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Competing Interests: Mitsuru Esaki is a consultant for AI Medical Service Inc. Ogino Haruei is part of an endowed course supported by Miyarisan Pharmaceutical Co., Ltd.; Fujifilm Medical Co., Ltd.; Terumo Corporation; and Fancl Corporation. Ihara Eikichi received lecture fees from Takeda Pharmaceutical Co., Ltd. and EA Pharma Co., Ltd. The other authors declare no conflicts of interest.

Background and Aims: We aimed to identify serum metabolites associated with mucosal and transmural inflammation in paediatric Crohn disease [pCD]., Methods: In all, 56 pCD patients were included through a pre-planned sub-study of the multicentre, prospective, ImageKids cohort, designed to develop the Paediatric Inflammatory Crohn magnetic resonance enterography [MRE] Index [PICMI]. Children were included throughout their disease course when undergoing ileocolonoscopy and MRE and were followed for 18 months, when MRE was repeated. Serum metabolites were identified using liquid chromatography/mass spectroscopy. Outcomes included: PICMI, the simple endoscopic score [SES], faecal calprotectin [FCP], and C-reactive protein [CRP], to assess transmural, mucosal, and systemic inflammation, respectively. Random forest models were built by outcome. Maximum relevance minimum redundancy [mRMR] feature selection with a j-fold cross-validation scheme identified the best subset of features and hyperparameter settings., Results: Tryptophan and glutarylcarnitine were the top common mRMR metabolites linked to pCD inflammation. Random forest models established that amino acids and amines were among the most influential metabolites for predicting transmural and mucosal inflammation. Predictive models performed well, each with an area under the curve [AUC] > 70%. In addition, serum metabolites linked with pCD inflammation mainly related to perturbations in the citrate cycle [TCA cycle], aminoacyl-tRNA biosynthesis, tryptophan metabolism, butanoate metabolism, and tyrosine metabolism., Conclusions: We extend on recent studies, observing differences in serum metabolites between healthy controls and Crohn disease patients, and suggest various associations of serum metabolites with transmural and mucosal inflammation. These metabolites could improve the understanding of pCD pathogenesis and assessment of disease severity., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background: Colonic fibrosis has important clinical implications in ulcerative colitis [UC]. Ultrasound imaging has emerged as a convenient and reliable tool in diagnosis of inflammatory bowel disease. We aimed to explore the potential use of ultrasound to evaluate UC fibrosis., Methods: Consecutive UC patients who had proctocolectomy from July 2022 to September 2023 were enrolled in the study. Patients underwent bowel ultrasound examination and ultrasound elastography imaging prior to surgery. Milan ultrasound criteria [MUC] were calculated and bowel wall stiffness was determined using two mean strain ratios [MSRs]. Degree of colonic fibrosis and inflammation was measured upon histological analysis. Receiver operating characteristic [ROC] analysis was used to evaluate the performance of ultrasound-derived parameters to predict fibrosis., Results: In all, 56 patients were enrolled with 112 segments included in analysis. The median fibrosis score was 2 [0-4] and the median Geboes score was 5 [0-13] and these two scores were significantly correlated [p < 0.001]. The muscularis mucosa thickness was significantly higher in moderate-severe fibrosis than none-mild fibrosis [p = 0.003] but bowel wall thickness was not [p = 0.082]. The strain ratios [p < 0.001] and MUC [p = 0.010] were significantly higher in involved than non-involved segments. The strain ratios were correlated with fibrosis score [p < 0.001] but not MUC [p = 0.387]. At ROC analysis, mean strain ratio 1 [MSR1] had an area under the curve [AUC] of 0.828 [cutoff value 3.07, 95% CI 0.746-0.893, p < 0.001] to predict moderate-severe fibrosis., Conclusion: Ultrasound elastography imaging could predict the degree of colonic fibrosis in UC. Application of this technique could help disease monitoring and decision making in UC patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Mucosal healing (MH) is an established treatment goal in inflammatory bowel disease (IBD). However, various definitions of MH exist. We aimed to identify how MH is defined in randomized controlled trials (RCTs) in ulcerative colitis (UC) and Crohn's disease (CD)., Methods: We searched MEDLINE, EMBASE, and the Cochrane library from inception to December 2023 for phase 2 and 3 RCTs of advanced therapies in IBD., Results: One hundred forty-four studies were included, 72 in UC and 72 in CD, published between 1997 and 2023. In UC, 64% (46/72) RCTs reported MH as an endpoint. 12 definitions of MH were found, from endoscopic assessment alone (35/46; 76%) to the more recent combination of histology and endoscopy (10/46; 22%). 96% (44/46) of studies used the Mayo Endoscopic Subscore. In CD, reporting of MH lagged behind UC, with only 12% (9/72) of trials specifically defining MH as an endpoint, 7 as "absence of ulceration," 2 as Simplified Endoscopic Score for CD score ≤2 or 0. Histological assessment was performed in 3 RCTs of CD. Centralized reading of endoscopy was used in 48% (35/72) of RCTs of UC and 22% (16/72) of CD. Only 1 RCT included transmural healing as an endpoint., Conclusions: A standard definition of MH in IBD is lacking. Definitions have evolved particularly in UC, which now includes the addition of histological evaluation. Transmural healing holds promise as a future target in CD. We support a greater standardization of definitions as we expect endpoints to become increasingly stringent and multimodal with computers automating the assessment., (© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Pathological assessment of colorectal polyps is considered the current reference standard for histologic diagnosis. About 10% of polyps sent to the pathology lab are returned with the diagnosis of mucosal folds, mucosal prolapse, or normal mucosa. 1,2 Two recent publications have indicated that disagreements between endoscopic optical diagnosis and the subsequent pathological diagnoses might be due to misdiagnosis in pathology. 3,4 We were therefore interested in re-evaluating pathology-based diagnosis of "mucosal polyps" using expert endoscopists and computer-assisted diagnosis (CADx) evaluation., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Intestinal ultrasound (IUS) is becoming a standard assessment tool in Crohn's disease (CD), but limited data exist on its ability to predict long-term objective outcomes. Therefore, we aimed to investigate the predictive value of IUS findings for long-term transmural healing (TH) and mucosal healing (MH) in CD., Methods: We prospectively included consecutive CD patients with active endoscopic disease and bowel wall thickness (BWT) >3.0 mm, initiating infliximab. Intestinal ultrasound parameters (ie, BWT, inflammatory mesenteric fat [i-fat], bowel blood flow and stratification) and International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) were collected at baseline, after 14 to 26 weeks (visit 1, postinduction) and 44 to 56 weeks (visit 2). Transmural healing (normalization of all IUS parameters) and MH (SES-CD ≤2) were assessed at visit 2., Results: One hundred twenty-nine patients were evaluated. At visit 2, 38.0% and 48.1% of patients achieved TH and MH, respectively. All the IUS parameters and IBUS-SAS showed improvement at visit 1 and visit 2 compared with the baseline (all P < .001). Multivariable analysis found that presence of i-fat at baseline (odds ratio [OR], 0.57; P = .008) and greater postinduction BWT (OR, 0.24; P < .001) were negative predictors for TH, while higher baseline (OR, 0.98; P = .013) and postinduction (OR, 0.94; P < .001) IBUS-SAS predicted negatively for MH. Postinduction BWT <4.5mm best predicted TH (AUC 0.85; P < .001), while postinduction IBUS-SAS <25.0 best predicted MH (AUC 0.82; P < .001). Moreover, colonic disease was associated with higher risk of TH (OR, 2.55; P = .027), and disease duration >24 months with lower risk of MH (OR, 0.27; P = .006)., Conclusions: Baseline and postinduction IUS findings reliably predict long-term TH and MH in patients with CD receiving infliximab., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Paneth cells play multiple roles in maintaining intestinal homeostasis. However, the clinical role of Paneth cell metaplasia (PCM) in ulcerative colitis (UC) remains unclear. We aimed to investigate the relationship between PCM and relapse in patients with UC and compare the usefulness of PCM with other histological indexes, including mucin depletion (MD) and basal plasmacytosis (BP)., Methods: Patients with UC in clinical remission (CR) who underwent colonoscopy to confirm a Mayo endoscopic subscore (MES) ≦1 with biopsies from the distal colon were enrolled into this retrospective cohort study. Biopsy samples were evaluated for histological findings of PCM, MD, and BP. Clinical relapse was defined as partial Mayo score ≧3 or medication escalation. Multivariate analysis was performed to determine independent predictors of relapse among the three histological findings, MES, and patient background, and relapse prediction models were generated., Results: Eighty-three patients were enrolled in this study (MES 0, n = 47; MES 1, n = 36). The number of PCM cases was significantly higher in patients with prolonged CR than that in those with relapse (p = 0.01). Multivariate analysis showed that the absence of PCM and MD were related to relapse in all the patients. In patients with MES 1, the absence of PCM was the only risk factor significantly and independently associated with relapse (hazard ratio, 4.51 [1.15-17.7]; p = 0.03)., Conclusion: The absence of PCM was a histological risk factor for relapse in patients with MES 1, implying a protective role for PCM in remission and a new index for mucosal healing., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background:  Recognition of submucosal invasive colorectal cancer (T1 CRC) is