Alica K Beutel, Menar Ekizce, Thomas J Ettrich, Thomas Seufferlein, Jessica Lindenmayer, Johann Gout, Alexander Kleger
{"title":"Organoid-based precision medicine in pancreatic cancer.","authors":"Alica K Beutel, Menar Ekizce, Thomas J Ettrich, Thomas Seufferlein, Jessica Lindenmayer, Johann Gout, Alexander Kleger","doi":"10.1002/ueg2.12701","DOIUrl":"https://doi.org/10.1002/ueg2.12701","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) ranks among the leading causes of cancer-related deaths worldwide. Despite advances in precision oncology in other malignancies, treatment of PDAC still largely relies on conventional chemotherapy. Given the dismal prognosis and heterogeneity in PDAC, there is an urgent need for personalized therapeutic strategies to improve treatment response. Organoids, generated from patients' tumor tissue, have emerged as a powerful tool in cancer research. These three-dimensional models faithfully recapitulate the morphological and genetic features of the parental tumor and retain patient-specific heterogeneity. This review summarizes existing precision oncology approaches in PDAC, explores current applications and limitations of organoid cultures in personalized medicine, details preclinical studies correlating in vitro organoid prediction and patient treatment response, and provides an overview of ongoing organoid-based clinical trials.</p>","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629447","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":"Differences in the burden of pediatric pancreatitis across countries and regions: One size does not fit all.","authors":"Chinenye Rebecca Dike, Sohail Z Husain","doi":"10.1002/ueg2.12665","DOIUrl":"https://doi.org/10.1002/ueg2.12665","url":null,"abstract":"","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606611","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":"Tofacitinib in chronic pouchitis: A step towards addressing an unmet need.","authors":"Jacob E Ollech","doi":"10.1002/ueg2.12691","DOIUrl":"https://doi.org/10.1002/ueg2.12691","url":null,"abstract":"","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606621","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 for Crohn's disease: Real-world efficacy through a meta-analytical lens.","authors":"Maria Manuela Estevinho, Virginia Solitano","doi":"10.1002/ueg2.12690","DOIUrl":"https://doi.org/10.1002/ueg2.12690","url":null,"abstract":"","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606624","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":"Early colorectal cancer diagnosis: A novel methylated stool DNA model enhanced the diagnostic efficiency.","authors":"Peng Yun, Kamila Kulaixijiang, Jiang Pan, Luping Yang, Nengzhuang Wang, Zheng Xu, Yaodong Zhang, Haifang Cai, Zi-Ye Zhao, Min Zhu, Hongli Yan","doi":"10.1002/ueg2.12696","DOIUrl":"https://doi.org/10.1002/ueg2.12696","url":null,"abstract":"<p><strong>Background: </strong>Methylated stool DNA (sDNA) is a reliable noninvasive biomarker for early colorectal cancer (CRC) diagnosis. However, there are barely any diagnostic panels that can achieve both a sensitivity and specificity exceeding 90% simultaneously.</p><p><strong>Objective: </strong>We aimed to identify a novel methylated sDNA panel and model for the early diagnosis of CRC.</p><p><strong>Methods: </strong>We conducted methyl-CpG binding domain isolated genome sequencing (MiGS) on CpG island methylation phenotype (CIMP)-positive (n = 3) and CIMP-negative CRC tissues (n = 3) and their corresponding normal adjacent tissues. Subsequently, by utilizing both the aforementioned data and public datasets, we identified a set of promising methylated sDNA markers for CRC. Next, we validated 5 of these genes using pyrosequencing in CRC patients (n = 31). Then, we developed a combined diagnostic model (CDM) for CRC based on the methylation status of PRDM12, FOXE1, and SDC2 by a Training cohort (n = 231). Finally, the performance of CDM was evaluated in an independent multicenter Validation cohort (n = 800).</p><p><strong>Results: </strong>A total of 1062 participants were included in this study. The area under the curve (AUC) of the CDM was 0.979 (95% CI: 0.960-0.997), and the optimal sensitivity and specificity were 97.35% and 99.05%, respectively, in the training cohort (n = 231). In the independent validation cohort (n = 800), the AUC was 0.950 (95% CI: 0.927-0.973), along with the optimal sensitivity of 92.75% and specificity of 97.21%. When CRC and advanced adenoma (AAD) were used as diagnostic targets, the model AUC was 0.945 (95% CI: 0.922-0.969), with an optimal sensitivity of 91.89% and a specificity of 95.21%. The model sensitivity for nonadvanced adenoma patients was 68.66%.</p><p><strong>Conclusion: </strong>The sDNA diagnostic model CDM, developed from both CIMP-P and CIMP-N, exhibited exceptional performance in CRC and could serve as a potential alternative strategy for CRC screening.</p>","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564771","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}
