Natural History Of Colorectal Cancer

Colorectal cancer can develop in all segments of the large intestine. Although its location somewhat influences the prognosis and obviously the approach for surgical treatment, from a biological point of view, it can be considered under one heading, i.e. colon cancer. Interestingly, cancers of the small intestine are very rare and certainly represent a distinct disease.

There is good morphological and molecular genetical evidence that colon carcinoma develops through several precursor stages (Figure 13.1). The earliest recognizable preneoplastic changes result in hyperplastic or dysplastic crypts. There is some debate whether one or the other of these, or both can give rise to adenomas and carcinomas. In contrast, it is generally agreed that adenomatous polyps are a precursor stage for many carcinomas. They are usually found as single benign tumors protruding into the lumen of the bowel and consist of a thickened, more or less disorganized epithelium. Multiple polyps are found in certain circumstances, e.g., in the familial cancer syndrome 'familial adenomatous polyposis coli' (FAP) discussed below. These polypous tumors are considered a type of adenoma and can be categorized into several substages according to the degree of growth and dysplasia.

Invasion of tumor cells through the basement membrane into the underlying mesenchyme is the diagnostic mark of carcinoma. Several tumor stages are distinguished in routine pathology according to the extent of invasion and the spread of the tumor mass. Localized colon carcinomas without metastases can often be cured by surgery. In many cases, 'adjuvant' chemotherapy is applied after surgery to kill remaining tumor cells. The prognosis of colon carcinoma becomes worse and the treatment much more difficult, if the tumor has spread to local lymph nodes or metastasized to the liver, lung and other organs. Surgery and chemotherapy can still be curative, but often only prolong survival.

The incidence of colon cancer varies considerable across the world, with the highest incidences in Western industrialized countries. Colon cancer is usually a disease of older people. However, the incidence remains different between countries with on average younger or older populations even after adjustment for age. The causes for these differences in incidence are not really understood. The best evidence points to dietary factors being responsible (^20.3).

Figure 13.1 Stages in the development of colorectal cancers The histologies show normal mucosa (left), an adenomatous polyp with moderate dysplasia (center), and invasive adenocarcinoma with tumor glands (arrows) in the submucosa (right).
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