Breakthroughs in IBD treatment and outcomes: Late ‐ breaking

Disclosure : This study was supported by Asian Endoscopic Research Forum (AERF)


Introduction: Inhibition of interleukin (IL)-23 has been demonstrated
as a safe and effective mechanism of action for treating various chronic inflammatory diseases, including Crohn's disease (CD).The phase 3b SEQUENCE study directly compared the efficacy and safety of risankizumab (RZB), a selective IL-23 p19 subunit inhibitor, and ustekinumab (UST), an IL-12/IL-23 p40 subunit inhibitor, in patients (pts) with moderate to severe CD.
Aims & Methods: SEQUENCE, an open-label, multicenter, randomized, efficacy assessment-blinded study, enrolled pts who previously failed ≥1 anti-TNF therapies and had a CD Activity Index score of 220-450, Simple Endoscopic Score for CD ≥6 for ileocolonic or colonic disease (≥4 for isolated ileal disease) excluding the presence of narrowing component, plus an average (avg) daily stool frequency ≥4 and/or avg daily abdominal pain score ≥2.In Part 1 of the trial, described herein, pts were randomized 1:1 to receive RZB (600 mg IV induction dosing at baseline [BL], weeks 4 and 8, followed by 360 mg SC maintenance dosing every 8 weeks [Q8w] starting at week 12) or UST (a single weight-based IV induction dose, followed by 90 mg SC maintenance dosing Q8w starting at week 8) over a period of 48 weeks. 1 Randomization was stratified by number of anti-TNF therapies failed (1, >1) and steroid use at BL (Y, N).A mandatory steroid taper started at week 2. Two primary endpoints were clinical remission at week 24 (non-inferiority of RZB vs. UST in 50% of planned subjects) and endoscopic remission at week 48 (superiority of RZB vs. UST).Ranked secondary endpoints included clinical remission at week 48, endoscopic response at weeks 48 and 24, steroid-free (SF) endoscopic remission at week 48, and SF clinical remission at week 48 (all tested for superiority of RZB vs. UST).
Safety was assessed throughout the trial.
d Intent-to-treat-1 (ITT-1) population included all randomized subjects who were randomized to RZB with the selected RZB dose (RZB 600 mg IV followed by RZB 360 mg SC) or UST and who received at least    1).Besides, they were also more likely to be diagnosed at an advanced rather than early stage of the disease (OR 1.45, 95% CI: 1.05-2.00).
Individuals who had participated in three or four screening rounds had a lower IC risk than those who had participated once (HR 0.75, 95% CI: 0.56-0.99).Screening round was not associated with stage distribution and sex was not associated with IC nor stage distribution.

Conclusion:
Our results indicate that a risk-stratified upper age limit in CRC screening based on prior f-Hb concentration may prevent CRC cases and CRC-related morbidity by early detection.While individuals with detectable f-Hb in their final FIT may benefit from additional screening, screening of the elderly is not without risks.Follow-up studies should therefore assess the benefit-risk ratio of a riskstratified upper age limit and identify the optimal screening scenario.
Disclosure: Nothing to disclose.
All three groups exceed the recommended thresholds of acceptability with satisfactory quickness.Globally, delayed bleeding and surgery due to complications occurred in 5.4% and 0.8% of cases, respectively, with no significant difference between the three groups.
Multivariate analysis found that size >50 mm, poor maneuverability, recurrent and appendiceal lesions, but not volume of the center were risk factors for both R1 resection (p < 0.001) and perforation (p < 0.001) suggesting that differences of outcomes can be explained by lesion characteristics.and control group which no epinephrine would be added.1).

Data
Based on the histology results, the CADe group exhibited a higher count of resected lesions with normal mucosa compared to the WLE group (0.21 [0.67] vs. 0.08 [0.30]; p < 0.04).

