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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
Identification of a Novel Activated NK-Associated Gene Score Associated with Diagnosis and Biological Therapy Response in Ulcerative Colitis. 鉴定与溃疡性结肠炎诊断和生物疗法反应相关的新型活化 NK 相关基因评分
IF 3 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-01-01 Epub Date: 2024-08-23 DOI: 10.1159/000540939
Siyuan Dong, Yu Zhang, Lingna Ye, Qian Cao
<p><strong>Introduction: </strong>Natural killer (NK) cells are associated with the pathogenesis of ulcerative colitis (UC); however, their precise contributions remain unclear. The present study aimed to investigate the diagnostic value of the activated NK-associated gene (ANAG) score in UC and evaluate its predictive value in response to biological therapy.</p><p><strong>Methods: </strong>Bulk RNA-seq and scRNA-seq datasets were obtained from the Gene Expression Omnibus (GEO) and Single Cell Portal (SCP) databases. In the bulk RNA-seq, differentially expressed genes (DEGs) were screened by the "Batch correction" and "Robust rank aggregation" (RRA) methods. The immune infiltration landscape was estimated using single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT. DEGs that correlated with activated NK cells were identified as activated NK-associated genes (ANAGs). Protein-protein interaction (PPI) analysis and least absolute shrinkage and selection operator (LASSO) regression were used to screen key ANAGs and establish an ANAG score. The expression levels of the four key ANAGs were validated in human samples by real-time quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence. The potential therapeutic drugs for UC were identified using the DSigDB database. Through scRNA-seq data analysis, the cell scores based on the ANAGs were calculated by "AddModuleScore" and "AUCell."</p><p><strong>Results: </strong>Immune infiltration analysis revealed a higher abundance of activated NK cells in noninflamed UC tissues (ssGSEA, p < 0.001; CIBERSORT, p < 0.01). Fifty-four DEGs correlated with activated NK cells were identified as ANAGs. The ANAG score was established using four key ANAGs (SELP, TIMP1, MMP7, and ABCG2). The ANAG scores were significantly higher in inflamed tissues (p < 0.001) and in biological therapy nonresponders (NR) tissues before treatment (golimumab, p < 0.05; ustekinumab, p < 0.001). The ANAG score demonstrated an excellent diagnostic value (AUC = 0.979). Patients with higher ANAG scores before treatment were more likely to experience a lack of response to golimumab or ustekinumab (golimumab, p < 0.05; ustekinumab, p < 0.001).</p><p><strong>Conclusion: </strong>This study established a novel ANAG score with the ability to precisely diagnose UC and distinguish the efficacy of biological treatment.</p><p><strong>Introduction: </strong>Natural killer (NK) cells are associated with the pathogenesis of ulcerative colitis (UC); however, their precise contributions remain unclear. The present study aimed to investigate the diagnostic value of the activated NK-associated gene (ANAG) score in UC and evaluate its predictive value in response to biological therapy.</p><p><strong>Methods: </strong>Bulk RNA-seq and scRNA-seq datasets were obtained from the Gene Expression Omnibus (GEO) and Single Cell Portal (SCP) databases. In the bulk RNA-seq, differentially expressed genes (DEGs) were screened by the "Batch correctio
导言:自然杀伤(NK)细胞与溃疡性结肠炎(UC)的发病机制有关,但其确切作用仍不清楚。本研究旨在探讨活化的 NK 相关基因(ANAG)评分在 UC 中的诊断价值,并评估其对生物疗法反应的预测价值:从基因表达总库(Gene Expression Omnibus,GEO)和单细胞门户(Single Cell Portal,SCP)数据库中获得了大量RNA-seq和scRNA-seq数据集。在批量RNA-seq中,通过 "批量校正 "和 "稳健秩聚集"(RRA)方法筛选差异表达基因(DEGs)。利用单样本基因组富集分析(ssGSEA)和 CIBERSORT 估算了免疫浸润情况。与活化 NK 细胞相关的 DEGs 被鉴定为活化 NK 相关基因(ANAGs)。蛋白质-蛋白质相互作用(PPI)分析和最小绝对收缩与选择算子(LASSO)回归用于筛选关键的 ANAGs 并确定 ANAG 分数。通过实时定量聚合酶链反应(RT-qPCR)和免疫荧光验证了四个关键ANAGs在人体样本中的表达水平。利用 DSigDB 数据库确定了潜在的 UC 治疗药物。通过scRNA-seq数据分析,用 "AddModuleScore "和 "AUCell "计算了基于ANAGs的细胞得分:结果:免疫浸润分析显示,非炎症 UC 组织中活化 NK 细胞的丰度更高(ssGSEA,P<0.001;CIBERSORT,P<0.01)。54个与活化NK细胞相关的DEGs被鉴定为ANAGs。利用四个关键的 ANAGs(SELP、TIMP1、MMP7 和 ABCG2)确定了 ANAG 分数。在炎症组织(P<0.001)和治疗前生物疗法无应答者(NR)组织(戈利木单抗,P<0.05;乌斯特库单抗,P<0.001)中,ANAG评分明显较高。ANAG 评分具有极高的诊断价值(AUC = 0.979)。治疗前ANAG评分较高的患者更有可能对戈利木单抗或乌斯特库单抗缺乏反应(戈利木单抗,P<0.05;乌斯特库单抗,P<0.001):本研究建立了一种新的 ANAG 评分标准,该评分标准能够精确诊断 UC 并区分生物治疗的疗效。
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引用次数: 0
Evidence-Based Clinical Guidelines for Chronic Constipation 2023. 2023 年慢性便秘循证临床指南。
