Colorectal Cancer
Colorectal cancer is a major public health problem in Western countries with the highest incidence rates reported in North America, Australia, New Zealand, and western Europe. An estimated 135,000 cases will be diagnosed in the United States in 2001 and a
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Colorectal Cancer
31
H.L. Kindler, R.L. Schilsky
31.1 Epidemiology and Risk Factors Colorectal cancer is a major public health problem in Western countries with the highest incidence rates reported in North America, Australia, New Zealand, and western Europe. An estimated 135,000 cases will be diagnosed in the United States in 2001 and approximately 57,000 people will die of the disease [1]. Colorectal cancer is the third most common cancer in men and women and the third most common cause of cancer death in both sexes. The age-specific incidence rises sharply after age 40, with 90% of cancers occurring in individuals age 50 and older. Within the large intestine, 69% of cancers occur in the colon and 31% in the rectum. More than half of all colonic cancers occur either in the sigmoid colon (35%) or in the cecum (22%), although, in recent years, right-sided lesions are becoming more common [2]. Although the specific etiology of colorectal cancer remains unknown, it is likely that the disease results from the accumulation of genetic mutations in
the colonic epithelium which ultimately result in the neoplastic phenotype. In some cases, genetic mutations may be inherited as germline mutations, often manifest as familial colon polyp or cancer syndromes. In other cases, somatic mutations in the colonic epithelium, perhaps related to environmental or nutritional exposures, ultimately result in the formation of colon cancer. In most cases, adenomatous polyps are precursors to the development of invasive cancer. Familial syndromes associated with an increased risk of colorectal cancer are summarized in Table 31.1. Familial adenomatous polyposis (FAP) is inherited in an autosomal dominant pattern and is characterized by the development of hundreds or thousands of adenomatous polyps throughout the colon and rectum. The average age of onset of polyps is during the 20s and virtually 100% of affected individuals will develop colorectal cancer by age 35–40 if total colectomy is not performed [3]. Germline mutations of the FAP gene located at chromosome 5q22 are detectable in all affected individuals and provide a means of diagnosing the disease prior to the onset
Table 31.1. Familial colon cancer syndromes
Feature
Age of onset Number of adenomas Adenoma distribution Cancer distribution Other cancers Germline mutation
Syndrome FAP a
HNPCC
20s >100 Left or total Random Periampullary APC gene at 5q22
40s 5 ng/ml) is the only clinical feature of colorectal cancer that has been consistently predictive of a poor prognosis.
31.3 Work-up and Staging 31.3.1 Evaluation of the Primary Tumor The presenting symptoms of colorectal cancer, while highly variable and often nonspecific, usually include rectal bleeding, change in bowel habits, and/or abdominal pain and discomfort. Right-
sided tumors frequently present with fatigue from the anemia that results from chronic occult blood loss. Left-sided tumors are more likely to present with bright red blood per rectum, constipation or diarrhea alternating with constipation, change in st
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