Conclusion
Abbreviations: AE, adverse event; BL, baseline; CD, Crohn's disease; CDAI, CD activity index; ITT, intention to treat; RZB, risankizumab; PY, patient years; SES-CD, simple endoscopic score for CD; TEAE, treatment emergent AE; UST, ustekinumab; wk, week.Clinical remission -CDAI <150.Endoscopic remission-SES-CD ≤ 4 and at least a 2-point reduction versus BL and no sub score >1 in any individual variable, as scored by a central reviewer blinded to treatment allocation.Endoscopic response -decrease in SES-CD > 50% from BL (or for pts with isolated ileal disease and a BL SES-CD of 4, at least a 2-point reduction from BL), as scored by central reviewer.Steroid-free endoscopic remission -endoscopic remission and not receiving steroids at the corresponding visit.Steroid-free clinical remission -clinical remission and not receiving steroids at the corresponding visit.*SEQUENCE Part 1 compared the efficacy and safety of RZB versus UST over 48 weeks, while Part 2 is an ongoing open-label long-term extension to evaluate the long-term safety of RZB in pts who received RZB in Part 1 and completed week 48 visit.a Categorical variables were analyzed using Cochran-Mantel-Haenszel (CMH) test.For both the primary and secondary endpoints, the non-responder imputation while incorporating multiple imputation to handle missing data (due to COVID-19 or geopolitical conflict) was used.Primary and secondary endpoints were tested sequentially in the order specified using the CMH risk difference estimate test stratified by the number of failed anti-TNF therapies (1, >1) and steroid use at baseline (yes, no).
Prediction of Inflammatory Bowel Disease, Aalborg University, PREDICT; Department of Clinical Medicine, København, Denmark, 2 Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark, 3 Department of Gastroenterology and Hepatology and Department of Chronic Diseases, Metabolism and Aging, Translational Research in Gastrointestinal Disorders -IB, University Hospitals Leuven and KU Leuven, Leuven, Belgium, 4 Edinburgh IBD Unit, University of Edinburgh, Edinburgh, UK Contact E-Mail Address: re107@ic.ac.ukIntroduction: Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is known to be associated with various extra-intestinal manifestations, impacting organ systems beyond the gastrointestinal tract.Identifying comorbidities in IBD and the timing of their development can provide valuable insight into the mechanisms underlying IBD development.Aims & Methods: We conducted the first population-and diseasewide phenomic association study in IBD, using >6 million ICD-10 coded healthcare contacts from 10 years before and up to 17 years after IBD diagnosis to investigate associations with 1583 diseases.In order to explore co-morbidities with potential aetiological significance with IBD, we additionally assessed the strength of association with all diseases in the pre-diagnosis compared with the postdiagnosis period.To correct for multiple testing, we adjust our significance threshold (p < 0.05) with the Bonferroni correction, resulting in an adjusted p-value of 7.90 � 10 −6 , which we refer to as disease-wide statistical significance.Results: We identified 312 disease associations with disease-wide statisitical significance and 125 of these diseases appear up to 10 years before diagnosis.The risk of immune-mediated diseases and extra-intestinal manifestations are among those diseases increased up to 10 years prior to IBD diagnosis (psoriasis: RR CD : 2.57, 95% CI: 2.00-

Introduction:
Endoscopic submucosal dissection (ESD) has become a standard therapy for early gastric cancer.The type of submucosal injection solution used during gastric ESD varies among different endoscopists.The use of epinephrine added solution may facilitate the procedure by inducing vasoconstriction, thus minimizing intraoperative haemorrhage and allowing clearer dissection plane.The efficacy of epinephrine added solution was previously reported in a single center retrospective study, demonstrating reduction in procedure time with the addition of epinephrine. 1 In this prospective double blinded international randomized study, we aim to investigate whether using epinephrine added solution, could significantly reduce procedure time and the number of intra-operative bleeding episodes.Aims & Methods: This trial was conducted in 12 institutions across four countries.Adult patients with biopsy confirmed gastric mucosal neoplasia undergoing ESD would be recruited.Patients with multiple or anastomotic lesions, on dual antiplatelet agent, warfarin and other direct oral anticoagulants would be excluded.They would be randomized to epinephrine group which 0.2 mL 1:1000 epinephrine diluted into each 20 mL of the original injection solution mixture,