Marjolijn Duijvestein, Reena Sidhu, Katharina Zimmermann, Emma V Carrington, Alexander Hann, Paula Sousa, Hugo R W Touw, Jeanin E van Hooft, Martina Müller
{"title":"The United European Gastroenterology green paper-climate change and gastroenterology.","authors":"Marjolijn Duijvestein, Reena Sidhu, Katharina Zimmermann, Emma V Carrington, Alexander Hann, Paula Sousa, Hugo R W Touw, Jeanin E van Hooft, Martina Müller","doi":"10.1002/ueg2.12698","DOIUrl":"10.1002/ueg2.12698","url":null,"abstract":"<p><p>Climate change, described by the World Health Organization (WHO) in 2021 as 'the single biggest health threat facing humanity', causes extreme weather, disrupts food supplies, and increases the prevalence of diseases, thereby affecting human health, medical practice, and healthcare stability. Greener Gastroenterology is an important movement that has the potential to make a real difference in reducing the impact of the delivery of healthcare, on the environment. The WHO defines an environmentally sustainable health system as one which would improve, maintain or restore health while minimizing negative environmental impacts. Gastroenterologists encounter the impacts of climate change in daily patient care. Alterations in the gut microbiome and dietary habits, air pollution, heat waves, and the distribution of infectious diseases result in changed disease patterns affecting gastrointestinal and hepatic health, with particularly severe impacts on vulnerable groups such as children, adolescents, and the elderly. Additionally, women are disproportionally affected, since climate change can exacerbate gender inequalities. Paradoxically, while healthcare aims to improve health, the sector is responsible for 4.4% of global carbon emissions. Endoscopy is a significant waste producer in healthcare, being the third highest generator with 3.09 kg of waste per day per bed, contributing to the carbon footprint of the GI sector. Solutions to the climate crisis can offer significant health co-benefits. Steps to reduce our carbon footprint include fostering a Planetary Health Diet and implementing measures for greener healthcare, such as telemedicine, digitalization, education, and research on sustainable healthcare practices. Adhering to the principles of 'reduce, reuse, recycle' is crucial. Reducing unnecessary procedures, which constitute a significant portion of endoscopies, can significantly decrease the carbon footprint and enhance sustainability. This position paper by the United European Gastroenterology aims to raise awareness and outline key principles that the GI workforce can adopt to tackle the climate crisis together.</p>","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":"1292-1305"},"PeriodicalIF":5.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508941","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}
Nikhilesh R Mazumder, Filip Jezek, Sardar Ansari, Elliot B Tapper, Anna S Lok
{"title":"The physiological determinants of symptom burden in cirrhosis with ascites.","authors":"Nikhilesh R Mazumder, Filip Jezek, Sardar Ansari, Elliot B Tapper, Anna S Lok","doi":"10.1002/ueg2.12675","DOIUrl":"10.1002/ueg2.12675","url":null,"abstract":"<p><strong>Background & aims: </strong>Paracentesis is commonly used to manage patient discomfort due to ascites. The relationship between ascites pressure, ascites volume, and patient discomfort has not been elucidated.</p><p><strong>Methods: </strong>We prospectively enrolled adult patients with non-malignant ascites undergoing outpatient therapeutic paracenteses from 2021 to 2024 at a tertiary care hospital. Patients completed a validated symptom questionnaire (ASI-7, maximum score 35) before, immediately after, and 1 week after paracentesis. An open-ended manometer was used to measure ascites pressure at the beginning and end of paracentesis. Mixed effect linear regression was performed to evaluate the relationships between patient characteristics, pressure, volume, and symptoms.