American Cancer Society

Atlas of
Clinical Oncology

Series Volumes
Blumgart, Fong, Jarnagin Hepatobiliary Cancer
Cameron Pancreatic Cancer
Carroll, Grossfeld, Reese Prostate Cancer
Char Tumors of the Eye and Ocular Adnexa
Clark, Duh, Jahan, Perrier Endocrine Tumors
Eifel, Levenback Cervical, Vulvar and Vaginal Cancer
Ginsberg Lung Cancer
Grossbard Malignant Lymphomas
Ozols Ovarian Cancer
Pollock Soft Tissue Sarcomas
Posner, Vokes, Weichselbaum Esophagus, Stomach and Small Bowel Cancer
Prados Brain Cancer
Raghavan Germ Cell Tumors
Shah Head and Neck Cancer
Silverman Oral Cancer
Sober, Haluska Skin Cancer
Steele, Richie Kidney Tumors
Volberding Viral Causes of Cancer
Wiernik Adult Leukemias
Willett Cancer of the Lower Gastrointestinal Tract
Winchester, Winchester Breast Cancer
Yasko Bone Cancer
 American Cancer Society
Atlas of
Clinical Oncology

Editors

GLENN D. STEELE JR, MD

University of Chicago
THEODORE L. PHILLIPS, MD
University of California
BRUCE A. CHABNER, MD
Harvard Medical School

Managing Editor

TED S. GANSLER, MD, MBA

Director of Health Content, American Cancer Society
 American Cancer Society
Atlas of
Clinical Oncology

Cancer of the
Lower Gastrointestinal
Tract
Christopher G. Willett, MD
Department of Radiation Oncology
Massachusetts General Hospital
Professor
Harvard Medical School
Boston, Massachusetts

2001
B.C. Decker Inc.
Hamilton • London

Exit
B.C. Decker Inc.
20 Hughson Street South
P.O. Box 620, L.C.D. 1
Hamilton, Ontario L8N 3K7
Tel: 905-522-7017; 1-800-568-7281
Fax: 905-522-7839
E-mail: info@bcdecker.com
Website: www.bcdecker.com

© 2001 American Cancer Society

All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by
any means, electronic, mechanical, photocopying, recording, or otherwise, without prior written permission from the publisher.
00 01 / UTP / 9 8 7 6 5 4 3 2 1

ISBN 1–55009–110–7
Printed in Canada

Sales and Distribution

United States U.K., Europe, Scandinavia, Japan
B.C. Decker Inc Middle East Igaku-Shoin Ltd.
P.O. Box 785 Harcourt Publishers Limited Foreign Publications Department
Lewiston, NY 14092-0785 Customer Service Department 3-24-17 Hongo
Tel: 905-522-7017; 1-800-568-7281 Foots Cray High Street Bunkyo-ku,Tokyo, Japan 113-8719
Fax: 905-522-7839 Sidcup, Kent Tel: 3 3817 5680
E-mail: info@bcdecker.com DA14 5HP, UK Fax: 3 3815 6776
Website: www.bcdecker.com Tel: 44 (0) 208 308 5760 E-mail: fd@igaku.shoin.co.jp
Fax: 44 (0) 181 308 5702
Canada E-mail: cservice@harcourt_brace.com Singapore, Malaysia, Thailand,
B.C. Decker Inc. Philippines, Indonesia, Vietnam,
20 Hughson Street South Australia, New Zealand Pacific Rim
P.O. Box 620, L.C.D. 1 Harcourt Australia Pry. Limited Harcourt Asia Pte Limited
Hamilton, Ontario L8N 3K7 Customer Service Department 583 Orchard Road
Tel: 905-522-7017; 1-800-568-7281 STM Division #09/01, Forum
Fax: 905-522-7839 Locked Bag 16 Singapore 238884
E-mail: info@bcdecker.com St. Peters, New South Wales, 2044 Tel: 65-737-3593
Website: www.bcdecker.com Australia Fax: 65-753-2145
Tel: (02) 9517-8999
Foreign Rights Fax: (02) 9517-2249
John Scott & Company E-mail: stmp@harcourt.com.au
International Publishers’ Agency Website: www.harcourt.com.au
P.O. Box 878
Kimberton, PA 19442
Tel: 610-827-1640
Fax: 610-827-1671

