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New Progress in the Study of Pathogenesis of Alcoholic Pancreatitis. 酒精性胰腺炎发病机制研究的新进展。
IF 3 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-01-17 DOI: 10.1159/000542548
Hanhui Li, Xiaoping Tan, Jie Li, Qing Zhang

Background: Alcoholic pancreatitis is a progressive condition characterized by susceptibility to recurrence, progression to chronic pancreatitis, complications, and high morbidity.

Summary: The main causes include long-term alcoholism, excessive drinking, the toxic effects of alcohol metabolites, interactions with biliary diseases, and genetic factors. Alcohol is the second leading cause of acute pancreatitis (AP) in the USA, accounting for one-third of all AP cases. A follow-up study on readmission revealed that the readmission rate of alcoholic acute pancreatitis (AAP) patients within 11 months was 43.1%, of which men dominated the admissions and readmissions of AAP. Among this population, 82.3% have alcohol use disorder, over half have tobacco use disorders, 6.7% have tobacco use disorder, 4.5% have opioid use disorder, and 18.5% of patients exhibit signs of potential alcoholic chronic pancreatitis. Numerous animal and clinical studies suggest that alcohol alone does not cause pancreatitis; rather, additional factors such as smoking, endotoxin lipopolysaccharide (LPS), genetic mutations, or other genetic predispositions - are necessary for the disease's progression.

Key messages: Given the high rates of admission and readmission for alcoholic pancreatitis, it is essential to further investigate its pathogenesis and pathological processes to develop more effective treatment strategies. Therefore, this paper summarizes the current understanding of the pathogenesis and treatment status of alcoholic pancreatitis, drawing on recently published literature and data to provide insights and references for future research and treatment efforts.

背景:酒精性胰腺炎是一种进行性疾病,其特点是易复发、进展为慢性胰腺炎、并发症和高发病率。摘要:主要原因包括长期酒精中毒、过量饮酒、酒精代谢物的毒性作用、与胆道疾病的相互作用以及遗传因素。在美国,酒精是导致急性胰腺炎(AP)的第二大原因,占所有AP病例的三分之一。一项关于再入院的随访研究显示,酒精性急性胰腺炎(AAP)患者11个月内的再入院率为43.1%,其中男性在AAP的入院和再入院中占主导地位。在这一人群中,82.3%有酒精使用障碍,一半以上有烟草使用障碍,6.7%有烟草使用障碍,4.5%有阿片类药物使用障碍,18.5%的患者表现出潜在的酒精性慢性胰腺炎的迹象。大量动物和临床研究表明,酒精本身不会引起胰腺炎;相反,其他因素,如吸烟、内毒素脂多糖(LPS)、基因突变或其他遗传易感性,对疾病的进展是必要的。鉴于酒精性胰腺炎的高入院率和再入院率,有必要进一步研究其发病机制和病理过程,以制定更有效的治疗策略。因此,本文总结了目前对酒精性胰腺炎发病机制和治疗现状的认识,并借鉴近期发表的文献和数据,为今后的研究和治疗工作提供见解和参考。
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引用次数: 0
Endocuff Vision-Assisted Colonoscopy Significantly Improves Adenoma Detection In A Shorter Withdrawal Time Compared With Standard Colonoscopy: A Randomized Controlled Trial. 与标准结肠镜检查相比,endocff视觉辅助结肠镜检查在更短的停药时间内显著提高了腺瘤的检测:一项随机对照试验。
IF 3 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-01-17 DOI: 10.1159/000543630
Duc Trong Quach, Thu Anh Nguyen, Mai Ngoc Luu, Uyen Pham-Phuong Vo, Vy Ly-Thao Tran, Truc Le-Thanh Tran, Tai Duy Nguyen, Nhan Quang Le, Toru Hiyama, Shinji Tanaka

Introduction: Although several studies in Western countries have shown that Endocuff Vision-assisted colonoscopy (EC) can improve the colorectal adenoma detection rate (ADR), such evidence in Asia is still scarce. This study aimed to evaluate the performance of EC in detecting colorectal adenomas in Vietnamese patients.

Methods: This was a randomized controlled trial conducted at a tertiary hospital in Vietnam. Subjects aged ≥ 18 years referred for colonoscopy for symptomatic investigation or screening were randomly assigned to the EC group or standard colonoscopy (SC) group. The primary outcome was the ADR. The secondary outcomes included the mean number of adenomas per procedure (MAP), caecal intubation time, and withdrawal time.