IF 3 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-01-01 Epub Date: 2024-08-19 DOI: 10.1159/000540912
Eikichi Ihara, Noriaki Manabe, Hidenori Ohkubo, Naotaka Ogasawara, Haruei Ogino, Kazuki Kakimoto, Motoyori Kanazawa, Hidejiro Kawahara, Chika Kusano, Shiko Kuribayashi, Akinari Sawada, Tomohisa Takagi, Shota Takano, Toshihiko Tomita, Toshihiro Noake, Mariko Hojo, Ryota Hokari, Tatsuhiro Masaoka, Tomohiko Machida, Noboru Misawa, Yoshiyuki Mishima, Hiroshi Yajima, Sayuri Yamamoto, Hiroshi Yamawaki, Tatsuya Abe, Yasumi Araki, Kunio Kasugai, Takeshi Kamiya, Akira Torii, Atsushi Nakajima, Koji Nakada, Shin Fukudo, Yasuhiro Fujiwara, Hiroto Miwa, Hiromi Kataoka, Akihito Nagahara, Kazuhide Higuchi
<p><p>The Japan Gastroenterological Association published the first version of its clinical guidelines for chronic constipation 2023. Based on the latest evidence, these guidelines describe the definition, classification, diagnostic criteria, diagnostic testing methods, epidemiology, pathophysiology, and treatment of chronic constipation. They include flowcharts for both diagnosis and treatment of chronic constipation. In the treatment of chronic constipation, the first step involves differentiating between secondary forms, such as organic disease-associated constipation, systemic disease-associated constipation, and drug-induced constipation. The next step is to determine whether the chronic constipation stems from a motility disorder, a form of primary chronic constipation. For functional constipation and constipation-predominant irritable bowel syndrome, treatment should be initiated after evaluating symptoms like reduced bowel movement frequency type or defecation difficulty type. The first line of treatment includes the improvement of lifestyle habits and diet therapy. The first drugs to consider for oral treatment are osmotic laxatives. If these are ineffective, secretagogues and ileal bile acid transporter inhibitors are candidates. However, stimulant laxatives are exclusively designated for as-needed use. Probiotics, bulk-forming laxatives, prokinetics, and Kampo medicines, for which there is insufficient evidence, are considered alternative or complementary therapy. Providing the best clinical strategies for chronic constipation therapy in Japan, these clinical guidelines for chronic constipation 2023 should prove useful for its treatment worldwide. The Japan Gastroenterological Association published the first version of its clinical guidelines for chronic constipation 2023. Based on the latest evidence, these guidelines describe the definition, classification, diagnostic criteria, diagnostic testing methods, epidemiology, pathophysiology, and treatment of chronic constipation. They include flowcharts for both diagnosis and treatment of chronic constipation. In the treatment of chronic constipation, the first step involves differentiating between secondary forms, such as organic disease-associated constipation, systemic disease-associated constipation, and drug-induced constipation. The next step is to determine whether the chronic constipation stems from a motility disorder, a form of primary chronic constipation. For functional constipation and constipation-predominant irritable bowel syndrome, treatment should be initiated after evaluating symptoms like reduced bowel movement frequency type or defecation difficulty type. The first line of treatment includes the improvement of lifestyle habits and diet therapy. The first drugs to consider for oral treatment are osmotic laxatives. If these are ineffective, secretagogues and ileal bile acid transporter inhibitors are candidates. However, stimulant laxatives are exclusively designated for
2023 年 7 月,日本胃肠病学协会发布了第一版《2023 年慢性便秘临床指南》。该指南以最新证据为基础,介绍了慢性便秘的定义、分类、诊断标准、诊断检测方法、流行病学、病理生理学和治疗方法。其中包括慢性便秘的诊断和治疗流程图。治疗慢性便秘的第一步是区分继发性便秘,如器质性疾病相关性便秘、系统性疾病相关性便秘和药物引起的便秘。下一步是确定慢性便秘是否源于运动障碍,即原发性慢性便秘的一种形式。对于功能性便秘和以便秘为主的肠易激综合征,应在评估排便次数减少型或排便困难型等症状后开始治疗。第一线治疗包括改善生活习惯和饮食疗法。口服治疗的首选药物是渗透性泻药。如果这些药物无效,则可选用促泌剂和回肠胆汁酸转运抑制剂。不过,刺激性泻药只能按需使用。益生菌、膨松性泻药、促动力药和堪布药(证据不足)被视为替代或补充疗法。这些《2023 年慢性便秘临床指南》为日本的慢性便秘治疗提供了最佳临床策略,对全球的慢性便秘治疗应该会有所帮助。
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引用次数: 0
C-Kit Immunohistochemical Expression as a Complementary Method to Assess Mast Cell Density in Helicobacter pylori-Mediated Gastritis. 将 C-Kit 免疫组化表达作为评估幽门螺旋杆菌介导的胃炎中肥大细胞密度的辅助方法
IF 3 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-01-01 Epub Date: 2024-09-13 DOI: 10.1159/000541387
Ava T Ismael, Rafal A Abdulhameed, Bushra A Hamdi, Rawaz D Tawfeeq, Aram Ommar

