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Competing Interests: Competing interests: None declared.

Background: We aimed to predict response to biologics in inflammatory bowel disease (IBD) using computerized image analysis of probe confocal laser endomicroscopy (pCLE) in vivo and assess the binding of fluorescent-labeled biologics ex vivo. Additionally, we investigated genes predictive of anti-tumor necrosis factor (TNF) response., Methods: Twenty-nine patients (15 with Crohn's disease [CD], 14 with ulcerative colitis [UC]) underwent colonoscopy with pCLE before and 12 to 14 weeks after starting anti-TNF or anti-integrin α4β7 therapy. Biopsies were taken for fluorescein isothiocyanate-labeled infliximab and vedolizumab staining and gene expression analysis. Computer-aided quantitative image analysis of pCLE was performed. Differentially expressed genes predictive of response were determined and validated in a public cohort., Results: In vivo, vessel tortuosity, crypt morphology, and fluorescein leakage predicted response in UC (area under the receiver-operating characteristic curve [AUROC], 0.93; accuracy 85%, positive predictive value [PPV] 89%; negative predictive value [NPV] 75%) and CD (AUROC, 0.79; accuracy 80%; PPV 75%; NPV 83%) patients. Ex vivo, increased binding of labeled biologic at baseline predicted response in UC (UC) (AUROC, 83%; accuracy 77%; PPV 89%; NPV 50%) but not in Crohn's disease (AUROC 58%). A total of 325 differentially expressed genes distinguished responders from nonresponders, 86 of which fell within the most enriched pathways. A panel including ACTN1, CXCL6, LAMA4, EMILIN1, CRIP2, CXCL13, and MAPKAPK2 showed good prediction of anti-TNF response (AUROC >0.7)., Conclusions: Higher mucosal binding of the drug target is associated with response to therapy in UC. In vivo, mucosal and microvascular changes detected by pCLE are associated with response to biologics in inflammatory bowel disease. Anti-TNF-responsive UC patients have a less inflamed and fibrotic state pretreatment. Chemotactic pathways involving CXCL6 or CXCL13 may be novel targets for therapy in nonresponders., (© 2022 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Histological remission is evolving as an important treatment target in UC. We aimed to develop a simple histological index, aligned to endoscopy, correlated with clinical outcomes, and suited to apply to an artificial intelligence (AI) system to evaluate inflammatory activity., Methods: Using a set of 614 biopsies from 307 patients with UC enrolled into a prospective multicentre study, we developed the Paddington International virtual ChromoendoScopy ScOre (PICaSSO) Histologic Remission Index (PHRI). Agreement with multiple other histological indices and validation for inter-reader reproducibility were assessed. Finally, to implement PHRI into a computer-aided diagnosis system, we trained and tested a novel deep learning strategy based on a CNN architecture to detect neutrophils, calculate PHRI and identify active from quiescent UC using a subset of 138 biopsies., Results: PHRI is strongly correlated with endoscopic scores (Mayo Endoscopic Score and UC Endoscopic Index of Severity and PICaSSO) and with clinical outcomes (hospitalisation, colectomy and initiation or changes in medical therapy due to UC flare-up). A PHRI score of 1 could accurately stratify patients' risk of adverse outcomes (hospitalisation, colectomy and treatment optimisation due to flare-up) within 12 months. Our inter-reader agreement was high (intraclass correlation 0.84). Our preliminary AI algorithm differentiated active from quiescent UC with 78% sensitivity, 91.7% specificity and 86% accuracy., Conclusions: PHRI is a simple histological index in UC, and it exhibits the highest correlation with endoscopic activity and clinical outcomes. A PHRI-based AI system was accurate in predicting histological remission., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Inflammatory bowel disease-related colorectal cancer (IBD-CRC) is one of the most serious complications of IBD contributing to significant mortality