Given its known risk profile, lack of plausible biological mechanism, success of surveillance colonoscopy, and, possibly, increased anti-inflammatory benefit from anti–TNF-α antibodies, unlike 5-ASA

therapies, thiopurines are very unlikely to be recommended as a pure chemopreventive agent in isolation. Anti-TNF agents are able to induce and maintain mucosal healing in the subset of patients with moderate to severe UC and Crohn’s disease, and Daporinad clinical trial as a result are likely providing additional chemopreventive benefits by reducing long-standing chronic inflammation. In addition, early investigations into the molecular mechanisms of TNF-α in colitis have suggested a possible direct antineoplastic role from TNF blockade. Using an in vivo dextran sulfate sodium (DSS) and azoxymethane mouse model for chronic colitis–induced selleck products cancer,

Popivanova and colleagues40 identified an increase in the levels of TNF-α and infiltrating leukocyte TNF receptor in the colonic mucosa and submucosa before the development of colonic tumors. Treating the mice with a human TNF-α antagonist, etanercept, resulted in decreased tissue injury, and low levels of inflammatory infiltrate and neutrophil-derived and macrophage-derived chemokines. Tumors were reduced in number and size and had poor angiogenesis, presumably from the suppressed COX-2 expression. The few studies that evaluate the efficacy of anti-TNF agents to reduce the risk of colitis-associated dysplasia and cancer have discordant findings. In a Dutch nationwide, nested case-control study of 173 cases of IBD-associated CRC from 1990 to 2006, the use of anti-TNF (OR 0.09, 95% CI 0.01–0.68; P = .02) was significantly protective for the development of CRC. However, in a nationwide population-based Danish cohort, there was no significant difference in the

risk of colitis-associated Anacetrapib CRC in IBD-exposed patients when compared with nonexposed patients (adjusted RR 1.06; 95% CI 0.33–3.40). Patients with a concomitant diagnosis of UC and PSC remain at a very high risk for the development of dysplasia and CRC. Ursodeoxycholic acid (UDCA) is a synthetic bile acid that has been proposed to have a molecular mechanism that can reduce the risk of dysplasia and CRC by decreasing the colonic concentration of bile acids, inhibiting Ras gene mutations and COX-2 expression, and having antioxidant activity. In a prospective, randomized, placebo-controlled trial of UDCA therapy in 52 patients with UC and PSC, 10% of patients receiving UDCA developed CRC versus 35% of patients not on UDCA therapy, resulting in a significant RR of 0.26 for developing colorectal dysplasia or cancer (95% CI 0.06–0.92; P = .034). 41 However, this prospective study has been countered by several studies reporting that long-term high-dose (28–30 mg/kg daily) UDCA is not protective in UC or PSC patients, and instead may increase the risk of colorectal neoplasia.