Introduction: Chronic gastritis is a group of conditions commonly characterized by stomach lining inflammation. The study aimed to investigate the clinical and pathological aspects that play a role in its development. Additionally, the study examines the use of CD117 as an immunohistochemistry marker in evaluating mast cell density (MCD).

Methods: This retrospective, cross-sectional study was conducted in Iraqi Kurdistan with a sample size of 380 patients. Patient data included gastritis type, neutrophil infiltration severity, mononuclear cell infiltration within the lamina propria, intestinal metaplasia, and glandular atrophy, which were categorized and given a score. The CD117 level was identified using an anti-human rabbit polyclonal antibody.

Results: A statistically significant association was revealed between Helicobacter pylori-mediated gastritis and non-specific gastritis with age, activity, H. pylori and MCD, dysplasia, and malignancy. Meanwhile, no association was found with gender, inflammatory infiltrate, intestinal metaplasia, and glandular atrophy. C-Kit exhibited a marked increase in MCD in patients with H. pylori-mediated gastritis, intestinal metaplasia, atrophy, and gastric carcinoma. However, a significant decrease in MCD was observed on repeating endoscopy evaluations for patients after treatment.

Conclusion: Regions that exhibit severe inflammation, metaplasia, atrophy, and carcinoma demonstrated an increase in MCD with H. pylori-mediated gastritis. A detailed investigation in clinical practice to screen early diagnosis and treatment needs to be performed in high H. pylori prevalence.