in this cohort of patients. IBD is often associated with diet and lifestyle-related gut microbial dysbiosis, the interaction of genetic and environmental factors, leading to chronic gut inflammation. According to the "common ground hypothesis", microbial dysbiosis and intestinal barrier impairment are at the core of the chronic inflammatory process associated with IBD-CRC. Among the many underlying factors known to increase the risk of IBD-CRC, perhaps the most important factor is chronic persistent inflammation. The persistent inflammation in the colon results in increased proliferation of cells necessary for repair but this also increases the risk of dysplastic changes due to chromosomal and microsatellite instability. Multiple pathways have been identified, regulated by many positive and negative factors involved in the development of cancer, which in this case follows the 'inflammation-dysplasia-carcinoma' sequence. Strategies to lower this risk are extremely important to reduce morbidity and mortality due to IBD-CRC, among which colonoscopic surveillance is the most widely accepted and implemented modality, forming part of many national and international guidelines. However, the effectiveness of surveillance in IBD has been a topic of much debate in recent years for multiple reasons - cost-benefit to health systems, resource requirements, and also because of studies showing conflicting long-term data. Our review provides a comprehensive overview of past, present, and future perspectives of IBD-CRC. We explore and analyse evidence from studies over decades and current best practices followed globally. In the future directions section, we cover emerging novel endoscopic techniques and artificial intelligence that could play an important role in managing the risk of IBD-CRC., Competing Interests: Conflict-of-interest statement: The authors have none to declare., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background and Aims: A composite endoscopic-histologic remission is increasingly explored as an important endpoint in ulcerative colitis (UC). We investigated combined endoscopic-histologic remission for predicting clinical outcomes at 12 months compared with endoscopic remission alone using the high definition virtual chromoendoscopy (VCE) Paddington International virtual ChromoendoScopy ScOre (PICaSSO) and histology scores., Methods: Ulcerative colitis patients, prospectively enrolled from 11 international centres, underwent VCE with targeted biopsies and followed up for 12 months. Endoscopic activity was assessed by Mayo Endoscopic Score (MES), Ulcerative Colitis Endoscopic Index Severity (UCEIS) followed by VCE-PICaSSO. Robarts Histopathological Index|Robarts Histological index≤3 without neutrophils in mucosa, and Nancy Histological index (NHI)≤ 1 were used to define histologic remission. Combined endoscopic-histologic remission was compared with endoscopic remission alone by Cox proportional hazards model and by two- and three-proportion analysis using pre-specified clinical outcomes., Results: 307 patients were recruited and 302 analysed. There was no difference in survival without specified clinical outcomes between PICaSSO defined endoscopic remission alone and endoscopic plus histologic remission in the rectum (HR 0.42, 95%CI 0.16-1.11 and HR 1.03, 95%CI 0.42-2.52 for Robarts Histological index and NHI respectively) at 12 months. There was however a significant survival advantage without specified clinical outcome events for UCEIS combined with histology compared with UCEIS alone (HR 0.30, 95%CI 0.12-0.75, p = 0.02) at 12 months (but not combined with NHI). For MES there was no advantage for predicting specified clinical outcomes at 12 months for endoscopy alone versus endoscopy plus histology, but there were differences in two and three proportion analysis at 6 months., Conclusion: Endoscopic remission by VCE-PICaSSO alone was similar to combined endoscopic and histologic remission for predicting specified clinical outcomes at 12 months. Larger studies with specific therapeutic interventions are required to further confirm