Preventing Neoplastic Progression in Ulcerative Colitis

DESCRIPTION (provided by applicant): This proposal will attempt to clarify issues of cancer prevention in ulcerative colitis (UC). Colorectal cancer (CRC) is the most ominous long-term complication of UC. To reduce mortality from CRC, most clinicians employ a system of surveillance, in which periodic colonoscopies are performed with multiple biopsies sent for histologic review. In this paradigm, patients found to have dysplasia or CRC are referred for surgery and patients free of dysplasia continue with surveillance examinations. Unfortunately, no published report demonstrates a mortality benefit for surveillance, but the lack of appeal for prophylactic colectomy or waiting for a symptomatic cancer to arise has led to near universal acceptance of this unproven practice. In an effort to better define high- and low-risk populations with longstanding UC, and to therefore improve upon the current practice of surveillance, the proposed project will assess surveillance, assessing the effect of long durations of dysplasia-free disease, use of anti-inflammatory medications, and the influence of colonic inflammation on the development of dysplasia or CRC. In Aim 1, key features of surveillance will be examined: sub-Aim 1 will assess whether duration of disease influence the rate of neoplastic development for a group of patients under surveillance;sub-Aim 2 will address the question of colonoscopy frequency for patients under surveillance;and sub-Aim 3 will attempt to determine the effect of "under-sampling," in which an inadequate number of biopsies are performed at surveillance. Aim 2 will address the important question of chemoprevention, looking at the effect of anti-inflammatory medications on the development of dysplasia and cancer. And finally, Aim 3 will examine the influence of colonic inflammation at surveillance on the subsequent development of colonic neoplasia. All of these studies will be performed by development and subsequent query of a large database that already holds the clinical, endoscopic, and histopathologic histories of over 500 patients with UC at a large, tertiary care center.