ORIGINAL ARTICLES

ULCERATIVE COLITIS AND CARCINOMA COLI

Patients with chronic colitis from inflammatory bowel disease (IBD) have an increased risk of colorectal cancer (CRC). Previously, to ameliorate this, prophylactic total colectomy was offered to patients who had chronic ulcerative colitis (UC); however, research has identified less invasive management options through better understanding of the pathogenesis of cancer in chronic inflammation, a more uniform histologic diagnosis by pathologists, and proper surveillance colonoscopy techniques. This article reviews the pathogenesis of neoplasia in IBD, and then reviews the risk factors for CRC in IBD, surveillance guidelines and their limitations, surveillance techniques, ileal pouch dysplasia, and chemoprevention. Although data for CRC risk in Crohn's disease (CD) are not as extensive, it has been suggested that the risks are comparable to UC.

The authors reviewed pathology reports of 590 patients who underwent total proctocolectomies or restorative proctocolectomies for chronic ulcerative colitis at the Mount Sinai Medical Center between 1987 and 1999. One hundred sixty of these patients had undergone colonoscopic examination within the year before surgery.

To avoid variations in pathological interpretations, one pathologist at Mount Sinai Medical Center reviewed 92% of the operative specimens and 98% of all the positive specimens. Five pathologists reviewed 98% of all operative specimens. Generally, 10–15 areas were sampled per pathological specimen. Seventy-seven specimens (13.1%) contained at least one focus of dysplasia. Invasive cancers were significantly more common among specimens with dysplastic changes (33/77 vs 5/513, p < 0.001). Specimens with dysplasia of any grade were 36 times more likely to harbor invasive carcinoma. Stage III colorectal cancer was found with indefinite or low grade dysplasia in five of 26 cases (19.2%). Tumor stage did not correlate with dysplasia grade. Preoperative colonoscopy identified neoplastic changes in 57 cases (69.5%). Dysplasia, cancer, or both were missed in 25 cases. Dysplastic lesions were correctly identified in only 31 cases (39.7%). Colonoscopically diagnosed dysplasia as a marker for the presence of a synchronous cancer had a sensitivity of 81% and a specificity of 79%. The authors report that the positive predictive value of a finding of preoperative dysplasia of any grade was 50%. The positive predictive value of a finding of low grade mucosal dysplasia was 70%.

The authors concluded that, until a better marker is found, a single confirmed diagnosis of dysplasia should be viewed as highly suspicious for the presence of a coexistent cancer. An advanced stage of colorectal cancer could be found in association with dysplastic changes of any grade.

The authors thus conclude that, because dysplasia grade does not predict tumor stage and advanced cancer can be found in association with dysplastic changes of any grade, confirmed dysplasia of any grade was an indication for colectomy.

It is proposed that in genetically susceptible individuals ulcerative colitis is caused by a bacterial metabolite of bile acids or cholesterol and that this substance is similar or identical to the bacterial metabolites implicated in the development of colon cancer. Since the responsible bacterial reactions may be dependent on vitamin K as an electron acceptor it is suggested that poorly absorbed vitamin K antagonists, specifically α-tocopherylquinone, may be capable of inhibiting these reactions and may therefore prove effective in treating ulcerative colitis and in preventing the development of colon cancer.