简介慢性胃炎是一组以胃黏膜炎症为常见特征的疾病。本研究旨在探讨导致慢性胃炎的临床和病理因素。此外,该研究还探讨了使用 CD117 作为免疫组化标记来评估肥大细胞密度(MCD):这项回顾性横断面研究在伊拉克库尔德斯坦进行,样本量为 380 例患者。患者数据包括胃炎类型、中性粒细胞浸润严重程度、固有层内单核细胞浸润、肠化生和腺体萎缩,并对其进行分类和评分。使用抗人兔多克隆抗体鉴定 CD117 水平:结果:幽门螺杆菌介导的胃炎和非特异性胃炎与年龄、活动度、幽门螺杆菌和 MCD、发育不良和恶性肿瘤有统计学意义。同时,与性别、炎症浸润、肠化生和腺体萎缩没有关联。在幽门螺杆菌介导的胃炎、肠化生、萎缩和胃癌患者中,C-Kit 显示 MCD 明显增加。然而,在治疗后对患者进行重复内镜评估时,观察到 MCD 明显下降:结论:在幽门螺杆菌介导的胃炎中,表现出严重炎症、化生、萎缩和癌变的区域的 MCD 会增加。在幽门螺杆菌高发区,需要在临床实践中进行详细调查,以筛查早期诊断和治疗。
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引用次数: 0
NEIL3 Upregulated by TFAP2A Promotes M2 Polarization of Macrophages in Liver Cancer via the Mediation of Glutamine Metabolism. 由 TFAP2A 上调的 NEIL3 通过谷氨酰胺代谢介导促进肝癌巨噬细胞的 M2 极化。
IF 3 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-01-01 Epub Date: 2024-09-27 DOI: 10.1159/000540804
Fabiao Zhang, Binfeng Wang, Wenlong Zhang, Yongfu Xu, Caiming Zhang, Xiangyang Xue

Introduction: Tumor-associated macrophages, which are part of the tumor microenvironment, are a major factor in cancer progression. However, a complete understanding of the regulatory mechanism of M2 polarization of macrophages (Mø) in liver cancer is yet to be established. This study aimed to investigate the potential mechanism by which NEIL3 influenced M2 Mø polarization in liver cancer.

Methods: Bioinformatics analysis analyzed NEIL3 expression and its enriched pathways in liver cancer tissue, as well as its correlation with pathway genes. The upstream transcription factor of NEIL3, TFAP2A, was predicted and its expression in liver cancer tissue was analyzed. The binding relationship between the two was analyzed by dual-luciferase reporter and chromatin immunoprecipitation experiments. qRT-PCR assessed NEIL3 and TFAP2A levels in liver cancer cells. Cell viability was detected by CCK-8, while CD206 and CD86 expression was detected by immunofluorescence. IL-10 and CCR2 expressions were assessed using qRT-PCR, and M2 Mø quantity was detected using flow cytometry. Reagent kits tested glutamine (Gln) consumption, α-ketoglutarate, and glutamate content, as well as NADPH/NADP+ and GSH/GSSG ratios. Expression of Gln transport proteins was detected using Western blot. An animal model was established to investigate the influence of NEIL3 expression on liver cancer growth.

Results: NEIL3 was highly expressed in liver cancer and promoted Mø M2 polarization through Gln metabolism. TFAP2A was identified as the upstream transcription factor of NEIL3 and was highly expressed in liver cancer. Rescue experiments presented that overexpression of NEIL3 reversed the suppressive effect of TFAP2A knockdown on Mø M2 polarization in liver cancer. In vivo experiments demonstrated that the knockdown of NEIL3 could significantly repress the growth of xenograft tumors.

Conclusion: This study suggested that the TFAP2A/NEIL3 axis promoted Mø M2 polarization through Gln metabolism, providing a theoretical basis for immune therapy targeting the liver cancer TME.

