Translational gastroenterology and hepatology最新文献

{"title":"Serum zinc concentration as a potential predictor of presarcopenia in patients with chronic liver disease: a preliminary study.","authors":"Mitsuyuki Suzuki, Toru Ishikawa, Kazuki Ohashi, Asami Hoshii, Hiroshi Hirosawa, Hirohito Noguchi, Terasu Honma","doi":"10.21037/tgh-23-77","DOIUrl":"10.21037/tgh-23-77","url":null,"abstract":"<p><strong>Background: </strong>Presarcopenia is a common complication of chronic liver disease. However, the relationship between serum zinc concentration and presarcopenia in patients with chronic liver disease remains unclear. Herein, we examined whether serum zinc concentration could predict presarcopenia in patients with chronic liver disease.</p><p><strong>Methods: </strong>Between October 2015 and December 2019, 278 patients with chronic liver disease (median age, 68 years; women/men, 133/145; hepatitis B virus/hepatitis C virus/negative hepatitis B surface antigen and negative anti-hepatitis C virus antibody, 55/124/99) who underwent abdominal computed tomography (CT) and simultaneous measurement of serum zinc concentration were included. Zinc deficiency and subclinical zinc deficiency were classified using serum zinc concentration cutoff values of <60 and <80 μg/dL [based on the Japanese Society of Clinical Nutrition (JSCN) guidelines], respectively. Additionally, presarcopenia was evaluated based on the skeletal muscle mass as per the Japan Society of Hepatology (JSH)'s sarcopenia criteria.</p><p><strong>Results: </strong>Univariate analysis revealed that the following factors were significantly associated with the presence of presarcopenia in patients with chronic liver disease: age (P<0.001), male sex (P<0.001), body mass index (BMI) (P<0.001), serum zinc concentration (P=0.005), fibrosis-4 index (P<0.001), and serum albumin concentration (P=0.03). Additionally, the median L3 skeletal muscle indices were as follows: men, non-presarcopenia group/presarcopenia group, 47.56/37.91 cm²/m² (P<0.001); women, non-presarcopenia group/presarcopenia group, 41.64/32.88 cm²/m² (P<0.001). Multivariate analysis using logistic regression analysis revealed that male sex [odds ratio (OR), 0.194; 95% confidence interval (CI): 0.089-0.419; P<0.001], BMI (OR, 0.666; 95% CI: 0.582-0.761; P<0.001), and serum zinc concentration <60 μg/dL (OR, 5.930; 95% CI: 1.480-23.80; P=0.01) were factors associated with presarcopenia. The OR for serum zinc concentration between 60 and 80 μg/dL was 1.910 (95% CI: 0.824-4.420; P=0.13).</p><p><strong>Conclusions: </strong>Low serum zinc levels may be an independent predictor of presarcopenia in patients with chronic liver disease.</p>","PeriodicalId":94362,"journal":{"name":"Translational gastroenterology and hepatology","volume":"9 ","pages":"20"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11074487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140878363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Viral esophagitis in non-human immunodeficiency virus patients: a case-control study.","authors":"Ahmad Al-Dwairy, Loai Azar, Tarek Bakain, Akram Ahmad, Stephanie Woo, Pichayut Nithagon, Walid Chalhoub","doi":"10.21037/tgh-23-44","DOIUrl":"10.21037/tgh-23-44","url":null,"abstract":"<p><strong>Background: </strong>Esophagitis, inflammation of the esophagus, can result from various causes, including reflux, infections, food allergies, medications, and trauma. Infectious esophagitis is the third most common cause after gastroesophageal reflux disease (GERD) and eosinophilic esophagitis worldwide. The primary causes of infectious esophagitis are candida esophagitis and viral esophagitis (VE) caused by herpes simplex virus (HSV) or cytomegalovirus (CMV). VE is typically associated with immunosuppression, with risk factors such as malignancy, chemotherapy, organ transplant, and human immunodeficiency virus (HIV). Infectious esophagitis is prevalent in about one-third of untreated acquired immunodeficiency syndrome (AIDS) patients, but recent reports indicate an increase in VE cases among immunocompetent individuals. This study aims to explore risk factors and patient demographics in non-HIV individuals.</p><p><strong>Methods: </strong>A case-control study that included patients 18 years and older diagnosed with HSV or CMV esophagitis who were identified through histopathologic examination or immunohistochemical staining. Cases were obtained by searching pathology reports between 2009-2022 from five MedStar Health Hospitals in the District of Columbia and Maryland. Controls were selected based on International Classification of Diseases (ICD) codes for esophagogastroduodenoscopy (EGD) with negative VE results within the same period. Patient demographics, comorbidities, laboratory parameters, endoscopic findings, and potential risk factors were collected through chart review.