From colonic polyps to colon cancer: pathophysiology, clinical presentation, screening and colonoscopic therapy.

UNLABELLED: Colon cancer is the most common nondermatologic cancer in Italy and throughout Europe, with about 250,000 cases annually in Europe, about half of whom die. Yet, colon cancer is largely preventable through intensive, mass screening programs to remove premalignant colonic polyps. The persistently high incidence and mortality is largely due to ineffective implementation of established screening protocols due to patient fears about screening tests, physician under-referral for screening, and test costs. Colon cancer mostly arises from adenomas, recognized as colonic polyps, but may occasionally arise from the sessile serrated adenoma. Adenomatous polyposis coli (APC) gene mutation is the key molecular step in adenoma formation. Mismatch repair gene mutation is a less common alternative pathway. Progression from adenomas to colon cancer is a multistep process, involving mutations of the DCC, k-ras, and p53 genes; loss of heterozygosity in which cells loose one allele of some genes from chromosomal loss; and DNA methylation which can silence DNA expression. Numerous environmental factors can increase the risk of colon cancer, presumably by modulating these molecular pathways. While colon cancer in an advanced and incurable stage often produces clinical findings, premalignant adenomatous polyps and early, highly curable, colon cancer are often asymptomatic. This phenomenon renders adenomas or early cancers difficult to detect by clinical presentation and provides the rationale for mass screening of asymptomatic adults over 50 years old for early detection and prevention of colon cancer. Colonoscopy is the primary screening test. All polyps identified at colonoscopy are removed by colonoscopic polypectomy. Endoscopic mucosal resection is required for deeply penetrating noncancerous polyps. Colonoscopy is repeated every ten years if the index colonoscopy revealed no lesions, but is repeated more frequently if adenomatous polyps were identified at this colonoscopy due to an increased risk of subsequent polyps or colon cancer. Flexible sigmoidoscopy every few years with annual fecal occult blood testing is a significantly less sensitive screening protocol. Virtual colonoscopy is controversial as a screening test due to widely variable reported

RESULTS: Computerized tomography is standardly used to preoperatively detect distant colon cancer metastases, while endosonography is being increasingly used for locoregional staging of rectal cancer. Stool genetic markers and videocapsule endoscopy are promising, but currently experimental, screening tests.