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CADe did not improve the detection of adenomas in Lynch syndrome in referral centers with a high adenoma detection rate. 1 , E. de-Madaria 2 , A. Ebigbo 3 , P. Vanek 4 , O. Elshaarawy 5 , A. M. Voiosu 6 , G. Antonelli 7 , R. Turro 8 , J. Gisbert 9 , O. P. Nyssen 9 , C. Hassan 10 , H. Messmann 11 , R. Jalan 12 , H. Demir 13 , B. Tinaz 14 , H. M. Introduction: Currently available artificial intelligence (AI) large language models (LLM) fail to translate effectively to clinical medicine, largely being relegated to question answering roles, documentation, and medical literature summarization.Recognizing this potential, we developed a proof of concept of a specialty-specific and multi-task clinical LLM: GastroGPT.Our study evaluated GastroGPT against leading general-purpose LLMs across key clinical tasks and diverse gastroenterology case scenarios.Aims & Methods: In this structured analysis, GastroGPT was compared to three state-of-the-art general purpose LLMs (LLM-A: GPT4, LLM-B: Bard, LLM-C: Claude) with highest known utility metrics (training and model parameters, published performance benchmarks, user adoption).All models were assessed on seven key clinical tasks and overall performance.Ten simulated cases covered general gastroenterology and sub-specialties across varying complexity, frequency, and demographics.Standardized prompts ensured structured comparisons.Expert panels, representing varied backgrounds, blindly rated model outputs overall and per task using a 10-point Likert scale, judging utility, style, practicality, and

