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    Treat to Target: The Role of Histologic Healing in Inflammatory Bowel Diseases: A Systematic Review and Meta-analysis. Gupta Akshita,Yu Amy,Peyrin-Biroulet Laurent,Ananthakrishnan Ashwin N Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association BACKGROUND:Endoscopic remission is a recognized therapeutic endpoint in inflammatory bowel disease (IBD; Crohn's disease (CD), ulcerative colitis (UC)). The impact of persistent histologic activity on long-term outcomes is less clear and limited by small studies. METHODS:We performed a systematic search of PubMed and Embase to identify eligible studies examining the association between histologic activity and relapse in patients with CD or UC in endoscopic remission. Studies were pooled together using random effects meta-analysis per the DerSimonian and Laird inverse variance method. The impact of different histologic scales, cut-offs, and individual features were examined. FINDINGS:Our meta-analysis included 28 studies contributing 2,806 patients (2677 UC; 129 CD). In UC, histologically active disease was associated with an overall increased risk of relapse (OR, 2.41; 95% CI, 1.91-3.04), with a similar effect noted in the subgroup with endoscopic Mayo endoscopic score of 0 vs 0 or 1. More rigorous Geboes cut-offs demonstrated numerically stronger impact on relapse rates-Geboes <3.1 (OR, 2.40; 95% CI, 1.57-3.65), Geboes <2.1 (OR, 3.91; 95% CI, 2.21-6.91) and Geboes 0 (OR, 7.40; 95% CI, 2.00-18.27). Among individual histologic features, basal plasmacytosis (OR, 1.94), neutrophilic infiltrations (OR, 2.30), mucin depletion (OR, 2.05), and crypt architectural irregularities (OR, 2.22) predicted relapse. There was no association between histologic activity and relapse in CD. CONCLUSIONS:In patients with UC in endoscopic remission, persistent histologic activity is associated with higher rates of relapse. Greater degree of normalization may have a stronger impact. 10.1016/j.cgh.2020.09.046
    The emerging role of histologic disease activity assessment in ulcerative colitis. Pai Rish K,Jairath Vipul,Vande Casteele Niels,Rieder Florian,Parker Claire E,Lauwers Gregory Y Gastrointestinal endoscopy BACKGROUND AND AIMS:Assessment of disease activity is essential for developing and determining appropriate therapy in patients with ulcerative colitis (UC). Validated clinical and endoscopic scoring systems have been established to accurately define disease activity. Clinical and endoscopic treatment targets have also been proposed, with gastroenterologists encouraged to optimize medical therapy to achieve these targets. Recently, histology has been recognized as an important prognostic factor and potential treatment target in patients with UC. METHODS:This review summarizes the recent literature regarding histologic scoring indices in UC and offers practical guidance to gastroenterologists on how to interpret histologic data. RESULTS:Substantial evidence indicates that histology accurately predicts clinical relapse, hospitalization, corticosteroid use, and development of dysplasia. Furthermore, compared with endoscopy, findings suggest that histology may be more predictive of these outcomes. Because microscopic disease activity can persist in the absence of clinical or endoscopic disease activity, histology may be the ideal marker of inflammation. Standardized definitions of histologic response and remission and a biopsy procurement protocol are needed to guide clinical decision making. It is recommended that overall assessment of disease severity be determined according to the worst affected biopsy fragment. Crypt architectural distortion, basal plasmacytosis, and neutrophilic activity should be reported. A 5-category classification system based on disease chronicity/activity and basal plasmacytosis is proposed. It is not yet necessary to report on the degree of mucosal eosinophilia or use a validated scoring system, although the latter may aid in determining therapeutic response. CONCLUSIONS:Although rarely used to measure inflammation and guide therapy, histologic disease activity is predictive of important clinical outcomes in UC. Randomized controlled trials are needed to determine whether histology should function as a treatment target. 10.1016/j.gie.2018.08.018
    Clinical, endoscopic and histological correlation and measures of association in ulcerative colitis. Fluxá Daniela,Simian Daniela,Flores Lilian,Ibáñez Patricio,Lubascher Jaime,Figueroa Carolina,Kronberg Udo,Pizarro Gonzalo,Castro Magdalena,Piottante Antonio,Vial María T,Quera Rodrigo Journal of digestive diseases OBJECTIVE:To determine the correlation between clinical, fecal, endoscopic and histological activity in patients with ulcerative colitis (UC). METHODS:A correlational cross-sectional analysis was performed in patients with UC who underwent colonoscopy between February and December 2016. Clinical, endoscopic, fecal and histological activities were determined using the partial Mayo subscore, Mayo endoscopic subscore and modified Mayo endoscopic subscore, fecal calprotectin and Geboes score and the presence of basal plasmacytosis, respectively. Scores were analyzed using Spearman's rank correlation