Notice: The authors and publisher have made every effort to ensure that the patient care recommended herein, including choice of drugs and
drug dosages, is in accord with the accepted standard and practice at the time of publication. However, since research and regulation constantly
change clinical standards, the reader is urged to check the product information sheet included in the package of each drug, which includes rec-
ommended doses, warnings, and contraindications. This is particularly important with new or infrequently used drugs.
Contributors

DAVID S. ALBERTS, MD EDWARD GIOVANNUCCI, MD, SCD

Arizona Cancer Center Associate Professor of Medicine
University of Arizona Channing Laboratory
Tucson, Arizona Department of Medicine
Prevention of Colorectal Cancer: Brigham and Women’s Hospital
Epidemiological Evidence and Chemoprevention & Harvard Medical School
Associate Professor of Nutrition and of
ANTHONY L. BACK, MD Epidemiology
Associate Professor Departments of Nutrition and Epidemiology
VA Puget Sound Health Care System Harvard School of Public Health
University of Washington Boston, Massachusetts
Seattle, Washington Prevention of Colorectal Cancer:
Palliative Care for Patients with Epidemiological Evidence and
Lower Gastrointestinal Tract Malignancies Chemoprevention

WILLIAM R. BRUGGE, MD TIMOTHY D. JENKINS, MD

Director, Gastrointestinal Endoscopy Instructor of Medicine
Massachusetts General Hospital University of Pennsylvania
Harvard Medical School Philadelphia, Pennsylvania
Boston, Massachusetts Genetics of Colorectal Carcinoma
Endoscopic Management of Colon
and Rectal Cancer BERNARD LEVIN, MD
Vice President for Cancer Prevention
JEFF CLARK, MD MD Anderson Cancer Center
Massachusetts General Hospital The University of Texas
Dana Farber Cancer Institute Houston, Texas
Assistant Professor in Medicine Colorectal Cancer Prevention and
Harvard Medical School Early Detection
Boston, Massachusetts
Systemic Therapy Approaches for MARÍA ELENA MARTÍNEZ, PHD, RD
Colorectal Cancer Arizona Cancer Center
University of Arizona
CAROLYN C. COMPTON, MD, PHD Research Assistant Professor
Professor and Chair College of Public Health
Department of Pathology Tucson, Arizona
McGill University Prevention of Colorectal Cancer:
Montreal, Quebec Epidemiological Evidence and
Pathology and Staging Chemoprevention

v
vi CONTRIBUTORS

MARK L. MONTGOMERY, MD KENNETH K. TANABE, MD

Scott and White Clinic
Texas A & M Health Science Center
Temple, Texas
Diagnostic Radiology of Colon and Rectal Cancer
PETER R. MUELLER, MD
Professor of Radiology
Harvard Medical School
Massachusetts General Hospital
Boston, Massachusetts
Diagnostic Radiology of Colon and Rectal Cancer
MARK J. OTT, MD
Massachusetts General Hospital
Division of Surgical Oncology
Assistant Professor of Surgery
Harvard Medical School
Boston, Massachusetts
Surgery of Primary Colon and Rectal Cancer
JEAN-PIERRE E.N. PIERIE, MD, PHD
Chief Resident in Surgery
Department of Surgery
University Medical Center Utrecht
Utrecht, The Netherlands
Surgery of Primary Colon and Rectal Cancer
ANIL K. RUSTGI, MD
T. Grier Miller Associate Professor of
Medicine & Genetics
Chief of Gastroenterology
University of Pennsylvania
Philadelphia, Pennsylvania
Genetics of Colorectal Carcinoma
Chief, Division of Surgical Oncology
Massachusetts General Hospital
Associate Professor of Surgery
Harvard Medical School
Boston, Massachusetts
Surgical Management of Metastatic Colon
and Rectal Cancer
ROGER J. WALTZMAN, MD
Mount Sinai Medical Center
Mount Sinai School of Medicine
Division of Medical Oncology
New York, New York
Palliative Care for Patients with Lower
Gastrointestinal Tract Malignancies
CHRISTOPHER G. WILLETT, MD
Professor, Harvard Medical School
Clinical Director
Department of Radiation Oncology
Massachusetts General Hospital
Boston, Massachusetts
Colon and Rectal Carcinoma: An Overview
Radiation Therapy in Colon and Rectal Cancer
Anal Cancer
SAM S. YOON, MD
Fellow, Division of Surgical Oncology
Massachusetts General Hospital and
Harvard Medical School
Boston, Massachusetts
Surgical Management of Metastatic Colon
and Rectal Cancer

