United European Gastroenterology Journal最新文献

{"title":"Pan-ERBB Inhibitors Synergize With KRAS Inhibitors in Rectal Cancer.","authors":"Jonas Buchloh, Melanie Spitzner, Hauke Zimmermann, Xin Fang, Constanza Tapia Contreras, Carolin Schneider, Tiago de Oliveria, Stefan Küffer, Michael Linnebacher, Felix Rühlmann, Lena Conradi, Matthias Wirth, Michael Ghadimi, Marian Grade, Jochen Gaedcke, Günter Schneider","doi":"10.1002/ueg2.70086","DOIUrl":"https://doi.org/10.1002/ueg2.70086","url":null,"abstract":"<p><strong>Background: </strong>Emerging RAS inhibitors show promise in treating KRAS-mutated malignancies, but resistance mechanisms limit their clinical efficacy. Given recent clinical findings associating KRAS mutations with reduced response to neoadjuvant therapy in rectal cancer (RC), we aimed to investigate their impact on treatment outcomes and explore potential therapeutic strategies.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of 390 rectal cancer patients to evaluate the association of KRAS mutations with disease-free survival (DFS) and response to therapy. We assessed the efficacy of KRAS inhibitors in rectal cancer cell lines, patient-derived organoids (PDOs), and patient-derived cell lines (PDCLs), and explored adaptive resistance mechanisms through transcriptomic profiling and unbiased drug screening experiments.</p><p><strong>Results: </strong>Mutant KRAS was associated with a reduced DFS and RCs harboring G12C and G12V mutations had less complete pathological responses to neo-adjuvant therapies. KRAS-mutated RC cells demonstrated adaptive resistance to KRAS inhibitors, characterized by transcriptomic restoration of oncogenic pathways, including MYC and E2F, and upregulation of ERBB2/3 expression. Consistently, drug screening identified EGFR family inhibitors as potent combinatorial partners, effectively overcoming KRAS inhibitor tolerance by inducing apoptosis. In patient-derived models, the pan-RAS inhibitor RMC-6236 combined with EGFR inhibitors demonstrated significant synergistic effects and prevented long-term tumor cell outgrowth.</p><p><strong>Conclusion: </strong>Our findings point to the negative impact of KRAS mutations, particularly G12C and G12V, on RC treatment outcomes. Adaptive resistance by upregulation of ERBB genes limits the efficacy of KRAS inhibitors. Combining these with pan-ERBB inhibitors enhances anti-tumor effects in patient-derived cellular RC models, showing its potential as an alternative to the combination with anti-EGFR antibodies.</p>","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145070631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inaccuracy and Bias in Endoscopic Size Estimation of Large Colorectal Polyps; Insights From a Prospective Cohort of 1828 En-Bloc Resections.","authors":"Kohei Shigeta, Kenichiro Imai, Kinichi Hotta, Nozomu Kobayashi, Ken Ohata, Yoji Takeuchi, Akiko Chino, Masayoshi Yamada, Yosuke Tsuji, Keita Harada, Hiroaki Ikematsu, Toshio Uraoka, Takashi Murakami, Shigetsugu Tsuji, Atsushi Katagiri, Shinichiro Hori, Tomoki Michida, Takuto Suzuki, Masakatsu Fukuzawa, Shinsuke Kiriyama, Kazutoshi Fukase, Yoshitaka Murakami, Hideki Ishikawa, Yutaka Saito","doi":"10.1002/ueg2.70100","DOIUrl":"https://doi.org/10.1002/ueg2.70100","url":null,"abstract":"<p><strong>Background and aims: </strong>Endoscopic size estimation of large colorectal polyps influences treatment decisions and clinical outcomes; however, its precision remains unclear. This study aimed to assess the accuracy of endoscopic size estimation for colorectal lesions ≥ 20 mm utilizing data from an endoscopic submucosal dissection (ESD) cohort.</p><p><strong>Methods: </strong>This post hoc analysis included only en bloc resected lesions treated by ESD. Patients with neuroendocrine tumors, recurrent lesions, colitis-associated dysplasia, or insufficient data were excluded. Size accuracy was defined as a margin of error < 5 mm. Outcomes included the frequency of size errors ≥ 10 mm and ≥ 20 mm, terminal digit preferences in estimated size, and predictors for lesions estimated endoscopically at 20 mm but pathologically ≥ 25 mm. The reference standard was pathological size.