the findings., (© 2021 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background: Endoscopic and histological remission are both important treatment goals in patients with ulcerative colitis (UC). We aimed to define cellular architecture, expression of molecular markers, and their correlation with endoscopic scores assessed by ultra-high magnification endocytoscopy (ECS) and histological scores., Methods: Patients with UC (n = 29) were prospectively recruited. The correlation among ECS score (ECSS), Mayo endoscopic score (MES), and histological scores were determined. Area under curve were plotted to determine the best thresholds for ECSS that predicted histological remission by Robarts (RHI) and Nancy Histological Index (NHI).Soluble analytes relevant to inflammation were measured in serum and mucosal culture supernatants using ProcartaPlex Luminex assays and studied by partial least square discriminant analysis and logistic model. Mucosal RNA sequencing and bioinformatics analysis were performed to define differentially expressed genes/pathways., Results: Endocytoscope scoring system correlated strongly with RHI (r = 0.89; 95% CI, 0.51-0.98) and NHI (r = 0.86; 95% CI, 0.42-0.98) but correlated poorly with MES (r = 0.28; 95% CI, 0.27-0.70). We identified soluble brain-derived neurotrophic factors (BDNF), macrophage inflammatory proteins (MIP-1 α) and soluble vascular cell adhesion molecule 1 (sVCAM-1) predicted histological remission. Mucosal biopsy cultures also identified sVCAM-1 associated with healed mucosa. RNA-seq analysis identified gene expressions shared between ECSS, RHI, or NHI defined healing. A number of gene expressions and pathways were identified including inflammation and metabolic and tumor suppressors that discriminated healed from nonhealed mucosa., Conclusions: Endocytoscopy represents an interesting tool that may sit between endoscopy and histology-but closer to the latter-identifying gene expression markers and pathways that are also identified by histology., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Background: Mucosal healing (MH) is a key treatment target in the management of inflammatory bowel disease (IBD) and is defined in endoscopic terms by the newly published PICaSSO score. Raman Spectroscopy (RS) is based on the scattering of inelastic light giving spectra that are highly specific for individual molecules. We aimed to establish spectral changes before and after treatment and whether Raman Spectroscopy is able to accurately differentiate between inflammation and MH., Methods: Biopsies were taken for ex vivo RS analysis alongside biopsies for histological analysis from IBD patients undergoing optical diagnosis endoscopic assessment. We compared pre- vs. post-biological treatment in IBD patients and healthy controls and active vs. MH in UC and CD. For spectral analysis, we used supervised self-organising maps for separation and classification., Results: A total of 23 patients (14 IBD, 9 HC) were recruited for comparison of pre- vs. post-biologic treatment and 74 IBD patients were included for the assessment of MH in IBD, giving 9700 Raman Spectra. Spectral differences were seen between pre- and post-treatment which were observed comparing MH vs. active inflammation. Reductions in intensity at 1003cm-1 and 1252cm-1 when a reduction in inflammation was seen post-treatment and when MH was present. MH was associated with an increase in intensity at 1304cm-1. The trained neural network differentiated MH from active inflammation with a sensitivity, specificity, PPV, NPV and accuracy in UC of 96.29% (sd 0.94), 95.03% (sd 1.52), 94.89% (sd 1.59), 96.33 (sd 0.97) and 95.65 (sd 0.99) and 96.19% (sd 1.46), 88% (sd 4.20), 86.60% (sd 5.39), 96.55% (sd 1.32) and 91.6% (sd 2.75) in CD respectively., Conclusion: We demonstrated RS can demonstrate biochemical changes following treatment of IBD and accurately differentiates MH from active inflammation in IBD and might be a future tool to personalise therapeutic management in IBD., Competing Interests: The authors have declared that no competing interests exist.