Results: There were 476 participants (241 in the EC group, 235 in the SC group) with a median age of 52 (interquartile range [IR]: 46, 58) years. There were no significant differences between the two groups regarding age, sex, smoking status, family history of colorectal cancer or indications for colonoscopy. Compared with the SC group, the EC group had significantly higher ADRs (35.7% vs. 22.6%, p = 0.002) and MAPs (0.68 vs. 0.39, p = 0.004). The intubation durations were comparable between the two groups. The withdrawal time in the EC group was shorter than that in the SC group (median [seconds]: 266 [IR: 224, 314] vs. 360 [IR: 310, 390], p < 0.001).

Conclusions: Compared with SC, EC significantly increased both the ADR and MAP in a shorter inspection time and could be a better choice for colonoscopy screening.

导论:虽然西方国家的一些研究表明,endocff Vision-assisted colonoscopy (EC)可以提高结直肠腺瘤的检出率(ADR),但在亚洲,这方面的证据仍然很少。本研究旨在评估EC在越南结直肠腺瘤检测中的表现。方法:在越南某三级医院进行随机对照试验。年龄≥18岁的受试者接受结肠镜检查进行症状调查或筛查,随机分为EC组或标准结肠镜(SC)组。主要结果是ADR。次要结果包括每次手术平均腺瘤数(MAP)、盲肠插管时间和取出时间。结果:共有476名参与者(EC组241名,SC组235名),中位年龄为52岁(四分位数间距[IR]: 46,58)岁。两组在年龄、性别、吸烟状况、结直肠癌家族史或结肠镜检查适应症方面无显著差异。与SC组相比,EC组的adr (35.7% vs. 22.6%, p = 0.002)和MAPs (0.68 vs. 0.39, p = 0.004)显著高于SC组。两组间插管时间具有可比性。EC组的停药时间短于SC组(中位[秒]:266 [IR: 224, 314]对360 [IR: 310, 390], p < 0.001)。结论:与SC相比,EC在较短的检查时间内显著提高了ADR和MAP,可作为结肠镜筛查的更好选择。
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引用次数: 0
Cost-effectiveness analysis of endoscopic treatment versus medication strategy for proton pump inhibitor-refractory gastroesophageal reflux disease. 质子泵抑制剂难治性胃食管反流病的内镜治疗与药物治疗的成本-效果分析
IF 3 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-12-30 DOI: 10.1159/000543365
Fumiaki Ishibashi, Sho Suzuki, Kentaro Mochida, Takao Tonishi, Yuichi Ishibashi

Introduction: Potassium-competitive acid blockers are effective against proton pump inhibitor-refractory gastroesophageal reflux disease; however, their long-term use is associated with economic disadvantages. Endoscopic procedures may reduce potassium-competitive acid blocker use. This study aimed to determine the optimal treatment strategy for patients with proton pump inhibitor-refractory gastroesophageal reflux disease from a cost-effectiveness perspective.

Methods: Using a Markov state transition model to simulate symptom changes in patients with proton pump inhibitor-refractory gastroesophageal reflux disease, the cost-effectiveness of two strategies was compared: endoscopic treatment (anti-reflux mucosectomy or endoscopic submucosal dissection for gastroesophageal reflux disease) followed by potassium-competitive acid blocker versus medication with high-dose potassium-competitive acid blocker. In both strategies, potassium-competitive acid blocker maintained symptoms at the lowest controllable dose. The time horizon varied from 10 to 50 years. The quality-adjusted life year and incremental cost-effectiveness ratio were calculated. Willingness-to-pay was set at 5,000,000 Japanese yen.

Results: The quality-adjusted life years gained were 0.90 and 0.95 for the endoscopic treatment and medication strategies, respectively. The incremental cost-effectiveness ratio varied with the follow-up period after the initial treatment, with the endoscopic treatment strategy being more cost-effective than the medication strategy at ≥50 years of follow-up. A dose reduction success rate of <84.1% for high-dose potassium-competitive acid blocker and an endoscopic treatment success rate of >66.8% were required to determine the superiority of the endoscopic treatment strategy at the 50-year follow-up after treatment.

Discussion/conclusions: The endoscopic treatment strategy is not cost-effective unless the patient is followed up for >50 years after the initial treatment.

