{"title":"Reply to \"Association between proton-pump inhibitor use and recurrence of hepatocellular carcinoma after hepatectomy: concerns to be addressed\".","authors":"C-T Ho, Ec-H Tan, P-C Lee, C-W Su","doi":"10.1111/jgh.16754","DOIUrl":"https://doi.org/10.1111/jgh.16754","url":null,"abstract":"","PeriodicalId":15877,"journal":{"name":"Journal of Gastroenterology and Hepatology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289112","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}
Nikhil Sonthalia, Vithal Kumbar, Awanish Tewari, Akash Roy, Uday C Ghoshal, Mahesh K Goenka
Background and AimAlthough rapid on‐site cytological evaluation (ROSE) for endoscopic ultrasound (EUS)‐guided tissue acquisition (EUS‐TA) may increase diagnostic yield, it is not widely available. Macroscopic on‐site evaluation (MOSE) is an alternative modality although it is not standardized for EUS‐guided fine‐needle biopsy (FNB). We evaluated diagnostic performance of MOSE compared with conventional technique of EUS‐TA using core biopsy needle.MethodsConsecutive patients undergoing EUS‐FNA for solid lesions were randomized to MOSE or conventional arms. The primary and secondary outcome measures were diagnostic accuracy, diagnostic yield, sensitivity, specificity, positive and negative predictive values, and the number of passes, respectively. The optimum parameters for macroscopic visible core (MVC, i.e., length, number) by MOSE to achieve accurate diagnosis were evaluated.ResultsNinety‐six patients (48 conventional and 48 MOSE) were enrolled. Mean lesion size was larger in MOSE arm (32.67 ± 7.22 vs 29.31 ± 6.98 mm, P = 0.023). Diagnostic accuracy (95.8% vs 91.6%), diagnostic yield (97.9% vs 95.8%), procedure duration, and adverse events of the two methods were similar. Median number of passes with MOSE was less (2 vs 3 P = 0.000). Area under the receiver operating characteristic curve showed that with MOSE, obtaining a total MVC length of 11.5 mm had 93.3% sensitivity, and 2.5 MVC cores (each 4 mm) had 86.7% sensitivity for malignancy diagnosis.ConclusionsEUS‐FNB with MOSE, a simple reliable technique, can achieve a high and comparable diagnostic accuracy with lesser number of passes. Obtaining longer length and greater number of MVC increase the sensitivity to diagnose malignancy with MOSE.
背景和目的虽然在内窥镜超声（EUS）引导下进行组织采集（EUS-TA）的现场快速细胞学评估（ROSE）可提高诊断率，但这种方法尚未普及。显微镜下现场评估（MOSE）是一种可供选择的方法，但它还没有被标准化用于 EUS 引导下的细针活检（FNB）。我们评估了 MOSE 与使用核心活检针进行 EUS-TA 的传统技术相比的诊断性能。主要和次要结果指标分别为诊断准确性、诊断率、敏感性、特异性、阳性和阴性预测值以及通过次数。还评估了通过 MOSE 获得准确诊断的宏观可见核心（MVC，即长度和数量）的最佳参数。MOSE臂的平均病灶大小更大（32.67 ± 7.22 vs 29.31 ± 6.98 mm，P = 0.023）。两种方法的诊断准确率（95.8% vs 91.6%）、诊断率（97.9% vs 95.8%）、手术时间和不良反应相似。MOSE 的中位通过次数较少（2 vs 3 P = 0.000）。接收器操作特征曲线下面积显示，使用 MOSE，获得 11.5 毫米的 MVC 总长度对恶性肿瘤诊断的敏感性为 93.3%，2.5 个 MVC 核心（每个 4 毫米）对恶性肿瘤诊断的敏感性为 86.7%。获得更长的MVC和更多的MVC可提高MOSE诊断恶性肿瘤的灵敏度。
{"title":"Endoscopic ultrasound‐guided fine needle biopsy using macroscopic on‐site evaluation technique reduces the number passes yet maintains a high diagnostic accuracy: A randomized study","authors":"Nikhil Sonthalia, Vithal Kumbar, Awanish Tewari, Akash Roy, Uday C Ghoshal, Mahesh K Goenka","doi":"10.1111/jgh.16744","DOIUrl":"https://doi.org/10.1111/jgh.16744","url":null,"abstract":"Background and AimAlthough rapid on‐site cytological evaluation (ROSE) for endoscopic ultrasound (EUS)‐guided tissue acquisition (EUS‐TA) may increase diagnostic yield, it is not widely available. Macroscopic on‐site evaluation (MOSE) is an alternative modality although it is not standardized for EUS‐guided fine‐needle biopsy (FNB). We evaluated diagnostic performance of MOSE compared with conventional technique of EUS‐TA using core biopsy needle.MethodsConsecutive patients undergoing EUS‐FNA for solid lesions were randomized to MOSE or conventional arms. The primary and secondary outcome measures were diagnostic accuracy, diagnostic yield, sensitivity, specificity, positive and negative predictive values, and the number of passes, respectively. The optimum parameters for macroscopic visible core (MVC, i.e., length, number) by MOSE to achieve accurate diagnosis were evaluated.ResultsNinety‐six patients (48 conventional and 48 MOSE) were enrolled. Mean lesion size was larger in MOSE arm (32.67 ± 7.22 <jats:italic>vs</jats:italic> 29.31 ± 6.98 mm, <jats:italic>P</jats:italic> = 0.023). Diagnostic accuracy (95.8% <jats:italic>vs</jats:italic> 91.6%), diagnostic yield (97.9% <jats:italic>vs</jats:italic> 95.8%), procedure duration, and adverse events of the two methods were similar. Median number of passes with MOSE was less (2 <jats:italic>vs</jats:italic> 3 <jats:italic>P =</jats:italic> 0.000). Area under the receiver operating characteristic curve showed that with MOSE, obtaining a total MVC length of 11.5 mm had 93.3% sensitivity, and 2.5 MVC cores (each 4 mm) had 86.7% sensitivity for malignancy diagnosis.ConclusionsEUS‐FNB with MOSE, a simple reliable technique, can achieve a high and comparable diagnostic accuracy with lesser number of passes. Obtaining longer length and greater number of MVC increase the sensitivity to diagnose malignancy with MOSE.","PeriodicalId":15877,"journal":{"name":"Journal of Gastroenterology and Hepatology","volume":"7 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252185","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}
Background and AimSelenium, an essential micronutrient for humans, has been shown to be protective against ulcerative colitis (UC), but the exact mechanism remains unclear. The role of selenium, protecting against ferroptosis of intestinal epithelial cells (IECs) in colitis, was investigated in this current study.MethodsSerum selenium level and ferroptosis‐related gene expression in the colonic mucosa were measured in UC patients and healthy controls. The effects of sodium selenite supplementation on experimental colitis were investigated in dextran sulfate sodium (DSS)‐treated mice. The influence of sodium selenite on IEC ferroptosis was evaluated through assessing cell death rate, intracellular ferrous iron content, lipid reactive oxygen species level, and mitochondrial membrane damage of DSS‐treated Caco‐2 cells. Moreover, glutathione peroxidase 4 (GPX4) and acyl‐CoA synthetase long‐chain family member 4, ferroptosis‐related genes, were detected in Caco‐2 cells and mouse intestines.ResultsSerum selenium was decreased in UC patients in comparison with healthy individuals. Additionally, serum selenium level was negatively correlated with disease activity and was associated with clinical inflammation and nutrition indicators. The expression of GPX4 in the mucosa of UC was positively correlated with serum selenium level. The in vivo experiments showed that selenium treatment ameliorated DSS‐induced colitis and inhibited ferroptosis in IECs. The in vitro results suggested that selenium supplementation inhibited DSS‐induced ferroptosis in Caco‐2 cells. GPX4 was upregulated after selenium supplementation both in vivo and in vitro.ConclusionsSerum selenium level was associated with IEC ferroptosis in UC patients. Selenium supplementation alleviates DSS‐induced colitis and inhibits ferroptosis in IECs by upregulating the expression of GPX4.