Background and study aims  Correct optical diagnosis of colorectal polyps is crucial to implement a resect and discard strategy. Training methods have been proposed to reach recommended optical diagnosis thresholds. The aim of our study was to present a systematic review and meta-analysis on optical diagnosis training. Methods  PubMed/Medline and Cochrane databases were searched between 1980 and October 2019 for studies reporting outcomes on optical diagnosis training of colorectal polyps. The primary outcome was optical diagnosis accuracy compared to histological analysis pre-training and post-training intervention. Subgroup analyses of experienced/trainee endoscopists, training methods, and small/diminutive polyps were included. Results  Overall, 16 studies met inclusion criteria, analyzing the impact of training on 179 endoscopists. Pre-training accuracy was 70.3 % (6416/9131 correct diagnoses) whereas post-training accuracy was 81.6 % (7416/9213 correct diagnoses) (risk ratio [RR] 1.17; 95 % confidence interval [CI]: 1.09-1.24, P  < 0.001). In experienced endoscopists, accuracy improved from 69.8 % (3771/5403 correct diagnoses) to 82.4 % (4521/5485 correct diagnoses) (RR 1.20; 95 % CI: 1.11-1.29, P  < 0.001). Among trainees, accuracy improved from 69.6 % (2645/3803 correct diagnoses) to 78.8 % (2995/3803 correct diagnoses) (RR 1.14; 95 % CI 1.06-1.24, P  < 0.001). In the small/diminutive polyp subgroup, accuracy improved from 68.1 % (3549/5214 correct diagnoses) to 77.1 % (4022/5214 correct diagnoses) in (RR 1.16 95 % CI 1.08-1.24 P  < 0.001). On meta-regression analysis, the improvement in accuracy did not differ between computerized vs. didactic training approaches for experienced ( P  = 0.792) and trainee endoscopists ( P  = 0.312). Conclusions  Optical diagnosis training is effective in improving accuracy of histology prediction in colorectal polyps. Didactic and computer-based training show comparable effectiveness in improving diagnostic accuracy., Competing Interests: Competing interests The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background & Aims: Endoscopic and histologic remission are important goals in the treatment of ulcerative colitis (UC). We investigated the correlation of the recently developed Paddington International Virtual ChromoendoScopy ScOre (PICaSSO) and other established endoscopic scores against multiple histological indices and prospectively assessed outcomes., Methods: In this prospective multicenter international study, inflammatory activity was assessed with high-definition and virtual chromoendoscopy in the rectum and sigmoid using the Mayo Endoscopic Score (MES), UC Endoscopic Index of Severity (UCEIS), and PICaSSO. Targeted biopsies were taken for assessment using Robarts Histological Index (RHI), Nancy Histological index (NHI), ECAP (Extent, Chronicity, Activity, Plus score), Geboes, and Villanacci. Follow-up data were obtained at 6 and 12 months after colonoscopy., Results: A total of 307 patients were recruited. There was strong correlation between PICaSSO and histology scores, significantly superior to correlation coefficients of MES and UCEIS with histology scores. A PICaSSO score of ≤3 detected histologic remission by RHI (≤3 + absence of neutrophils) with area under the receiver operating characteristic curve (AUROC) 0.90 (95% confidence interval [CI] 0.86-0.94) and NHI (≤1) AUROC 0.82 (95% CI 0.77-0.87). The interobserver agreement for PICaSSO was 0.88 (95% CI 0.83-0.92). At 6- and 12-months follow-up, PICaSSO score ≤3 predicted better outcomes than PICaSSO >3 (hazard ratio [HR] 0.19 [0.11-0.33] and 0.22 [0.13-0.34], respectively),} as well as PICaSSO 4-8 (HR 0.25 [0.12-0.53] and 0.22 (0.12-0.39), respectively) and similar to histologic remission., Conclusion: In this first real-life multicenter study, the PICaSSO score correlated strongly with multiple histological indices. Furthermore, PICaSSO score predicted specified clinical outcomes at 6 and 12 months, similar to histology. Thus, PICaSSO can be a useful endoscopic tool in the therapeutic management of UC., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: In real-world clinical practice, biologics in inflammatory bowel diseases (IBD) may be discontinued for a variety of reasons, including discontinuation initiated by gastroenterologists. The aims of the study are to report outcomes after discontinuation and predictors of prognosis after a minimum follow-up of 24 months; outcomes of gastroenterologist-initiated discontinuation with resulting direct cost implications on the health system were also studied., Methods: IBD patients who discontinued their first-use biologics between January 2013 and December 2016 were identified at our tertiary centre. Reasons for discontinuation and pre-defined adverse outcomes (AO) were recorded. Data were analysed using univariable and multivariable logistic regressions within a machine learning technique to predict AO. Gastroenterologist-initiated discontinuations were analysed separately, and Kaplan-Meier survival analysis performed; direct costs of AO due to discontinuation were assessed., Results: A total of 147 patients discontinued biologics (M = 74; median age 39 years; Crohn's Disease = 