</p><p><strong>Results: </strong>Out of 40,224 cases between 2009-2022, 50 cases of VE were identified, with 30 cases attributed to HSV, 19 cases to CMV, and one case of HSV/CMV coinfection. Hematemesis was the predominant symptom in patients with HSV (33%), while dysphagia was more prevalent in CMV patients (42%). The most common finding during EGD was ulceration in HSV patients (67%) and esophagitis in CMV patients (37%). Patients with VE had a higher likelihood of a history of immunosuppressive therapy, organ transplant, active malignancy, and systemic steroid use. However, a significant portion (34%) had no identifiable risk factors.</p><p><strong>Conclusions: </strong>The study's findings contribute to a better understanding of the clinical characteristics and risk factors associated with VE in non-HIV patients. The identification of immunosuppression and specific risk factors can aid in early detection, appropriate management, and targeted interventions for VE. Further research is warranted to explore the rising incidence of VE in immunocompetent individuals and to optimize preventive strategies and treatment approaches for this condition.</p>","PeriodicalId":94362,"journal":{"name":"Translational gastroenterology and hepatology","volume":"9 ","pages":"19"},"PeriodicalIF":0.0,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11074486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140878364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing the protective effects of local and remote ischemic preconditioning against ischemia-reperfusion injury in hepatectomy: a systematic review and network meta-analysis.","authors":"Yaru Chen, Jin Yan, Kai Wang, Zhenghua Zhu","doi":"10.21037/tgh-23-95","DOIUrl":"10.21037/tgh-23-95","url":null,"abstract":"<p><strong>Background: </strong>Local ischemic preconditioning (LIPC) has been proven to be a protective strategy against hepatic ischemia-reperfusion injury (HIRI) during hepatectomy. Growing evidence suggests remote ischemic preconditioning (RIPC) has the potential to reduce liver injury in hepatectomy. Few studies have directly compared the protective effects of these two mechanical preconditioning strategies. Therefore, we performed a network meta-analysis to compare the efficacy of LIPC and RIPC for hepatic injury during liver resection.</p><p><strong>Methods: </strong>We searched Cochrane, PubMed, Embase, and China National Knowledge Infrastructure (CNKI) from the database inception to January 2023. We included studies directly comparing the effectiveness of LIPC and RIPC and those comparing LIPC or RIPC with no-preconditioning in liver resection. Postoperative liver function and surgical events were analyzed. Data were expressed as standardized mean differences (SMDs) or odds ratios (ORs) and analyzed using network meta-analysis with random effects model.</p><p><strong>Results: </strong>Following the screening of 268 citations, we identified 26 eligible randomized clinical trials (RCTs) involving 1,476 participants (LIPC arm: 789, RIPC arm: 859, no-preconditioning arm: 1,072). LIPC and RIPC were superior to no-preconditioning in reducing postoperative serum transaminase levels [aspartate aminotransferase (AST): SMD RIPC versus no-preconditioning: -2.05, 95% confidence interval (CI): -3.39, -0.71; SMD LIPC versus no-preconditioning: -1.10, 95% CI: -2.07, -0.12; alanine aminotransferase (ALT): SMD RIPC versus no-preconditioning: -2.24, 95% CI: -4.15, -0.32; SMD LIPC versus no-preconditioning: -1.32, 95% CI: -2.63, -0.01]. No significant difference was observed between RIPC and LIPC in postoperative liver function and surgical outcomes (AST: SMD RIPC versus LIPC: -0.95, 95% CI: -2.52, 0.62; ALT: SMD RIPC versus LIPC: -0.91, 95% CI: -3.11, 1.28). In addition, the subgroup analysis revealed the potential benefits of RIPC in improving liver function, especially in patients who diagnosed with cirrhosis or underwent major resection.</p><p><strong>Conclusions: </strong>RIPC and LIPC could serve as effective strategies in relieving HIRI during hepatectomy. No significant differences were observed between LIPC and RIPC, however, RIPC may be an easily applicable strategy to relieve liver injury in hepatectomy.