Patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) in remission are significantly more likely to have inflammation of the right colon, based on endoscopic and histologic markers, than patients with UC without PSC, researchers report in the January issue of Clinical Gastroenterology and Hepatology. These findings provide insight into cause of colorectal cancer in UC patients with PSC.
Patients with UC-PSC have a unique phenotype of UC—they are more likely to have pancolitis, backwash ileitis, and rectal sparing than patients with UC without PSC. Colitis in patients with PSC is often asymptomatic or milder than observed in patients with UC alone. So, the increased risk of colorectal cancer in these patients could be due to subclinical disease and delayed diagnosis of UC.
Noa Krugliak Cleveland et al compared subclinical disease activity in patients with UC with vs without PSC. They performed a retrospective analysis of 38 patients with UC-PSC and 140 patients with pancolitis.
Cleveland et al found that patients with UC-PSC had a 4-fold higher risk for endoscopic activity and a 5-fold higher risk for histologic markers of disease activty in the right colon than patients with only UC (see figure).
Patients with UC-PSC also had a greater degree of histologic than endoscopic inflammation in the proximal colon and significantly less histologic activity in the rectum on multivariate analysis.
Cleveland et al state that these findings could explain previous observations of a greater prevalence of right-sided CRC and more advanced CRC at time of cancer diagnosis in patients with UC and PSC. They recommend that clinicians routinely assess histologic disease activity in the proximal colon of patients with UC-PSC in clinical remission—even in patients without endoscopic inflammation.
How would the combination of UC and PSC increase risk of proximal colon neoplasms? The authors propose that cholestasis in patients with PSC leads to a build-up of secondary bile acids, which can have carcinogenic effects. Bile acid concentrations are highest on the right side, which could contribute to CRC development there. Ursodeoxycholic acid (UDCA) has been proposed to reduce carcinogenesis by reducing levels of the secondary bile acid deoxycholic acid. In a randomized controlled trial evaluating the effect of UDCA in patients with UC-PSC, 10% of the patients receiving UDCA developed colorectal neoplasia compared with 35% in the control group (relative risk, 0.26).
Studies are needed to learn more about the distinct pattern of inflammation in patients with PSC and UC, which could help manage patients more effectively. The authors state that a goal of management for these patients should be mucosal healing, but it is not clear whether this can be achieved or whether it will reduce the risk of cancer. Long-term prospective studies are needed to assess the effects of mucosal healing on prevention of neoplasia in this population.