A Pilot First-in-Human Study of Embrace,a Polyethylene Glycol-Based Liquid Embolic Agent,in the Embolization of Malignant and Benign Hypervascular Tumors

PurposeTo investigate the safety and efficacy of an aqueous polyethylene glycol-based liquid embolic agent, Embrace Hydrogel Embolic System (HES), in the treatment of benign and malignant hypervascular tumors.Materials and MethodsA prospective, single-arm, multicenter study included 8 patients, 5 males and 3 females, with a median age of 58.5 years (30–85 years), who underwent embolization in 8 tumors between October 2019 and May 2020. Technical success was defined as successful delivery of HES to the index vessel, with disappearance of >90% of the targeted vascular enhancement or, for portal vein embolization, occlusion of the portal branches to the liver segments for future resection. The volume of HES administered, ease of use (5 point Likert scale), administration time, and adverse events (AEs) were recorded. Evaluation was performed at 7, 30, and 90 days via clinical assessment and blood testing, and follow-up imaging was performed at 30 days.ResultsEight patients were enrolled, and 10 embolizations were performed in 8 lesions. Tumors included hepatocellular carcinoma (n = 4), renal angiomyolipoma (n = 3), and intrahepatic cholangiocarcinoma (n = 1). Technical success was 100%, and the average ease of use was 3.3 ± 1.0 SD. The HES delivery time was 1–28 minutes (median, 16.5 minutes), and the HES volume injected was 0.4–4.0 mL (median, 1.3 mL). All patients reached 30-day follow-up with imaging, and 6 patients reached 90-day follow-up. There were 3 serious AEs in 2 patients that were unrelated to the embolic agent.ConclusionHES resulted in a 100% embolization technical success rate. The product ease of use was acceptable, and no target vessel recanalization was noted on follow-up imaging at 30 days.     

Diagnosis of intrahepatic cholangiocarcinoma by Raman spectroscopy provides high efficiency: A protocol for systematic review and meta-analysis

Background:We aim to evaluate the efficiency of Raman spectroscopy (RS) in diagnosing suspected patients with intrahepatic cholangiocarcinoma (ICC), manifested by diagnostic sensitivity, specificity, and accuracy.Methods:We will research widely the articles concerning the use of RS in ICC through authenticated database including PubMed/Medline, EMBASE, Web of Science, Ovid, Web of Knowledge, Cochrane Library, and CNKI between January 2012 and November 2020, retrieving at least 1500 spectra with strict criteria. This study will be carried out in accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We are going to summarize the test performance using random effects models.Results:Based on the pooled sensitivity, specificity, and diagnostic accuracy, we intend to provide the relative diagnostic efficiency in ICC through RS.Conclusion:Through this systematic review and meta-analysis, we intend to provide the pooled sensitivity, specificity and diagnostic accuracy of RS in the diagnosis of suspected ICC. Other parameters like positive likelihood ratios (LR), negative LR, diagnostic odds ratio (DOR), and area under curve (AUC) of the summary receiver operating characteristics (SROC) curve will also be calculated and related figures will be drawn to help illustrate the efficacy of RS in the diagnosis of ICC.     

Efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) created using covered stents of different diameters: A systematic review and meta-analysis

PurposeThe purpose of this study was to make a systematic review and meta-analysis to determine the stent diameter (8 mm vs. 10 mm) that conveys better safety and clinical efficacy for transjugular intrahepatic portosystemic shunt (TIPS).Materials and methodsFour databases were used to identify clinical trials published from inception until March 2020. Data were extracted to estimate and compare one-year and three-year overall survivals, hepatic encephalopathy, variceal rebleeding, and shunt dysfunction rates between patients with 8 mm covered stents and those with 10 mm covered stents.ResultsFive eligible studies were selected, which included 489 patients (316 men, 173 women). The 8 mm covered stent group had higher efficacy regarding one-year or three-year overall survival (odds ratio [OR], 2.88; P = 0.003) and (OR, 1.81; P = 0.04) and lower hepatic encephalopathy (OR, 0.69; P = 0.04) compared with 10 mm covered stent group. There were no significant differences in variceal rebleeding rate (OR 0.80; P = 0.67). However, shunt dysfunction was lower in 10 mm covered stent group (OR, 2.26; P = 0.003).ConclusionsOur results suggest that the use of 8 mm covered stents should be preferred to that of 10 mm covered stents for TIPS placement when portal pressure is frequently monitored.     

