Victor W S Kung, John Broad, Raj Makwana, Alexandra Palmer, Nicholas Baidoo, Sarah Epton, Shezan Elahi, Joanne Chin-Aleong, Mohamed Thaha, Charles H Knowles, Gareth J Sanger
{"title":"The impact of long-course chemoradiotherapy on the myenteric plexus, neuromuscular functions and responses to prokinetic drugs in the human rectum.","authors":"Victor W S Kung, John Broad, Raj Makwana, Alexandra Palmer, Nicholas Baidoo, Sarah Epton, Shezan Elahi, Joanne Chin-Aleong, Mohamed Thaha, Charles H Knowles, Gareth J Sanger","doi":"10.1002/ueg2.12653","DOIUrl":"10.1002/ueg2.12653","url":null,"abstract":"<p><strong>Background & aims: </strong>The long-term effects of chemoradiotherapy on human rectum are poorly understood. The aims were to investigate changes in inflammatory status, myenteric neuron numbers/phenotype, neuromuscular functions and prokinetic drug efficacy.</p><p><strong>Methods: </strong>Macroscopically normal proximal-to-mid rectum was obtained from 21 patients undergoing surgery for bowel cancer, 98 days (range: 63-350) after concurrent capecitabine and pelvic radiotherapy, and 19 patients without chemoradiotherapy. Inflammatory status was measured by H&E, CD45 staining and qPCR. Myenteric neurons were examined by immunohistochemistry. Neuromuscular functions and drug efficacy were studied using exogenous agents and electrical field stimulation (EFS) to activate intrinsic nerves.</p><p><strong>Results: </strong>Inflammation was not detected. Numbers of myenteric ganglia/neurons were unchanged (11.7 ± 2.4 vs. 10.3 ± 2.2 neurons/mm myenteric plexus with/without chemoradiotherapy) as were the numbers of cholinergic/nitrergic neurons. EFS stimulated cholinergic and nitrergic neurons so the contractile response of the muscle was the sum of both but dominated by cholinergic (causing contraction) or less often, nitrergic activity (relaxation), followed, after termination of EFS, by neuronally mediated contraction. Inhibition of nitric oxide synthase (by L-NAME 300 μM) more clearly defined EFS-evoked contractions. The 5-HT<sub>4</sub> agonist prucalopride 10 μM and the cholinesterase inhibitor donepezil 1 µM, respectively increased and greatly increased the composite contractile response to EFS (measured as 'area-under-the curve') and the contractions isolated by L-NAME (respectively, by 22 ± 14% and 334 ± 87%; n = 11/8). After chemoradiotherapy, nitrergic-mediated muscle relaxations occurred more often during EFS (in 29.8 ± 6.1% preparations vs. 12.6 ± 5.1% without chemoradiotherapy, n = 21/18). With L-NAME, the ability of prucalopride to facilitate EFS-evoked contraction was lost and that of donepezil approximately halved (contractions increased by 132 ± 36%; n = 8).</p><p><strong>Conclusions: </strong>Several months after chemoradiotherapy, the rectum was not inflamed and myenteric neuron numbers/phenotype unchanged. However, nitrergic activity was increased relative to cholinergic activity, and prokinetic-like drug activity was lost or greatly reduced. Thus, chemoradiotherapy causes long-term changes in neuromuscular functions and markedly reduces the efficacy of drugs for treating constipation.</p>","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":"1417-1428"},"PeriodicalIF":5.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wei-Ying Chen, Yi-Peng Lu, Yu-Wen Chien, Li-Jung Elizabeth Ku, Jung-Der Wang
{"title":"Impact of colorectal cancer screening programme on survival and employment in Taiwan: A nationwide analysis of real-world data.","authors":"Wei-Ying Chen, Yi-Peng Lu, Yu-Wen Chien, Li-Jung Elizabeth Ku, Jung-Der Wang","doi":"10.1002/ueg2.12685","DOIUrl":"10.1002/ueg2.12685","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) leads to life loss and a significant economic burden, which could be reduced by CRC screening.</p><p><strong>Objective: </strong>We assessed the potential savings of lives and employment to evaluate the effectiveness of the Taiwan CRC Screening Programme.