简介肿瘤相关巨噬细胞(TAMs)是肿瘤微环境(TME)的一部分,是癌症进展的一个主要因素。然而,人们对肝癌中巨噬细胞(Mø)M2极化的调控机制尚未建立完整的认识。本研究旨在探讨 NEIL3 影响肝癌 M2 Mø 极化的潜在机制:生物信息学分析了NEIL3在肝癌组织中的表达及其富集通路,以及其与通路基因的相关性。预测了 NEIL3 的上游转录因子 TFAP2A,并分析了其在肝癌组织中的表达。qRT-PCR 评估了肝癌细胞中 NEIL3 和 TFAP2A 的水平。细胞活力通过 CCK-8 检测,CD206 和 CD86 的表达通过免疫荧光检测。IL-10 和 CCR2 的表达通过 qRT-PCR 进行评估,M2 Mø 的数量通过流式细胞术进行检测。试剂盒检测了谷氨酰胺(Gln)消耗量、α-酮戊二酸和谷氨酸含量,以及 NADPH/NADP+ 和 GSH/GSSG 比率。使用 Western 印迹法检测 Gln 转运蛋白的表达。建立动物模型研究 NEIL3 表达对肝癌生长的影响:结果:NEIL3在肝癌中高表达,并通过Gln代谢促进Mø M2极化。TFAP2A被鉴定为NEIL3的上游转录因子,并在肝癌中高表达。拯救实验表明,NEIL3的过表达逆转了TFAP2A敲除对肝癌Mø M2极化的抑制作用。体内实验表明,敲除 NEIL3 可显著抑制异种移植肿瘤的生长:该研究表明,TFAP2A/NEIL3轴通过Gln代谢促进Mø M2极化,为针对肝癌TME的免疫疗法提供了理论依据。
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引用次数: 0
Clinical Efficacy and Safety of Treatments for Exocrine Pancreatic Insufficiency: A Systematic Literature Review. 胰腺外分泌功能不全治疗方法的临床疗效和安全性:系统性文献综述。
IF 3 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-01-01 Epub Date: 2024-09-19 DOI: 10.1159/000541326
Paula Chu, Jasmina Mioc, Peter O'Donovan, Owen Henry
<p><strong>Introduction: </strong>Exocrine pancreatic insufficiency (EPI) is caused by multiple clinical conditions such as cystic fibrosis and chronic pancreatitis (CP). Standard management of EPI includes pancreatic enzyme replacement therapy (PERT) along with consultation with a dietitian. While PERTs have been on the market for several decades, newer publications on their clinical efficacy and safety raised the need for a comprehensive review of the literature. We aimed to identify the available evidence on the clinical efficacy and safety of treatments for EPI to understand the current treatment landscape and unmet need in patients with EPI.</p><p><strong>Methods: </strong>A systematic literature review (SLR) was conducted in Embase, Medline, and Evidence-Based Medicine databases from 2010 to 2022; conference proceedings from 2020 to 2022 were also searched. Articles were screened independently by two reviewers at abstract and full-text stage against predefined eligibility criteria.</p><p><strong>Results: </strong>We identified 26 journal publications and two conference abstracts, reporting on 22 randomized control trials, four observational studies, and two single-arm interventional studies. The most reported treatment was pancrelipase, specifically Creon® (n = 12). Fourteen studies reported coefficient of fat absorption (CFA) results. Across studies, patients experienced a considerable increase in CFA post-initiation of treatment regardless of intervention or timepoint. Mean change in CFA ranged from 7.5% in patients with CP who received placebo to 36% in patients with CP treated with Creon®. Ten studies reported coefficient of nitrogen absorption (CNA). Where reported, pancrelipase (including Creon®) increased CNA levels in EPI patients compared to placebo. Only one study compared PERT brands head-to-head: no significant differences were reported in the CNA-72 h values (Creon® 82.0% [SE: 1.2] vs. Zenpep® 80.9% [SE: 1.2]). Loss of body weight and low body mass index (BMI) are important features of EPI. Overall, treatment with PERT increased BMI and body weight, or limited their decline, with increases ranging from 0.1 to 6.1 kg. Based on the 18 studies that reported safety outcomes, PERT was considered safe and well tolerated.</p><p><strong>Conclusions: </strong>This SLR confirmed that PERT is an effective and tolerable treatment option for patients with EPI. However, nutritional parameters and health-related quality of life data were sparsely reported, and future clinical trials should look to incorporate these data given their importance in clinical practice and patient outcomes.</p><p><strong>Introduction: </strong>Exocrine pancreatic insufficiency (EPI) is caused by multiple clinical conditions such as cystic fibrosis and chronic pancreatitis (CP). Standard management of EPI includes pancreatic enzyme replacement therapy (PERT) along with consultation with a dietitian. While PERTs have been on the market for several decades, newer publ
