摘录

I received help from many people during the preparation of this book. Mr. Mike Liddicoat, M.L.I.S., of the Community Health Library of Los Gatos generously gave his time to obtain reprints of articles that I used in my research. My colleagues Richard S. Coughlin, M.D. (colorectal surgery), Robert Filpi, M.D. (radiology), S. Robert Freedman, M.D. (pathology), Wallace Sampson, M.D. (medical oncology), and Mark M. Segall, M.D. (colorectal surgery), were kind enough to review portions of the book and provide useful criticism. Dick Coughlin allowed me to use his compilation of screening guidelines and recommendations; Bob Filpi also provided me with illustrative x-rays and useful articles on the radiology of colon cancer; similarly, Robert B. Abington, M.D. (nuclear medicine), was kind enough to give me a folder of reprints on PET scanning and nuclear scintigraphy. Mahendra Ranchod, M.D. (pathology), kindly provided me with photographs of colon cancer specimens from his pathology teaching files, and Mark Segall provided me with endoscopic photographs of colon cancer from his patient files. Photographs have also been obtained from my own patient files. Other illustrations are acknowledged in the text. This book would not have been written had I not been asked by Miriam Bloom, Ph.D., to do it. I am grateful for her guiding hand along the way. I am grateful for the privilege of having been physician to so many wonderful patients who have given me my truest education in medicine. My wife, Karen, and children, Melissa and Greg, have shown great patience with me, as I have monopolized use of the family computer and kept articles and books strewn throughout the study for months while getting this project completed. Finally, I would like to dedicate this book to the memory of my father and first teacher of science, George Adour Adrouny, Ph.D., who died during the writing of the manuscript. As professor of biochemistry at Tulane University School of Medicine, he touched the lives of many students. From him I learned not only biochemistry but also the value of perseverance, intellectual curiosity and honesty, and a lasting love and respect for language, especially word origins, clear thinking, and clear writing. Audrey Hepburn. Ronald Reagan. "Tip" O'Neill. Eric Davis. Darryl Strawberry. Charles Schulz. Jay Monahan. Vince Lombardi. All of these famous people, and hundreds of thousands of ordinary people, have had it. "It," of course, is colorectal cancer. Colorectal cancer is a significant health problem in the United States and the rest of the western world. It is the third most common cause of cancer worldwide. In the United States, it is the second most common cause of cancer in both men and women. However, the public is not as well acquainted with this disease as it should be. While colorectal cancer has been quietly ignored for decades, other cancers, including cancer of the lung, breast, ovary, and prostate, have been grabbing headlines for years. However, the image of colon cancer languishing in medical awareness purgatory is slowly beginning to change. The public is becoming aware of the value of screening for this disease. While breast cancer can be detected early by mammography and prostate cancer by PSA (prostate specific antigen) blood testing, colon cancer can be detected in its premalignant or asymptomatic stages when prevention or cure is possible. (Note: in this book, the terms colon, colorectal, large bowel , and large intestine are used interchangeably, although when the discussion concerns distinct regions of the large intestine, the colon is distinguished from the rectum.) The advent of fiberoptic endoscopy in recent decades has reformed our way of thinking about the disease and has provided unprecedented intelligence about its natural history. Colorectal cancer can be viewed as a disease confined to a geometrically and anatomically distinct plane of tissue that is readily accessible to direct examination. Therefore, prospects for elimination of the disease exist in a not too distant realm. Indeed, the incidence of colorectal cancer has declined in recent years, probably because of screening and early diagnosis of potentially malignant polyps. This book begins with a review of the demographics of colon and rectal cancer and high-risk conditions for the disease. The polyp-to-carcinoma sequence (key to understanding this disease) is explained, along with the polyposis syndromes. The normal anatomy and physiology of the colon is next reviewed, followed by a discussion of colon carcinogenesis. Important information about the genetics of the disease, much of which was uncovered in seminal research of the 1990s, is given in chapter 3. The "look" (signs) and "feel" (symptoms) of colon cancer are covered next. The importance of symptoms such as bleeding, abdominal pain, and change