Microscopic heterogeneity in ulcerative colitis: implications for microscopic measurement of disease activity

Abstract

Growing interest in histological measurements of inflammatory\xa0 activity to determine therapeutic efficacy and endpoints in IBD has been accompanied by progress in developing and validating scoring instruments for this purpose.1–5 Four histological grading instruments, the Geboes score, Nancy index, Robarts Histological Index (RHI)\xa0and modified Riley score, have recently demonstrated responsiveness to clinical changes based on data from a phase II trial of ozanimod.6 Further refinement of the operating characteristics of these instruments and definition of threshold values for remission can be expected.7 \n\nLess attention has been given to pre-analytical factors which might affect the histological assessment of disease activity and the definition of therapeutic endpoints, such as biopsy sampling density and target selection. Clinical consensus guidelines have thus far provided only empirical guidance. The European Crohn’s and Colitis Organisation (ECCO) guidelines for initial IBD diagnosis recommend two forceps biopsies from each of five sites in the colorectum and terminal ileum and separate biopsies from endoscopically distinct regions8 but do not address sampling density and target selection in other clinical situations. Likewise, uniform standards for biopsy sampling in therapeutic drug trials are lacking. One study has reported good endoscopic concordance between the rectosigmoid and proximal colon at baseline …