Breakthroughs in screening and management of colorectal lesions: Late-breaking abstracts Monday, 16 October 2023 10:00- 11:00/A1 LB06 COLD VS. HOT SNARE RESECTION OF NON- PEDUNCULATED POLYPS ≥2CM IN THE COLORECTUM -FIRST RESULTS FROM THE PROSPECTIVE, RANDOMIZED, CONTROLLED, MULTICENTRIC CHRONICLE-TRIAL Introduction:
Knowledge on the long-term disease course of microscopic colitis (MC) is unknown, and rests on retrospective studies.No predictive markers of disease course and disease activity have been identified.This 5-year prospective follow-up of a European incidence cohort aims to address these questions.Disease activity at 1 year after diagnosis was predictive of activity after 5 years.Budesonide was the most frequently applied treatment, while use of immunosuppressants and biologicals was rare.Follow-up of MC patients should reflect the recurrent course of disease, and physicians should inform them accordingly.Randomised trials on alternatives to longtime budesonide use are warranted.For the removal of diminutive colorectal polyps <10 mm cold snare (CS) resection is standard of care.For polyps ≥20 mm endoscopic mucosal resection (EMR) with a hot snare (HS) is recommended, which is usually accomplished in piece meal technique.1Recently,a retrospective trial showed a favorable safety profile and a comparable recurrence rate for CS-EMR in comparison to HS-EMR for sessile serrated adenomas (SSA) ≥20 mm 2 .We investigated if CS-EMR is superior to HS-EMR for the removal of larger, non-pedunculated, colorectal polyps.Nogales 1 , C. Carbonell Blanco 1 , M. Pellisé 2 , J. F. Martínez Sempere 3 , F. Riu Pons 4 , C. Mangas-Sanjuan 3 , M. Daca Alvarez 5 , H.
3.29; RR UC : 1.54, 95% CI: 1.25-1.87;enteropathicarthropathies:RRCD:3.57,95%CI:2.65-4.78;RRUC:1.8,95%CI:1.38-2.32).This was also the case for gastroenterological and liver disorders (gall stones: CD : 2.56, 95% CI: 2.30-2.86;HRUC:1.92,95%CI:1.79-2.07)orherpessimplexinfections(HRCD:4.04,95%CI:2.76-5.91;HRUC:1.69,95%CI:1.2-2.38)wereprimarilyseenpostdiagnostically.Of potential aetiological importance to CD, diagnosis with infectious mononucleosis (RR: 1.87, 95% CI: 1.37-2.52)waslimitedtothepre-diagnosticperiod.Disclosure: AE, GP, and MB report no competing interests.LB05 | THE DISEASE COURSE OF MICROSCOPIC COLITIS -A 5-YEAR PROSPECTIVE EUROPEAN INCIDENCE COHORT (PRO-MC)B.Verhaegh 1 , A. Münch 2 , S. Wildt 3 , W. Cebula 4 , A.-R. Diac 5 , M. Alkhalaf6, N. Pedersen 7 , D. Guagnozzi 8 , J. Kupcinskas 9 , V. Kiudelis 10 , F.Fernández-Bañares 11 , G. E. Tontini 12 , I. Lyutakov 13 , G. Macaigne 14 , S.Miehlke 15 , H. Hjortswang 16 , L. K. Munck 17 Contact E-Mail Address: verhaeghbas@gmail.comIntroduction:1Treatment with budesonide was initiated in 51%, 29% was treated with loperamide or bulging agents, and 20% was not treated.During 5-year follow-up, only 5% of the patients followed a quiescent disease course, i.e., no disease activity or treatment ever since diagnosis.Sustained clinical remission was achieved in 21%, 35% and 55% after 1, 3 and 5 years, respectively.In contrast, 33% had a relapsing disease course, and 7% exhibited a chronic active course with continuous activity and/or treatment.The disease course did not differ between CC and LC.Stool frequency at baseline was not predictive.A quiescent disease course since diagnosis or achieving sustained clinical remission during the first or second year, was associated with a 70% chance of being in clinical remission after 5 years (p < 0.001).In contrast, 57% of cases with a chronic active disease course in the first year had a chronic active or relapsing disease course throughout 5-year follow-up (p = 0.02).uouslysincediagnosis.Bulging agents (15%) and loperamide (21%) were regularly applied after 5 years, mainly in relapsing cases.Of those in clinical remission, 17% used loperamide on demand.Treatment with thiopurines (<1%) and biologicals (<2%) during follow-up was rare.Conclusion: Five years after diagnosis, 40% of MC patients had a relapsing or chronic active disease course, resulting in an impaired quality of life.Aims & Methods: In this prospective, randomized, controlled trial non-pedunculated colorectal polyps ≥20 mm were randomly assigned to CS-EMR or HS-EMR.Primary endpoint was major complication (=perforation or clinically significant post-endoscopic bleeding [CSPEB]), secondary endpoints were intraprocedural bleeding (IPB), postpolypectomy syndrome (PPS), technical success, resection speed and recurrence rate after 4 months.higherafterCS-EMRcarefulselection of the target lesion should be made.CS-EMR should be considered as new standard of care for suspected SSA, LST non-granular type with no macroscopic signs of malignancy and selected LST granular-type homogenous ≥20 mm.terology, Hospital Clinic, Barcelona, Spain, 6 Gastroenterology (GI Endoscopy Unit), Hospital Germans Trias i Pujol, Barcelona, Spain, 7 Gastroenterology, Hospital Universitario de Salamanca, Salamanca, Spain, 8 Servicio Aparato Digestivo, Hospital Universitario de Navarra, Pamplona, Spain Contact E-Mail Address: oscarnogalesrincon@gmail.com Introduction: Cold snare EMR (CS-SEMR) in large non-pedunculated colonic lesions is an alternative to the standard procedure (C-EMR), with a better theoretical safety profile.Robust scientific evidence on its efficacy is not available.Aims & Methods: Objectives: Primary: to compare the efficacy between the two techniques, measured as the absence of recurrence at 6 months.Secondary: to compare safety profile and technical aspects.theCS-EMR group versus C-EMR group: 33.6 versus 16.7% (p = 0.007), and 35.1 versus 15.2% (p = 0.002) in ITT and PP analysis, respectively.En bloc and R0 resection rates were higher in C-EMR versus CS-EMR: 23.7% versus 1.7% p = 0.001, and 21.1% versus 1.7% p = 0.001, respectively.There was no difference in the rate of complications: delayed bleeding (CS-EMR 2.6% vs. C-EMR 3.5% Netherlands Contact E-Mail Address: b.vanstigt@erasmusmc.nl Introduction: Colorectal cancer (CRC) screening programmes have been shown effective in reducing CRC incidence and mortality.Risk stratification offers opportunities for further optimisation of screening programmes by better balancing the harms and benefitsof screening.To this day, nearly all population screening programmes only differentiate their screening approach by age, resulting in a fixed upper age limit of screening.While further risk stratification based on prior faecal haemoglobin (f-Hb) concentration seems promising, studies are mainly limited to the target population of screening.Risk-stratified screening beyond the upper age limit might however be beneficial as well considering the increasing life expectancy and the benefit-risk ratio of screening widely varying amongst elderly.Factors associated with CRC stage were identified using a multivariable logistic regression analysis.Results:A total of 311,655 individuals with a complete follow-up (24 months) after a negative FIT were included.Within this population, the overall IC risk was 21.6 per 10,000 individuals with a negative FIT.Individuals with detectable f-Hb (>0 µg Hb/g faeces) in the final screening round developed IC more often than those without(HR 4.85,) (Table Existence of structured colorectal cancer (CRC)screening programs across Europe is inconsistent, moreover, participation rates vary greatly.Similarly, such a program as well as mandatory colonoscopy quality assurance are lacking in Austria.Overview of IC risk, including results of a Cox regression analysis with IC as a dependent variable and sex, screening round and prior f-Hb concentration as independent variables.Through the implementation of novel strategies and training programs, ESD has been proved more effective than piecemeal endoscopic mucosal resection (EMR) for large colorectal lesions, without a significantly higher risk of adverse events, according to recent high-quality data.Reproducibility outside experts centers has been questioned.