</p><p><strong>Results: </strong>Among 1889 lesions (1809 patients), 61 lesions (60 patients) were excluded. Finally, 1828 lesions (1749 patients) were evaluated. The accuracy of endoscopic size estimation was 53.4%. Errors ≥ 10 and ≥ 20 mm occurred in 19.1% and 4.5% of lesions, respectively. Endoscopic size estimation showed a strong terminal digit preference for 0 (65.2%) and 5 (30.0%). Among 366 lesions estimated at 20 mm, 97 (26.5%) were pathologically ≥ 25 mm. Polypoid lesions [odds ratio (OR) 2.8, 95% confidence interval (CI) 1.1-6.8] and laterally spreading tumors granular type (OR 2.0, 95% CI: 1.1-3.5) were predictors of underestimation.</p><p><strong>Conclusions: </strong>Endoscopic size estimation of large colorectal lesions can be inaccurate and influenced by digit bias, underscoring the need for improved measurement techniques (UMIN000010136).</p>","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145070654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasmapheresis in Acute Hypertriglyceridemia-Induced Pancreatitis-The PHIP-JuGa-Study.","authors":"Jonas J Staudacher, Elisabeth Blüthner, Katharina Murillo, Manja Boldt, Karim Hamesch, Leah Kruse, Sabrina Sulzer, Christoph Ammer-Herrmenau, Yvonne Huber, Julia Weinmann-Menke, Charlotte Kramer, Jakob Garbe, Rene Wilke, Marcus M Mücke, Myriam W Heilani, Elisabeth Orgler-Gasche, Marlies Vornhülz, Georg Beyer, Lara Wiesehahn, Annekatrin Schwanstecher, Marcus Hollenbach, Hendrik Luxenburger, Dominik Bettinger, Sophie Schlosser-Hupf","doi":"10.1002/ueg2.70097","DOIUrl":"https://doi.org/10.1002/ueg2.70097","url":null,"abstract":"<p><strong>Background and aims: </strong>The incidence of acute pancreatitis is increasing in the Western world. About 10% of cases are caused by hypertriglyceridemia. Plasmapheresis was shown to reduce serum triglyceride (TG) levels, and current apheresis guidelines recommend its use in severe acute hypertriglyceridemia-induced pancreatitis (HIP). However, data on safety and efficacy are lacking. This study aimed to evaluate the clinical efficacy of plasmapheresis in hypertriglyceridemia-induced pancreatitis.</p><p><strong>Methods: </strong>This is a retrospective multicenter cohort study of patients hospitalized for an episode of hypertriglyceridemia-induced pancreatitis from January 1, 2012 to December 31, 2022. The predefined composite primary endpoint was in-hospital mortality and organ failure. To reduce allocation bias, we performed propensity score matching.</p><p><strong>Results: </strong>245 episodes of hypertriglyceridemia-induced pancreatitis from 13 German centers were included. Of those, 95 episodes were treated with plasmapheresis. After propensity score matching, the final cohort consisted of 60 well-balanced pairs. Plasmapheresis was not associated with a difference in the primary composite outcome, in-hospital mortality, and organ failure (8/60 vs. 5/60; χ²(1) = 0.776; p = 0.378), nor was there any difference in the severity of pancreatitis episodes. It showed only a moderate reduction of serum triglyceride compared to the non-plasmapheresis group, but a significantly longer hospital stay in the plasmapheresis group (12 days; IQR 14 vs. 9 days; IQR 11; U = 1356; Z = -2.46; p = 0.014).</p><p><strong>Conclusions: </strong>Plasmapheresis in patients with hypertriglyceridemia-induced pancreatitis was not associated with a better clinical outcome compared with conservative treatment in this propensity score-matched retrospective cohort study. Outside clinical studies, this costly and potentially complicative treatment should be considered with caution.</p>","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145024220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time to Leave no Stone Unturned?: Long-Term Clinical Outcome of d-SOVP-Guided Lithotripsy on Quality of Life in Chronic Pancreatitis.","authors":"Charlotte L van Veldhuisen, Robert C Verdonk","doi":"10.1002/ueg2.70106","DOIUrl":"https://doi.org/10.1002/ueg2.70106","url":null,"abstract":"","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145024278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary Sclerosing Cholangitis Worsens Prognosis in Patients With Inflammatory Bowel Disease: A Propensity-Matched Cohort Study.","authors":"Ferdinando D'Amico, Mariangela Allocca, Francesca Lusetti, Tommaso Lorenzo Parigi, Francesca Rusconi, Gema Hernandez, Alba Segovia-Hilara, Virginia Solitano, Alessandra Zilli, Federica Furfaro, Gionata Fiorino, Pietro Invernizzi, Laurent Peyrin-Biroulet, Vipul Jairath, Silvio Danese","doi":"10.1002/ueg2.70058","DOIUrl":"https://doi.org/10.1002/ueg2.70058","url":null,"abstract":"<p><strong>Background: </strong>Few data are available on the impact of primary sclerosing cholangitis (PSC) on inflammatory bowel disease (IBD).