High expression of HVEM is associated with improved prognosis in intrahepatic cholangiocarcinoma

Herpesvirus entry mediator (HVEM) displays dual signals in T-cell activation according to the ligands and intracytoplasmic effectors it interacts with. High HVEM expression may play an immunosuppressive role in several malignancies. The present study investigated the clinical impact of HVEM on intrahepatic cholangiocarcinoma (ICC), including its prognostic value, and association with clinicopathological features and immune status. The clinical data of 102 consecutive patients with ICC who underwent surgical treatment from January 2012 to December 2017 were collected. The expression of HVEM and different types of tumor-infiltrating lymphocytes (TILs) were investigated in ICC tissue samples by immunohistochemical staining. HVEM expression was detected in the tumor tissues of 92 (90.2%) patients with ICC. Patients with high HVEM expression were more likely to have increased peripheral blood lymphocyte (PBL) concentrations (P=0.031), decreased CEA (P=0.036), low TNM stage (P=0.043) and high frequencies of small-duct histological type (P=0.021) and BAP1 retained expression (P=0.010). Survival analysis showed that high HVEM expression was a favorable independent predictor of overall postoperative survival (P=0.034, hazard ratio=0.486, 95% confidence interval=0.249–0.945). In addition, no significant association of HVEM expression with CD4⁺ (P=0.512), CD8⁺ (P=0.750) or CD45RO⁺ (P=0.078) TILs was identified in the ICC tissues. These results indicate that HVEM may serve as a favorable prognostic marker for ICC. Furthermore, co-stimulatory signals from HVEM may play a dominant role in the progression of ICCs, which can be explained by an increase in the number of PBLs rather than a change in the number of TILs. However, the function of the HVEM network in ICC progression is complex and requires further study.     

Efficacy and Safety of Transjugular Intrahepatic Portosystemic Shunt Creation for Budd-Chiari Syndrome: A Systematic Review and Meta-Analysis

PurposeTo assess the critical role of transjugular intrahepatic portosystemic shunt (TIPS) in the management of Budd-Chiari syndrome (BCS), as the data with respect to the safety and outcome of TIPS in patients with BCS are scarce because of the rarity of the disease.Materials and MethodsA comprehensive search of literature of various databases from 2000 to October 2021 was conducted for studies evaluating the outcome of TIPS in patients with BCS. The primary outcomes of the analysis were technical and clinical success, adverse events and mortality associated with TIPS, dysfunction of TIPS, need for TIPS revision, need for liver transplantation (LT), and 1-year survival.ResultsA total of 33 studies (1,395 patients) were included in this meta-analysis. The pooled rates and 95% confidence intervals of various outcomes were 98.6% (97.6–99.7) for technical success, 90.3% (86.0–94.6) for clinical success, 10.0% (6.5–13.6) for major adverse events, 0.5% (0.2–1.0) for TIPS-related mortality, 11.6% (7.8–15.4) for post-TIPS hepatic encephalopathy (HE), 40.1% (32.5–47.7) for TIPS dysfunction, 8.6% (4.9–12.4) for the need for TIPS revision, 4.5% (2.8–6.2) for the need for LT, and 94.6% (93.1–96.1) for 1-year survival. Publication bias was seen with all outcomes except for post-TIPS HE, TIPS dysfunction, and the need for LT.ConclusionsThe existing literature supports the feasibility, safety, and efficacy of TIPS in the treatment of BCS. Deciding the optimal timing of TIPS in BCS needs further studies.     

Clinical Outcomes and Patency after Transjugular Intrahepatic Portosystemic Shunt Reduction for Overshunting Adverse Events