</p><p><strong>Methods: </strong>Through interlinkages among Taiwan Cancer Registry, National Mortality Registry, Taiwan CRC Screening Database, and National Health Insurance claim data, we enroled patients with colorectal adenocarcinoma, aged 50-74 years and diagnosed during 2004-2017, and followed them up to 2018. Life expectancy (LE), lifetime employment duration (LED), loss-of-LE and loss-of-LED were calculated, compared with age-, sex- and calendar year-matched cohorts. Assuming no difference within a specific stage for screen-detected versus non-screen detected CRC and weighting them by different stage distributions, we compared the total loss-of-LE and loss-of-LED.</p><p><strong>Results: </strong>The cohort enroled 77,169 patients with colorectal adenocarcinoma, which included 31,728 women (mean [SD] age, 62.5 [7.1] years) and 45,441 men (mean [SD] age, 62.8 [6.8] years). The mean loss-of-LE and loss-of-LED in women were 6.0 (95% confidence interval [CI] 5.7-6.3) and 1.0 (95% CI 0.8-1.1) year(s), whereas those in men were 5.1 (95% CI 4.9-5.4) and 1.1 (95% CI 1.0-1.2) years, respectively. Among the cohort, 53,678 cases had the screening information. On average, screening potentially saved 2.9 (95% CI 2.6-3.2) years of life expectancy plus 0.5 (95% CI 0.4-0.6) years of employment per case in women and 2.7 (95% CI 2.5-3.0) years plus 0.6 (95% CI 0.5-0.7) years in men, respectively.</p><p><strong>Conclusion: </strong>The Taiwan CRC Screening Programme is associated with the savings of lives and employment duration. Future studies are warranted to evaluate the cost-effectiveness of beginning screening at a younger age after accounting for saving employment loss and possibly adjusting lead time bias.</p>","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":"1450-1460"},"PeriodicalIF":5.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nodular Regenerative Hyperplasia: Report of 82 Patients and Systematic Review of Literature.","authors":"Edeline Kaze, Pamela Baldin, Hubert Piessevaux, Géraldine Dahlqvist","doi":"10.1002/ueg2.12708","DOIUrl":"10.1002/ueg2.12708","url":null,"abstract":"<p><strong>Background: </strong>Data about the clinical significance and outcome of patients with nodular regenerative hyperplasia are limited.</p><p><strong>Objective: </strong>The aim of this study was to describe the clinical and histopathological characteristics of patients with nodular regenerative hyperplasia and compare our findings with the literature.</p><p><strong>Methods: </strong>From January 2015 to March 2021, patients with a diagnosis of nodular regenerative hyperplasia were included. They were extracted from the database of the pathology department of Cliniques universitaires Saint-Luc. Clinical and histological data were retrospectively recorded and complications of portal hypertension and mortality were analyzed. We also performed a systematic review of the literature.</p><p><strong>Results: </strong>Eighty-two histology-proven nodular regenerative hyperplasia were included. The mean age at diagnosis was 58 ± 14 years. At least one clinical sign of portal hypertension was present in 37 patients (45%), and liver tissue sampling was performed for 29 of them for evaluation of portal hypertension. Conversely, nodular regenerative hyperplasia was an incidental discovery in 27 patients (33%), mostly after liver resection for metastasis (n = 15) or protocol biopsy in liver-transplanted patients (n = 9). The 5-year liver-related mortality was 5%. The 5-year non-liver-related mortality was 20%. Patients diagnosed by clinical suspicion (n = 55) were compared to patients diagnosed incidentally (n = 27). Patients with an incidental diagnosis had more frequently a condition associated with nodular regenerative hyperplasia than patients diagnosed clinically (93% vs. 66%, p = 0.008) and they developed significantly lower liver-related complications (4% vs. 27%, p = 0.01). A systematic review allowed us to compare our patients with 10 case series in the literature.</p><p><strong>Conclusion: </strong>The clinical spectrum of patients with nodular regenerative hyperplasia is heterogeneous, including patients with clinical liver manifestations and patients diagnosed incidentally who could remain free of liver-related complications. This suggests that nodular regenerative hyperplasia could be a histological epiphenomenon as well as a clinical entity.</p>","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":"1404-1416"},"PeriodicalIF":5.