{"title":"Selenium alleviates dextran sulfate sodium‐induced colitis and inhibits ferroptosis of intestinal epithelial cells via upregulating glutathione peroxidase 4","authors":"Mengxue Zhao, Hongqian Wang, Yumeng Zhang, Chuang Lv, Jing Guan, Xi Chen","doi":"10.1111/jgh.16738","DOIUrl":"https://doi.org/10.1111/jgh.16738","url":null,"abstract":"Background and AimSelenium, an essential micronutrient for humans, has been shown to be protective against ulcerative colitis (UC), but the exact mechanism remains unclear. The role of selenium, protecting against ferroptosis of intestinal epithelial cells (IECs) in colitis, was investigated in this current study.MethodsSerum selenium level and ferroptosis‐related gene expression in the colonic mucosa were measured in UC patients and healthy controls. The effects of sodium selenite supplementation on experimental colitis were investigated in dextran sulfate sodium (DSS)‐treated mice. The influence of sodium selenite on IEC ferroptosis was evaluated through assessing cell death rate, intracellular ferrous iron content, lipid reactive oxygen species level, and mitochondrial membrane damage of DSS‐treated Caco‐2 cells. Moreover, glutathione peroxidase 4 (GPX4) and acyl‐CoA synthetase long‐chain family member 4, ferroptosis‐related genes, were detected in Caco‐2 cells and mouse intestines.ResultsSerum selenium was decreased in UC patients in comparison with healthy individuals. Additionally, serum selenium level was negatively correlated with disease activity and was associated with clinical inflammation and nutrition indicators. The expression of GPX4 in the mucosa of UC was positively correlated with serum selenium level. The <jats:italic>in vivo</jats:italic> experiments showed that selenium treatment ameliorated DSS‐induced colitis and inhibited ferroptosis in IECs. The <jats:italic>in vitro</jats:italic> results suggested that selenium supplementation inhibited DSS‐induced ferroptosis in Caco‐2 cells. GPX4 was upregulated after selenium supplementation both <jats:italic>in vivo</jats:italic> and <jats:italic>in vitro</jats:italic>.ConclusionsSerum selenium level was associated with IEC ferroptosis in UC patients. Selenium supplementation alleviates DSS‐induced colitis and inhibits ferroptosis in IECs by upregulating the expression of GPX4.","PeriodicalId":15877,"journal":{"name":"Journal of Gastroenterology and Hepatology","volume":"15 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252186","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}
Background and AimCurrently, hepatitis B virus‐related acute liver failure (HBV‐ALF) has limited treatment options. Studies have shown that histone lactylation plays a role in the progression of liver‐related diseases. Therefore, it is essential to explore lactylation‐related gene (LRGs) biomarkers in HBV‐ALF to provide new information for the treatment of HBV‐ALF.MethodsTwo HBV‐ALF‐related datasets (GSE38941 and GSE14668) and 65 LRGs were used. First, the differentially expressed genes (DEGs) were derived from differential expression analysis, the key module genes from weighted gene co‐expression network analysis; and LRGs were used to intersect to obtain the candidate genes. Subsequently, the feature genes obtained from least absolute shrinkage and selection operator regression analysis and support vector machine analysis were intersected to obtain the candidate key genes. Among them, genes with consistent and significant expression trends in both GSE38941 and GSE14668 were used as biomarkers. Subsequently, biomarkers were analyzed for functional enrichment, immune infiltration, and sensitive drug prediction.ResultsIn this study, five candidate genes (PIGM, PIGA, EGR1, PIGK, and PIGL) were identified by intersecting 6461 DEGs and 2496 key module genes with 65 LRGs. We then screened four candidate key genes from the machine learning algorithm, among which PIGM and PIGA were considered biomarkers in HBV‐ALF. Moreover, the results of enrichment analysis showed that the significant enrichment signaling pathways for biomarkers included allograft rejection and valine, leucine, and isoleucine degradation. Thereafter, 11 immune cells differed significantly between groups, with resting memory CD4+ T cells having the strongest positive correlation with biomarkers. Methylphenidate hydrochloride is a potential therapeutic drug for PIGM.ConclusionTwo genes, PIGM and PIGA, were identified as biomarkers related to LRGs in HBV‐ALF, providing a basis for understanding HBV‐ALF pathogenesis.
{"title":"Bioinformatics and experimental validation were combined to explore lactylation‐related biomarkers in HBV‐associated acute liver failure","authors":"Hao Pei, Yue‐qiao Chen, Feng‐lan Wu, Yan‐yan Zhang, Xue Zhang, Jian‐yu Li, Li‐yi Pan, Yu Chen, Yu‐wen Huang","doi":"10.1111/jgh.16739","DOIUrl":"https://doi.org/10.1111/jgh.16739","url":null,"abstract":"Background and AimCurrently, hepatitis B virus‐related acute liver failure (HBV‐ALF) has limited treatment options. Studies have shown that histone lactylation plays a role in the progression of liver‐related diseases. Therefore, it is essential to explore lactylation‐related gene (LRGs) biomarkers in HBV‐ALF to provide new information for the treatment of HBV‐ALF.MethodsTwo HBV‐ALF‐related datasets (GSE38941 and GSE14668) and 65 LRGs were used. First, the differentially expressed genes (DEGs) were derived from differential expression analysis, the key module genes from weighted gene co‐expression network analysis; and LRGs were used to intersect to obtain the candidate genes. Subsequently, the feature genes obtained from least absolute shrinkage and selection operator regression analysis and support vector machine analysis were intersected to obtain the candidate key genes. Among them, genes with consistent and significant expression trends in both GSE38941 and GSE14668 were used as biomarkers. Subsequently, biomarkers were analyzed for functional enrichment, immune infiltration, and sensitive drug prediction.ResultsIn this study, five candidate genes (<jats:italic>PIGM</jats:italic>, <jats:italic>PIGA</jats:italic>, <jats:italic>EGR1</jats:italic>, <jats:italic>PIGK</jats:italic>, and <jats:italic>PIGL</jats:italic>) were identified by intersecting 6461 DEGs and 2496 key module genes with 65 LRGs. We then screened four candidate key genes from the machine learning algorithm, among which <jats:italic>PIGM</jats:italic> and <jats:italic>PIGA</jats:italic> were considered biomarkers in HBV‐ALF. Moreover, the results of enrichment analysis showed that the significant enrichment signaling pathways for biomarkers included allograft rejection and valine, leucine, and isoleucine degradation. Thereafter, 11 immune cells differed significantly between groups, with resting memory CD4+ T cells having the strongest positive correlation with biomarkers. Methylphenidate hydrochloride is a potential therapeutic drug for <jats:italic>PIGM</jats:italic>.ConclusionTwo genes, <jats:italic>PIGM</jats:italic> and <jats:italic>PIGA</jats:italic>, were identified as biomarkers related to LRGs in HBV‐ALF, providing a basis for understanding HBV‐ALF pathogenesis.","PeriodicalId":15877,"journal":{"name":"Journal of Gastroenterology and Hepatology","volume":"65 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252010","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}
Zhen Yang, Haibin Xu, Luan Li, Kaiming Leng, Guangjun Shi
Background and AimPopulation‐based studies comparing clinical characteristics and survival disparities between patients with small bowel adenocarcinoma (SBA) and small bowel neuroendocrine tumors (SBNETs) in the United States are limited.MethodsData for patients with SBA or SBNETs, obtained from the Surveillance, Epidemiology, and End Results database for the years between 2000 and 2018 were analyzed.ResultsBetween 2000 and 2018, the age‐adjusted incidence of SBA experienced a marginal increase whereas SBNETs demonstrated a significant increase, emerging as the predominant subtype of small bowel cancer (SBC). Diagnoses peaked at ages 65–69 years for SBA and 60–64 years for SBNETs, with the latter exhibiting a heightened age‐specific incidence and maintaining equilibrium in gender distribution. Clinicopathologic disparities revealed SBA's duodenal predilection, larger tumor size, and advanced stages, contrasting with SBNETs' ileal predilection, early‐stage presentation, and superior outcomes. SBNETs patients underwent surgery more frequently but received less chemotherapy and radiation than SBA patients. Factors intricately correlated with a diagnosis of SBNETs included female gender, White race, advanced age, marital status, recent diagnoses, superior tumor differentiation, smaller size, distal location, and early‐stage presentation. Survival analysis unveiled a remarkable 79% reduction in the mortality risk for SBNETs compared with SBA. Subgroup analysis further confirmed the consistently favorable survival advantages of SBNETs, highlighting the clinical relevance of histological classification in prognostication.ConclusionCompared with SBA, SBNETs exhibited distinctive clinicopathological features characterized by a higher inclination toward low‐grade and early‐stage manifestations, thereby contributing to superior survival outcomes.
