Colorectal Cancer _ ___________________________________________________________________________
Limitations of Colonoscopic Surveillance As discussed, interval colorectal cancers are advanced adenomas that develop after polypectomy or negative baseline colonoscopy and before the next screening colonoscopy, a 10-year period for most patients. Within five years of negative screening colonoscopy, the risk of developing advanced adenomas is 1.3% to 2.4%. The greatest risk of interval colorectal cancer is within five years of screening colonoscopy, usually resulting from missed lesions progressing to diagnosable colorectal cancer [167]. Studies suggest that most interval colorectal cancers result from missed lesions during baseline colonoscopy. Failure to detect lesions is directly associated with colonoscopy examination quality [146; 168]. Residual neoplastic tissue from incomplete adenoma removal can also progress to malignancy. Interval colorectal cancers may differ from prevalent colorectal cancers by more frequent location in the proximal colon and by molecular/genetic properties that confer more aggressive growth. The relationship is established between inadequate colonoscopy quality and risk of interval cancer following colonoscopy. Halting Surveillance Colonoscopy risks increase with advancing age and at some point outweigh the benefits of surveillance and screening. The USPSTF recommends clinicians selectively offer screening for colorectal cancer in adults 76 to 85 years of age [121]. Evidence indicates that the net benefit of screening all persons in this age group is small. In determining whether this service is appropriate in individual cases, patients and clinicians should consider the patient’s overall health, prior screening history, and preferences. Patients with high-risk adenoma may especially benefit from continued surveillance. PATHOPHYSIOLOGY The pathogenesis and pathophysiology of colorectal cancer is very complex, and the following section is intended to be a brief overview. There are three broad pathways by which colorectal carcinoma develops [169]:
Importantly, sporadic (i.e., in the absence of an apparent inherited disorder) colorectal cancers originating from polyps and hereditary colorectal cancers (i.e., originating from inherited colorectal cancer predisposition syndromes) share in common the sequences of gene-level altered function and mutation that transform benign tissue to precancerous lesion to malignancy. The distinction is that germline mutations underlie the well-described inherited colorectal cancer syndromes, while sporadic cancers arise from a stepwise accumulation of somatic genetic mutations [171]. With very few exceptions, the pathogenesis and pathophysiology of colon and rectal cancer is identical. Unless otherwise stated, the following information pertains to both.
HISTOLOGIC CHARACTERISTICS OF COLORECTAL CANCER Cellular Classification
Data from more than 180,000 patients with colorectal cancer were entered into the Surveillance, Epidemiology, and End Results (SEER) cancer database from 1975–2015 and analyzed [10]. Histologic subtypes in the population were overwhelmingly adenocarcinoma (92.1%); others included neuroendocrine carcinoid (4.4%), unspecified carcinoma (0.8%), and squamous cell (0.7%). The relative five-year survival rates were highest for carcinoid tumors (90.1%) and lowest for neuroendocrine tumors (14.4%) [10]. The SEER cancer database for 1975–2018 does not include information on histologic subtypes of colorectal cancer [172]. Colorectal Cancer Precursor Lesions Colorectal lesions present as a broad spectrum of neoplasms that range from benign growths to invasive tumors. Most colorectal cancers develop slowly over years, typically beginning as non-cancerous polyps on the inner lining of the colon or rectum. Some, but not all, polyps develop into cancer, and the risk of malignant progression is influenced by polyp type. Colorectal lesions are classed into three groups [173]: • Adenomatous polyps (adenomas): These polyps have the greatest malignant potential and are termed pre- cancerous. • Non-neoplastic and inflammatory polyps: These are generally not pre-cancerous, but when located in the ascending colon, the risk of pre-cancerous status or development into adenomas and cancer is increased. Includes hyperplastic, juvenile, hamartomatous, inflammatory, and lymphoid polyps. • Dysplasia: A non-polyp pre-cancerous condition of the colorectal lining, usually associated with inflammatory bowel disease.
• The chromosome instability (CIN) pathway • The microsatellite instability (MSI) pathway • Inflammatory bowel disease dysplasia
Colorectal tumors first develop through one of these pathways, but once established as malignancy, the final common pathway to metastases is identical and involves the spread of cancer cells to locoregional lymph nodes and dissemination to and colonization of the liver (through enteric venous drainage) and the lungs (via hematogenous transport) [170].
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