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INTRODUCTION

Lower gastrointestinal cancers include malignant tumors of the colon, rectum, and anus.

COLORECTAL CANCER

INCIDENCE

Image not available. Cancer of the large bowel is second only to lung cancer as a cause of cancer death in the United States: 135,430 new cases occurred in 2017, and 50,260 deaths were due to colorectal cancer. The incidence rate has decreased significantly during the past 25 years, likely due in large part to enhanced and more compliantly followed screening practices. Similarly, mortality rates in the United States have decreased by ~25%, resulting largely from earlier detection and improved treatment.

POLYPS AND MOLECULAR PATHOGENESIS

Most colorectal cancers, regardless of etiology, arise from adenomatous polyps. A polyp is a grossly visible protrusion from the mucosal surface and may be classified pathologically as a nonneoplastic hamartoma (e.g., juvenile polyp), a hyperplastic mucosal proliferation (hyperplastic polyp), or an adenomatous polyp. Only adenomas are clearly premalignant, and only a minority of adenomatous polyps evolve into cancer. Adenomatous polyps may be found in the colons of ~30% of middle-aged and ~50% of elderly people; however, <1% of polyps ever become malignant. Most polyps produce no symptoms and remain clinically undetected. Occult blood in the stool is found in <5% of patients with polyps.

A number of molecular changes are noted in adenomatous polyps and colorectal cancers that are thought to reflect a multistep process in the evolution of normal colonic mucosa to life-threatening invasive carcinoma. These developmental steps toward carcinogenesis include, but are not restricted to, point mutations in the K-ras protooncogene; hypomethylation of DNA, leading to gene activation; loss of DNA (allelic loss) at the site of a tumor-suppressor gene (the adenomatous polyposis coli [APC] gene) on the long arm of chromosome 5 (5q21); allelic loss at the site of a tumor-suppressor gene located on chromosome 18q (the deleted in colorectal cancer [DCC] gene); and allelic loss at chromosome 17p, associated with mutations in the p53 tumor-suppressor gene (see Fig. 67-2). Thus, the altered proliferative pattern of the colonic mucosa, which results in progression to a polyp and then to carcinoma, may involve the mutational activation of an oncogene followed by and coupled with the loss of genes that normally suppress tumorigenesis. It remains uncertain whether the genetic aberrations always occur in a defined order. Based on this model, however, cancer is believed to develop only in those polyps in which most (if not all) of these mutational events take place.

Clinically, the probability of an adenomatous polyp becoming a cancer depends on the gross appearance of the lesion, its histologic features, and its size. Polyps may be pedunculated (stalked) or sessile (flat-based), adenomatous or serrated. Invasive cancers develop more frequently in sessile, serrated (i.e. “flat”) polyps. Histologically, adenomatous polyps may be tubular, villous (i.e., papillary), or tubulovillous. Villous adenomas, most of which are sessile, become malignant more than three times as often as tubular adenomas. The likelihood that any polypoid lesion in the large ...

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