导读:钾竞争酸阻滞剂对质子泵抑制剂难治性胃食管反流病有效;然而,长期使用它们会带来经济上的缺点。内镜手术可减少钾竞争性酸阻滞剂的使用。本研究旨在从成本-效果的角度确定质子泵抑制剂难治性胃食管反流病患者的最佳治疗策略。方法:采用马尔可夫状态转换模型模拟质子泵抑制剂难治性胃食管反流病患者的症状变化,比较两种策略的成本-效果:内镜治疗(抗反流粘膜切除术或内镜下粘膜剥离治疗胃食管反流病)后服用钾竞争酸阻滞剂与大剂量钾竞争酸阻滞剂。在这两种策略中,钾竞争性酸阻滞剂在最低可控剂量下维持症状。时间范围从10年到50年不等。计算质量调整寿命年和增量成本-效果比。支付意愿设定为500万日元。结果:内镜治疗和用药策略获得的质量调整生命年分别为0.90和0.95。初始治疗后的增量成本-效果比随随访时间而变化,在≥50年的随访中,内镜治疗策略比药物治疗策略更具成本效益。在治疗后50年的随访中,需要66.8%的减剂量成功率来确定内镜治疗策略的优越性。讨论/结论:内镜治疗策略不具有成本效益,除非患者在初始治疗后随访50年。
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引用次数: 0
Current status of artificial intelligence use in colonoscopy. 人工智能在结肠镜检查中的应用现状。
IF 3 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-12-26 DOI: 10.1159/000543345
Masashi Misawa, Shin-Ei Kudo

Background: Artificial intelligence (AI) has significantly impacted medical imaging, particularly in gastrointestinal endoscopy. Computer-aided detection and diagnosis systems (CADe and CADx) are thought to enhance the quality of colonoscopy procedures.

Summary: Colonoscopy is essential for colorectal cancer screening, but often misses a significant percentage of adenomas. AI-assisted systems employing deep learning offer improved detection and differentiation of colorectal polyps, potentially increasing adenoma detection rates by 8%-10%. The main benefit of CADe is in detecting small adenomas, whereas it has a limited impact on advanced neoplasm detection. Recent advancements include real-time CADe systems and CADx for histopathological predictions, aiding in the differentiation of neoplastic and non-neoplastic lesions. Biases such as the Hawthorne effect and potential overdiagnosis necessitate large-scale clinical trials to validate the long-term benefits of AI. Additionally, novel concepts such as computer-aided quality improvement systems are emerging to address limitations facing current CADe systems.

Key messages: Despite the potential of AI for enhancing colonoscopy outcomes, its effectiveness in reducing colorectal cancer incidence and mortality remains unproven. Further prospective studies are essential to establish the overall utility and clinical benefits of AI in colonoscopy.

背景:人工智能(AI)已经显著影响了医学成像,特别是胃肠道内窥镜检查。计算机辅助检测和诊断系统(CADe和CADx)被认为可以提高结肠镜检查的质量。结肠镜检查在结直肠癌筛查中是必不可少的,但经常遗漏相当比例的腺瘤。采用深度学习的人工智能辅助系统改善了结肠直肠息肉的检测和分化,可能将腺瘤的检出率提高8%-10%。CADe的主要优点是检测小腺瘤,而它对晚期肿瘤检测的影响有限。最近的进展包括用于组织病理学预测的实时CADe系统和CADx,有助于区分肿瘤和非肿瘤病变。霍桑效应和潜在的过度诊断等偏见需要大规模的临床试验来验证人工智能的长期效益。此外,计算机辅助质量改进系统等新概念正在出现,以解决当前CADe系统面临的局限性。关键信息:尽管人工智能在提高结肠镜检查结果方面具有潜力,但其在降低结直肠癌发病率和死亡率方面的有效性仍未得到证实。进一步的前瞻性研究对于确定人工智能在结肠镜检查中的整体效用和临床益处至关重要。
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引用次数: 0
Deep Learning-Based Detection of Malignant Bile Duct Stenosis in Fluoroscopy Images of Endoscopic Retrograde Cholangiopancreatography. 基于深度学习的内镜逆行胆管造影透视图像中恶性胆管狭窄的检测。
IF 3 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-12-13 DOI: 10.1159/000543049
Kien Vu Trung, Marcus Hollenbach, Gregory Patrick Veldhuizen, Oliver Lester Saldanha, Jakob Garbe, Jonas Rosendahl, Sebastian Krug, Patrick Michl, Jürgen Feisthammel, Thomas Karlas, Jochen Hampe, Albrecht Hoffmeister, Jakob Nikolas Kather