Full cohort Low- volume center Middle- volume center High- volume center p-value (full cohort) p-value (low vs. middle) p-value (low vs. high) p-value (middle vs. high)
Colorectal cancer (CRC) risk reduction through colonoscopy is a well-documented strategy within Lynch syndrome (LS), a genetic disorder characterized by 50%-70% lifetime CRC susceptibility.In LS, CRC arises from small, proximal, and flat adenomas, following an accelerated adenoma-carcinoma sequence.Although artificial intelligence-assisted colonoscopy (CADe) has shown to increase adenoma detection among individuals at average risk, its efficacy within the LS context remains unexplored.The mean adenomas detected per colonoscopy (APC), guided the sample size calculation and primary outcome.Out of the initially randomized 430 individuals, 414 patients were included for final analysis: 204 in the intervention group and 210 in the control group.Baseline characteristics were welldistributed between the two groups.Comparable mean withdrawal times were observed for CADe (12.5 min) and WLE (13.1 min; p = 0.3).Adenoma detection rate was 35.3% in the whole cohort (CADe: 33.3% vs. WLE: 37.1%; p 0.42).The overall APC and the APC categorized by adenoma size, location, and morphology did not exhibit statistically significant differences between groups.CADe demonstrated a significant increase in the serrated lesions detection rate (38.7% vs. 26.7%;Relativerisk1.31[1.08-1.59];p 0.01) and in the number of 5-9 mm serrated lesions per colonoscopy (Table Contact E-Mail Address: Dr.ayman1977@gmail.comIntroduction:Gastriccancer(GC) is the fourth most prevalent cancerrelated death factor.It has a great prognosis and is treatable when diagnosed at an early stage or early lesions that are likely to be precancerous, such as atrophic gastritis (AG).Pepsinogen is the most reliable non-invasive biomarker for the diagnosis of severe AG or GC.However, its application is still controversial, and it is advised to utilize it carefully and with caution since the populations' cut-off values vary.(94%),specificity(88.4%),positivepredictive value (PPV) of 100%, and negative predictive value (NPV) of 100%.Conclusion: Serum Pg1 and Pg1/Pg2 ratio demonstrated a very high diagnostic value for diagnosis of AG and GC and is a promising future tumor marker.Introduction: Aims & Methods: A prospective, parallel, randomized, multicenter study was conducted to compare CADe-assisted colonoscopy (intervention) with standard white-light endoscopy (WLE, control) in individuals harboring pathogenic/likely pathogenic MLH1, MSH2, MSH6, or EpCam variants associated with LS.Results: Performance between WLE and CADe.
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