</p>","PeriodicalId":94362,"journal":{"name":"Translational gastroenterology and hepatology","volume":"9 ","pages":"13"},"PeriodicalIF":0.0,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11074492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140878357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Family history as a major prerequisite for microsatellite instability screening in colorectal cancer is a poor selection tool.","authors":"Daniel Jakob, Valerie Orth, Daniel Gödde, Hubert Zirngibl, Peter C Ambe","doi":"10.21037/tgh-23-71","DOIUrl":"10.21037/tgh-23-71","url":null,"abstract":"<p><strong>Background: </strong>Deficient mismatch repair (MMR) leading to microsatellite instability (MSI) in tumors is thought to be present in over 15% of colorectal cancer (CRC) cases. Testing CRC for MSI has traditionally been recommended following the fulfillment of clinical criteria. However, the performance of clinical criteria, especially the family history, as a selection tool for MSI screening in CRC is questionable.</p><p><strong>Methods: </strong>We retrospectively investigated the incidence of high degree MSI (MSI-H) tumors in an unselected population of CRC patients and compared its prevalence between individuals with and without family history of cancers within the spectrum of MSI-H tumors as defined in the revised Bethesda criteria.</p><p><strong>Results: </strong>The study population included 274 patients, 70 with positive and 204 without family history of MSI-H tumors with complete data including findings from MSI analysis. The overall incidence of MSI-H CRC was 18.98%. There was no statistically significant difference in the incidence of MSI-H CRC amongst both groups. The sensitivity and specificity of family history with regard to the presence of an MSI-H tumor in this collective was 36.5% and 77.5%, respectively.</p><p><strong>Conclusions: </strong>A relevant number of cases with high MSI-H CRC may be missed secondary to screening based on clinical criteria like family history alone. Thus, systematic screening independent of clinical characteristics, especially family history of cancer should be recommended in all cases with CRC.</p>","PeriodicalId":94362,"journal":{"name":"Translational gastroenterology and hepatology","volume":"9 ","pages":"17"},"PeriodicalIF":0.0,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11074476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140878325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of intra-operative ketamine on postoperative outcomes in abdominal surgery: a narrative review.","authors":"Daniela Kerguelen Murcia, Joy S Li, Uma R Phatak","doi":"10.21037/tgh-23-97","DOIUrl":"10.21037/tgh-23-97","url":null,"abstract":"<p><strong>Background and objective: </strong>Ketamine offers a promising solution to common postoperative issues in abdominal surgery, including pain, nausea, opioid use, and opioid-related side effects. The purpose of this literature review is to analyze the benefits and potential adverse effects associated with the intraoperative utilization of ketamine during abdominal surgeries.</p><p><strong>Methods: </strong>A comprehensive search of PubMed and Ovid MEDLINE was conducted by two independent reviewers. Studies were included if they targeted adult patients and evaluated intra-operative use of ketamine for abdominal operations.</p><p><strong>Key content and findings: </strong>We identified 13 studies of intraoperative use of ketamine in abdominal surgery. The results of these studies showed improved pain management as demonstrated by lower pain scores, decreased hyperalgesia, and a decreased need for additional analgesics. The results also demonstrated a decrease in opioid consumption during the critical 24-hour postoperative period. However, a few studies reported undesirable side effects such as hallucinations and delirium.</p><p><strong>Conclusions: </strong>The intraoperative use of ketamine holds promise as a valuable adjunct to anesthesia during abdominal surgeries. Studies support its use in improving post-operative pain and decreasing opioid consumption. Due to risks of adverse effects, further studies in larger patient populations may help identify which patients will benefit the most. This review offers a succinct selection of the pertinent literature.</p>","PeriodicalId":94362,"journal":{"name":"Translational gastroenterology and hepatology","volume":"9 ","pages":"25"},"PeriodicalIF":0.0,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11074488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140878326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Esophageal carcinoma with <i>SMARCA4</i> mutation: a narrative review for this rare entity.","authors":"Jing Xu, Zhikai Chi","doi":"10.21037/tgh-23-84","DOIUrl":"10.21037/tgh-23-84","url":null,"abstract":"<p><strong>Background and objective: </strong>Esophageal carcinoma with switch/sucrose nonfermenting (SWI/SNF)-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 (<i>SMARCA4</i>) mutation is a rare