Introduction: The accurate distinction between benign and malignant biliary strictures (BS) poses a significant challenge. Despite the use of bile duct biopsies and brush cytology via endoscopic retrograde cholangiopancreaticography (ERCP), the results remain suboptimal. Single-operator cholangioscopy can enhance the diagnostic yield in BS, but its limited availability and high costs are substantial barriers. Convolutional Neural Network (CNN)-based systems may improve the diagnostic process and enhance reproducibility. Therefore, we assessed the feasibility of using deep learning to differentiate BS using fluoroscopy images during ERCP.

Methods: We conducted a retrospective review of adult patients (n=251) from three university centers in Germany (Leipzig, Dresden, Halle) who underwent ERCP. We developed and evaluated a deep learning-based model using fluoroscopy images. The performance of the classifier was evaluated by measuring the area under the receiver operating characteristic curve (AUROC) and we utilized saliency map analyses to understand the decision-making process of the model.

Results: In cross-validation experiments, malignant BS were detected with a mean AUROC of 0.89 ± 0.03. The test set of the Leipzig cohort demonstrated an AUROC of 0.90. In two independent external validation cohorts (Dresden, Halle), the deep learning-based classifier achieved an AUROC of 0.72 and 0.76, respectively. The artificial intelligence model's predictions identified plausible characteristics within the fluoroscopy images.

Conclusion: By using a deep learning model, we were able to discriminate malignant BS from benign biliary conditions. The application of artificial intelligence enhances the diagnostic yield of malignant BS and should be validated in a prospective design.

导言:准确区分良性和恶性胆道狭窄(BS)是一个重大挑战。尽管通过内窥镜逆行胆管胰胆管造影(ERCP)进行胆管活检和刷细胞学检查,结果仍然不理想。单个操作人员的胆道镜检查可以提高BS的诊断率,但其有限的可用性和高昂的费用是主要障碍。基于卷积神经网络(CNN)的系统可以改善诊断过程并提高可重复性。因此,我们评估了在ERCP期间使用透视图像使用深度学习来区分BS的可行性。方法:我们对来自德国三所大学中心(莱比锡、德累斯顿、哈雷)接受ERCP的成年患者(n=251)进行了回顾性研究。我们利用透视图像开发并评估了一种基于深度学习的模型。通过测量接收者工作特征曲线(AUROC)下的面积来评估分类器的性能,并利用显著性图分析来了解模型的决策过程。结果:在交叉验证实验中,检测到恶性BS,平均AUROC为0.89±0.03。莱比锡队列的检验集显示AUROC为0.90。在两个独立的外部验证队列(Dresden, Halle)中,基于深度学习的分类器分别实现了0.72和0.76的AUROC。人工智能模型的预测在透视图像中识别出合理的特征。结论:通过使用深度学习模型,我们能够区分恶性BS和良性胆道疾病。人工智能的应用提高了恶性BS的诊断率,应在前瞻性设计中进行验证。
{"title":"Deep Learning-Based Detection of Malignant Bile Duct Stenosis in Fluoroscopy Images of Endoscopic Retrograde Cholangiopancreatography.","authors":"Kien Vu Trung, Marcus Hollenbach, Gregory Patrick Veldhuizen, Oliver Lester Saldanha, Jakob Garbe, Jonas Rosendahl, Sebastian Krug, Patrick Michl, Jürgen Feisthammel, Thomas Karlas, Jochen Hampe, Albrecht Hoffmeister, Jakob Nikolas Kather","doi":"10.1159/000543049","DOIUrl":"https://doi.org/10.1159/000543049","url":null,"abstract":"<p><strong>Introduction: </strong>The accurate distinction between benign and malignant biliary strictures (BS) poses a significant challenge. Despite the use of bile duct biopsies and brush cytology via endoscopic retrograde cholangiopancreaticography (ERCP), the results remain suboptimal. Single-operator cholangioscopy can enhance the diagnostic yield in BS, but its limited availability and high costs are substantial barriers. Convolutional Neural Network (CNN)-based systems may improve the diagnostic process and enhance reproducibility. Therefore, we assessed the feasibility of using deep learning to differentiate BS using fluoroscopy images during ERCP.</p><p><strong>Methods: </strong>We conducted a retrospective review of adult patients (n=251) from three university centers in Germany (Leipzig, Dresden, Halle) who underwent ERCP. We developed and evaluated a deep learning-based model using fluoroscopy images. The performance of the classifier was evaluated by measuring the area under the receiver operating characteristic curve (AUROC) and we utilized saliency map analyses to understand the decision-making process of the model.</p><p><strong>Results: </strong>In cross-validation experiments, malignant BS were detected with a mean AUROC of 0.89 ± 0.03. The test set of the Leipzig cohort demonstrated an AUROC of 0.90. In two independent external validation cohorts (Dresden, Halle), the deep learning-based classifier achieved an AUROC of 0.72 and 0.76, respectively. The artificial intelligence model's predictions identified plausible characteristics within the fluoroscopy images.</p><p><strong>Conclusion: </strong>By using a deep learning model, we were able to discriminate malignant BS from benign biliary conditions. The application of artificial intelligence enhances the diagnostic yield of malignant BS and should be validated in a prospective design.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"1-24"},"PeriodicalIF":3.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Estimation of Invasion Depth of Early Colorectal Cancer Using Endoscopic Ultrasonography and Magnifying Chromoendoscopy: A Meta-Analysis. 利用内窥镜超声波检查和放大色内窥镜检查估算早期结直肠癌的浸润深度:一项荟萃分析。
IF 3 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-27 DOI: 10.1159/000542620
Runhua Chen, Yafang Huang, Fusheng Liu

