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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: 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: 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: 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.)

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.