110) with median follow-up of 40 months (range 24-60 months). In the total cohort, there were fewer AO among gastroenterologist-initiated discontinuations compared with patient-initiated; 54% (of the total group) had AO within 6 months. Among 59 gastroenterologist-initiated discontinuations, 23 (40%) had IBD-related AO within 6 months and 53 (90%) patients had AO by end of follow-up. Some 44 (75%) patients needed to restart biologics during follow-up, and direct costs due to AO and restart of biologics were high., Conclusions: The proportion of patients who have AO following discontinuation of biologics is high; clinicians need to carefully consider predictors of poor prognosis and high relapse rates when discussing discontinuation. The direct costs of managing AO probably offset theoretical economic gains, especially in the era where cost of biologics is reducing. Biologics should probably be continued without interruptions in most patients who have achieved remission for the duration these remain effective and safe., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)

Background: Strictures related to Crohn's disease due to fibrosis are a result of an exaggerated tissue remodelling response to inflammation, characterized by accumulation of collagen-rich extracellular matrix produced by mesenchymal cells., Objectives: The objective of this study was to characterize histological changes seen in resected 'fibrotic' strictures to better understand individual components of intestinal stenosis., Methods: We identified patients undergoing surgery for ileal Crohn's disease secondary to symptomatic stricturing disease (Montreal B2) using the histopathology database at Queen Elizabeth Hospital in Birmingham, UK, between 2012 and 2017. Phenotypic data were recorded and resection specimens reviewed. Two independent pathologists applied the semiquantitative scoring system previously developed by us to the microscopic images. Data were analyzed using the possible maximum total score (%PMTS)., Results: Forty-eight patients (M = 25) were included. with median disease duration of 7 years (range 0.25-39 years); nearly two-thirds had ileocolonic distribution (L3). In this cohort, despite presurgery diagnosis of noninflamed fibrosis, chronic inflammation was noted to be a prominent component of all strictures. The histological scoring showed presence of several other prominent findings such as muscular hyperplasia and volume expansion.There was statistically significant positive correlation between chronic inflammation and fibrosis and muscular hyperplasia., Conclusion: The histological features of Crohn's disease-related strictures show multiple changes in multiple layers and not simply fibrosis. In our cohort, despite the observation prior to surgery that strictures were clinically considered fibrotic, the finding of chronic inflammation as a dominant component at a histological level in the resection is important. The findings might suggest that one of the main drivers of progressive fibrosis is the inflammatory component, which probably is never fully resolved.

The incidence and prevalence of ulcerative colitis are increasing globally. Although the exact cause and pathogenesis of this disease is unclear, research has led to a better understanding of the condition and to identification of new targets for therapy, which in turn has encouraged the development of new therapies. As well as biologic therapies, which have changed the way inflammatory bowel disease is managed, small molecules have been developed for the treatment of ulcerative colitis. These small molecule treatments are orally administered and are likely to bring a substantial shift in the way this chronic disease is treated. Oral therapies offer many advantages over infusion therapies, such as ease of use, increased acceptability by patients, and reduction of cost. This Review focuses not only on oral therapies that have been approved for use in ulcerative colitis, but also on those that are in development, providing a comprehensive overview for clinicians of available oral therapies and drugs that are likely to become available. We have also reviewed drugs that have shown promise in preclinical studies and could be effective future therapies., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The traditional management of inflammatory bowel disease (IBD) based on symptom control is not considered valid anymore by most specialists in this field, and a new paradigm called "treat to target" has been introduced. This is based on the assessment of disease activity using objective measures. The identification of noninvasive biomarkers is crucial to diagnosis and monitor IBD because frequent endoscopic examinations are costly and uncomfortable for the patient. In this review, we focus on blood markers that may be able to assess mucosal healing (MH) in IBD and recent advances in this area. Introduction of commercial panel to predict MH opens the way for further developments so that colonoscopy or fecal markers may be avoided in some patients. This may also permit frequent monitoring for therapeutic response and achieve MH. It is a challenging area of research to identify a panel of biomarkers that may reflect