surgery enables patient to continue normal activities and capabilities by retaining such body parts as their larynx, which is essential for speech. Some oncologists deliver chemoradiation intravenously to tumors. Researchers have tested the potential for using herpes simplex virus type 1 to treat tumors in mucous membranes. Speech and physical therapists, nutritionists, prosthodontists, plastic surgeons, and other specialists enhance treatment of epidermoid cancers in mucous membranes. Psychologists offer emotional support because an estimated 40 percent of mucous membrane cancer patients suffer intense depression. Prognosis, prevention, and outcomes: Patients with epidermoid cancers in mucous membranes are most likely to survive if their malignancies are detected at an early stage, with an estimated 90 percent survival rate. Medical professionals estimate that more than 50 percent of cases, however, remain undiagnosed until tumor growth has expanded to later stages, increasing fatalities within five years of diagnosis, compared with other cancers. Elizabeth D. Schafer, Ph.D. u
For Further Information Egan, Conleth A., et al. “Anti-Epiligrin Cicatricial Pemphigoid and Relative Risk for Cancer.” The Lancet 357, no. 9271 (June 9, 2001): 1850. Gallegos-Hernández, José-Francisco, et al. “The Number of Sentinel Nodes Identified as Prognostic Factor in Oral Epidermoid Cancer.” Oral Oncology 41, no. 9 (October, 2005): 947-952. Sonis, Stephen T., Douglas E. Peterson, Deborah B. Mc-
Salem Health: Cancer Guire, and David A. Williams, eds. “Mucosal Injury in Cancer Patients: New Strategies for Research and Treatment.” Journal of the National Cancer Institute Monographs 29 (2001): 1-54. u
Other Resources
American Cancer Society Detailed Guide: Oral and Oropharyngeal Cancer http://www.cancer.org/docroot/CRI/ CRI_2_3x.asp?dt=60 National Cancer Institute Head and Neck Cancer: Treatment http://www.cancer.gov/cancertopics/treatment/ head-and-neck See also Gastrointestinal cancers; Head and neck cancers; Laryngeal cancer; Lung cancers; Mucinous carcinomas; Nasal cavity and paranasal sinus cancers; Oral and oropharyngeal cancers; Salivary gland cancer; Skin cancers; Squamous cell carcinomas; Throat cancer; Urinary system cancers.
u Epstein-Barr virus Category: Carcinogens and suspected carcinogens Also known as: EBV, human herpesvirus 4 (HHV-4) Related cancers: Burkitt lymphoma, a type of non-Hodgkin lymphoma (NHL), nasopharyngeal carcinoma Definition: Epstein-Barr virus is one of the eight known types of human herpesviruses and is a member of the gamma subtype of this group. Like many herpesvirus species, Epstein-Barr virus appears to establish a lifelong presence in the human body, remaining quiescent for long periods of time and then inexplicably becoming active. Causally related to mononucleosis, it is also associated with a variety of human cancers, such as Burkitt lymphoma and nasopharyngeal carcinoma, and is therefore considered to be a carcinogenic virus. Exposure routes: Humans are the only known reservoir of Epstein-Barr virus, which is present in oropharyngeal secretions and is most commonly transmitted through saliva; transmission of the virus requires intimate contact with the saliva (found in the mouth) of an infected person. Transmission through the air or blood does not usually occur. Epstein-Barr virus is causally related to infectious mononucleosis (IM), a disease characterized by the proliferation of single-nucleus white blood cells, resulting in fever, sore
Epstein-Barr virus throat, and sometimes hepatitis. Infectious mononucleosis may be contagious for a period of weeks. However, isolation measures are not practical, since Epstein-Barr virus is frequently present in the saliva of healthy persons, who may carry and spread the virus intermittently for life. Transmission of Epstein-Barr virus is therefore practically impossible to prevent. Where found: The Centers for Disease Control and Prevention (CDC) estimates that 95 percent of adult Americans between the ages of thirty-five and forty have been infected by Epstein-Barr virus, but it is less prevalent in children and teenagers, a pattern observed in the developed world but not in developing regions such as Africa and Asia. In Africa, for example, most children have been infected by the virus by the age of three. Epstein-Barr virus has also been associated with nasopharyngeal cancers in Asia (especially China) and Burkitt lymphoma in equatorial Africa and Papua New Guinea. In tropical regions, Burkitt lymphoma has been shown to coexist with malaria. In the United States, Epstein-Barr virus has also been associated with nasopharyngeal cancers in immigrants from Asia. The incidence of Burkitt lymphoma has been increasing. Non-Hodgkin lymphomas are found in people whose immune systems have been compromised by drug therapy and disease. At risk: Epstein-Barr virus has been shown to take advantage of those with weakened immune systems; Burkitt lymphoma, a non-Hodgkin lymphoma (NHL), is found in organ transplant patients undergoing immunosuppression therapy, as well as those living with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrom (AIDS) who are immunocompromised by their disease. Because Burkitt lymphoma typically occurs in tropical climes where malaria is endemic, it is believed that the immune systems of those with malaria are altered, resulting in tumor production. Epstein-Barr virus is also associated with nasopharyngeal carcinoma, which is prevalent in those of Chinese ancestry; both genetic and environmental factors such as a diet high in nitrosamines may also contribute to cancer development. Environmental/ occupational exposure to pesticides and solvents shows no significant pattern of positive association with EpsteinBarr virus and related cancers. Etiology and symptoms of associated cancers: Occurring in nearly all regions of the world, Epstein-Barr virus is among the most ubiquitous of viruses, and most people will become infected with Epstein-Barr virus sometime during their lifetimes. In the United States, as soon as maternal antibodies disappear, infants become vulnerable 431
Epstein-Barr virus
Salem Health: Cancer
Oral hairy leukoplakia caused by Epstein-Barr virus in an immunosuppressed HIV-positive patient. (Sol Silverman, Jr., D.D.S./Centers for Disease Control)
to Epstein-Barr virus infection. In adolescents, infection with the Epstein-Barr virus results in infectious mononucleosis in 35 to 50 percent of cases. Although the symptoms of infectious mononucleosis usually dissipate within several months, the Epstein-Barr virus lies dormant in a few cells in the throat and blood for the remainder of the person’s life. From time to time, the virus may reactivate and is often present in the saliva, suppressing the immune system by causing repeated mutations in B cells, which may then proliferate unabated, resulting in tumors. Epstein-Barr virus establishes a lifelong latent infection in the body’s immune system that may later result in the emergence of Burkitt lymphoma and nasopharyngeal carcinoma. The initial symptoms of Burkitt lymphoma may include a swollen lymph node in the upper body or abdomen. If the tumor is found in the chest, breathing difficulties may ensue. In others, itching, weight loss, fever, and fatigue may be present. Commonly, Burkitt lymphoma results in formation of a large tumor mass in the jawbone. Adults with AIDS often develop tumors in various parts of the body. Symptoms of nasopharyngeal can432
cer may include a lump in the neck or nose, numbness on the side of the face, headaches, ear pain, and difficulty speaking and breathing. History: In the latter part of the nineteenth century and in the early part of the twentieth century, the medical community in the United States and in Europe began to report on a novel syndrome of fever, sore throat, and swollen glands that was later termed mononucleosis and later found to be causally related to Epstein-Barr virus. EpsteinBarr virus was discovered in the 1960’s from a biopsy of a tumor associated with Burkitt lymphoma and was the first virus to be directly linked to human cancer; in 1964 Michael Epstein and Yvonne Barr isolated virus particles from cell lines derived from Burkitt lymphoma, hence the name, Epstein-Barr virus. Subsequently, Epstein-Barr virus was found to be the main viral cause of cancer in humans, having an etiological role in Burkitt lymphoma and other B-cell lymphomas as well as nasopharyngeal carcinoma. Cynthia Racer, M.A., M.P.H.
Salem Health: Cancer u For Further Information Robertson, E. S. Epstein-Barr Virus. Portand, Oreg.: Caister Academic Press, 2005. Tselis, A., and H. B. Jenson. Epstein-Barr Virus. New York: Taylor & Francis, 2006. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Eleventh Report on Carcinogens. Research Triangle Park, N.C.: Author, 2005. Young, L. S., and A. B. Rickinson. “Epstein-Barr Virus: Forty Years On.” Nature Reviews: Cancer 4, no. 10 (2004): 757-768.
See also Blood cancers; Burkitt lymphoma; Carcinoma of unknown primary origin (CUP); Epidermoid cancers of mucous membranes; Head and neck cancers; Hodgkin disease; Immune response to cancer; Infectious cancers; Leiomyosarcomas; Leukoplakia; Lymphomas; NonHodgkin lymphoma; Oncogenic viruses; Proto-oncogenes and carcinogenesis; Risks for cancer; Throat cancer; Viral oncology; Virus-related cancers.
u Erionite
Erythroplakia catalysts, desiccants, oil and gas absorbents, pesticides, purification of water, and the cleanup of wastewater. Etiology and symptoms of associated cancers: Through inhalation of erionite dust, erionite fibers can lodge in lung and mesothelial tissue. Due to the shape of the fibers, their surface reactivity, their ability to selectivity adsorb molecules from air and liquids, and their resistance to dissolution in fluids within the lung, erionite is extremely irritating and toxic to the lungs and mesothelium, producing malignant tumors in the lungs and in the thoracic and abdominal cavities. History: Mineral ores containing erionite have been mined commercially in the United States since the early 1960’s. During the 1960’s and the 1970’s, it was one of four commercially important zeolites. Erionite is found in many different rock types and geological settings but is rarely found in pure form. Until the late 1980’s, erionite was used as a catalyst in a hydrocarbon-cracking process. During the 1980’s, erionite was linked with the development of mesothelioma and lung cancer in some villages in Turkey where residents experienced chronic exposure to erionite. The use of erionite was banned in the United States by the Environmental Protection Agency in 1991. Alvin K. Benson, Ph.D.
Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1994 Also known as: Erionit, erionita
See also Asbestos; Silica, crystalline.
Related cancers: Mesothelioma, lung cancer
u Erythroplakia
Definition: Erionite is a colorless or white crystalline solid that forms woollike fibers and belongs to a group of minerals known as zeolites.
Category: Diseases, symptoms, and conditions Also known as: Oral cancer
Exposure routes: Inhalation Where found: Erionite is found in rock deposits in Arizona, California, Nevada, Oregon, South Dakota, and Utah in the United States and in the Faroe Islands. It is found with associated minerals that include calcite, opal, pyrite, halite, and other zeolites. Before the late 1980’s, a few homes were built in the western United States with blocks that contain erionite. At risk: Workers involved in the production and mining of erionite and its related minerals known as zeolites are at risk for contamination. As erionite occurs naturally as a mineral in outcrops of Earth’s crust, residents or tourists in areas where it is found can be exposed to it. The general public is at risk for contamination from erionite that is contained within zeolites that are used in a variety of applications that include animal feed, pet litter, soil conditioners,
Related conditions: Leukoplakia Definition: Erythroplakia is a precancerous soft, reddened patch found on the floor of the mouth, the tongue, or the soft palate. Risk factors: Smoking and alcohol consumption, especially in combination, are known risk factors for erythroplakia; use of smokeless tobacco and smoking marijuana also are considered potential risk factors. Etiology and the disease process: A history of smoking and use of alcohol may be an underlying cause of erythroplakia, but sometimes there is not an identifiable cause. This type of oral lesion has a high rate of developing cancer. Incidence: Oral cancers usually appear in older adults (over sixty years) and represent approximately 3 percent of all malignancies in men and approximately 2 percent of all malignancies in women. 433
Esophageal cancer Symptoms: There may be no early symptoms other than the reddened patch; some lesions may be mixed with white patches (this is called erythroleukoplakia). Later symptoms may include bleeding, loose teeth, and a change in the fit of dentures. Screening and diagnosis: Early detection is important, and screening exams should be performed by primary care physicians and dentists. When a suspicious reddened patch is found in the mouth, a biopsy is taken; this can be done by the primary care physician or by a head and neck specialist. Oral tumors are staged using the TNM system that describes the size of the primary tumor (T), the involvement of the regional lymph nodes (N), and whether the cancer has spread (metastasis, M). A numerical rating is assigned to each letter, and a stage grouping of 0-IV is assigned based on the ratings for the three categories. Treatment and therapy: Excision of the oral cancer is usually the necessary treatment; radiation therapy may be used alone or in combination with surgical treatment. The treatment team is multidisciplinary and may include a head and neck surgeon, an oral and maxillofacial pathologist, a general pathologist, a radiation oncologist, a neuroradiologist, a reconstructive surgeon, a medical oncologist, a general dentist, an oral and maxillofacial surgeon, a maxillofacial prosthodontist, a dental hygienist, a nurse specialist, a speech pathologist, a nutritionist, and a tobacco cessation counselor. Prognosis, prevention, and outcomes: The prognosis of oral cancers depends on the pathology findings and the extent of the lesion. A complete head and neck evaluation should be done to look for other cancers. As tobacco and alcohol use are known risk factors, avoiding or ceasing use will help prevent erythroplakia. Vicki Miskovsky, B.S., R.D. See also Alcohol, alcoholism, and cancer; Chewing tobacco; Leukoplakia; Oral and oropharyngeal cancers.
u Esophageal cancer Category: Diseases, symptoms, and conditions Also known as: Cancer of the esophagus Related conditions: Barrett esophagus Definition: Esophageal cancer is a disease caused by a malignant tumor that forms in the tissues of the esophagus. The two main types are adenocarcinoma and squamous cell carcinoma. 434
Salem Health: Cancer Risk factors: Gastroesophageal reflux disease (heartburn) causes about one-third of all esophageal cancers, particularly adenocarcinoma. Tobacco use of any form and heavy alcohol consumption are major risk factors for squamous cell carcinoma. Individuals who both smoke and drink excessively have a synergistic (greater than additive) risk of developing esophageal cancer. People with a diet low in fruits and vegetables have a higher incidence of esophageal cancer, and there is evidence that a high intake of refined cereals and red and processed meats can be detrimental as well. Obese people have a greater risk for adenocarcinoma, primarily through an increased incidence of acid reflux disease. Etiology and the disease process: The esophageal wall has several layers. The inner lining is called the mucosa and has two parts: the epithelium and lamina propria. The epithelium consists of thin, flat squamous cells. The submucosa lies under the mucosa, followed by two layers of muscle. The esophageal wall is connected to various lymph nodes. Esophageal tumors begin in the epithelial layer. Risk factors such as tobacco use and heavy alcohol consumption may case squamous cell carcinoma. This cancer tends to spread linearly across the submucosal layer. Adenocarcinoma occurs largely because of chronic acid reflux and develops mainly in the lower esophagus. Acid reflux occurs when the lower esophageal sphincter between the stomach and esophagus malfunctions and allows gastric contents to reflux back into the esophagus. Acid reflux can cause inflammation and erosion of the epithelium. When the healing process takes place, the squamous cells can be replaced by glandular cells that look like the cells that line the stomach. This abnormal epithelium is termed Barrett esophagus. Although this abnormal epithelium is more resistant to acid reflux, a person with the condition is at higher risk to develop adenocarcinoma. When adenocarcinoma develops, it spreads by penetration through the full thickness of the esophageal wall. Both types of esophageal cancer can spread via the lymph nodes and eventually throughout the body. Incidence: Each year about 13,200 people in the United States are diagnosed with esophageal cancer, and 12,500 die of the disease. The risk of developing esophageal cancer increases with age, with the highest incidence between ages fifty-five and seventy. Men are two to four times more likely to contract the disease than women are. Blacks are six times more likely than whites to acquire squamous cell carcinoma, while adenocarcinoma is four times more frequent in whites than in blacks. Adenocarcinoma has increased more than fourfold in the United States over the
Salem Health: Cancer last thirty years. People with Barrett esophagus have a highly increased risk for developing adenocarcinoma, estimated between thirty and one hundred times normal. Certain regions of the world have a very high incidence of squamous cell carcinoma, such as northern Iran and northern China. Symptoms: The most common symptom of esophageal cancer is dysphagia (difficulty in swallowing). Dysphagia primarily involves solid foods and can progress rapidly in severity (over a period of weeks to months). This symptom does not usually appear until at least half of the esophagus is blocked by a tumor. Weight loss can occur because of reduced food intake or muscle wasting from cancer-caused changes in metabolism. Other symptoms such as hoarseness, pain in the chest or throat, or vomiting of blood can be caused by tumor spread. Screening and diagnosis: When a patient complains of symptoms to the physician, many diagnostic tests are available. A barium swallow begins with a patient drinking a barium solution that coats the normally smooth surface of the esophageal lining. Subsequent X rays can reveal early cancers that appear as small, round bumps or flat, raised areas. Advanced cancers reveal larger irregular areas and a narrowing of the esophagus. Upper endoscopy or esophagoscopy is a procedure involving the use of a flexible viewing tube called an endoscope. The doctor can view suspicious growths and abnormalities in the esophagus and take biopsies for laboratory examination. Endoscopic ultrasound involves attaching a small ultrasound probe to the endoscope. The probe sends very sensitive sound waves that penetrate deep into tissues. This technique can determine how far the tumor has spread into the tissues. Computed tomography (CT) is used to determine the extent (stage) of the cancer, rather than an initial diagnosis. The CT scan takes many X-ray images as it rotates around the body. A computer then translates this information into thin sections of the body. The scans can show tumors in the esophagus, lymph nodes, and other organs where the cancer may have spread. A positron emission tomography (PET) scan involves injecting a small amount of radioactive glucose tracer into the patient’s vein. The tumors show up brighter on the resultant scan. The PET scan indicates the presence or absence of malignancy based on the increased metabolic activity of tumors. PET scans can detect cancer before the anatomic and structural changes shown by tumors have time to develop. This test is valuable in detecting cancer spread to distant lymph nodes or throughout the body.
Esophageal cancer
Stage at Diagnosis and Five-Year Relative Survival Rates for Esophageal Cancer, 1996-2004 Stage Localizeda Regionalb Distantc Unstaged
Cases Diagnosed (%) Survival Rate (%) 24 30 30 16
33.7 16.9 2.9 10.8
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 a Cancer still confined to primary site b Cancer has spread to regional lymph nodes or directly beyond the primary site c Cancer has metastasized
The progression of esophageal cancer is described by staging classification systems. The National Cancer Institute uses the following staging system: • Stage 0: The cancer is confined to the epithelial layer. It is also called carcinoma in situ, meaning “in place.” • Stage I: Cancer has spread to the submucosal layer. • Stage IIA: Cancer has spread to the muscle layer or to the outer wall of the esophagus. • Stage IIB: Cancer may have spread to any of the first three layers of the esophagus and to nearby lymph nodes. • Stage III: Cancer has spread to the outer walls of the esophagus and may have spread to tissues or lymph nodes near the esophagus. • Stage IVA: Cancer has spread to nearby or distant lymph nodes. • Stage IVB: Cancer has spread to distant lymph nodes or organs in other parts of the body. Treatment and therapy: Surgery is the most common treatment for esophageal cancer; however, there are many risks involved. The surgeon removes the cancerous part of the esophagus and may remove lymph nodes and part of the stomach if the cancer is advanced. Surgery is mainly useful for Stages 0 to I, when it is most likely to be curative. If surgery is contemplated for Stages III and IV, it is usually done in combination with other therapies such as chemotherapy and radiation. Surgery is not feasible for cancers that have spread beyond the esophagus. Radiation is most effective when used with other therapies. Radiation is used to relieve symptoms of dysphagia, or in combination with chemotherapy to shrink tumors before surgery. Radiation used alone is rarely curative. 435
Esophageal speech Chemotherapy helps to sensitize cancer cells to radiation, so chemotherapeutic agents are often used in combination, with or without surgery. The most effective agent is cisplatin. Fluorouracil has synergistic activity with cisplatin so is often used in combination. Other chemotherapeutic agents showing promise include paclitaxel, irinotecan, and oxaliplatin. Chemotherapy alone is rarely curative. Photodynamic therapy can be used to treat very early cancers that are on or just under the epithelial lining. It is also used for palliative therapy to alleviate dysphagia. A nontoxic chemical is injected into the blood and allowed to accumulate in the tumor. A special laser light is focused on the tumor through an endoscope. The light converts the chemical to a toxic form that kills tumor cells. Prognosis, prevention, and outcomes: Esophageal cancer is a very deadly cancer with an overall curative success of less than 10 percent. By the time symptoms appear, the disease is incurable in half the cases. The benefit of a screening program to detect esophageal cancer at an earlier stage has not been demonstrated. Even monitoring patients with gastrointestinal reflux disease for the presence of Barrett esophagus has not been shown to improve survival rate. The best preventive measures are to minimize the risk factors. David A. Olle, M.S. u For Further Information Koshy, Mary, et al. “Multiple Management Modalities in Esophageal Cancer.” The Oncologist 9 (2004): 137159. Rankin, Sheila C., ed. Carcinoma of the Esophagus. New York: Cambridge University Press, 2008. Sharma, Prateek, and Richard Sampliner, eds. Barrett’s Esophagus and Esophageal Adenocarcinoma. 2d ed. Malden, Mass.: Blackwell, 2006. u
Other Resources
American Cancer Society http://www.cancer.org MayoClinic.com Esophageal Cancer http://www.mayoclinic.com/health/ esophageal-cancer/DS00500 National Cancer Institute Esophageal Cancer http://www.cancer.gov/cancertopics/types/ esophageal/ 436
Salem Health: Cancer See also Alcohol, alcoholism, and cancer; Bacteria as causes of cancer; Barium swallow; Barrett esophagus; Cardiomyopathy in cancer patients; Cigarettes and cigars; Endoscopy; Esophagectomy; Esophagitis; Fanconi anemia; Gastrointestinal cancers; Gastrointestinal oncology; Oral and oropharyngeal cancers; Stent therapy; Thoracotomy; Upper gastrointestinal (GI) endoscopy.
u Esophageal speech Category: Lifestyle and prevention; social and personal issues Definition: Esophageal speech, also called esophageal voice, is speech produced by swallowing air and forcing it out again through the esophagus. Patients who have had their larynx, or voice box, removed because of cancer have to practice esophageal speech to communicate verbally. Anatomy and physiology: The larynx (voice box) is a 2inch (5-centimeter, or cm), tube-shaped organ in the neck toward the front of the body between the pharynx (throat) and the trachea (windpipe). The larynx is part of the body’s respiratory (breathing) system. One of its main functions is to protect the airway to the lungs from food or drink “going down the wrong tube.” The pharynx is a hollow tube about 5 inches (12 cm) long that starts behind the nose and ends at the top of the trachea and esophagus. The trachea, also part of the respiratory system, connects the larynx to the lungs. The esophagus is a muscular tube that connects the mouth and pharynx to the stomach. It lies between the trachea and the spine. The esophagus is part of the digestive system. When food is chewed and swallowed, the esophagus contracts to push the food down into the stomach, where digestion takes place. Briefly, the human speech process begins when air streams from the lungs and passes over the vocal folds (vocal cords) in the larynx. The steady airstream causes the vocal folds to vibrate, which produces sound waves. The sound waves are then shaped and modified by the pharynx, tongue, lips, palate, and teeth to produce intelligible speech sounds. Throat cancer: Throat cancer—also called vocal cord cancer, laryngeal cancer, and cancer of the glottis—strikes the vocal folds, larynx, or other areas of the throat. It appears as a malignant tumor in almost any part of the throat. Although a person’s genes may contribute to the development of throat cancer, the most common cause is smoking. Excessive alcohol use also increases the risk of developing throat cancer. Throat cancer occurs most often in adults
Salem Health: Cancer
Esophageal speech
older than the age of fifty and in men ten times more often than in women. In the early stages, doctors can successfully treat throat cancer with radiation therapy or chemotherapy or a combination of the two. Following such treatments, most patients are able to keep their larynx and speak more or less normally. In the later stages of the disease, the most common treatment is surgery to remove the larynx along with the cancerous tumor. When a patient needs surgery, the type of operation depends on the size and exact location of the tumor. Surgeons may remove part of the larynx (partial laryngectomy) or the entire larynx (total laryngectomy). Speaking after a laryngectomy: Patients without a voice box must learn to speak all over again. Several methods and a number of medical devices are available to help patients recover their ability to speak. One of the most common techniques is esophageal speech. With esophageal speech, the patient learns to take air into the mouth and swallow it or force it into the esophagus and then trap the air by locking the tongue to the roof of the mouth. The air is now in the digestive system, not in the respiratory system as normal. The patient then forces the air through the esophagus and back up into the mouth, much like a controlled belch. This causes the air to vibrate, along with the walls of the esophagus and the throat, and produce a low-pitched sound that becomes the patient’s voice. The patient then shapes the voiced sound into recognizable words, as normal speakers do, with the tongue, lips, palate, and teeth. The esophageal voice emits a low-pitched guttural, croaking, sometimes soft and barely audible sound that many listeners find difficult to understand. Because they must learn to train parts of their body for a new purpose, many patients find esophageal speech more difficult than speech they might produce with special medical devices. On the plus side, esophageal speech costs patients less than some other techniques because it does not require special equipment. Living without a larynx: People who have had their larynx removed are known as laryngectomees. They must contend with more than learning to speak a new way. When the larynx is taken out, it leaves an opening in the neck called a tracheostoma, or stoma, for short. Patients cough, sneeze, and breathe through the stoma. They be-
come neck breathers. The trachea is exposed through the stoma, so they need to take special care of the stoma. They have to keep it clean and moist. They have to cover it when showering and shaving. They usually have to avoid activities such as swimming or water skiing. They have to watch for a buildup of dried mucus, a substance that lubricates and moistens the esophagus. They must be especially careful of coughing and sneezing, which can expel large amounts of phlegm, a mucus of the respiratory system. They must eat much more slowly. They also must cope with the changes in their physical appearance. Wendell Anderson, B.A. u
For Further Information Lazaroff, M. The Complete Idiot’s Guide to Anatomy and Physiology. Indianapolis, Ind.: Alpha Books, 2004. Prosek, R., and L. Vreeland. “The Intelligibility of TimeDomain-Edited Esophageal Speech.” Journal of Speech, Language, and Hearing Research 44, no. 3 (2001): 525-534. Thomas, J., and R. Keith. Looking Forward: The Speech and Swallowing Guidebook for People with Cancer of the Larynx or Tongue. New York: Thieme, 2005.
u
Other Resources
American Cancer Society Speech After Laryngectomy http://www.cancer.org/docroot/MBC/content/ MBC_3_2X_Speech_After_Laryngectomy .asp?sitearea=MBC
A tumor on the wall of an esophagus. (CNRI/Photo Researchers, Inc.)
437
Esophagectomy WebWhispers http://www.webwhispers.org See also Cordectomy; Electrolarynx; Laryngeal cancer; Laryngeal nerve palsy; Laryngectomy; Laryngoscopy; Parathyroid cancer; Throat cancer; Tracheostomy; Upper gastrointestinal (GI) series.
u Esophagectomy Category: Procedures Also known as: Transhiatal esophagectomy, transthoracic esophagectomy, esophagogastrectomy Definition: Esophagectomy is the surgical removal of part of the esophagus for the treatment of cancer or the relief of cancer symptoms. How much of the esophagus is removed is variable, depending on the location of the malignancy or obstruction. The top part of the stomach may also be removed (a procedure referred to as esophagogastrectomy). After removal of the cancer or obstruction, the stomach is connected to the remaining part of the esophagus, which is restructured into a tube to form a new esophagus. Cancers diagnosed and treated: Esophageal cancer; highgrade dysplasia with Barrett esophagus; end-stage benign diseases including achalasia, hiatal hernia, and gastroesophageal reflux disease (GERD) Why performed: An esophagectomy may be recommended as a treatment option for patients with cancer of the esophagus or high-grade dysplasia that occurs with Barrett esophagus. It also may be performed to provide relief of symptoms associated with benign conditions that affect swallowing, such as achalasia, hiatal hernia, and gastroesophageal reflux disease. Esophagectomy is the only surgical treatment currently available for the treatment of esophageal cancer, and it is most successful when performed for patients with early-stage disease. Because of the complexity of the procedure, an esophagectomy should be performed by an experienced thoracic surgeon at a medical center that specializes in the care of patients with esophageal diseases. Research has shown that patients who undergo an esophagectomy at hospitals with thoracic surgeons who perform large numbers of procedures have improved clinical outcomes and lower mortality rates than do patients who have an esophagectomy at lower-volume hospitals. Patient preparation: Tests performed before the procedure include a complete cardiac evaluation, esophageal manometry, esophagoscopy with biopsy, endoscopic ul438
Salem Health: Cancer trasound, computed tomography (CT) scan, positron emission tomography (PET) scan, and blood tests. Chemotherapy or radiation therapy may be performed to reduce the size of the tumor before surgery. One week before the procedure, patients must stop taking aspirin and products containing aspirin, ibuprofen, and anticoagulants, as directed by the physician. Steps of the procedure: General anesthesia is administered. The surgical technique and type of incisions vary, depending on the location and extent of the cancer, the patient’s pulmonary function, and the surgeon’s recommendations. Surgical techniques include the following: • transhiatal esophagectomy, in which incisions are made in the abdomen and left side of the neck, but not in the chest • transthoracic esophagectomy (Ivor-Lewis procedure), in which incisions are made in the chest wall (thoracotomy) and upper abdomen • triincisional esophagectomy (McKeown esophagectomy), in which incisions are made in the right chest, abdomen, and left side of the neck • minimally invasive esophagectomy, in which several 1-inch incisions are made between the ribs, a thoracoscope (small video-scope) is used to view the surgical area, and surgical instruments are inserted through the other incisions; this procedure minimizes trauma, decreases postoperative pain, and promotes a shorter hospital stay and a quicker recovery The esophagus, the tumor or obstruction, and affected lymph nodes are removed. The gastrointestinal system is reconstructed: The stomach is connected to the remaining part of the esophagus. Surgery may last from four to seven hours. After the procedure: The patient recovers in an intensive care unit (ICU) for twenty-four to forty-eight hours. The patient is intubated to aid breathing and has a chest tube to drain fluid and air. Medications are given to manage pain. A feeding tube is placed in the small intestine (jejunostomy or J-tube) to provide adequate nutrition during the early postoperative period when the patient is unable to eat by mouth. The patient performs deep breathing and coughing exercises to remove lung secretions. Recovery in the hospital takes about seven days, and full recovery usually occurs within six to eight weeks. The patient is able to advance gradually from clear liquids to soft foods during recovery at home. The J-tube is removed after the esophagus has healed, usually within four weeks after the procedure. The patient’s swallowing mechanism is usually restored, as well as the ability to taste food. In
Salem Health: Cancer some cases, surgical treatment with an esophagectomy may be followed by chemotherapy or radiation therapy. Risks: The risks of this procedure include leaks from the internal suture line, pneumonia, pulmonary edema, respiratory distress, bleeding, infection, abnormal heart rhythms, pneumothorax (collapsed lung), and persistent pain. The risk of heart attack is rare. Strictures or narrowed areas may occur at the site where the esophagus and stomach were reconstructed, causing difficulty swallowing in 10 to 15 percent of patients. The mortality rate (rate of death) associated with esophagectomy ranges from 3 to 8 percent. Results: Despite the risks, surgical advancements have improved the long-term success of the procedure. Twoyear survival rates for patients who undergo an esophagectomy for the treatment of esophageal cancer range from 35 to 42 percent, and five-year survival rates range from 15 to 24 percent, with higher survival rates in patients with early-stage cancers. Surgery performed for the relief of dysphagia (difficulty swallowing) improves symptoms in 80 percent of patients, according to the American Cancer Society. Angela M. Costello, B.S. u For Further Information Ercan, S., et al. “Does Esophagogastric Anastomic Technique Influence the Outcome of Patients with Esophageal Cancer?” Journal of Thoracic and Cardiovascular Surgery 129 (2005): 623-631. Ma, J. Y., et al. “Clinicopathologic Characteristics of Esophagectomy for Esophageal Carcinoma in Elderly Patients.” World Journal of Gastroenterology 12, no. 8 (2006): 1296-1299. MacKenzie, D. J., et al. “Care of Patients After Esophagectomy.” Critical Care Nurse 24, no. 1 (February, 2004): 16-31. Van Lanshott, J. J., et al. “Hospital Volume and Hospital Mortality for Esophagectomy.” Cancer 91 (2001): 1574. u
Other Resources
American Cancer Society http://cancer.org American College of Chest Physicians http://www.chestnet.org National Cancer Institute http://www.cancer.gov Society of Thoracic Surgeons—Patient Section http://www.sts.org/sections/patientinformation/
Esophagitis See also Alcohol, alcoholism, and cancer; Bacteria as causes of cancer; Barium swallow; Barrett esophagus; Candidiasis; Cardiomyopathy in cancer patients; Cigarettes and cigars; Endoscopy; Esophageal cancer; Esophagitis; Fanconi anemia; Gastrointestinal cancers; Gastrointestinal oncology; Hematemesis; Oral and oropharyngeal cancers; Premalignancies; Stent therapy; Stomatitis; Thoracotomy; Upper gastrointestinal (GI) endoscopy.