of bowel habits is reviewed, followed by a look at the important tests useful for the diagnosis and staging of the disease. The stages of colon cancer are then summarized, including discussion of the prognosis according to each stage and theories of how colon cancer spreads. Treatment of colon cancer is discussed in two chapters, including surgical approaches to the disease according to where in the large bowel the cancer lies, and then review of adjuvant therapies (treatments given in addition to surgery) and treatment of advanced disease with chemotherapy. Laparoscopic surgery is given considerable attention, although it is not yet clear exactly what role this form of surgery will have in the future. In the next chapter, I review strategies for early detection and prevention of the disease. Standard approaches such as digital rectal examination, fecal occult blood testing, and endoscopy for early detection are discussed, along with recommendations concerning use of these tests for screening. Various preventive strategies such as diet, vitamins, and drugs are also covered, as are recommendations regarding genetic screening. I conclude with a look at developing diagnostic tests such as "virtual colonoscopy" and developing therapies such as vaccines and monoclonal antibodies, and provide additional information about genetic markers and screening, as well as potential genetic therapies. A number of original and review articles on the disease were drawn upon as references. Major text chapters which provided valuable general information include "Adenocarcinoma of the Colon and Rectum" by Glenn Steele, Jr., Joel Tepper, Bina T. Motwani, and Howard W. Bruckner in Cancer Medicine (Third Edition), edited by James F. Holland, Emil Frei III, Robert C. Bast, Jr., Donald W. Kufe, Donald L. Morton, and Ralph R. Wiechselbaum, and "Colon Cancer" by Alfred M. Cohen, Bruce D. Minsky, and Richard L. Schilsky in Cancer: Principles and Practice of Oncology (Fourth Edition), edited by Vincent T. DeVita, Jr., Samuel Hellman, and Steven Rosenberg. The chapter "Colorectal Cancer" by Glenn Steele, Jr., in Cancer Surgery (edited by Robert J. McKenna, Sr., and Gerald P. Murphy) provides superb discussion on general aspects of the disease as well as specific issues, such as laparoscopic procedures and sphincter-saving operations. Gastrointestinal Oncology, edited by James D. Ahlgren and John S. Macdonald, provides several very illuminating chapters on the subject, particularly the chapter "Colorectal Cancer: Surgical Approach" by Lee E. Smith. Excellent reviews of colorectal anatomy, physiology, and pathology are to be found in "The Small and Large Intestine" by Jerry S. Trier, Charles L. Krone, and Marvin H. Sleisenger in Gastrointestinal Disease (Third Edition), edited by Marvin H. Sleisenger and John S. Fordtran; The Large Intestine, edited by Sidney F. Phillips, John H. Pemberton, and Roy G. Shorter; Diseases of the Colon, Rectum and Anal Canal, edited by Joseph B. Kirsner and Roy G. Shorter; and Morson and Dawson's Gastrointestinal Pathology (Third Edition) by Basil C. Morson, Ian M. P. Dawson, David W. Day, Jeremy R. Jass, Ashley B. Price, and Geraint T. Williams. Who Gets Colon Cancer and Why Putting the Problem in Perspective Although there is data to show that colorectal cancer incidence and mortality have been waning in recent decades, cancers of the colon and rectum still cause approximately 40,000 deaths in America annually. There are about 140,000 new cases diagnosed each year. In comparison, about 182,000 women each year are diagnosed with breast cancer, and about 164,000 men and women each year are diagnosed with lung cancer. A total of 180,000 men are diagnosed with prostate cancer annually. In total, about 1.2 million new cases of all types of cancer are diagnosed annually, so it is evident that colon cancer constitutes a large portion, a little more than 10 percent, of the cancer problem in the United States, and is the fourth most frequent type of cancer. As an overall cause of cancer mortality, colorectal cancers are second only to lung cancer. For women, however, colon cancer ranks third behind lung and breast cancer as a cause of mortality, and, for men, it ranks third behind lung and prostate. The lifetime risk of colorectal cancer in the general population is 2.5 to 5 percent. This means that twenty-five to fifty out of one thousand people will get colon cancer in their lifetimes. This risk is increased two- or threefold if there is a first-degree relative (parent, sibling, or child) who has had an adenomatous polyp or cancer. Colon cancer occurs twice as often in developed countries than in developing countries, with the highest rates being found in North America, Europe, Australia, and New Zealand. The incidence of colon cancer in Japan has been rising steadily since the end of