</p><p><strong>Results: </strong>One hundred and fifty paracentesis procedures among 48 unique patients with an average Model for End Stage Liver Disease-Sodium 3.0 of 16.7 were included. An average of 6.5 L was drained, which reduced abdominal pressure from a mean of 13.7 to 6.0 cm H<sub>2</sub>O (10.1 to 4.4 mmHg, p < 0.001) and mean symptom score from 22.6 to 6.5 (p < 0.001). Regression models identified that symptoms and abdominal pressure linearly correlated above a pressure of 6 cm H<sub>2</sub>O or ASI-7 score of 16 (p < 0.01). Taller patients required about 670 ml additional drainage per inch above the cohort mean height (5'8″) to achieve the same symptom relief.</p><p><strong>Conclusions: </strong>Pressure measured at the bedside can be used to explore changes in abdominal pressure during paracentesis. Pressure, volume, and patient level factors such as height contribute to patient symptoms but cannot fully explain discomfort associated with ascites and relief after paracentesis.</p>","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":"1222-1229"},"PeriodicalIF":5.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393723","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}
Stefan Schreiber, Brian G Feagan, Edouard Louis, Tadakazu Hisamatsu, Toshifumi Hibi, Louis Dron, Corinne Jamoul, Haridarshan Patel, Kristina Harris, Virginia Taliadouros, Alessandra Oortwijn, Laurent Peyrin-Biroulet
{"title":"Distinct trajectories of symptomatic response in ulcerative colitis during filgotinib therapy: A post hoc analysis from the SELECTION study.","authors":"Stefan Schreiber, Brian G Feagan, Edouard Louis, Tadakazu Hisamatsu, Toshifumi Hibi, Louis Dron, Corinne Jamoul, Haridarshan Patel, Kristina Harris, Virginia Taliadouros, Alessandra Oortwijn, Laurent Peyrin-Biroulet","doi":"10.1002/ueg2.12686","DOIUrl":"10.1002/ueg2.12686","url":null,"abstract":"<p><strong>Background: </strong>Filgotinib is an oral, once-daily, Janus kinase 1 preferential inhibitor approved for treatment of ulcerative colitis (UC) following the phase 2b/3 SELECTION trial. Identification of patient populations and factors associated with long-term treatment response trajectories may improve UC management.</p><p><strong>Objective: </strong>We aimed to identify and describe distinct patient subgroups of response to filgotinib based on partial Mayo Clinic Score (pMCS) trajectories over time.</p><p><strong>Methods: </strong>In these post hoc analyses of SELECTION, group-based trajectory modeling (GBTM) was applied to pMCS to describe groups of distinct, symptom-based patient trajectories using data from patients who responded to filgotinib 200 or 100 mg and continued receiving filgotinib up to week 58. Patient demographics, disease characteristics, and week 10 response were compared between the groups. Achievement of a patient-level multi-component endpoint of comprehensive disease control (CDC) was assessed in each group.</p><p><strong>Results: </strong>GBTM identified five distinct patient populations with different response trajectories; 67.5% of patients had beneficial trajectories. The beneficial trajectory groups generally had higher proportions of patients who were recently diagnosed (<1 year), were receiving filgotinib 200 mg and were biologic-naive versus the relapsing trajectory groups (4%-9% vs. 4%-5%; 43%-65% vs. 36%-46%; 54%-70% vs. 35%-58%, respectively). Furthermore, 55.4% of patients had sustained beneficial trajectories, with low baseline endoscopic subscores (≥43% of patients had a subscore of 2) and strong week 10 FCP responses (≥61% of patients with >50% decrease in FCP from baseline). Sustained beneficial trajectory groups had a higher probability of achieving CDC at week 58 than other groups (31%-32% vs. 0%-7%).</p><p><strong>Conclusions: </strong>Beneficial long-term response trajectories and achievement of CDC with filgotinib were associated with being biologic-naive and having less severe disease at baseline. Early estimation of sustained and CDC may facilitate patient identification and development of personalized management strategies in UC.</p><p><strong>Clinicaltrials: </strong></p><p><strong>Gov identifier: </strong>NCT02914522.</p>","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":"1243-1255"},"PeriodicalIF":5.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508924","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}