difficult, with sensitivities of 35 %-60 % in Western countries. We evaluated the real-life effects of training in the OPTICAL model, a recently developed structured and validated prediction model, in Dutch community hospitals., Methods:  In this prospective multicenter study (OPTICAL II), 383 endoscopists from 40 hospitals were invited to follow an e-learning program on the OPTICAL model, to increase sensitivity in detecting T1 CRC in nonpedunculated polyps. Real-life recognition of T1 CRC was then evaluated in 25 hospitals. Endoscopic and pathologic reports of T1 CRCs detected during the next year were collected retrospectively, with endoscopists unaware of this evaluation. Sensitivity for T1 CRC recognition, R0 resection rate, and treatment modality were compared for trained vs. untrained endoscopists., Results:  1 year after e-learning, 528 nonpedunculated T1 CRCs were recorded for endoscopies performed by 251 endoscopists (118 [47 %] trained). Median T1 CRC size was 20 mm. Lesions were mainly located in the distal colorectum (66 %). Trained endoscopists recognized T1 CRCs more frequently than untrained endoscopists (sensitivity 74 % vs. 62 %; mixed model analysis odds ratio [OR] 2.90, 95 %CI 1.54-5.45). R0 resection rate was higher for T1 CRCs detected by trained endoscopists (69 % vs. 56 %; OR 1.73, 95 %CI 1.03-2.91)., Conclusion:  Training in optical recognition of T1 CRCs in community hospitals was associated with increased recognition of T1 CRCs, leading to higher en bloc and R0 resection rates. This may be an important step toward more organ-preserving strategies., Competing Interests: The authors declare that P. Siersema received grants or speaker's fees from Pentax Japan, The E-Nose Company The Netherlands, Microtech China, Lucid Diagnostics USA, Magentiq Eye Israel, Norgine UK/The Netherlands, and Motus GI USA; A. Masclee received research grants from the Dutch Cancer Society (KWF) and the Dutch Organization for Health Research and Innovation (ZonMW); L. Moons acts as a consultant for Boston Scientific. The other authors declare that no conflicts of interest exist., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Molecular endoscopy in inflammatory bowel disease (IBD) has made the translation from preclinical studies to clinical trials. The so far performed in vivo studies, using fluorescent antibodies, have addressed areas of heightened clinical interest with unmet needs. These include the distribution of targeted therapies within the mucosa, which could elucidate the most fitting dosing for the individual patient, the mode of action of currently used treatments, and subsequently also the prediction of therapeutic response. Altogether, molecular endoscopy might enable us to base individualized therapeutic decisions on preceded in vivo molecular analysis to optimize treatment in IBD., Competing Interests: Disclosure R. Atreya has served as a speaker, or consultant, or received research grants from AbbVie, Abivax, AstraZeneca, Bristol-Myers Squibb, Celltrion Healthcare, Galapagos, Johnson&Johnson, Lilly, MSD, Pfizer, and Takeda Pharma. DFG-SFB/TRR241 Project No. C02 and IBDome, CRU5024 B04 are funded by the German Research Council (DFG). Further supported by the FIBROTARGET project. The FIBROTARGET project has received funding from the European Union’s Horizon Europe Research & Innovation program under grant agreement no. 101080523. Funded by the European Union. Views and opinions expressed are those of the author(s) only and do not necessarily reflect those of the European Union or European Health and Digital Executive Agency (HADEA). Neither the European Union nor the granting authority can be held responsible for them. T. Rath has received speaker fees from Olympus Medical, PENTAX Medical, Mauna Kea Technologies, Medtronic, Takeda, Galapagos, Falk, Janssen, AbbVie, Repha, Medical Tribune, and Lilly. M F. Neurath has served as advisor or speaker for Pentax, Roche Pharma, Takeda Pharma, Pfizer, MSD, PPM, Janssen, Gilead, Dr Falk Pharma, Boehringer Ingelheim, Amgen, and AbbVie., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Capsule endoscopy has been proven as an efficient and accurate tool in the diagnosing and monitoring patients with inflammatory bowel disease, especially Crohn's disease (CD). The current European Crohn's and Colitis Organization guidelines recommend small bowel disease assessment in newly diagnosed CD, wherein small bowel capsule endoscopy (SBCE) is of prime importance. SBCE plays an essential role in assessing mucosal healing in patients with CD, serving as a monitoring tool in a treat to target strategy, and is capable of identifying high-risk patients for future flares., Competing Interests: Disclosures U. Kopylov received speaker and consultancy fees from Abbvie, BMS, Elly Lilly, Celtrion, Medtronic, Janssen, Pfizer, Roche, and Takeda, and research support from Abbvie, Elli Lilly, Medtronic Takeda, and Janssen. The remaining authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Inflammatory bowel disease (IBD) patients are at an increased risk of developing colorectal cancer. Dysplasia is often found in flat, subtle mucosal abnormalities; therefore, early detection is essential. Innovative enhanced endoscopy imaging techniques are increasingly available for endoscopists managing IBD, allowing an in-depth, close to histology evaluation of mucosal pattern and vascular architecture. These new tools enable an earlier and more accurate detection and assessment of dysplasia, leading to improved patientoutcomes. This review provides an exhaustive overview of these techniques and their applicability in the clinical practice., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Recent advances in the field of endoscopy have found fertile ground for application in inflammatory bowel diseases (IBD). Mucosal healing is a primary goal of IBD therapy, and current evidence shows that histologic remission (HR) is an additional desirable outcome. However, with the use of standard endoscopy, a considerable number of patients with histologically active disease go unrecognized. This narrative article examines the role, current or potential, of each endoscopic technique, from standard white-light endoscopy to molecular imaging, in the assessment of mucosal healing and HR in IBD., Competing Interests: Disclosure None to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Three-dimensional (3D) imaging of vascular networks is essential for the investigation of vascular patterning and organization. Here, we present a step-by-step protocol for the 3D visualization of the vasculature within whole-mount preparations of the mouse intestinal muscularis propria layer. We then detail the quantitative analysis of the resulting images for parameters such as vessel density, vessel diameter, the number of endothelial cells, and proliferation. The protocol can be easily extended to study cell-cell interactions such as neuro-vascular or immune-vascular interactions. For complete details on the use and execution of this protocol, please refer to Schrenk et al. 1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: The clinical effects of risankizumab (a monoclonal antibody that selectively targets the p19 subunit of IL-23) for the treatment of ulcerative colitis are unknown., Objective: To evaluate the efficacy and safety of risankizumab when administered as an induction and a maintenance therapy for patients with ulcerative colitis., Design, Setting, and Participants: Two phase 3 randomized clinical trials were conducted. The induction trial was conducted at 261 clinical centers (in 41 countries) and enrolled 977 patients from November 5, 2020, to August 4, 2022 (final follow-up on May 16, 2023). The maintenance trial was conducted at 238 clinical centers (in 37 countries) and enrolled 754 patients from August 28, 2018, to March 30, 2022 (final follow-up on April 11, 2023). Eligible patients had moderately to severely active ulcerative colitis; a history of intolerance or inadequate response to 1 or more conventional therapies, advanced therapies, or both types of therapies; and no prior exposure to risankizumab., Interventions: For the induction trial, patients were randomized 2:1 to receive 1200 mg of risankizumab or placebo administered intravenously at weeks 0, 4, and 8. For the maintenance trial, patients with a clinical response (determined using the adapted Mayo score) after intravenous treatment with risankizumab were randomized 1:1:1 to receive subcutaneous treatment with 180 mg or 360 mg of risankizumab or placebo (no longer receiving risankizumab) every 8 weeks for 52 weeks., Main Outcomes and Measures: The primary outcome was clinical remission (stool frequency score ≤1 and not greater than baseline, rectal bleeding score of 0, and endoscopic subscore ≤1 without friability) at week 12 for the induction trial and at week 52 for the maintenance trial., Results: Among the 975 patients analyzed in the induction trial (aged 42.1 [SD, 13.8] years; 586/973 [60.1%] were male; and 677 [69.6%] were White), the clinical remission rates at week 12 were 132/650 (20.3%) for 1200 mg of risankizumab and 20/325 (6.2%) for placebo (adjusted between-group difference, 14.0% [95% CI, 10.0%-18.0%], P < .001). Among the 548 patients analyzed in the maintenance trial (aged 40.9 [SD, 14.0] years; 313 [57.1%] were male; and 407 [74.3%] were White), the clinical remission rates at week 52 were 72/179 (40.2%) for 180 mg of risankizumab, 70/186 (37.6%) for 360 mg of risankizumab, and 46/183 (25.1%) for placebo (adjusted between-group difference for 180 mg of risankizumab vs placebo, 16.3% [97.5% CI, 6.1%-26.6%], P < .001; adjusted between-group difference for 360 mg of risankizumab vs placebo, 14.2% [97.5% CI, 4.0%-24.5%], P = .002). No new safety risks were detected in the treatment groups., Conclusion and Relevance: Compared with placebo, risankizumab improved clinical remission rates in an induction trial and in a maintenance trial for patients with moderately to severely active ulcerative colitis. Further study is needed to identify benefits beyond the 52-week follow-up., Trial Registration: ClinicalTrials.gov Identifiers: NCT03398148 and NCT03398135.