variant of malignant esophageal epithelial neoplasm, which is characterized by the loss of SMARCA4/BRG1 protein on immunohistochemistry or alterations in the <i>SMARCA4</i> gene on sequencing. Only a few case series and case reports of esophageal carcinoma with <i>SMARCA4</i> mutations have been published in the English literature; the rarity of the disease poses significant diagnostic challenges for surgical pathologists and could potentially lead to delayed or suboptimal patient care. Herein, we reviewed the available literature on esophageal carcinoma with <i>SMARCA4</i> mutations to discuss its epidemiology, clinical presentation, pathological and molecular features, diagnostic challenges, treatment, and prognosis.</p><p><strong>Methods: </strong>The PubMed, Scopus, Ovid, and Google Scholar databases were extensively reviewed. The references included in the articles were cross-examined to identify any missing articles. We searched for all published literature on esophageal carcinoma with <i>SMARCA4</i> mutations from inception of the databases to date.</p><p><strong>Key content and findings: </strong>Esophageal carcinoma with <i>SMARCA4</i> mutations is most common in middle-aged and older men. Barrett esophagus and gastroesophageal reflux disease (GERD) are the most associated risk factors. Dysphagia was the most common initial clinical presentation. Esophagogastroduodenoscopy (EGD) is the preferred diagnostic modality. Microscopically, the tumor cells exhibited epithelioid features mixed with variable components of rhabdoid and glandular differentiation. The tumor cells showed variable immunoreactivity for cytokeratin and sometimes weakly expressed neuroendocrine or B-lymphocyte markers (Pax5), which are potential diagnostic pitfalls. Melanoma marker tests showed negative results. The SMARCB1/INI1 protein remains intact, and a definitive diagnosis necessitates the presence of either SMARCA4/BRG1 protein loss or <i>SMARCA4</i> gene mutations. Esophageal carcinoma with <i>SMARCA4</i> mutations shows overly aggressive behavior and presents with advanced stages of disease; most patients succumb to the disease within 1 year of initial diagnosis.</p><p><strong>Conclusions: </strong>Esophageal carcinoma with <i>SMARCA4</i> mutation is an overly aggressive disease, and further research on the affected molecular pathway may help improve its prognosis.</p>","PeriodicalId":94362,"journal":{"name":"Translational gastroenterology and hepatology","volume":"9 ","pages":"24"},"PeriodicalIF":0.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11074479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140878324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PIM1 inhibitor SMI-4a attenuated concanavalin A-induced acute hepatitis through suppressing inflammatory responses.","authors":"Xinwan Wu, Yuwei Chen, Meiru Jiang, Long Guo","doi":"10.21037/tgh-23-93","DOIUrl":"10.21037/tgh-23-93","url":null,"abstract":"<p><strong>Background: </strong>Serine/threonine kinase 1 (PIM1) plays a crucial role in cell growth, differentiation, and apoptosis. However, its role in the pathogenesis of concanavalin A (ConA)-induced acute hepatitis is not well understood. PIM1 kinase inhibitor can reduce the expression of PIM1. This study aims to investigate the effects of PIM1 kinase inhibitor and its protective mechanism in ConA-induced acute hepatitis.</p><p><strong>Methods: </strong>C57/BL six mice were injected with ConA (20, 15, and 12 mg/kg) to induce acute hepatitis, and PIM1 kinase inhibitor SMI-4a (60 mg/kg) was administered orally 24 h before ConA injection. The survival rate of the mice was observed after ConA injection. The levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured. Serum inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was performed on liver tissue collected at different time points. The major cytokines expression in liver tissue was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The number of macrophages, T-cell and neutrophils in liver tissue were detected by flow cytometry (FCM). PIM1 in liver tissue was detected by western blot (WB) and qRT-PCR. SMI-4a (80 µM) was pretreated for 24 h and ConA (400 µg/mL) was stimulated for 12 h in RAW264.7 cell model. Phosphorylated p65 (p-p65) and cleaved caspase-3 (c-caspase-3) in liver tissue and macrophages were detected by WB.