{"title":"Small bowel neuroendocrine tumors: Unique features and low lethality compared with small bowel adenocarcinoma","authors":"Zhen Yang, Haibin Xu, Luan Li, Kaiming Leng, Guangjun Shi","doi":"10.1111/jgh.16740","DOIUrl":"https://doi.org/10.1111/jgh.16740","url":null,"abstract":"Background and AimPopulation‐based studies comparing clinical characteristics and survival disparities between patients with small bowel adenocarcinoma (SBA) and small bowel neuroendocrine tumors (SBNETs) in the United States are limited.MethodsData for patients with SBA or SBNETs, obtained from the Surveillance, Epidemiology, and End Results database for the years between 2000 and 2018 were analyzed.ResultsBetween 2000 and 2018, the age‐adjusted incidence of SBA experienced a marginal increase whereas SBNETs demonstrated a significant increase, emerging as the predominant subtype of small bowel cancer (SBC). Diagnoses peaked at ages 65–69 years for SBA and 60–64 years for SBNETs, with the latter exhibiting a heightened age‐specific incidence and maintaining equilibrium in gender distribution. Clinicopathologic disparities revealed SBA's duodenal predilection, larger tumor size, and advanced stages, contrasting with SBNETs' ileal predilection, early‐stage presentation, and superior outcomes. SBNETs patients underwent surgery more frequently but received less chemotherapy and radiation than SBA patients. Factors intricately correlated with a diagnosis of SBNETs included female gender, White race, advanced age, marital status, recent diagnoses, superior tumor differentiation, smaller size, distal location, and early‐stage presentation. Survival analysis unveiled a remarkable 79% reduction in the mortality risk for SBNETs compared with SBA. Subgroup analysis further confirmed the consistently favorable survival advantages of SBNETs, highlighting the clinical relevance of histological classification in prognostication.ConclusionCompared with SBA, SBNETs exhibited distinctive clinicopathological features characterized by a higher inclination toward low‐grade and early‐stage manifestations, thereby contributing to superior survival outcomes.","PeriodicalId":15877,"journal":{"name":"Journal of Gastroenterology and Hepatology","volume":"187 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252187","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}
<p><b>47</b></p><p><b>University of California San Francisco (UCSF) criteria and liver dysfunction predict hepatocellular carcinoma (HCC) recurrence after surgery for HCC: A large multi-centre study</b></p><p><b>Conner Blackmore</b><sup>1,2</sup>, Ian Lockart<sup>2,3</sup>, Yuen Kang Joseph Yeoh<sup>2</sup>, Ciara Flynn<sup>2</sup>, Gregory Dore<sup>3,4</sup>, Mark Danta<sup>2,3</sup>, Jacob George<sup>5,6,7,8</sup>, Basheer Alshiwanna<sup>1,2,9</sup>, Maryam Alavi<sup>4</sup>, Behzad Hajarizadeh<sup>4</sup> and Miriam Tania Levy<sup>1,2,9</sup></p><p><sup>1</sup><i>Liverpool Hospital, Sydney, Australia;</i> <sup>2</sup><i>Faculty of Medicine, UNSW, Sydney, Australia;</i> <sup>3</sup><i>St Vincent's Hospital, Sydney, Australia;</i> <sup>4</sup><i>The Kirby Institute, Sydney, Australia;</i> <sup>5</sup><i>Storr Liver Centre, Sydney, Australia;</i> <sup>6</sup><i>Westmead Institute for Medical Research, Sydney, Australia;</i> <sup>7</sup><i>Westmead Hospital, Sydney, Australia;</i> <sup>8</sup><i>Faculty of Medicine, University of Sydney, Sydney, Australia;</i> <sup>9</sup><i>Ingham Institute for Applied Medical Research, Sydney, Australia</i></p><p><b><i>Background and Aim:</i></b> Primary liver cancer is the third leading cause of cancer-related death worldwide, with hepatocellular carcinoma (HCC) accounting for 80% of primary liver cancers. Liver resection is a curative treatment for early HCC (more than 2cm or when inaccessible to locoregional ablation), however there is a paucity of literature on predicting the likelihood of HCC recurrence following resection. We evaluated factors related to recurrence following primary HCC resection with curative intent.</p><p><b><i>Methods:</i></b> We retrospectively reviewed the electronic medical records of patients with HCC who underwent primary resection at three tertiary referral hospitals in Australia between January 2008 and May 2022. Baseline and follow-up characteristics, including liver disease, patient, and tumour characteristics were collected. The incidence rate of HCC recurrence following curative resection, and the factors associated with recurrence risk was evaluated.</p><p><b><i>Results:</i></b> A total of 242 patients underwent surgical resection with a median follow up of 36.6 months (IQR: 13.8-60.5). The overall survival rate at 3 years was 54%, with total disease-free survival at 3 years 29%. Underlying HCC aetiology was hepatitis C virus (HCV) in 73 (30%), hepatitis B virus (HBV) in 98 (41%) and non-viral in 71 (29%). Clear histological margins and complete post-operative radiological response was achieved in 190 (79%) patients with 1 (0.4%) 90-day mortality. Recurrence occurred in 94 (39%) with median time to recurrence of 18.8 months (IQR: 8.6-35]). The incidence rate of recurrence was 10.5 per 100 person-years (95% CI: 8.6 – 12.9). Multivariate Cox regression analysis identified an increased risk of HCC recurrence was independently associated with: MELD score > 7 (aHR: 2.36; 95% C
