9 Clinically the achievement of a healed mucosa has been associated with a modified course of IBD, including a reduction in rates of clinical relapse, fewer inpatient hospitalizations, and decreased lifetime risk of surgery.10, 11 and 12 Evidence that a healed bowel mitigates the development of IBD-associated dysplasia and CRC

has been insufficient. With the increased interest in endoscopic mucosal healing in clinical trials, it is hoped that additional evidence will demonstrate a direct link between this end point and subsequent reduction in CRC risk. Clinical trials to date have varied definitions ranging from endoscopic resolution of all mucosal ulcerations to endoscopic scoring indices, PF-01367338 order with very few studies evaluating histologic healing. Therefore, a remaining challenge is

SGI-1776 cost this discrepancy between the clinical trials definition of mucosal healing through endoscopic measures and the available evidence related to risk for neoplasia in colitis, which is histologically measured. More recently, the US Food and Drug Administration has expressed interest in histologic assessment of bowel healing, which undoubtedly will lead to additional study and resource allocation. Nonetheless, as the bar is raised to achieve deeper levels of mucosal healing, one of the significant challenges is the poor correlation between macroscopic mucosal healing as gauged by endoscopic assessment and endoscopist interpretation, and histologically measured disease control as measured by biopsy sampling and pathologist interpretation. In a study of 152 IBD patients in clinical

remission undergoing routine surveillance colonoscopy, Baars and colleagues8 found that only 67% of patients in clinical remission had histologically active inflammation, and of these patients 50% were endoscopically normal. Similarly, in a study of 82 asymptomatic patients with ulcerative Paclitaxel mouse colitis (UC), Rubin and colleagues identified that more than 30% of patients had endoscopic inflammation and 89% had histologic evidence of active inflammation.13 If it is considered that a strict definition of mucosal healing should include resolution of histologic inflammation in addition to an endoscopic assessment of healing, these studies demonstrate the real-world challenge to this approach and emphasize the importance of further study. A well-described challenge to the use of mucosal healing as a primary end point of the treatment of IBD is the trade-off between risks and benefits (and costs) in patients who feel well, but require escalation of therapy to achieve deeper levels of disease control.