</p><p><strong>Results: </strong>Different concentrations of ConA caused different acute hepatitis mortality, 12 mg/kg concentration within 24 h of the mortality showed a gradient increase. The levels of AST and ALT increased significantly at 12 h after ConA injection. PIM1 expression was upregulated at 12 h. SMI-4a can suppress the PIM1 expression. SMI-4a suppressed cytokines production, AST, and ALT in ConA-treated serum. SMI-4a suppressed the major cytokines in liver tissue. Tests in liver tissue showed that SMI-4a reduced the number of T cells, neutrophils, and macrophages. SMI-4a inhibited the inflammatory response by downregulating the expression of p-p65. Meanwhile, apoptosis was decreased by decreasing the expression of c-caspase-3.</p><p><strong>Conclusions: </strong>In conclusion, the protective effect of SMI-4a against acute hepatitis is by reducing the inflammatory response and apoptosis. These findings suggest that SMI-4a may have therapeutic potential in the treatment of autoimmune hepatitis.</p>","PeriodicalId":94362,"journal":{"name":"Translational gastroenterology and hepatology","volume":"9 ","pages":"14"},"PeriodicalIF":0.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11074483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140878359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of irritable bowel syndrome: a narrative review.","authors":"Bhavana Tetali, Suraj Suresh","doi":"10.21037/tgh-23-96","DOIUrl":"10.21037/tgh-23-96","url":null,"abstract":"<p><strong>Background and objective: </strong>As our understanding of the pathophysiology of irritable bowel syndrome (IBS) has advanced, so too has the therapeutic landscape, offering a myriad of approaches to alleviate symptoms and enhance the well-being of patients. This review paper is dedicated to a comprehensive exploration of the diverse therapeutic modalities available for managing IBS. By delving into the complexities of IBS therapeutics, our aim is to contribute to the enhancement of patient care and the overall quality of life for patients grappling with this complex condition.</p><p><strong>Methods: </strong>This review utilized information from PubMed/MEDLINE using the key search term \"irritable bowel syndrome\" as well as the 2020 American College of Gastroenterology (ACG) and 2022 American Gastroenterological Association (AGA) society guidelines on IBS. The search was restricted to articles in the English language only and included peer-reviewed observational studies and randomized controlled trials (RCTs) in adult patients from April 22, 2020 to October 16, 2023.</p><p><strong>Key content and findings: </strong>This review will start with an overview of the current guidelines for pharmacologic therapies for IBS as recommended by the ACG and the AGA, with an emphasis on clinical trials published after the most recent guidelines. It will then delve into the literature on dietary modifications, probiotics, fecal microbiota transplant, behavioral therapy, and complementary and alternative medicine approaches to IBS.</p><p><strong>Conclusions: </strong>It is evident that the management of IBS has transcended a one-size-fits-all approach. As the field of IBS management continues to evolve, it is imperative for physicians to stay informed and receptive to the array of therapeutic options available, ultimately providing patients with the most effective and personalized care.</p>","PeriodicalId":94362,"journal":{"name":"Translational gastroenterology and hepatology","volume":"9 ","pages":"26"},"PeriodicalIF":0.0,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11074491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140878328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resection and reconstruction of the largest abdominal vein system (the inferior vena cava, hepatic, and portal vein): a narrative review.","authors":"Junichi Kaneko, Yoshihiro Hayashi, Yusuke Kazami, Yujiro Nishioka, Akinori Miyata, Akihiko Ichida, Yoshikuni Kawaguchi, Nobuhisa Akamatsu, Kiyoshi Hasegawa","doi":"10.21037/tgh-23-90","DOIUrl":"10.21037/tgh-23-90","url":null,"abstract":"<p><strong>Background and objective: </strong>As tumors invade major abdominal veins, surgical procedures are transformed from simple and basic to complicated and challenging. In this narrative review, we focus on what is currently known and not known regarding the technical aspects of major abdominal venous resection and its reconstruction, patency, and oncologic benefit in a cross-cutting perspective.</p><p><strong>Methods: </strong>A systematic literature search was performed in PubMed and Semantic Scholar from inception up to October 18, 2023. We reviewed 106 papers by title, abstract, and full text regarding resection or reconstruction of the inferior vena cava, hepatic vein confluence, portal vein (PV), and middle hepatic vein (MHV) tributaries in living donor liver transplantation (LDLT) in a cross-cutting perspective.