Introduction: Magnifying chromoendoscopy (MCE) and endoscopic ultrasonography (EUS) are often used as diagnostic tools to estimate the depth of invasion in early colorectal cancers (CRCs). The aim of this study was to compare MCE with EUS in distinguishing between slight submucosal invasion (invasion depth <1,000 μm) and massively submucosal invasion in patients with early CRCs, since slight submucosal invasion is currently considered as an indication for endoscopic resection and submucosal cancer with massively submucosal invasion should be surgically treated due to an increased risk of lymph node metastasis.

Methods: For this meta-analysis, relevant studies were identified from PubMed, Embase, and the Cochrane Library databases between the time of the establishment and April 2023. Data on the yield of tumors were extracted, pooled, and analyzed by STATA15.0 software. The sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio in differentiating massive submucosal invasion from slight submucosal invasion were calculated for both diagnostic modalities.

Results: Twenty-six studies involving 12,586 lesions were included: sixteen were studies on MCE and 7 were studies on EUS and 3 were studies on both MCE and EUS. The pooled sensitivity of MCE was 0.78 (95% CI 0.72-0.83), the specificity was 0.95 (0.95% CI 0.91-0.97), the positive likelihood ratio was 15.4 (0.95% CI 8.7-27.4), and the negative likelihood ratio was 0.23 (0.95% CI 0.18-0.30). The pooled sensitivity of EUS was 0.88 (95% CI 0.81-0.93), the specificity was 0.87 (0.95% CI 0.80-0.91), the positive likelihood ratio was 6.7 (0.95% CI 4.4-10.3), and the negative likelihood ratio was 0.13 (0.95% CI 0.08-0.23).

Conclusion: The sensitivity tended to be higher in EUS than MCE for early CRCs with massively submucosal invasion, whereas the specificity was significantly lower in EUS than in MCE.