World War II. The lowest incidence rates are found in Africa and India. Both hereditary and environmental factors are important in causing the disease. The majority of colon cancer cases are considered to be sporadic, that is, occurring predominantly under the influence of environmental factors. However, there are distinct genetic syndromes that may predispose a person to colon cancer. A small percentage of colon cancer cases are believed to be due to these hereditary conditions (see below). Sex and Age Colon cancer shows perhaps only a small sexual bias, as men are affected slightly more by this disease than women. The male:female ratio varies from 1.0 to 1.4 depending on the tumor registry that is reporting the data. Rectal cancer, however, is much more common in men than women. The risk of colon cancer increases with age. The majority of cases occur in people over the age of sixty. In people between the ages of forty and fifty years the incidence of colorectal cancer is fifteen new cases per hundred thousand persons, while in persons more than eighty years of age the incidence rises to more than four hundred new cases per hundred thousand. Colorectal cancer in the young (under age twenty) accounts for less than 1 percent of all cases. In this age group, the incidence rate is far higher in blacks than in whites (the opposite of what occurs in adults). The young group of patients tends to have a remarkably high incidence of a particular type of colorectal cancer known as mucinous (which means that the cancer produces mucin, the major component of mucus, in large quantities). Diet does not seem to be a factor, since exposure to potential carcinogens is short (compared to the length of time which adults over the age of fifty have had). Polyposis (growths in the bowel which may later become cancer) are not a factor either. The youngest case of colon cancer ever reported was in a nine-month-old baby. Although breast cancer seems to attract more attention than colon cancer as a women's health care issue, it is of interest to note that for a woman of age sixty-five, the risk of colorectal cancer nearly equals the risk of breast cancer. Concern has been raised that the high morbidity and mortality of colorectal cancer in women is grossly underappreciated by the general public. This is reflected by surveys of women that have shown that compliance by women with colorectal screening tests was much lower than for breast cancer. For example, less than 24 percent of women over the age of fifty had had sigmoidoscopy (examination of the lower portion of the colon with a sigmoidoscope instrument), while nearly 50 percent had had mammography and more than 50 percent had been screened for cervical cancer. There is more focused attention on breast, ovarian, and cervical cancer than on colorectal cancer in women, leading some to suggest that the public perception is that colorectal cancer is "a man's disease," when in fact it is not. Women who take hormone replacement therapy (estrogen or estrogen and progesterone) in their postmenopausal years derive benefit from it as a protection against colorectal cancer. One study suggested that the risk of colorectal cancer was cut in half after five to ten years of hormone therapy. It has been suggested that women who take hormone replacement therapy (HRT) may have healthier behaviors in general and may be more likely to have regular medical examinations, including screening tests for early colon cancer detection. But HRT may be beneficial through biochemical and cellular mechanisms. HRT may reduce production of bile acids (byproducts of fat digestion), which are thought to have colon-cancer-promoting effects, and may directly prevent or reduce colon cancer cell growth by a variety of other means. Diet, Environment, and Heredity Evidence suggests that the main environmental factor is diet. Other environmental exposures, such as smoking, are likely to be involved in causing colon cancer but are not as well documented or understood. Diets having a higher composition of cereal fiber (fiber is composed of plant cellulose and hemicellulose, which provide structural integrity to the cell walls of plants), fruits, and vegetables are thought to reduce the risk of colon cancer, while diets high in fat intake and low in fiber are thought to increase the risk. Thus in geographic areas such as Asia and Africa where dietary customs place emphasis on low-fat, high-fiber foods, fruits, and vegetables, people have lower incidence of colon cancer than in the United States and Europe. The exact reason (or reasons) for the protective effect of cereal fiber is not known. Continue... Excerpted from Understanding Colon Cancer by A. Richard Adrouny Copyright © 2002 by University Press of Mississippi Excerpted by permission. All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.