inflammation and healing to serve as a surrogate of MH., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aim: Dye-based chromoendoscopy (DCE) with targeted biopsies is recommended for inflammatory bowel disease (IBD) surveillance. However, DCE has not yet been widely adopted into clinical practice. We evaluated quality indicators in IBD surveillance following introduction of structured changes in service delivery., Methods: In August 2016, we introduced a number of changes to IBD surveillance practice in our endoscopy unit. These included training using interactive videos/images in a structured module, DCE as standard by using a foot-pedal operated pump jet, allocation of 45-minute procedure timeslots, targeted biopsies (except in high-risk patients), scoring of endoscopic disease activity, and lesion detection/morphology characterization. All IBD surveillance colonoscopies were allocated to a small team of four DCE-trained endoscopists. We compared quality measures for surveillance procedures carried out pre- and post-August 2016. The two groups were compared using chi-squared statistics RESULTS: A total of 598 IBD surveillance procedures (277 pre-August 2016 and 321 post-August 2016) were done and included in the study. Use of DCE increased (54.2% vs 76.0% P < 0.0005) whereas random biopsy surveillance decreased (12.3% vs 3.1% P < 0.0005). Use of Paris classification (26.1% vs 57.0% P < 0.0005) and Kudo pit pattern increased (21.7% vs 59.0% P < 0.0005). There was also an increase in lesion detection rate (24.9% vs 33.1% P < 0.05)., Conclusions: Implementation of extensive changes in practice of surveillance colonoscopy resulted in significant improvement in quality indicators within a short period of time. Training, education and audit may continue to facilitate the adoption of DCE and further improve quality of performance in IBD surveillance., (© 2019 Japan Gastroenterological Endoscopy Society.)

Purpose: Lower gastrointestinal bleeding (LGIB) is common and risk stratification scores can guide clinical decision-making. There is no robust risk stratification tool specific for LGIB, with existing tools not routinely adopted. We aimed to develop and validate a risk stratification tool for LGIB., Methods: Retrospective review of LGIB admissions to three centres between 2010 and 2018 formed the derivation cohort. Using regressional analysis within a machine learning technique, risk factors for adverse outcomes were identified, forming a simple risk stratification score-The Birmingham Score. Retrospective review of an additional centre, not included in the derivation cohort, was performed to validate the score., Results: Data from 469 patients were included in the derivation cohort and 180 in the validation cohort. Admission haemoglobin OR 1.07(95% CI 1.06-1.08) and male gender OR 2.29(95% CI 1.40-3.77) predicted adverse outcomes in the derivation cohort AUC 0.86(95% CI 0.82-0.90) which outperformed the Blatchford 0.81(95% CI 0.77-0.85), Rockall 0.60(95% CI 0.55-0.65) and AIM65 0.55(0.50-0.60) scores and in the validation cohort AUC 0.80(95% CI 0.73-0.87) which outperformed the Blatchford 0.77(95% CI 0.70-0.85), Rockall 0.67(95% CI 0.59-0.75) and AIM 65 scores 0.61(95% CI 0.53-0.69). The Birmingham Score also performs well at predicting adverse outcomes from diverticular bleeding AUC 0.87 (95% CI 0.75-0.98). A score of 7 predicts a 94% probability of adverse outcome., Conclusion: The Birmingham Score represents a simple risk stratification score that can be used promptly on patients admitted with LGIB.

Background: Drug-induced colitis is a known complication of therapies that alter the immune balance, damage the intestinal barrier or disturb intestinal microbiota. Immune checkpoint inhibitors (ICI) directed against cancer cells may result in activated T lymphocyte-induced immune-related adverse events (AEs), including immune-related colitis and hepatitis. The aim of this review article is to summarize the incidence of gastrointestinal (GI) and hepatic AEs related to ICI therapy. We have also looked at the pathogenesis of immune-mediated AEs and propose management strategies based on current available evidence., Methods: A literature search using PubMed and Medline databases was undertaken using relevant search terms pertaining to names of individual drugs, mechanism of action, related AEs and their management., Results: ICI-related GI AEs are common, and colitis appears to be the most common side effect, with some studies reporting incidence as high as 30%. The incidence of both all-grade colitis and hepatitis were highest with combination therapy with anti-CTLA-4/PD-1; severity of colitis was dose-dependent (anti-CTLA-4). Early intervention is associated with better outcomes., Conclusion: ICI-related GI and hepatic AEs are common and clinicians need to be aware. Patients with GI AEs benefit from early diagnosis using endoscopy and computed tomography. Early intervention with oral steroids is effective in the majority of patients, and in steroid-refractory colitis infliximab and vedolizumab have been reported to be useful; mycophenolate has been used for steroid-refractory hepatitis., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2019.)