Competing Interests: Competing interests: None declared.

Percutaneous transhepatic lymphatic embolization (PTLE) and peroral esophagogastroduodenoscopy (EGD) duodenal mucosal radiofrequency (RF) ablation were performed to manage protein-losing enteropathy (PLE) in patients with congenital heart disease. Five procedures were performed in 4 patients (3 men and 1 woman; median age, 49 years; range, 31-71 years). Transhepatic lymphangiography demonstrated abnormal periduodenal lymphatic channels. After methylene blue injection through transhepatic access, subsequent EGD evaluation showed methylene blue extravasation at various sites in the duodenal mucosa. Endoscopic RF ablation of the leakage sites followed by PTLE using 3:1 ethiodized oil-to-n-butyl cyanoacrylate glue ratio resulted in improved symptoms and serum albumin levels (before procedure, 2.6 g/dL [SD ± 0.2]; after procedure, 3.5 g/dL [SD ± 0.4]; P = .004) over a median follow-up of 16 months (range, 5-20 months). Transhepatic lymphangiography and methylene blue injection with EGD evaluation of the duodenal mucosa can help diagnose PLE. Combined PTLE and EGD-RF ablation is an option to treat patients with PLE., (Copyright © 2024 SIR. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: RA has served as a speaker, or consultant, or received research grants from AbbVie, Abivax, AstraZeneca, Bristol-Myers Squibb, Celltrion Healthcare, Galapagos, Janssen-Cilag, Lilly, MSD, Pfizer, Takeda Pharma.

Pseudomelanosis duodeni is characterized by endoscopic findings of black or black-brown speckled pigmentation in the duodenal mucosa, usually diagnosed via biopsy. This report presents a case of a 75-year-old male presented with left lower abdominal pain, change in bowel habits, and decreased appetite. Gastroduodenoscopy and biopsies of the duodenum and antrum lead to the diagnosis of pseudomelanosis duodeni., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.)

Objectives: Distinguishing between intramucosal cancer and submucosal invasive cancer is vital for optimal treatment selection for patients with superficial nonampullary duodenal adenocarcinoma (SNADAC); however, standard diagnostic systems for diagnosing invasion depth are as yet undetermined., Methods: Of 205 patients with SNADAC who underwent treatment at our institution between 2006 and 2022, 188 had intramucosal cancer and 17 had submucosal invasive cancer. The clinical, endoscopic, and pathological features used in the preoperative diagnosis of invasion depth and the diagnostic performance of endoscopic ultrasonography (EUS) were retrospectively analyzed in 85 patients., Results: The oral side of the papilla tumor location, protruded or mixed macroscopic type, and moderately-to-poorly differentiated adenocarcinoma based on biopsy specimens were significantly more frequent in submucosal invasive cancer than in intramucosal cancer (88% vs. 48%; 94% vs. 42%; 47% vs. 0%, respectively). From the relationship between the endoscopic features and the submucosal invasive cancer incidence, submucosal invasion risk was stratified as: (i) low-risk (risk, 2%), all lesions located on the anal side of the papilla and superficial macroscopic type on the oral side of the papilla; and (ii) high-risk (risk, 23%), protruded or mixed macroscopic type on the oral side of the papilla. Based on the biopsy specimens, all eight patients with moderately-to-poorly differentiated adenocarcinoma had submucosal invasive cancer. Furthermore, EUS was not associated with invasion depth's diagnostic accuracy improvements., Conclusion: Optimal treatment indications for SNADAC can be selected based on the risk factors of submucosal invasion by tumor location, macroscopic type, and biopsy diagnosis., (© 2023 Japan Gastroenterological Endoscopy Society.)