导言:胰腺外分泌功能不全(EPI)是由囊性纤维化(CF)和慢性胰腺炎(CP)等多种临床疾病引起的。EPI 的标准治疗方法包括胰酶替代疗法(PERT)以及营养师咨询。虽然胰酶替代疗法已上市数十年,但有关其临床疗效和安全性的最新出版物提出了对文献进行全面回顾的必要性。我们旨在确定有关 EPI 治疗方法的临床疗效和安全性的现有证据,以了解 EPI 患者目前的治疗情况和尚未满足的需求:在Embase、Medline和循证医学数据库中对2010-2022年的文献进行了系统性回顾;还检索了2020-2022年的会议论文集。文章在摘要和全文阶段由两名审稿人根据预先设定的资格标准进行独立筛选:我们发现了 26 篇期刊论文和 2 篇会议论文摘要,报告了 22 项随机对照试验、4 项观察性研究和 2 项单臂介入性研究。报道最多的治疗方法是胰脂酶,特别是 Creon®(12 项)。14项研究报告了脂肪吸收系数(CFA)结果。在所有研究中,无论干预措施或时间点如何,患者在开始治疗后脂肪吸收系数都有显著增加。脂肪吸收系数的平均变化范围从接受安慰剂治疗的 CP 患者的 7.5% 到接受 Creon® 治疗的 CP 患者的 36%。十项研究报告了氮吸收系数(CNA)。据报道,与安慰剂相比,胰脂酶(包括 Creon®)可提高 EPI 患者的 CNA 水平。只有一项研究对 PERT 品牌进行了正面比较:CNA-72 h 值无显著差异(Creon® 82.0% [SE 1.2] 与 Zenpep® 80.9% [SE 1.2])。体重下降和体重指数(BMI)低是 EPI 的重要特征。总体而言,使用 PERT 治疗可增加体重指数和体重,或限制其下降,增加幅度从 0.1 公斤到 6.1 公斤不等。根据18项报告安全性结果的研究,PERT被认为是安全且耐受性良好的:该系统性文献综述证实,PERT 是 EPI 患者有效且可耐受的治疗方案。然而,营养参数和与健康相关的生活质量数据的报道很少,鉴于这些数据在临床实践和患者预后中的重要性,未来的临床试验应考虑纳入这些数据。
{"title":"Clinical Efficacy and Safety of Treatments for Exocrine Pancreatic Insufficiency: A Systematic Literature Review.","authors":"Paula Chu, Jasmina Mioc, Peter O'Donovan, Owen Henry","doi":"10.1159/000541326","DOIUrl":"10.1159/000541326","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Exocrine pancreatic insufficiency (EPI) is caused by multiple clinical conditions such as cystic fibrosis and chronic pancreatitis (CP). Standard management of EPI includes pancreatic enzyme replacement therapy (PERT) along with consultation with a dietitian. While PERTs have been on the market for several decades, newer publications on their clinical efficacy and safety raised the need for a comprehensive review of the literature. We aimed to identify the available evidence on the clinical efficacy and safety of treatments for EPI to understand the current treatment landscape and unmet need in patients with EPI.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A systematic literature review (SLR) was conducted in Embase, Medline, and Evidence-Based Medicine databases from 2010 to 2022; conference proceedings from 2020 to 2022 were also searched. Articles were screened independently by two reviewers at abstract and full-text stage against predefined eligibility criteria.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;We identified 26 journal publications and two conference abstracts, reporting on 22 randomized control trials, four observational studies, and two single-arm interventional studies. The most reported treatment was pancrelipase, specifically Creon® (n = 12). Fourteen studies reported coefficient of fat absorption (CFA) results. Across studies, patients experienced a considerable increase in CFA post-initiation of treatment regardless of intervention or timepoint. Mean change in CFA ranged from 7.5% in patients with CP who received placebo to 36% in patients with CP treated with Creon®. Ten studies reported coefficient of nitrogen absorption (CNA). Where reported, pancrelipase (including Creon®) increased CNA levels in EPI patients compared to placebo. Only one study compared PERT brands head-to-head: no significant differences were reported in the CNA-72 h values (Creon® 82.0% [SE: 1.2] vs. Zenpep® 80.9% [SE: 1.2]). Loss of body weight and low body mass index (BMI) are important features of EPI. Overall, treatment with PERT increased BMI and body weight, or limited their decline, with increases ranging from 0.1 to 6.1 kg. Based on the 18 studies that reported safety outcomes, PERT was considered safe and well tolerated.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This SLR confirmed that PERT is an effective and tolerable treatment option for patients with EPI. However, nutritional parameters and health-related quality of life data were sparsely reported, and future clinical trials should look to incorporate these data given their importance in clinical practice and patient outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Exocrine pancreatic insufficiency (EPI) is caused by multiple clinical conditions such as cystic fibrosis and chronic pancreatitis (CP). Standard management of EPI includes pancreatic enzyme replacement therapy (PERT) along with consultation with a dietitian. While PERTs have been on the market for several decades, newer publ","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"45-61"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.

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 nonneoplastic 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 (BSs) 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-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 BSs 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。
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引用次数: 0
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Digestion
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