Confocal laser endomicroscopy: A new gold standard for the assessment of mucosal healing in ulcerative colitis

Background and Aim Endoscopic assessment of mucosal healing in ulcerative colitis ( UC ) is increasingly accepted as a measure of disease activity, therapeutic goal, and the key prognostic indicator. While regular endoscopy evaluates appearance of the mucosal surface, confocal laser endomicroscopy ( CLE ) enables in vivo visualization of subepithelial mucosa at 1000× magnification during ongoing endoscopy. Our aims were to determine using CLE whether endoscopically normal appearing colonic mucosa in patients with UC in remission ( UC ‐ IR ) has fully regenerated mucosal structures, resolved inflammation, and to identify the mechanisms. Methods Twelve patients (six controls and six with UC ‐ IR ) underwent colonoscopy using CLE and intravenous fluorescein infusion. During colonoscopy, CLE images of colonic mucosa and conventional mucosal biopsies were obtained and evaluated using image‐analysis systems. We quantified; (i) regeneration of colonic crypts and blood microvessels; (ii) cyclooxygenase 2 (COX2) expression; (iii) mitochondrial DNA (mt DNA ) mutations; (iv) inflammatory infiltration; and (v) vascular permeability ( VP ). Results In control subjects, CLE demonstrated normal colonic crypts and microvasculature. COX 2 expression was minimal, and < 7% crypts showed mt DNA mutations. Colonic mucosa of UC ‐ IR patients had impaired and distorted crypt regeneration, increased COX 2, 69% crypts with mt DNA mutations, persistent inflammation, and abnormal vascular architecture with increased VP (all P  < 0.001 vs normal mucosa). Conclusions (i) Endoscopically normal appearing colonic mucosa of patients with UC ‐ IR remains abnormal: CLE demonstrates impaired crypt regeneration, persistent inflammation, distinct abnormalities in angioarchitecture and increased vascular permeability; molecular imaging showed increased COX 2 and mt DNA mutations; (ii) CLE may serve as a new gold standard for the assessment of mucosal healing in UC .