337磷-32联合植入和化疗：利用倾向分数加权地标分析与标准疗法的比较及其对局部晚期胰腺癌血管影响的评估使用倾向分数加权地标分析与标准疗法进行比较，并评估其对局部晚期胰腺癌血管的影响Amanda H Lim1,2、Darshan Nitchingham1、Jana Bednarz2,3、Madison Bills4、Laxmi Lanka5、Berry Allen6、Alvin Tan6、Rohit Joshi7、William Hsieh4、Benjamin Crouch4、Joshua Zobel1、John-Edwin Thomson8、EuLing Neo8、Romina Safaeian1、EdmundJoshua Zobel1、John-Edwin Thomson8、EuLing Neo8、Romina Safaeian1、Edmund Tse1,2、Christopher Rayner1,2、Andrew Ruszkiewicz2,9,10、Jayden Wong11、Nimit Singhal12、Dylan Bartholomeusz1,4、Frank Weilert13 和 Nam Nguyen1,21澳大利亚阿德莱德皇家医院胃肠病学和肝病学部；2University of Adelaide, Adelaide, Australia; 3SAHMRI Women and Kids Theme, South Australia Health and Medical Research Institute, Adelaide, Australia；4 澳大利亚阿德莱德皇家阿德莱德医院核医学科；5 新西兰汉密尔顿怀卡托医院放射科；6 新西兰汉密尔顿怀卡托医院核医学科；7 澳大利亚伊丽莎白谷莱尔麦克温医院医学肿瘤科；8 澳大利亚阿德莱德皇家阿德莱德医院肝胆外科；9Surgical Pathology, SA Pathology, Adelaide, Australia; 10Centre of Cancer Biology, University of South Australia, Adelaide, Australia; 11Department of Oncology, Waikato Hospital, Hamilton, New Zealand; 12Department of Oncology, Royal Adelaide Hospital, Adelaide, Australia; 13Department of Gastroenterology, Waikato Hospital, Hamilton, New Zealand背景和目的：胰腺癌的致死率很高。瘤内血管不畅导致其对化疗的反应有限。标准化疗与内窥镜超声（EUS）引导下的phophorus-32（32P）微粒瘤内植入相结合，对局部晚期胰腺癌（LAPC）取得了令人鼓舞的效果。然而，目前还缺乏比较研究。因此，我们采用倾向分数加权分析法（PSWA）对化疗和 32P 植入疗法与标准疗法进行了比较。我们还旨在使用对比增强型超声波（CE-EUS）评估植入 32P 后胰腺肿瘤血管的变化：我们进行了一项回顾性队列研究，将 2017 年 8 月至 2023 年 1 月期间在 2 个中心接受联合疗法的 LAPC 患者与来自单一中心的标准疗法患者进行了比较。采用地标分析来解决不朽时间偏倚问题。采用PSWA以减少选择偏倚的影响。主要结果是一线治疗开始后24个月的总生存期，治疗效果以受限平均生存时间（RMST；平均无事件生存时间）表示。在接受联合治疗的亚组患者中，在植入前、植入后 4 周和 12 周进行了 CE-EUS。对静脉注射造影剂后 90 秒的时间强度曲线进行分析，以确定峰值强度和强度增加：共考虑了 104 名患者。地标日期定为一线化疗开始后 3 个月。在排除了地标日期前死亡的患者后，101 名患者被纳入 PSWA（35 对 66 名仅接受化疗的患者）。据估计，与单纯化疗（347 天，95%CI 308-392）相比，采用联合疗法的患者在化疗开始后 24 个月内的 RMST 延长了 112 天（459 天，95%CI 393-536）。据估计，采用联合疗法后，24 个月内局部无进展的限制性平均时间延长了 112 天（95%CI 36-187），降期概率提高了 22.3%（95%CI 5.12-39.5，P=0.03）。分别有 18 名和 15 名患者在植入后 4 周和 12 周继续进行 CE-EUS 随访。植入后4周和12周，肿瘤内对比增强的基线（植入前、化疗后）中位强度增益分别从32.15（IQR 18.08-54.35）增至46.85（IQR 35.05-76.6；p=0.007）和66.3（IQR 54.7-76.3；p=0.001）：这是首次对LAPC患者进行化疗和32P植入与标准疗法的比较研究，研究结果表明，化疗和32P植入对患者的生存、疾病控制和分期均有益处。354同步神经系统和胃弥漫大 B 细胞淋巴瘤：病例报告Thant Zaw1、Ajish Radhamma1、2、Sharon Avery1 和 Montri Guratsakul1,21澳大利亚凯恩斯北凯恩斯医院；2 澳大利亚史密斯菲尔德詹姆斯库克大学简介：胃弥漫大B细胞淋巴瘤（DLBCL）是一种常见的胃淋巴瘤，以其侵袭性而闻名，通常对治疗有反应。然而，由于治疗方案有限，治疗同步中枢神经系统（CNS）DLBCL尤其具有挑战性。
{"title":"Gastrointestinal Cancer","authors":"","doi":"10.1111/jgh.16697","DOIUrl":"https://doi.org/10.1111/jgh.16697","url":null,"abstract":"<p><b>47</b></p><p><b>University of California San Francisco (UCSF) criteria and liver dysfunction predict hepatocellular carcinoma (HCC) recurrence after surgery for HCC: A large multi-centre study</b></p><p><b>Conner Blackmore</b><sup>1,2</sup>, Ian Lockart<sup>2,3</sup>, Yuen Kang Joseph Yeoh<sup>2</sup>, Ciara Flynn<sup>2</sup>, Gregory Dore<sup>3,4</sup>, Mark Danta<sup>2,3</sup>, Jacob George<sup>5,6,7,8</sup>, Basheer Alshiwanna<sup>1,2,9</sup>, Maryam Alavi<sup>4</sup>, Behzad Hajarizadeh<sup>4</sup> and Miriam Tania Levy<sup>1,2,9</sup></p><p><sup>1</sup><i>Liverpool Hospital, Sydney, Australia;</i> <sup>2</sup><i>Faculty of Medicine, UNSW, Sydney, Australia;</i> <sup>3</sup><i>St Vincent's Hospital, Sydney, Australia;</i> <sup>4</sup><i>The Kirby Institute, Sydney, Australia;</i> <sup>5</sup><i>Storr Liver Centre, Sydney, Australia;</i> <sup>6</sup><i>Westmead Institute for Medical Research, Sydney, Australia;</i> <sup>7</sup><i>Westmead Hospital, Sydney, Australia;</i> <sup>8</sup><i>Faculty of Medicine, University of Sydney, Sydney, Australia;</i> <sup>9</sup><i>Ingham Institute for Applied Medical Research, Sydney, Australia</i></p><p><b><i>Background and Aim:</i></b> Primary liver cancer is the third leading cause of cancer-related death worldwide, with hepatocellular carcinoma (HCC) accounting for 80% of primary liver cancers. Liver resection is a curative treatment for early HCC (more than 2cm or when inaccessible to locoregional ablation), however there is a paucity of literature on predicting the likelihood of HCC recurrence following resection. We evaluated factors related to recurrence following primary HCC resection with curative intent.</p><p><b><i>Methods:</i></b> We retrospectively reviewed the electronic medical records of patients with HCC who underwent primary resection at three tertiary referral hospitals in Australia between January 2008 and May 2022. Baseline and follow-up characteristics, including liver disease, patient, and tumour characteristics were collected. The incidence rate of HCC recurrence following curative resection, and the factors associated with recurrence risk was evaluated.</p><p><b><i>Results:</i></b> A total of 242 patients underwent surgical resection with a median follow up of 36.6 months (IQR: 13.8-60.5). The overall survival rate at 3 years was 54%, with total disease-free survival at 3 years 29%. Underlying HCC aetiology was hepatitis C virus (HCV) in 73 (30%), hepatitis B virus (HBV) in 98 (41%) and non-viral in 71 (29%). Clear histological margins and complete post-operative radiological response was achieved in 190 (79%) patients with 1 (0.4%) 90-day mortality. Recurrence occurred in 94 (39%) with median time to recurrence of 18.8 months (IQR: 8.6-35]). The incidence rate of recurrence was 10.5 per 100 person-years (95% CI: 8.6 – 12.9). Multivariate Cox regression analysis identified an increased risk of HCC recurrence was independently associated with: MELD score > 7 (aHR: 2.36; 95% C","PeriodicalId":15877,"journal":{"name":"Journal of Gastroenterology and Hepatology","volume":"39 S1","pages":"25-49"},"PeriodicalIF":3.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jgh.16697","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142230939","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}
<p><b>13</b></p><p><b>Comparative analysis of chronic kidney disease risk: Inflammatory bowel disease vs. autoimmune diseases</b></p><p><b>Ming-che Chuang</b><sup>1</sup>, Cheng-Li Lin<sup>2</sup>, Fuu-Jen Tsai<sup>3,4</sup> and Tsung-Yu Tsai<sup>1,4,5</sup></p><p><sup>1</sup><i>Center for Digestive Medicine, Department of Internal Medicine, China Medical University, Taichung, Taiwan (R.O.C.);</i> <sup>2</sup><i>Management Office for Health Data (DryLab), Clinical Trial Center (CTC),, China Medical University, Taichung, Taiwan (R.O.C.);</i> <sup>3</sup><i>Department of Medical Research, China Medical University Hospital, Taichung, Taiwan(R.O.C.);</i> <sup>4</sup><i>School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan (R.O.C.);</i> <sup>5</sup><i>School of Medicine, China Medical University, Taichung, Taiwan(R.O.C.)</i></p><p><b><i>Background and Aim:</i></b> Autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and type I diabetes mellitus, increase the risk of chronic kidney disease (CKD). Similarly, inflammatory bowel disease (IBD) patients also face an elevated risk of CKD, yet this is frequently disregarded due to an assumption that the occurrence and severity of kidney dysfunction are lower compared to other autoimmune diseases. However, the comparison of CKD risk between autoimmune diseases and IBD remains unknown. In this study, we aim to evaluate the risk of CKD between patients with autoimmune disease and IBD.