Chapter 087. Gastrointestinal Tract Cancer (Part 6)

Gastric (Nonlymphoid) Sarcoma Leiomyosarcomas and GISTs make up 1–3% of gastric neoplasms. They most frequently involve the anterior and posterior walls of the gastric fundus and often ulcerate and bleed. Even those lesions that appear benign on histologic examination may behave in a malignant fashion. These tumors rarely invade adjacent viscera and characteristically do not metastasize to lymph nodes, but they may spread to the liver and lungs. The treatment of choice is surgical resection. Combination chemotherapy should be reserved for patients with metastatic disease. All such tumors should be analyzed for a mutation in the c-kit receptor. GISTs...
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Chapter 087. Gastrointestinal Tract Cancer (Part 6) Chapter 087. Gastrointestinal Tract Cancer (Part 6) Gastric (Nonlymphoid) Sarcoma Leiomyosarcomas and GISTs make up 1–3% of gastric neoplasms. Theymost frequently involve the anterior and posterior walls of the gastric fundus andoften ulcerate and bleed. Even those lesions that appear benign on histologicexamination may behave in a malignant fashion. These tumors rarely invadeadjacent viscera and characteristically do not metastasize to lymph nodes, but theymay spread to the liver and lungs. The treatment of choice is surgical resection.Combination chemotherapy should be reserved for patients with metastaticdisease. All such tumors should be analyzed for a mutation in the c-kit receptor.GISTs are unresponsive to conventional chemotherapy; ~50% of patientsexperience objective response and prolonged survival when treated with imatinibmesylate (Gleevec) (400–800 mg PO daily), a selective inhibitor of the c-kittyrosine kinase. Many patients with GIST whose tumors have become refractoryto imatinib subsequently benefit from sunitinib (Sutent), another inhibitor of the c-kit tyrosine kinase. Colorectal Cancer Incidence Cancer of the large bowel is second only to lung cancer as a cause of cancerdeath in the United States: 153,760 new cases occurred in 2007, and 52,180 deathswere due to colorectal cancer. The incidence rate has remained relativelyunchanged during the past 30 years, while the mortality rate has decreased,particularly in females. Colorectal cancer generally occurs in persons ≥50 years. Polyps and Molecular Pathogenesis Most colorectal cancers, regardless of etiology, arise from adenomatouspolyps. A polyp is a grossly visible protrusion from the mucosal surface and maybe classified pathologically as a nonneoplastic hamartoma (juvenile polyp), ahyperplastic mucosal proliferation (hyperplastic polyp), or an adenomatous polyp.Only adenomas are clearly premalignant, and only a minority of such lesionsbecomes cancer. Adenomatous polyps may be found in the colons of ~30% ofmiddle-aged and ~50% of elderly people; however, normally suppress tumorigenesis. It remains uncertain whether the geneticaberrations always occur in a defined order. Based on this model, however, canceris believed to develop only in those polyps in which most (if not all) of thesemutational events take place. Clinically, the probability of an adenomatous polyp becoming a cancerdepends on the gross appearance of the lesion, its histologic features, and its size.Adenomatous polyps may be pedunculated (stalked) or sessile (flat-based).Cancers develop more frequently in sessile polyps. Histologically, adenomatouspolyps may be tubular, villous (i.e., papillary), or tubulovillous. Villous adenomas,most of which are sessile, become malignant more than three times as often astubular adenomas. The likelihood that any polypoid lesion in the large bowelcontains invasive cancer is related to the size of the polyp, being negligible (5 years of growth before becoming clinicallysignificant; colonoscopy need not be carried out more frequently than every 3years.