Background and Aim: The aim of this randomized trial was to evaluate the performance of self-training versus didactic training in order to increase the diagnostic accuracy of diminutive/small colonic polyp histological prediction by trainees., Methods: Sixteen trainees reviewed 78 videos (48 iSCAN-OE and 30 NBI) of diminutive/small polyps in a pretraining assessment. Trainees were randomized to receive computer-based self-learning (n = 8) or didactic training (n = 8) using identical teaching materials and videos. The same 78 videos, in a different randomized order, were assessed. The NICE (NBI International Colorectal Endoscopic) and SIMPLE (Simplified Identification Method for Polyp Labeling during Endoscopy) classification systems were used to classify diminutive/small polyps., Results: A higher proportion of high-confidence predictions of polyps was made by the self-training group versus the didactic group using both the SIMPLE classification (77.1% [95% CI 73.4-80.3] vs 69.9% [95% CI 66.1-73.5%] [P = 0.005]) and the NICE classification (77% [95% CI 73.2-80.4%] vs 69.8% [95% CI 66-73.4%] [P = 0.006]). When using NICE, sensitivity of the self-training group compared with the didactic group was 72% versus 83% (P = 0.0005), and the accuracy was 66.1% versus 69.1%. The training improved the confidence of participants and SIMPLE was preferred over NICE., Conclusion: Self-learning for the prediction of diminutive/small polyp histology is a method of training that can achieve results similar to didactic training. Availability of adequate self-learning teaching modules could enable widespread implementation of optical diagnosis in clinical practice., (© 2019 Japan Gastroenterological Endoscopy Society.)

Background: Biological therapy is currently widely used to treat IBD. Infliximab, adalimumab and golimumab are currently licensed anti-TNF therapies. Biosimilar anti-TNF monoclonal antibodies are increasingly used. Anti-TNF therapies are widely used and their adverse effects are well characterised, and may cause significant morbidity and mortality in a small proportion of exposed patients. Gastroenterologists need to understand the mechanisms for these effects, recognise these swiftly and manage such events appropriately., Aim: To cover the range of potential adverse reactions as a result of biologic therapy and specifically management of these events., Methods: A Medline and Pubmed search was undertaken. Search terms included were "anti-TNF," "infliximab" or "adalimumab" or "golimumab" combined with the keywords "ulcerative colitis" or "Crohn's disease" or "inflammatory bowel disease" and then narrowed to articles containing the keywords "complications," "side effects" or "adverse events" or "safety profile." International guidelines were also reviewed where relevant., Results: Adverse events discussed in this review include infusion reactions, blood disorders and infections (including bacterial, viral, fungal and opportunistic infections) as well as autoimmune, dermatological disorders, cardiac and neurological conditions. Malignancies including solid organ, haematological and those linked to viral disease are discussed., Conclusions: Anti-TNF therapy has wide-ranging effects on the immune system resulting in a spectrum of potential adverse events in a small proportion of patients. Research advances are improving the understanding, recognition and management of these adverse events., (© 2019 John Wiley & Sons Ltd.)