</p><p><b><i>Methods:</i></b> Using the National Health Insurance database in Taiwan, we compared 11336 patients who were diagnosed with autoimmune disease with 2834 IBD patients during 2009-2019. Autoimmune diseases included as fellow: systemic lupus erythematosus, rheumatoid arthritis, psoriasis, systemic sclerosis, Sjogren's syndrome, Bechet’s disease, polymyositis, dermatomyositis, ankylosing spondylitis, autoimmune thyroiditis, and type 1 diabetes mellitus. We applied Cox regression analysis to estimate hazard ratios (HRs) for CKD in autoimmune disease and IBD.</p><p><b><i>Results:</i></b> The mean follow-up of patients with autoimmune disease and IBD was 6.06 and 5.99 years in this study (Table 1). We found that 346 events developed in 68669 person-year in patients with autoimmune disease compared with 78 events in 16988 person-year in patients with IBD (adjusted HR [aHR]: 1.09; 95% confidence interval [95% CI]: 0.85 to 1.39, p=0.51). However, we further divided IBD patients into ulcerative colitis group and Crohn's disease group and then evaluated the CKD risk with autoimmune disease separately. 29 events developed in patients with Crohn’s disease (aHR: 1.84; 95% CI, 1.25 to 2.69, p=0.002), and 49 events developed in patients with ulcerative colitis (aHR: 0.88; 95% CI: 0.65 to 1.18, p=0.39) (Table 2). The cumulative incidence of CKD was higher in patients with Crohn’s disease compared to the autoimmune disease patients (Figure 1).</p><p><b>15</b></p><p>
结论全球报告的皮质类固醇在 IBD 中的使用率参差不齐（13%-57%），我国报告的使用率处于较低水平，但大部分比较数据都是在较长时间内调查得出的。令人欣慰的是，当地的使用似乎是短期的，"深度缓解 "和 "疗程结束 "是停止使用的常见原因。在这个庞大的澳大利亚和新西兰队列中，鸦片剂的使用情况与国际数据相当。有趣的是，虽然皮质类固醇主要用于治疗 IBD，但鸦片制剂的使用似乎与其他合并症有关。对这些合并症（包括精神健康）进行检查对于进一步确定优化护理的机会非常重要。 241可预测溃疡性结肠炎患者服用维多利珠单抗两年临床缓解情况的简化评分系统的开发与验证Thanaboon Chaemsupaphan1,2、Aviv Pudipeddi1,3、Huiyu Lin1,4、Sudarshan Paramsothy1,3,5、Viraj Kariyawasam6 和 Rupert Leong1,3,51澳大利亚悉尼协和医院消化内科和肝脏服务部；2Division of Gastroenterology, Department of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand; 3Faculty of Medicine and Health, University of Sydney, Sydney, Australia; 4Department of Gastroenterology, Tan Tock Seng Hospital, Singapore; 5Faculty of Medicine and Health Sciences, Macquarie University, Australia; 6Department of Gastroenterology and Hepatology, Blacktown and Mount Druitt Hospital, Australia背景和目的：维多珠单抗是一种肠道选择性先进疗法，对治疗溃疡性结肠炎（UC）安全有效。患者一旦诱导成功，就有可能失去反应，导致病情最终复发。我们旨在确定这些预测因素，并开发一套实用的评分系统，以确定维多珠单抗的持续疗效：我们对从韦多珠单抗免疫调节剂强制撤药研究（VIEWS）中招募的前瞻性 UC 受试者进行了逻辑回归。所有患者在基线时均无皮质类固醇临床和内镜改善，并继续使用维多珠单抗。确定了两年无皮质类固醇临床缓解的预测因素，并将其模拟为VIEWS评分，然后在另一个UC队列中进行了验证：结果：在衍生队列的 62 名患者中，48 人（77.4%）在两年内保持了临床缓解。缓解的预测因素包括女性（OR:6.0）、抗肿瘤坏死因子幼稚期（OR:3.8）、基线组织学缓解（OR:10.8）、硫嘌呤联合应用（OR:3.6）和粪便钙蛋白水平≤250 μg/g（OR:6.3）。将这些因素纳入VIEWS评分后，预测两年临床缓解的AUROC曲线为0.89（95%CI:0.81-0.98）（图A：衍生队列，B：验证队列）。在验证队列的 64 名 UC 患者中，40 人（62.5%）在两年后仍保持临床缓解，AUROC 为 0.77（95%CI:0.60-0.94）。在截断阈值为4时，VIEWS评分识别两年临床缓解的敏感性为88.4%，特异性为63.6%：这项研究首次确定了服用维度利珠单抗的 UC 患者持续临床缓解的预测因素并提出了评分系统。对于复发风险较高的患者，与硫嘌呤联合治疗可能是有益的。亚太地区胃肠病学家对炎症性肠病组织学应用的认识和观点Thanaboon Chaemsupaphan1,2、Aviv Pudipeddi1,3、Huiyu Lin1,4、Hsin-Yun Wu5、Julajak Limsrivilai2、Shu-chen Wei6 和 Rupert Leong1,3,71澳大利亚悉尼协和遣返总医院胃肠病学和肝脏服务部；泰国曼谷玛希隆大学 Siriraj 医院医学系肠胃科；3 澳大利亚悉尼悉尼大学医学与健康学院；4 新加坡陈笃生医院胃肠病学部；5 台湾大学医院金山分院内科胃肠病学与肝病学部；6 台湾大学医院内科胃肠病学与肝病学部；7 澳大利亚悉尼麦考瑞大学医学与健康科学学院简介：近来，组织学结果作为炎症性肠病患者的潜在新治疗目标受到广泛关注。然而，亚太地区的胃肠病学家是否对组织学的应用有足够的了解并持积极态度，目前仍不清楚。本研究旨在通过一项全面调查来评估他们的知识和态度：方法：2023 年 5 月至 9 月，我们对亚太地区的胃肠病学家进行了横断面调查，其中包括 2022 年澳大利亚调查的数据。 71）和第 1 天（P=0.002，AUC=0.75）与第 3 个月的结肠切除术有关。同样，需要切除结肠的患者与不需要切除结肠的患者相比，第3天粪便中的IL-6更高（159.0 pg/mL vs 110.7 pg/mL，P=0.02，AUC 0.69）。需要进行结肠切除术的患者在IFX术后第3天的粪便TNF中位数为6.3 pg/mL，而避免结肠切除术的患者则降至检测限以下（P=0.004）。第 3 天粪便 TNF 预测结肠切除术（AUC=0.72），尤登指数阈值≥7.07 pg/mL，敏感性为 50%，特异性为 89.8%，PPV 为 43.8%，NPV 为 91.9%：结论：早期血清和粪便细胞因子可预测 ASUC 的预后。IFX治疗后3天粪便TNF持续存在与无应答和结肠切除术有关，可能有助于识别早期IFX再给药的受益患者。无应答者IL-6升高表明另一种免疫途径被激活，可能受益于非TNF靶向疗法：从溃疡性结肠炎患者出现硬化性肠系膜炎到小肠滤泡性淋巴瘤的挑战性诊断奥德赛Rebecca Cohen、Denis Rubtsov、Myat Khaing、Reuben Malloy、Ruth Ducommun 和 Ayesha Chapagain澳大利亚布里斯班查尔斯王子医院简介：硬化性肠系膜炎（SM）是一种影响肠系膜的罕见纤维化非肿瘤性疾病。肠系膜硬化症最常见于患者出生后的第 5 或第 6 个 10 年，可能会模仿炎症性肠病（IBD）发作，从而延误肠系膜硬化症的诊断。文献认为，既往手术、自身免疫和副肿瘤性疾病是潜在的诱发因素。非霍奇金淋巴瘤（NHL）是 SM 最常见的相关肿瘤。本病例研究重点介绍了一名患有溃疡性结肠炎（UC）和SM的患者后来被诊断为非霍奇金淋巴瘤（NHL，亚型滤泡性淋巴瘤（FL））的过程：一名 55 岁的男子因腹痛被转诊到我们的三级医疗中心，腹部计算机断层扫描（CT）显示肠系膜和腹膜后淋巴结病变，疑似淋巴瘤。他的直肠乙状结肠 UC（蒙特利尔分类 E2）病史于 2013 年确诊，接受美沙拉嗪治疗后病情完全缓解。对他进行了广泛的检查，首先进行了氟脱氧葡萄糖（FDG）正电子发射断层扫描（PET），显示腹膜后增厚、肠系膜淋巴结病变和小肠（SB）中的FDGavid灶（图1.A）。肠道磁共振（MR）显示，以肠系膜根部为中心的软组织广泛浸润融合，回肠近端信号改变，总体上提示淋巴瘤继发腹膜后纤维化。内镜超声显示肠系膜
{"title":"IBD Clinical","authors":"","doi":"10.1111/jgh.16702","DOIUrl":"https://doi.org/10.1111/jgh.16702","url":null,"abstract":"<p><b>13</b></p><p><b>Comparative analysis of chronic kidney disease risk: Inflammatory bowel disease vs. autoimmune diseases</b></p><p><b>Ming-che Chuang</b><sup>1</sup>, Cheng-Li Lin<sup>2</sup>, Fuu-Jen Tsai<sup>3,4</sup> and Tsung-Yu Tsai<sup>1,4,5</sup></p><p><sup>1</sup><i>Center for Digestive Medicine, Department of Internal Medicine, China Medical University, Taichung, Taiwan (R.O.C.);</i> <sup>2</sup><i>Management Office for Health Data (DryLab), Clinical Trial Center (CTC),, China Medical University, Taichung, Taiwan (R.O.C.);</i> <sup>3</sup><i>Department of Medical Research, China Medical University Hospital, Taichung, Taiwan(R.O.C.);</i> <sup>4</sup><i>School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan (R.O.C.);</i> <sup>5</sup><i>School of Medicine, China Medical University, Taichung, Taiwan(R.O.C.)</i></p><p><b><i>Background and Aim:</i></b> Autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and type I diabetes mellitus, increase the risk of chronic kidney disease (CKD). Similarly, inflammatory bowel disease (IBD) patients also face an elevated risk of CKD, yet this is frequently disregarded due to an assumption that the occurrence and severity of kidney dysfunction are lower compared to other autoimmune diseases. However, the comparison of CKD risk between autoimmune diseases and IBD remains unknown. In this study, we aim to evaluate the risk of CKD between patients with autoimmune disease and IBD.