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"UEG Journal and Impact on Clinical Practice.","authors":"Joost P H Drenth","doi":"10.1002/ueg2.12722","DOIUrl":"10.1002/ueg2.12722","url":null,"abstract":"","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":"1340-1341"},"PeriodicalIF":5.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Upadacitinib Versus Filgotinib in Ulcerative Colitis: Is the Evidence Sufficient to Inform Treatment Decisions?","authors":"Sudheer Kumar Vuyyuru, Yuhong Yuan, Vipul Jairath","doi":"10.1002/ueg2.12709","DOIUrl":"10.1002/ueg2.12709","url":null,"abstract":"","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":"1344-1345"},"PeriodicalIF":5.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nik Dekkers, Hao Dang, Manon de Graaf, Kate Nobbenhuis, Daan A Verhoeven, Jolein van der Kraan, Wouter H de Vos Tot Nederveen Cappel, Alaa Alkhalaf, Henderik L van Westreenen, Kirill Basiliya, Koen C M J Peeters, Marinke Westerterp, Pascal G Doornebosch, James C H Hardwick, Alexandra M J Langers, Jurjen J Boonstra
{"title":"T1 colorectal cancer patients' perspective on information provision and therapeutic decision-making after local resection.","authors":"Nik Dekkers, Hao Dang, Manon de Graaf, Kate Nobbenhuis, Daan A Verhoeven, Jolein van der Kraan, Wouter H de Vos Tot Nederveen Cappel, Alaa Alkhalaf, Henderik L van Westreenen, Kirill Basiliya, Koen C M J Peeters, Marinke Westerterp, Pascal G Doornebosch, James C H Hardwick, Alexandra M J Langers, Jurjen J Boonstra","doi":"10.1002/ueg2.12628","DOIUrl":"10.1002/ueg2.12628","url":null,"abstract":"<p><strong>Background: </strong>Decision-making after local resection of T1 colorectal cancer (T1CRC) is often complex and calls for optimal information provision as well as active patient involvement.</p><p><strong>Objective: </strong>The aim was to evaluate the perceptions of patients with T1CRC on information provision and therapeutic decision-making.</p><p><strong>Methods: </strong>This multicenter cross-sectional study included patients who underwent endoscopic or local surgical resection as initial treatment. Information provision was assessed using the EORTC QLQ-INFO25 questionnaire. In patients with high-risk T1CRC, we evaluated decisional involvement and satisfaction regarding the choice as to whether to undergo additional treatment after local resection, and the level of decisional conflict using the Decisional Conflict Scale.</p><p><strong>Results: </strong>Ninety-eight patients with T1CRC were included (72% response rate; 79/98 endoscopic and 19/98 local surgical resection; 45/98 high-risk T1CRC). Median time since local resection was 28 months (IQR 18); none had developed recurrence. Unmet information needs were reported by 29 patients (30%; 18 low-risk, 11 high-risk), mostly on post-treatment related topics (follow-up visits, recovery time, recurrence prevention). After local resection, 24 of the 45 high-risk patients (53%) underwent additional treatment, while others were subjected to surveillance. Higher-educated patients were more often actively involved in decision-making (93% vs. 43%, p = 0.002) and more frequently underwent additional treatment (79% vs. 40%, p = 0.02). Decisional conflict (p = 0.19) and satisfaction (p = 0.78) were comparable between higher- and lower-educated high-risk patients.</p><p><strong>Conclusion: </strong>Greater attention should be given to the post-treatment course during consultations following local T1CRC resection. The differences in decisional involvement and selected management strategies between higher- and lower-educated high-risk patients warrant further investigation.</p>","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":"1367-1377"},"PeriodicalIF":5.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141731435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Derk C F Klatte, Jihane Meziani, Djuna L Cahen, Merel van Diepen, Marco J Bruno, Monique E van Leerdam