</p><p><strong>Objective: </strong>We conducted a retrospective study using TriNetX to compare the outcomes of patients with IBD and those with concomitant IBD and PSC.</p><p><strong>Methods: </strong>All patients with a confirmed diagnosis of Crohn's disease (CD), ulcerative colitis (UC), or indeterminate colitis with or without PSC were eligible. One-to-one propensity score matching was employed to balance demographic parameters, comorbid conditions, and IBD medications between cohort 1 (IBD) and cohort 2 (IBD and concomitant PSC). The primary endpoint was a composite endpoint including the risk of mortality, hospitalization, and surgery. Risks were expressed as Hazard Ratio (HR) with a 95% confidence interval (CI).</p><p><strong>Results: </strong>A total of 398,980 IBD patients were analyzed (cohort 1: 395,874 and cohort 2: 3106). After propensity-score-matching, 3007 patients from each group were included (mean age 48.1 ± 19.4 years, female 40%, UC 75% CD 24.8%). Approximately 1%-2% of patients were treated with advanced therapies. Cohort 2 patients had a higher risk of experiencing the composite endpoint compared to cohort 1 group (HR:1.32, 95%CI:1.23-1.42). Similarly, a higher risk of hospitalization and mortality was identified in subjects with IBD and concomitant PSC (HR:1.32, 95% CI: 1.22-1.43 and HR: 1.69, 95%CI: 1.46-1.96). Both CD and UC patients with concomitant PSC had a higher risk of achieving the composite endpoint (HR: 1.18, 95%CI: 1.02-1.37 and HR: 1.29, 95%CI: 1.18-1.40). An increased risk of mortality and hospitalization was found both in patients with CD (HR: 2.16, 95%CI:1.58-2.95, and 1.20, 95%CI:1.03-1.41) and UC (HR: 1.87, 95%CI: 1.57-2.22 and HR: 1.27, 95%CI:1.16-1.40) and concomitant PSC.</p><p><strong>Conclusion: </strong>In this administrative study of patients with IBD and PSC, concomitant PSC was associated with an increased risk of mortality and hospitalization.</p>","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recommendations for Digital Single-Operator Cholangiopancreatoscopy: Turning Vision Into Practice!","authors":"Michiel Bronswijk, Giuseppe Vanella","doi":"10.1002/ueg2.70109","DOIUrl":"https://doi.org/10.1002/ueg2.70109","url":null,"abstract":"","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145024237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Waiting for Perfection or Acting on Reality? Burnout in Gastroenterology Needs Action Now.","authors":"Francesca Manza, Mohamed G Shiha, Martina Müller, Reena Sidhu","doi":"10.1002/ueg2.70107","DOIUrl":"https://doi.org/10.1002/ueg2.70107","url":null,"abstract":"","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145024281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vedolizumab Achieves Pan-Enteric Mucosal Healing in Crohn's Disease: A Prospective Observational Study.","authors":"Offir Ukashi, Adi Lahat, Bella Ungar, Hadar Levy, Adi Talan Asher, Pinhas Eidler, Shomron Ben-Horin, Rami Eliakim, Uri Kopylov","doi":"10.1002/ueg2.70103","DOIUrl":"https://doi.org/10.1002/ueg2.70103","url":null,"abstract":"<p><strong>Background: </strong>Mucosal healing (MH) is a key treatment goal in Crohn's disease (CD). However, evidence on pan-enteric MH (PE-MH) in CD patients treated with vedolizumab remains limited. We aimed to assess vedolizumab efficacy in achieving PE-MH using PillCam Crohn's capsule.