</p><p><b><i>Methods:</i></b> Using the National Health Insurance database in Taiwan, we compared 11336 patients who were diagnosed with autoimmune disease with 2834 IBD patients during 2009-2019. Autoimmune diseases included as fellow: systemic lupus erythematosus, rheumatoid arthritis, psoriasis, systemic sclerosis, Sjogren's syndrome, Bechet’s disease, polymyositis, dermatomyositis, ankylosing spondylitis, autoimmune thyroiditis, and type 1 diabetes mellitus. We applied Cox regression analysis to estimate hazard ratios (HRs) for CKD in autoimmune disease and IBD.</p><p><b><i>Results:</i></b> The mean follow-up of patients with autoimmune disease and IBD was 6.06 and 5.99 years in this study (Table 1). We found that 346 events developed in 68669 person-year in patients with autoimmune disease compared with 78 events in 16988 person-year in patients with IBD (adjusted HR [aHR]: 1.09; 95% confidence interval [95% CI]: 0.85 to 1.39, p=0.51). However, we further divided IBD patients into ulcerative colitis group and Crohn's disease group and then evaluated the CKD risk with autoimmune disease separately. 29 events developed in patients with Crohn’s disease (aHR: 1.84; 95% CI, 1.25 to 2.69, p=0.002), and 49 events developed in patients with ulcerative colitis (aHR: 0.88; 95% CI: 0.65 to 1.18, p=0.39) (Table 2). The cumulative incidence of CKD was higher in patients with Crohn’s disease compared to the autoimmune disease patients (Figure 1).</p><p><b>15</b></p><p>","PeriodicalId":15877,"journal":{"name":"Journal of Gastroenterology and Hepatology","volume":"39 S1","pages":"155-261"},"PeriodicalIF":3.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jgh.16702","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142230940","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}
<p><b>102</b></p><p><b>Therapeutic targeting of α-specific PI3K improves chemotherapy efficacy by inhibiting hepatic stellate cell activation in liver cancer</b></p><p><b>Qi Ruan</b><sup>1,2</sup>, Lu Cao<sup>1</sup>, Haotian Yang<sup>1,3</sup>, Leslie Burke<sup>1</sup>, Kim Bridle<sup>1,3</sup>, Darrell Crawford<sup>1,3</sup> and Xiaowen Liang<sup>1,2,3</sup></p><p><sup>1</sup><i>Gallipoli Medical Research, Brisbane, Australia;</i> <sup>2</sup><i>Fazer Institute, Brisbane, Australia;</i> <sup>3</sup><i>School of Medicine, Brisbane, Australia</i></p><p><b><i>Background and Aim:</i></b> Transarterial chemoembolization (TACE), administrating high dose of cisplatin, is a standard treatment for unresectable primary liver cancer. However, Liver cancer remains clinically challenging due to chemotherapy resistance, which has been associated with cancer-associated fibroblasts (CAFs). Activated hepatic stellate cells (HSCs), the main origin of CAFs in the tumour microenvironment (TME), contribute to fibrogenesis and treatment resistance. Understanding the molecular mechanisms of HSC activation in response to chemotherapy would identify potential targets to enhance treatment efficacy in liver cancer.</p><p><b><i>Methods:</i></b> CAFs subpopulations and the expression of alpha-smooth muscle actin (αSMA) were analysed in human hepatocellular carcinomas (HCC) patients with or without TACE using a single cell RNA sequencing dataset and immunohistochemistry staining on tumour tissues. The effect of chemotherapeutic drugs on HSC activation was examined <i>in vitro</i> by mixed-cell spheroids and conditioned medium (CM) of cisplatin pretreated Huh7 and HuCCT1 cells (human HCC and intrahepatic cholangiocarcinoma (ICC) cell lines). A pFRET HSP33 plasmid was transfected in LX2 cells (human HSC line) to monitor intracellular ROS levels in different CM. RNA sequencing profiled differential gene expression in primary HSCs in Huh7 cell CM treated with or without cisplatin. In the preclinical models of HCC and ICC, activation markers of HSCs and PI3K signalling were investigated in the tumour tissues after cisplatin treatment. Finally, PI3K α-specific inhibitors, HS-173 and alpelisib, were tested to determine their effectiveness in inhibiting chemotherapy-induced HSC activation. Combination treatment of cisplatin and alpelisib was administered to the orthotopic HCC mouse model, with tumour volume, PI3K signalling, and collagen deposition assessed using western blot and Masson trichrome staining.</p><p><b><i>Results:</i></b> The proportion of CAFs shifted towards the enrichment in COL1A1+ and ACTA2+ subpopulations, and increased αSMA expression was observed in tumour tissues of liver cancer patients after TACE treatment. LX2 cells were significantly activated by cisplatin-pretreated Huh7 and HuCCT1 cells through the paracrine effects. Increased ROS level was found in LX2 cells cultured in CM of Huh7 cells pretreated with cisplatin, indicating ROS mediated HSC activation.
102治疗靶向α特异性PI3K抑制肝癌肝星状细胞活化提高化疗疗效阮琦1,2, 曹璐1, 杨浩天1,3, Leslie Burke1, Kim Bridle1,3, Darrell Crawford1,3 和梁晓文1,2,31澳大利亚布里斯班加利波利医学研究中心；2Fazer 研究所，澳大利亚布里斯班；3医学院，澳大利亚布里斯班：经动脉化疗栓塞术（TACE）是一种治疗无法切除的原发性肝癌的标准方法，可使用大剂量顺铂。然而，由于化疗耐药性，肝癌在临床上仍具有挑战性，而化疗耐药性与癌症相关成纤维细胞（CAFs）有关。活化的肝星状细胞（HSCs）是肿瘤微环境（TME）中CAFs的主要来源，有助于纤维化和治疗耐药。了解造血干细胞在化疗反应中的激活分子机制将确定提高肝癌疗效的潜在靶点：方法：利用单细胞RNA测序数据集和肿瘤组织的免疫组化染色分析了接受或未接受TACE治疗的人类肝细胞癌（HCC）患者的CAFs亚群和α-平滑肌肌动蛋白（αSMA）的表达。化疗药物对造血干细胞活化的影响是通过混合细胞球和顺铂预处理的 Huh7 和 HuCCT1 细胞（人类 HCC 和肝内胆管癌 (ICC) 细胞系）的条件培养基 (CM) 在体外进行检测的。在 LX2 细胞（人造血干细胞系）中转染 pFRET HSP33 质粒，以监测不同 CM 中细胞内 ROS 的水平。RNA 测序分析了用或不用顺铂处理 Huh7 细胞 CM 中原发性造血干细胞的不同基因表达。在 HCC 和 ICC 临床前模型中，研究了顺铂治疗后肿瘤组织中造血干细胞和 PI3K 信号的活化标志物。最后，对PI3K α特异性抑制剂HS-173和alpelisib进行了测试，以确定它们在抑制化疗诱导的造血干细胞活化方面的有效性。对正位HCC小鼠模型进行顺铂和alpelisib联合治疗，使用Western印迹和Masson三色染色法评估肿瘤体积、PI3K信号传导和胶原沉积：结果：TACE治疗后，肝癌患者肿瘤组织中CAFs的比例向COL1A1+和ACTA2+亚群富集转变，αSMA表达增加。顺铂预处理的 Huh7 和 HuCCT1 细胞通过旁分泌效应明显激活了 LX2 细胞。在用顺铂预处理的Huh7细胞的CM中培养的LX2细胞中发现ROS水平升高，表明ROS介导了造血干细胞的活化。RNA测序显示顺铂诱导的造血干细胞活化过程中存在PI3K信号传导。在HCC和ICC小鼠模型的肿瘤组织中评估了PI3K信号分子，发现顺铂治疗后p110α及其下游的AKT和ERK显著增加。此外，靶向 p110α 可抑制顺铂诱导的造血干细胞活化。顺铂加 alpelisib 治疗可显著减轻 HCC 正位小鼠的肿瘤负荷，抑制 PI3K 信号传导，减少胶原沉积。新型 GPR119 激动剂 ps318 对饮食诱导肥胖小鼠肝脏健康的慢性影响Mohan Patil1、Dinesh Thapa1、Leon Warne2、Elena Dallerba3、Massimiliano Massi3、Rodrigo Carlessi1,4 和 Marco Falasca51 科廷医学院、科廷健康创新研究所、科廷大学、澳大利亚珀斯本特利；2 澳大利亚西珀斯 Little Green Pharma；3School of Molecular and Life Sciences, Curtin University, Perth, Australia; 4Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Perth, Nedlands, 6009, Australia; 5Department of Medicine and Surgery, University of Parma, Parma, 43125, Italy背景和目的：G-蛋白偶联受体-119（GPR119）激动剂已成为治疗非酒精性脂肪肝（NAFLD）的一种前景广阔的治疗策略。我们开发了一种新型小分子 GPR119 激动剂 ps318，它是一种油酰基-来苏磷脂酰肌醇（O-LPI）模拟物，可能靶向肠道胰高血糖素样肽-1（GLP-1）分泌的肠道定位受体。本研究调查了化合物 ps318 单药治疗和与西他列汀联合治疗对高脂饮食（HFD）诱导的肥胖小鼠肝脏健康状况的慢性影响：用高脂饮食（45% 千卡脂肪）喂养四周大的健康雄性 C57BL6/J 小鼠 20 周。随机分配的动物（n=10）连续十周口服复方 ps318，以剂量递增的方式提高复方的耐受性。治疗以 10 毫克/千克/天的剂量开始，每周递增 10 毫克/千克，直到最后两周达到 90 毫克/千克/天的最大剂量。