u Esophagitis Category: Diseases, symptoms, and conditions Also known as: Inflammation of the esophagus Related conditions: Gastroesophageal reflux disease (GERD), Barrett esophagus, heartburn (pyrosis), difficulty swallowing (dysphagia), painful swallowing (odynophagia) Definition: Esophagitis is a general condition in which the esophagus, the muscular tube connecting the mouth to the stomach, is inflamed. Different medical conditions are associated with esophagitis, including GERD, a condition in which the stomach contents flow backward into the esophagus, and nonreflux esophagitis. Serious gastrointestinal complications of esophagitis include a narrowing of the esophagus (strictures), ulcers, and in rare cases a risk of esophageal cancer. Risk factors: Factors that may increase the risk of developing esophagitis include pregnancy, obesity, scleroderma, smoking, alcohol, caffeine, chocolate, fatty or spicy foods, spinal cord injury, and certain medications (such as nonsteroidal anti-inflammatory drugs, or NSAIDs, including aspirin and ibuprofen). Etiology and the disease process: The etiology of esophagitis differs depending on the cause of the inflammation. In GERD-associated esophagitis, a backflow (reflux) of acidic fluid from the stomach (containing gastric acid, pepsin, and sometimes bile) to the esophagus causes irritation of the epithelium (the cells lining the esophagus). In some instances, a premalignant condition called Barrett esophagus can develop, which can increase the risk of developing esophageal cancer. However, the risk of esophageal cancer in patients with Barrett esophagus is relatively small: less than 1 percent of Barrett esophagus patients a year. Nonreflux esophagitis may be caused by infection (viral, bacterial, fungal, or parasitic organisms), chemicals (ingestion of a caustic chemical or medication), radiation therapy (physically damaging the lining of the esophagus 439
Esophagitis leading to inflammation and ulceration), or in rare instances immune-mediated disorders (eosinophilic esophagitis). Incidence: Esophageal reflux symptoms are estimated to occur in 33 to 44 percent of the general population on a monthly basis with up to 7 to 10 percent of people having daily symptoms. Radiation esophagitis occurs in up to 80 percent of patients receiving radiation therapy to the esophagus. Symptoms: The most common symptom is heartburn (pyrosis). Other common symptoms of esophagitis include upper abdominal discomfort, nausea, bloating, and fullness. Less common symptoms of esophagitis include dysphagia, odynophagia, cough, hoarseness, wheezing, and vomiting of blood (hematemesis). Screening and diagnosis: A physician can establish a diagnosis of GERD based on patient history alone. However, if symptoms are severe or do not respond to treatment, the physician may order diagnostic tests designed to determine mucosal injury, amount of reflux, and pathophysiology, including barium X-ray series, endoscopy, an ambulatory acid (pH) probe test, and an esophageal impedance test. During a barium X-ray series, the patient drinks a barium solution that, through a series of X rays, provides a picture of the shape and condition of the esophagus, stomach, and upper intestine (duodenum). X rays can also reveal a hiatal hernia, an esophageal narrowing, or a growth. During an endoscopy, or an esophagogastroduodenoscopy (EGD), a flexible tube with a light and camera (endoscope) is inserted down the throat and can reveal inflammation of the esophagus or stomach. A biopsy may also be taken during an EGD to test for Barrett esophagus, esophageal cancer, or the presence of a bacterium that may cause peptic ulcers. An ambulatory acid (pH) probe test can identify when and for how long stomach acid flows back into the esophagus. A flexible tube (catheter) is inserted through the nose into the esophagus to position a probe in the esophagus just above the stomach. The other end of the catheter is attached to a small computer that records acid measurements. The probe remains in place for one or two days while measurements are recorded. The esophageal impedance test is similar to the ambulatory acid probe test except that it measures whether gas or liquids reflux back into the esophagus. Treatment and therapy: The goals of treatment are to provide symptom relief, heal ulcerations, and prevent complications. Reflux esophagitis is managed with over440
Salem Health: Cancer the-counter agents, such as H2-receptor antagonists (cimetidine, ranitidine, famotidine, nizatidine) and with lifestyle changes such as altering eating habits (for example, avoiding alcohol, caffeine, carbonated beverages, chocolate, fatty foods, or overly large meals), ceasing to smoke cigarettes, and sleeping with the head of the bed elevated by about 4 to 6 inches. Proton pump inhibitors (omeprazole, lansoprazole, pantoprazole, esomeprazole, or rabeprazole) are frequently prescribed and appear effective at relieving symptoms and healing erosive esophagitis in up to 90 percent of patients. Infectious esophagitis is treated with antibiotics, whereas glucocorticoids are effective in patients with immune-mediated esophagitis. Radiation esophagitis treatment involves symptom management (similar to reflux esophagitis) and prevention (radioprotectors, varying treatment doses and schedules). For severe cases, a temporary feeding tube can be inserted into the stomach or surgery may be required to treat the injuries. To treat pain associated with esophagitis, a prescription analgesic can be gargled with and swallowed. Prognosis, prevention, and outcomes: Though the response to therapy may be different depending on the specific cause of the esophagitis, the disorders that cause esophagitis usually respond to treatment. Anita P. Kuan, Ph.D. u
For Further Information Icon Health. Esophagitis: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References. San Diego, Calif.: Author, 2004. Parkman, Henry, and Robert S. Fisher, eds. The Clinician’s Guide to Acid/Peptic Disorders and Motility Disorders of the Gastrointestinal Tract. Thorofare, N.J.: SLACK, 2006. Yamada, T., ed. Textbook of Gastroenterology. 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2003. Zoler, Mitchel L., and Robert Finn. “Drug Update: Gastroesophageal Reflux Disease.” Family Practice News 32, no. 9 (2002): 25.
u
Other Resources
Cleveland Clinic Health Information Center Esophagitis http://www.clevelandclinic.org/health/health-info/ docs/2800/2896.asp?index=10138 International Foundation for Functional Gastrointestinal Disorders http://aboutgimotility.org/
Salem Health: Cancer MayoClinic.com GERD http://www.mayoclinic.com/health/gerd/DS00967 MedlinePlus Esophagitis http://www.nlm.nih.gov/medlineplus/ency/article/ 001153.htm See also Alcohol, alcoholism, and cancer; Bacteria as causes of cancer; Barium swallow; Barrett esophagus; Candidiasis; Cardiomyopathy in cancer patients; Cigarettes and cigars; Endoscopy; Esophageal cancer; Esophagectomy; Fanconi anemia; Gastrointestinal cancers; Gastrointestinal oncology; Hematemesis; Oral and oropharyngeal cancers; Stent therapy; Stomatitis; Thoracotomy; Upper gastrointestinal (GI) endoscopy.
u Essiac Category: Complementary and alternative therapies Also known as: Flor-Essence, Herbal Essence, NAP Herbal Tea, Tea of Life, Vitalitea Definition: Essiac is an herbal mixture that was originally used by the Ojibwa tribe in Canada to cure cancerous tumors. The Ojibwa formula comprised four herbs: burdock root (Arctium lappa), slippery elm inner bark (Ulmus fulva), sheep sorrel (Rumex acetosella), and Indian rhubarb root (Rheum palmatum). Later formulas added watercress (Nasturtium officinale), blessed thistle (Cnicus benedictus), red clover (Trifolium pretense), and kelp (Laminaria digitata). Essiac was popularized in the early 1920’s by Rene Caisse (pronounced “reen kays”), a Canadian public health nurse. (Essiac is Caisse’s surname spelled backward.) For the next fifty years, despite government obstacles, she used Essiac to treat cancer in both Canada and the United States. Cancers treated or prevented: Essiac is very versatile. The Ojibwa used the herbal mixture to treat various tumors, including breast and stomach cancer. The herbs have also been used to treat leukemias and melanoma in addition to cancer of the bone, colon, esophagus, lung, and prostate. Delivery routes: Essiac is available in dry (capsules) and liquid (tea or extract) formulas. It is sold as a dietary supplement and therefore is not regulated as a drug. How this substance works: Each of the four basic herbs in Essiac has been reported to possess antioxidant and
Estrogen receptor downregulator (ERD) anticancer activity. The original claim was that Essiac softened, shrank, and discharged tumors from the body, thereby changing tumors into normal tissue. While there is no scientific evidence to support these claims, ongoing studies of Essiac continue both to refute and to confirm Essiac’s benefits. Essiac was found to be ineffective in controlling tumors in both older and recent studies by the Memorial SloanKettering Cancer Center and the U.S. National Cancer Institute (the 1950’s to 1980’s), the University of British Columbia (2005), and the University of Michigan (2006). A 2006 study by the National Institute for Occupational Safety and Health, however, determined that Essiac tea possesses potent antioxidant and DNA-protective activity, properties that are common to natural anticancer agents. A Canadian study in 2005 confirmed that Essiac was beneficial to a man with prostate cancer. Despite these controversial findings, Essiac continues to be a popular herbal remedy used as an adjunct to treat breast cancer, prevent secondary problems, improve quality of life, and control negative side effects of conventional breast cancer treatment. Side effects: Serious side effects, such as liver and kidney damage, are uncommon. Other side effects may include headache, nausea and vomiting, diarrhea or constipation, and low blood sugar. Renée Euchner, R.N. See also Anthraquinones.
u Estrogen receptor
downregulator (ERD) Category: Chemotherapy and other drugs; cancer biology ATC code: 102BA03 Definition: Estrogen receptor downregulator (ERD) is a compound that prevents the action of estrogen by attenuation of estrogen-receptor-mediated transcription and suppression of estrogen-dependent gene expression. The only known ERD is fulvestrant (Faslodex), which is described as “pure” ER antagonist, as it lacks the agonistic effects exhibited by other estrogen receptor modulators. Subclasses of this drug group are antiestrogens and selective estrogen receptor modulators (SERMs), the latter of which also downregulate the estrogen receptor but are selective in their antagonistic action. Cancers treated or prevented: Breast cancer 441
Estrogen-receptor-sensitive breast cancer Delivery routes: Intraperitoneal injection How this drug works: Estrogen is the female hormone that is mainly secreted in the ovaries and acts on female organs such as the breasts and uterus. Estrogen is responsible for activating the endothelial cells of the uterus during menstrual cycles. It performs its function by binding with specific receptors, called estrogen receptors (ER), that are present in various parts of the body. This binding is critical in inducing conformational changes of the ER protein, resulting in induction of expression in associated genes, ultimately leading to proliferation of endothelial cells. In cancer patients, proliferation of cancerous cells is triggered by estrogen binding to ER. Preventing estrogen from binding to its receptor is therefore a viable pharmacological strategy in cancer research. The estrogen receptor downregulator fulvestrant is a steroidal analog of the hormone 17β-estradiol. Fulvestrant was approved by the Food and Drug Administration (FDA) in 2002 for treating cancer. It binds to estrogen receptors and blocks downstream processes such as receptor dimerization, leading to blockade of induction of gene expression. Fulvestrant also expedites degradation of ER protein, resulting in drastic downregulation of ER levels. Estrogen cannot exert its proliferative action in the absence of ER, and thus the progression and spread of cancer can be controlled by fulvestrant treatment. Fulvestrant is administered to postmenopausal women whose cancer has metastasized and does not respond to traditional medications, such as the classic antiestrogen tamoxifen. Fulvestrant has about a hundredfold higher affinity for ER than tamoxifen and, unlike tamoxifen, does not have any agonistic effects on ER. Tamoxifen prevents proliferation of cells in the breast but acts like estrogen and exerts agonistic effects in the uterus. Clinical trials using fulvestrant have shown decelerated cancer growth and delayed recurrence rates. Using fulvestrant in combination therapy for cancer is now considered a treatment option. Side effects: The side effects of fulvestrant are nausea, vomiting, constipation, diarrhea, abdominal pain and hot flashes. Geetha Yadav, Ph.D. See also Antiestrogens; Breast cancers; Estrogen-receptorsensitive breast cancer; Hormonal therapies; Hormone receptor tests; Hormone replacement therapy (HRT); Phytoestrogens; Progesterone receptor assay; Receptor analysis.
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u Estrogen-receptor-sensitive
breast cancer Category: Diseases, symptoms, and conditions Also known as: Estrogen-receptor-positive breast cancer, hormone-dependent breast cancer Related conditions: Breast cancer, fibroadenomas, breast cysts, fibrocystic breasts Definition: Estrogen-receptor-sensitive breast cancer is the diagnosis given for a breast cancer that is driven by estrogen stimulation. It is by far the most common type of breast cancer. Breast cancer cells are primarily epithelial. About 75 percent of breast cancers originate in the ducts of the breast, in which cells are larger than normal epithelial cells and exhibit a variety of patterns, and 15 percent originate in the lobules, in which cells are smaller, uniform, and appear in rows. Rare, invasive cancers compose the remaining 10 percent. Risk factors: Age and gender are the strongest risk factors, with about 75 percent of cases occurring in women over age fifty, although younger women tend to have more aggressive tumors. Early menstruation (before age twelve), late menopause (after age fifty-five), and reproductive history (late pregnancy) are associated with higher risk, possibly because of the longer lifetime exposure to growth-stimulating estrogen. Inherited mutations in the tumor-suppressor genes BRCA1 and BRCA2 and a family history of the disease can increase risk as well. Etiology and the disease process: Although the cause of estrogen-receptor-sensitive breast cancer is unknown, estrogen appears to be involved with the proliferation and progression of the disease. Estrogen is produced by the ovaries, adrenal glands, and some fat tissue. In normal breast cells, especially the milk glands, estrogen stimulates cell division both directly and through its influence on other hormones (such as progesterone) and growth factors. Researchers believe that higher than normal amounts of estrogen can increase the rate of cell division (and the risk for chance mutations) and trigger the proliferation of cells already harboring genetic mutations. Even after cancer has developed, estrogen-receptor-sensitive cells depend on estrogen stimulation for continued growth and possibly for survival. Incidence: Estrogen-receptor-sensitive breast cancer is the most common cancer in women in the United States (excluding nonmelanoma skin cancers). After steadily increasing during the previous two decades, breast cancer incidence began to decrease between 2001 and 2003 from
Salem Health: Cancer approximately 100 to 75 per 100,000 in the United States, with a couple hundred thousand cases diagnosed each year and a little over 1 million cases worldwide. Symptoms: The classic symptom for this type of cancer is a palpable lump in the breast. Other symptoms include a noticeable difference in breast size or shape, breast swelling, nipple discharge or inversion, dimpling of the skin, orange peel consistency of skin, and enlarged lymph nodes in the area of the armpit or collarbone.
Estrogen-receptor-sensitive breast cancer
Breast Cancer Stages Stage
Tumor Size
Node Involvement
Metastasis
I
Less than 2 centimeters
No
No
IIA, IIB
2-5 centimeters
Possible
No
IIIA, IIIB, IIIC
More than 5 centimeters; cancer may extend to chest wall
Possible for IIIA; most likely for IIIB and IIIC
No
IV
N/A
N/A
Yes
Screening and diagnosis: The breast self-exam in combination with the clinical exam and mammogram, during which X rays are taken of the breasts to detect masses too small to feel, are the best screening tools available. Newer options include ultrasound, which can differentiate between cysts and solid tumors and is useful in diagnosing younger women who typically have higher breast density; magnetic resonance imaging (MRI), used to visualize tumor size and locate additional tumors; and computer-aided detection (CAD), which scans a mammogram for undetected tumors. In the future, nuclear medicine studies may be utilized as additional screening and diagnostic tools. Biopsy is necessary to confirm cancer, and the type of biopsy selected depends on size, location, and number of masses, as well as the patient’s medical history. A fineneedle aspiration biopsy uses a very thin needle to draw out fluid from abnormal tissue, a core biopsy uses a larger needle to remove a tissue sample, a Mammotome (or vacuum-assisted) biopsy inserts a probe that suctions and slices several tissue samples, and surgical biopsy removes all or part of the abnormal tissue. Surgical biopsy may be ultimately necessary for confirmation of cancer. Tumors are described using the TNM (tumor/lymph node/metastasis) classification system, which corresponds with four main breast cancer stages. Treatment and therapy: Treatment options include a breast-conserving lumpectomy (removal of the tumor and part of the surrounding tissue) or a modified radical mastectomy (removal of the breast, lymph nodes, and fatty tissue associated with the breast and lining of the chest). Both surgeries are a drastic improvement over the disfiguring Halstead radical mastectomy that was used until the 1970’s. Postoperative radiation is recommended, followed with chemotherapy, which consists of a combination of cyclophosphamide (Cytoxan), methotrexate or doxorubicin
(Adriamycin), and 5-fluorouracil (5-FU). Because this type of breast cancer responds to hormone stimulation, hormone therapy that antagonizes the estrogen receptor (either tamoxifen or one of the newer aromatase inhibitors) is used in addition to chemotherapy. Prognosis, prevention, and outcomes: Due to increased screening and the advantages of hormone therapy, survival rates are greater than 80 percent for women with estrogen-receptor-sensitive breast cancer. Mortality has decreased since the 1980’s from 33 deaths per 100,000 to 25 deaths, although it remains the second leading cause of cancer deaths in women. (Lung cancer is the first.) Because the cause is unknown, preventive measures are difficult to outline. Researchers are investigating possible links between estrogen-receptor-sensitive breast cancer and oral contraceptives, environmental factors, silicone implants, obesity, hormone replacement therapy, smoking, alcohol, and lack of exercise. Amber L. Fields, M.S. u
For Further Information DeGregorio, Michael W., and Valerie J. Wiebe. Tamoxifen and Breast Cancer. New Haven, Conn.: Yale University Press. 1996. Hartmann, Lynn C., and Charles L. Loprinzi. Mayo Clinic Guide to Women’s Cancers. New York: Kensington, 2005. Ricks, Delthia. Breast Cancer Basics and Beyond. Alameda, Calif.: Hunter House Books, 2005.
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Other Resources
American Cancer Society http://www.cancer.org BreastCancer.org http://www.breastcancer.org 443
Ethnicity and cancer National Cancer Institute http://www.cancer.gov See also Antiestrogens; Breast cancers; Estrogen receptor downregulator (ERD); Hormonal therapies; Hormone receptor tests; Hormone replacement therapy (HRT); Phytoestrogens; Progesterone receptor assay; Receptor analysis.
u Ethnicity and cancer Category: Social and personal issues Definition: For socioeconomic, dietary, lifestyle, environmental, and genetic reasons, cancer affects various population groups differently. This is quite apart from strictly individual causes that may also play out in the incidence and mortality rates of carcinomas. Ethnicity: An ethnic group is distinguished by common cultural and frequently racial or linguistic, social, or religious characteristics. When there is prolonged mingling of ethnic groups within a geographic area or when an ethnic group is exposed to a new environment, as in the case of immigrants to the United States, the distinguishing features of a particular ethnic group will become blurred. Even the group’s distinctive health profile will be modified by virtue of changes in not only environment but also income, educational level, and thus diet, lifestyle, and access to medical care—in short, socioeconomic status (SES). Although socioeconomic status, which varies among different ethnicities, has considerable bearing on the incidence of cancer, inherited predispositions also play an important role in determining which ethnic group is afflicted by what type of cancer. Therefore, some ethnic differences in health indicators, including cancer markers, appear to be independent of socioeconomic status. Making general statements about the importance of particular factors becomes harder when comparing different ethnic groups. Although some minority older adults, particularly blacks and generally American Indians and Alaska Natives, are considerably less healthy than older whites, others, particularly Hispanics and Asian Americans and Pacific Islanders (AAPIs), are often healthier. There are many inconsistencies, and correlations are difficult, to begin with because the terms race and ethnicity are variously defined. For example, not all cancer-related data distinguish between nonwhite Hispanics and Latinos and white Hispanics and Latinos. Despite these caveats, a few correlations can be hypothesized. 444
Salem Health: Cancer Some generalizations: According to the Centers for Disease Control and Prevention, the five leading causes of cancer death for American men in 2004, expressed as ageadjusted death rates per 100,000 people, were lung, 70.3; prostate, 25.4; colon and rectum, 21.6; pancreas, 12.3; and leukemias, 9.7. The five leading causes of cancer death for American women in 2004 were lung, 40.9; breast, 24.4; colon and rectum, 15.2; pancreas, 9.2; and ovary, 8.8. Although the cancers most likely to cause death remained largely the same among ethnic groups, their rankings differed. In men, lung and colorectal cancer retained their rankings (one and three) throughout the ethnic groups, but in Asian Americans and Pacific Islanders, liver cancer replaced prostate cancer as the number-two cause of mortality. Liver cancer also was the third cause of death in male American Indians and Alaska Natives and Hispanics. Stomach cancer was the fifth-ranked cause of cancer death among male blacks and Asian Americans and Pacific Islanders. In women, lung cancer was the number-one cause of mortality except for Hispanics, in whom the first- and second-ranked causes of death were reversed. Colorectal cancer was the third cause of death in all female ethnic groups. Liver cancer was the fourth cause of death among female American Indians and Alaska Natives. For all forms of cancer in 2004, the incidence and mortality rates per 100,000 population broken down by ethnic categories were as follows: whites, 455.4 and 184.1, respectively; blacks, 469.6 and 228.1; Hispanics, 356.5 and 122.8; Asian Americans and Pacific Islanders, 289.8 and 110.9, and American Indians and Alaska Natives, 261.3 and 127.9. Cancer and the role of ethnicity: Worldwide, there are regional variations in the incidence of specific types of cancer according to the ethnicities predominant in those areas. The stomach cancer common in Japan and Scandinavia is thought to be of dietary origin, while the liver cancer common in parts of Africa and Asia is believed to be a result of infection with the hepatitis B virus. However, when people from these areas immigrate to the United States, they often acquire the health profile of Americans through consuming more red meat and living a more sedentary lifestyle. For example, Chinese Americans, who no longer follow the fish, rice, and vegetable diet and active lifestyle of their ancestors, tend to have a higher rate of colorectal cancer as a result. Nature and nurture both appear to be relevant in explaining cancer trends among different ethnic groups. Factors in human geography can explain only part of the incidence of cancer; genetics also plays a role. For example, Ashkenazi women have a higher rate of breast and often
Salem Health: Cancer ovarian cancer than women in the population at large. Although rare in the general population, the A636P mutation is detected in up to 7 percent of Ashkenazi Jews with earlyage-of-onset colorectal cancer and may account for up to one-third of hereditary nonpolyposis colorectal cancer (HNPCC) in the Ashkenazi Jewish population. The difficulty of linking ethnicity to hereditary cancers stems from the fact that ethnicity and socioeconomic differences are intertwined. Failure to consider this may lead to inappropriate attribution of differences to ethnic—and thus genetic—factors rather than to socioeconomic status, which in turn may misdirect health care research and funding. The incidence of cancer falls as levels of education and income rise. Ethnic groups with a higher proportion of members with lower socioeconomic status, such as African Americans and Hispanics, tend to be less knowledgeable about health matters, have fewer financial resources to devote to them, and be more likely to be uninsured than groups with higher socioeconomic status. Some statistics: African Americans The incidence rates of the two most common forms of cancer—prostate for men and breast cancer for women— vary considerably by ethnicity. African Americans, with an incidence rate of 180.6 per 100,000 people, had the highest rate of prostate cancer, followed by whites, with a rate of 134.7 per 100,000. However, the incidence rate of breast cancer was higher in white women, with 113.0 per 100,000 versus 95.4 per 100,000 for black women. In 2004, in men the incidence of all invasive cancers combined per 100,000 people was 303.5 among African Americans, 224.8 among whites, 152.8 among Hispanics, 151.2 among American Indians and Alaska Natives, and 137.0 among Asian Americans and Pacific Islanders. In women, the incidence rates were 182.8 among African Americans, 156.4 for whites, 110.7 for American Indians and Alaska Natives, 101.9 for Hispanics, and 92.3 for Asian Americans and Pacific Islanders. African Americans experience disproportionately high age-adjusted cancer incidence and mortality rates, but few studies have separated the impact of lower socioeconomic status from that of genetics. In 2004, the cancer death rate for African Americans was 303.5 per 100,000 people versus 224.8 per 100,000 for white Americans. However, studies have shown that within comparable strata of education and income, African Americans aged twenty-five and over have a similar or lower incidence of all cancers combined when compared with white Americans. This implies that many of the disparities in cancer incidence associated with ethnicity may be caused by factors linked to poverty rather than to genetics. Lower socioeconomic
Ethnicity and cancer status limits educational attainment, reduces access to medical screening or care, and is often associated with greater exposure to tobacco use, heavy alcohol consumption, poor nutrition, physical inactivity, overweight and obesity, and other risk factors. Nevertheless, just why cancer incidence and death rates are higher in African American men remains somewhat baffling, although mortality rates may be influenced by the tendency for cancer to be diagnosed at a later stage among people with lower socioeconomic status, which results in poorer survival rates. Other ethnic groups: Besides African Americans, other ethnic groups in the United States have distinctive cancer patterns. Relative to whites, age-adjusted incidence and mortality rates among Mexican Americans are higher for gallbladder, stomach, and cervical cancer. American Indian men and women have lower incidence rates of most cancers other than those of the gallbladder, stomach, and cervix. Japanese Americans have higher rates of stomach and liver cancer. Chinese Americans have higher rates of nasopharyngeal, liver, and stomach cancer. Native Hawai-
Five-Year Relative Survival Rates Among Whites and African Americans, 1995-2000 Survival Rates (%) Site of Cancer
Whites African Americans
All sites Lung Breast Colon and rectum Prostate Bladder Uterus (corpus uteri) Non-Hodgkin lymphoma Oral cavity and pharynx Leukemia Melanoma of skin Pancreas Kidney Stomach Ovary Cervix uteri
65.5 15.4 88.9 64.1 100.0 82.7 86.1 60.3 60.9 47.8 90.7 4.2 63.9 21.5 44.0 74.0
55.2 13.2 75.2 54.6 96.0 61.9 63.1 50.5 39.0 38.6 74.0 3.8 63.5 24.2 37.9 65.7
Source: Data from U.S. Department of Commerce, Statistical Abstract of the United States: 2004-2005, 124th ed. (Washington, D.C.: U.S. Dept. of Commerce, Economics and Statistics Administration, Bureau of the Census, Data User Services Division, 2004)
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Ethnicity and cancer
Salem Health: Cancer
Incidence Rates per 100,000 People of Prostate Cancer (for men) and Breast Cancer (for women) by Ethnicity/Race, 1988-1992 Prostate (men) 180.6 46.1 52.5 46.0 69.8 57.2 88.3 24.2 40.0 134.7
Ethnicity/Race African American Alaska Native American Indian Chinese Filipino Hawaiian Japanese Korean Vietnamese White
Breast (women) 95.4 78.9 31.6 55.0 73.1 105.6 82.3 28.5 37.5 113.0
Source: Data from B. A. Miller et al., eds. Racial/Ethnic Patterns of Cancer in the United States, 1988-1992 (Bethesda, Md.: National Cancer Institute, 1996) Note: Incidence rates are age standardized to the U.S. population of 1970.
ians have higher death rates from esophagus, liver, pancreas, lung, breast, and cervical cancer. Filipinos have a lower risk of most cancers other than those of the stomach, liver, oral cavity, and esophagus. Again, many of these ethnic differences are believed to reflect differences in tobacco use, dietary habits, infectious exposures, or access to medical care. Some of these higher incidence rates, however, can be attributed to specific causes. For example, the high rate of stomach cancer among recent migrants from Latin America, Asia, and parts of Africa correlates with a higher prevalence of chronic helicobacterial infection in childhood and a greater consumption of salted and smoked foods but lower consumption of fresh fruits and vegetables. Similarly, ethnic groups with increased incidence of liver cancer usually have a higher prevalence of infection with the hepatitis B virus or less commonly hepatitis C virus. The incidence of cervical cancer may reflect exposure to human papillomavirus (HPV), especially when sexual activity begins early and with multiple partners, as is the case with some ethnic groups, whereas the survival rate from cervical cancer varies according to the use of Pap tests and early treatment. In some ethnicities, darker skin, with its increased pigmentation and melanosomal dispersion, helps protect people from skin tumors, but this may change with increased participation in outdoor activities and the depletion of the protective ozone layer in the stratosphere. 446
The future: Research into cancer has brought increased understanding of the major environmental determinants of cancer, such as infections, diet, tobacco, and exposure to ultraviolet (UV) rays and certain chemicals. Differential exposure to these risks explains to a considerable degree why ethnic groups have varying rates of cancer, especially as, because of socioeconomic status and culture, they differ in levels of early screening, diagnosis, and access to health care. However, it appears that, for many cancers, an important component of risk differentials among various ethnic groups is related to genetic susceptibility. The development of genotyping techniques opens prospects for additional investigations, so that research can focus on possible underlying genetic mechanisms to solve the enigmas still being posed by interethnic variations in cancer incidence and mortality rates. Peter B. Heller, Ph.D. u
For Further Information Aguirre-Molina, Marilyn, et al., eds. Health Issues in the Latino Community. San Francisco: Jossey-Bass, 2001. American Cancer Society. Cancer Facts and Figures for African Americans. Atlanta: American Cancer Society, 2007. Bulatao, Randy A., and Norman B. Anderson. Understanding Racial and Ethnic Differences in Health in Late Life: A Research Agenda. Washington, D.C.: National Academies Press, 2004. Johnson, Bernett L., Jr., et al. Ethnic Skin: Medical and Surgical. St. Louis: Mosby, 1998. Kedar-Barnes, I., and P. Rozen. “The Jewish People: Their Ethnic History, Genetic Disorders, and Specific Cancer Susceptibility.” Familial Cancer 3, nos. 3/4 (2004): 193-199. Lillie-Blanton, Marsha D., et al. Key Facts: Race, Ethnicity, and Medical Care. Menlo Park, Calif.: Henry J. Kaiser Family Foundation, 2003. Macbeth, Helen, and Prakash Shetty, eds. Health and Ethnicity. London: Taylor & Francis, 2001. Miller, Barry A., et al., eds. Racial/Ethnic Patterns of Cancer in the United States, 1988-1992. Bethesda, Md.: National Cancer Institute, 1996. Purnell, Larry D., and Betty J. Paulanka. Transcultural Health Care: A Culturally Competent Approach. 2d ed. Philadelphia: E. A. Davis, 2003. Vlahov, David, et al. Racial/Ethnic Differences in Screening for Colon Cancer. Atlanta: International Society on Hypertension in Blacks and New York Cancer Project, 2005.
Salem Health: Cancer u
Other Resouces
Centers for Disease Control and Prevention U.S. Cancer Statistics http://apps.nccd.cdc.gov/uscs M. D. Anderson Cancer Center Race, Ethnicity, and Cancer http://www.mdanderson.org/topics/ethnicity See also African Americans and cancer; Africans and cancer; Ashkenazi Jews and cancer; Asian Americans and cancer; Cancer clusters; Family history and risk assessment; Geography and cancer; Latinos/Hispanics and cancer; Native North Americans and cancer; Poverty and cancer.
u Ethylene oxide Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 2000 Also known as: 1,2-epoxyethane, oxacyclopropane, dimethylene oxide, oxirane Related cancers: Leukemia, stomach, lymphatic, pancreatic, and brain cancers Definition: Ethylene oxide is a flammable, colorless gas at temperatures above 51.3 degrees Fahrenheit. It is a three-atom ring made of two carbon atoms and one oxygen atom. Each of the two carbon atoms is bonded to two hydrogen atoms.
Ewing sarcoma History: Ethylene oxide has been produced in large quantities in the United States since 1921. Annual production ranges between 2.6 million and 3.4 million metric tons. It is one of the top twenty-five chemicals in volume. Well over half of the production is consumed in the synthesis of the antifreeze, ethylene glycol. Five studies of workers exposed to ethylene oxide, beginning in the mid-1980’s, showed that exposure produces statistically significant excess tumor appearance. There are difficulties in the interpretation of each of these studies, but a causal relationship between the compound and tumor production is likely. Animal studies involving rats, mice, and hamsters clearly show its carcinogenicity. Federal regulations exist for the control of ethylene oxide. The Department of Transportation (DOT) lists the chemical as hazardous and requires special marking, labeling, and transporting precautions. The Environmental Protection Agency (EPA) requires that the manufacture of ethylene oxide meet provisions for the control of volatile organic compounds (VOCs). Also, under the Clean Air Act, the compound is listed as one of thirty-three hazardous air pollutants that present the greatest threat to public health, and the EPA requires that as little as ten pounds of the substance must be reported. The Occupational Safety and Health Administration (OSHA) has set the permissible exposure limit at one part per million. K. Thomas Finley, Ph.D. See also 1,3-Butadiene; Diethanolamine (DEA); Formaldehyde.
Exposure routes: Inhalation, ingestion, skin contact
u Ewing sarcoma
Where found: Fumigation of foodstuffs, sterilization of hospital instruments, and various synthetic chemical operations
Category: Diseases, symptoms, and conditions Also known as: Ewing’s sarcoma, Ewing sarcoma of the bone, extraosseus Ewing sarcoma, extraskeletal Ewing sarcoma, Ewing tumor, Ewing angioendothelioma, Ewing endothelial sarcoma, Ewing syndrome, malignant primary bone tumor, red bone marrow tumor, neural tumor
At risk: Workers in the detergent, fungicide, and synthetic chemical fields, especially those related to ethylene glycol manufacture Etiology and symptoms of associated cancers: The high reactivity of ethylene oxide is shown by ring opening and the introduction of new carbon groups at reactive sites in deoxyribonucleic acid (DNA). This type of reaction takes place largely at a nitrogen atom of guanosine. Such modified nucleic acid fragments have been observed in mice and are most prevalent in the liver, kidney, spleen, and testis. A variety of mutations and reverse mutations have also been found. Gene mutations and heritable translocations are common.
Related conditions: Primitive neuroectodermal tumor, peripheral primitive neuroectodermal tumor, Askin’s tumor, osteosarcoma Definition: Ewing sarcoma is a rare disease involving cancer cells found in bones and soft tissue. It usually occurs in the pelvis, ribs, arm bone (humerus), shoulder blade, or leg bone (femur). It gets its name from James Ewing, who in the 1920’s first described the disease as being separate from other known types of cancers such as lym447
Ewing sarcoma phoma or neuroblastoma. Ewing noticed that this type of cancer responded well to radiation. It belongs to a group of tumors sometimes called the Ewing family of tumors because of the close molecular relationship between these kinds of tumors. Risk factors: More than 90 percent of people who develop this disease have an unusual rearrangement between chromosomes: A piece of chromosome 11 and a piece of chromosome 22 have switched places (called a gene translocation). However, this translocation is not inherited or
Salem Health: Cancer passed on genetically, so family members of those affected with Ewing sarcoma have no more risk of developing the cancer than the general population does. Male teenagers are most often diagnosed with this disease. The cancer is thought to be linked somehow to the rapid growth that occurs during puberty. Whites are more likely to develop this disease than are Asians and African Americans. Very rarely, Ewing sarcoma can develop as a secondary tumor in patients who have had radiation therapy for another type of cancer. Etiology and the disease process: Because this cancer occurs most often during the teenage years, there may be a link between the onset of puberty and early stages of this disease. Ewing sarcoma usually starts in a bone, though it can start in soft tissue. The most common starting place for these tumors is in the pelvis or in the leg bones. The tumors may then spread to the chest cavity, other bones, bone marrow, lungs, kidneys, or heart when tumor cells enter the bloodstream and travel elsewhere in the body. This disease may also spread to the central nervous system or lymph nodes, but this is much less common. Incidence: This disease occurs most often in male children and teenagers, mostly between ten and twenty years old. However, female children and teenagers also develop this disease. In the United States, this cancer affects children less than three years of age at a rate of 0.3 per million and teenagers between the ages of fifteen and nineteen at a rate of 4.6 per million. People over the age of twenty-five rarely develop this type of cancer. Experts estimate that in the United States each year about 200 new cases of this cancer are diagnosed in children and about 20 in adults. These tumors make up about 30 percent of the bone cancers in children. Symptoms: Symptoms of Ewing sarcoma involve pain (which may be worse at night), swelling (especially when the tumor is located in the long bones of the arm or leg), redness, tenderness, stiffness, a mass that grows quickly and may feel warm, or a bone that breaks unexpectedly. Some patients have fever, fatigue, anemia, or weight loss. Numbness, tingling, or paralysis can also be symptoms if the tumor is located near nerves.