导言:放大色内镜(MCE)和内镜超声检查(EUS)通常被用作诊断工具,以估计早期结直肠癌(CRC)的侵犯深度。本研究的目的是比较 MCE 和 EUS 在区分轻微粘膜下侵犯(侵犯深度
{"title":"Estimation of Invasion Depth of Early Colorectal Cancer Using Endoscopic Ultrasonography and Magnifying Chromoendoscopy: A Meta-Analysis.","authors":"Runhua Chen, Yafang Huang, Fusheng Liu","doi":"10.1159/000542620","DOIUrl":"10.1159/000542620","url":null,"abstract":"<p><strong>Introduction: </strong>Magnifying chromoendoscopy (MCE) and endoscopic ultrasonography (EUS) are often used as diagnostic tools to estimate the depth of invasion in early colorectal cancers (CRCs). The aim of this study was to compare MCE with EUS in distinguishing between slight submucosal invasion (invasion depth <1,000 μm) and massively submucosal invasion in patients with early CRCs, since slight submucosal invasion is currently considered as an indication for endoscopic resection and submucosal cancer with massively submucosal invasion should be surgically treated due to an increased risk of lymph node metastasis.</p><p><strong>Methods: </strong>For this meta-analysis, relevant studies were identified from PubMed, Embase, and the Cochrane Library databases between the time of the establishment and April 2023. Data on the yield of tumors were extracted, pooled, and analyzed by STATA15.0 software. The sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio in differentiating massive submucosal invasion from slight submucosal invasion were calculated for both diagnostic modalities.</p><p><strong>Results: </strong>Twenty-six studies involving 12,586 lesions were included: sixteen were studies on MCE and 7 were studies on EUS and 3 were studies on both MCE and EUS. The pooled sensitivity of MCE was 0.78 (95% CI 0.72-0.83), the specificity was 0.95 (0.95% CI 0.91-0.97), the positive likelihood ratio was 15.4 (0.95% CI 8.7-27.4), and the negative likelihood ratio was 0.23 (0.95% CI 0.18-0.30). The pooled sensitivity of EUS was 0.88 (95% CI 0.81-0.93), the specificity was 0.87 (0.95% CI 0.80-0.91), the positive likelihood ratio was 6.7 (0.95% CI 4.4-10.3), and the negative likelihood ratio was 0.13 (0.95% CI 0.08-0.23).</p><p><strong>Conclusion: </strong>The sensitivity tended to be higher in EUS than MCE for early CRCs with massively submucosal invasion, whereas the specificity was significantly lower in EUS than in MCE.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"1-19"},"PeriodicalIF":3.0,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effects of a Protease Inhibitor Camostat Mesilate on Gut Microbial Function in Patients with Irritable Bowel Syndrome: A Pilot Randomized Placebo-Controlled Study. 蛋白酶抑制剂甲磺酸卡莫司他对肠易激综合征患者肠道微生物功能的影响:随机安慰剂对照试验研究。
IF 3 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-25 DOI: 10.1159/000542758
Motoyori Kanazawa, Kentaro Miyamoto, Michiko Kano, Kyoko Inooka, Kentaro Oka, Motomichi Takahashi, Nariyasu Mano, Shin Fukudo

Introduction: Increased fecal protease activity, which may induce visceral hypersensitivity, has been observed in patients with irritable bowel syndrome (IBS). Serine proteases modulate FK506 binding protein (FKBP)-type peptidylprolyl cis-trans isomerase (PPIase) activity associated with immune and glucocorticoid receptor functions. The aim was to investigate whether camostat mesilate (CM), a serine protease inhibitor, modifies fecal bacterial function related to FKBP-type PPIases in patients with IBS.

Methods: Randomly assigned 16 patients with IBS received 200 mg po tid of CM and 16 patients received placebo for 14 days. Self-reported adequate relief (AR) as a primary endpoint, IBS Symptom Severity Scale (IBS-SSS), and colonic motor and pain thresholds to colorectal distention were assessed before and after treatment. The fecal bacterial content was inferred from 16S rRNA gene sequence data using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States and the Kyoto Encyclopedia of Genes and Genomes database.

Results: CM significantly increased the relative abundance of Streptococcus and the functional abundances of serine protease and FKBP-type PPIase FkpA, FklB and SlyD more than placebo after treatment. CM treatment was not superior to placebo in proportion of AR although colonic motor response partially changed.

Conclusion: CM modulated the fecal microbiome composition and functional potentials that are related to FKBP-type PPIase activity in IBS patients. These findings suggest that protease inhibitors may modify gut microbial function along with abnormal immunological and/or stress responses that underlie pathophysiology of IBS.