</p><p><strong>Key content and findings: </strong>The oncologic benefit of aggressive hepatic vein resection with suitable reconstruction against adenocarcinoma remains unclear, and further studies are required to clarify this point. A superior mesenteric/PV resection is now a universal, indispensable, and effective procedure for pancreatic ductal adenocarcinoma. Although many case series using tailor-made autologous venous grafts have been reported, not only size mismatch but also additional surgical incisions and a longer operation time remain obstacles for venous reconstruction. The use of autologous alternative tissue remains only an alternative procedure because the patency rate of customized tubular conduit type to interpose or replace the resected vein is not known. Unlike arterial replacement, venous replacement using synthetic vascular grafts is still rarely reported and there are several inherent limitations except for reconstruction of tributaries of MHV in LDLT.</p><p><strong>Conclusions: </strong>Various approaches to abdominal vein resection and replacement or reconstruction are technically feasible with satisfactory results. Synthetic vascular grafts may be appropriate but have a certain rate of complications.</p>","PeriodicalId":94362,"journal":{"name":"Translational gastroenterology and hepatology","volume":"9 ","pages":"23"},"PeriodicalIF":0.0,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11074493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140878361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nivolumab plus ONC201 plus in microsatellite stable (MSS) metastatic colorectal cancer (mCRC) patients: a Brown University Oncology Research Group phase Ib/II study (BrUOG379).","authors":"Khaldoun Almhanna, Rimini Breakstone, Alexander Raufi, Roxanne Wood, Amy Webber, Sopha Dionson, Lindsay Cavanagh, Attila A Seyhan, Howard Safran, Wafik El-Deiry","doi":"10.21037/tgh-23-69","DOIUrl":"10.21037/tgh-23-69","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors alone, or in combination with chemotherapy failed to provide meaningful clinical activity for patients with microsatellite stable (MSS) colorectal cancer (CRC). ONC201 is a small molecule that inactivates AKT and ERK signaling and actives the TRAIL pathway. Preclinical studies indicated potential benefits of combining ONC201 with checkpoint inhibitors. This is a phase Ib/II trial of ONC201 plus nivolumab for patient with MSS CRC who progressed on standard treatment.</p><p><strong>Methods: </strong>Enrolled patients received ONC201 plus nivolumab in a dose de-escalation fashion to determine the maximum tolerated dose (MTD). Additional patients were enrolled in the dose-expansion cohort. ONC201 at a dose of 625 mg was given orally at day -7 of cycle 1, followed by weekly dosing. Nivolumab was given every 2 weeks at 240 mg IV starting on day 1 of every cycle (cycle =28 days). The primary end point was dose-limiting toxicity (DLT) during the observation window (run-in dose day -7, cycle 1 to assessment pre-dosing cycle 2). The plan was to enroll 28 additional patients at the MTD so that a total of 34 patients would be treated at the MTD. Pharmacokinetics (PKs) and tumor biopsies were collected at several time points per study protocol.</p><p><strong>Results: </strong>A total of 13 patients (8 patients in the dose escalation *6 evaluable*) were enrolled between December 4, 2019 and March 2021. All patients had received ≥2 previous lines of chemotherapy and had confirmed microsatellite stability or mismatch repair-proficient tumors. No DLTs were observed with 625 mg ONC201 in the first three patients. Three additional patients were enrolled at the same dose to confirm safety. Two patients progressed during the DLT period and had to be replaced. During the dose-expansion part, five patients were enrolled and none required dose reduction or modification. No objective tumor response was observed in the 13 treated patients. Disease progression was confirmed at the time of the first imaging evaluation at 8 weeks following cycle 2. Post discussion at the Data and Safety Monitoring Board (DSMB) on May 25, 2021, the principal investigator (PI) and Committee voted to close the study to new patient enrollment prior to reaching accrual of 34 patients, secondary to lack of efficacy.</p><p><strong>Conclusions: </strong>In this study of patients with advanced MSS CRC, combination ONC201/nivolumab was well-tolerated; objective responses to ONC201/nivolumab were not observed.</p>","PeriodicalId":94362,"journal":{"name":"Translational gastroenterology and hepatology","volume":"9 ","pages":"15"},"PeriodicalIF":0.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11074474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140878358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}