A fibula with Ewing sarcoma. (©Ism/Phototake—All rights reserved)
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Screening and diagnosis: Because this disease is so rare, no screening is recommended. When Ewing sarcoma is suspected, doctors generally use X rays to determine if there is a suspicious growth. A magnetic resonance imaging (MRI) scan or blood tests also may be helpful in making a diagnosis. If Ewing sarcoma is suspected, two addi-
Salem Health: Cancer tional tests are used to see if the disease has spread: a computed tomography (CT) scan, which usually includes the lungs to see if the disease has spread there, and a bone scan. Ewing sarcoma may initially be mistaken for a bone infection (osteomyelitis) or another type of bone cancer (osteosarcoma). A sample of the tumor (biopsy) is necessary to confirm the diagnosis of Ewing sarcoma. A biopsy may be performed with a fine needle, taking only a small sample of the tumor, or by surgery, where all or a large part of the tumor is removed. Sometimes, bone marrow also is biopsied to determine if the disease has spread there. There is no formal staging for Ewing sarcoma. Gauging the extent of this disease is done by simply determining whether the cancer has spread into other tissues. Treatment and therapy: Ewing sarcoma is usually a very aggressive disease. By the time of diagnosis, nearly all patients with Ewing sarcoma have some spreading of the disease throughout the body. Most patients are treated with chemotherapy, sometimes before and after surgery, to ensure treatment of any tumors throughout the body. Surgery or radiation may also be used at the local site of the main tumor if the tumor can be removed without damaging vital organs. Sometimes surgery involves removing bones, which can be replaced or rebuilt with artificial bones or bone grafts. With Ewing sarcoma, radiation therapy usually involves radiation that comes from a machine outside the body rather than from implanted radiation seeds. Radiation therapy can shrink large tumors to alleviate symptoms if the tumor cannot be removed with surgery. Other types of treatment may include rehabilitation, including occupational or physical therapy. Patients may also need supportive care to help with side effects of chemotherapy, radiation, or surgery. Some patients may benefit from a transplant of blood stem cells or bone marrow. Diagnosis of Ewing sarcoma usually occurs during the teenage years, sometimes an already turbulent period. Surgery may cause disfigurement during a period of life when looks are very important. Support groups in which teens meet other people with this condition may be especially helpful in dealing with the psychological trauma that this disease can cause. Generally, patients with Ewing sarcoma benefit from treatment at a children’s hospital or medical center with doctors who have experience treating pediatric cancers. Prognosis, prevention, and outcomes: The prognosis for patients with this disease depends on how far the disease has spread, the size and location of the main tumor, and how responsive the tumors are to chemotherapy. For pa-
Ewing sarcoma tients who at diagnosis show no signs of the spread of the disease and choose an aggressive course of treatment involving chemotherapy, surgery, and radiation, survival rates at five years are 70 to 75 percent. However, at diagnosis, at least 15 percent of these patients already have cancer throughout their bodies, generally because symptoms are so vague and nonspecific. These patients have a five-year survival rate of 30 percent. Children under the age of eleven, female children and teenagers, those with smaller tumors, and those who have tumors below the elbow or below the calf have the highest survival rates. People who have had Ewing sarcoma need continual follow-up care. Even if the cancer is treated and its spread stopped, it often develops again in the place where it first arose and tends to spread throughout the body. Health issues may spring up later that are caused by the type of treatment given. These issues may involve heart and lung problems, slowed or decreased growth and development, and problems with sexual development. It is important for a patient who has had this disease to be regularly monitored for these types of concerns. There is no known way to prevent Ewing sarcoma. However, not everyone with the gene translocation develops this disease. Scientists are investigating why the gene translocation causes the disease only in some people to see if there are ways to block this cancer from forming. Research is also under way to determine new and improved techniques for diagnosing this cancer earlier in the disease process. Marianne M. Madsen, M.S. u
For Further Information Icon Health. Ewing’s Sarcoma: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References. San Diego, Calif.: Author, 2004. Pappo, Alberto S., ed. Pediatric Bone and Soft Tissue Sarcomas. New York: Springer, 2005. Theroux, Nicole. Ewing’s Sarcoma Family of Tumors: A Handbook for Families. Glenview, Ill.: Association of Pediatric Oncology Nurses, 1999. u
Other Resources
Cancer Index Ewing’s Sarcoma: Frequently Asked Questions http://www.cancerindex.org/ccw/faq/ewings.htm The Cure Our Children Foundation Ewing’s Sarcoma and Pediatric Cancer Support Group Resources Page http://www.cureourchildren.org 449
Exenteration Ewing’s Research Foundation http://www.letsbeatthis.org National Cancer Institute Ewing Family of Tumors Treatment http://www.cancer.gov/cancertopics/pdq/treatment/ ewings/healthprofessional See also Amputation; Bone cancers; Limb salvage; Neuroectodermal tumors; Pediatric oncology and hematology; Spinal axis tumors; Tumor markers; Young adult cancers.
u Exenteration Category: Procedures Definition: Exenteration is a major surgical procedure in which the entire contents of a body cavity, such as the pelvis or the orbit (eye socket), are totally removed. Cancers treated: In female patients, cancer of the reproductive organs such as the uterus, cervix, and Fallopian tubes; in male patients, cancer of the prostate and certain ducts and glands; for both genders, cancer of the rectum and cancers of the eye and surrounding tissues Why performed: Exenteration of the pelvis in female patients is performed when less radical surgery, chemotherapy, and radiotherapy have failed in the management of advanced and/or invasive cases of vaginal, cervical, uterine, and rectal cancer. Most often, previously treated patients with recurrent cervical cancer undergo the procedure. Cancer that has spread or metastasized is rarely treatable with exenteration; because of characteristic distant metastasis, ovarian cancer does not lend itself to the procedure. In male patients, pelvic exenteration is indicated when prostate and/or rectal cancer is unresponsive to radiation and hormonal therapy and when biopsy demonstrates recurrent cancer and ultrasound shows rectal involvement. Orbital exenteration is indicated for large orbital tumors, or the extension of intraocular tumors, most commonly when squamous and basal cell carcinoma affecting the orbit and its contents are unmanageable by simple removal or irradiation. Patient preparation: For exenteration of the pelvis, along with laboratory tests, patients are evaluated with pelvic and rectal exams. Imaging procedures include rectal and liver ultrasound, computed tomography (CT) scans, chest X rays, bone scans, and magnetic resonance imaging (MRI) to determine the extent and/or spread of the cancer. 450
Salem Health: Cancer Biopsy may confirm a recurrence of cancer. Immediately preceding the operation, the patient is given a bowel prep and antibiotics to prevent postsurgical infection. In orbital exenteration, a physical exam, history, laboratory tests, and imaging methods such as ultrasound, CT scans, angiography (to examine the orbital blood vessels), and biopsy are employed. Patients may undergo preoperative radiation and/or chemotherapy. Steps of the procedure: Total pelvic exenteration is an ultraradical surgery comprising total resection (removal) of female reproductive organs (cervix, uterus, tubes, ovaries, and vagina), part of the lower urinary tract (urethra and bladder) and rectum, as well as the muscles that form the pelvic floor. The process commences with a generous midline (vertical) incision in the abdomen that allows for exploration; during the operation, biopsies may be taken to assess the presence of cancer. If a tumor cannot be found or if pathology shows that the cancer has spread to the pelvic sidewall or has metastasized to the lymph nodes, then the procedure should be discontinued. If a decision is made to continue, then pelvic blood vessels are clamped and the organs are removed. Before the incision is closed, a urostomy and a colostomy may be performed. A urostomy diverts urine to a small pouch created from the small intestine, which is then connected to the abdominal wall so that urine can pass through a stoma (small opening) for collection. A colostomy attaches the colon to the abdominal wall so that fecal waste may exit the body via a stoma for collection in a small bag. Variations of pelvic exenteration include anterior exenteration, in which the rectum is left intact, and posterior exenteration, in which the bladder and the urethra are spared. In male patients, removal of the bladder and prostate is called a cystoproctectomy. In orbital exenteration, the entire contents of the globe are removed, including the eyeball, surrounding tissues, and part of the bony orbit. In certain patients, the eyelids and conjunctiva may be spared. Less radical procedures include evisceration, which spares the extraocular muscles, and enucleation, in which the eye is removed while all other orbital structures are spared. After the procedure: With pelvic exenteration, a drainage tube is placed into the incision site; there is usually discharge, bleeding, and quite a bit of tenderness and pain for at least a few days. While side effects vary, they often include difficulty with urination, particularly if catheterization is involved. Before the patient is sent home, stitches are removed and a pain medication is prescribed. After orbital exenteration, the majority of patients ex-
Salem Health: Cancer perience headache for several days, which may dissipate with the use of pain medications. An ocular ointment containing antibiotics and steroids may also be prescribed. Risks: With pelvic exenteration, morbidity and mortality depend on the specific procedure and the condition of the patient; the elderly and those with comorbidities are most affected. There is a 30 to 44 percent chance of complications such as kidney failure, fistula formation, and bowel obstruction during the procedure, a mortality rate of 2 to 5 percent, and a five-year survival rate of 23 to 61 percent. The success with rectal anastomosis depends on the degree of resection and concurrent reconstructive procedures; complications such as leaks and fistulas may occur in 30 to 50 percent of cases. Overall, a poor prognosis is associated with recurrence of cancer, a tumor larger than 3 centimeters, involvement of the resection margin or pelvic sidewall, and nodal metastasis. With orbital exenteration, there may be ear pathology, sinusitis, chronic orbital pain that throbs, orbital cysts, and recurrence of cancer. A five-year survival rate of 64 percent has been observed. Results: While pelvic exenteration may often be a lifesaving measure, patients should be made aware of postoperative sequelae so as to attenuate the psychological distress related to lifestyle changes such as dealing with permanent catheterization, a colostomy and/or urostomy, and loss of sexual functions. The services of a psychologist and sex therapist may be required. In addition, a variety of postoperative reconstructive procedures are available to support the pelvis and even create a “neovagina” in female patients. Orbital exenteration will require that the patient adapt to a dramatic change in appearance and loss of eyesight in the affected eye. Wearing an eye patch is a popular option for many patients; after the site has healed, a temporary prosthesis such as a plastic eye may be used. Later, a permanent prosthesis may be attached. Cynthia Racer, M.A., M.P.H. u
For Further Information Ben Simon, G. J., R. M. Schwarcz, R. Douglas, et al. “Orbital Exenteration: One Size Does Not Fit All.” American Journal of Ophthalmology no. 139, no. 6 (2005): 7-11. Della Rocca, Robert, Edward H. Bedrossian, Jr., and Bryan Arthurs, eds. Ophthalmic Plastic Surgery: Decision Making and Techniques. New York: McGrawHill, 2002. Nemet, A. Y., P. Martin, R. Benger, et al. “Orbital Exenteration: A Fifteen-Year Study of Thirty-eight Cases.”
Exercise and cancer Ophthalmic Plastic & Reconstructive Surgery 23, no. 6 (November/December, 2007): 468-472. O’Donovan, Peter J., and Ellis G. R. Downes, eds. Advances in Gynaecological Surgery. San Francisco: GMM, 2002. Rock, John A., and Howard W. Jones III, eds. Te Linde’s Operative Gynecology. 9th ed. Philadelphia: Lippincott Williams & Wilkins, 2003. Stolzenburg, J.-U., M. T. Gettman, and E. N. Liatsikis, eds. Endoscopic Extraperitoneal Radical Prostatectomy: Laparoscopic and Robot-Assisted Surgery, London: Springer, 2007. See also Lacrimal gland tumors; Nasal cavity and paranasal sinus cancers; Urinary system cancers; Vaginal cancer.
u Exercise and cancer Category: Lifestyle and prevention Definition: Regular exercise has been found to reduce cancer risk and mortality. The more time a person spends in occupational or leisure activities requiring physical exertion, the lower the risk of cancer. For those who have cancer, regular exercise has been shown to improve recovery and help manage the side effects of treatments. Protective effects of exercise: Many studies have found an inverse relationship between exercise and many types of cancer. Exactly how exercise protects individuals against various cancers is difficult to determine. A number of logical theories have been presented. Regular exercise has a positive effect on the blood by lowering glucose and insulin levels and improving white blood cell function. Hormonal changes include an increase in steroid hormones from the adrenal cortex and improvements in the insulin effects on cancer-fighting T cells. Exercise is also believed to improve vitamin C metabolism. All of these effects could protect the body from cancer. A more complex area where benefits are likely is cell division, which is rapid in cancers. Exercise increases anti-inflammatory cytokines, which decrease cell division. It also has beneficial effects in preventng the activation of cancer genetic material called oncogenes. Another effect is the promotion of interferon production, which decreases viral reproduction. By decreasing cell reproduction, exercise may slow cancer growth. Rehabilitation effects of exercise: The main goal of exercise for those who have cancer is to maintain or improve the physical capabilities of the body, resulting in an im451
Exercise and cancer
Salem Health: Cancer
proved quality of life during and after treatment. No obvious effects of exercise on the immune system of cancer patients have been identified at this time. Some of the immediate effects of exercise on the cancer patient are decreased nausea and lessened symptoms of fatigue. Part of the goal of exercise for cancer patients is to protect them from other health problems. Exercise helps them maintain healthy weights by decreasing fat but also de-
creasing the loss of muscle due to inactivity and treatments. Exercise increases blood flow throughout the body, reducing blood clot formation, particularly in the legs. Longer-term health risks such as osteoporosis (loss of bone) and cardiovascular disease are lowered by regular exercise. Psychological benefits can also be obtained by cancer patients who exercise. Decreased anxiety and depression and improved self-esteem have been found. The ability to be more independent and do normal daily activities can Physical Activity Recommendations contribute to this improved psychologfor Healthy Adults from the Centers for ical state. With all of these potential Disease Control and Prevention benefits, cancer patients are advised to participate in exercise programs with Aerobic or Cardio Activity individualized exercise prescriptions. Option 1: 30 minutes (minimum) of moderate-intensity exercise most days of the week
• • • • • • • • • • • • • •
Walking, moderate to brisk pace (3-4.5 mph) on level surface Bicycling 5-9 mph, level terrain Yoga Ballroom dancing Tennis, doubles Golf, wheeling clubs and walking Shooting baskets Swimming recreationally Horseback riding Gardening and yard work Moderate housework (scrubbing the floor on all fours, carrying out trash) Hand washing and waxing a car Walking, running, or climbing when playing with children Walking while pushing or pulling a child in a stroller
Option 2: 20 minutes (minimum) of vigorous-intensity exercise 3 days a week
• • • • • • • • • • • • • •
Jogging or running Walking briskly up a hill Roller skating or in-line skating briskly Bicycling more than 10 mph or on uphill terrain Karate, judo Jumping rope Stair climber machine at fast pace Professional or energetic ballroom dancing Tennis, singles Competitive sports such as football, basketball, soccer Ice skating quickly or speed skating Swimming laps Heavy yard work or gardening (felling trees, digging ditches) Racewalking or jogging while pushing a sports stroller
Strength Building Activity 2 days a week
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Weight lifting, 6 to 8 exercises, with 8 to 12 repetitions per exercise
Exercise prescription and cancer: Cancer patients must check with their physicians before beginning an exercise program. It is generally recommended that patients first complete a supervised exercise test to determine which types of exercise can be done safely. Exercise tests should not be conducted if the patient has dizziness, shortness of breath, fever, or nausea and vomiting. Exercise tests are usually conducted on a treadmill or stationary bicycle, paying close attention to symptoms and fatigue. This is not be a maximal test to exhaustion but rather a submax test. The information obtained from the exercise test is used to complete an exercise prescription. Mode, frequency, intensity, duration, and progression are considered. The type of exercise recommended includes activities that work the large muscle groups such as walking and cycling. It is recommended that cancer patients exercise three to five times per week. In cases in which patients have low levels of conditioning, shorter sessions are attempted every day. Cancer patients are advised to exercise at a lower intensity than the general population. For healthy people, the typical heart rate range considered desirable for exercise is 70 to 85 percent of maximum heart rate, and in cancer patients, it is 60 to 70 percent of maximum
Salem Health: Cancer heart rate. The recommended duration of the exercise session is twenty to thirty continuous minutes. However, many cancer patients may not be able to exercise that long. In these cases, the patients can space out the twenty to thirty minutes with periodic rest intervals. The goal is gradually to shorten the length and frequency of rest periods until the patient can complete the exercise session without stopping. In the healthy population, people progress by gradually increasing intensity, duration, or frequency. This may not be possible for cancer patients because of treatments that may cause regression. Therefore periodic modifications in the exercise program may need to be made. Several precautions are advised for cancer patients. Treatments frequently lower blood counts, resulting in increased risk for infections, anemia, and bleeding. Blood counts are monitored during treatment and used to determine appropriate exercise times. Patients are advised to stop exercise during periods of low blood counts. Sodium and potassium levels can decrease with excessive vomiting. This decrease can lead to other health complications, and exercise should be avoided during these times. Treatments also can cause severe fatigue. When patients are fatigued, less intense exercise, or a break in exercise, is appropriate. For cancer patients, lifting heavy weights and exercising on uneven floors that can affect balance are not advised. Conditions that warrant contacting a physician are swollen ankles; unexplained weight loss; shortness of breath with low-level activity; or exercise-induced nausea, vomiting, or unrelieved pain. Dizziness or blurred vision that does not go away with rest needs immediate attention from a physician. By paying attention to these safety measures, cancer patients can exercise safely and effectively. Exercise, cancer, and fatigue: Cancer treatments such as chemotherapy and radiation cause fatigue in most patients. Incorporating exercise into the treatment gives the expectation of greater fatigue and less willingness to participate. However, appropriate, low-level aerobic exercise can actually decrease fatigue. Strategies exist to improve exercise adherence during cancer treatments. One important factor is rest. Physical activity and rest must be balanced so there is no interference with nighttime sleep. This is best accomplished with a regular daily routine in which exercise takes place during times when the patient feels best. Reducing stress with regular relaxation techniques is helpful, along with a balanced diet that includes adequate protein. Getting plenty of fresh air, such as exercising outside, is beneficial.
Exercise and cancer
The more time people exert themselves physically, whether as part of work or leisure, the lower their risk of cancer. (PhotoDisc)
Perspective and prospects: Although much progress is being made in the fight against cancer, it will continue to be one of the major health problems. New drugs and other treatments to force cancer into remission will be developed, giving more hope to cancer patients. However, lifestyle interventions involving exercise, nutrition, and stress management can also be used to help treat and minimize treatment side effects. At the least, lifestyle interventions will improve the quality of life of cancer patients. The correlation between cancer prevention and exercise has not been investigated to the same extent as exercise and cardiovascular disease. The cardiovascular benefits of exercise were found many years ago, and many studies have been conducted to determine the best exercise practices. As more research is conducted, the mechanisms for decreasing cancer risk will become more evident and the specific types of exercises associated with both prevention and treatment of specific cancers will be identified. This will give health professionals more options for fighting cancer and improving the quality of life for cancer survivors. 453
External beam radiation therapy (EBRT) In the meantime, cancer patients can participate in appropriate exercise programs that include low-intensity aerobic activities. Health care professionals as well as exercise leaders and trainers need to be continually updated about cancer and the benefits of exercise as additional information is found. Cancer is a challenging disease and all strategies must be used to reduce risk and improve outcomes. Bradley R. A. Wilson, Ph.D. u For Further Information McTiernan, Anne. Cancer Prevention and Management Through Exercise and Weight Control. Boca Raton, Fla.: CRC Press, 2006. Schneider, Carole M., Carolyn A. Dennehy, and Susan D. Carter. Exercise and Cancer Recovery. Champaign, Ill.: Human Kinetics, 2003. Schwartz, Anna L. Cancer Fitness: Exercise Programs for Patients and Survivors. New York: Fireside, 2004. Stidwill, Howard. Exercise Therapy and the Cancer Patient: A Guide for Health Care Professionals and Their Patients. Belgium, Wis.: Champion Press, 2006. u
Other Resources
American Cancer Society Physical Activity and the Cancer Patient http://www.cancer.org/docroot/MIT/content/ MIT_2_3x_physical_activity_and_the_cancer_ patient.asp?sitearea=MIT National Cancer Institute Energy Balance: Weight and Obesity, Physical Activity, Diet http://www.cancer.gov/cancertopics/energybalance See also Aging and cancer; Anxiety; Chemoprevention; Dietary supplements; Fiber; Macrobiotic diet; Nutrition and cancer prevention; Prevention; Self-image and body image; Smoking cessation; Stress management.
u External beam radiation
therapy (EBRT)
Salem Health: Cancer Cancers treated: Most cancers, with approximately 60 percent of all cancer patients receiving radiation Why performed: EBRT is performed as a curative treatment alone or in combination with chemotherapy, surgery, and other treatments. EBRT may also be used to treat symptoms or side effects from cancer, such as spinal cord compression and metastases. Patient preparation: The patient will be referred to a radiation oncologist for a consult visit to determine if external beam radiation therapy is appropriate. Prior to receiving treatment, patients have a simulation using a computed tomography (CT) scanner or other device to visualize the area to be treated. A simulation may take one to two hours. Small marks may be applied to the skin to provide assistance in positioning the radiation beams. The simulation data are used to plan the radiation dose amounts to be given by the linear accelerator. Accurate tumor targeting is the key to protecting normal tissues while killing cancer cells. Steps of the procedure: The treatment plan will outline the patient position on the treatment table, define the number of treatments to be given, and prescribe the daily total dose to be given. The patient usually has four to six weeks of treatment, five days a week, with two days a week off for normal cells to rest and recover. The patient may need to change into a hospital gown. In the treatment room, the staff will position the patient carefully and then leave the room to program the linear accelerator with the required treatment data. The total time for positioning and radiation administration is about fifteen minutes. After the procedure: Treatments are generally done on an outpatient basis, and the patient may leave immediately after the daily treatment. Patients are not radioactive following treatments. Risks: External beam radiation therapy is a local treatment, so risks are generally associated with the site being treated. Skin reactions, similar to sunburn, may occur. Fatigue is often associated with EBRT, but the cause is unknown. There is a risk of a second cancer caused by the radiation. There is also a risk that the radiation will not kill all the cancer cells.
Category: Procedures Also known as: Radiotherapy
Results: Expected after external beam radiation therapy is expected to kill cancer cells and thus reduce tumor size. Patricia Stanfill Edens, R.N., Ph.D., FACHE
Definition: External beam radiation therapy (EBRT) uses a linear accelerator to generate high-energy radiation beams or a machine with a radioactive source, cobalt 60, to kill cancer cells by altering their genetic material.
See also Afterloading radiation therapy; Brachytherapy; Cervical cancer; Computed tomography (CT) scan; Medulloblastomas; Radiation oncology; Radiation therapies; Thyroid cancer.
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Eye cancers
u Eye cancers Category: Diseases, symptoms, and conditions Also known as: Intraocular cancers, uveal cancers Related conditions: Retinal detachment, angle-closure glaucoma Definition: Eye cancers are malignant tumors of the eye, which is made up of the globe, the orbit, and the adnexal structures. The globe (or eyeball) is filled with a fluid called vitreous humor and contains the retina and the uvea. The uvea consists of the iris (pigmented area surrounding the pupil), choroid (pigmented lining of the eyeball that brings blood to the retina and the front of the eye), and ciliary body (made up of the cells producing the aqueous humor and the muscles that control the shape of the lens). Cancers that develop in the globe (retina and uvea) are called intraocular cancers. The orbit is made up of the tissues surrounding the eyeball, including the muscles that control the directional movement of the globe and the nerves of the eye. Tumors in these tissues are called orbital cancers. The adnexal structures consist of the eyelids and the tear glands. Cancers that occur in these structures are called adnexal cancers. Risk factors: For intraocular melanoma, the risk factors include advanced age (the peak age is seventy), being white, and having light (blue or green) eye color, fair skin, and the ability to tan. For retinoblastoma in children, 10 percent of patients have retinoblastoma in their family history. If the disease is passed from parent to child, the child often has retinoblastoma in both eyes. Etiology and the disease process: The most common intraocular or uveal eye cancers are melanomas, although these are rare, with approximately 4.3 new cases per 1 million people. Most intraocular melanomas initially do not cause any symptoms, but as the tumor grows, symptoms may include distortion of the pupil, blurred vision, and decreased visual acuity caused by secondary retinal detachment. Extensive retinal detachment can be accompanied by secondary angle-closure glaucoma. Other tumors that can resemble intraocular melanomas in clinical presentation are metastatic carcinoma, posterior scleritis, and benign tumors such as nevi and heman-
giomas. This should be considered when making a diagnosis of intraocular melanoma. Approximately 90 percent of intraocular melanomas occur in the choroid and are called choroidal melanomas. Choroidal melanomas are primary intraocular cancers, that is, cancers that originate in the eye. They initiate from pigmented cells in the choroid and have the potential to become malignant (metastasize to other organs). The remaining intraocular melanomas are melanomas of the iris. These tumors often grow from pigmented spots in the iris that may be present for many years before developing into tumors. They are relatively slow growing and rarely metastasize, and therefore are associated with a better prognosis than choroidal melanomas. Another kind of intraocular cancer is intraocular lymphoma, which can be either Hodgkin disease or nonHodgkin lymphoma. These lymphomas typically originate in the lymph nodes but can also originate in the stomach, lungs, and eye. Primary intraocular lymphomas are rare and are always of the non-Hodgkin type. These cancers usually occur in elderly or immunosuppressed people. Adnexal tumors affecting the eyelid include basal cell carcinomas, which constitute 85 to 95 percent of all malignant eyelid tumors; squamous cell carcinoma; sebaceous cell carcinoma; and malignant melanoma. Basal cell carcinomas and squamous cell carcinomas are most common in elderly people with fair skin. Basal cell carcinomas commonly occur in the inner part of the lower eyelid and are often nodular, appearing as raised pearly bumps with tiny blood vessels. Sebaceous cell carcinomas originate in the
Malignant melanoma on the iris. (Sue Ford/Photo Researchers, Inc.)
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Eye cancers eyelid tear glands in elderly people and can be highly malignant, returning after removal and invading the eye socket and lymph nodes. Malignant melanomas are associated with unusual or changing pigmentation. Tumors of the conjunctiva can be squamous cell carcinoma, malignant melanoma, or lymphoma. Secondary intraocular cancers originate in other organs in the body and spread (metastasize) to the eye. Breast and lung cancers are most likely to metastasize to the eye, especially the uvea. Tumors can also metastasize from the prostate, kidneys, thyroid, and the gastrointestinal tract, though this occurs less frequently than metastasis from the breast and lung. Retinoblastoma is the most common form of eye cancer in children. It is most common in children younger than the age of five, and affects boys and girls in equal proportion. Approximately 75 percent of retinoblastoma cases are unilateral (affecting one eye). Some 90 percent of patients do not have a family history of retinoblastoma. Incidence: In 2008, about 2,390 adults were estimated to be diagnosed with cancer of the eye and orbit and 240 were estimated to die of the cancer. The incidence of intraocular melanomas, the most common form of intraocular cancer, is approximately 4.3 new cases per 1 million people. Retinoblastoma affects 1 in every 15,000 to 30,000 live babies per year, with 350 new cases annually. It affects all races with similar frequency. Symptoms: Symptoms of intraocular tumors may include distortion of the pupil, blurred vision, bulging eyes, watery eyes, pain in or around the eye (rare), and decreased visual acuity caused by secondary retinal detachment. Extensive retinal detachment may be accompanied by secondary angle-closure glaucoma. Other symptoms may include floaters, where spots, flashes, or wavy lines appear in the visual field; loss of peripheral vision, where objects to the side cannot be seen; and a pigmented spot on the iris that enlarges with time (this could be a sign of iris melanoma). Symptoms of retinoblastoma include a white pupil reflex (leukocoria or cat’s-eye reflex) instead of the normal black pupil or red reflex. Screening and diagnosis: Diagnosis of eye tumors can be performed by means of an eye examination with an ophthalmoscope or slit lamp. This is the single most important diagnostic test for eye tumors. For example, most choroidal melanomas can be diagnosed by visual examination of the pupil for the presence of tumors. Choroidal melanomas range in shape and pigmentation, from dark brown to unpigmented. However, most choroidal melanomas are 456
Salem Health: Cancer brown to gray-green in color and have a dome or nodular shape. Other tumors may need additional tests, which include echography or ultrasound, in which sound waves are directed at the eye from a small probe placed on the eye. The reflection patterns are then analyzed to determine if tumors are present. Another diagnostic technique is called fluorescein angiography and involves the introduction of eye drops that cause pupil dilation followed by the injection of a fluorescent dye into a vein in the arm. The dye passes through the blood vessels in the back of the eye and a camera takes a series of photographs, from which the physician can determine if a tumor is present. Echography and fluorescein angiography can also be used to distinguish between eye tumors and hemorrhages or macroaneurysms that may occur in the choroid or below the retinal epithelium. The most invasive diagnostic test that can be performed is the eye biopsy. This involves inserting a long narrowbored needle into the eye and extracting tissue for examination with a microscope. The risk of ocular mortality associated with an eye biopsy, however, is a serious drawback to this diagnostic test and influences many physicians to use alternative means of diagnosis. Staging of intraocular tumors involves determining the tumor thickness (apical height) and width (basal diameter). Tumor sizes are classified as small (apical height of 1 millimeter, or mm, to 3 mm, basal diameter equal to or greater than 5 mm), medium (apical height of 2 mm to 10 mm, basal diameter less than 16 mm), large (apical height greater than 10 mm, basal diameter equal to or greater than 16 mm), and diffuse (horizontal, flat growth pattern and tumor thickness 20 percent or less than the greatest basal dimension). Diffuse tumors are rare and have a poorer prognosis. Physicians also determine if the tumor has metastasized and, if so, to what extent. Metastasis of the tumor to preauricular, submandibular, or cervical lymph node regions indicates that subconjunctival extension has occurred. Systemic metastasis usually occurs first in the liver and may also occur in the lung, bone, and subcutaneous sites. Metastasis or spreading of the cancer to the optic nerve, eye socket, or meninges is very rare and is called extraocular extension. The American Joint Committee on Cancer has developed a method for intraocular cancer staging. Metastasis of retinoblastoma tumors is rare but when it occurs, tumors can spread to the brain, central nervous system, and bones. Treatment and therapy: One of the most commonly used methods of treating eye cancers is radiation therapy, which can shrink tumors but usually does not eliminate them en-
Salem Health: Cancer
Eye cancers
Stage at Diagnosis and Five-Year Survival Rates for Eye and Orbit Cancer, 1996-2004 Stage Localizeda Regionalb Distantc Unstaged
Cases Diagnosed (%) Survival Rate (%) 75 9 4 12
86.7 68.7 70.4 77.6
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 a Cancer still confined to primary site b Cancer has spread to regional lymph nodes or directly beyond the primary site c Cancer has metastasized
tirely. It can take two forms: plaque radiation therapy and external-beam, charged-particle radiation therapy. Plaque radiation therapy uses plaques with radioactive pellets on one side and gold coating on the other side. An incision is made in the conjunctiva, and plaques are sewn to the outside of the eye directly over the tumor with the side coated with radioactive pellets facing the tumor. Plaque radiation therapy has a five-year control rate of more than 90 percent but has the disadvantage of a high risk of secondary cataracts. External-beam, charged-particle radiation therapy involves irradiating tumors with precisely focused radiation from a cyclotron, a piece of equipment that is available only at specialized centers. This type of therapy specifically kills tumor tissue without damaging surrounding healthy eye tissue and appears to have a control rate similar to that of plaque radiation therapy. The drawbacks are the need for specialized equipment with limited availability, the need for patient cooperation during the procedure (the eye needs to be held still so that the radiation beam can be directed at the tumor), and the possibility of anteriorsegment complications. Other treatments include local tumor resection, which is used for ciliary body or anterior choroidal tumors that have smaller basal dimensions and greater thickness. The eye tumor can also be treated with chemotherapy, which is administered intravenously and delivered to the eye through the bloodstream. In cases in which treatment of the tumor is unsuccessful, surgery may be required to remove the eye (enucleation). The empty eye socket can then be filled with an eyeball implant made of synthetic material.
Newer treatments include photocoagulation with white light and laser radiation, transpupillary thermotherapy, and cryotherapy. Photocoagulation involves the destruction of small tumors by directing light through the pupil into the tumor. Newer photocoagulation techniques use a diopexy probe that directs the light through the wall of the eye instead of through the pupil. This method can be used alone or together with plaque radiation therapy and cryotherapy. Cryotherapy involves applying a penlike probe to the sclera just next to the tumor and freezing the tumor while the patient is under local or general anesthesia. This usually has to be repeated multiple times before the tumor is destroyed and can cause swelling of the eye and eyelids. Prognosis, prevention, and outcomes: The prognosis of intraocular cancers depends on several factors, including cell type, tumor size, location of the anterior margin, the extent of ciliary body involvement, extraocular extension, and tumor recurrence. Cell type is the most commonly used factor for predicting cancer prognosis. Intraocular melanomas usually consist of spindle cells and epithelioid cells. Spindle cells have less potential for metastasis than epithelioid cells, and a tumor that is mostly made up of spindle cells is considered to have a better prognosis than one that consists mostly of epithelioid cells. Recurrent melanoma always has a poor prognosis, regardless of cell type or stage. The treatment selected depends on the tumor size, age and health of the patient, site of recurrence, and previous treatment. The prognosis for retinoblastoma is usually very good, with most children (more than 95 percent) surviving to live normal lives. Ing-Wei Khor, Ph.D. u
For Further Information “Malignant Melanoma of the Uvea.” In AJCC Cancer Staging Manual, edited by Frederick L. Greene et al. 6th ed. New York: Springer-Verlag, 2002. Singh, A. D., L. Bergman, and S. Seregard. “Uveal Melanoma: Epidemiologic Aspects.” Ophthalmology Clinics of North America 18 (2005): 75-84. u
Other Resources
American Cancer Society What Is Eye Cancer? http://www.cancer.org/docroot/CRI/content/ CRI_2_4_1x_What_is_eye_cancer_74.asp?sitearea= Bascom Palmer Eye Institute Ocular Oncology http://www.eyecancermd.org/eye_cancers.html 457
Eyelid cancer Cancer Help UK Symptoms of Eye Cancer http://www.cancerhelp.org.uk/help/ default.asp?page=18546 Collaborative Ocular Melanoma Study About Choroidal Melanoma http://www.jhu.edu/wctb/coms/general/about-mm/ coms1.htm Eyecancernetwork http://www.eyecancer.com Memorial Sloan-Kettering Cancer Center Retinoblastoma http://www.mskcc.org/mskcc/html/2867.cfm National Cancer Institute Intraocular (Eye) Melanoma Treatment http://www.cancer.gov/cancertopics/pdq/treatment/ intraocularmelanoma/healthprofessional See also Eyelid cancer; Gonioscopy; Lacrimal gland tumors; Neurofibromatosis type 1 (NF1); Ophthalmic oncology; Orbit tumors; Retinoblastomas; Rhabdomyosarcomas; Rothmund-Thomson syndrome; Sjögren syndrome.
u Eyelid cancer Category: Diseases, symptoms, and conditions Related conditions: Eye cancers Definition: Eyelid cancer can occur as one of a variety of types of cancer that begin on or around the eyelid. The most common types of eyelid cancer are slow to spread and can often be successfully be treated with surgery to remove the tumor followed by eyelid reconstruction. Risk factors: The main risk factors for eyelid cancer are light skin tone, skin that easily burns or freckles, and frequent exposure to the sun. Eyelid cancer is most common in people over the age of fifty. Men are affected slightly more often than women. Individuals who have skin around the eye that has been sunburned, burned, or that has been injured because of a disease or infection are believed to be at higher risk for eyelid cancer. A history of other skin cancers is also thought to increase the risk. Etiology and the disease process: There are four main types of eyelid cancers. Basal cell carcinoma and squamous cell carcinoma are usually slow growing and do not tend to spread to other areas of the body. Sebaceous gland carcinoma and malignant melanoma are more aggressive, 458
Salem Health: Cancer faster growing, and much more likely to spread. Basal cell carcinoma is a cancer that develops in the lower epidermis. Squamous cell carcinoma begins in the top layer of the epidermis. Sebaceous gland carcinoma arises in the glands of the eyelid. Melanoma begins in the very bottom layer of the epidermis in the cells called melanocytes. From these beginnings, eyelid cancer can spread to the lymph nodes, areas around the eyelid, and to other areas of the body. Incidence: Eyelid cancer is not a very common form of cancer. According to the American Society of Clinical Oncology, in the United States the annual rates of eyelid cancer are 19.6 cases for every 100,000 men, and 13.3 cases for every 100,000 women. The most common form of eyelid cancer is basal cell carcinoma, which makes up between 85 and 95 percent of reported cases of eyelid cancer. Sebaceous cell carcinoma makes up about 5 percent of reported cases, sebaceous gland carcinoma between 1 and 5 percent of cases, and malignant melanoma a little less than 1 percent of cases. Symptoms: The main symptom of eyelid cancer is usually an abnormality in the skin of the eyelid or the surrounding area. Often, the eyelid cancer presents as a small bump, sometimes with small red veins in it. The area may differ in color from the surrounding skin and may seem to change colors or grow in size. The eyelashes in the affected area may be missing. There may be a sore that is crusted over or will not heal, or a tear that does not seem to heal properly. Other possible symptoms include swelling or thickening of the eyelid, and an eyelid infection that will not go away or keeps returning. There is often no pain associated with the discolored or bumpy area. Screening and diagnosis: The ophthalmologist will determine if the suspicious bump or discoloration is cancerous. If cancer seems likely, a biopsy will be performed. During the biopsy some or all of the suspected lesion is removed. It is then sent to a lab, where a pathologist performs tests and examines it under a microscope to determine if cancer is present and, if so, the type and possible extent. Eyelid cancer is staged based on the size of the tumor, if the cancer has spread to the nearby lymph nodes, and whether it has spread to any other parts of the body. Treatment and therapy: For many cases of eyelid cancer, especially basal cell carcinomas, the biopsy procedure may actually be all the treatment required. If it is determined that the biopsy removed all the cancerous tissue, no other procedures may be necessary. Most eyelid cancers are treated primarily with surgery. Other procedures, such as cryosurgery, in which the cancerous cells are frozen off, may be necessary. If the cancer has spread to any other
Salem Health: Cancer parts of the body, appropriate treatment will be required. Radiation and chemotherapy are not usually required for eyelid cancers that have not spread. Because surgical removal of the cancerous tissue is usually the primary treatment option, reconstructive surgery is frequently required after the cancer has been removed. Prognosis, prevention, and outcomes: The prognosis for cases of eyelid cancer that are caught early is generally very good. According to the American Society of Clinical Oncology, estimates indicate a cure rate of up to 95 percent for basal cell carcinoma. The prognosis for each person depends on the stage at which the cancer was diagnosed and other factors. Sebaceous cell carcinoma is not always treatable with as much success as basal cell carcinoma, because it is more likely to have spread and has a higher incidence of recurrence. Malignant melanoma is most likely to not be treatable successfully because of its tendency to spread to other areas of the body quickly. The best way to prevent eyelid cancer is to take the precautions that are generally recommended to prevent any form of skin cancer, such as avoiding prolonged exposure to intense sun, wearing UV-protective sunglasses, and always wearing sunscreen. Helen Davidson, B.A.
