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abstract & commentary
Synopsis: Cancer risk is increased in ulcerative colitis, and administration of oral ursodiol might reduce the risk of carcinogenesis.
Source: Tung BY, et al. Ann Intern Med. 2001;134:89-95.
Patients with both ulcerative colitis (uc) and sclerosing cholangitis have a particularly high risk of colonic neoplasia. Adenocarcinoma may occur in 50% of such patients with longstanding colitis, a rate at least twice that of UC without cholangitis. Ursodiol improves liver biochemical indices of liver function in sclerosing cholangitis, and it incidentally appears to result in dramatic lowering of cancer risk (adjusted odds ratio, 0.14; confidence interval, 0.03-0.64).
Many experts believe that UC is associated with an increased risk of colonic adenocarcinoma (0.5-1%/y of disease). Primary sclerosing cholangitis (PSC) is an inflammatory condition of the bile ducts occurring in 2-4% of patients with UC. Combined UC and PSC are associated with a markedly increased risk of colonic adenocarcinoma to as high as 50% of all such patients after 25 years of colitis. Factors important in development of colorectal cancer in the general population include a high fat diet that predisposes to formation of secondary bile acids. Use of aspirin and NSAIDs has been associated with reduced risk for cancer and colon polyps. Ursodiol is often given to patients with sclerosing cholangitis since it appears to improve liver function. Ursodiol seems to inhibit colon carcinogenesis in animal models.
The present study included 59 patients with UC and PSC. Forty-one had used ursodiol and 18 had not done so. Dysplasia on biopsies was found in 32% of patients who had ever used ursodiol and in 72% of patients who had never been exposed to this medication.
Comment by Malcolm Robinson, MD, FACP, FACG
Although this small study does not definitely prove that ursodiol will prevent or reduce dysplasia and neoplasia in UC, these results are certainly intriguing. Controlled, prospective, randomized studies should be undertaken. Moreover, this apparently benign medical intervention could also prove useful in the prevention of colonic neoplasia in other settings. Further information about ursodiol and carcinogenesis in other groups with increased risk of colon cancer will be awaited with great interest.