Background: The Endoscopic Healing Index (EHI) analyzes biomarkers in a patient's peripheral blood to assess mucosal healing. We aimed to characterize the effectiveness of the EHI as a predictor of disease activity in a real world clinical setting., Methods: This retrospective study looked at patients treated and followed up at the University of Chicago Medicine IBD center who had EHI tests done as part of routine clinical care. The results of the EHI were compared with radiological imaging or endoscopy performed within 3 months of the EHI in order to determine accuracy at diagnosing active inflammation., Results: Fifty-five patients with CD and with an available EHI were included in this study. Four (50%) patients with an EHI of < 20 (n = 8) had evidence of objective inflammation. A cutoff of ≤ 20 had a sensitivity of 89% and specificity of 23.5% for predicting no evidence of any objective inflammation with an AUROC of 0.69. This score had a negative predictive value (NPV) of 50% and positive predictive value (PPV) of 72.3%. A cutoff EHI of 30 tended to classify patients as either having objective evidence of inflammation or not more often than FCAL (Correctly classifying inflammation: 89% vs 64%, respectively; p = 0.32)., Conclusion: In this real world analysis, the EHI showed poor predictive value for the absence of active inflammation as assessed by imaging or endoscopy, has limited utility in confirming deep remission and should be used with another objective modality., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Stricture is a common complication in Crohn's disease (CD). Accurate identification of strictures that poorly respond to biologic therapy is essential for making optimal therapeutic decisions. The aim of this study was to determine the association between ultrasound characteristics of strictures and their therapeutic outcomes., Methods: Consecutive CD patients with symptomatic strictures scheduled for biologic therapy were retrospectively recruited at a tertiary hospital. Baseline intestinal ultrasound was conducted to assess stricture characteristics, including bowel wall thickness, length, stratification, vascularity, and creeping fat wrapping angle. Patients were followed up for a minimum of 1 year, during which long-term outcomes including surgery, steroid-free clinical remission, and mucosal healing were recorded. Statistical analyses were performed., Results: A total of 43 patients were enrolled. Strictures were located in the ileocecal region (39.5%), colon (37.2%), anastomosis (20.9%), and small intestine (2.3%). The median follow-up time was 17 months (interquartile range 7-25), with 27 patients (62.8%) undergoing surgery. On multivariant analysis, creeping fat wrapping angle > 180° (odds ratio: 6.2, 95% confidence interval [CI]: 1.1-41.1) and a high Limberg score (odds ratio: 2.3, 95% CI: 1.4-6.0) were independent predictors of surgery, with an area under the curve of 0.771 (95% CI: 0.602-0.940), accuracy of 83.7%, sensitivity of 96.3%, and specificity of 62.5%. On Cox survival analysis, creeping fat >180° was significantly associated with surgery (hazard ratio, 5.2; 95% CI: 1.2-21.8; P = 0.03). In addition, creeping fat was significantly associated with steroid-free clinical remission ( P = 0.015) and mucosal healing ( P = 0.06)., Discussion: Intestinal ultrasound characteristics can predict outcomes in patients with stricturing CD who undertook biologic therapy., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background A watch-and-wait regimen for locally advanced rectal cancer after neoadjuvant chemotherapy and radiation therapy (NCRT) relies on identifying complete tumor response. However, the concordance between a complete response at combined T2-weighted and diffusion-weighted MRI (T2DWI) and pathologic complete response (pCR; ie, ypT0N0) in the tumor is unsatisfactory. Purpose To assess whether identification of mucosal linear enhancement (MLE) at arterial-phase contrast-enhanced (CE) T1-weighted MRI is associated with ypT0 status in patients with locally advanced rectal cancer after NCRT and to evaluate whether combining MLE at CE T1-weighted MRI and negative lymph node metastasis (LNM) at T2DWI can improve identification of pCR. Materials and Methods This retrospective study included patients with locally advanced rectal cancer who underwent total mesorectal excision after NCRT between July 2020 and July 2023 at a tertiary referral academic center. Restaging MRI included T2DWI and arterial-phase CE T1-weighted MRI for primary tumor assessment and T2DWI for evaluation of LNM status. Imaging features associated with ypT0 status were identified at multivariable regression analysis. Results In total, 239 patients (mean age, 58 years ± 12 [SD]; 180 male patients) were assessed. MLE was more common in the ypT0 group than in the ypT1-4 group after NCRT (73% vs 4%, respectively; P < .001). MLE was associated with higher odds of ypT0 status in an adjusted analysis (odds ratio, 137; 95% CI: 25, 767; P < .001). The combination of MLE and negative LNM status achieved an area under the receiver operating characteristic curve of 0.84 (95% CI: 0.79, 0.88) for pCR. Conclusion MLE at CE MRI was associated with higher odds of complete tumor response. Combining MLE and negative LNM status showed good performance for identifying complete tumor response and may exclude residual tumors after NCRT in patients with locally advanced rectal cancer. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Schoellnast in this issue.

Background and Aim: Image enhancement endoscopy techniques, such as linked color imaging (LCI) and autofluorescence imaging (AFI), have shown promise in diagnosing mucosal inflammation in ulcerative colitis (UC). However, no studies have directly compared the diagnostic efficacy of LCI and AFI. This prospective observational study aimed to compare their diagnostic accuracy for histological healing in UC., Methods: This study included 81 UC patients, resulting in a total of 204 endoscopic images captured using LCI and AFI, respectively. Spearman's rank correlation coefficients assessed the correlation between LCI and AFI coloration and Geboes histopathology score (GHS). Six endoscopists, who were blinded to clinicopathological features, evaluated these images, and subsequently, the diagnostic accuracy was evaluated., Results: Spearman's rank correlation coefficients between LCI index, AFI index (reverse gamma value), and GHS were 0.324 and -0.428, respectively (P < 0.001), indicating a significant correlation between LCI and AFI coloration and histological healing. In LCI and AFI classifications, mean values for diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 76.3 ± 2.2 versus 77.8 ± 2.7, 91.8 ± 4.0 versus 83.2 ± 7.6, 53.4 ± 10.0 versus 70.0 ± 5.3, 74.0 ± 3.5 versus 80.0 ± 1.6, and 82.9 ± 5.2 versus 75.5 ± 7.5, respectively. No significant difference in diagnostic accuracy existed between LCI and AFI classifications. However, LCI displayed higher sensitivity than AFI while AFI showed higher specificity compared with LCI (P < 0.05)., Conclusions: LCI and AFI offer comparable diagnostic accuracy for histological healing. Clinically, it is necessary to recognize diagnostic features characterized by higher sensitivity in LCI and greater specificity in AFI., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Introduction: Endoscopy is still the gold, standard for assessing disease activity in Crohn's disease (CD). Its invasiveness, poor acceptability, and cost limit its use in the era of tight control and treat-to-target management. Fecal calprotectin (FC) and intestinal ultrasound (IUS) are non-invasive alternatives to colonoscopy to assess disease activity. We aimed to evaluate the performance of IUS and FC to assess mucosal healing in CD., Methods: All consecutive CD patients who underwent colonoscopy for mucosal healing assessment and IUS and/or FC within four weeks between September 2019 and April 2022 were included in a prospective cohort. The bowel-wall thickness (BWT) and color Doppler signal (CDS) were assessed for each segment. Endoscopic remission was defined by a CDEIS score < 3., Results: In total, 153 patients were included, of whom 122 showed endoscopic mucosal healing. Eighty-two (53.6 %) were female, the median was age 36 years (IQR, 28-46), and the median disease duration was 10 years (IQR, 4-19). The sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) of a BWT < 3 mm to predict endoscopic mucosal healing were 56 %, 88 %, 95 %, and 36 %, respectively (patients misclassified as mucosal healing, 2.5 %). The best FC threshold (< 92.9 µg/g) provided similar results: 77 %, 89 %, 96 %, and 67 %, respectively (patients misclassified, 2.2 %). The association of an FC < 250 µg/g with a BWT < 3 mm and the absence of CDS increased the Sp and PPV: Se 58 %, Sp 95 %, PPV 97 %, VPN 43 %; patients misclassified, 1.3 %., Conclusion: Noninvasive evaluation of mucosal healing by IUS or calprotectin efficiently identifies patients with CD who have achieved endoscopic mucosal healing., Competing Interests: Declaration of competing interest CY: consultant and lecture fees from Abbvie, Takeda, Janssen, Amgen, and Galapagos MF: consultant and lecture fees from Abbvie, Takeda, Janssen, Amgen, Galapagos, Gilead, Biogen, Fresenius, Pfizer, Lilly, Celltrion, Ferring, Tillots, and Nordic Pharma VH: AAA, Merck KGaA, Amgen, Servier, Deciphera, Ipsen, and Pierre Fabre The other authors have nothing to declare., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