Eyelid cancer u
For Further Information Albert, Daniel M., and Arthur Polans, eds. Ocular Oncology. New York: Marcel Dekker, 2003. Bospene, Edwin B., ed. Eye Cancer Research Progress. New York: Nova Science, 2007. Fekrat, Sharon, and Jennifer S. Weizer, eds. All About Your Eyes. Durham, N.C.: Duke University Press, 2006.
u
Other Resources
Eyecancernetwork Squamous Carcinoma of the Eyelid http://www.eyecancer.com/patient/ Condition.aspx?nID=54&Category=Eyelid+Tumors &Condition=Squamous+Carcinoma+of+the+Eyelid Vision Channel Skin Cancer of the Eyelids http://www.visionchannel.net/skincancer/index.shtml See also Eye cancers; Gonioscopy; Lacrimal gland tumors; Neurofibromatosis type 1 (NF1); Ophthalmic oncology; Orbit tumors; Retinoblastomas; Rothmund-Thomson syndrome; Sjögren syndrome.
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Fallopian tube cancer
u Fallopian tube cancer Category: Diseases, symptoms, and conditions Also known as: Fallopian tube adenocarcinoma, Fallopian tube sarcoma, Fallopian tube mixed mesodermal tumor, broad ligament tumor Related conditions: Cancer of the uterus, cancer of the ovary, peritoneal carcinomatosis Definition: Fallopian tube cancer is a rare cancer in one of the Fallopian tubes, which lie on both sides of the top of the uterus (womb). These tubes serve as the site of fertilization for oocytes (eggs) released from the ovary and sperm ascending from the vagina, and then as passageways by which the zygote (fertilized egg) returns to the uterus to implant and where the fetus grows and develops. Cancer of the Fallopian tube is primary (originating in the Fallopian tube) in 10 to 20 percent of cases; the majority of Fallopian tube cancers, however, are metastatic from the ovary, uterus, or gastrointestinal tract (stomach and intestines). Risk factors: The major risk factors for Fallopian tube cancers are thought to be chronic inflammation in the form of endometriosis or pelvic infections, although this has not been proven. Other possible risk factors include a history of infertility and low parity (fewer than two children). Fallopian tube cancer is a disease of older women, diagnosed at an average age of fifty-nine years, with those diagnosed ranging between ages twenty-six and eighty-five. Oral contraceptive use and pregnancy may reduce a woman’s risk of Fallopian tube cancer. Etiology and the disease process: Based on molecular studies, cancer of the Fallopian tube and ovary share abnormalities of the genes TP53 and ERBB-2, suggesting similar genetic risks and environmental factors. Incidence: Fallopian tube cancer is the rarest cancer involving the female genital tract, accounting for approximately 1 percent of all gynecologic malignancies. The incidence of Fallopian tube cancer in the United States is 3.6 cases per million women per year, with approximately 300 cases diagnosed in the United States each year. Any woman’s individual lifetime risk of Fallopian tube cancer is therefore small. Symptoms: For the most part, cancer of the Fallopian tube is a disease without specific symptoms. Symptoms that are associated with cancer of the Fallopian tube include an abnormal, watery vaginal discharge or excessive bleeding; such symptoms occur in approximately 50 percent of 460
Salem Health: Cancer those with Fallopian tube cancer. Pain and a palpable pelvic mass are infrequently associated with Fallopian tube cancer. Occasionally, the pain associated with Fallopian tube cancer mimics appendicitis. Screening and diagnosis: No routine screening exists or is recommended for Fallopian tube cancer. Most often, the diagnosis of Fallopian tube cancer is made at the time of exploratory surgery to evaluate the patient’s symptoms, such as pelvic pain or a mass. Aside from nonspecific symptoms and the triad of symptoms in postmenopausal women (pelvic pain, a pelvic mass, and vaginal bleeding or discharge), the diagnosis should be suspected when cancer cells show up on microscopic evaluation of vaginal discharge with a negative Pap smear and biopsy of the uterus. An abdominal mass can be further evaluated with a pelvic ultrasound, computed tomography (CT) scan, magnetic resonance imaging (MRI), or a laparoscopic examination of the pelvis (outpatient surgery performed through the belly button with a small, lighted instrument). Definitive diagnosis of primary Fallopian tube cancer, as opposed to metastatic cancer, requires that the tumor be contained within the cavity of the Fallopian tube (lumen), the lining of the Fallopian tube (mucosa) be involved with the tumor, and a transition be demonstrated between the portion of the tube involved and that not involved with cancer. Cancer of the Fallopian tube is based on International Federation of Gynecology and Obstetrics (FIGO) staging. Stage 0 is cancer limited to the lining of the Fallopian tube (mucosa). Stage I is cancer limited to one tube with extension into the muscular layer of the tube but not to the external surface of the tube. Stage II cancer involves one or both tubes with extension beyond the Fallopian tube. Stage III cancer involves one or both tubes with spread beyond the pelvic cavity. Stage IV cancer involves one or both Fallopian tubes with distant metastases (for example, the lungs). Unlike ovarian cancer, which is usually advanced at the time of diagnosis, approximately 50 percent of Fallopian tube cancers are Stage I or II at the time of diagnosis, and 50 percent are Stage III or IV. Treatment and therapy: Because Fallopian tube cancer is generally diagnosed during surgery, staging is performed at that time to determine the extent of disease so that optimal treatment can be offered. Treatment includes a hysterectomy (removal of the uterus), a bilateral salpingo-oophorectomy (removal of both Fallopian tubes and ovaries), inspection of the surfaces of the lining of the abdominal cavity (the peritoneum) for cancer cells, sampling of lymph nodes, and removal of the omentum (a fatty layer covering the intestines).
Salem Health: Cancer For Stage I disease, surgery alone is recommended unless the peritoneum is positive. In that case, postoperative radiation or chemotherapy is offered. For Stages II through IV, postoperative chemotherapy is the standard treatment. A second laparoscopy is often performed on completion of chemotherapy or radiation therapy to confirm control of the disease. A blood test, the cancer antigen 125 (CA 125), can be ordered to monitor disease recurrence. Prognosis, prevention, and outcomes: The five-year survival for all stages of Fallopian tube cancer is approximately 40 to 50 percent. Patients diagnosed with Stage I Fallopian tube cancer have five-year survival rates of 65 percent; those with Stage II, 50 to 60 percent; and those with Stages III and IV, 10 to 20 percent. D. Scott Cunningham, M.D., Ph.D. u For Further Information Ajithkumar, T. V., A. L. Minimole, M. M. John, and O. S. Ashokkumar. “Primary Fallopian Tube Carcinoma.” Obstetrics and Gynecological Survey 60 (2005): 247-252. Pectasides, D., and T. Economopoulos. “Fallopian Tube Carcinoma: AReview.” Oncologist 11 (2006): 902-912. u
Other Resources
Abramson Cancer Center of the University of Pennsylvania Fallopian Tube Cancer: The Basics Http://www.oncolink.com/types/article .cfm?c=6&s=49&ss=801&id=9502 Eyes on the Prize Gynecologic Cancer: Fallopian Tube Cancer http://www.eyesontheprize.org/FAQ/gynca/ fall_tube.html See also Adenomatoid tumors; BRCA1 and BRCA2 genes; Culdoscopy; Endometrial cancer; Endometrial hyperplasia; Exenteration; Family history and risk assessment; Fertility issues; Gynecologic cancers; Gynecologic oncology; Hormonal therapies; Hysterectomy; Hystero-oophorectomy; Leiomyomas; Oophorectomy; Ovarian cancers; Ovarian cysts; Pelvic examination; Salpingectomy and salpingooophorectomy; Uterine cancer.
Family history and risk assessment
u Family history and risk
assessment Category: Medical specialties; social and personal issues Also known as: Cancer genetics risk assessment, assessment of inheritance patterns Definition: Individuals who have a familial risk of developing cancer are those who also have with a strong family history of cancer, including affected relatives with unusual or multiple cancers or family members diagnosed at atypically early ages. Although having a family history can increase one’s risk of cancer, it does not necessarily mean that one will go on to develop cancer. Inheritance patterns and incidence of cancer in family members: In any discussion of family risk for cancer, it is important to note that individuals can inherit an increased risk of developing cancer, but they do not inherit the disease itself. In fact, a known risk of developing cancer can actually reduce a family member’s susceptibility to cancer by encouraging that individual to adopt healthy behaviors, such as regular medical checkups, good eating and exercise habits, and, for some, prophylactic treatments. Although some individuals may be aware of a family history of cancer, others must be identified by the prudent physician or other health care professional so that they may be appropriately referred for genetic counseling and testing. Cancers have different inheritance patterns, and the risk of a family member who has an affected first-order relative may vary with the type of cancer. For example, research indicates that pancreatic cancer is currently considered attributable to a genetic mutation (an event that changes the genetic structure or genotype of an individual or organism). The majority of genetic mutations that lead to cancer occur in genes that control growth through exposure to carcinogens or errors made by cells when they divide or replicate. Research has shown that patients with hereditary pancreatitis (not to be confused with chronic pancreatitis of common etiology) have a 40 percent increased risk of developing pancreatic cancer. Most research indicates that pancreatic cancer risk involves patients with a paternal inheritance pattern of disease (hereditary pancreatitis), while some research reports evidence of a maternal inheritance pattern. In addition, mutations of BRCA1, a gene known to suppress tumors, have been associated with increased risk of developing pancreatic cancer. Breast cancer is not inherited; rather, it is caused by somatic (environmental) mutations in breast cells during one’s life. BRCA2, another gene known to suppress tumors, has been linked with an increased risk of breast can461
Family history and risk assessment cer, as well as with prostate and pancreatic cancers in men. A higher incidence of the skin cancer melanoma is also more common in individuals with BRCA2 mutations than those without. In addition to BRCA1 and BRCA2 genes, variations of which have been linked to some forms of breast cancer, presence of the following genes in an individual increases the risk of breast cancer by causing syndromes that also increase the risk of developing other types of cancer: CDH1, PTEN, STK11, and TP53. The presence of variations in the following genes has also been associated with breast cancer: AR, ATM, BARD1, BRIP1, CHEK2, DIRAS3, ERBB2, NBN, PALB2, RAD50, and RAD51. Although not all the evidence implicates variations in these genes as risk factors for developing breast cancer, the evidence is strongest for ATM and CHEK2. An accumulation of genetic mutations in genes responsible for cell growth, cell division, or repairing deoxyribonucleic acid (DNA) promotes cancercell proliferation resulting in tumor growth. Inherited patterns or cancer syndromes that increase risk of breast and ovarian cancer include breast-ovarian cancer syndrome, nonpolyposis colorectal cancer syndrome, Cowden syndrome, Peutz-Jegher syndrome, and Li-Fraumeni syndrome, and inherited mutations that increase the risk for other types of cancers. Some cancers follow established hereditary patterns such as autosomal dominant inheritance. An autosomal dominant inheritance pattern consists of one mutated copy of the particular gene in each cell transmitted by one affected parent, occurring in every generation of an affected family. The pedigree of a family affected by a hereditary cancer syndrome will indicate whether that cancer has been inherited as an autosomal dominant disorder—in which case as many as half of the offspring of each carrier may develop a cancer related to the inherited syndrome. Two cancers that follow this pattern are a hereditary form of breast-ovarian cancer syndrome and Lynch cancer family syndrome, which is characterized by increased incidence of cancer of the right colon and increased incidence of endometrial cancer and multiple primary malignant neoplasms. Another type of autosomal dominant hereditary pattern, hereditary nonpolyposis, is responsible for between 2 and 7 percent of all cases of colorectal cancer. Mutations in the genes (including MLH1, MSH2, MSH6, and PMS2) that are responsible for repairing errors made when cells are copied can lead to uncontrolled cell growth and possibly cancer. This condition also increases an individual’s risk for cancers of the stomach, small intestine, liver, gallbladder ducts, upper urinary tract, skin, brain, and prostate. Women who inherit this disorder are at greater risk for endometrial and ovarian cancers. 462
Salem Health: Cancer Several hereditary cancer syndromes have been identified for which there are effective diagnostic tests and options for managing the disease, including those for cancers of the breast, ovary, colon, and endometrium, to name a few. These hereditary syndromes include hereditary nonpolyposis colorectal cancer (HNPCC); familial adenomatous polyposis (FAP), an inherited colorectal cancer syndrome; hereditary breast and ovarian cancer (HBOC); and multiple endocrine neoplasia 2 (MEN 2) in conjunction with parathyroid hyperplasia, which has been linked to thyroid cancer. Individuals genetically tested and found to have any of these syndromes can discuss specific options for managing their susceptibility for cancer with a genetic counselor. Genetic screening and testing: Routine screening for most cancers in the general population is neither recommended nor effective in reducing mortality from cancer. Moreover, because incidence of cancer varies in mutation carriers by type of cancer, screening and genetic testing must be approached by the type of inherited cancer and its risk patterns. For example, only 10 to 15 percent of breast cancer cases are thought to be familial, with about onethird caused by an inherited genetic mutation in a BRCA1 or BRCA2 gene. Over a woman’s lifetime, the incidence of breast cancer in a mutation carrier may be more than 50 percent, and an inherited BRCA1 mutation is also associated with increased risk of ovarian cancer. It is therefore recommended that only affected relatives with a family history of an inherited gene mutation BRCA1 or BRCA2 be screened. It should be noted that estimates of how many women with an altered gene will develop breast cancer range from 36 to 85 percent, and estimates of how many women with one of these altered genes will develop ovarian cancer range from 16 to 60 percent. Most research related to BRCA1 and BRCA2 has been done with large families and many affected individuals. Some of the incidence in these affected individuals may be due to other genetic as well as environmental factors; thus, risk estimates may not accurately reflect the risk in the general population of women, or in any individual woman. It must be emphasized, therefore, that genetic screening and testing is primarily for individuals to ascertain their inherited risk of developing cancer. Genetic testing can be used to determine who can benefit from regular, comprehensive cancer screenings, procedures to reduce the risk of acquiring the cancer, lifestyle and behavioral changes, medication, or prophylactic surgery. Genetic counseling: For those individuals who do have a significant inherited risk for cancer, the health professional performing genetic counseling will ask the client
Salem Health: Cancer to gather a family medical history and map a pedigree or family tree to illustrate the family history of the cancer. A variety of health professionals may perform genetic counseling and testing, including genetic counselors, nurses with advanced training and practice, psychologists, social workers, and physicians. The client begins the family-risk-assessment process by talking to relatives, obtaining medical records of relatives, and noting any medical conditions that have occurred in the family and at what ages. It is recommended that the client chart a separate tree for each side of the family, maternal and paternal, recording the country of birth and ethnicity as well. For example, certain breast cancer genes have been associated with Ashkenazi East European descent. The National Society of Genetic Counselors (NSGC) recommends initially talking to first-order relatives (parents and siblings), then contacting second-order relatives going back one generation at a time, collating birth, marriage, and death certificates to form the chart or family tree and document a pedigree. A genetic counselor will often prefer a pedigree with three generations of family history. Some of the facts to include in constructing a pedigree are the name of each relative, age at death and cause of death if deceased, medical conditions and ages when these conditions were acquired, birth defects, fertility problems, learning challenges, and lifestyle patterns (exercise, smoking, drinking, addictions, obesity, and so on). Gathering information on lifestyle behaviors of affected family members is critical; apart from genes, families share lifestyles and environments that may contribute to increased risk of cancer and other disease conditions by altering genes. All this information is useful to the client personally, and it can also help identify inheritance patterns of disorders that may place offspring at risk. After constructing the pedigree, the client will submit it to the counselor, who will thoroughly review the client’s personal, medical, and family history and evaluate the results. The client will meet with the counselor to hear the evaluation, discuss how the results relate to individual risk, and develop a personal prevention program. For example, the counselor will discuss hereditary cancer syndromes and what to look for to see if any syndromes are also present in family members. If the results of the pedigree indicate the utility of genetic testing and the client wishes to go forward, the client will be asked to complete an informed consent form. The form will describe the benefits and limitations of testing for genetic susceptibility, as well as the particular policies and financial procedures associated with the site where the testing will be performed. There are myriad tests for various hereditary cancers; DNA sequencing is the most sensi-
Family history and risk assessment tive and reliable method used to test for a hereditary cancer syndrome. Once the lab informs the physician of the test results, the client will meet with the health professional performing the counseling for disclosure of the test results. These results will be discussed within the context of the family’s history so that risks can be communicated effectively. The counselor will also advise the client on any need to notify family members of a hereditary genetic mutation associated with an elevated risk for cancer. This is the time for the client to discuss perceived and real risks of cancer, emotional issues surrounding cancer, support systems, coping skills, and decision making. Pros and cons of genetic testing: Most cancer is not due to the inheritance of a single genetic mutation. Sporadic cancers—those not due to a known, specific hereditary pattern—comprise the majority, 90 percent of all cancers diagnosed. Nevertheless, those with a hereditary inheritance pattern of a cancer are better positioned to adopt riskreducing behaviors if they know they are at higher risk for certain types of cancer than others in the general population. Moreover, individuals who learn of their risk and begin risk-reduction behaviors at an early age may be able to reduce the risk of passing the mutation to offspring. There are tremendous psychological effects and social costs for an individual who learns of his or her hereditary risk of developing cancer. A risk of family cancer can alter one’s lifestyle, inform family planning, or encourage family members to be tested. Those who are found not to have a hereditary risk may be relieved but may nonetheless be motivated to make healthy lifestyle changes. Specific interventions and potentially life-saving management options are available to individuals found to be at elevated risk of cancer following a genetic screening test. Some of these options include tamoxifen, a chemotherapy for breast cancer; colonoscopy to detect early colon cancer; and removal of ovaries and Fallopian tubes. Some studies have found that prophylactic hysterectomy with bilateral salpingo-oophrectomy (removal of the ovaries and Fallopian tubes) is an effective strategy for preventing endometrial and ovarian cancer in women with Lynch syndrome. Women with a BRCA genetic mutation who have had their ovaries removed reduce their risk of breast cancer by 50 percent or more. Studies have shown that women at increased risk of breast cancer are less likely to develop the cancer if they take tamoxifen, a treatment for advanced breast cancer. For those at greatest risk of developing breast cancer, prophylactic bilateral mastectomy has been shown to greatly reduce (but not eliminate) the risk of developing breast cancer. While genetic tests for cancer risk provide valuable in463
Fanconi anemia formation to the patient and the physician, they are also fraught with controversy. Genetic tests may show increased risk, but they cannot determine degrees of risk or what actual risk an individual will have of developing cancer. A physician must evaluate the benefits and limitations of information on familial risk when deciding who to refer for genetic counseling and testing. The American Cancer Society and other organizations publish guidelines available online; these identify current clinical recommendations, promulgated by the U.S. Department of Health and Human Services, for who should be screened and tested for different types of cancers. Susan H. Peterman, M.P.H. u For Further Information Foulkes, William D., and Shirley V. Hodgson, eds. Inherited Susceptibility to Cancer: Clinical, Predictive, and Ethical Perspectives. New York: Cambridge University Press, 1998. Frank, Thomas S., and Mark H. Skolnick. “Testing for Hereditary Cancer Risk: Pandora or Prometheus?” Journal of Clinical Endocrinology and Metabolism 84, no. 6 (1999): 1882-1885. Hass, Jennifer S., et al. “Do Physicians Tailor Their Recommendations for Breast Cancer Risk Reduction Based on Patient’s Risk?” Journal of General Internal Medicine 19, no. 4 (2004): 302-309. Morrison, Patrick J., Shirley V. Hodgson, and Neva E. Haites, eds. Familial Breast and Ovarian Cancer: Genetics, Screening, and Management. New York: Cambridge University Press, 2002. Schmeler, Kathleen, et al. “Prophylactic Surgery to Reduce the Risk of Gynecological Cancers in the Lynch Syndrome.” New England Journal of Medicine 354 (January 19, 2006): 261-269. U.S. Preventive Services Task Force. “Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility: Recommendation Statement.” Annals of Internal Medicine 143 (2005): 355-361. Utsunomiya, Joji, John J. Mulvihill, and Walter Weber, eds. Familial Cancer and Prevention: Molecular Epidemiology, a New Strategy Toward Cancer Control. New York: Wiley-Liss, 1999. u
Other Resources
American Medical Association Family History http://www.ama-assn.org/ama/pub/category/ 2380.html 464
Salem Health: Cancer National Institutes of Health Genetics Home Reference http://ghr.nlm.nih.gov U.S. Department of Health and Human Services U.S. Surgeon General’s Family History Initiative http://www.hhs.gov/familyhistory See also African Americans and cancer; Africans and cancer; Ashkenazi Jews and cancer; Asian Americans and cancer; Cancer clusters; Childhood cancers; Chromosomes and cancer; Cytogenetics; Gene therapy; Genetic counseling; Genetic testing; Genetics of cancer; Hereditary cancer syndromes; Hereditary diffuse gastric cancer; Hereditary leiomyomatosis and renal cell cancer (HLRCC); Hereditary mixed polyposis syndrome; Hereditary non-VHL clear cell renal cell carcinomas; Hereditary pancreatitis; Hereditary papillary renal cell carcinomas; Hereditary polyposis syndromes; Latinos/Hispanics and cancer; Mitochondrial DNA mutations; Native North Americans and cancer; Oncogenes; Proto-oncogenes and carcinogenesis; Risks for cancer; Young adult cancers.
u Fanconi anemia Category: Diseases, symptoms, and conditions Also known as: Fanconi’s anemia, FA, aplastic anemia with congenital abnormalities Related conditions: Leukemia, liver tumors, brain tumors, and cancers of the head, neck, esophagus, and female reproductive system Definition: Fanconi anemia is a rare inherited disease that affects bone marrow, resulting in reduced blood cell production. It is not the same as Fanconi syndrome, which is a rare kidney disorder. Bone marrow is the central part of the bones in which blood cells are produced. Red blood cells transport oxygen to the cells, white blood cells protect the body against infection, and platelets cause wounds to clot. Damage to the bone marrow decreases the production of all these types of blood cells. Having this condition predisposes people to developing several kinds of cancers, including acute myelocytic leukemia (AML) and squamous cell carcinoma. These cancers will arise in a person with Fanconi anemia at a much earlier age than the cancers would normally occur. Risk factors: Fanconi anemia is a recessive inherited disease, which means that both parents must have the disease genes for their children to develop it. Each child who has
Salem Health: Cancer two parents with the disease genes will have a 25 percent chance of developing the condition. Etiology and the disease process: Fanconi anemia is an inherited disease that stems from changes, called mutations, in genes. Genes hold the instructions for cells to make different proteins, which carry out various functions throughout the body. In people with Fanconi anemia, defective genes prevent the production of proteins that are needed for cells to work normally. Incidence: Although the exact number of people with Fanconi anemia is unknown, it is estimated that between 1 in 100 and 1 in 600 people carry the genetic defect responsible for the condition. Approximately 1 in 360,000 people are born with the disease. The symptoms of Fanconi anemia most often emerge when a child is between the ages of three and twelve, although symptoms can stay dormant until later in life. The disease occurs equally in both genders and among all races; however, there is a higher risk among people of Ashkenazi Jewish descent. Between 18 and 20 percent of people with Fanconi anemia develop leukemia. Symptoms: Because the disease results in fewer white blood cells, it leaves a person more susceptible to infections. A lower red blood cell count leads to fatigue, and the reduction in platelets can interfere with normal blood clotting. The first signs of the disease are often nosebleeds or bruising. People who have Fanconi anemia may have stunted growth; misshapen, missing, or extra thumbs; abnormal arm, hip, spine, or rib bones; a small head or eyes; kidney problems; an abnormal stomach, esophagus, or intestinal tract; mental retardation; and learning disabilities. Patches of unevenly colored skin (café-au-lait spots) are also common. Men may have smaller than normal genitals. People with Fanconi anemia are more likely to develop leukemia, as well as cancers of the head, neck, and esophagus. Women with the disease are at greater risk for cancers of the reproductive tract. Screening and diagnosis: The primary test for Fanconi anemia is a chromosome breakage test, which mixes the patient’s white blood cells with special chemicals to see whether the chromosomes break more easily than they should. Doctors can also diagnose the disease by removing a sample of bone marrow with a needle through a procedure known as bone marrow aspiration and examining that sample under a microscope to look for signs of low blood cell production. Another method is a bone marrow biopsy, in which a small needle inserted into the bone removes a piece of bone marrow for testing. Often patients will also
Fanconi anemia have a complete blood count to look for low numbers of white blood cells, red blood cells, and platelets. Other screening methods include developmental tests and a kidney ultrasound. If there is a family history of Fanconi anemia, the condition can be diagnosed before a child is born using amniocentesis and chorionic villus sampling (CVS). Treatment and therapy: A bone marrow transplant can treat blood cell problems, although it cannot reduce the risk of developing cancer or other problems (such as bone malformations) associated with Fanconi anemia. The bone marrow transplant is most likely to be successful if taken from a matched sibling. Patients may take artificial versions of male hormones called androgens, which improve red blood cell counts and may also help improve white blood cell counts in certain patients. Taking hemopoietic growth factors, such as erythropoietin, also can increase blood counts, as can having a blood transfusion. Researchers are looking into whether gene therapy to correct the genetic mutation might one day benefit patients with Fanconi anemia. Prognosis, prevention, and outcomes: Because this is an inherited disorder, there is no way to prevent it, although it is possible to screen a fetus for the disease while still in the womb. The average life expectancy for someone with Fanconi anemia is age twenty-two, although survival can vary from one person to another. New research and improved bone marrow transplantation outcomes are prolonging the life spans of many individuals with this disease. Stephanie Watson, B.S. u
For Further Information Frohnmayer, Lynn. Fanconi Anemia: A Handbook for Families and Their Physicians. Eugene, Oreg.: Fanconi Anemia Research Fund, 2000. Schindler, D., and H. Hoehn. Fanconi Anemia: A Paradigmatic Disease for the Understanding of Cancer and Aging. Basel, Switzerland: S. Karger, 2007. Shamin, Ahmad, and Sandra H. Kirk, eds. Molecular Mechanisms of Fanconi Anemia. New York: Springer, 2006.
u
Other Resources
Fanconi Anemia Research Fund http://www.fanconi.org MedlinePlus Fanconi’s Anemia http://www.nlm.nih.gov/medlineplus/ency/article/ 000334.htm 465
Fatigue See also Acute lymphocytic leukemia (ALL); Acute myelocytic leukemia (AML); Anemia; Aplastic anemia; Blood cancers; Genetics of cancer; Myelodysplastic syndromes; Nijmegen breakage syndrome; Urinalysis.
u Fatigue Category: Diseases, symptoms, and conditions Also known as: Asthenia, tiredness, exhaustion, lack of energy Related conditions: Anemia
Salem Health: Cancer Medication used as supportive care (for example, to treat depression or vomiting) can cause fatigue. Another cause of fatigue is lack of sleep, which may be caused by pain, emotional issues, depression, and anxiety. Poor nutrition, caused by lack of interest in food or an inability to eat because of mucositis, diarrhea, nausea, or vomiting, has been implicated in fatigue. Surgery for cancer may be the cause of fatigue, which often lessens as the patient recuperates and heals. One way that cancer can cause fatigue is by spreading to bone marrow, where it destroys red blood cell production and leads to anemia, the most commonly reported cause of fatigue. Both chemotherapy and radiation therapy can destroy bone marrow and cause anemia.
Definition: Fatigue describes a condition of tiredness that has many interrelated physical and emotional factors and impairs a patient’s feeling of well-being. Fatigue related to cancer or cancer treatment is a persistent sense of tiredness that can cause distress and depression and affect a patient’s ability to continue normal daily aspects of living. While patients with cancer may have fatigue as a chronic condition, this fatigue is not the same as “chronic fatigue syndrome.” Cancer-related fatigue differs from the fatigue of overwork or excessive exercise as it is not relieved by sleep or rest. It should be noted, however, that each patient is unique and that some cancer patients do not report cancer-related fatigue; other patients report having only mild to moderate cancer-related fatigue for a short period of time.
Incidence: Depending on the type of cancer and its treatment, approximately 15 to 95 percent of patients with cancer report feeling mentally and physically fatigued.
Risk factors: In the setting of cancer, fatigue may be caused by the type of cancer and its stage, chemotherapy or radiation therapy, stress, anemia, depression, chronic pain, lack of sleep, lack of proper nutrition, nausea and vomiting, infections, dehydration and electrolyte imbalance, and weight loss.
Screening and diagnosis: Because of the complex nature of cancer-related fatigue and its many presumptive causes, it is necessary to carefully rule out causes before effective treatment can occur. It is imperative to understand the pattern of fatigue, including when it started, how long it lasted, and how it changed the patient’s daily activity pattern. If fatigue was reported only after radiation therapy, for example, depression and other medications could be ruled out as the cause. The kind of cancer and its stage is important to know, as are known treatment-related symptoms. The side effects of chemotherapeutic agents or other medications may be instructive in determining the cause of fatigue. The health care provider should understand the patient’s sleep patterns before starting treatment for cancer as well as during treatment for cancer. It is important to know if the patient’s eating habits have changed. Patients should be screened for depression, as this is a common cause of fatigue. Patients may be depressed because of their cancer or because they fear losing their jobs, are having financial difficulties, or are upset about their inability to perform their normal daily activities. Anemia, which is a common cause of fatigue, can be
Etiology and the disease process: The causes of fatigue in patients with cancer are not clearly understood and appear to be multiple. Fatigue can be one of the first symptoms of the presence of cancer and can also be an indication of disease progression. The disease of cancer itself can cause fatigue, primarily through the release of cytokines, which are thought to induce fatigue, the increased need of cancer cells to maintain their high rate of metabolism, and the alteration of hormone levels. The stress of having cancer also can be the cause of fatigue. Treatments can lead to fatigue as the body tries to deal with the insult of cytotoxins or radiation and tries to rebuild cells after treatment. Many biological therapies (those that attempt to strengthen the patient’s immune system to fight cancer) have flulike symptoms, including fatigue, as side effects. 466
Symptoms: Fatigue is manifested by extreme tiredness and inability to perform normal daily functions. Fatigue can then lead to other symptoms, such as depression or poor nutrition (if the patient is unable to shop for groceries or cook). Because of the nature of cancer-related fatigue and its interactions with risk factors and other conditions, it is difficult to pinpoint a single symptom. Common symptoms, however, can include dizziness, confusion, inability to think clearly, loss of balance, being bedridden for more than one day, and worsening conditions (for example, increased vomiting, pain, or depression).
Salem Health: Cancer determined through blood tests. Depression scores can be determined through the use of various screens. No staging is available, however, for grading cancer-related fatigue. Treatment and therapy: To be treated properly, the source of fatigue—whether is it physical, emotional, or psychological—must be determined. Because anemia is the most common cause of fatigue, blood tests generally are done to check for low red blood cell counts, low hemoglobin concentration, or both. Anemia can be corrected by blood transfusions or by administration of an erythropoiesisstimulating protein, such as epoetin alfa. Fatigue due to lack of sleep, depression, or poor nutrition generally can be helped by administration of supportive care, such as drugs, or correction of an underlying cause, such as the inability to shop for and prepare food. Patients may be able to help themselves by being aware of what causes their fatigue. It may be important to schedule regular naps or limit the number of visitors. It is important to save energy for important tasks and to ask for help with other tasks. Energy levels may be maintained by scheduling regular eating times, including healthy snacks, limiting caffeine and alcohol, and drinking increased amounts of fluids. Some patients report that mild to moderate exercise also helps fight cancer-related fatigue, allows for a better frame of mind, and increases the ability to sleep at night. Exercise can include aerobic or resistance training. Relief of cancer-related fatigue may also come from practicing yoga or meditation. Research suggests that psychosocial interventions, such as group or individual therapy, education, stress management, or support groups, also have a positive effect on cancer-related fatigue. Prognosis, prevention, and outcomes: Because cancerrelated fatigue is often caused by many overlapping factors, it is difficult to predict which patients will be most affected. Fatigue may subside once treatments are completed and the patient’s bone marrow has recovered. Fatigue may increase as the cancer stage progresses and the cancer spreads in the body. MaryAnn Foote, M.S., Ph.D. u
For Further Information Hofman, Maarten, et al. “Cancer-Related Fatigue: The Scale of the Problem.” The Oncologist 12 (May, 2007): 4-10. Morrow, G. R. “Cancer-Related Fatigue: Causes, Consequences, and Management.” The Oncologist 12 (May, 2007): 1-3. Ryan, J. L., et al. “Mechanisms of Cancer-Related Fatigue.” The Oncologist 12 (May, 2007): 22-34.