{"title":"Hepatology Basic Science","authors":"","doi":"10.1111/jgh.16699","DOIUrl":"https://doi.org/10.1111/jgh.16699","url":null,"abstract":"<p><b>102</b></p><p><b>Therapeutic targeting of α-specific PI3K improves chemotherapy efficacy by inhibiting hepatic stellate cell activation in liver cancer</b></p><p><b>Qi Ruan</b><sup>1,2</sup>, Lu Cao<sup>1</sup>, Haotian Yang<sup>1,3</sup>, Leslie Burke<sup>1</sup>, Kim Bridle<sup>1,3</sup>, Darrell Crawford<sup>1,3</sup> and Xiaowen Liang<sup>1,2,3</sup></p><p><sup>1</sup><i>Gallipoli Medical Research, Brisbane, Australia;</i> <sup>2</sup><i>Fazer Institute, Brisbane, Australia;</i> <sup>3</sup><i>School of Medicine, Brisbane, Australia</i></p><p><b><i>Background and Aim:</i></b> Transarterial chemoembolization (TACE), administrating high dose of cisplatin, is a standard treatment for unresectable primary liver cancer. However, Liver cancer remains clinically challenging due to chemotherapy resistance, which has been associated with cancer-associated fibroblasts (CAFs). Activated hepatic stellate cells (HSCs), the main origin of CAFs in the tumour microenvironment (TME), contribute to fibrogenesis and treatment resistance. Understanding the molecular mechanisms of HSC activation in response to chemotherapy would identify potential targets to enhance treatment efficacy in liver cancer.</p><p><b><i>Methods:</i></b> CAFs subpopulations and the expression of alpha-smooth muscle actin (αSMA) were analysed in human hepatocellular carcinomas (HCC) patients with or without TACE using a single cell RNA sequencing dataset and immunohistochemistry staining on tumour tissues. The effect of chemotherapeutic drugs on HSC activation was examined <i>in vitro</i> by mixed-cell spheroids and conditioned medium (CM) of cisplatin pretreated Huh7 and HuCCT1 cells (human HCC and intrahepatic cholangiocarcinoma (ICC) cell lines). A pFRET HSP33 plasmid was transfected in LX2 cells (human HSC line) to monitor intracellular ROS levels in different CM. RNA sequencing profiled differential gene expression in primary HSCs in Huh7 cell CM treated with or without cisplatin. In the preclinical models of HCC and ICC, activation markers of HSCs and PI3K signalling were investigated in the tumour tissues after cisplatin treatment. Finally, PI3K α-specific inhibitors, HS-173 and alpelisib, were tested to determine their effectiveness in inhibiting chemotherapy-induced HSC activation. Combination treatment of cisplatin and alpelisib was administered to the orthotopic HCC mouse model, with tumour volume, PI3K signalling, and collagen deposition assessed using western blot and Masson trichrome staining.</p><p><b><i>Results:</i></b> The proportion of CAFs shifted towards the enrichment in COL1A1+ and ACTA2+ subpopulations, and increased αSMA expression was observed in tumour tissues of liver cancer patients after TACE treatment. LX2 cells were significantly activated by cisplatin-pretreated Huh7 and HuCCT1 cells through the paracrine effects. Increased ROS level was found in LX2 cells cultured in CM of Huh7 cells pretreated with cisplatin, indicating ROS mediated HSC activation. ","PeriodicalId":15877,"journal":{"name":"Journal of Gastroenterology and Hepatology","volume":"39 S1","pages":"50-58"},"PeriodicalIF":3.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jgh.16699","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142230910","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}
<p><b>93</b></p><p><b>The biogeography of the mucosa-associated microbiota is associated with the presence and symptom severity of inflammatory bowel disease, proton pump inhibitor usage, and visceral sensitivity</b></p><p>Peter Sternes<sup>3</sup>, <b>Ayesha Shah</b><sup>1,2</sup>, Camila Ayela Pintos<sup>3</sup>, Thomas Fairlie<sup>1</sup>, Natasha Koloski<sup>1</sup>, Seungha Kang<sup>2</sup>, Simon McIlroy<sup>3</sup>, Mark Morrison<sup>2</sup>, Gene Tyson<sup>3</sup> and Gerald Holtmann<sup>1,2</sup></p><p><sup>1</sup><i>Princess Alexandria Hospital, Metro South Health, Woolloongabba, Australia;</i> <sup>2</sup><i>University of Queensland, Brisbane, Australia;</i> <sup>3</sup><i>Queensland University of Technology, Brisbane, Australia</i></p><p><b><i>Background and Aims:</i></b> We aimed to assess and compare the biogeography of the mucosa associated microbiome (MAM) in patients with inflammatory bowel disease (IBD) and controls in different segments of the gastrointestinal tract, and explore the links between the MAM, gastrointestinal symptoms and use of proton pump inhibitors (PPI).</p><p><b><i>Methods:</i></b> We recruited 59 controls (without structural abnormalities and gastrointestinal symptoms),44 patients with ulcerative colitis (UC) and 31 with Crohn’s disease (CD). Biopsies from various segments of the upper and lower gastrointestinal tract were collected. Microbial composition was assessed via 16S rRNA gene amplicon analysis and the bacterial load of the mucosal biopsies were assessed via qPCR. The MAM was examined in the context of disease status, PPI usage, the severity of gastrointestinal symptoms, and the symptom response to a standardized nutrient challenge (SNC).</p><p><b><i>Results:</i></b> Microbial communities of the MAM in the upper and lower gastrointestinal tract are different. Compared to controls, IBD patients were characterised by relative and absolute depletion of numerous butyrate and/or propionate producing genera, with the largest differentiation being the depletion of <i>Faecalibacterium</i> in the lower GI tract of CD patients. PPI users had enrichment of <i>Faecalibacterium</i>in the lower GI tract. The severity of gastrointestinal symptoms, as well as the symptom response to the SNC, were significantly associated with MAM composition in the GI tract.</p><p><b><i>Conclusion:</i></b> The absolute and relative composition of the MAM is variable across different segments of the GI tract and is different in patients with IBD and controls. Gastrointestinal symptoms are associated with quantitative changes of bacterial taxa along the GI tract.</p><p><b>125</b></p><p><b>Frequency of NUDT15 polymorphisms in a multicultural Australian IBD population</b></p><p><b>Tessa Greeve</b><sup>1,2</sup>, Georgia Sun<sup>1</sup> and Gregory Moore<sup>1,2</sup></p><p><sup>1</sup><i>Monash Health, Melbourne, Australia;</i> <sup>2</sup><i>Monash University, Melbourne, Australia</i></p><p><b><i>Background and Aim:</i></b> Thiopurine
