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Minerva Gastroenterologica e Dietologica 2007 December;53(4):351-73


language: English

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

Cappell M. S.

Division of Gastroenterology William Beaumont Hospital, Royal Oak, MI, USA


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. Colonos-copy 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 colonos-copy 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.

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