导言:在肠易激综合征(IBS)患者中观察到粪便蛋白酶活性增加,这可能会诱发内脏超敏反应。丝氨酸蛋白酶可调节与免疫和糖皮质激素受体功能相关的FK506结合蛋白(FKBP)型肽基脯氨酰顺反异构酶(PPI酶)的活性。目的是研究一种丝氨酸蛋白酶抑制剂甲磺酸卡莫司他(CM)是否能改变与FKBP型PPI酶相关的粪便细菌功能,从而改善肠易激综合征患者的病情:方法:随机分配 16 名肠易激综合征患者服用 200 毫克 CM,16 名患者服用安慰剂 14 天。在治疗前后评估了作为主要终点的自我报告的充分缓解(AR)、肠易激综合征症状严重程度量表(IBS-SSS)以及结肠运动阈值和结肠直肠胀痛阈值。粪便中的细菌含量是根据 16S rRNA 基因序列数据,利用未观察状态重建群落系统发育调查(PICRUSt)和京都基因和基因组百科全书(KEGG)数据库推断出来的:结果:中药治疗后链球菌的相对丰度以及丝氨酸蛋白酶和FKBP型PPI酶FklB和SlyD的功能丰度均明显高于安慰剂。虽然结肠运动反应发生了部分变化,但中药治疗在AR比例上并不优于安慰剂:结论:CM 可调节肠易激综合征患者粪便微生物组的组成以及与 FKBP 型 PPI 酶活性相关的功能潜能。这些研究结果表明,蛋白酶抑制剂可能会改变肠道微生物功能,同时改变导致肠易激综合征病理生理学的异常免疫和/或应激反应。
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引用次数: 0
Surveillance after Endoscopic Resection for Colorectal Tumors: A Comprehensive Review. 内镜下结直肠肿瘤切除术后的监控:全面回顾。
IF 3 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-21 DOI: 10.1159/000542665
Kinichi Hotta, Takahisa Matsuda, Yasushi Sano, Takahiro Fujii, Yutaka Saito

Background: The goal of surveillance after the endoscopic resection of colorectal tumors is to reduce colorectal cancer (CRC) incidence and mortality. Considering the effective use of the limited endoscopic capacity and the cost of surveillance, it is desirable to develop a surveillance program that is as minimal as possible. In Europe (European Society of Gastrointestinal Endoscopy [ESGE]) and the USA (Multi-Society Task Force [MSTF]), after the results of the National Polyp Study (NPS) were established, guidelines were developed that stratified risk based on initial endoscopy, and surveillance programs for each risk group were proposed. More than 10 years later, the "colonoscopy screening and surveillance guidelines" were developed with the basic principle of "aiming for zero CRC deaths during surveillance, bowel preservation, and emphasis on patient quality of life" as the guideline principles in Japan.

Summary: Randomized controlled trials to evaluate the appropriate surveillance intervals after endoscopic resection of colorectal tumors, the NPS, the Nottingham Study, and the Japan Polyp Study (JPS), are summarized. The ESGE, USMSTF, and Japanese guidelines compared low-risk adenoma, high-risk adenoma, advanced neoplasia, piecemeal resection, and serrated lesions by category.

Key messages: Surveillance guidelines based on risk stratification were developed in Japan. Guidelines are meaningful only when they are effectively utilized in clinical practice. They must also be revised based on new evidence. It is hoped that new knowledge will be accumulated, especially in Japan, on topics that are currently lacking.

背景:在内镜下切除结直肠肿瘤后进行监测的目的是降低结直肠癌(CRC)的发病率和死亡率。考虑到如何有效利用有限的内镜能力和监控成本,最好是制定一个尽可能少的监控计划。在欧洲(欧洲消化内镜学会(ESGE))和美国(多学会工作组(MSTF)),国家息肉研究(NPS)的结果确定后,根据最初的内镜检查结果制定了风险分层指南,并针对每个风险组别提出了监测计划。10 多年后,日本制定了 "结肠镜筛查和监测指南",其基本原则是 "监测期间结直肠癌死亡人数为零、保留肠道、重视患者生活质量":总结了评估结直肠肿瘤内镜切除术后适当监测间隔的随机对照试验(RCT):NPS、诺丁汉研究和日本息肉研究(JPS)。ESGE、USMSTF和日本指南对低风险腺瘤、高风险腺瘤、晚期肿瘤、片状切除和锯齿状病变进行了分类比较:关键信息:日本制定了基于风险分层的监测指南。指南只有在临床实践中得到有效利用才有意义。指南还必须根据新的证据进行修订。希望能积累新的知识,尤其是在日本,以解决目前缺乏的课题。
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引用次数: 0
DYRK2 regulates epithelial-mesenchymal transition restriction in pancreatic cancer liver metastasis by inhibiting Twist. DYRK2通过抑制Twist调节胰腺癌肝转移中的上皮-间质转化限制。
IF 3 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-19 DOI: 10.1159/000541039
Hang Pan, Yin Liu, Kejiu Bao, Yulin Wang, Yuping Zhang, Lina Zhou

Objectives: To explore the underlying variables and molecular pathways leading to pancreatic cancer liver metastasis.