{"title":"Pancreatic cancer surveillance: Risk stratification of individuals with a germline CDKN2A pathogenic variant.","authors":"Derk C F Klatte, Jihane Meziani, Djuna L Cahen, Merel van Diepen, Marco J Bruno, Monique E van Leerdam","doi":"10.1002/ueg2.12662","DOIUrl":"10.1002/ueg2.12662","url":null,"abstract":"<p><strong>Background: </strong>Individuals carrying a germline CDKN2A pathogenic variant (PV) are at a high risk of developing pancreatic ductal adenocarcinoma. Risk stratification could allow tailored surveillance.</p><p><strong>Objective: </strong>To develop a Fine-Gray prediction model for the risk of PDAC in carriers of a CDKN2A PV.</p><p><strong>Methods: </strong>Data from two large Dutch pancreatic cancer surveillance programs were used. A limited set of predictor variables were selected bsased on previous literature and the clinical expertise of the study group.</p><p><strong>Results: </strong>A total of 506 CDKN2A PV carriers were included, among whom we showed a substantial lifetime risk of PDAC (23%). The model identifies having a first-degree relative with PDAC (B = 0.7256) and a history of smoking (B = 0.4776) as significant risk factors. However, the model shows limited discrimination (c-statistic 0.64) and calibration.</p><p><strong>Conclusion: </strong>Our study highlights the high lifetime risk of PDAC in carriers of a CDKN2A PV. While identifying significant risk factors such as family history of PDAC and smoking, our prediction model shows limited precision, highlighting the need for additional factors such as biomarkers to improve its clinical utility for tailored surveillance of high-risk individuals.</p>","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":"1399-1403"},"PeriodicalIF":5.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Louis Onghena, Yves van Nieuwenhove, Hans Van Vlierberghe, Lindsey Devisscher, Sarah Raevens, Xavier Verhelst, Sander Lefere, Anja Geerts
{"title":"Prior metabolic and bariatric surgery is an independent determinant of severity of decompensation in alcohol-associated liver disease.","authors":"Louis Onghena, Yves van Nieuwenhove, Hans Van Vlierberghe, Lindsey Devisscher, Sarah Raevens, Xavier Verhelst, Sander Lefere, Anja Geerts","doi":"10.1002/ueg2.12642","DOIUrl":"10.1002/ueg2.12642","url":null,"abstract":"<p><strong>Background: </strong>Patients with a history of metabolic and bariatric surgery (MBS) are susceptible to developing alcohol use disorder, potentially resulting in end-stage liver disease, with a paucity of data on the evolution of cirrhosis.</p><p><strong>Aims: </strong>Our aim was to describe the demographics and mortality in hospitalizations over time in individuals diagnosed with cirrhosis due to alcohol-associated liver disease (ALD) in relation to prior MBS.</p><p><strong>Methods: </strong>We included patients hospitalized at the Ghent University Hospital between 1/1/2010 and 01/09/2023 with cirrhosis due to ALD. Data were retrieved retrospectively from all hospitalizations.</p><p><strong>Results: </strong>46/275 (16.7%) of individuals with cirrhosis admitted with ALD had a history of MBS; they were predominantly female (76.1%), in contrast to the non-MBS population (29.7%) (p < 0.0001) and were significantly younger at the time of diagnosis (46 vs. 58 years, p < 0.0001). Liver disease evolved at a faster pace in the MBS group with a shorter time to first hospitalization (5 vs. 13 months, p = 0.036), and consecutive hospitalizations. The proportion with primary hospitalization due to acute-on-chronic liver failure (ACLF) was significantly larger in the MBS group (60.9% vs. 27.6%, p < 0.0001), and throughout the following hospitalizations, ACLF remained more prevalent in the MBS group. Modeled transplant-free survival was lower in the MBS group (p = 0.004), with ACLF as the main cause of death. The weekly amount of alcohol consumed during drinking periods and duration of use were significantly lower in the MBS group.</p><p><strong>Conclusions: </strong>MBS patients hospitalized with ALD develop acute decompensation at a faster pace, with more overall ACLF hospitalizations, and higher cumulative mortality, despite being 12 years younger on average.</p><p><strong>Clinical trial registration: </strong>Not applicable.</p>","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":"1440-1449"},"PeriodicalIF":5.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mucosal Healing in Inflammatory Bowel Diseases: Still too Many Irons on the Fire.","authors":"Gabrio Bassotti, Vincenzo Villanacci","doi":"10.1002/ueg2.12707","DOIUrl":"10.1002/ueg2.12707","url":null,"abstract":"","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":"1509-1510"},"PeriodicalIF":5.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}