Fecal occult blood test (FOBT) u
Other Resources
American Cancer Society Exercise to Keep Active Http://www.cancer.org/docroot/MIT/MIT_2_ 1x_ExerciseToStayActive.asp Anemia.com http://www.anemia.com MedlinePlus Anemia http://www.nlm.nih.gov/medlineplus/anemia.html National Cancer Institute Fatigue http://www.cancer.gov./cancerinfo/pdq/ supportivecare/fatigue/Patient/page2 See also Aids and devices for cancer patients; Anxiety; Chemotherapy; Home health services; Hospice care; Living with cancer; Palliative treatment; Psychosocial aspects of cancer; Radiation therapies; Relationships; Side effects; Stress management; Support groups; Symptoms and cancer.
u Fecal occult blood test (FOBT) Category: Procedures Also known as: Stool occult blood, guaiac smear test Definition: A fecal occult blood test (FOBT) is a simple chemical test on stool (feces) that detects the iron-containing components of hidden or trace amounts of blood. It tests for digestive tract bleeding, a possible indicator of colorectal cancer. Cancers diagnosed: Colon (large intestine) cancer, rectal cancer, gastric (stomach) cancer Why performed: Sometimes hidden blood in the stool is the only sign of cancer in its early stages, before symptoms appear. As a result, the FOBT is most frequently used as a colorectal cancer screening test. Benign (noncancerous) and malignant (cancerous) polyps, tumors, and other tissues that protrude into the intestine can bleed intermittently. The FOBT can detect this abnormal bleeding. It does not diagnose disease. It screens for bleeding that may be caused by gastrointestinal cancer. Other maladies cause blood loss in the digestive tract and anemia, a low red blood cell count. Therefore, the FOBT is sometimes used to determine the cause of unexplained anemia. It is also used to find the cause of abdominal pain. 467
Fecal occult blood test (FOBT)
Salem Health: Cancer with the test by producing misleading results. They should avoid the following foods for two to three days before the test to prevent false positive results: red meats such as beef, cold cuts, lamb, liver, and processed meats; fish; fruits such as apples, oranges, bananas, grapefruit, grapes, lemons, and melons; poultry; and vegetables such as beets, broccoli, cabbage, carrots, cauliflower, cucumbers, horseradish, mushrooms, radishes, and turnips. Patients should stop taking the following medications for seven days before the test to prevent false positive results: aspirin and products that contain aspirin; other nonsteriodal anti-inflammatory drugs (NSAIDS), such as ibuprofen and naproxen; colchicine gout drugs; corticosteroids; oxidizing drugs, such as iodine, bromides, and boric acid; and reserpine. Patients should stop taking dietary iron supplements for seven days before the test to prevent false positive results and should take no more than 250 milligrams of vitamin C per day to prevent false negative results.
A fecal occult blood test can detect blood in the feces, an early sign of cancer. (©IMANE/Image Point FR/Corbis)
Normally, a small amount of blood, a quarter of a teaspoonful or less, leaves digestive tract blood vessels daily and moves into the stool. The FOBT does not react to this small amount of blood. A daily blood loss of at least ten milliliters, or two teaspoonfuls, is required to produce a positive test. Patient preparation: People who prepare for the FOBT pay attention to their health conditions. They avoid the FOBT when their other situations cause digestive or urinary bleeding, which can produce false positive results. Interfering conditions include anal fissures, gum bleeding after dental procedures, colitis, constipation, diverticulitis, esophagitis, gastroesophageal reflux disease (GERD), gastritis, hemorrhoids, inflammatory bowel disease, menstrual periods, nosebleeds, peptic ulcers, severe throat irritation, and urinary tract infections. Before FOBT testing, patients restrict certain food, medications, and dietary supplements that can interfere 468
Steps of the procedure: Medical facility personnel perform FOBT tests, and patients can do their own testing at home. The manufacturer’s instructions must be followed to ensure accurate testing. A small sample of stool is placed onto a chemically treated test card, pad, or wipe. A chemical solution is added to the sample. The appearance of a blue color indicates a positive result—blood in the stool sample. Absence of blue color indicates a negative result—no blood in the stool sample. In one commonly used test, three stool samples are collected on three-part cards over three days, to better detect intermittent bleeding. The collection cards, pads, or wipes must be protected from heat, light, and chemicals during the collection period. The American Cancer Society and other medical organizations recommend an annual screening FOBT for all adults beginning at age fifty. They also recommend that others have the test as needed because of personal or family histories of intestinal polyps or colorectal cancer. These organizations emphasize that negative FOBT tests do not replace regular medical checkups, and they recommend regular medical examinations for everyone. In 2001, immunochemical fecal occult blood test (iFOBTs) became available for detecting blood in the stool. They test for a globelike protein component of blood instead of the iron-containing component detected in the traditional FOBT. They are sensitive and specific for digestive tract bleeding, and they avoid direct stool handling. These new tests have the advantage of eliminating the need to avoid foods, medications, and supplements before testing.
Salem Health: Cancer After the procedure: People who receive positive FOBT results have blood in the stool. They undergo specific follow-up testing, such as sigmoidoscopy, colonoscopy, computed tomography (CT) scans, and X rays, to determine the cause. People who receive negative FOBT results follow medical professionals recommendations for regular cancer screening. Risks: The FOBT is safe and painless and does not cause physical harm, but it is not a foolproof indicator of cancer. Digestive tract bleeding can be intermittent, and negative results can occur in people who have colorectal cancer. Results: A normal FOBT result is negative, which means that blood is not present in the tested stool sample. An abnormal test result is positive, which means that blood is present in the tested stool sample. Occult blood appears in the stool because of colorectal cancer or other medical conditions. It is important to determine the cause and source of bleeding to diagnose, treat, and resolve the situation. Susan E. Ullmann, M.T. (ASCP), M.A. u For Further Information Fishbach, Frances Talaska, with Marshall Barnett Dunning III. A Manual of Laboratory Diagnostic Testing. 7th ed. Philadelphia: Williams & Wilkins, 2004. Pagana, Kathleen Deska, and Timothy J. Pagana. Mosby’s Manual of Diagnostic Laboratory Tests. 3d ed. St. Louis: Mosby Elsevier, 2006. Segen, Joseph C., and Joseph Stauffer. The Patient’s Guide to Medical Tests. New York: Facts On File, 1997.
See also Anal cancer; Colon polyps; Colorectal cancer; Colorectal cancer screening; Diverticulosis and diverticulitis; Gastrointestinal cancers; Immunochemical fecal occult blood test (iFOBT); Polyps; Rectal cancer; Screening for cancer; Stomach cancers.
u Fertility drugs and cancer Category: Carcinogens and suspected carcinogens Definition: An association between the use of fertility drugs—clomiphene citrate, follicle-stimulating hormone (FSH), human menopausal gonadotropin (MG), and gonadotropin-releasing hormone analog (GnRH)—and ovarian cancer exists if there is a statistically significant increase in the risk of cancer during the lifetime of the user of fertility drugs. Although the major concern regarding fertility drugs and cancer since the 1990’s has focused on
Fertility drugs and cancer ovarian cancer, some experts have also suggested a possible relationship between fertility drugs and cancers of the breast and uterus. Because fertility drugs evoke changes in hormone levels, the potential risk should be extended to any cancer that can be triggered or modulated by hormones, as well as any indirect effects on the offspring of the user of fertility drugs. Fertility drugs and cancer: A woman’s risk of ovarian cancer is multifactorial; however, it is known that some factors increase the risk for ovarian cancer, while other factors decrease the risk. Specifically, ovarian cancer is known to increase with age, when there is a family history of ovarian cancer, and in women who have never had a child. In contrast, the risk of ovarian cancer is decreased in women who breast-feed, have at least one child, and use oral contraceptives. In considering these risk factors together, current scientific thinking is that ovarian cancer is related to the process of ovulation in most, if not all, cases. It has been suggested, but not proven, that ovarian cancer follows an abnormal repair process on the surface of the ovary following the release of the egg during ovulation. Thus, increasing the number of ovulations (incessant ovulation), either by having no interruption of ovulation due to pregnancy or by inducing ovulation with fertility drugs, would theoretically increase the risk of ovarian cancer. Conversely, inhibiting ovulation vis-à-vis pregnancy or pregnancies, breast-feeding, or through the use of oral contraceptives, would theoretically decrease the risk of ovarian cancer by decreasing the lifetime number of ovulations. In determining the risk of fertility drugs and ovarian cancer, it is important to take into consideration confounding factors. Although some epidemiologic studies have indeed shown an increased risk of ovarian cancer in women who have used fertility drugs, when all factors are accounted for statistically, it has been concluded that it is actually infertility, rather than the fertility drugs, that has led to an increased risk of ovarian cancer. For example, in one study involving more than twelve thousand women who were followed for an average of nearly twenty years, it was found that the risk of ovarian cancer was increased twofold because of infertility alone, and there was no statistical risk of ovarian cancer due to just the fertility drugs. Because the peak onset of ovarian cancer occurs during the seventh decade of life, it will be important to continue such studies longitudinally to verify this finding. It is noteworthy, though, that an association has been demonstrated between the use of clomiphene citrate and cancer of the uterus. Given that clomiphene citrate is chemically similar to tamoxifen (a drug routinely used to 469
Fertility drugs and cancer
Salem Health: Cancer
Common Fertility Drugs Drug Name
Brand Names
Clomiphene citrate
Clomid Serophene Milophene
Human chorionic gonadotropin (HCG) Pregnyl Menotropin
Pergonal Humegon
Urofollitropin
Metrodin
Urofollitropin (highly purified)
Fertinex
Source: U.S. Food and Drug Administration
treat patients with breast cancer after surgery), which is known to be associated with cancer of the uterus, further studies are needed to verify this association. Ovarian cancer: Approximately 25,000 women are diagnosed with ovarian cancer each year in the United States. The current lifetime incidence of ovarian cancer for any given woman is approximately 1 in 70. Unfortunately, the symptoms of ovarian cancer in its early stages are minimal to none. In advanced cases, most women with ovarian cancer complain of abdominal pain, vaginal bleeding, abdominal bloating and distension, or a change in bowel habits. There is no accepted screening protocol for ovarian cancer, unlike cervical cancer (which can be detected by a Pap smear) or breast cancer (which can be found by selfexam, a clinical breast exam, and mammography). It is recommended by the American College of Obstetricians and Gynecologists that all women have a manual pelvic examination as part of their annual well-woman examination. During the manual pelvic examination, the examiner palpates (feels) the ovaries. Although not recommended for women at low risk for ovarian cancer, for those at high risk, a blood test (cancer antigen 125, or CA 125) and a vaginal ultrasound in which the ovarian volume is determined may be beneficial. The standard treatment for ovarian cancer is surgical, in the form of a total abdominal hysterectomy and removal of both ovaries with postoperative chemotherapy. The five-year survival rate for patients with ovarian cancer is 50 percent, depending on the stage at the time of diagnosis and the treatment rendered. The risk of ovarian cancer can
470
be reduced by breast-feeding, using oral contraceptives, and undergoing a tubal ligation, although the mechanism of protection for the latter is unclear. For women who are prescribed fertility drugs, when used as prescribed for less than twelve cycles with monitoring by a specially trained physician (reproductive endocrinologist), there are no convincing scientific studies that have shown an increased risk for ovarian cancer. D. Scott Cunningham, M.D., Ph.D. u
For Further Information Althuis, M. D. “Uterine Cancer After Use of Clomiphene Citrate to Induce Ovulation.” American Journal of Epidemiology 161 (2005): 607-615. Ayhan, A. “Association Between Fertility Drugs and Gynecologic Cancers, Breast Cancer, and Childhood Cancers.” Acta Obstetricia et Gynecologica Scandinovica 83 (2004): 1104-1111. Brinton, L. “Long-Term Effects of Ovulation-Stimulating Drugs on Cancer Risk.” Reproductive BioMedicine Online 15 (2007): 38-44. Brinton, L. A., et al. “Ovarian Cancer Risk After the Use of Ovulation-Stimulating Drugs.” Obstetrics and Gynecology 103 (2004): 1194-1203. Venn, A., D. Healy, and R. McLachlan. “Cancer Risk Associated with a Diagnosis of Infertility.” Best Practice and Research Clinical Obstetrics and Gynaecology 17 (2003): 343-367. u
Other Resources
National Cancer Institute Ovarian Cancer Prevention http://www.cancer.gov/cancertopics/pdq/prevention/ ovarian/healthprofessional Ovarian Cancer National Alliance Q: Do Fertility Drugs Increase Your Risk of Developing Ovarian Cancer? Http://www.ovariancancer.org/index.cfm? Fuseaction=Feature.showFeature&CategoryID= 6&FeatureID=124 See also Childbirth and cancer; Estrogen-receptor-sensitive breast cancer; Fertility issues; Gynecologic cancers; Hormone receptor tests; Hormone replacement therapy (HRT); Infertility and cancer; Ovarian cancers; Ovarian cysts; Pregnancy and cancer; Sterility.
Salem Health: Cancer
u Fertility issues Category: Social and personal issues Definition: Some cancers and cancer treatments pose a risk to a cancer survivor’s fertility. Infertility or sterility can be temporary or permanent. Although in many cases there are few options to address the underlying causes of infertility, patients may be able to preserve their fertility before undergoing cancer treatment and conceive a child after treatment naturally or through the use of assisted reproductive technologies. Infertility and cancer: For natural conception to occur, men must have at least one testicle that produces enough healthy sperm, the hormones to regulate sperm production, the ability to make semen, and the ability to ejaculate the semen. Women need at least one ovary that makes mature and viable eggs, a Fallopian tube through which the egg can move and be fertilized, a uterus capable of maintaining a pregnancy, and the hormones necessary for ovulation and pregnancy. Chemotherapy and radiation in the course of cancer treatments can damage or kill cells required for production of sperm (sperm stem cells) and immature eggs (oocytes) or mature eggs. These treatments can also affect the production and regulation of hormones required for reproduction. Male and female reproductive structures can be damaged by radiation or removed or damaged by surgery. Fertility preservation: Infertility can cause a great deal of psychological distress for cancer survivors. It is advised that cancer patients discuss fertility issues with their oncologists and consult a fertility specialist before treatment. Specialists can inform patients of their risk, if known, of becoming infertile after treatment. In some cases, there are fertility preservation methods that can be undertaken before or during treatment. Patients must weigh the costs and benefits as some preservation methods may alter the efficacy of the cancer treatment, especially if the cancer is hormonally sensitive or affects the reproductive organs. Another possibility in some cases is delaying cancer treatments to pursue fertility preservation. Ferility preservation procedures, including long-term storage of sperm, can be expensive. Assisted reproductive technologies can assist in conception after treatment, but not all patients will want to pursue them or be able to pay for them. Fertility preservation before puberty: Many parents are concerned about protecting a prepubescent child’s fertility from the effects of cancer treatment. Treatments can pre-
Fertility issues vent, delay, or accelerate puberty. The effects on fertility may be permanent or may not be evident until later in life, when they can shorten a person’s reproductive years. Unfortunately, preserving fertility in a child can be a challenge. Fertility-sparing treatment methods that protect reproductive organs from radiation or conservative surgery on reproductive structures may prevent damage to a child’s reproductive systems. Because prepubescent boys and girls cannot make mature sperm or eggs, respectively, researchers are investigating whether testicular or ovarian function can be restored by transplanting back testicular or ovarian tissue that was collected and frozen before treatment. Parenthood for cancer survivors: Cancer survivors confront many issues when considering parenthood after treatment. Oncologists typically advise waiting two to five years after treatment before trying to conceive naturally or through assisted reproduction technologies. Fertility may improve over time as damage to sperm or eggs is naturally repaired. Some cancer treatments also damage the heart and lungs, which can complicate a pregnancy; therefore, women may benefit from waiting. Oncologists also recommend waiting to see if the cancer returns. The likelihood of reoccurrence affects a person’s decision to become a parent. When considering parenthood, many survivors have concerns about the possible impact of the cancer or cancer treatments on the health of a baby. Although it has not been studied extensively, the findings to date do not show any increase in birth defects in children born to cancer survivors. Some are also concerned about their children inheriting a so-called cancer gene or the genetic tendency to develop cancer. Genetic counselors may be able to estimate that risk. Survivors who are unable to conceive a child who is genetically related to both parents still have options for parenthood. A sperm donor can be used to fertilize a partner’s egg. Similarly, donated eggs can be fertilized by a partner’s sperm. In these cases, the child would be genetically related to one parent. Women whose eggs are unable to be fertilized may still be able to carry a pregnancy. These women can use donated embryos created through in vitro fertilization. Survivors may also consider adoption. Many adoption agencies require a letter from an oncologist that the prospective parent is cancer-free and is expected to have a normal lifespan and good quality of life. Some agencies require survivors to be cancer-free for a certain amount of time before being eligible for adoption. Amanda McQuade, Ph.D. 471
Fever u For Further Information Falker, E. S. The Ultimate Insider’s Guide to Adoption: Everything You Need to Know About Domestic and International Adoption. New York: Hachette USA, 2006. Lee, S. J., et al. “American Society of Clinical Oncology Recommendations on Fertility Preservation in Cancer Patients.” Journal of Clinical Oncology 24, no. 18 (2006): 2917-2931. Oktay, K. H., L. Beck, and J. D. Reinecke. One Hundred Questions and Answers About Cancer and Fertility. Sudbury, Mass.: Jones and Bartlett, 2008. u
Other Resources
American Academy of Adoption Attorneys http://adoptionattorneys.org/ Fertile Hope http://www.fertilehope.org International Council on Infertility Information Dissemination, Inc. http://www.inciid.org/ Lance Armstrong Foundation http://www.livestrong.org See also Childbirth and cancer; Fertility drugs and cancer; Gynecologic cancers; Hormonal therapies; Infertility and cancer; Ovarian cancers; Ovarian cysts; Pregnancy and cancer; Sterility.
u Fever Category: Diseases, symptoms, and conditions Also known as: Hyperpyrexia Related conditions: Infection and sepsis in cancer treatment, myelosuppression, neutropenia Definition: Fever is a pyrogen-mediated elevation of the core body temperature. This is in distinction to hyperthermia, which is an unregulated rise in core temperature as occurs in heat stroke. Pyrogens may originate outside the body (exogenous) or be produced within the body (endogenous). The exogenous pyrogens are typically microorganisms or their toxins and products but also include drugs, antigen-antibody complexes, and other substances. Endogenous pyrogens are various chemicals produced by host cells and are called cytokines. Risk factors: Fever may be caused by cancer. Although many types of malignant neoplasms may cause fever, 472
Salem Health: Cancer some of the most common are lymphomas, leukemias and preleukemias, and renal cell carcinoma. However, fever in cancer patients is more often a consequence of treatment than of the cancer. The protective barrier provided by the skin and mucous membranes may be breached by surgery or vascular catheter placement, providing entrance points for invading microbes, which produce infection and fever. A similar phenomenon may result from chemotherapeutic cancer drugs that destroy not only the cancer cells but also oral and mucous membrane lining cells, inducing mucositis. Drugs may also kill bone marrow cells (myelosuppression and neutropenia), which impairs bodily defense mechanisms against infectious agents. The vascular catheters used to administer drugs, intravenous fluids, and blood components are risks for infection, and the risk increases the longer the catheter is left in place. Administration of blood components can produce fever through a variety of mechanisms. The antibiotics used to treat infection, like many other drugs, may produce fever, complicating therapy. Some antibiotics, such as sulfonamides and chloramphenicol, can cause neutropenia and fever. Finally, antibiotics may alter the normal flora of the patient, allowing overgrowth of problem organisms. Fungi, such as those of the Candida species, may overgrow on the skin and in the gastrointestinal tract, causing infection. An anaerobic-toxin-producing bacterium called Clostridium difficile can overgrow in the colon, causing fever and diarrhea. Venous thrombosis can also cause fever. Some cancers, especially adenocarcinomas, are associated with a hypercoagulable state. Venous stasis may be a consequence of an obstructing tumor mass or lymphadenopathy, immobility (bedrest or surgery), and dehydration. Some antineoplastic drugs can result in endothelial injury. All these factors can contribute to the formation of fever-associated thrombi. Etiology and the disease process: Fever is a complex process and is not completely understood. The process is initiated by the production of endogenous pyrogens or cytokines. Cytokines are polypeptide proteins that are produced by host cells, probably mononuclear macrophages. Cytokines, including interleukin-1, tumor-necrosis factor, and interleukin-6, produce the rapid onset of fever by acting directly on the brain (hypothalamus). The release of cytokines is induced by the exogenous pyrogens or some endogenous molecules. Exogenous pyrogens are usually microbes and their products (including toxins). An example of an endogenous molecule would be a complement-binding antigen-antibody complex. Finally, the hypothalamus produces prostaglandin E2, which or-
Salem Health: Cancer chestrates physiologic changes that increase core temperature. Fever is an adaptive response that, for the most part, is beneficial. Increased temperature is associated with increased production of antibacterial substances (superoxides and interferon), increased neutrophil migration, and increased T-cell proliferation, all of which are beneficial in the fight against invading microbes. Nonetheless, fever is metabolically demanding, and prolonged fever can be deleterious to the patient. High fever can damage organs and contribute to circulatory collapse or failure. Incidence: The relationship between fever and cancer may be examined by looking first at fever in patients who are not diagnosed with cancer or any other causative disease process and second at fever in patients with a specific cancer that has already been diagnosed. In patients with an undiagnosed fever or fever of undetermined origin, an underlying malignancy has been found to be causative in 9 to 30 percent of patients. Lymphoreticular neoplasms, such as Hodgkin disease and nonHodgkin lymphoma, are the most common. The age of patients with fever of undetermined origin influences the percentage of neoplasms: Children tend to have fewer cancers and more infections, while elderly adults tend to have higher percentages of cancers. The incidence of fever in patients in whom cancer is already diagnosed varies widely, as it depends on many variables, including the type and severity of the cancer, treatments employed, and comorbid illnesses. Fever is a common problem in cancer patients. Symptoms: At the onset of a fever, body heat is conserved by vasoconstriction, and the patient initially feels cool, especially in the hands and feet. Shivering occurs when muscles act to produce heat. Finally, the patient feels warm as the higher setpoint for core temperature is reached. Sweating and vasodilatation (flushing) occur only with heat loss and the subsequent falling temperature. Screening and diagnosis: For patients with fever of undetermined origin, a detailed history and careful physical examination are important and can provide critical information. Sometimes fever patterns themselves can be revealing. A sudden onset of fever, particularly if preceded by rigors or chills, is indicative of bacteremia or fungemia. Pel-Epstein fever is associated with Hodgkin disease and is characterized by three to ten days of fever followed by three to ten days without a fever. An initial battery of laboratory and radiologic tests is followed by an ordering sequence of more tests depending on the results of previous
Fever tests. Ultimately, a biopsy of an abnormal mass, lymph node, or bone marrow is usually required for diagnosis of a specific cancer as a cause of a fever with an undetermined origin. Patients with previously diagnosed cancer present equally challenging problems in the determination of fever etiology. The most serious immediate issue is to determine if the patient has a life-threatening infection, and empiric antibiotic therapy is commonly administered as a safeguard. After a thorough history is taken and a physical examination is conducted, the patient will undergo screening blood and urine tests, radiologic studies, cultures of blood, and other tests to determine the possible sources of infection. If there are no indications of infection and empiric antibiotic therapy has no beneficial effect, then noninfectious causes must be sought. Drugs, venous thrombosis, and neoplastic fever are all possible. When other causes of fever have failed to be detected by any means and neoplastic fever appears likely, treating the patient with the nonsteroidal anti-inflammatory agent naproxen can aid in the diagnosis. Naproxen appears to have a unique ability to suppress tumor fever but not significantly effect fevers of nonneoplastic origin. Treatment and therapy: Antipyretic therapy is generally provided only when the patient is uncomfortable or the fever is causing problems such as cardiovascular failure due to fever-induced tachycardia. The fever is not routinely treated because it is a continuing clue to the underlying diagnosis; treatment of the cause of the fever leads to final resolution. Complicating infections are treated with antibiotics, and associated catheters and other foreign bodies are removed whenever possible. If infection is associated with neutropenia, granulocyte colony-stimulating factor is administered to restore the neutrophil numbers. Drugs are discontinued when necessary, and blood clots are removed or treated. Neoplastic fever can be treated with naproxen while the cancer is being removed or treated with other measures. Prognosis, prevention, and outcomes: The prognosis depends on many factors but is often related to the ability to successfully control infection in the cancer patient with fever. Correspondingly, unresolved immunosuppression or uncontrolled neoplastic growth can render infections difficult or impossible to resolve. For most patients, successful treatment can be accomplished once a specific etiology for the fever has been established. Prevention is mainly directed at infections complicating cancers and antineoplastic therapies. Careful manage473
Fiber
Salem Health: Cancer
ment of vascular catheters, minimization of immunosuppressive periods, and prophylactic antibiotics during critical times can all help prevent infections and fever. H. Bradford Hawley, M.D. u For Further Information Chang, Jae C., and H. Bradford Hawley. “Neutropenic Fever of Undetermined Origin (N-FUO): Why Not Use the Naproxen Test?” Cancer Investigation 13 (1995): 448-450. Cunha, Burke A., ed. “Fever.” Infectious Disease Clinics of North America 10 (1996): 1-222. Dinerello, Charles A., and Jeffrey A. Gelfand. “Fever and Hyperthermia.” In Harrison’s Principles of Internal Medicine, edited by Dennis L. Kasper et al. 16th ed. New York: McGraw-Hill, 2005. Mackowiak, Philip A., ed. Fever: Basic Mechanisms and Management. 2d ed. Philadelphia: Lippincott Williams & Wilkins, 1997. Murray, Henry W., ed. FUO: Fever of Undetermined Origin. New York: Futura, 1988. u
Other Resources
American Cancer Society Fever http://www.cancer.org/docroot/MBC/content/ MBC_2_3X_Fever.asp?sitearea=MBC National Cancer Institute Fever, Sweats, and Hot Flashes http://www.cancer.gov/cancertopics/pdq/ supportivecare/fever/Patient/page2
A diet rich in fiber from complex carbohydrates—grain, fruit, and vegetables—may reduce the risk of cancer. (U.S. Department of Agriculture)
See also Candidiasis; Coughing; Cytokines; Fatigue; Infection and sepsis; Mucositis; Myelosuppression; Nausea and vomiting; Neutropenia; Night sweats; Nonsteroidal anti-inflammatory drugs (NSAIDs); Pneumonia; Side effects; Symptoms and cancer; Tumor lysis syndrome.
Cancers treated or prevented: Colorectal cancers, spastic bowel syndrome
u Fiber Category: Lifestyle and prevention Definition: Fiber is a natural structural chemical component of plants responsible for strength and architectural form. Examples of plant fiber include cellulose, hemicellulose, pectins, and lignins. Most plant fiber is difficult to digest and absorb because it is chemically complex and insoluble. Dietary fiber functions to clean out the digestive tract and move waste quickly through the intestines. 474
Delivery routes: Fruits, vegetables, leafy greens, grains, or oral supplements as tablets or liquid form How this substance works: Fiber in diets helps maintain optimal movement of food and wastes through the lower human digestive tract. Fiber helps cleanse the intestinal tract and colon, preventing the formation of pockets of residue. There are two basic types of dietary fiber, insoluble fiber and soluble fiber. Water-soluble fiber absorbs water in the intestines and via enzymatic activity mixes food into a gel on which intestinal enzymes work. Conversely, insoluble fiber is the more valuable in reducing risk of cancer as it is considerably more difficult to digest; thus carcinogens and toxins in the food are not released in the presence of the metabolically active cells of the intestinal lining but rather pass harmlessly out of the body. It follows
Salem Health: Cancer that the less time carcinogens are in contact with the intestinal walls, the lower the risk of cancer should be because of decreased exposure to carcinogens carried in food and food wastes. Insoluble fiber is sometimes referred to as the “scrub brush” for the human internal digestive tract because it “scrubs” the intestines clean as it passes through the small intestine and colon. This type of fiber acts to absorb many times its own weight in water, which softens the waste in the intestine and facilitates motion through the body, thereby decreasing irritation, constipation, and blockage. Research has shown that fiber increases peristalsis, the involuntary muscular contractions of the digestive system. Regular and efficient peristalsis resulting from increased bulk in soft stools decreases the period of time that toxins are in contact with intestinal tissue. Fiber may also bind to carcinogens, lessening their proximity to internal cells. Water absorbed by fiber dilutes toxins, rendering them less harmful and decreasing the risk of cancer. Fiber can also help absorb intestinal acids such as bile, hydrochloric acid, and other irritants that may predispose cells to disease. Fiber can promote intestinal health by encouraging the growth of beneficial bacteria while discouraging the growth of harmful bacteria. A high-fiber diet may also reduce the incidence of diverticulosis and irritable bowel syndrome, both implicated in intestinal cancer. Human studies suggesting an inverse relationship between insoluble dietary fiber intake and colorectal cancer incidence remain inconclusive because of the complexity of the disease. Many other factors, including heredity and lifestyle, play a role in the appearance of disease. An overwhelming majority of the long-term cohort studies, however, have pointed to dietary fiber as a means of reducing the risk for colorectal cancer. Side effects: Some studies also show that excessive amounts of fiber may interfere with the absorption of certain minerals such as calcium, copper, iron, magnesium, selenium, and zinc. Excessive dietary fiber may also lead to constipation and occasional blockage. The frequency and intensity of both of these negative side affects can be reduced with the use of softening agents such as psyllium. Dwight G. Smith, Ph.D. See also Chemoprevention; Colonoscopy and virtual colonoscopy; Colorectal cancer; Cruciferous vegetables; Diarrhea; Diverticulosis and diverticulitis; Fruits; Gastrointestinal cancers; Gastrointestinal complications of cancer treatment; Hemorrhoids; Laxatives; Nutrition and cancer prevention; Nutrition and cancer treatment; Polyps; Premalignancies; Prevention; Risks for cancer; Stomach cancers.
Fibroadenomas
u Fibroadenomas Category: Diseases, symptoms, and conditions Also known as: Complex fibroadenomas, juvenile fibroadenomas, giant fibroadenomas Related conditions: Fibrocystic breast disease, cytosarcoma phyllodes, breast cysts Definition: Fibroadenomas are benign breast tumors that are characteristically smooth-surfaced, round or oval in shape, and freely movable on palpation (feeling with the fingers). They can range in size from 1 to 15 centimeters (cm). A fibroadenoma consists of homogeneous (closely related) fibrous tissue. In rare instances, a fibroadenoma can contain a breast cancer. This is more likely in a complex fibroadenoma. A complex fibroadenoma contains several specific tissue changes. They are sclerosing adenosis (hardening of glandular breast tissue) and apocrine metaplasia (conversion of milk-producing cells into an abnormal form). Although a fibroadenoma is not considered a precursor to breast cancer, it is thought that having a complex fibroadenoma slightly increases a woman’s risk of developing breast cancer in the future. Juvenile and giant fibroadenomas occur only in teenagers or young adults and can grow as large as 15 cm. Cytosarcoma phyllodes is a rare type of breast cancer that can occur within a fibroadenoma. Typically, this type of cancer does not spread beyond the breast tissue. Risk factors: Fibroadenomas require the presence of estrogen to develop and grow, so they occur between menarche and menopause. Generally, after menopause, an existing fibroadenoma will stop growing and may even disappear. If a woman takes estrogen after menopause, she can develop a fibroadenoma. Etiology and the disease process: A fibroadenoma arises from a single milk duct in the breast and is made up of both glandular (milk-producing cells) and epithelial cells (skin cells that line the duct). There is no fluid inside a fibroadenoma. It develops from an overgrowth of the affected breast tissue. The cause of the overgrowth of tissue is unknown, although estrogen is required for fibroadenoma development. Fibroadenomas generally stop growing at 2 to 3 cm, although they occasionally grow larger. They may also enlarge during pregnancy and at times of higher estrogen levels during the menstrual cycle. Immunosuppressive medications appear to have an effect on the growth and development of fibroadenomas. Studies have demonstrated that 50 percent of women who 475
Fibrocystic breast changes receive the immunosuppressive drug, cyclosporine, after a kidney transplant will develop one or more fibroadenomas. Incidence: The fibroadenoma is the most common type of benign breast tumor. In women over the age of forty, 8 to 10 percent will develop a fibroadenoma at some time during their lives. Roughly one-third of fibroadenomas are complex fibroadenomas. Symptoms: In women younger than age forty, fibroadenomas usually appear as palpable (can be felt) breast masses. After age forty, they may be discovered as a palpable breast mass, or they may appear on mammography as a breast mass that is not palpable. Fibroadenomas are not painful. Screening and diagnosis: Screening is not carried out specifically for fibroadenomas, but some are picked up while screening for breast cancer in women over the age of forty. Breast fibroadenomas may be diagnosed by breast self-examination if they are palpable, or by mammography. On a mammogram, a fibroadenoma appears as a dense area in the breast, and in women over age forty, it may have areas of calcification (mineral deposits). Since it is not possible to determine whether a breast density is a fibroadenoma or breast cancer on mammography, subsequently, a breast ultrasound is performed. On an ultrasound, a fibroadenoma looks like a clear area with defined edges, much as a breast cyst does. The only way to determine whether a density is, indeed, a fibroadenoma is to biopsy it. A biopsy may be performed using a fine needle, a core needle, or surgical incision. A pathologist examines the tissue under a microscope and decides whether it is cancer or a fibroadenoma. A cancer is present inside 3 percent of fibroadenomas. Typically, these fibroadenomas are larger than usual and have irregular margins that are less clearly defined. In 1 percent of cases, what appears to be a fibroadenoma is actually cytosarcoma phyllodes. Because a fibroadenoma is not cancer, there is no staging for it. If breast cancer is found within a fibroadenoma, it is staged as a breast cancer. Treatment and therapy: A fibroadenoma may be totally removed at the time of biopsy by surgical excision or core needle biopsy. If it is not removed, it will be monitored annually for growth and changes by mammography, magnetic resonance imaging (MRI), or ultrasound. Prognosis, prevention, and outcomes: Since fibroadenomas are benign tumors, the prognosis is excellent for women who develop them. There is a slight increase in the 476
Salem Health: Cancer risk of subsequently developing breast cancer. Before menopause, there is no way to prevent a fibroadenoma from developing. After menopause, a woman can prevent a fibroadenoma by avoiding any type of systemic estrogen therapy. Christine M. Carroll, R.N., B.S.N., M.B.A. u
For Further Information Chinyama, Catherine N. Benign Breast Disease: Radiology, Pathology, Risk Assessment. New York: Springer, 2004. Ganschow, Pamela, et al., eds. Breast Health and Common Breast Problems: A Practical Approach. Philadelphia: American College of Physicans, 2004. Love, Susan, and Karen Lindsey. Dr. Susan Love’s Breast Book. 5th ed. Cambridge, Mass.: Da Capo Press, 2005.
u
Resources
American Cancer Society http://www.cancer.org Imaginins.com http://www.imaginis.com WebMd Breast, Fibroadenoma http://www.emedicine.com/radio/topic109.htm See also Adenocarcinomas; Breast cancer in men; Breast cancer in pregnant women; Breast cancers; Breast ultrasound; Caffeine; Calcifications of the breast; Estrogenreceptor-sensitive breast cancer; Fibrocystic breast changes; Lumps; Phyllodes tumors.