A 62-year-old woman undergoing screening colonoscopy was found to have a submucosal protrusion in the mid-rectum. Evaluation with a curvilinear echoendoscope revealed it to be a 1.8×1.1cm, hypoechoic mass originating from muscularis propria (MP) . Endoscopic submucosal excavation (ESE) was attempted, but despite adequate dissection of the submucosa, the mass remained poorly defined appearing as a slight elevation in the background of flat muscle. Repeat visualization of the lesion status post submucosal dissection was performed with the curvilinear echoendoscope. A biopsy forceps was introduced as a movable landmark which could be visualized on both synchronized endosonographic and optical views, so as to clearly identify the margin of the lesion . Incision of the MP overlying the identified margin allowed for precise exposure of the mass, which was further excavated and finally resected.

Background and Aims: Image-enhanced endoscopy has attracted attention as a method for detecting inflammation and predicting outcomes in patients with ulcerative colitis (UC); however, the procedure requires specialist endoscopists. Artificial intelligence (AI)-assisted image-enhanced endoscopy may help nonexperts provide objective accurate predictions with the use of optical imaging. We aimed to develop a novel AI-based system using 8853 images from 167 patients with UC to diagnose "vascular-healing" and establish the role of AI-based vascular-healing for predicting the outcomes of patients with UC., Methods: This open-label prospective cohort study analyzed data for 104 patients with UC in clinical remission. Endoscopists performed colonoscopy using the AI system, which identified the target mucosa as AI-based vascular-active or vascular-healing. Mayo endoscopic subscore (MES), AI outputs, and histologic assessment were recorded for 6 colorectal segments from each patient. Patients were followed up for 12 months. Clinical relapse was defined as a partial Mayo score >2 RESULTS: The clinical relapse rate was significantly higher in the AI-based vascular-active group (23.9% [16/67]) compared with the AI-based vascular-healing group (3.0% [1/33)]; P = .01). In a subanalysis predicting clinical relapse in patients with MES ≤1, the area under the receiver operating characteristic curve for the combination of complete endoscopic remission and vascular healing (0.70) was increased compared with that for complete endoscopic remission alone (0.65)., Conclusions: AI-based vascular-healing diagnosis system may potentially be used to provide more confidence to physicians to accurately identify patients in remission of UC who would likely relapse rather than remain stable., Competing Interests: Disclosure The following authors disclosed financial relationships: Y. Maeda: grants from the Japan Society for the Promotion of Science during the conduct of the study. S. Kudo and M. Misawa: consultant and speaker fees from Olympus Corp. All of the other authors disclosed no financial relationships., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Introduction: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system. Recent evidence suggests that lymphocyte trafficking in the intestines could play a key role in its etiology. Nevertheless, it is not clear how intestinal tissue is involved in the disease onset nor its evolution. In the present study, we aimed to evaluate intestinal inflammation dynamic throughout the disease course and its potential impact on disease progression., Methods: We used tissue immunophenotyping (immunohistofluorescence and flow cytometry) and a recently described molecular magnetic resonance imaging (MRI) method targeting mucosal addressin cell adhesion molecule-1 (MAdCAM-1) to assess intestinal inflammation in vivo in two distinct animal models of MS (Experimental Autoimmune Encephalomyelitis - EAE) at several time points of disease progression., Results: We report a positive correlation between disease severity and MAdCAM-1 MRI signal in two EAE models. Moreover, high MAdCAM-1 MRI signal during the asymptomatic phase is associated with a delayed disease onset in progressive EAE and to a lower risk of conversion to a secondary-progressive form in relapsing-remitting EAE. During disease evolution, in line with a bi-directional immune communication between the gut and the central nervous system, we observed a decrease in T-CD4 + and B lymphocytes in the ileum concomitantly with their increase in the spinal cord., Conclusion: Altogether, these data unveil a crosstalk between intestinal and central inflammation in EAE and support the use of molecular MRI of intestinal MAdCAM-1 as a new biomarker for prognostic in MS patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm most often arising from the pleura and rarely in extra-pleural locations, including the gastrointestinal tract. We describe two cases of a SFT presenting as submucosal colonic lesion and review the literature on this lesion. One submucosal lesion was localized in the cecum and was 10 mm in size. The second lesion presented as a 17 mm submucosal rectal lesion. Both lesions presented as well-circumscribed submucosal lesions arranged in short fascicles, blending with abundant collagenous stroma. In both cases, the spindle cells were positive for CD34, STAT6 and CD99, and molecular studies showed NAB2:STAT6 fusion supporting the diagnosis of SFT. Both patients are alive and well 10 and 5 years post-excision, respectively. In conclusion, SFT can occur in the colon as a submucosal lesion and should be included in the differential diagnosis of colonic mesenchymal lesions., (© 2024. Japanese Society of Gastroenterology.)

