Evaluation of optimal biopsy location for assessment of histological activity, transcriptomic and immunohistochemical analyses in patients with active Crohn’s disease

Abstract

Background:The appropriate location for biopsy procurement relative to an ulcer in active Crohn's disease is unknown.Aim: To explore the relationship between biopsy location, histological disease activity, proinflammatory gene expression and the presence of inflammatory cells.Methods: Fifty-one patients with Crohn's disease and ulcers >0.5 cm diameter in the colon and/or ileum were prospectively enrolled at three centres. Biopsies were obtained from 0 mm, 7 to 8 mm and 21 to 24 mm from the edge of the largest ulcer.Histological activity was blindly assessed with the Global Histological Disease Activity Score, the Robarts Histopathology and Nancy Histological indices. Messenger ribonucleic acid (mRNA) levels for interleukins-6, -8 and -23 (p19 and p40 subunits), CD31 and S100A9 were measured using quantitative polymerase chain reaction. The number of CD3+, CD68+ and myeloperoxidase-positive cells was quantified by immunohistochemistry. Data were analysed using mixed models with location and segment as fixed effects and patients as random effect to account for correlation among segments within a patient.Results: Histological disease activity scores (P < 0.0001), proinflammatory gene expression levels (P < 0.005) and numbers of myeloperoxidase-positive cells (P < 0.0001) were highest in biopsies from the ulcer edge in the colon and ileum, with decreasing gradients observed with distance from the edge (P < 0.05). No differences between colonic and ileal samples were detected for the parameters measured at any location. Conclusions:Biopsies from the ulcer edge in patients with Crohn's disease yielded the greatest histological disease activity and mRNA levels and had similar readouts in the colon and ileum. Research is needed to confirm this conclusion for other measures.

Endoscopic, Radiologic, and Histologic Healing With Vedolizumab in Patients With Active Crohn’s Disease

“…Histologic assessment of treatment response has some issues in CD. 12 Inflammation in CD is characteristically discontinuous, leading to potential sampling errors on histologic evaluation. Unlike endoscopic assessments, which can directly evaluate the extent of disease at the macroscopic level, histologic evaluations only allow for the determination of microscopic disease extent at the site of biopsy.…”

“…Histology, another potential outcome measure, has not been widely used in CD trials because of the lack of a validated scoring system, complex heterogeneity of disease location, and the patchy nature of microscopic inflammation. 12 Nevertheless, quantification of inflammation on endoscopic biopsies seems to be a clinically relevant goal in CD trials, given recent developments in validating tools for histologic assessment in ulcerative colitis trials. 13 Vedolizumab is an anti-a4b7-integrin humanized immunoglobulin G1 monoclonal antibody that selectively blocks T-lymphocyte trafficking into the gastrointestinal mucosa.…”

Editorial: assessing histological disease activity in Crohn’s disease—a call for standardisation of mucosal biopsy location. Authors' reply

“…The authors' declarations of personal and financial interests are unchanged from those in the original article …”

“…We thank Drs Bryant and Costello for their comments on our study . To date, there have been no empirical data to support the traditional dogma of procuring biopsies from the edge of an ulcer, a practice perhaps inferred from similar approaches in the upper gastrointestinal tract in patients with gastric ulcers.…”

Editorial: assessing histological disease activity in Crohn’s disease—a call for standardisation of mucosal biopsy location

“…Clarity on this question is fundamental to the validity of any histological disease activity metric in IBD. Novak et al formally evaluate the influence of mucosal biopsy procurement in relation to colonic and ileal ulceration in Crohn's disease, using histological indices, immunohistochemistry, and transcriptomics . An adapted version of the Global Histological Disease Activity Score was used, alongside the Robarts Histopathology (RHI) and Nancy Histological indices (NHI), which have both been validated in ulcerative colitis .…”