Scientific Abstract
Proposal No. IBD-0219
Principal Investigator: David Paul Hurlstone, MB ChB, M.D.
Applicant Organization: Sheffield Teaching Hospitals NHS Foundation Trust (England, United Kingdom)
Project Title: A randomized Phase II clinical trial to investigate the diagnostic utility of confocal chronoscopic endomicroscopy for the detection and characterization of intraepithelial neoplasia in chronic ulcerative colitis
Period of Award: October 8, 2007 - October 7, 2008
Background summary:
As intraepithelial neoplasia and colitis-associated cancer can occur in macroscopically normal mucosa, random biopsies at 10 cm intervals throughout the colorectum are currently recommended during screening colonoscopy1. Historically, the probability for detection of neoplastic change was thought to correlate with the numbers of biopsies taken2. However, recent data suggests that pan-chromoscopy using methylene blue or indigo carmine and targeted biopsies, can improve the detection of intraepithelial neoplasia in chronic ulcerative colitis (CUC) when compared to conventional colonoscopic screening protocols3. Kiesslich and colleagues showed that chromoscopy permitted a more accurate diagnosis of extent and inflammatory activity in CUC, but also enhanced the detection of intraepithelial neoplasia and cancer in colitis (p=0.0002 and p=0.003) respectively3, data now validated by the Sheffield group4, 5. Rutter and colleagues have also demonstrated a statistically increased dysplasia detection rate using indigo carmine pan-colorectal chromoscopy6.
Novel endoscopic imaging technology of potential clinical benefit for intraepithelial neoplasia detection in chronic ulcerative colitis:
Miniaturization of a novel confocal laser endomicroscope (Optiscan Pty., Notting Hill, Victoria, Australia) has now permitted functional integration into the distal tip of a conventional video colonoscope (Pentax EC3870K; Pentax, Tokyo), enabling in vivo surface and subsurface (z axis) cellular resolution imaging during ongoing video endoscopy7. Kiesslich and colleagues have recently reported their randomised controlled data regarding the efficacy of targeted endomicroscopy for the diagnosis of intraepithelial neoplasia in CUC. When considering the primary outcome analysis of histologically confirmed intraepithelial neoplasia, chromoscopic endomicroscopy significantly improved the yield as compared to controls (p<0.007) and was able to resolve discrete cellular structure in vivo.
Both chromoscopy3, 5, 6, 8, 9 and chromoscopic assisted endomicroscopy10 have, therefore, shown to increase the yield of intraepithelial neoplasia in CUC screening colonoscopy. However, previous studies have compared the diagnostic yield of endomicroscopy with conventional ‘white light’ endoscopy and hence the overall objective increase of endomicroscopy targeted biopsies as compared to chromoscopy guided alone is not apparent10. These data are important to quantify if endomicroscopy is to assume a potential ‘gold standard’ for intraepithelial neoplasia detection in CUC.
Study hypothesis:
The a priori hypothesis is to demonstrate that surveillance colonoscopy using chromoscopic assisted endomicroscopy may increase the total number of intraepithelial neoplastic lesions detected in patients with CUC as compared to pan-colonic chromoscopy alone.
Methodology:
A prospective randomised controlled study to compare the diagnostic yield of intraepithelial neoplasia and cancer in patients undergoing CUC screening using chromoscopy assisted endomicroscopy vs. pan-colonic chromoscopy assisted colonoscopy.