Background: Narrow-band imaging (NBI) is a readily accessible imaging technique that enhances mucosal visualisation, allowing for a more accurate assessment of duodenal villi. However, its role in the diagnosis of coeliac disease (CD) in clinical practice remains limited., Methods: We systematically searched several databases in June 2023 for studies evaluating the diagnostic accuracy of NBI for detecting duodenal villous atrophy (VA) in patients with suspected CD. We calculated the summary sensitivity, specificity, and likelihood ratios using a bivariate random-effects model. The study followed PRISMA guidelines and was registered at PROSPERO (CRD42023428266)., Results: A total of 6 studies with 540 participants were included in the meta-analysis. The summary sensitivity of NBI to detect VA was 93% (95% CI, 81% - 98%), and the summary specificity was 95% (95% CI, 92% - 98%). The area under the summary receiver operating characteristic curve was 0.98 (95% CI, 96 - 99). The positive and negative predictive values of NBI were 94% (95% CI, 92% - 97%) and 92% (95% CI, 90% - 94%), respectively., Conclusion: NBI is an accurate non-invasive tool for identifying and excluding duodenal VA in patients with suspected CD. Further studies using a validated classification are needed to determine the optimal role of NBI in the diagnostic algorithm for CD., Competing Interests: Conflict of interest None declared., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: Colonic mucosal hypoxia is associated with mucosal inflammation in ulcerative colitis (UC). We aimed to assess the clinical usefulness of hypoxia imaging colonoscopy for the evaluation of clinical, endoscopic, and histologic disease activities of UC., Methods: This retrospective cohort study comprised 100 consecutive patients with UC who underwent hypoxia imaging colonoscopy between September 2022 and September 2023 at the University of Tsukuba Hospital. Colonic tissue oxygen saturation (StO 2 ) was measured at the biopsy sites, and StO 2 values between different disease activities were compared. Receiver-operating characteristic (ROC) analysis was used to calculate the area under the ROC curve (AUROC)., Results: A significant correlation was identified between rectal StO 2 and the Simple Clinical Colitis Activity Index, with moderate accuracy to predict bowel urgency at a 40.5% cutoff (AUROC, .74; 95% confidence interval [CI], .62-.87). Our analysis of 490 images showed median StO 2 values for Mayo endoscopic subscores 0, 1, 2, and 3 as 52% (interquartile range [IQR], 48%-56%), 47% (IQR, 43%-52%), 42% (IQR, 38.8%-47%), and 39.5% (IQR, 37.3%-41.8%), respectively. Differences for all pairs were significant. Median StO 2 was 49% (IQR, 44%-54%) for Geboes scores 0 to 2, significantly higher than histologically active disease (Geboes score ≥3). At a colonic StO 2 cutoff of 45.5%, AUROCs for endoscopically and histologically active diseases were .79 (95% CI, .74-.84) and .72 (95% CI, .66-.77)., Conclusions: StO 2 obtained by hypoxia imaging colonoscopy is useful for assessing clinical, endoscopic, and histologic activities of UC, suggesting that StO 2 may be a novel and objective endoscopic measurement., Competing Interests: Disclosure The following authors disclosed financial relationships: S. Akiyama: received honoraria (lecture fees) from AbbVie. K. Tsuchiya: received honoraria (lecture fees) from Takeda Pharmaceutical Co, Ltd. All other authors disclosed no financial relationships., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Data on the correlation between inflammatory mesenteric fat (i-fat), detected by intestinal ultrasound (IUS), and the prognosis of Crohn's disease (CD) remains limited., Aims: To investigate the impact of IUS-detected i-fat on long-term clinical outcomes., Methods: We retrospectively enrolled 171 active CD patients who initiated infliximab. Clinical remission (CR), mucosal healing (MH) and transmural healing (TH) were assessed at week-14 and 1 year., Results: Baseline i-fat was detected in 107 patients, while 64 without i-fat. At week-14 and 1 year, patients with i-fat showed lower rates of CR (61.7% vs. 87.5%; 62.3% vs. 86.7%), MH (20.6% vs. 46.9%; 38.6% vs. 65.0%) and TH (10.3% vs. 31.3%; 21.6% vs. 51.7%), compared to those without (all p<0.01). Multivariable analysis revealed that baseline i-fat was a negative predictor for CR (OR=0.212) and MH (OR=0.425) at week-14, and CR (OR=0.340) and TH (OR=0.364) at 1 year (all p<0.05). At week-14, 56 patients with baseline i-fat recovered to without i-fat. Patients with i-fat recovery had higher rates of CR (86.8% vs. 23.1%), MH (58.5% vs. 7.7%) and TH (34.0% vs. 2.6%) at 1 year than those with i-fat at week-14 (all p<0.001)., Conclusion: IUS-detected i-fat correlated poor long-term clinical outcomes in CD with infliximab., Competing Interests: Conflict of interest There are no conflicts of interests to declare., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Several features of drug-induced mucosal alterations have been observed in the upper gastrointestinal tract, i.e., the esophagus, stomach, and duodenum. These include pill-induced esophagitis, desquamative esophagitis, worsening of gastroesophageal reflux, chemotherapy-induced esophagitis, proton pump inhibitor-induced gastric mucosal changes, medication-induced gastric erosions and ulcers, pseudomelanosis of the stomach, olmesartan-related gastric mucosal inflammation, lanthanum deposition in the stomach, zinc acetate hydrate tablet-induced gastric ulcer, immune-related adverse event gastritis, olmesartan-asso-ciated sprue-like enteropathy, pseudomelanosis of the duodenum, and lanthanum deposition in the duodenum. For endoscopists, acquiring accurate knowledge regarding these diverse drug-induced mucosal alterations is crucial not only for the correct diagnosis of these lesions but also for differential diag-nosis of other conditions. This minireview aims to provide essential information on drug-induced mucosal alterations observed on esophagogastroduodenoscopy, along with representative endoscopic images., Competing Interests: Conflict-of-interest statement: Iwamuro M has received lecture fees from Otsuka Pharmaceutical Co., Ltd. and Ono Pharmaceutical Co., Ltd., as well as grants from Taisho Pharmaceutical Co., Ltd., Zeria Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd., and Abbott Japan Co., Ltd. Kawano S has received lecture fees from Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Astellas Pharma Inc., AstraZeneca PLC, Viatris Inc., Zeria Pharmaceutical Co., Ltd., and EA Pharma Co., Ltd., along with grants from Taisho Pharmaceutical Co., Ltd., Zeria Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd., and Abbott Japan Co., Ltd. Otsuka M has received lecture fees from Chugai Pharmaceutical Co., Ltd., Gilead Sciences, Inc., Merck & Co., Inc., Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, AbbVie GK, EA Pharma Co., Ltd., and Kowa Company, Ltd., along with grants from Taisho Pharmaceutical Co., Ltd., Zeria Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd., and Abbott Japan Co., Ltd., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

For ulcerative colitis (UC), the variability in inflammatory activity along the colon poses a challenge in management. The focus on achieving endoscopic healing in UC is evident, where the UC Endoscopic Index of Severity and Mayo Endoscopic Subscore are commonly used for evaluation. However, these indices primarily consider the most severely affected region. Liu et al recent study validates the Toronto Inflammatory Bowel Disease Global Endoscopic Reporting (TIGER) score offering a comprehensive assessment of inflammatory activity across diverse segments of the colon and rectum and a reliable index correlating strongly with UC Endoscopic Index of Severity and moderately with Mayo Endoscopic Subscore (MES). Despite recommendation, certain aspects warrant further investigation. Fecal calprotectin, an intermediate target, correlates with TIGER and should be explored. Determining TIGER scores defining endoscopic remission and response, evaluating agreement with histological activity, and assessing inter-endoscopist agreement for TIGER require scrutiny. Exploring the correlation between TIGER and intestinal ultrasound, akin to MES, adds value., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background/aims: Small rectal neuroendocrine tumors (NETs) can be treated with modified endoscopic mucosal resection (EMR). However, an optimal EMR method remains to be established. We aimed to assess the non-inferiority of Tip-in EMR versus precut EMR (EMR-P) for treating rectal NETs., Methods: This prospective, multicenter, randomized controlled trial enrolled patients with rectal NETs of < 10 mm in diameter. The patients were randomly assigned to EMR-P and Tip-in EMR groups in a 1:1 ratio. Primary outcome was margin-negative (R0) resection rate between the two methods, with a noninferiority margin of 10%., Results: Seventy-five NETs in 73 patients, including 64 eligible lesions (32 lesions in each, EMR-P and Tip-in EMR groups), were evaluated. In a modified intention-to-treat analysis, R0 resection rates of the EMR-P and Tip-in EMR groups were 96.9% and 90.6%, respectively, which did not demonstrate non-inferiority (risk difference, -6.3 [95% confidence interval: -18.0 to 5.5]). Resection time in the EMR-P group was longer than that in the Tip-in EMR group (p < 0.001). One case of intraprocedural bleeding was reported in each group., Conclusion: We did not demonstrate the non-inferiority of Tip-in EMR compared to EMR-P for treating small rectal NETs. However, the R0 resection rates for both techniques were high enough for clinical application.

This study examined the utility of the combined use of transabdominal ultrasonography (TUS) and fecal immunochemical testing (FIT) to detect mucosal inflammation, vis-a-vis the Mayo endoscopic subscore (MES), in ulcerative colitis (UC). Sixty-three UC patients who underwent TUS and FIT were retrospectively enrolled. For TUS, the colon was divided into five segments, and the bowel wall thickness was measured and evaluated. The accuracy of FIT (> 100 ng/ml) in detecting mucosal inflammation (MES>0) was 0.93, whereas that of TUS (BWT>2 mm) in each segment was 0.84-0.97. The combined use of TUS and FIT may be helpful in noninvasive treatment strategies., Competing Interests: No potential conflict of interest relevant to this article was reported.