DAVID P. RYAN, MD
Instructor in Medicine
Harvard Medical School
Assistant in Medicine
Massachusetts General Hospital
Boston, Massachusetts
Colon and Rectal Carcinoma: An Overview
Anal Cancer
Contents

1 Colon and Rectal Carcinoma: An Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

David P. Ryan, MD, Christopher G. Willett, MD

2 Prevention of Colorectal Cancer: Epidemiologic Evidence and Chemoprevention . . . . . . . . . . . 7

María Elena Martínez, PhD, RD, Edward Giovannucci, MD, ScD, David S. Alberts, MD

3 Genetics of Colorectal Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33

Timothy D. Jenkins, MD, Anil K. Rustgi, MD

4 Colorectal Cancer Prevention and Early Detection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45

Bernard Levin, MD

5 Pathology and Staging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53

Carolyn C. Compton, MD, PhD

6 Endoscopic Management of Colon and Rectal Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82

William R. Brugge, MD

7 Diagnostic Radiology of Colon and Rectal Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96

Mark L. Montgomery, MD, Peter R. Mueller, MD

8 Surgery of Primary Colon and Rectal Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107

Mark J. Ott, MD, Jean-Pierre E.N. Pierie, MD, PhD

9 Radiation Therapy in Colon and Rectal Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124

Christopher G. Willett, MD

10 Systemic Therapy Approaches for Colorectal Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150

Jeff Clark, MD

11 Surgical Management of Metastatic Colon and Rectal Cancer . . . . . . . . . . . . . . . . . . . . . . . . . 170

Sam S. Yoon, MD, Kenneth K. Tanabe, MD

12 Anal Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 196

David P. Ryan, MD, Christopher G. Willett, MD

13 Palliative Care for Patients with Lower Gastrointestinal Malignancies . . . . . . . . . . . . . . . . . . . 214

Anthony L. Back, MD, Roger J. Waltzman, MD
Preface

Cancer of the Lower Gastrointestinal Tract, An American Cancer Society monograph, is a timely analysis of
the biology, diagnosis, and therapy of cancer of the colon, rectum, and anus. This monograph is intended as
a useful resource for physicians, scientists, medical students, and allied health personnel in the disciplines of
gastroenterology, oncology, and pathology. Renowned contributors from different medical disciplines have
written their chapters in a thoughtful, provocative, and visual fashion.
This monograph is divided into 13 chapters. Early chapters (1–2) address the etiology, risk factors, and
prevention of colon and rectal cancer followed by chapters (3–5) detailing the revolutionary developments in
the genetics and pathology of this malignancy. Chapter 4 comprehensively reviews and outlines the preven-
tion, early detection, and contemporary screening guidelines of colon and rectal cancer. These sections are
then followed by chapters (6–7) on endoscopy and diagnostic radiology of colon and rectal cancer. The cur-
rent multimodality treatment of primary colon and rectal cancer is discussed in three integrative chapters
(8–10) from the vantage points of surgery, radiation therapy, and chemotherapy. The challenges and devel-
opments in the management of patients with metastatic colon and rectal cancer (surgery, chemotherapy, and
innovative and targeted therapies) are presented in two chapters (10–11). Although the focus of this book is
colon and rectal cancer, one chapter is dedicated to a comprehensive examination of the epidemiology, biol-
ogy, and evolving therapy of a unique malignancy, cancer of the anus (12). Finally, the monograph concludes
with an excellent discussion of the complex and difficult issues of palliative care for patients with cancer of
the lower gastrointestinal tract (13).
I would like to thank Bruce Chabner, MD, and Glenn Steele, Jr, MD, PhD, for their helpful suggestions.

Christopher G. Willett, MD
August, 2000

ix
 Dedication

To my friend and colleague, Ira J. Spiro, MD, PhD.