However, IBD-associated adenocarcinoma does not seem to follow the discrete adenoma-to-CRC sequence of events.3 Rather, a progression, from inflamed mucosa to low-grade dysplasia (LGD) to high-grade dysplasia (HGD) to invasive adenocarcinoma, in IBD remains presumed and unproven. In fact, neoplasia in colitis takes different forms, a fact that

has resulted in difficulty Forskolin price classifying, identifying, and developing appropriate prevention strategies for it. Cells from colonic mucosa in patients with chronic colitis have the molecular fingerprints of dysplasia and cancer, including genomic instability (aneuploidy), aberrant DNA methylation, and p53 mutations, even before there is any histologic evidence of dysplasia or cancer.4 It is thought that such a “field effect” of CRC risk is induced by chronic long-standing mucosal inflammation. Most recently, the degree of inflammation has been shown to be a significant risk factor for neoplasia in IBD.5 and 6 In addition to the presence and degree of severity of active endoscopic/histologic colonic inflammation, additional established IBD-associated dysplasia and CRC risk factors include extent and duration of disease, family history of CRC, concomitant primary sclerosing cholangitis (PSC), find more young age at diagnosis, and presence of postinflammatory polyps and strictures.4 and 6 Of these risks, the only

modifiable risk factor may be the degree of active inflammation. Therefore, it has been proposed that effective disease control Thalidomide through abrogation of inflammation may also reduce

CRC risk in the individual patient. Although the culmination of this evidence to date supports the clinician-adopted theory that treating to achieve mucosal healing will reduce the risk of CRC in patients with IBD, it remains uncertain how these recommendations can be practically applied by clinicians trying to develop effective dysplasia and CRC prevention strategies in IBD. This article summarizes the potential for medical therapy to reduce the risk of CRC via primary and secondary prevention, and offers practical ways in which a goal of mucosal improvement or healing may be incorporated into clinical practice (Box 1). Primary chemoprevention Medical therapy reduces inflammation over time The end point of escalation of therapy in IBD has traditionally been based on adequate symptom control.7 Despite patient satisfaction in the achievement of clinical remission, in many patients this goal is believed to be insufficient in achieving additional goals of stable remission over time and changing the natural history of the disease. In fact, multiple lines of investigation have demonstrated that a significant proportion of IBD patients in clinical (symptomatic) remission continue to have active mucosal inflammation, both endoscopically and histologically.