</p><p><strong>Methods: </strong>This prospective, open-label observational study included CD patients with intestinal inflammation (SB-Lewis score [LS] ≥ 220 and/or colonic-Eliakim score [ES] > 0) who initiated vedolizumab and were followed with C-reactive protein (CRP), fecal calprotectin (FCP), and PillCam Crohn's capsule at baseline and after 14 and 52 weeks. In cases of exclusive SB involvement, colonic preparation and assessment were omitted. LS and ES were calculated when applicable. The primary outcome was PE-MH, defined as LS < 135 for SB-VCE assessment, and ES = 0 for PE-VCE assessment. Secondary outcomes included SB-MH (LS < 135), colonic-MH (ES = 0) and biochemical remission (FCP < 150 μg/g). An exploratory outcome for SB-MH was defined as a LS < 350, which has previously been shown to predict future flares in CD.</p><p><strong>Results: </strong>Of the 60 screened patients, 44 were enrolled (median age: 29.0 [22.0-45.5] years; 43.2% male; Ileum [L1]-54.5%, Colon [L2]-41.0%, Ileo-colon [L3]-4.5%). At week 52, 7/44 (15.9%) patients reached PE-MH compared to baseline (risk difference [RD] 15.9%, 95% confidence interval [CI] 5.1%-26.7%, p = 0.016). 8/44 (18.2%) and 9/44 (20.5%) patients achieved SB-MH at week 52 and 14, respectively, compared to 2/44 (4.5%) at baseline. Using the less stringent SB-MH criterion (LS < 350), rates improved significantly at week 52 versus baseline (45.5% vs. 25.0%, p = 0.049). All study indices decreased during follow-up (baseline, week 14, week 52): CRP (11.8, 5.8, 5.0: p = 0.152), FCP (758, 418, 158: p = 0.004), LS (900, 225, 225, p < 0.001), and ES (18.0, 4.0, 4.0: p < 0.001). 14/44 (31.8%) patients reached biochemical remission (p = 0.049) at week 52 compared to 5/44 (11.4%) at baseline.</p><p><strong>Conclusion: </strong>Vedolizumab treatment led to significant biochemical and endoscopic improvement, including SB-MH and PE-MH, through 52 weeks.</p>","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abdominal Bloating and Distension: Common Symptoms but Limited Evidence.","authors":"Juha Taavela, Mohamed G Shiha","doi":"10.1002/ueg2.70108","DOIUrl":"https://doi.org/10.1002/ueg2.70108","url":null,"abstract":"","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Remimazolam Preserves Oxygen Reserve and Improves Sedation Safety Compared to Propofol in Endoscopic Retrograde Cholangiopancreatography.","authors":"Jee Hoon Kim, Kyuho Lee, Sung Jin Lee, Galam Leem, Hee Seung Lee, Jeong Youp Park, Seungmin Bang, Seung Woo Park, Namo Kim, Moon Jae Chung","doi":"10.1002/ueg2.70105","DOIUrl":"https://doi.org/10.1002/ueg2.70105","url":null,"abstract":"<p><strong>Background: </strong>Remimazolam is a short-acting benzodiazepine with less cardiorespiratory depression compared with propofol. The Oxygen Reserve Index (ORi) reflects oxygenation status in the mild hyperoxic range and can detect subtle respiratory depression induced by sedatives.</p><p><strong>Objective: </strong>We compared remimazolam and propofol in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) and assessed the ORi to evaluate the impact of these sedatives on oxygen reserve.</p><p><strong>Methods: </strong>Patients scheduled for ERCP were enrolled and randomly assigned to either the remimazolam or the propofol group. They received 0.1 mg kg^-1 remimazolam or 1.0 mg kg^-1 propofol, with bolus injections of either 2 mg remimazolam or 20 mg propofol added as required, according to the group allocation. The primary outcome was the incidence of oxygen reserve depletion, defined as an ORi reduction to 0.00.</p><p><strong>Results: </strong>Among the 102 patients, oxygen reserve depletion was more frequent in the propofol group (70.6% vs. 41.2%, odds ratio 0.29, 95% confidence interval 0.13-0.66, p = 0.003). The time from sedative injection to endoscope insertion, length of stay in the recovery room, and overall procedure time were comparable between the groups. Patients in the remimazolam group reported a lower incidence of procedural recall, fewer complaints of inadequate sedation, and higher satisfaction scores than those in the propofol group.</p><p><strong>Conclusions: </strong>Remimazolam effectively preserved the oxygen reserve compared with propofol, lowering the risk of hypoxia during sedation. Remimazolam was also associated with more favorable recovery profiles for patients undergoing ERCP, making it a safe and preferred sedative for this procedure.</p><p><strong>Trail registration: </strong>Clinicaltrials.gov: NCT06359834.</p>","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}