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      Discrepancies between patient-reported outcomes, and endoscopic and histological appearance in UC

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          Abstract

          Objective

          Both endoscopy and histology may be included in the definition of mucosal healing in UC. This study aimed to establish the association between patient-reported outcomes, specifically symptom measures, and the presence of inflammation as measured by endoscopy and histology in UC.

          Design

          Using patient data from an observational multicentre study of UC (n=103), rectal bleeding (RB) and stool frequency (SF) symptom subscores of the Mayo Clinic Score (MCS) were compared with the endoscopic subscore (MCSe) and histology. Faecal calprotectin and biopsy cytokine expression were also evaluated.

          Results

          When identifying UC patients with inactive disease, RB scores were superior to SF scores and the combination (sensitivity/specificity: MCSe=0/1, RB 77%/81%, SF 62%/95%, RB+SF 54%/95%; MCSe=0, RB 87%/66%, SF 76%/83%, RB+SF 68%/86%). Across different definitions of mucosal healing (MCSe≤1; 0; or 0 plus inactive histology), a larger subset of patients reported increased SF (39%, 25% and 27%, respectively) compared with RB (24%, 13% and 10%). Faecal calprotectin and inflammatory cytokine expression were higher in patients with active disease compared with patients with mucosal healing, but there were no differences between patients using increasingly stringent definitions of mucosal healing.

          Conclusions

          Endoscopically inactive disease is associated with absence of RB but not with complete normalisation of SF. Achieving histological remission did not improve symptomatic relief. In addition, in these patients, higher inflammatory biomarker levels were not observed. These data suggest that non-inflammatory changes, such as bowel damage, may contribute to SF in UC.

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          Most cited references11

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          Ulcerative colitis.

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            Early mucosal healing with infliximab is associated with improved long-term clinical outcomes in ulcerative colitis.

            In the Active Ulcerative Colitis Trial (ACT)-1 and ACT-2, patients with ulcerative colitis treated with infliximab were more likely than those given placebo to have a clinical response, undergo remission, and have mucosal healing. We investigated the association between early improvement (based on endoscopy) and subsequent clinical outcome. Patients underwent endoscopic evaluations at weeks 0, 8, 30, and 54 (ACT-1 only), and were categorized into 4 subgroups by week 8 (Mayo endoscopy subscore, 0-3). The association of week 8 endoscopy subscores, subsequent colectomy risk, symptoms and corticosteroid use outcomes were analyzed. Mucosal healing was defined as a Mayo endoscopy subscore of 0 (normal) or 1 (mild). Infliximab-treated patients with lower week 8 endoscopy subscores were less likely to progress to colectomy through 54 weeks of follow-up evaluation (P=.0004). This trend was not observed among patients given placebo (P=.47). Patients with lower endoscopy subscores achieved better symptomatic and corticosteroid use outcomes at weeks 30 and 54 (P<.0001, infliximab; P<.01, placebo). Among patients who achieved clinical response at week 8, trends in subsequent clinical outcomes by week 8 endoscopy subscores were generally consistent with that for the overall patient population; no trends were observed among patients who achieved clinical remission. The degree of mucosal healing after 8 weeks of infliximab was correlated with improved clinical outcomes including colectomy. Similar trends were observed for all outcomes except colectomy among the subgroup with clinical response at week 8. The degree of mucosal healing at week 8 among those in clinical remission did not predict subsequent disease course. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.
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              A reproducible grading scale for histological assessment of inflammation in ulcerative colitis.

              Evaluation of histological activity in ulcerative colitis needs to be reproducible but has rarely been tested. This could be useful both clinically and in clinical trials. To develop reproducible criteria which are valid in the assessment of acute inflammation (activity) and chronicity, and to evaluate these features in an interobserver variability study. A six grade classification system for inflammation was developed which could also be fine tuned within each grade. The grades were: 0, structural change only; 1, chronic inflammation; 2, lamina propria neutrophils; 3, neutrophils in epithelium; 4, crypt destruction; and 5, erosions or ulcers. Ninety nine haematoxylin-eosin sections from endoscopically inflamed and non-inflamed mucosa from patients with distal ulcerative colitis were assessed in two separate readings by three pathologists independently and without knowledge of the clinical status. Interobserver agreement was compared pairwise using kappa statistics. Initially, kappa values between the observers were 0.20, 0.42, and 0.26, which are too low to be of value. Following development of a semiquantitative pictorial scale for each criterion, kappa values improved to 0.62, 0.70, and 0.59. For activity defined by neutrophils between epithelial cells, kappa values were 0.903, 1.000, and 0.907. Complete agreement was reached in 64% of samples of endoscopically normal and in 66% of endoscopically inflamed tissue. Neutrophils in epithelium correlated with the presence of crypt destruction and ulceration. A histological activity system was developed for ulcerative colitis that showed good reproducibility and modest agreement with the endoscopic grading system which it complemented. It has potential value both clinically and in clinical trials.
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                Author and article information

                Journal
                Gut
                Gut
                gutjnl
                gut
                Gut
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                0017-5749
                1468-3288
                December 2017
                2 September 2016
                : 66
                : 12
                : 2063-2068
                Affiliations
                [1 ]Division of Gastroenterology, Icahn School of Medicine at Mount Sinai , New York, New York, USA
                [2 ]Genentech Research and Early Development , South San Francisco, California, USA
                [3 ]Department of Morphology and Molecular Pathology, University Hospital Gasthuisberg , Leuven, Belgium
                [4 ]Division of Gastroenterology and Hepatology, Mayo Clinic , Rochester, Minnesota, USA
                Author notes
                [Correspondence to ] Professor Jean-Frédéric Colombel, Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA; jean-frederic.colombel@ 123456mssm.edu
                Article
                gutjnl-2016-312307
                10.1136/gutjnl-2016-312307
                5749342
                27590995
                c2f5cedc-e263-4aa9-a679-f0e21396b7d0
                Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

                History
                : 23 May 2016
                : 25 July 2016
                : 15 August 2016
                Funding
                Funded by: Genentech, http://dx.doi.org/10.13039/100004328;
                Categories
                1506
                Inflammatory Bowel Disease
                Original article
                Custom metadata
                unlocked

                Gastroenterology & Hepatology
                ulcerative colitis,endoscopy,histopathology,gastrointestinal bleeding,diarrhoea

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