u Fibrocystic breast changes Category: Diseases, symptoms, and conditions Also known as: Fibrocystic conditions of the breast Related conditions: Cysts, mastaglia, trigger-zone breast pain, fibroadenoma, fibrosis, hyperplasia Definition: Fibrocystic changes in the breast are benign (noncancerous) and related to normal hormonal fluctuations during a woman’s menstrual cycle. The word refers to thickening of tissue (fibro) and fluid-filled sacs (cysts) in the breast. The term loosely groups several different benign conditions, some of which can cause physical symptoms of discomfort or pain, known as mastaglia; other conditions may be visible on mammograms but not noticeable physically. In the past, the term “fibrocystic breast disease” was
Salem Health: Cancer used, a misleading label, given that the majority of women experience some breast changes or have mammograms that reveal them. Risk factors: Women in their childbearing years or postmenopausal women taking hormone replacement therapy may be prone to several types of fibrocystic changes. Because these changes are related to menstrual-cycle hormones, they usually cease after natural menopause. Etiology and the disease process: Fibrocystic breast changes are not a disease. They include several different categories of benign changes in breast tissue caused by the fluctuations of hormones during a woman’s menstrual cycle. Each month a woman’s body prepares for pregnancy, and hormones stimulate milk-producing cells, creating as much as three to six teaspoons of fluid within each breast, which is then reabsorbed if pregnancy does not occur. The fluid can collect in sacs and form cysts. Breast pain may be cyclical, appearing at the time of a woman’s ovulation or just before or during her menstrual period. Cyclical breast pain may be related to the presence of cysts and the pressure they cause. However, the number of cysts or the amount of lumpiness a woman has does not necessarily relate to the amount of pain she experiences. Cyclical pain is usually most intense at the beginning and the end of the childbearing years, in a woman’s teens and again in her forties. Pain also may be noncyclical, with no apparent pattern related to the menstrual schedule. Often it is in a specific area of the breast and is known as trigger-zone pain. It can be constant or intermittent. The reasons for noncyclical breast pain are unclear. For some women, old trauma, like a blow to the breast or a biopsy, is sometimes a cause of noncyclical pain. There is some evidence that for some women, different levels of the hormone progesterone or a sensitivity to hormones produced by the thyroid may be the cause of the pain. Other breast changes included under the term “fibrocystic changes” include fibrosis and hyperplasia. Fibrosis occurs in some women when the normal fatty tissue of the breast is replaced over time with fibrous tissue, which may feel firm or rubbery. Some women develop extra cells within the lobules of the breast, the tubes designed to move milk through the breast. These areas of extra cells are called hyperplasia and show up only on mammograms. They are not cause for concern unless the cells begin to change from their normal shape. This rare condition is called atypical hyperplasia. It does not cause cancer. Incidence: Varying estimates indicate that anywhere from 40 to 90 percent of women have some form of fibrocystic
Fibrocystic breast changes changes, which supports the theory that the symptoms are mostly related to normal changes in the breasts. Symptoms: Symptoms of fibrocystic changes vary according to the type of change a woman experiences. She may have feelings of heaviness, tenderness, or swelling of the breasts. Cysts are usually felt as smooth and are generally round and movable when prodded. If they are deep within the breast, they may feel hard because of the breast tissue overlaying them. Cysts may simply cause a feeling of lumpiness throughout the breast, or because of pressure on the breasts caused by collected fluid within the cysts, they may cause tenderness or actual pain. However, pain cannot always be attributed to cysts or other specific causes. The amount of pain may differ between a woman’s right and left breast. The intensity of pain can vary from month to month for the same woman. Breast pain can sometimes be intense enough to interfere with a woman’s normal life. Some women experience no physical symptoms, but breast examinations or mammograms may reveal cysts or areas of fibrosis. Screening and diagnosis: It is important for a woman to become familiar with the way her breasts feel at different times of the month so that she can identify any obvious changes. Annual breast examinations as part of a physical examination are also important to track any changes. Women over age forty should have routine annual mammograms. If breast examination reveals suspect lumps, mammograms may be needed at an earlier age. Women with hyperplasia may need more frequent breast examinations or follow-up mammograms. A woman should bring any defined lumps or masses or persistent breast pain to her doctor’s attention. A doctor may attempt to aspirate a suspect lump with a fine needle to determine whether it is a cyst or a solid lump. If it is a cyst, the doctor can puncture the cyst with the needle and draw the fluid out of the cyst. In this case, generally no further action is needed. However, the doctor may choose to have a pathologist check the fluid for cancer cells. If a lump yields no fluid and proves to be solid, a mammogram is generally done for further diagnosis. The technology of ultrasound has been improved for the creation of diagnostic images of the breast. Although it is generally not a good tool for screening, it is useful in the further diagnosis of areas of concern first identified on mammograms. Because it uses sound waves to create images of the breast, ultrasound is particularly useful for distinguishing between cysts and solid masses and between benign and cancerous lumps. For women with fibrocystic changes in the breast, which often cause the breast tissue to be particu477
Fibrosarcomas, soft-tissue larly dense and may make mammograms difficult for radiologists to read, ultrasound is often a more accurate diagnostic tool. Biopsy may be required to analyze cells to rule out cancer. This can be done by a needle core biopsy, where a doctor removes a sample of cells from the area of the breast. Alternatively, it can be done by surgical biopsy, in which case the whole lump or suspect area is cut out of the breast. Treatment and therapy: Cysts generally need no treatment. If a cyst is very large and therefore creates a lot of pressure resulting in pain, a doctor may use a needle to aspirate it and remove the fluid in the cyst as described above. Once the fluid is gone, this deflates the cyst and resolves the pressure it caused. Most cyclical changes in the breast do not cause enough discomfort to require any treatment. Breast pain generally can be relieved with anti-inflammatory drugs such as ibuprofen or naproxen. A bra with good support, like a sports bra, can relieve pressure and the related pain. Birth control pills can be used to treat more intense breast pain because they level out the fluctuations in hormonal levels. Some women have found relief from symptoms by consuming fewer products that contain caffeine (such as coffee, tea, and chocolate) or using primrose oil or other herbal remedies. However, research has not provided convincing data that these make a difference for women overall. There is some evidence that a low-fat diet may reduce symptoms of cyclical breast pain. Prognosis, prevention, and outcomes: About 54 percent of benign breast conditions go away by themselves over time. None cause cancer. Only one, atypical hyperplasia, is associated with any added risk of cancer. Women with atypical hyperplasia who also have a family history of breast cancer may have a slightly increased risk of cancer over their lifetimes. Charlotte Crowder, M.P.H., ELS u
For Further Information Chinyama, Catherine N. Benign Breast Diseases: Radiology, Pathology, Risk Assessment. New York: Springer, 2004. Love, Susan, and Karen Lindsey. Dr. Susan Love’s Breast Book. 5th ed. Cambridge, Mass.: Da Capo Press, 2005. Mansel, R. E., ed. Recent Developments in the Study of Benign Breast Disease: The Proceedings of the Fifth International Benign Breast Symposium. Park Ridge, N.J.: Parthenon, 1993. 478
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Other Resources
MayoClinic.com Fibrocystic Breast Disease: Any Link to Cancer? http://www.mayoclinic.com/health/ fibrocystic-breast-changes/AN00715 Medline Plus Fibrocystic Breast Disease http://www.nlm.nih.gov/medlineplus/ency/article/ 000912.htm See also Breast cancers; Caffeine; Estrogen-receptorsensitive breast cancer; Fibroadenomas; Lumps.
u Fibrosarcomas, soft-tissue Category: Diseases, symptoms, and conditions Related conditions: Angiosarcoma, alveolar soft part sarcoma, clear-cell sarcoma, dermatofibrosarcoma protuberans, desmoid tumors, desmoplastic small-cell tumor, elastofibroma, epithelioid hemangioendothelioma, epithelioid sarcoma, fibroma, fibrous histiocytoma, fibromatosis, gastrointestinal stromal tumor, glomangiosarcoma, leiomyosarcoma, liposarcoma, lymphangiosarcoma, Kaposi sarcoma, musculoaponeurotic fibromatosis, neurofibrosarcoma, rhabdomyosarcoma, superficial fibromatosis, synovial sarcoma, and malignant versions of fibrous histiocytoma, granular cell tumor, hemangiopercytoma, mesenchymoma, peripheral nerve sheath tumor, and schwannoma Definition: Fibrosarcomas are soft-tissue sarcomas (malignant tumors) of the fibroblasts, the cells that produce the fibrous tissues that connect, support, or surround other organs and tissues in the body (such as those around the joints). They usually occur in the arms, legs, or torso area, most commonly in the legs. They are one of many types of soft-tissue sarcomas. They are called “soft tissue” to distinguish them from osteosarcomas, tumors that develop in the bone. Fibrosarcomas are often grouped together with the other soft-tissue sarcomas because these diseases share certain characteristics and have similar treatment options. Risk factors: Most soft-tissue sarcomas have no known cause. However, there are several factors that may increase the risk of developing these types of cancer. Radiation therapy, usually for other types of cancer, is the bestdocumented risk factor for this disease, possibly because radiation may inactivate the lymph nodes. Surgical removal of the lymph nodes also seems to play a part in development of this disease.
Salem Health: Cancer
Fibrosarcomas, soft-tissue
Another risk factor for this type of disease is exposure to certain chemicals, usually at the workplace. Chemicals that may cause this type of cancer are arsenic, herbicides, vinyl chloride, and wood preservatives. This disease is also associated with certain genetic mutations. People with alterations in the FH gene, the NF1 gene, the TP53 tumor-suppressor gene, or the RB1 gene and who have the diseases associated with these genetic mutations (Li-Fraumeni syndrome and neurofibromatosis, also called von Recklinghausen disease) are much more likely to develop soft-tissue sarcomas, including fibrosarcoma. Other diseases that seem to increase the risk for softtissue sarcomas are basal-cell nevus syndrome, Gardner syndrome, tuberous sclerosis, and Werner syndrome. Etiology and the disease process: Fibrosarcomas begin in the cells that develop fibrous tissues. They start as a lump in these fibrous tissues, usually those that surround the joints in the arms, legs, and torso. The lump is usually painless; however, the tumor may grow, pressing against other tissues such as nerves and muscles, and cause pain. These tumors can spread throughout the body, most commonly to the lungs. Incidence: Soft-tissue sarcomas are rare, and developing fibrosarcoma is even rarer. Only about 9,000 new cases of soft-tissue sarcoma are diagnosed in the United States each year. This type of cancer is most common in people between the ages of twenty and sixty, with most patients being age fifty or older. However, it can occur in people of any age, including infants.
raphy (CT) scan or magnetic resonance imaging (MRI) to help diagnose and stage this disease. These tests can help determine the size of the tumor and whether its location will allow for surgical removal. The stages of this disease depend on how abnormal the cells of the tumor appear, the size of the tumor, and how likely the tumor is to begin to spread and grow. Staging of this disease follows the TNGM system. These letters represent the size of the primary tumor (T), whether the disease has spread to the lymph nodes (N), the grade of the tumor (G), and whether the tumor has spread or metastasized (M). The size of the tumor (T) is assigned a number based on the size of the primary tumor as follows: • T1: Tumor is 5 centimeters or less. • T1a: Superficial (near the surface) tumor • T1b: Deep tumor • T2: Tumor is larger than 5 centimeters. • T2a: Superficial tumor • T2b: Deep tumor Lymph node involvement (N) is assigned a number as follows: • N0: No evidence of cancer is found in nearby lymph nodes. • N1: Evidence of cancer is found in nearby lymph nodes.
Symptoms: This type of cancer is most likely to develop in the arms, legs, or torso. It usually appears as a lump or mass and is not usually painful or swollen. There are generally no other symptoms. Screening and diagnosis: No screening test is available for fibrosarcoma. The only way to accurately diagnose this type of tumor is with a biopsy, surgical removal of part of the tumor. The tumor section is then examined under a microscope to determine whether the cells are cancerous. These cells may also be tested for the genetic mutations that are risk factors in this disease to determine the most effective treatment. Doctors may use a computed tomog-
Fibrosarcoma nodules on the thumb and palm. (Custom Medical Stock Photo)
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Fibrosarcomas, soft-tissue
Salem Health: Cancer
Stage at Diagnosis and Five-Year Relative Survival Rates for Soft Tissue Cancer, Including Heart Cancer, 1996-2004 Stage Localizeda Regionalb Distantc Unstaged
Cases Diagnosed (%) Survival Rate (%) 53 25 15 7
84.7 60.0 16.0 54.2
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 a Cancer still confined to primary site b Cancer has spread to regional lymph nodes or directly beyond the primary site c Cancer has metastasized
The grade of the tumor is assigned a number as follows: • G0: Grade of tumor cannot be assessed. • G1: The tumor is well defined without reaching into surrounding tissues. • G2: The tumor has moderately reached into surrounding tissues. • G3: The tumor has reached well into surrounding tissues. • G4: The tumor cannot be distinguished from surrounding tissues. The spread of the disease (M) is divided into two categories: • M0: No disease is present elsewhere in the body. • M1: Disease is present in a distant body area. After the TNGM state of the cancer is determined, a stage is assigned. • Stage I: Low grade and either superficial or deep (G1 or G2, any T or N, and M at 0) • Stage II: High grade and either superficial or deep (G3 or G4, any T or N, and M at 0) • Stage III: High grade, large, and deep (G3 or G4, T2b, N and M at 0) • Stage IV: Any spread of disease to lymph nodes or other sites (any G, any T, and either N1 or M1) Treatment and therapy: Treatment for fibrosarcoma usually starts with surgery to remove the tumor and some of the healthy tissue surrounding it. The surgeon must ensure that all edges of the tumor have been removed, and sometimes this involves removing a large amount of tis480
sue. In about 10 to 15 percent of cases, this may even involve amputation of an arm or leg to ensure that the entire tumor is removed; however, surgeons often try to use limb-sparing techniques to avoid amputation. Some patients may need reconstructive surgery after removal of the tumor. Radiation therapy (using high-energy rays to kill the cancerous cells or implanting a tumor with radioactive materials) also may be used with this type of cancer, especially if the cancer’s location makes it difficult to remove the entire tumor or avoid damaging other body parts. Radiation therapy may be used along with surgery to ensure that any cancerous cells that may have been left behind are killed. It may also be used when limb-sparing techniques were used to avoid amputation to ensure that any remaining cancer cells are killed. Chemotherapy (using drugs in the blood stream to kill cancer cells) may also be used with fibrosarcomas. If the cancer has certain gene mutations, it may be treated with drugs specifically developed to target that mutation. Chemotherapy could be used before surgery to try to shrink the tumor before removal. MRIs or CT scans may be used after surgical removal to determine if the entire tumor was removed and to make sure the tumor is not growing back. Prognosis, prevention, and outcomes: Prognosis depends on the patient’s age, the size of the tumor, how deep or superficial the tumor is, and the likelihood of the tumor’s spread at the time of diagnosis. Patients with soft-tissue sarcomas such as fibrosarcoma need to receive follow-up care to ensure that there is no recurrence of the disease. Outcomes are generally better for patients who are less than sixty years old or have tumors smaller than 5 centimeters. Marianne M. Madsen, M.S. u
For Further Information Baker, Laurence H., ed. Soft Tissue Sarcomas. Boston: Martinus Nijhoff, 1983. Montgomery, Elizabeth, and Alan D. Aaron, eds. Clinical Pathology of Soft-Tissue Tumors. London: Informa Healthcare, 2001. Pollock, Raphael E., ed. Soft Tissue Sarcomas. Lewiston, N.Y.: BC Decker, 2002.
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Other Resources
American Cancer Society http://cancer.org
Salem Health: Cancer National Cancer Institute Soft Tissue Sarcomas: Questions and Answers http://www.cancer.gov/cancertopics/factsheet/ Sites-Types/soft-tissue-sarcoma See also Amputation; Bone cancers; Dermatofibrosarcoma protuberans (DFSP); Limb salvage; Mediastinal tumors; Sarcomas, soft-tissue.
u Financial issues Category: Social and personal issues Definition: Financial issues related to cancer include the financial burden on cancer patients and their families, the costs to insurers and employers, and the financial implications of cancer for the economy and government. Some of the economic issues include the rising costs of new treatments, bankruptcies caused by medical bills, and the high cost to society in terms of lost productivity, excess mortality, and morbidity related to cancer. Overall cost of cancer: In 2005, cancer expenditures in the United States totaled about $209.9 billion. Of that total, about $74 billion was paid for inpatient and outpatient care, drugs, and devices—around $250 for every man, woman, and child. This amount represents less than 5 percent of all medical spending and less than 1 percent of the total U.S. gross domestic product (GDP, a measure of all the goods and services produced in the economy). This may be somewhat surprising, given that cancer accounts for nearly a quarter of all deaths in the United States. However, cancer is mostly a disease of old age and is frequently terminal. Although treating cancer can be expensive compared with the cost of treating many other diseases, the cost of chronic illnesses that require medical care over an extended period (such as diabetes) can be much higher. However, cancer expenditures may be of greater concern in the future, as the baby boomers swell the ranks of Medicare from 42.5 million people in 2005 to about 70 million in 2030. Cancer expenditures are growing at about the same rate as overall medical spending, at 4 to 5 percent per year after adjusting for inflation. This may seem somewhat counterintuitive because the incidence of many types of cancer has been increasing and many intensive and expensive forms of treatment have been introduced in the twentyfirst century. At the same time, the average length of hospital stay has been decreasing, and there has been an increase in the number of early-stage cancers detected because of improved screening programs.
Financial issues Morbidity and premature mortality are called “indirect” costs, because they represent lost resources rather than outgoing payments. Although indirect costs are hard to measure and sometimes controversial, accounting for these costs gives a clearer picture of the total burden of a disease. The additional economic burden of cancer-related morbidity and mortality is estimated at about $135.9 billion per year. This breaks down into $17.5 billion in lost work productivity—including both absenteeism and “presenteeism” (reduced productivity while at work)— and $118.4 billion in lost earnings because of premature deaths. The main measure of premature mortality is years of life lost (YLL), which can be calculated as person-years of life lost in a specified period based on average age at diagnosis and patterns of mortality. Such calculations are then translated into dollar amounts, although doing so requires making assumptions regarding the labor market that are subject to error. In 1997 in the United States, the estimated cost from the top fifteen types of cancer was 6.6 million YLL. Dividing the YLL by the number of deaths for each cancer site produces an additional statistic, the average years of life lost (AYLL), which is a measure of the premature mortality burden of cancer to the individual patient. Prostate cancer patients experience the lowest AYLL at six years, while brain tumor patients have the highest at just over twenty years. Costs of treatment: The cost of medical treatment for a single case of cancer depends mainly on the type of cancer and the seriousness of the disease (size of the tumor, how much the cancer has spread, whether it can be treated with surgery, and so on). Other factors that influence the cost of care include the age and sex of the patient, how many other illnesses the patient has, and where the patient receives care (geographically and by setting, such as an academic hospital or specialty facility). In addition, some patients are charged less than others. Patients with no insurance are often charged full price, which can be many times the cost billed to patients with insurance because of negotiated discounts. In a study of more than 38,000 cancer patients followed for an average of eleven months, the mean cost of treating cancer was about $32,000, with monthly costs ranging from $1,800 for prostate cancer to $7,300 for pancreatic cancer. The largest component of care was inpatient hospital bills, followed by outpatient office visits. The mean monthly cost for drug treatments ranged from $10 for prostate cancer to $750 for ovarian cancer. The cost of drugs used to treat cancer has been the subject of controversy in recent years. Although drug costs ac481
Financial issues
Salem Health: Cancer
cer. More than three-quarters of those who filed for bankruptcy because of medical expenses said that they had health insurance at the time of their diExpenditures Percentage of All Percentage Cancer Treatment (billions; in agnosis. One estimate is that, on averof All New Cancers (1998) 2004 dollars) Expenditures Cancer age, out-of-pocket medical costs consume more than a quarter of the total Lung 12.7 9.6 13.3 annual income of low-income people. Colorectal 10.7 8.4 11.7 Breast 15.9 8.1 11.2 A national survey of cancer patients Prostate 16.8 8.0 11.1 conducted by USA Today, Harvard UniLymphoma 4.6 4.6 6.3 versity, and the Kaiser Family FoundaHead and neck 2.8 3.2 4.4 tion found that about 25 percent had Bladder 4.4 2.9 4.0 used up most or all of their savings. Leukemia 2.4 2.6 3.7 More than 10 percent said they had exOvarian 1.9 2.2 3.1 perienced problems paying for necessiKidney 2.6 1.9 2.7 ties like food and shelter, and 3 percent Endometrial 2.9 1.8 2.5 had declared bankruptcy because of the Cervix 0.8 1.7 2.4 financial cost of dealing with cancer. Pancreas 2.3 1.5 2.1 One in twelve respondents said that they Melanoma 4.0 1.5 2.0 Esophagus 1.0 0.8 1.1 delayed or did not get care because of All other 14.2 13.4 18.4 the cost. Although 95 percent of patients in the survey had health insurTotal 100% $72.1 100% ance, nearly 1 in 4 said that their insurSource: National Cancer Institute ance plan paid less than they expected Note: Based on cancer prevalence in 1998 and cancer-specific costs for 1997-1999, for a bill, 13 percent said their plan projected to 2004 using consumer price index would not cover a treatment they received, and 10 percent reached their maximum allowance for coverage. count for only about 10 percent of total health care spendIn the same survey, 44 percent of cancer patients reing, the prices charged by pharmaceutical companies are ported that they were employed outside the home when more transparent to consumers than prices charged by they were diagnosed. Most said that their employers treated other medical providers because consumers often pay them well. The Americans with Disabilities Act (1990) more out of pocket for drugs. In addition, there is great and the Family and Medical Leave Act (1993) protect cancontroversy over the cost-effectiveness of some of the cer patients to some extent, because they require employnewer drugs. In many cases, using one of the new drugs ers to make reasonable accommodations for the limitawill not extend a patient’s life more than a few months, yet tions of cancer patients on the job and entitle patients and the cost of the drug can be prohibitive. their caregivers up to twelve weeks of unpaid leave with continued benefits. One cost of cancer usually borne by patients and their Financial impact on patients: Cancer can be a very exfamilies is the time and money associated with medical appensive disease. Many types of cancer are complicated to pointments. These costs include transportation to and from treat and often require the services of a team of medical medical offices or clinics, time lost from work and leisure, providers, including surgeons and specialists in radiation child care, and housing and incidental costs for out-ofand chemotherapy. Cancer care may require many abtown trips to specialty care centers. In fact, the nonprofit sences from work for diagnosis and treatment, and long organization CancerCare (www.cancercare.org) reports hospital inpatient stays are required for many interventhat getting help with transportation costs is the most comtions. Patients may find that they need second opinions on monly requested and provided service it offers. biopsies and therapy. Patients with insurance may have to A number of organizations offer financial assistance to fight with insurers to get them to pay for treatments. cancer patients. State Medicaid plans cover the cost of care A recent survey found that more than half of bankfor needy patients, and there is additional assistance availruptcy filings are caused by medical expenses, and the able through some states’ Free Care pools. The Federal highest out-of-pocket expenses were associated with can-
Estimated National Spending on Medical Treatment for the Fifteen Most Common Cancers
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Salem Health: Cancer Breast and Cervical Cancer Early Detection Program covers costs associated with cases of cancer detected through one of the national screening programs. Pharmaceutical companies and nonprofit groups have patient assistance programs in place to help with the cost of cancer drugs, either by providing them free or at heavily discounted rates. Although there are hundreds of these patient assistance programs, they are underpublicized and underused. Financial impact on employers: Cancer-related costs to employers include medical costs paid by employersponsored insurance plans, disability costs, and lost productivity. In addition, other people may have to fill in for the cancer patient, or a part-time or temporary person may need to be hired. In a study of one of America’s largest companies, researchers analyzed insurance claims for medical care, absenteeism, and disability costs for all patients who were diagnosed with cancer between 1995 and 1997 and compared these expenditures with a sample of people who were similar in sex, job function, and type of health plan. They found that the average excess cost of cancer patients was more than $83,000, and total annual health care costs for cancer patients were more than five times higher than for similar people without cancer. The cost of medical care was only about half of the total incremental cost to the employer. The cost of disability payments and absences from work made up the other half of costs borne by the employer. Efforts to contain costs: Most medical care in the United States is paid for by a third party, such as Medicaid (for the poor and disabled), Medicare (for people over the age of sixty-five), or a private or employer-sponsored insurance company. These third-party payers have instituted a number of measures to contain costs associated with treating cancer. For example, most new drugs are required to show cost-effectiveness before payers will add them to their formularies (lists of approved treatments). Other cost-containment measures include cost-sharing, required preauthorizations, and retrospective claim denials. The idea behind cost-sharing is to correct a so-called irrationality in the market: The fact that patients are insulated from the true cost of their health care leads them to have higher demand for goods and services than they otherwise would. Cost-sharing has been criticized as unjust because distributing health care benefits according to the ability to pay discriminates against the poor and lower-middle classes. By law, Medicare is not allowed to set or negotiate prices for reimbursing physicans, hospitals, and drug companies. In the case of cancer drugs, since 2003 Medicare has been overhauling its systems with the intention of eliminating incentives that favor aggressive and expensive
Financial issues treatments over equivalent alternatives. Historically, the problems have arisen because the Medicare reimbursement rate for many drugs was far higher than the actual cost of purchasing them. Medicare was and is required by law to cover cancer drugs if they are being used for their Food and Drug Administration-approved indication or another approved indication. The resulting profits around certain cancer drugs have been shown to influence prescribing patterns. Medicare officials are also concerned about overtreatment, such as screening and monitoring procedures that are conducted more often than the evidence and guidelines recommend. In reaction to these and other issues, Medicare administrators have instituted a number of steps toward increasing the transparency and quality of cancer care. Lisa M. Lines, M.P.H. u
For Further Information Brown, M. L., J. Lipscomb, and C. Snyder. “The Burden of Illness of Cancer: Economic Cost and Quality of Life.” Annual Review of Public Health 22 (2001): 91-113. Brown, M. L., G. F. Riley, N. Schussler, and R. D. Etzioni. “Estimating Health Care Costs Related to Cancer Treatment from SEER-Medicare Data.” Medical Care 40, suppl. 8 (August, 2002): IV-104-117. Chang, S., et al. “Estimating the Cost of Cancer: Results on the Basis of Claims Data Analyses for Cancer Patients Diagnosed with Seven Types of Cancer During 1999 to 2000.” Journal of Clinical Oncology 22, no. 17 (September 1, 2004): 3524-3530. National Institutes of Health. Disease-Specific Estimates of Direct and Indirect Costs of Illness and NIH Support. Bethesda, Md.: Author, 2000.
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Other Resources
American Cancer Society Costs of Cancer http://www.cancer.org/docroot/MIT/content/ MIT_3_2X_Costs_of_Cancer.asp National Cancer Institute Cost of Cancer Care http://healthservices.cancer.gov/areas/economics/ care.html See also Advance directives; Counseling for cancer patients and survivors; Health maintenance organizations (HMOs); Insurance; Living will; Managed care; Medicare and cancer; Poverty and cancer; Preferred provider organizations (PPOs); Survivorship issues. 483
5Q minus syndrome
u 5Q minus syndrome Category: Diseases, symptoms, and conditions Also known as: 5Q-syndrome, 5QMS Related conditions: Myelodysplastic syndrome Definition: 5Q minus syndrome is a rare genetic disorder in which a portion of the long arm (Q) of chromosome 5 is missing. Production of blood cells is affected, and this syndrome can lead to treatment-resistant anemia. 5Q minus syndrome is one in a series of blood disorders collectively called myelodysplastic syndromes (MDS’s). Risk factors: Risk factors are unknown. Gene mutation is probably spontaneous, although there is not enough data to suggest a familial pattern of transmission. Etiology and the disease process: Chromosomes are numbered by size and position of the centromere (point of connection of identical halves). Chromosome 5 is a large chromosome. In 5Q minus syndrome, a portion of the deoxyribonucleic acid (DNA) in the long arm (Q) is absent, leading to lack of output from the missing genes. These genes define growth and differentiation of cells that manufacture most of the blood cells. Thus, bone marrow cells are often deformed and have abnormal growth and maturation. Other missing genes code for interleukins, chemical signals involved in immune protection. Incidence: Although most forms of myelodysplastic syndromes are secondary and show up increasingly with age, 5Q minus syndrome is congenital and shows up early in life. Symptoms: The primary symptoms are anemia, low total white cell count, and increased bone marrow blast cells. Patients with 5Q minus syndrome also have elevated platelet counts, something that distinguishes this group from other myelodysplastic syndromes. Because red blood cells are not manufactured properly, patients are anemic and require regular transfusions of red blood cells. In many cases, this anemia fails to respond to transfusions or other stimuli. Screening and diagnosis: Total white blood cell count, monocyte and platelet count, and bone marrow biopsy are the best diagnostic tools. A definitive karyotype (analysis of chromosome count and pattern) helps to set 5Q minus syndrome apart from other myelodysplastic syndromes. Treatment and therapy: There have been few breakthroughs in therapy. Hematopoietic growth factors and granulocyte-macrophage colony-stimulating factor have been tried with little success. Immunosuppressive drugs 484
Salem Health: Cancer do not help most patients. One study involving the experimental leukemia drug lenalidomide showed substantial improvement to the point of being transfusion independent and going into cytogenic remission (the genetic abnormality was no longer displayed). Studies with bone marrow transplantation in patients with myelodysplastic syndromes have shown positive results, but no specific data on those patients with 5Q minus syndrome have been published. Prognosis, prevention, and outcomes: Due to the rarity of this disease, prognosis is difficult to quantify. Progression to acute leukemia generally occurs, and long-term outcome is poor. Kerry L. Cheesman, Ph.D. See also Acute myelocytic leukemia (AML); Anemia; Bone marrow aspiration and biopsy; Bone marrow transplantation (BMT); Chromosomes and cancer; Colonystimulating factors (CSFs); Interleukins; Leukemias; Leukopenia; Myelodysplastic syndromes; Myelosuppression; Transfusion therapy.
u Flow cytometry Category: Procedures Definition: Cytometry refers to the measurement of the physical and/or chemical characteristics of cells, or, by extension, of other biological particles. Flow cytometry is a process in which such measurements are made while the cells or particles pass, preferably in single file, through the measuring apparatus in a fluid stream. Cancers diagnosed: Hematological (blood) cancers Why performed: Flow cytometry is widely used in the clinical setting for a number of cytometry-based procedures, such as immunophenotyping, cell sorting, enumeration of CD34-positive stem cell precursors, enumeration of lymphocyte subsets (B cells, T cells, and natural killer or NK cells), and fetal bleed tests in fetomaternal hemorrhage. The technique is performed on a sample of cells obtained from blood, bone marrow, or other tissue, such as a lymph node. Flow sorting extends flow cytometry by using electrical or mechanical means to divert and collect cells with one or more measured characteristics falling within a range or ranges of values set by the user. A rapid analysis of a cell sample is possible with an instrument called a cytometer that can count fifty thousand cells per second. Prior to cytometry, cells had to be counted manually under a microscope, a labor-intensive task sub-
Salem Health: Cancer ject to operator error. Components of a cytometer include a fluidics system, an optical system composed of one or more monochromatic lasers or other light source with filters to serve as an excitation beam, electronics to detect emissions from the cells, and a computer to analyze the data collected. The flow cytometry technique is widely used for diagnostics and disease monitoring of hematopoietic malignancies. Immunophenotyping of hematological cancers has developed as a clinically valuable but technically complicated diagnostic procedure. It involves a variety of methodological features, in-process strategic judgments, and an extensive knowledge of clinical, morphological, and other laboratory features of the disease processes. A number of various internal quality-control steps are necessary to guarantee reliable results with respect to instrument setup and calibration, selection and validation of monoclonal antibody panels, and process control. The data provide a wide range of hematological information essential for establishing a diagnosis in blood cancers. In leukemias, for example, knowing cell lineage and maturation helps distinguish specific forms of leukemia. Testing by flow cytometry is performed to distinguish an abnormal population of hematopoietic cells and to determine the cellular lineage of malignant cells, clonality, cellular maturation, and heterogeneity within the cancerous cell populations. Flow cytometric analysis, called immunophenotyping, allows cells to be characterized by their size, complexity, and patterns of expression of surface and cellular markers. Multiparameter flow cytometry is the simultaneous use of multiple fluorochromes, which allows completion of the full diagnostic test with fewer cells, thus reducing the size of the specimen needed. Immunophenotyping by flow cytometry is used for the initial diagnosis of hematopoietic malignancies, for monitoring the response to treatment administered for the malignancy, and for determining the presence of minimal residual disease that may indicate recurrence of the cancer. Patient preparation: The specimen, on which the process of cytometry is performed, is generally bone marrow aspirate, although a sample of peripheral blood can also be used. The patient is given instructions by the health care provider based upon the need for a bone marrow procedure versus blood collection. Steps of the procedure: The procedure of immunophenotyping is based on the ability of hematopoietic cells of different lineages and different levels of differentiation to present specific surface, cytoplasmic, or nuclear markers. These markers, called clusters of differentiation (CD), are molecules on the cell surface, as recognized by specific
Flow cytometry sets of antibodies, that are used to identify the cell type, stage of differentiation, and activity of a cell. The procedure of immunophenotyping consists of three main steps: sample preparation, flow cytometric data acquisition, and analysis and interpretation of results. To prepare a sample, cells are labeled with the antibodies tagged by specific fluorochromes, which includes staining with fluorochrome-bound monoclonal antibodies, lysis of red blood cells, and fixation in a formalin-containing reagent. This staining protocol is used for all directly conjugated reagents. A so-called whole blood lysing system is used to prepare immunologically stained leukocytes for flow cytometry analysis. In the process of flow cytometric data acquisition, cells are run through a fluidic stream so that single cells can be analyzed one at a time. Then multiple parameters are collected on each cell and analyzed for forward-angle light scatter, ninety-degree light scatter, and fluorescent signal information from up to six different fluorochromes simultaneously. All data can be stored in the form of list-mode files for later reanalysis. After the procedure: Patients receive aftercare instructions according to how the sample is obtained. If sedation is used, then limitations and restrictions are communicated to the patient by health care practitioners. Risks: Potential risks of a bone marrow biopsy and aspirate or blood collection are incorporated into a consent form explained at the facility where the procedure is accomplished and signed by the patient prior to obtaining the sample for analysis. Results: Data can be analyzed and displayed in a variety of formats, such as single-parameter histograms, dot-plots (display of distribution of two antigens on an x-y plot), or three-dimensional plots of three antigens. Data are analyzed using a gating strategy, in which specific gates are set around the subpopulations of cells based on common parameters measured on all cells. The quantification of each cell type, its light-scatter properties, its intensity of fluorescence, and certain patterns of surface or cytoplasmic marker expression serve as an indication of hematopoietic abnormalities. The pattern of antigen expression on all the cells is analyzed and compared with the distribution of normal cells. Data interpretation is based on the knowledge of specific cell phenotypes affiliated with certain types of leukemia and lymphomas. Abnormal phenotypes, however, are not always associated with disease progression. Therefore, results of flow cytometric analysis have to be used in conjunction with other diagnostic procedures and clinical evaluations. Linda August Vrooman, R.N., B.S.N., O.C.N. 485
Folic acid u For Further Information Givan, Alice Longobardi. Flow Cytometry: First Principles. 2d ed. New York: Wiley-Liss, 2001. Langdon, Simon P., ed. Cancer Cell Culture: Methods and Protocols. Totowa, N.J.: Humana Press, 2004. McCarthy, Desmond A., and Marion G. Macey, eds. Cytometric Analysis of Cell Phenotype and Function. New York: Cambridge University Press, 2001. Radbruch, Andreas, ed. Flow Cytometry and Cell Sorting. 2d ed. New York: Springer, 2000.