Methods: Hs766T and Hs766T-L3 cells were used to create in vitro and in vivo pancreatic cancer liver metastasis models. DYRK2 involvement in pancreatic cancer metastasis was investigated using cell adhesion assays, wound healing assays, and migration and invasion assays. To examine the link between DYRK2 expression and epithelial-mesenchymal transition, Western blot, quantitative real-time PCR, immunofluorescence assays, and immunoprecipitation (IP) were utilized. We found that mice with DYRK2 overexpression had a lower incidence of liver metastasis compared to controls.

Results: DYRK2 expression decreased pancreatic cancer tumorigenic activities, including proliferation, migration, and invasion. By analyzing the expression levels of epithelial-mesenchymal transition markers and IP results after overexpressing DYRK2, we found that DYRK2 decreased Twist levels by increasing Twist ubiquitination, thereby inhibiting epithelial-mesenchymal transition.

Conclusions: Our findings provide theoretical and experimental support for the ongoing development of DYRK2-based targeted therapies for pancreatic cancer liver metastases.

目的:探讨导致胰腺癌肝转移的潜在变量和分子通路:方法:使用 Hs766T 和 Hs766T-L3 细胞创建体外和体内胰腺癌肝转移模型。方法:用 Hs766T 和 Hs766T-L3 细胞创建体外和体内胰腺癌肝转移模型,使用细胞粘附试验、伤口愈合试验以及迁移和侵袭试验研究 DYRK2 参与胰腺癌转移的情况。为了研究 DYRK2 表达与上皮-间质转化之间的联系,研究人员采用了 Western 印迹、定量实时 PCR、免疫荧光检测和免疫沉淀(IP)等方法。我们发现,与对照组相比,DYRK2过表达的小鼠肝转移发生率较低:结果:DYRK2的表达降低了胰腺癌的致瘤活性,包括增殖、迁移和侵袭。通过分析过表达DYRK2后上皮-间质转化标志物的表达水平和IP结果,我们发现DYRK2通过增加Twist泛素化降低了Twist水平,从而抑制了上皮-间质转化:我们的研究结果为目前开发基于 DYRK2 的胰腺癌肝转移靶向疗法提供了理论和实验支持。
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引用次数: 0
Endoscopic Resection for Colorectal Tumors. 结肠直肠肿瘤的内窥镜切除术。
IF 3 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-04 DOI: 10.1159/000541605
Yuichiro Hirai, Naoya Toyoshima, Yutaka Saito

Background: Endoscopic resection techniques for colorectal tumors are constantly evolving with improvements.

Summary: Over the past decade, there has been a paradigm shift toward cold polypectomy for the removal of small lesions (<10 mm), known as the "cold revolution". In recent years, underwater endoscopic mucosal resection (EMR) has emerged as an alternative to conventional EMR and has been gaining popularity for resection of intermediate and large-sized lesions (≥10 mm). Although colorectal endoscopic submucosal dissection (ESD) requires a high level of advanced skills, improvements in dissection techniques and devices have facilitated the procedure. In Japan, the safety and efficacy of ESD for resecting large lesions (≥20 mm) have been demonstrated in a large-scale, multicenter, prospective cohort study (CREATE-J). ESD is also being increasingly adopted in Western countries. As endoscopic resection continues to advance and include large and more complex defects, a variety of closure techniques and new devices are being developed. Meanwhile, the number of endoscopic resections for T1-colorectal cancer (T1-CRC), including those intended for total excisional biopsy, has been increasing owing to the aging population and improvements in endoscopic technique.

Key messages: This review provides a broad summary of endoscopic resection for colorectal tumors including advancements in closure techniques and devices for mucosal defects, as well as the potential role of endoscopic resection for patients with T1-CRC.

背景:摘要:在过去的十年中,切除小病灶的模式已经向冷息肉切除术转变:本综述广泛总结了结直肠肿瘤的内镜切除术,包括粘膜缺损闭合技术和装置的进步,以及内镜切除术对 T1-CRC 患者的潜在作用。
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