title: Confocal laser endomicroscopy: a new gold standard for the assessment of mucosal healing in ulcerative colitis.
abstract: OBJECTIVE
  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 (mtDNA) mutations; (iv) inflammatory infiltration; and (v) vascular permeability (VP).
  
  
  RESULTS
  In control subjects, CLE demonstrated normal colonic crypts and microvasculature. COX2 expression was minimal, and < 7% crypts showed mtDNA mutations. Colonic mucosa of UC-IR patients had impaired and distorted crypt regeneration, increased COX2, 69% crypts with mtDNA 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 COX2 and mtDNA mutations; (ii) CLE may serve as a new gold standard for the assessment of mucosal healing in UC.
authors.affiliation: Institut des Maladies de l'Appareil Digestif, CIC INSERM 04 et Service d'Hépato-Gastroentérologie, CHU de Nantes, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Macé
authors.forename: Amrita
authors.initials: A
authors.lastname: Ahluwalia
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Coron
authors.forename: Marc
authors.initials: M
authors.lastname: Le Rhun
authors.forename: Arnaud
authors.initials: A
authors.lastname: Boureille
authors.forename: Céline
authors.initials: C
authors.lastname: Bossard
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Mosnier
authors.forename: Tamara
authors.initials: T
authors.lastname: Matysiak-Budnik
authors.forename: Andrzej S
authors.initials: AS
authors.lastname: Tarnawski
mesh_terms: D000328:Adult; D000368:Aged; D003093:Colitis, Ulcerative / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics; D016099:Endoscopy, Gastrointestinal / Q000379:methods* / Q000592:standards; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology* / Q000502:physiology; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods* / Q000592:standards; D008875:Middle Aged; D057054:Molecular Imaging / Q000379:methods* / Q000592:standards*; D009154:Mutation; D014945:Wound Healing
chemical_list: D004272:DNA, Mitochondrial; D051546:Cyclooxygenase 2
keywords: COX2; angiogenesis; confocal laser endomicroscopy (CLE); mitochondrial DNA (mtDNA) mutation; mucosal healing; ulcerative colitis