See also Immunocytochemistry and immunohistochemistry; Myelodysplastic syndromes.
u Folic acid Category: Lifestyle and prevention Also known as: Folate, pteroylglutamic acid Definition: Folate is a water-soluble B vitamin found naturally in foods such as lentils, green leafy vegetables, broccoli, cereals, citrus fruits, and liver. It is an essential cofactor for deoxyribonucleic acid (DNA) synthesis and replication and is necessary for the production of normal red blood cells. Folic acid is the synthetic, oxidized form used in commercial vitamin supplements and food fortification. Cancers treated or prevented: Colorectal cancer, breast cancer Delivery routes: Natural dietary sources, fortified foods, oral supplements How this substance works: Folate is an essential cofactor in the de novo synthesis of purines and thymidylate and therefore plays a role in DNA synthesis, replication, stability, and repair. Evidence suggests that folate deficiency can lead to DNA damage and is associated with macrocytic anemia, neural tube defects, and cancer. In 1998, the U.S. Food and Drug Administration (FDA) began requiring the fortification of all flour and cereal grains with folic acid. These products are thus a major source of folic acid in the U.S. population. Large epidemiological studies that followed subjects for many years have found that higher dietary intake of folate and folic acid supplementation decreased the risk of colon and breast cancer. A possible explanation for its protective effect is that folate prevents DNAdamage that may lead to the development of cancer. Side effects: Research results on the benefits of folate in preventing cancer are inconsistent. Despite population studies showing positive effects of higher folate intake, 486
Salem Health: Cancer studies in animals and humans also have shown that folic acid supplementation increased the risk of breast cancer and the development of colon polyps. These mixed results suggest that folate has a dual role in the development of cancer. In normal tissues, folate appears to suppress the development of cancer, presumably by preventing mutations. Once early lesions or tumors have developed, however, folate appears to promote their progression in colorectal and breast cancers. In these cases, folic acid may provide a source of nucleotides for rapidly proliferating tissues, including tumors. Indeed, antifolate drugs are sometimes used in the treatment of cancer. Thus, the timing, dose, and form of folate appear to be critical in whether this substance prevents or actually promotes certain types of cancers. For these reasons, the National Institutes of Health (NIH) do not currently recommend folic acid supplements to reduce the risk of cancer. Linda Hart, M.S., M.A. See also Anemia; Antimetabolites in chemotherapy; Antineoplastics in chemotherapy; Antioxidants; Colon polyps; Dietary supplements; Free radicals; Fruits; Mesothelioma; Myelofibrosis.
u Formaldehyde Category: Carcinogens and suspected carcinogens RoC status: Reasonably anticipated human carcinogen since 1981 Also known as: Formalin, formic aldehyde, methaldehyde, methanol, methyl aldehyde, methylene glycol, methylene oxide Related cancers: Squamous cell carcinomas of the upper respiratory tract Definition: Formaldehyde is a flammable, colorless gas at standard temperature and pressure with a strong, irritating odor. It is highly soluble in water and is most commonly encountered as a 37 percent aqueous solution known as formalin, which usually also contains 10 to 15 percent methanol to prevent formaldehyde polymerization. Because of its simple molecular structure and reactivity, formaldehyde is widely used as a starting material in plastics manufacturing. Because it irreversibly links proteins and nucleic acids to one another, it is useful as a disinfectant and a fixative/ preservative in biomedical applications. Exposure routes: Inhalation Where found: Manufacturing plants, prefabricated dwellings, hospitals, mortuaries, smog
Salem Health: Cancer At risk: Workers involved in tissue fixation and in manufacturing plastics, particleboard, wood paneling, and furniture; occupants of prefabricated dwellings Etiology and symptoms of associated cancers: When formaldehyde reacts with adjacent primary amine groups in proteins or other biomolecules, the resulting covalent bond prevents normal mobility and functioning of the joined molecules. Repeated or sustained exposure to high concentrations (greater than 15 parts per million) of inhaled formaldehyde is sufficient to cause tissue damage, mutations, and increased cell turnover, which can result in malignant transformation. Cells in the upper respiratory tract (the nasopharynx) are especially liable to formalininduced cancers, which take the form of squamous cell carcinomas. Formaldehyde’s carcinogenicity has been demonstrated only in rodents exposed to very high gas concentrations over long periods of time, and extrapolation to human carcinogenicity is speculative. History: Formaldehyde was first described and chemically synthesized in the 1800’s, although it exists in small quantities in the atmosphere naturally and is a product of amino acid metabolism in the body. Its widespread adoption in the chemical industry prompted several large studies to search for diseases associated with exposure. More than thirty epidemiologic studies have addressed formaldehyde carcinogenicity in humans, and no consistent pattern of response has been found. One expert panel concluded that no evidence existed to show a relationship between formaldehyde exposure and human cancer and if a risk did exist, it had to be very small. Because of its many other adverse health effects, formaldehyde is subject to occupational and residential monitoring, with variable exposure limits in different jurisdictions. John B. Welsh, M.D., Ph.D. See also Air pollution; Artificial sweeteners; Astrocytomas; Chewing tobacco; Coke oven emissions; Lung cancers; Mineral oils; Nasal cavity and paranasal sinus cancers; Occupational exposures and cancer; Tobaccorelated cancers.
u Fox Chase Cancer Center Category: Organizations Definition: The Fox Chase Cancer Center is a cancer research facility and treatment hospital in Philadelphia, Pennsylvania. The one-hundred-bed hospital of Fox Chase Cancer Center is one of the few hospitals in the United States devoted solely to cancer care.
Fox Chase Cancer Center History and founding: In 1974 the Fox Chase Cancer Center was formed when the American Oncologic Hospital combined with the Institute for Cancer Research. The American Oncologic Hospital, established in 1904, is notable as the first cancer hospital in the United States. The Institute for Cancer Research, founded in 1927, was established for basic research of normal and abnormal cell growth. The Institute for Cancer Research (ICR), later known as the Fox Chase Cancer Center, contributed significantly to the field of cancer research and treatment. Many important discoveries, including the identification of vitamin B12 by Mary Bennett in 1946, were made in the Fox Chase research laboratories. The Nobel Prize in Physiology and Medicine was awarded to Baruch Blumberg in 1976 for his discovery of the hepatitis B virus (HBV) and development of the HBV vaccine. Considered the first anticancer vaccine, the HBV vaccine has reduced the incidence of liver cancer. Fox Chase Cancer Center established the Partners program in 1986 to unite a group of community hospitals with the center to make the most current cancer treatments available in a wide geographic area. In 1995 Fox Chase Cancer Center was a founding member of the National Comprehensive Cancer Network (NCCN), a program of twenty-one nonprofit academic centers working on cancer research, treatment, and prevention. The Research Institute for Cancer Prevention was opened at Fox Chase in 2000 and includes the Prevention Pavilion of Fox Chase, where individuals have access to prevention-oriented resources. Current facilities: The Fox Chase Cancer Center research facilities and hospital are in the northeast section of Philadelphia. The hospital is one of the few in the United States that is solely devoted to the care of cancer patients. Its Partners program includes a group of community hospitals in Pennsylvania, New Jersey, and Delaware, where patients can receive treatment closer to home yet still have access to the most up-to-date cancer treatment based on the translation of cancer research results. The program also provides access to participation in clinical trials. Other collaborative programs with which Fox Chase is involved are a bone marrow transplantation program with Temple University, the National Comprehensive Cancer Network, and the Oncology Physicians Network (OPN). Fox Chase operates a mobile mammography van as part of its corporate and community outreach program; additional outreach programs provide screening services for other cancers. More than eighty research laboratories are part of Fox Chase. Research programs are structured in three divi487
Fred Hutchinson Cancer Research Center sions: medical science, basic science, and population science. The medical science research programs include breast cancer, developmental therapeutics, ovarian cancer, and prostate cancer. The basic science research programs include biomolecular structure and function, cellular and developmental biology, genome stability, immunobiology, tumor cell biology, and viral pathogenesis. Fox Chase’s population science program studies groups of people with high risk for cancer, works to build approaches for risk reduction, and is involved with cancer prevention trials; the specific research programs include a cancer prevention and control program and a human genetics program. Specialization: Cancer prevention and early detection of cancers are Fox Chase priorities; patient services include the Prostate Risk Assessment Program as well as risk assessment programs for familial melanoma and gastrointestinal tumors. The Internet Risk Assessment Program was developed at Fox Chase to address the need for risk assessment and counseling of family members who are geographically separated. Cancer prevention and screening programs are offered by Fox Chase outreach services at low or no cost to the community. Community partners, such as the Black Women’s Health Alliance and local churches, work with Fox Chase to reach underserved minority populations. The outreach programs at Fox Chase also provide cancer awareness, screening, and education services in corporate settings. Fox Chase provides multidisciplinary treatment centers for adult patients with solid tumors and hematologic malignancies. A multidisciplinary pain management center is located at Fox Chase, and the Lippincott Hospice Program provides home-based care to terminally ill adult cancer patients and their families. An additional area of renown is a Fox Chase collaboration with Temple University Health System, forming the Fox Chase-Temple Bone Marrow Transplant Program. A special clinical studies wing of the hospital has ten patient beds for individuals enrolled in phase I clinical trials, which enroll small numbers of individuals for assessment of the safety of a new drug treatment and the determination of its maximum safe dose and optimal dosing schedule. Fox Chase is known for its oncology nursing and has achieved American Nurse Credentialing Center Magnet status. Vicki Miskovsky, B.S., R.D. u
For Further Information Eyre, Harmon, and Dianne Partie Lange, eds. Informed Decisions: The Complete Book of Cancer Diagnosis, Treatment, and Recovery. 2d ed. Atlanta: American Cancer Society, 2002. 488
Salem Health: Cancer Hoffman, Barbara, ed. A Cancer Survivor’s Almanac: Charting Your Journey. Minneapolis: Chronimed, 1996. Morra, Marion, and Eve Potts. Choices. 4th ed. New York: HarperCollins, 2003. Teeley, Peter, and Philip Bashe. The Complete Revised and Updated Cancer Survival Guide: The Most Comprehensive, Up-to-Date Guide for Patients and Their Families. Rev. ed. New York: Broadway Books, 2005. u
Other Resources
Fox Chase Cancer Center http://www.fccc.edu National Comprehensive Cancer Network Fox Chase Cancer Center http://www.nccn.org/members/profiles/fccc.asp See also American Association for Cancer Research (AACR); American Cancer Society (ACS); American Institute for Cancer Research (AICR); Dana-Farber Cancer Institute; Duke Comprehensive Cancer Center; Fred Hutchinson Cancer Research Center; Jonsson Comprehensive Cancer Center (JCCC); M. D. Anderson Cancer Center; Mayo Clinic Cancer Center; Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI); National Science Foundation (NSF); Prevent Cancer Foundation; Robert H. Lurie Cancer Center.
u Fred Hutchinson Cancer
Research Center Category: Organizations Definition: The Fred Hutchinson Cancer Research Center is a nonprofit biomedical research institution in downtown Seattle, Washington. A partnership of the Hutchinson Center with the University of Washington and Children’s Hospital and Regional Medical Center forms the Seattle Cancer Care Alliance (SCCA), which provides clinical care to adult and pediatric patients. History and founding: William B. Hutchinson, a native of Seattle, attended the University of Washington, where he was captain of the baseball team. Hutchinson was offered a contract with a Class AAA baseball team in California after graduation but chose instead to attend medical school at McGill University in Montreal. After he came back to Seattle in 1940 to practice medicine, he returned to baseball as team physician to the Seattle Rainiers baseball team. His love for baseball and other sports was also mani-
Salem Health: Cancer fest in his work with local youth athletic programs. In 1956 he founded the Pacific Northwest Research Foundation, an institution for research into heart surgery, diseases of the endocrine system, and cancer. Hutchinson’s brother Fred shared his brother’s talent for baseball. He was a major league pitcher for the Detroit Tigers from 1939 through 1953 and later was the team manager for the Tigers, the St. Louis Cardinals, and the Cincinnati Reds. In 1964 Fred Hutchinson was diagnosed with lung cancer, and he died of the illness the same year. In memory of his brother, William B. Hutchinson established the Fred Hutchinson Cancer Research Center (FHCRC) in 1965 as a division of the Pacific Northwest Research Foundation. The FHCRC separated from the Pacific Northwest Research Foundation in 1972, and the independent FHCRC opened its facility in 1975. Current facilities: The Fred Hutchinson Cancer Research Center is one of thirty-nine centers nationwide designated by the National Cancer Institute (NCI) as a comprehensive cancer center. The National Cancer Institute designation is awarded to cancer centers deemed to have earned scientific excellence in cancer research and that provide a full range of cancer diagnostic and treatment services. The Seattle Cancer Care Alliance (SCCA) was formed in 1998 as a partnership of the Fred Hutchinson Cancer Research Center, University of Washington Medicine (made up of the University of Washington School of Medicine, Harborview Medical Center, University of Washington Medical Center, and University of Washington Neighborhood Clinics), and Children’s Hospital and Regional Medical Center. The mission of the Seattle Cancer Care Alliance is to unite research and outstanding patient care to provide state-of-the-art cancer treatment. Another collaboration, formed in 2002, between the Fred Hutchinson Cancer Research Center, the University of Washington, and Children’s Hospital and Regional Medical Center is the Fred Hutchinson/University of Washington Cancer Consortium. The consortium allows participating institutions to combine their expertise to further cancer research with the development of leading research programs spanning many types of cancer. A large faculty of researchers involved in basic, clinical, and public health disciplines contribute efforts in seventeen research programs. The National Cancer Institute designation as a comprehensive cancer center now includes the consortium. The Fred Hutchinson Cancer Center is the only comprehensive cancer center in the Pacific Northwest designated by the National Cancer Institute. The institute contracts with the Fred Hutchinson Cancer Research Center
Fred Hutchinson Cancer Research Center through the Partnership Program to provide services to the states of Alaska, Idaho, Nevada, Oregon, and Washington, and to operate as one of four contact centers. A contact center serves as a clearinghouse of cancer information for the United States, Puerto Rico, the U.S. Virgin Islands, and the U.S. Associated Pacific Territories. Research: Three Nobel Prize winners in medicine have come from the Fred Hutchinson Cancer Research Center. E. Donnell Thomas received the prize, shared with Joseph E. Murray, in 1990 for research into cell and organ transplantation in treating people. Lee Hartwell received the prize along with R. Timothy Hunt and Paul M. Nurse for research into the key regulators of the cell cycle. Linda B. Beck shared the prize in 2004 with Richard Axel from Columbia University for research into odorant receptors and the organization of the olfactory system. Research at the FHCRC focuses on improving the quality of life for people worldwide through its initiatives in cancer prevention and early detection of cancers and by focusing on new therapies, such as immunotherapy (fighting cancer by using the individual’s own immune system) and organ and cell transplantation, carrying on the research of Nobel Prize winner Thomas. Specialization: Direct patient services offered through the Seattle Cancer Care Alliance (SCCA) include adult and pediatric oncology services using multidisciplinary teams. Some areas of special expertise at the FHCRC include treatment of leukemias (cancers of the blood and the bone marrow, where blood cells are made) and treatment of lymphomas (cancers of the lymph nodes). The FHCRC is known internationally for its early work with bone marrow transplants and performs all types of donor transplants for bone marrow, peripheral blood stem cells, and umbilical cord blood from related and unrelated donors. Vicki Miskovsky, B.S., R.D.
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For Further Information Dollinger, M. Everyone’s Guide to Cancer Therapy: How Cancer Is Diagnosed, Treated, and Managed Day to Day. 4th ed. Kansas City, Mo.: Andre McMell, 2002. Eyre, Harmon, and Dianne Partie Lange, eds. Informed Decisions: The Complete Book of Cancer Diagnosis, Treatment, and Recovery. 2d ed. Atlanta: American Cancer Society, 2002. Raju, Tonse N. K. The Nobel Chronicles: A Handbook of Nobel Prizes in Physiology or Medicine, 1901-2000. Bloomington, Ind.: AuthorHouse, 2002. 489
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Other Resources
Fred Hutchinson Cancer Research Center http://www.fhcrc.org National Comprehensive Cancer Center Fred Hutchinson Cancer Research Center http://www.nccn.org/members/profiles/ hutchinson.asp See also American Association for Cancer Research (AACR); American Cancer Society (ACS); American Institute for Cancer Research (AICR); Dana-Farber Cancer Institute; Duke Comprehensive Cancer Center; Fox Chase Cancer Center; Jonsson Comprehensive Cancer Center (JCCC); M. D. Anderson Cancer Center; Mayo Clinic Cancer Center; Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI); National Science Foundation (NSF); Prevent Cancer Foundation; Robert H. Lurie Cancer Center.
u Free radicals Category: Carcinogens and suspected carcinogens Also known as: Radicals, reactive species Related cancers: Cancers of the skin, airways, gastrointestinal tract, liver, bladder, prostate, and kidney, as well as leukemia and other cancers Definition: Free radicals are molecules with one or more unpaired electrons. Although there are stable radical species, the most common of which is oxygen, the presence of unpaired electrons most frequently confers high reactivity and oxidizing potential to free radicals. The most abundant free radicals in biological systems are molecules in which the unpaired electron belongs to an oxygen atom. They are known as reactive oxygen species and are mainly, but not exclusively, derived from the incomplete reduction of oxygen during mitochondrial respiration, which generates the superoxide anion radical (O2-). Superoxide is converted to hydrogen peroxide (H2O2) in a reaction driven by the enzyme superoxide dismutase. Hydrogen peroxide is converted to water and detoxified by glutathione peroxidase and catalase. Hydrogen peroxide is not a free radical; however, when produced in excess (for example, in leukocytes during the respiratory burst that takes place in inflammatory processes) or when its enzymatic detoxifying mechanisms are deficient, hydrogen peroxide can be converted to hydroxyl radical (OH) in the presence of transition metals such as iron or copper. The hydroxyl radical is the most deleterious of the reactive oxygen species be490
Free radicals. (Custom Medical Stock Photo)
cause it can hydroxylate or abstract an electron from most macromolecules, including enzymes, membrane lipids, and DNA, the latter sometimes resulting in mutagenesis. In addition to reactive oxygen species, another significant free radical in the cell is nitric oxide (NO), which is synthesized from arginine by nitric oxide synthase. Nitric oxide fills essential physiological functions but it can also act as an oxidant. Living organisms have developed enzymatic and nonenzymatic mechanisms to neutralize free radicals. When the generation of free radicals overpowers the capacity of the natural antioxidant defense systems, however, oxidative stress occurs. Signs of oxidative stress have been found in many forms of human cancer. Exposure routes: The pathologically related free radicals originate within the body as a product of normal aerobic metabolic processes and inflammatory reactions, but some environmental agents, such as radiation and pollutants, with diverse routes of exposure, can increase the production of free radicals. Where found: Free-radical-generating agents are diverse, as are their sources. The most common are tobacco smoke,
Salem Health: Cancer sunlight, X rays, and automobile exhausts. Others include the carcinogens benzene, inorganic arsenic compounds, cadmium compounds, aflatoxins, and asbestos. At risk: Populations at highest risk are those with a low dietary intake of antioxidants or genetic deficiencies in antioxidant enzymes (for example, glutathione peroxidase) or deoxyribonucleic acid (DNA) repair mechanisms, along with tobacco smokers, people who spend a long time in areas of heavy traffic or who are directly exposed to sunlight, and those with chronic inflammatory conditions. Etiology and symptoms of associated cancers: The carcinogenic potential of free radicals arises from their ability to damage DNA, modify proteins by oxidation, and induce lipid peroxidation. The most frequently found form of oxidative DNA damage is hydroxylation of purine and pyrimidine bases. Other consequences of free radical actions for DNA are the generation of strand brakes, deamination, and formation of etheno adducts. Oxidative modifications of proteins include nitration, nitrosylation, and acetylation, among others. In addition, one of the most damaging effects of free radicals is lipid peroxidation because of its self-propagating nature, which greatly affects the properties and functioning of cell membranes. Furthermore, lipid peroxidation products, such as the reactive aldehydes malondialdehyde and 4-hydroxynonenal, can damage DNA and proteins in the same way as free radicals. DNA oxidative damage can cause mutations in cancerrelated genes, such as tumor-suppressor genes or oncogenes, and lead to the initiation and progression of cancer. Likewise, carcinogenesis can be induced by posttranslational oxidative modification of proteins involved in the regulation of cell growth, signal transduction pathways, DNA repair, or other mechanisms of cellular homeostasis. For instance, free radicals are known to induce the transcription of the proto-oncogenes FOS (also known as c-fos), JUN (c-jun), and MYC (c-myc), which stimulate cell growth. Also, posttranslational oxidative modifications of TP53 (p53), a tumor-suppressor protein, can inhibit its antiproliferative activity. Lastly, free radicals can promote not only tumor growth but also tumor migration and metastasis, by activating matrix metalloproteinases and stimulating the release of vascular endothelial growth factor. A current view of free radical actions supports the notion that these species do not act in a purely stochastic manner but are second messengers in redox-sensitive mechanisms of regulation of gene expression and enzyme activity. Aberrant and sustained redox signaling in oxidative stress situations leads to pathological changes, including cancer.
Fruits History: The relevance of free radicals in biological systems was first proposed by Denham Harman in 1956 in his classic article “Aging: A Theory Based on Free Radical and Radiation Chemistry.” Harman viewed age-related diseases as the result of an accumulation of oxidative damage. In the same year, in vitro studies showing the ability of oxygen reactive species to induce chromosome fragmentation in the presence of iron suggested for the first time the hypothesis of free-radical-induced carcinogenesis. Since then, the concept has been extended and free radicals have been found to be involved in most pathological conditions. Reyniel Cruz-Aguado, Ph.D. u
For Further Information Halliwell, B. “Oxidative Stress and Cancer: Have We Moved Forward?” Biochemistry Journal 401 (2007): 1-11. Hussain, S. P., L. J. Hofseth, and C. C. Harris. “Radical Causes of Cancer.” Nature Reviews. Cancer 3 (2003): 276-285. Wu, W. S. “The Signaling Mechanism of ROS in Tumor Progression.” Cancer Metastasis Reviews 25 (2006): 695-705.
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Other Resources
American Cancer Society http://www.cancer.org National Cancer Institute Antioxidants and Cancer Prevention: Fact Sheet http://www.cancer.gov/cancertopics/factsheet/ antioxidantsprevention See also Antioxidants; Beta-carotene; Bone cancers; Carotenoids; Coenzyme Q10; Curcumin; Diethanolamine (DEA); Fruits; Green tea; Helicobacter pylori; Herbs as antioxidants; Liver cancers; Lutein; Lycopene; Mesothelioma; Nutrition and cancer prevention; Phenolics; Resveratrol; Wine and cancer.
u Fruits Category: Lifestyle and prevention Definition: Botanically, a fruit is defined as the ripened ovary of an angiosperm, or flowering plant. In the human diet, fruit generally refers to sweet and fleshy parts of certain plants. Examples of fruits include cherries, peaches, plums, apples, strawberries, and oranges. 491
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Salem Health: Cancer mation of cancer cells by regulation of communication between cancer cells. Ascorbic acid, or vitamin C, functions in a similar manner and can be found in citrus fruits and strawberries. Folic acid, also found in citrus fruits, is involved in the synthesis, repair, and function of deoxyribonucleic acid (DNA), while dietary fiber encourages peristalsis and, in turn, the elimination of harmful wastes and estrogens.
How fruits help: Overall, the benefits of moderate fruit intake in the diet include cell differentiation (which decreases cell proliferation), antioxidant potential, increase in activity of naturally protective enzymes, lower estrogen levels, and enhanced immune function. Research shows a strong relationship between overall health and fruit consumption. Total cancer risk is often reported to decrease by at least 12 percent in populations that receive adequate amounts of fruit per the dietary guidelines Fruits, like the cherries from which this supplement is made, contain compounds thought to help prevent cancer. (AP/ Wide World Photos) of the U.S. Department of Health and Human Services and the U.S. Department of Agriculture. The correlation is almost certainly stronHow phytochemicals work: Fruits contain many phyger than results indicate, as studies on the relationship betochemicals that are believed to have an inverse relationtween increased fruit intake and reduced cancer rates must ship to cancer incidence or at least act as a protective agent track a healthy person over many years to assess the relaagainst cancer-causing substances in the human body. tionship to subsequent cancer incidence—this involves reSome of these chemicals believed to be active include liance on memory before the cancer diagnosis. Additional allium compounds, carotenoids, coumarins, dietary fiber, studies analyzing the relationship between increased fruit dithiolthiones, flavonoids, folic acid, endole-3-carbinol, in diet and reduction of various cancers have begun. inositol hexaphosphate, isoflavones, isothiocyanates, Dlimonene, phytosterols, protease inhibitors, saponins, seSide effects: Generally no side effects are experienced lenium, and vitamins, especially vitamins C and E. by eating fruit. However, excessive dietary intake of fruit Carotenoids, including alpha- and beta-carotene, lutein, may cause gastrointestinal discomfort in some individand lycopene, are found in yellow and orange vegetables uals and increase the incidence or extent of diarrhea in and fruits and act as antioxidants to maintain the functionothers. ing of the immune system. Antioxidants bind to free radiDwight G. Smith, Ph.D. cals in the human body. Free radicals are unstable molecules that lack a sufficient number of electrons and can See also Antioxidants; Beta-carotene; Bioflavonoids; Cadamage genetic material and proteins. This disrupts cell rotenoids; Chemoprevention; Coenzyme Q10; Dietary supmolecules and chemical processes, making cells more susplements; Fiber; Folic acid; Free radicals; Herbs as antioxceptible to cancer. When the amount and availability of idants; Isoflavones; Lutein; Lycopene; Macrobiotic diet; free radicals in cells and tissues is decreased, the likeliNutrition and cancer prevention; Phytoestrogens; Prevenhood of cells becoming cancerous is similarly decreased. tion; Resveratrol; Saw palmetto; Sun’s soup; Wine and Studies have also suggested that carotenoids stimulate the cancer. manufacture of detoxifying enzymes and inhibit the for-
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u Gallbladder cancer Category: Diseases, symptoms, and conditions Also known as: Gallbladder carcinoma Related conditions: Bile duct cancer (cholangiocarcinoma) Definition: Gallbladder cancer is a rare cancer that starts in the lining of the gallbladder. The gallbladder stores bile, a liquid necessary for the breakdown of fat. The vast majority of gallbladder cancers—more than 80 percent— are of a type known as adenocarcinoma. Other types of gallbladder cancer include squamous cell carcinoma and small-cell carcinoma. Risk factors: Gallbladder cancer occurs more frequently in women than in men (a 4:1 ratio) and usually in people older than age fifty, with most patients in their mid- to late sixties. In the United States, Native Americans and Hispanics are at the highest risk for the disease. Worldwide, high incidence of the disease occurs in Chile, Bolivia, and parts of Asia. Obesity and a sedentary lifestyle have been identified as risk factors for gallbladder cancer. About 80 percent of gallbladder cancer patients have gallstones. However, only 0.5 percent of patients with gallstones will go on to develop gallbladder cancer. Cysts in the bile ducts also raise the risk of gallbladder cancer. Calcification (hardening) in parts of the gallbladder increases the risk of gallbladder cancer. People with calcifications throughout the entire gallbladder wall have no higher risk than the general population. Etiology and the disease process: There is strong circumstantial evidence that gallbladder cancer results from constant inflammation of the gallbladder. Gallstone disease causes repeated irritation and inflammation of the gallbladder. Most patients with gallbladder cancer have gallstones in addition to their cancer. Patients with large gallstones (greater than 3 centimeters, or cm) are at ten times the risk for developing gallbladder cancer. Also supporting the inflammation theory is the fact that repeated infections in the gallbladder seem to increase a person’s risk of this cancer. Gallbladder cancer spreads through the lymph nodes and lymph vessels as well as the blood vessels. Lymph vessels, which extend into every organ in the body, collect abnormal or foreign cells into the lymph nodes. This is why gallbladder cancer surgery often includes removal of the lymph nodes in the area of the gallbladder, liver, and pancreas. Another route through which the cancer spreads is directly into the liver. Because there is no separation be-
Gallbladder cancer tween the gallbladder and liver tissues, a gallbladder tumor can directly enter the liver. Incidence: The disease is rare. There are approximately 7,000 new cases of gallbladder cancer each year in the United States. According to the American Cancer Society, the incidence of the disease decreased by 50 percent between 1973 and 2007. On average, there are 2.5 cases of the disease for every 100,000 people in the United States. Symptoms: Unfortunately, symptoms of gallbladder cancer do not appear until the disease is advanced. When they do appear, they are not specific and are often identical to symptoms of other (benign) gallbladder or liver problems. Symptoms of gallbladder cancer may include the following: • Enlarged liver • Fever • Jaundice (yellowing of the skin and whites of the eyes) • Loss of appetite • Nausea or vomiting • Pain in the upper right part of the abdomen • Severe itching • Swelling of the stomach due to fluid accumulation (ascites) • Weight loss Screening and diagnosis: There is no test to screen for gallbladder cancer. Because the symptoms are often the same as for other liver or biliary diseases, unless doctors find the cancer during surgery to remove gallstones, diagnosis is usually delayed until the cancer is advanced and symptoms appear. Tests for suspected gallbladder cancer include the following: • A complete physical examination • Liver function tests • Cancer antigen (CA) 19-9 assay (while this test identifies a marker that is not specific for gallbladder cancer, it may focus suspicion in combination with other test results) • Endoscopic retrograde cholangiopancreatography (ERCP), an X ray of the bile ducts that uses a lighted tube (endoscope) passed from the mouth to the small intestine; a smaller tube inside the endoscope delivers a special dye into the bile ducts, and X rays of the dye can help diagnose blockage or narrowing of the ducts • Blood tests, which may show abnormal amounts of certain chemicals in the blood • Percutaneous transhepatic cholangiography (PTHC), an X ray of the liver and bile ducts during which a special dye is injected into the liver and X rays follow the dye 493
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through the bile ducts; PTHC helps diagnose blockage or narrowing of the bile ducts • Biopsy, the examination of a tissue sample under a microscope • Computed tomography (CT) scan and magnetic resonance imaging (MRI), usually the best diagnostic tools to verify gallbladder cancer In the United States, staging of gallbladder cancer is done according to the criteria of the American Joint Commission on Cancer (AJCC). These criteria use the TNM (tumor/lymph nodes/metastasis) staging system, which looks at the tumor location, whether the cancer has invaded any near or distant lymph nodes, and whether the cancer has spread (metastasized) to other parts of the body. The TNM system for gallbladder cancer is as follows: • TX: Primary tumor cannot be evaluated. • T0: No evidence of primary tumor is found. • Tis: The cancer is limited to the innermost layer of the gallbladder (mucosa). • T1a: The tumor invades the lamina propria (the layer next to the mucosa). • T1b: The tumor invades the muscle layer (the next layer). • T2: The tumor invades the layer surrounding the muscle; it does not extend beyond the outer covering of the gallbladder (serosa) or into the liver. • T3: The tumor goes through the serosa or into the liver or one other organ, such as the stomach, small intestine, or pancreas. • T4: The tumor invades the main portal vein (connecting the digestive tract to the liver) or hepatic artery, or invades multiple organs outside the liver. • NX: Regional lymph nodes cannot be assessed. • N0: No regional lymph node spread is found. • N1: Regional lymph node spread is found. • MX: Distant metastasis cannot be assessed. • M0: No distant metastasis is found. • M1: Distant metastasis is found. Staging is as follows: • Stage 0: Tis, N0, M0 • Stage IA: T1, N0, M0 • Stage IB: T2, N0, M0 • Stage IIA: T3, N0, M0 • Stage IIB: T1, N1, M0; T2, N1, M0; or T3, N1, M0 • Stage III: T4, any N, M0 • Stage IV: Any T, any N, M1
There are several types of gallbladder removal surgery (cholecystectomy): • Simple cholecystectomy: Removal of the gallbladder alone • Extended cholecystectomy: Removal of the gallbladder, a small area of the liver right next to the gallbladder, and area lymph nodes • Radical cholecystectomy: Removal of the gallbladder, a wedge-shaped part of the liver, the common bile duct, tissues between the liver and the small intestine, and the lymph nodes along the path between the liver and the small intestine The type of surgery a patient will have depends on how the cancer was found and how advanced it is. When surgery is not a treatment option, palliative surgery may help relieve symptoms. Palliative surgery is not intended to treat or control the disease. Follow-up radiation after surgery helps prolong survival in some patients. Chemotherapy may be added to surgery and radiation. Two chemotherapy drugs that show some success in treating gallbladder cancer are 5-fluorouracil (5-FU) and gemcitabine. Radiation and chemotherapy (alone or in combination) can also be used before surgery to try to shrink a large tumor. When surgery is no longer an option, patients should consider enrolling in clinical trials of new treatments.
Treatment and therapy: Currently, the only realistic treatment option is surgery. Removal of the gallbladder can cure patients with Stage 0 or I cancer, and the cure rate is 80 to 100 percent.