Background: Characterization of colonic lesions in inflammatory bowel disease (IBD) remains challenging. We developed an endoscopic classification of visual characteristics to identify colitis-associated neoplasia using multimodal advanced endoscopic imaging (Frankfurt Advanced Chromoendoscopic IBD LEsions [FACILE] classification)., Methods: The study was conducted in three phases: 1) development - an expert panel defined endoscopic signs and predictors of dysplasia in IBD and, using multivariable logistic regression created the FACILE classification; 2) validation - using 60 IBD lesions from an image library, two assessments of diagnostic accuracy for neoplasia were performed and interobserver agreement between experts using FACILE was determined; 3) reproducibility - the reproducibility of the FACILE classification was tested in gastroenterologists, trainees, and junior doctors after completion of a training module., Results: The experts initially selected criteria such as morphology, color, surface, vessel architecture, signs of inflammation, and lesion border. Multivariable logistic regression confirmed that nonpolypoid lesion, irregular vessel architecture, irregular surface pattern, and signs of inflammation within the lesion were predictors of dysplasia. Area under the curve of this logistic model using a bootstrapped estimate was 0.76 (0.73 - 0.78). The training module resulted in improved accuracy and kappa agreement in all nonexperts, though in trainees and junior doctors the kappa agreement was still moderate and poor, respectively., Conclusion: We developed, validated, and demonstrated reproducibility of a new endoscopic classification (FACILE) for the diagnosis of dysplasia in IBD using all imaging modalities. Flat shape, irregular surface and vascular patterns, and signs of inflammation predicted dysplasia. The diagnostic performance of all nonexpert participants improved after a training module., Competing Interests: Dr Iacucci has received an unrestricted research grant from Pentax USA. Dr. Sanduleanu has received an unrestricted research grant from Pentax Europe., (© Georg Thieme Verlag KG Stuttgart · New York.)

Aim: To examine beliefs about irritable bowel syndrome (IBS) management among primary care physicians., Background: There have been considerable advances in evidence synthesis concerning management of IBS in the last five years, with guidelines for its management in primary care published by the National Institute for Health and Care Excellence (NICE)., Methods: This was a cross-sectional web-based questionnaire survey of 275 primary care physicians. We emailed a link to a SurveyMonkey questionnaire, containing 18 items, to all eligible primary care physicians registered with three clinical commissioning groups in Leeds, UK. Participants were given one month to respond, with a reminder sent out after two weeks., Findings: One-hundred and two (37.1%) primary care physicians responded. Among responders, 70% believed IBS was a diagnosis of exclusion, and >80% checked coeliac serology often or always in suspected IBS. Between >50% and >70% believed soluble fibre, antispasmodics, peppermint oil, and psychological therapies were potentially efficacious therapies. The respondents were less convinced that antidepressants or probiotics were effective. Despite perceived efficacy of psychological therapies, 80% stated these were not easily available. Levels of use of soluble fibre, antispasmodics, and peppermint oil were in the range of 40% to >50%. Most primary care physicians obtained up-to-date evidence about IBS management from NICE guidelines. Most primary care physicians still believe IBS is a diagnosis of exclusion, and many are reluctant to use antidepressants or probiotics to treat IBS. More research studies addressing diagnosis and treatment of IBS based in primary are required.

Objective: Functional gastrointestinal disorders (FGIDs) are common in the community. Many patients will consult a physician in primary care, but the burden that these diseases represent to secondary care has not been studied for many years. We therefore examined this subject., Design: Unselected consecutive new adult patient referrals were recruited during a 3-year period from January 2010 until December 2012. Medical records were reviewed retrospectively and the following data were recorded: age and sex of the patient, symptoms reported or signs noted at the first consultation, all investigations requested and ultimate diagnosis after investigation to the level deemed appropriate by the consulting physician., Setting: A luminal gastroenterology clinic at a teaching hospital., Results: There were a total of 613 new patient referrals (mean age 54.2 years, 357 (58.2%) female). In total, 214 (34.9%) patients were diagnosed as having an FGID. Among the 214 patients diagnosed with an FGID, 65.9% were female, compared with 54.1% without an FGID (p=0.005). Mean age of those with an FGID was 47.9 years, compared with 57.5 years among those without (p<0.001). The total number of symptoms reported was significantly higher among patients with an FGID, but the total number of investigations did not differ., Conclusions: More than one-third of new patient referrals to a luminal gastroenterology clinic were diagnosed with an FGID. These conditions form a large part of the workload in secondary care gastroenterology, and primary care commissioning needs to reflect this.