Background and Aims: The Milan ultrasound criteria [MUC] is a validated score to assess endoscopic activity in ulcerative colitis [UC]. MUC > 6.2 detects Mayo endoscopic score [MES] > 1. In this study we evaluated the predictive value of MUC for biologic treatment response, using colonoscopy [CS] as a reference standard., Methods: Consecutive UC patients starting biologic therapy were included, and underwent CS, IUS, clinical assessment and faecal calprotectin [FC] measurement at baseline and within 1 year. In addition, IUS, clinical and FC assessments were performed at week 12. The primary objective was to evaluate whether ultrasound improvement [MUC ≤ 6.2] at week 12 predicted endoscopic improvement at reassessment [MES ≤ 1]. Endoscopic remission was defined as MES = 0., Results: Forty-nine patients were included [59% under infliximab, 29% under vedolizumab, 8% under adalimumab, 4% under ustekinumab]. MUC ≤ 6.2 at week 12 was the only independent predictor for MES ≤ 1 and MES = 0 at reassessment (odds ratio [OR] 5.80, p = 0.010; OR 10.41, p = 0.041; respectively). MUC ≤ 6.2 at week 12 showed a negative predictive value of 96% for detecting MES = 0. A ≥2 reduction of the MUC predicted MES = 0 (area under the curve [AUC] 0.816). MUC ≤ 4.3 was the most accurate cut-off value for MES = 0 [AUC 0.876]. Guyatt's responsiveness ratio for the MUC was 1.73 [>0.8]., Conclusion: MUC ≤ 6.2 at week 12 predicts long-term endoscopic response. MUC is accurate in monitoring treatment response and may be used in both clinical trials and routine practice., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background/aim: Lymphoid follicles hyperplasia (LH) is sometimes observed in the normal colon as small, round, yellowish-white nodules. LH is associated with food hypersensitivity and bowel symptoms and histologically characterized as intense infiltration of lymphocytes or plasmacytes. It is suggested that LH represents inflammatory immune response in the colonic mucosa. We investigated the presence of LH in the normal colonic mucosa and its association with incidence of colorectal lesions including colorectal cancer, adenoma and hyperplastic polyp., Patients/methods: 605 participants undergoing colonoscopy for various indications were enrolled. Presence of LH in the proximal colon (appendix, cecum and the ascending colon) was observed using the blue laser imaging (BLI) endoscopy, a new generation image enhanced endoscopy (IEE) system. LH was defined as well demarcated white nodules. Elevated LH with erythema was distinguished as LH severe. Association between presence of LH and occurrence of colorectal lesions was investigated., Results: Prevalence of all colorectal lesions and adenoma were significantly lower in LH severe group compared to the LH negative group (P = 0.0008, 0.0009, respectively). Mean number of all colorectal lesions and adenoma were also lower in LH severe group compared to the LH negative group (P = 0.005, 0.003 respectively). The logistic regression with adjustment for gender and age demonstrated that presence of LH severe held significantly lower risk of all colorectal lesions (OR = 0.48, 95%CI = 0.27-0.86) and adenoma (OR = 0.47, 95%CI = 0.26-0.86)., Conclusion: LH in the colonic mucosa visualized by IEE is useful endoscopic finding to predict risk of colorectal adenoma., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Tahara et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Aims: This study examines colonic histological features in ulcerative colitis [UC] in endoscopic remission to determine which cell types and biopsy sites best predict a patient's likelihood of remaining in remission., Methods: This is a retrospective chart, endoscopy and histology review of 166 patients with UC in endoscopic remission followed in a single inflammatory bowel disease practice over a median of 6 years [range, 2-11 years]. Clinical remission was based on global physician assessment and colonoscopy reports, and clinical relapse on chart review. Histological features of previous injury and also number and location of plasma cells and eosinophils were assessed. We evaluated all of these features semi-quantitatively using a standard set of illustrations for the grade to maintain consistency. Multiple logistic regression and survival analyses were used to identify features associated with relapse., Results: Clinical relapse occurred in 44 patients. Ulceration, especially in the left colon, was highly predictive of relapse. In the absence of acute inflammation of ulceration, the variables most predictive of relapse were increased plasma cells in the basal 20% of the lamina propria, and eosinophils in the left colon. The variable most predictive of persistent remission was the presence of intra-epithelial eosinophils whether in the surface epithelium or within crypts, especially in the right colon. Lamina propria eosinophils [grade > 2] throughout the colon predicted relapse., Conclusion: In the absence of neutrophils or ulceration, left-sided plasmacytosis in the basal 20% of the lamina propria and increased lamina propria eosinophils provide the best indicators of relapse in UC in clinical and endoscopic remission., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

To characterize the associations between clinical disease activity with endoscopic and histologic (endohistologic) mucosal healing in Crohn's disease, we performed a secondary analysis of prospectively collected data on 424 ileocolonoscopies from 258 unique adults at a tertiary referral center from 2014 to 2021. One-third of patients (34%, 25/73) in endoscopic-histologic remission reported gastrointestinal symptoms. The 2-item patient-reported outcome measure for abdominal pain and stool frequency correlated weakly with endoscopic (Simple Endoscopic Score for Crohn's Disease; r = 0.17, 95% CI 0.08-0.26, P = 0.0003) and histologic disease activity (Global Histologic Disease Activity Score; r = 0.14, 95% CI 0.03-0.24, P = 0.015). Overall, gastrointestinal symptoms correlate poorly with endohistologic disease activity., (Copyright © 2022 by The American College of Gastroenterology.)

Background and Objective: Celiac Disease (CD) is characterized by gluten intolerance in genetically predisposed individuals. High disease prevalence, absence of a cure, and low diagnosis rates make this disease a public health problem. The diagnosis of CD predominantly relies on recognizing characteristic mucosal alterations of the small intestine, such as villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis. However, these changes are not entirely specific to CD and overlap with Non-Celiac Duodenitis (NCD) due to various etiologies. We investigated whether Artificial Intelligence (AI) models could assist in distinguishing normal, CD, and NCD (and unaffected individuals) based on the characteristics of small intestinal lamina propria (LP)., Methods: Our method was developed using a dataset comprising high magnification biopsy images of the duodenal LP compartment of CD patients with different clinical stages of CD, those with NCD, and individuals lacking an intestinal inflammatory disorder (controls). A pre-processing step was used to standardize and enhance the acquired images., Results: For the normal controls versus CD use case, a Support Vector Machine (SVM) achieved an Accuracy (ACC) of 98.53%. For a second use case, we investigated the ability of the classification algorithm to differentiate between normal controls and NCD. In this use case, the SVM algorithm with linear kernel outperformed all the tested classifiers by achieving 98.55% ACC., Conclusions: To the best of our knowledge, this is the first study that documents automated differentiation between normal, NCD, and CD biopsy images. These findings are a stepping stone toward automated biopsy image analysis that can significantly benefit patients and healthcare providers., Competing Interests: Declaration of Competing Interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2022. Published by Elsevier B.V.)

The intestinal epithelial barrier, among other compartments such as the mucosal immune system, contributes to the maintenance of intestinal homeostasis. Therefore, any disturbance within the epithelial layer could lead to intestinal permeability and promote mucosal inflammation. Considering that disintegration of the intestinal epithelial barrier is a key element in the etiology of ulcerative colitis, further assessment of barrier integrity could contribute to a better understanding of the role of epithelial barrier defects in ulcerative colitis (UC), one major form of chronic inflammatory bowel disease. Herein, we employ fast, non-destructive, and label-free non-linear methods, namely coherent anti-Stokes Raman scattering (CARS), second harmonic generation (SHG), two-photon excited fluorescence (TPEF), and two-photon fluorescence lifetime imaging (2P-FLIM), to assess the morpho-chemical contributions leading to the dysfunction of the epithelial barrier. For the first time, the formation of epithelial barrier gaps was directly visualized, without sophisticated data analysis procedures, by the 3D analysis of the colonic mucosa from severely inflamed UC patients. The results were compared with histopathological and immunofluorescence images and validated using transmission electron microscopy (TEM) to indicate structural alterations of the apical junction complex as the underlying cause for the formation of the epithelial barrier gaps. Our findings suggest the potential advantage of non-linear multimodal imaging is to give precise, detailed, and direct visualization of the epithelial barrier in the gastrointestinal tract, which can be combined with a fiber probe for future endomicroscopy measurements during real-time in vivo imaging., (© 2023. The Author(s).)

