Histological Inflammation in the Endoscopically Uninflamed Mucosa is Associated With Worse Outcomes in Limited Ulcerative Colitis

Abstract

Background The Montreal classification categorizes patients with ulcerative colitis (UC) based on their macroscopic disease extent. Independent of endoscopic extent, biopsies through all colonic segments should be retrieved during index colonoscopy. However, the prognostic value of histological inflammation at diagnosis in the inflamed and uninflamed regions of the colon has never been assessed. Methods This was a multicenter retrospective cohort study of newly diagnosed patients with treatment-naïve proctitis and left-sided UC. Biopsies from at least 2 colonic segments (endoscopically inflamed and uninflamed mucosa) were retrieved and reviewed by 2 pathologists. Histological features in the endoscopically inflamed and uninflamed mucosa were scored using the Nancy score. The primary outcomes were disease complications (proximal disease extension, need for hospitalization or colectomy) and higher therapeutic requirements (need for steroids or for therapy escalation). Results Overall, 93 treatment-naïve patients were included, with a median follow-up of 44 months (range, 2-329). The prevalence of any histological inflammation above the endoscopic margin was 71%. Proximal disease extension was more frequent in patients with histological inflammation in the endoscopically uninflamed mucosa at diagnosis (21.5% vs 3.4%, P = 0.04). Histological involvement above the endoscopic margin was the only predictor associated with an earlier need for therapy escalation (adjusted hazard ratio, 3.69; 95% confidence interval, 1.05-13.0); P = 0.04) and disease complications (adjusted hazard ratio, 4.79; 95% confidence interval, 1.10-20.9; P = 0.04). Conclusions The presence of histological inflammation in the endoscopically uninflamed mucosa at the time of diagnosis was associated with worse outcomes in limited UC.

Molecular Activity of Inflammation and Epithelial-Mesenchymal Transition in the Microenvironment of Ulcerative Colitis

“…39,40 Histological activity, recently focused as a new therapeutic target for the deep remission in UC, 41 in the uninflamed regions, is associated with patients' prognosis. 42 However, not all histological scoring systems are validated, and there are possible discrepancies within or/ and between interpreters. 43,44 In our study, the discrepancy in the genetic expression of inflammation and tissue remodeling (EMT) was shown between non-MH and MH groups whose histological activities did not differ.…”

When disease extent is not always a key parameter: Management of refractory ulcerative proctitis

“…The identification of risk factors for a disabling disease course of UP could aid clinicians in accelerating the step-up treatment algorithm. Recently, histologic inflammation in the endoscopically uninflamed mucosa at the time of diagnosis was associated with worse outcomes in limited UC and especially disease complications, including colectomy (adjusted hazard ratio, 4.79; 95% confidence interval, 1.10–20.9; p ​= ​0.04) ( de Frias Gomes et al., 2021 ). Younger age at diagnosis (HR 0.98, 95% CI 0.96–0.99) and continuous active disease (HR 2.18, 95% CI 1.27–3.73) were identified as independent risk factors for proximal disease extension in a single center historical cohort of incident UC cases ( Sahami et al., 2017 ).…”

Construction of a molecular inflammatory predictive model with histone modification-related genes and identification of CAMK2D as a potential response signature to infliximab in ulcerative colitis

“…For both patients and clinicians, selecting from various treatment options frequently presents a clinical challenge. Prior studies indicate that intestinal inflammation of patients with UC is associated with long-term outcomes and drug response ( 2 , 3 ). Disease molecular measures may augment current endpoints and provide a more profound understanding of the disease mechanism ( 4 ).…”