test. To determine the association between scores and some clinical variables and active UC, univariate and multivariate logistic regressions were used. RESULTS:Altogether 105 procedures (93 patients) were included. In 64.8% of the procedures, the mucosa was inflamed; however, 14.7% did not show histological inflammation. Endoscopic remission was observed in the other 35.2% of procedures; however, in biopsies 21.6% exhibited histological inflammation. Mayo endoscopic subscore and modified Mayo endoscopic score were well correlated but were only moderately correlated with clinical and histological scores. Furthermore, there was a moderate correlation between Mayo endoscopic score and Geboes score. Conversely, histological scores were poorly correlated with partial Mayo score. In multivariate analysis, Geboes score and basal plasmacytosis were predictive of active disease (OR 3.505, 95% CI 1.544-7.959 and OR 3.240, 95% CI 1.123-9.349, respectively), whereas biological therapy was found to be protective against UC (OR 0.021, 95% CI 0.000-0.641). CONCLUSION:Clinical, endoscopic and histological activities were moderately correlated, while Geboes score and basal plasmacytosis were predictive of endoscopically active UC. 10.1111/1751-2980.12546
    Histological Markers of Clinical Relapse in Endoscopically Quiescent Ulcerative Colitis. Kevans David,Kirsch Richard,Dargavel Callum,Kabakchiev Boyko,Riddell Robert,Silverberg Mark S Inflammatory bowel diseases BACKGROUND:In ulcerative colitis (UC) patients who have achieved mucosal healing, active microscopic colonic mucosal inflammation is commonly observed. We aimed to assess the association between histological activity and disease relapse in endoscopically quiescent UC. METHODS:Ulcerative colitis patients with endoscopically quiescent disease and ≥12 months of follow-up were included. Biopsies were reviewed for the presence of basal plasmacytosis (BPC) and active histological inflammation, defined as a Geboes score (GS) ≥3.2. Primary outcome measures were disease relapse at 18 months and time to first relapse after index colonoscopy. RESULTS:Seventy-six UC patients (51% male; mean age, 38.6 years; median follow-up [range], 75.2 [2-118] months) were included. Sixty-two percent had an endoscopic Mayo score of 0 at index colonoscopy. Basal plasmacytosis was present in 46% and active histological inflammation in 30% of subjects. Presence of BPC was associated with a significantly shorter time to disease relapse (P = 0.01). Active histological inflammation was significantly associated with clinical relapse at 18 months (P = 0.0005) and shorter time to clinical relapse (P = 0.0006). Multivariate analysis demonstrated active histological inflammation to be independently associated with clinical relapse at 18 months and time to clinical relapse. CONCLUSIONS:In endoscopically quiescent UC, active histological inflammation and the presence of BPC are adjunctive histological markers associated with increased likelihood of disease relapse. Although prospective studies are required, the presence of these histological markers should be a factor considered when making therapeutic decisions in UC. 10.1093/ibd/izz308
    Prognostic value of serologic and histologic markers on clinical relapse in ulcerative colitis patients with mucosal healing. Bessissow Talat,Lemmens Bart,Ferrante Marc,Bisschops Raf,Van Steen Kristel,Geboes Karel,Van Assche Gert,Vermeire Séverine,Rutgeerts Paul,De Hertogh Gert The American journal of gastroenterology OBJECTIVES:Endoscopic mucosal healing is a key endpoint for the treatment of ulcerative colitis (UC). The role of microscopic activity in predicting disease relapse has not been fully assessed. We aimed to investigate the predictive role of serologic and histologic markers on disease relapse in UC patients with endoscopically inactive disease. METHODS:Adult UC patients with endoscopically inactive disease (Mayo 0) and a 12-month follow-up between 2008 and 2011 were retrospectively included. An expert pathologist evaluated all colonic biopsies for histologic activity (Geboes score) and the presence of basal plasmacytosis. Blood samples collected around the time of endoscopy were analyzed. Disease relapse, defined as a clinical Mayo score ≥3, was documented during follow-up. RESULTS:The study cohort consisted of 75 patients (53% men, median age 47 years). Despite normal endoscopy, histology showed inflammatory activity with a Geboes score ≥3.1 in 40% and basal plasmacytosis in 21% of patients. At 12 months, clinical relapse was observed in 20% (n=15) of patients. Presence of basal plasmacytosis (P=0.007) and a Geboes score ≥3.1 (P=0.007) were predictive of disease relapse. Using multivariate analysis, the presence of basal plasmacytosis was predictive of clinical relapse (odds ratio (OR) 5.13 (95% confidence interval (CI): 1.32-19.99), P=0.019), whereas the use of biologicals at endoscopy favored remission (OR 0.24 (95% CI: 0.05-1.01), P=0.052). CONCLUSIONS:We demonstrated that the presence of basal plasmacytosis predicts UC clinical relapse in patients with complete mucosal healing. We recommend closer follow-up and optimization of medical therapy in patients with basal plasmacytosis. 10.1038/ajg.2012.301