Background: Large or transmural defects induced by gastrointestinal endoscopic manipulations are difficult to close, although complete closure is recommended for better recovery. Endoscopic purse-string assisted suturing (EPSS) has been used in clinical practice and has proven to be an effective and safe technique for the closure of large mucosal defects. However, details regarding the efficacy of endoscopic pre-purse-string suture (P-EPSS) are unknown, especially that it offers several advantages over conventional EPSS (C-EPSS)., Aim: To elucidate the outcomes of EPSS-assisted closure in different clinical situations, and evaluate the efficacy of P-EPSS., Methods: This retrospective observational study included a total of 180 patients who underwent closure assisted by P-EPSS ( n = 63) or C-EPSS ( n = 117) between July 2014 and June 2020. The P-EPSS and C-EPSS groups were compared and the intergroup differences in aspects such as the lesion size, location, and mor-phology, incidence of complete closure, intraoperative perforation, and delayed adverse events were evaluated. Data on the features and clinical course of cases with adverse events were collected for further analysis., Results: Patients with lesion size larger than 3 cm, lesions located at the fundus of stomach, or submucosal tumors originating from the deep mucosa were more likely to undergo P-EPSS-assisted closure. The P-EPSS group showed a sign-ificantly higher proportion of intraoperative perforation (56% vs 17%) and a much shorter procedure time (9.06 ± 6.14 min vs 14.84 ± 7.25 min). Among adverse events, the incidence of delayed perforation (5% vs 4%; P = 0.82) and delayed bleeding (3% vs 4%; P = 0.96) did not differ significantly between the groups. Multivariate analysis revealed that lesions with incomplete closure [odds ratio (OR) = 21.33; 95% confidence interval (CI): 5.45-83.45; P < 0.01] or size greater than 3 cm (OR = 3.14; 95%CI: 1.08-9.18; P = 0.039) showed a statistical tendency to result in an increase in delayed adverse events., Conclusion: The present study revealed that EPSS could achieve secure complete closure of mucosal defect. P-EPSS could shorten the procedure and yield complete closure of mucosal defects. Rather than closure-type selection, incomplete closure or lesion size larger than 3 cm were associated with worse outcomes., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Mucosal healing (MH) is recognized as a therapeutic target in ulcerative colitis (UC) because of evidence that it is associated with favorable clinical outcomes. Current endoscopic assessment of MH by conventional white-light endoscopy is subject to several important clinical issues including the subjective nature of assessment, intra- and interobserver variability, and persistent microscopic inflammation, even in mucosa it was observed as quiescent on conventional endoscopy., Summary: Advances in image-enhancement technologies enable the provision of high-contrast images that emphasize the mucosal structures, blood vessel patterns, and color tones of the intestinal mucosa, and recently, several image-enhanced endoscopy (IEE) techniques have become available for the assessment of MH in UC. Narrow-band imaging and dual-red imaging facilitate visualization of mucosal vascular structures, which is useful for detecting minor inflammation and predicting relapse because of the capturing of information on incomplete vascular regeneration in patients with UC. Linked-color imaging (LCI) is optimized to emphasize the redness of the mucosa and blood vessels, and is superior for depicting subtle color changes arising from mucosal inflammation. LCI could possibly be used to stratify UC patients with MH on conventional endoscopy. Autofluorescence imaging and i-scan can also depict subtle histological changes underlying the healing of mucosa in UC, revealing them as simple color changes., Key Messages: Accumulating evidence suggests that IEE techniques could overcome current unmet needs in the endoscopic assessment of MH in UC and contribute to improving therapy based on treat-to-target strategies., (© 2022 S. Karger AG, Basel.)

Background and Aims: Apart from endoscopic healing as an established treatment goal in patients with inflammatory bowel disease (IBD), histologic remission is an emerging endpoint that might even better predict disease outcome, especially in ulcerative colitis (UC). Within this study, we aimed to evaluate whether endocytoscopy (EC) as an in vivo contact microscopy technology can accurately assess histologic inflammation and predict the further course of disease in UC patients., Methods: Initially, a new and intuitive EC score reflecting the entire spectrum of microscopic disease activity in UC was consensually developed. Subsequently, this score was independently validated in 46 patients with UC who underwent close-meshed follow-up during which major adverse outcomes (MAOs; defined as disease flare, IBD-related hospitalization, IBD-related surgery, necessity for initiation or escalation therapy) were recorded. Results of EC grading of inflammatory activity were compared against 2 validated histologic scores in UC. Diagnostic performance of endoscopic remission under white-light endoscopy (Mayo Endoscopic Score and Ulcerative Colitis Endoscopic Index of Severity), EC, and histology were compared for the prediction of MAOs., Results: Endocytoscopic assessment of inflammatory activity in UC based on the newly developed ErLangen Endocytoscopy in ColiTis score showed strong correlation with histopathologic scoring (Robarts Histopathology Index, r = .70; Nancy Histologic Index, r = .73) and was superior to white-light endoscopy for grading of microscopic disease activity, with a sensitivity of 88%, specificity of 95.2%, and area under the curve of .916. Furthermore, EC exhibited a high interobserver agreement for in vivo grading of microscopic inflammation and was comparably accurate as histopathology for forecasting the occurrence of MAOs in UC., Conclusions: Endocytoscopic grading of inflammatory activity along a newly developed scoring system enabled real-time histology in UC patients and better predicted clinical outcome in UC patients than endoscopic remission., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Introduction: Recent meta-analysis showed that ulcerative colitis (UC) is a risk factor for cardiovascular disease (CVD). Dyslipidemia is a well-established risk factor for CVD. However, evidence regarding inflammatory bowel disease (IBD), including UC and lipid profiles, is limited. Additionally, no study has assessed the association between endoscopic activity and lipid profiles in patients with IBD. Therefore, we aimed to clarify the association between mucosal healing (MH) and lipid profiles in patients with UC., Methods: A total of 221 Japanese patients with UC were enrolled in this analysis. Total cholesterol (T-chol), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) were divided into tertiles (high, moderate, and low) based on the distributions, respectively. Self-administered questionnaire was used to obtain information regarding medication for dyslipidemia. Complete MH and MH are based on Mayo endoscopic subscore 0 and 0-1, respectively., Results: The percentage of complete MH was 30.8%. In patients without medication for dyslipidemia, high HDL-C (>66 mg/dL) was significantly positively associated with complete MH (adjusted odds ratio [OR] 2.58, 95% CI: 1.04-6.64, p for trend = 0.037). In patients with nonproctitis, a positive association between HDL-C and complete MH was found (adjusted OR 3.54, 95% CI: 1.22-11.01, p for trend = 0.020). T-chol and TG were not associated with MH, regardless of medication for dyslipidemia., Conclusions: Complete MH was significantly positively associated with HDL-C in UC patients without medication for lipid. The disease extent might affect the association between complete MH and HDL-C., (© 2022 S. Karger AG, Basel.)