结论：在我们的 IBD 群体中，NUDT15 变体的流行率明显高于之前在澳大利亚 IBD 群体中报道的流行率（4），这可能是由于之前研究的队列中欧洲血统占多数。在本研究中，一半的 NUDT15 等位基因携带者出生在澳大利亚，这很可能是祖先从高风险国家移民而来。这些结果表明，鉴于澳大利亚人口的多元文化特性，仅靠 TPMT 检测不足以识别硫嘌呤相关危害的高危人群。 参考文献 1. Van Gennep, S, Konté, K, Meijer, B, Heymans, MW, D'Haens, GR, Löwenberg, M, et al. Systematic review with meta-analysis: risk factors for thiopurine-induced leukopenia in IBD.Aliment Pharmacol Ther. 2019; 50(5):484-506. 2. Yang, S-K, Hong, M, Baek, J, Choi, H, Zhao, W, Jung, Y, et al. A common missense variant in NUDT15 confers susceptibility to thiopurine-induced leukopenia.自然遗传学》。 2014; 46(9):1017-20. 3. 澳大利亚胃肠病学会2018年炎症性肠病临床更新》（Gastroenterological Society of Australia Inflammatory Bowel Disease Clinical Update 2018. 2018. 4. Afrin，S，Simms，LA，Lord，A，Radford-Smith，GL. 澳大利亚炎症性肠病人群中的Nudix水解酶15（NUDT15）功能缺失变异。254 异位调节大麻素 1 受体作为炎症性肠病的新型治疗策略Dinesh Thapa1、Leon Warne1、Mohan Patil1、Marco Falasca2 和 Rodrigo Carlessi11Curtin 大学，澳大利亚本特利；2 帕尔马大学，意大利帕尔马背景和目的：由于目前的治疗方法主要是缓解症状，因此炎症性肠病（IBD）急需新型疗法。大麻素 1 受体（CB1R）是内源性大麻素系统的一部分，已被证明在 IBD 中失调。虽然四氢大麻酚（THC）主要通过对 CB1R 的正交调制而被证明可减轻 IBD，但其治疗应用受到行为副作用的限制。以 CB1R 的异构位点为靶点的药物已显示出对不同疾病的疗效，且无行为副作用。本研究利用小鼠 IBD 模型研究了 CB1R 异构调节剂 ZCZ011 单独或与亚治疗 THC 联用治疗 IBD 的作用：方法：8-10 周龄的雌性 BALB/c 小鼠在饮用水中添加 4% 的葡聚糖硫酸钠（DSS）7 天，然后再添加 3 天的普通水。每天腹腔注射 THC（2.5、5 和 10 毫克/千克）和/或 ZCZ011（20、30 和 40 毫克/千克），单独或联合用药，共 11 天。每天对小鼠的体重、粪便稠度和隐血/直肠出血情况进行评分，以计算疾病活动指数（DAI）。第 11 天，对小鼠实施安乐死，使用髓过氧化物酶 (MPO) 活性测定法评估结肠、脾脏、肾脏和肝脏的炎症情况，并测量器官的重量/长度。使用多重检测法评估结肠裂解物中细胞因子和趋化因子的表达。毒理学参数包括全血细胞计数（CBC）和肝/肾生化指标：结果：DSS 攻击小鼠的 DAI 评分、炎症和疼痛行为增加，结肠长度减少，MPO 活性和细胞因子表达增加，肝脏和脾脏重量增加。10 毫克/千克的 THC（2.5 毫克/千克和 5 毫克/千克）能显著减轻 IBD，表现为 DAI 评分降低、MPO 活性增强和结肠长度增加。第 8 天后，单独使用 ZCZ011 的效果减弱。然而，2.5 毫克/千克 THC 和 20 毫克/千克 ZCZ011 的组合能显著减轻 IBD，表现为 DAI 评分降低、无疼痛行为、结肠长度增加和 MPO 活性降低。体重和器官重量与健康对照组相当。THC 和 ZCZ011，特别是 2.5 毫克/千克 THC 和 20 毫克/千克 ZCZ011 的组合，未观察到毒性。262 抗原特异性调节性 T 细胞治疗炎症性肠病玛丽-李（Marie Lee）2、印第安纳-佐考（Indiana Zorkau）2、约书亚-奥伊（Joshua Ooi）2、彼得-埃根惠森（Peter Eggenhuizen）2 和里玛-戈德伯格（Rimma Goldberg）11 澳大利亚克莱顿莫纳什健康中心肠胃病学系；澳大利亚墨尔本莫纳什大学炎症性疾病中心医学系2背景和目的：炎症性肠病（IBD）是由炎症效应 T 细胞反应和调节性 T 细胞（Tregs）的不平衡引起的，调节性 T 细胞无法充分抑制免疫介导的病理变化。目前治疗 IBD 的方法主要是广泛的免疫抑制或阻断特定的促炎细胞因子，但由于 T 细胞免疫反应的失衡问题没有得到充分解决，一半以上的患者治疗失败。
{"title":"IBD Basic Science","authors":"","doi":"10.1111/jgh.16701","DOIUrl":"https://doi.org/10.1111/jgh.16701","url":null,"abstract":"<p><b>93</b></p><p><b>The biogeography of the mucosa-associated microbiota is associated with the presence and symptom severity of inflammatory bowel disease, proton pump inhibitor usage, and visceral sensitivity</b></p><p>Peter Sternes<sup>3</sup>, <b>Ayesha Shah</b><sup>1,2</sup>, Camila Ayela Pintos<sup>3</sup>, Thomas Fairlie<sup>1</sup>, Natasha Koloski<sup>1</sup>, Seungha Kang<sup>2</sup>, Simon McIlroy<sup>3</sup>, Mark Morrison<sup>2</sup>, Gene Tyson<sup>3</sup> and Gerald Holtmann<sup>1,2</sup></p><p><sup>1</sup><i>Princess Alexandria Hospital, Metro South Health, Woolloongabba, Australia;</i> <sup>2</sup><i>University of Queensland, Brisbane, Australia;</i> <sup>3</sup><i>Queensland University of Technology, Brisbane, Australia</i></p><p><b><i>Background and Aims:</i></b> We aimed to assess and compare the biogeography of the mucosa associated microbiome (MAM) in patients with inflammatory bowel disease (IBD) and controls in different segments of the gastrointestinal tract, and explore the links between the MAM, gastrointestinal symptoms and use of proton pump inhibitors (PPI).</p><p><b><i>Methods:</i></b> We recruited 59 controls (without structural abnormalities and gastrointestinal symptoms),44 patients with ulcerative colitis (UC) and 31 with Crohn’s disease (CD). Biopsies from various segments of the upper and lower gastrointestinal tract were collected. Microbial composition was assessed via 16S rRNA gene amplicon analysis and the bacterial load of the mucosal biopsies were assessed via qPCR. The MAM was examined in the context of disease status, PPI usage, the severity of gastrointestinal symptoms, and the symptom response to a standardized nutrient challenge (SNC).</p><p><b><i>Results:</i></b> Microbial communities of the MAM in the upper and lower gastrointestinal tract are different. Compared to controls, IBD patients were characterised by relative and absolute depletion of numerous butyrate and/or propionate producing genera, with the largest differentiation being the depletion of <i>Faecalibacterium</i> in the lower GI tract of CD patients. PPI users had enrichment of <i>Faecalibacterium</i>in the lower GI tract. The severity of gastrointestinal symptoms, as well as the symptom response to the SNC, were significantly associated with MAM composition in the GI tract.</p><p><b><i>Conclusion:</i></b> The absolute and relative composition of the MAM is variable across different segments of the GI tract and is different in patients with IBD and controls. Gastrointestinal symptoms are associated with quantitative changes of bacterial taxa along the GI tract.</p><p><b>125</b></p><p><b>Frequency of NUDT15 polymorphisms in a multicultural Australian IBD population</b></p><p><b>Tessa Greeve</b><sup>1,2</sup>, Georgia Sun<sup>1</sup> and Gregory Moore<sup>1,2</sup></p><p><sup>1</sup><i>Monash Health, Melbourne, Australia;</i> <sup>2</sup><i>Monash University, Melbourne, Australia</i></p><p><b><i>Background and Aim:</i></b> Thiopurine ","PeriodicalId":15877,"journal":{"name":"Journal of Gastroenterology and Hepatology","volume":"39 S1","pages":"146-154"},"PeriodicalIF":3.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jgh.16701","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142230912","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}
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