Prognosis, prevention, and outcomes: Because the disease is often diagnosed at an advanced stage, the prognosis is usually poor. The median survival time from diagnosis is less than six months. The five-year survival rate is 5 per-
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Stage at Diagnosis and Five-Year Relative Survival Rates for Gallbladder Cancer, 1988-2001 Stage a
Localized Regionalb Distantc Unstaged
Cases Diagnosed (%)
Survival Rate (%)
21.5 39.9 35.9 2.7
41.7 13.6 1.2 13.1
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007) a Cancer still confined to primary site b Cancer has spread to regional lymph nodes or directly beyond the primary site c Cancer has metastasized
Salem Health: Cancer cent. However, the prognosis depends on the stage of the cancer at diagnosis. When diagnosed early (usually during surgery to remove gallstones), patients can be completely cured. Lifestyle modifications, such as weight loss and an exercise program, may help prevent gallbladder cancer. Adi Ferrara, B.S. u For Further Information Icon Health. Gallbladder Cancer: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References. San Diego, Calif.: Author, 2004. Ko, A., E. H. Rosenbaum, and M. Dollinger. Everyone’s Guide to Cancer Therapy: How Cancer Is Diagnosed, Treated, and Managed Day to Day. 5th ed. Kansas City, Mo.: Andrews McMeel, 2007. Sarg, M. J., and A. D. Gross. The Cancer Dictionary. 3d ed. New York: Facts On File, 2006. u
Other Resources
American Cancer Society Detailed Guide: Gallbladder Cancer Http://www.cancer.org/docroot/CRI/CRI_2_3x .asp?rnav=cridg&dt=68 Clinical Trials Registry http://clinicaltrials.gov/ National Cancer Institute Gallbladder Cancer http://www.cancer.gov/cancertopics/types/ gallbladder/ See also Bile duct cancer; CA 19-9 test; Cholecystectomy; Endoscopic retrograde cholangiopancreatography (ERCP); Endoscopy; Gastrointestinal cancers; Hepatic arterial infusion (HAI); Laparoscopy and laparoscopic surgery; Nuclear medicine scan; Obesity-associated cancers; Pancreatitis; Percutaneous transhepatic cholangiography (PTHC); Ultrasound tests.
u Gallium scan Category: Procedures Also known as: Nuclear medicine scan, radioisotope scan Definition: A gallium scan is a nuclear medicine imaging study that evaluates specific tissues based upon their uptake of an administered radioactive isotope. During a gallium scan, the tracer (gallium 67 citrate) is injected into a vein. It travels through the bloodstream into
Gallium scan the tissues—primarily the bones, liver, and intestines. It usually takes a few days for the tracer to accumulate in the tissues, so in most cases a scan is done two days after an injection of the tracer and repeated at three days. Areas of increased tracer uptake show up as bright, or “hot,” spots on an X ray. Delineated problem areas may be caused by infection, inflammation, or tumor (rapid cell division). The gallium scan was the standard for cancer diagnosis and staging until it was replaced by positron emission tomography (PET) scans. Gallium 67 is often used in conjunction with a bone scan (using technetium 99m phosphate) as “a double tracer” technique to overlay areas of inflammation within organ systems. Gallium is less dependent on blood flow than technetium and may identify foci that would otherwise be missed. Cancers diagnosed: Major cancers such as lymphoma, malignant bone tumors, and soft-tissue sarcomas; can be used to identify most neoplasms, whether benign or malignant Why performed: A gallium scan is performed to detect the presence of cancerous tissue. It may be employed to determine whether a cancer has spread (metastasized) to other parts of the body or to monitor the effectiveness of cancer treatment. It can also be used to diagnose inflammatory conditions such as pulmonary fibrosis or sarcoidosis; to monitor the response to antibiotic treatment; to detect an abscess or certain infections, especially in the bones; and to detect an unknown source of infection that is causing a fever. Patient preparation: Gallium accumulates in the large intestine (colon) before being eliminated in the stool. Patients may need to take a laxative the night before the scan and have an enema one to two hours prior to the scan to prevent gallium in the colon from interfering with pictures being taken of the area. The doctor and radiologist should also be informed of possible pregnancy, breast-feeding activity, and the use of a barium enema within the previous four days or medicine (such as Pepto-Bismol) that contains bismuth, as barium and bismuth can interfere with the test results. Steps of the procedure: A gallium scan is performed by a nuclear medicine technologist. The scan pictures are interpreted by a radiologist or nuclear medicine specialist. The arm is cleaned with soap, betadine, and/or alcohol around the injection site. A small amount of the radioactive chemical is then injected through a vein. After administration of the tracer, the patient is brought back to the radiology facility and scans are completed at forty-eight hours and repeated at seventy-two hours. 495
Gallium scan
Salem Health: Cancer The protocol for scanning requires the removal of all jewelry. Most clothes are removed, and the patient is provided with a cloth gown or paper covering. The patient lies in a supine position (on the back) upon a table. A large scanning (gamma) camera will be positioned closely above the patient. After the initial injection, the camera will scan for radiation released by the tracer and produce pictures of the tracer in the tissues. These images serve as a baseline to compare subsequent scan data completed in the next two to three days. The camera will move slowly above and around the body. The camera does not produce any radiation, so the patient is not exposed to any additional source of radioactive material. Different positioning may be attempted so that an area of interest can be viewed from different angles. Restricted movement is necessary during each scan to avoid blurring of the acquired images. Often, the patient will be asked to hold his or her breath briefly during some of the scans to minimize chest movement that occurs with respiration. Each scan can take approximately sixty to ninety minutes. After the procedure: A gallium scan is painless. There are no activity restrictions postscan. Risks: There is a risk of damage to cells and tissues exposed to any level of radiation, including the low level of radiation released by a radioactive tracer such as gallium. Allergic reactions to radioactive tracers are rare. Most of the tracer will be eliminated from the body (in the urine or stool) within four days. Occasionally, some soreness or swelling can develop at the injection site. These symptoms can be relieved by applying moist, warm compresses to the affected area. Results: A gallium scan utilizes a special radiographic camera to obtain pictures of certain tissues in the body after a radioisotope makes them visible. The results of the scan are available within forty-eight hours after the scans are completed. The entire process takes approximately five days. John L. Zeller, M.D., Ph.D. u
Full-body gallium scan showing cancer that has spread from the lungs to the rib and vertebra. (Scott Camazine/Photo Researchers, Inc.)
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For Further Information Hussain, R., D. Christie, V. Gebski, et al. “The Role of the Gallium Scan in Primary Extranodal Lymphoma.” Journal of Nuclear Medicine 39, no. 1 (1998): 95-98. Maderazo, E., N. Hickingbotham, C. Woronick, et al. “The Influence of Various Factors on the Accuracy of Gallium-67 Imaging for Occult Infection.” Journal of Nuclear Medicine 29, no. 5 (1988): 608-615. Mettler, Fred A., Jr., and Milton J. Guiberteau. Essentials
Salem Health: Cancer
Gamma Knife
of Nuclear Medicine Imaging. 5th ed. Philadelphia: Saunders/Elsevier, 2006. Ziessman, Harvey A., Janis P. O’Malley, and James H. Thrall. Nuclear Medicine: The Requisites. 3d ed. Philadelphia: Mosby Elsevier, 2006. u
Other Resources
American College of Radiology http://www.acr.org Society of Nuclear Medicine http://www.snm.org See also Burkitt lymphoma; Imaging tests; Nuclear medicine scan; Radionuclide scan.
u Gamma Knife Category: Procedures Also known as: Radiosurgery, stereotactic radiosurgery (SRS), stereotactic radiotherapy Definition: The Gamma Knife, not actually a knife, is a large precision system that delivers 201 intensely focused gamma-radiation beams to treat tumors and other problems of the brain and nervous system. It resembles a computed tomography (CT) scanner. Gamma Knife technology was developed by Lars Leskell (1907-1986), a Swedish neurosurgeon.
A nurse explains how the Gamma Knife works. (AP/Wide World Photos)
Cancers treated: Cancerous tumors that originate elsewhere in the body but have spread to the brain Why performed: Gamma Knife “surgery” is a noninvasive alternative to traditional open-brain surgery. The precisely focused radiation beams of the Gamma Knife allow surgeons to treat very small, deep-seated tumors without damaging nearby brain tissue. Patient preparation: Patients should not eat or drink anything after midnight the night before the procedure. They should inform their doctor if they are taking medication to control diabetes, are allergic to shellfish or iodine, or have implanted medical devices in the body. Patients must remove glasses, contact lenses, jewelry, makeup, nail polish, wigs, and dentures. Steps of the procedure: Surgeons apply a local anesthetic and use four screws to attach a lightweight frame to the patient’s head. The frame prevents the head from moving and allows surgeons to identify the treatment target accurately.
With the head frame in place, surgeons take electronic images of the brain to establish the exact size, shape, and location of the target. From the images, surgeons develop a specific treatment plan. For the treatment, the patient lies on a couch. A helmet is attached to the head frame. The couch slides into the Gamma Knife unit, where radiation destroys the tumor. The patient is awake during the procedure, which lasts from a few minutes to more than an hour, depending on the size and location of the tumor. After the procedure: When the treatment is completed, the head frame is removed. In most cases, the patient goes home the same day and returns to a normal routine in a day or two. Risks: Because surgeons make no incisions, the risk of complications from use of the Gamma Knife is low. Some patients feel minor soreness from the head frame. Some patients experience mild headache, dizziness, or nausea, which last only a short while. 497
Gardner syndrome The dose of radiation outside the target is very low and poses little risk. Occasionally, patients experience swelling in the brain, which is temporary and treatable. Results: The effects of radiation treatments take time: weeks, months, or even years. Wendell Anderson, B.A. See also Acoustic neuromas; Astrocytomas; Cobalt 60 radiation; Meningiomas.
u Gardner syndrome Category: Diseases, symptoms, and conditions Also known as: Gardner’s syndrome, familial adenomatous polyposis, familial polyposis coli, hereditary adenomatosis of the colon and rectum, bone tumor-epidermoid cyst-polyposis Related conditions: Colon and rectal polyps, cancer Definition: Gardner syndrome is a rare, genetically linked disorder that is classified as a variant form of familial adenomatous polyposis (FAP), a group of disorders most commonly identified by the growth of numerous polyps in the large intestine or colon. In Gardner syndrome, large amounts of benign tissue form in multiple organs. As with FAP, this includes colon polyps as well as skull tumors, cysts and fibrous tumors in the skin, extra teeth, and a congenital eye condition. Gardner syndrome significantly increases an affected person’s risk of developing colorectal cancer, small bowel cancer, pancreatic cancer, and papillary thyroid cancer. Early diagnosis of the disorder is essential as colon polyps resulting from Gardner syndrome have a 100 percent chance of becoming cancerous. Risk factors: Gardner syndrome is genetically linked, meaning that it is associated with a defect, or mutation, in one or more genes. A person with family members with the disease or with the defective gene is at high risk of developing this disorder. It is estimated that 20 percent of patients do not have a family history of Gardner syndrome or FAP, which indicates a spontaneous mutation of the gene. Etiology and the disease process: Normally, during conception, the body receives two copies of every gene, one each from the mother and the father. It takes only one copy of a defective gene, from either the mother or father, for a person to be affected by Gardner syndrome. This disease is caused by a mutation in the gene called APC (adenomatous polyposis coli). The defective APC gene initiates changes 498
Salem Health: Cancer in at least three other genes, causing what is known as the adenoma-to-carcinoma sequence, which allows cells in the colon to increase in number and causes the lining of the colon to thicken. Most people who receive this defective gene develop the disease. Although the way Gardner syndrome develops varies from person to person, it always presents a high risk of developing polyps, tumors, and cancer, especially in the colon. Other physical changes that occur (with their percentage of risk when known) include congenital hypertrophy of the retinal pigmented epithelium (55 to 88 percent), epidermoid cysts (53 percent), stomach and small intestine polyps (90 percent), thyroid cancer, desmoids (10 to 35 percent), dental abnormalities (70 percent), hepatoblastoma, and bone tumors. Incidence: Gardner syndrome is considered to be rare, with only 1 case per 1 million people, whereas the incidence of FAP is 1 case per 8,000 people. An increased risk for the development of thyroid cancer and desmoid tumors has been noted in women with Gardner syndrome. Most patients with Gardner syndrome have already been diagnosed with polyps when they reach puberty. From 80 to 90 percent of polyps are located in the left colon, including the splenic flexure and descending, sigmoid, and rectosigmoid colons. Cancers typically develop between ages twenty and thirty but can occur at any age. Symptoms: The patient with Gardner syndrome may experience a wide variety of symptoms, depending on the body systems affected. The most common are gastrointestinal symptoms and include rectal bleeding, pain, diarrhea or constipation, nausea, and vomiting. Multiple cysts may be found on the patient’s body, particularly on the face, scalp, and extremities. They usually cause no symptoms but may become itchy or inflamed. Screening and diagnosis: When a person has a family history of Gardner syndrome, blood tests can be performed for deoxyribonucleic acid (DNA) analysis and to look for mutations in the APC gene. A positive test result for an APC mutation is sufficient for diagnosis. Laboratory testing to determine the extent of the disease includes stools for occult blood, thyroid function studies, and liver function tests as well as basic chemistries, blood counts, and electrolyte levels. Imaging studies include upper and lower gastrointestinal series, esophagogastroduodenoscopy, colonoscopy, computed tomography (CT) scanning, magnetic resonance imaging (MRI), and ultrasonography to screen for polyps and tumors, as well as skull, facial, and dental X rays to evaluate oral abnormalities and screen for tumors. Most testing procedures should be performed on an annual basis after initial diagnosis.
Salem Health: Cancer Treatment and therapy: Extensive surgery is indicated when colon polyps are identified in a patient with Gardner syndrome because of the risk of colon cancer. Osteomas of the skull and dental abnormalities should be removed if they interfere with normal function or are deforming. Cysts on the skin may require removal if they are producing symptoms or are disfiguring. The necessity of surgery to remove other tumors is evaluated based on their location, type of tumor, patient’s surgical risk, and potential risks of not removing them. Chemotherapy, using doxorubicin with dacarbazine or high-dose tamoxifen, has been shown to reduce polyps following colon surgery. Treatment with sulindac, a nonsteroidal anti-inflammatory drug, is recommended for every patient following a total colectomy; oral calcium has been shown to reduce the colon cancer risk; and sulindac, tamoxifen, or a combination of both is recommended for other manifestations of the disease. Research into other treatments, including gene therapy, is ongoing. Prognosis, prevention, and outcomes: The five-year survival rate for patients older than forty-five who do not have surgery to remove the colon is 0 percent; with surgery, it is nearly 100 percent. The recurrence rate after surgery ranges from 30 percent in twenty years to 45 percent in thirty years. There is no prevention for Gardner syndrome. Dorothy P. Terry, R.N.
Garlic and allicin
u Garlic and allicin Category: Lifestyle and prevention Also known as: Allium sativum Definition: Garlic (Allium sativum) is a nontoxic plant bulb in the Allium genus, which includes onions, leeks, and shallots. Allicin, a chemical created by enzymes when garlic is processed, produces garlic’s odor and taste. Cancers treated or prevented: Gastric (stomach) cancer, colon cancer, breast cancer, prostate cancer, throat cancer Delivery routes: Oral ingestion by pill or in food How this compound works: Historically, humans have consumed garlic for medicinal purposes to soothe digestive and circulatory problems. Aware of nutritional strategies to prevent and control diseases, scientists initiated cancer research exploring garlic and its allyl sulfur components in the mid-twentieth century. Researchers identified allicin as garlic’s most significant chemical that could fight cancer. Allicin is created as the enzyme alliinase reacts with alliin when garlic bulbs are sliced or crushed. Scientists hypothesized that biochemical processes in garlic which boost distribution of antioxidants might prevent cancerous cells from forming and increasing. Studies regarding use of garlic and allicin for cancer prevention and treatment have given rise to both skepti-
u For Further Information Butler, Jonathan, et al. “Gardner Syndrome: Review and Report of a Case.” Oral Oncology Extra 5, no. 41 (May, 2005): 89-92. Hansmann, A., et al. “High-Dose Tamoxifen and Sulindac as First-Line Treatment for Desmoid Tumors.” Cancer 100, no. 3 (February 1, 2004): 612-620. Pomery, Chris. DNA and Family History. Toronto, Ont.: Dundurn Press Limited, 2004. u
Other Resources
MedicineNet.com Gardner Syndrome http://www.medicinenet.com/gardner_syndrome/ article.htm National Cancer Institute http://www.cancer.gov See also Bone cancers; Colon polyps; Desmoid tumors; Fibrosarcomas, soft-tissue; Hereditary polyposis syndromes; Sarcomas, soft-tissue; Thyroid cancer; Turcot syndrome.
Garlic has been studied for cancer prevention and treatment. (Object Gear)
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Gastric polyps cism and optimism. In 1990, the National Cancer Institute (NCI) studied the potential use of allium vegetables, including garlic, for stomach cancer. That year, researchers attended the First World Congress on the Health Significance of Garlic in Washington, D.C. Despite some scientists’ suggestion that garlic and its allyl sulfur components could prevent or inhibit malignancies, experts emphasized that garlic’s anticancer effectiveness had not been scientifically proven. By the early twenty-first century, international researchers had published several thousand scientific journal articles discussing allium plants. Studies focused on garlic’s effect on gastric, colon, breast, prostate, and throat cancers. Investigators achieved promising laboratory results regarding allicin use in mice. At the Weizmann Institute of Science at Rehovot, Israel, scientists delivered alliinase and alliin to malignant tumors, where they produced allicin that entered and destroyed those cells. When researchers combined allicin with rituximab, an anticancer drug, they found that this mixture killed 95 percent of cancerous cells in mice. In October, 2006, the University of California, Berkeley Wellness Letter noted that the cancer-fighting properties of garlic and allicin remained uncertain because tests had been limited to animal subjects and cell cultures and were inconclusive. That newsletter discounted previous studies as presenting minimal evidence, stressing that clinical scientific trials using humans were necessary to declare definitively anticancer properties expressed by garlic and allicin. Although garlic and allicin have not been scientifically shown to cure cancer in humans, they contribute to healthy diets. People with cancer often consume garlic to strengthen their immune systems and receive other health benefits relevant to cholesterol and heart concerns. Garlic can be consumed raw, cooked, or in synthetic formats, providing people varying amounts and versions of allyl sulfur compounds. Side effects: Garlic, when ingested regularly as part of diet, may cause halitosis and body odors. These effects are mitigated by taking it in pill form. Some people develop gas, bloating, diarrhea, or heartburn when taking garlic, which can be mitigated by taking enteric-coated supplements. Finally, because garlic and allicin can increase prothrombin time (PT), a measure of how long it takes for blood to form clots, people taking blood thinners such as warfarin (Coumadin) and anyone about to undergo surgery should consult their physicians before taking these substances. Elizabeth D. Schafer, Ph.D. See also Fruits; Herbs as antioxidants; Nutrition and cancer prevention; Phytoestrogens; Prevention. 500
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u Gastric polyps Category: Diseases, symptoms, and conditions Also known as: Stomach polyps Related conditions: Gastritis, familial adenomatous polyposis, Peutz-Jeghers syndrome, gastric carcinoid tumors Definition: Gastric polyps are small tissue growths on the lining of the stomach. Risk factors: Risk factors for gastric polyps are chronic inflammation and the long-term use of proton pump inhibitors. Etiology and the disease process: The cause of gastric polyps is not completely understood. Hyperplastic polyps are thought to arise from irritation or chronic inflammation of the stomach lining. The nature of the causative agent has not been clearly established; suggested irritants include coffee, tea, and gastric acid. Long-term use of proton pump inhibitors is associated with development of hyperplastic and carcinoid polyps; this may be related to the decrease in stomach acid, which in turn causes an in-
Stomach cancer often develops near the bottom and top of the stomach. Some types of gastric polyps have the potential to become cancerous. (Kairos, Latin Stock/Photo Researchers, Inc.)
Salem Health: Cancer
Gastrinomas
crease in gastrin, a hormone that supports cell growth. Familial cancer syndromes such as familial adenomatous polyposis and Peutz-Jeghers syndrome have been linked with gastric polyps, suggesting that genetic mutations have a role in polyp formation.
u Gastrinomas
Incidence: The largest endoscopic study, of almost 13,000 patients during a four-year period, showed that gastric polyps were found in 157 patients (1.2 percent). About 66 percent of the gastric polyps were in patients over age sixty. The gastric polyps were hyperplastic (75.6 percent), inflammatory (17.8 percent), and adenomatous (6.6 percent). No correlation with stomach cancer and no gender preponderance were found with gastric polyps.
Related conditions: Peptic ulcers, gastroesophageal reflux disease (GERD), multiple endocrine neoplasia type 1 (MEN 1), liver cancer
Symptoms: Patients usually have no symptoms. However, if they are symptomatic, they may develop bleeding from the stomach or obstruction (blockage of the digestive tract). Screening and diagnosis: Most gastric polyps are discovered and diagnosed incidentally when endoscopy of the stomach is performed for an unrelated reason. Upper endoscopy is a procedure using an endoscope, a flexible tube with a small camera and an instrument for biopsy that is introduced through the upper digestive tract; it allows visual examination of the esophagus, stomach, and upper duodenum, the first part of the small intestine. No staging is applicable for gastric polyps. Treatment and therapy: Gastric polyps can be removed during endoscopy and examined in the laboratory. Multiple polyps may require removal of the largest polyp and sampling from the remaining polyps; there is no need to remove all polyps. Treatment will be based on the nature of these polyps. Prognosis, prevention, and outcomes: The majority of gastric polyps are benign. Hyperplastic polyps are also generally benign. The polyps associated with familial adenomatous polyposis and Peutz-Jeghers syndrome can become adenomatous in nature. Adenomatous polyps have an increased risk for cancer transformation; therefore, regular surveillance with upper endoscopy is warranted for these familial conditions. Miriam E. Schwartz, M.D., M.A., Ph.D., and Colm A. Ó’Moráin, M.A., M.D., M.Sc., D.Sc. See also Achlorhydria; Adenocarcinomas; Adenomatous polyps; Barium swallow; Gastrinomas; Gastrointestinal cancers; Gastrointestinal oncology; Gastrointestinal stromal tumors (GISTs); Helicobacter pylori; Krukenberg tumors; Small intestine cancer; Stomach cancers.
Category: Diseases, symptoms, and conditions Also known as: Gastrin-secreting tumors, ZollingerEllison syndrome, nonislet cell pancreatic cancer
Definition: Gastrinomas are slow-growing tumors that secrete large quantities of the peptide hormone gastrin. Gastrinomas most often arise in the wall of the duodenum, the pancreas, or the pancreatic lymph nodes. Risk factors: Gastrinomas arise spontaneously or in association with the rare genetic disorder multiple endocrine neoplasia type 1 (MEN 1). Men have double the risk of developing gastrinoma relative to women. Approximately 60 percent of all MEN 1 patients will develop pancreatic gastrinomas. Etiology and the disease process: The large amount of gastrin produced by gastrinomas causes the stomach to produce massive quantities of acid. The acid causes ulcers to form in the stomach and duodenum and can irritate and inflame the esophagus. The acid also produces water and ion imbalances in the small intestine, resulting in diarrhea. More than 50 percent of gastrinomas are malignant, usually metastasizing to nearby lymph nodes and the liver. Incidence: Gastrinomas are exceedingly rare tumors, occurring in 1 to 3 people per million. Gastrinomas are usually diagnosed when people are in their forties but can occur at any age. Symptoms: The most common symptom of gastrinoma is persistent upper abdominal pain due to severe or recurring ulcers. Chronic diarrhea is the second most frequent symptom, followed by heartburn. Other symptoms include nausea, vomiting, weight loss, and ulcer-related gastrointestinal bleeding. Screening and diagnosis: Initial diagnosis is made by measuring gastrin levels in the blood and acid output by the stomach after an overnight fast. Elevated levels of both are a presumptive diagnosis of gastrinoma. Somatostatin receptor scintigraphy is the preferred imaging technology to locate the tumor and check for metastasis. Treatment and therapy: Treatment of gastrinoma involves controlling acid production and surgical removal of tumors. Proton pump inhibitor medications are the most potent agents to block acid secretion. Chemotherapy with streptomycin, 5-fluorouracil, and doxorubicin can shrink 501
Gastrointestinal cancers tumors and control metastasis-associated symptoms but does not prolong survival time. Prognosis, prevention, and outcomes: The five-year survival rate for patients with isolated, operable tumors is 86 percent, and surgery is curative in 20 to 30 percent of cases. For patients with liver metastasis or numerous, diffuse tumors, the five-year survival rate is 20 percent. Tumors that have spread to the liver are usually inoperable and are the main cause of death in gastrinoma patients. Tumor recurrence is monitored by regular screening of fasting gastrin levels. Lifelong treatment with medications to control acid production is often necessary. Pamela S. Cooper, Ph.D. See also Cyclin-dependent kinase inhibitor-2A(CDKN2A); Endocrinology oncology; Gastrointestinal cancers; Islet cell tumors; Liver cancers; Multiple endocrine neoplasia type 1 (MEN 1); Neuroendocrine tumors; Pancreatic cancers; Small intestine cancer; Stomach cancers; ZollingerEllison syndrome.
Salem Health: Cancer Exposure to rubber, leather, or certain dyes increases the risk of esophageal cancer, while industrial dusts and fumes increase the risk for gastric cancer. Exposure to nitrosamine is a factor for cancer of the small intestine. A family history of polyps increases risk for gastric cancer. A history of some types of polyps; ulcerative colitis; cancer of the breast, ovary, or uterus; and cancer among firstdegree relatives are risk factors for colon cancer. Diet is a greater risk factor for gastric cancer in Japan, Korea, parts of Eastern Europe, and Latin America than in the United States, possibly because of diets high in dried, smoked, salted, and pickled foods. Diets high in fat and low in fruits, vegetables, and other high-fiber foods are risk factors for colorectal cancer. Although cancer of the small intestine is unusual, certain inherited disorders may be risk factors. A history of genital warts, fistulas, fissures, genital herpes, gonorrhea, radiation dermatitis, homosexuality, symptomatic human immunodeficiency virus (HIV) disease, hemorrhoids, or anal degenerative skin changes increases the risk of anal cancer.
Definition: Gastrointestinal cancers are malignant tumors in the various organs of the gastrointestinal tract—the esophagus, stomach, colon, small intestine, rectum, and anus—formed when normal cells enlarge and divide abnormally.
Etiology and the disease process: Although the causes of many gastrointestinal cancers are unknown, for some of these cancers, causative agents or factors have been found. Alcohol and tobacco abuse appear to be causes of esophageal cancer in North America; in other parts of the world, exposure to environmental carcinogens and diets deficient in riboflavin, magnesium, nicotinic acid, and zinc are causative factors. Chewing betel nuts and smoking bidi are major factors in India. The exact cause of stomach cancer is unknown, but carcinogens, notably nitrites found in smoked foods or used as preservatives, are suspect. Risk factors for colorectal cancer are diets high in saturated fat and low in fiber and calcium, a lack of exercise, and parasitic infestation of Schistosomiasis japonicum. Cancer of the small intestine is rare, and its causes are unknown. The primary cause of anal cancer is chronic irritation.
Risk factors: Major risk factors for developing gastrointestinal cancers are age, gender, race, tobacco use, exposure to carcinogens, family history, and diet. Esophageal cancer and cancer of the small intestine usually appear after a person reaches the age of sixty; stomach, over fiftyfive; colorectal, over fifty; and anal, over forty. Four times as many men as women develop esophageal cancer, and twice as many men as women get stomach cancer. More women are likely to have anal cancer of the inner part of the anus, while more men have outer involvement. African Americans are more likely to have gastric cancer than white Americans. Tobacco use may put people at risk for esophageal and gastric cancer.
Incidence: Incidence rates vary by the affected digestive tract organ. Esophageal cancer occurs much more often in China, Singapore, Iran, Puerto Rico, Switzerland, and France than in North America. In the United States, three times as many men as women are stricken, and blacks outnumber whites 3.5 to 1. Stomach and colorectral cancer is most common in industrialized countries with high living standards; colorectal cancer is uncommon in Asian and Third World countries. Environmental and dietary factors in westernized countries probably account for the higher incidence. Cancer of the small intestine is almost twice as common in men as in women, and blacks are almost twice as likely to have it as whites. It is rare among American In-
u Gastrointestinal cancers Category: Diseases, symptoms, and conditions Also known as: Abdominal and intestinal neoplasms Related conditions: Cancer of the gallbladder and bile duct, pancreas, and liver; a Helicobacter pylori infection; pernicious anemia; acid reflux disease; gastric polyps; familial polyposis; ulcerative colitis; Crohn disease
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Gastrointestinal cancers
Estimated New Cases and Deaths from Gastrointestinal Cancers in 2008 Cancer Esophagus Stomach Colon and rectum Small intestine Anus
Newly Diagnosed Cases
Deaths
16,470 21,500 148,810 6,110 5,070
14,280 10,880 49,960 1,100 680
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008
dians and native Alaskans, and relatively rare among Hispanics and Asians and Pacific Islanders. Anal cancer accounts for only 1 percent or 2 percent of gastrointestinal cancers worldwide. Symptoms: Symptoms vary depending on the part of the gastrointestinal tract that is affected. Esophageal cancer is marked by difficulty in swallowing; a feeling of fullness, pressure, or burning as food passes down the tract; indigestion; heartburn; vomiting; choking on food; weight loss; coughing and hoarseness; and pain behind the breastbone or in the throat. Stomach cancer may present no symptoms in the early stages; later, they are often vague and include indigestion or heartburn; abdominal pain or discomfort; nausea and vomiting; diarrhea or constipation; bloating after meals; loss of appetite; weakness and fatigue; and vomiting of blood or bloody stools. Colorectal cancer symptoms result from local obstruction or, in more advanced stages, from extension to adjacent organs. In early stages, symptoms are usually vague and vary according to the location of the tumor. In later stages, symptoms include pallor, cachexia, ascites, enlarged liver, and dilatation of lymphatic vessels. About 10 percent of people with cancer of the small intestine experience no symptoms, but most patients have abdominal pain or distension because of obstruction, as well as weight loss, nausea and vomiting, fever, change in bowel habits, and general malaise. Anal cancer may exhibit no symptoms in early stages; later, there may be bleeding, pressure, pain, itching, and a palpable mass. Screening, diagnosis, and staging: Routine screening tests for gastrointestinal cancers are not generally performed, but a colonoscopy is used in people over the age of fifty to look for signs of polyps that might lead to colon cancer. People should monitor digestive symptoms, particularly if these change or if they develop gastrointestinal re-
flux desease (acid reflux, or GERD), and immediately discuss such symptoms with their doctor. After symptoms have appeared, diagnosis usually begins with the physician performing a physical examination and taking a family medical history. Endoscopy, biopsy, and imaging tests such as a barium swallow, computed tomography (CT), and magnetic resonance imaging (MRI) are used for further study. When symptoms of esophageal cancer appear, a thorough family medical history is done and a complete physical examination is performed. An X-ray study (barium swallow) or an esophagoscopy can find changes in the shape of the esophagus. The doctor can do a tissue biopsy through the endoscope and brush cells from the esophageal wall for examination by a pathologist. If cancer is found, additional tests to determine the extent of involvement include a CT scan, an MRI scan, a laryngoscopy, or a bronchoscopy. These tests will determine staging, or classification of the extent of the cancer. For esophageal cancer the stages are as follows: • Stage I: Cancer is in only a small part of the esophagus; it has not spread to nearby tissues, lymph nodes, or other organs. • Stage II: Cancer is in a large portion of the esophagus; it has spread to all sides of the esophagus but not to other tissues. • Stage III: Cancer has spread to tissues or lymph nodes near the esophagus but not to other parts of the body. • Stage IV: Cancer has spread to other parts of the body. When symptoms of stomach cancer appear, the doctor will take a medical history, do a physical examination, and order additional tests: a fecal occult blood test, an upper gastrointestinal series (barium swallow), and an endoscopy. If cancer is identified, staging is as follows: • Stage 0: Cancer is only in the innermost layer of the stomach wall. • Stage I: Cancer is in the second or third layers of the stomach wall but has not spread to nearby lymph nodes, or it is in the second layer and nearby lymph nodes. • Stage II: Cancer is in the second layer of the stomach wall and in more distant lymph nodes; in only the third (muscle) layer and the nearby lymph nodes; or in all four stomach wall layers but not in lymph nodes or other organs. • Stage III: Cancer is in the third layer and more distal lymph nodes; in all four layers of the stomach wall and nearby or more distant lymph nodes; or in all four layers and nearby tissues, with or without nearby lymph node involvement. • Stage IV: Cancer has spread to nearby tissues and to distant lymph nodes or to other parts of the body. 503
Gastrointestinal cancers
Salem Health: Cancer
Although only tumor biopsy can verify colorectal cancer, several other tests that can aid in detection include digital examination, proctoscopy or sigmoidoscopy, colonoscopy, computed tomography scan, and barium X rays. The staging is as follows: • Stage I: Cancer is present in the innermost and middle tissue layers of the colon. • Stage II: Cancer has spread beyond the middle layers and into nearby tissues around the colon or rectum, or has spread through the peritoneum or to nearby organs.
•
Stage III: Cancer has spread from the innermost layer to the middle layers and is in as many as three lymph nodes; or has spread to three lymph nodes and beyond the middle layers, to tissues nearby the colon or rectum, or into nearby organs or through the peritoneum; or to four or more lymph nodes and to or beyond the middle layers of the colon wall, to tissues nearby the colon or rectum, or to nearby organs or through the peritoneum. • Stage IV: Cancer has spread to nearby lymph nodes and distant sites such as the lungs or liver.
Esophagus Liver Liver (hepatic) ducts Gallbladder
Pancreas
Stomach Cystic duct
Duodenum
Bile/pancreatic duct opening
Small intestine
Colon Appendix Rectum
Cancer can affect most parts of the gastrointestinal system.
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Salem Health: Cancer Treatment for cancer of the small intestine is usually determined by cell type: adenocarcinomatous, lymphomatous, sarcomatous, or carcinoid. However, staging is done for lymphoma: • Stage I: Cancer in only one lymph node area or one area or organ outside the lymph nodes • Stage II: Cancer found either in two or more lymph nodes on the same side of the diaphragm or in only one area or organ outside the lymph nodes • Stage III: Lymph node involvement on both sides of the diaphragm and possible spread to an area or organ near the lymph nodes • Stage IV: Metastasis to one or more organs outside the lymph system or to only one organ outside the lymph system, but to lymph nodes far away from the organ involved The following stages are used for anal cancer: • Stage 0 (carcinoma in situ): Cancer is only in the top layer of anal tissue. • Stage I: Cancer has spread beyond the top layer of anal tissue but involves less than an inch. • Stage II: Cancer has spread beyond the top layer and is larger than an inch; no lymph node or organ is involved. • Stage IIIA: Cancer involves lymph nodes around the rectum or has spread to nearby organs such as the vagina or bladder. • Stage IIIB: Cancer has invaded lymph nodes in the middle of the abdomen or in the groin, or has spread to both nearby organs and lymph nodes around the rectum. • Stage IV: Cancer has spread to distant lymph nodes within or outside the abdomen. Treatment and therapy: Treatment of gastrointestinal cancers may vary depending on the tumor’s location, size, extent, and cell type, as well as the patient’s age and general health, but usual treatments include surgery to remove the tumor and nearby lymph nodes, radiation therapy to shrink the tumor before surgery or to destroy any cancerous cells remaining after surgery, and chemotherapy, alone or combined with radiation therapy. The ideal treatment for stomach cancer is radical surgery, involving a total or subtotal gastrectomy and the removal of a portion of tissue around the stomach. Another treatment option is biological therapy (immunotherapy), designed to help the body’s immune system attack and destroy the malignant cells With colorectal cancer, after surgery, if the healthy sections of the colon cannot be reconnected, a colostomy may be performed, allowing evacuation of body waste through an opening (stoma) in the abdomen. The small intestine is very sensitive to radiation, limiting the usefulness of this therapy, however. The size of the tumor may determine the method
Gastrointestinal cancers of treatment of anal cancer. Superficial in situ tumors (less than 1 inch) may require only local excision or radiotherapy alone. Tumors 1 to 2 inches are best treated by chemotherapy and radiation. Larger tumors may require chemotherapy, radiation, and surgery. Prognosis, prevention, and outcomes: Five-year survival rates for gastrointestinal cancers are as follows: • Esophageal cancer: Stage 0, excellent; Stage I, over 50 percent; Stage II, 10 to 15 percent; Stage III, less than 10 percent; Stage IV, unusual. • Stomach cancer: Stage 0, over 90 percent; Stage I, a 52 to 85 percent rate for distal cancers (stomach outlet), but only 10 to 15 percent for proximal cancers (stomach entry); Stage II, 20 percent or less; Stage III, 17 percent for distal cancers, less for proximal tumors; Stage IV, less than 5 percent. • Colorectal cancer: Stage I , 80 percent; Stage II, 50 percent; Stage III, about 25 percent; Stage IV, only 5 percent. • Cancer of the small intestine: Adenocarcinoma type, 20 percent if it is resectable; sarcoma type, about 50 percent if surgical removal is possible; lymphoma type, 25 percent for diffuse lymphoma, but 50 percent or higher for nodular lymphoma; and for the carcinoid type, about 54 percent. • Anal cancer: Stage 0 (in situ), 100 percent; Stage I, over 95 percent; Stage II, 75 percent; Stage