PurposeTo assess clinical outcomes and patency after transjugular intrahepatic portosystemic shunt (TIPS) reduction for overshunting adverse events.Materials and MethodsThis multicenter, retrospective observational study included 33 patients (male-to-female ratio, 20:13; mean age, 59 years; mean Model for End-Stage Liver Disease [MELD] score, 15) who underwent TIPS reduction between 2007 and 2020. Procedure indications included medically refractory hepatic encephalopathy (HE) (85%), post-TIPS hepatic insufficiency (HI) (12%), and heart failure (3%). The measured outcomes included improvement in HE (classified using the West Haven system) and HI, patency of reduced TIPS, and transplant-free survival (TFS).ResultsTIPS reductions were successfully performed using parallel stent (94%) or other (6%) techniques at a median of 120 days after TIPS creation (HE, median, 164 days; HI, median, 5 days). The portosystemic pressure gradient increased from a mean of 10 to 17 mm Hg (P < .001). The overall HE rate after TIPS reduction was 54%; HE was persistent, improved, and resolved in 21%, 32%, and 46% cases, respectively. In patients with HI, the MELD score increased from a mean of 22 before TIPS to 34 after TIPS (P = .061), but without improvement (0%) in HI after TIPS reduction (mean MELD score, 30; P = .266). Recurrent ascites occurred in 14% of the patients. The median shunt patency was 961 days (95% confidence interval, 476–1,447). The 30-day, 6-month, 1-year, and 3-year shunt patency rates were 92%, 81%, 74%, and 37%, respectively. The median TFS was not reached. The 30-day, 6-month, 1-year, and 3-year survival rates were 97%, 90%, 81%, and 60%, respectively.ConclusionsAlthough TIPS reduction may be an effective and durable approach to treat post-TIPS medically refractory HE, shunt reduction may not achieve meaningful benefit for HI.     

儿童高胆红素血症

儿童高胆红素血症常表现为黄疸，是儿童特别是婴幼儿普遍存在的一种症状，各种病理生理学、解剖学、感染性、自身免疫性疾病及遗传代谢性因素及疾病均可引起黄疸。不同的原因导致的黄疸其严重程度及预后不同，并且有不同的时间敏感性和不同的治疗计划。早期诊断和评估、并给予个性化的优化治疗至关重要。随着分子检测技术的发展，二代测序技术使临床医生能够快速有效的对临床实践中无法通过常规血液检查直接诊断的疾病进行分子学诊断，进而精准治疗。文章主要介绍儿童高胆红素血症常见病因及其诊治策略。     

Prognostic value of preoperative inflammatory markers in resectable biliary tract cancer – Validation and comparison of the Glasgow Prognostic Score and Modified Glasgow Prognostic Score in a Western cohort

IntroductionEstablished preoperative prognostic factors for risk stratification of patients with biliary tract cancer (BTC) are lacking. A prognostic value of the inflammation-based Glasgow Prognostic Score (GPS) and Modified Glasgow Prognostic Score (mGPS) in BTC has been indicated in several Eastern cohorts. We sought to validate and compare the prognostic value of the GPS and the mGPS for overall survival (OS), in a large Western cohort of patients with BTC.Material and methodsWe performed a retrospective single-center study for the period 2009 until 2017. 216 consecutive patients that underwent surgical exploration with a diagnosis of perihilar cholangiocarcinoma (PHCC), intrahepatic cholangiocarcinoma (IHCC), or gallbladder cancer (GBC) were assessed. GPS and mGPS were calculated where both CRP and albumin were measured pre-operatively (n = 168/216). Survival was analyzed by Kaplan-Meier estimate and uni-/multivariate Cox regression.ResultsGPS and mGPS were negatively associated with survival (p < 0.001/p < 0.001), and the association was significant in all three subgroups. GPS, but not the mGPS, identified an intermediate risk group: with GPS = 1 having better OS than GPS = 2 (p = 0.003), but worse OS than GPS = 0 (p = 0.008). In multivariate analyses of resected patients, GPS (p = 0.001) and mGPS (p = 0.03) remained significant predictors of survival, independent of postoperatively available risk factors.ConclusionsPreoperative GPS and mGPS are independent prognostic factors in BTC. The association to OS was shown in all patients undergoing exploration, in resected patients only, and in both cholangiocarcinoma and gallbladder cancer. Furthermore, GPS – which weights hypoalbuminemia higher – could identify an intermediate risk group.     

基于TCGA数据初步探查肝内胆管癌预后相关基因

目的 分析tCGA数据库中肝内胆管癌（ICC）高通量测序数据，寻找其预后相关基因，构建风险模型，并研究其在ICC组织中表达及作用通路。方法 下载tCGA数据库中33例ICC组织和8例癌旁组织中的RNA-seq表达矩阵数据和患者临床资料信息，利用edgeR软件包进行基因差异表达分析，通过单因素Cox回归分析筛选出预后相关差异基因，对差异基因绘制生存曲线，筛选出具有临床意义的基因，经多因素Cox回归分析并构建风险模型，通过京都基因与基因组百科全书（KEGG）通路富集分析了解预后相关基因的作用通路。结果 通过edgeR分析后得到6 617个差异基因（筛选标准为|log2 Fold Change|＞1，P＜0.05），其中高表达组4 094个，低表达组2 523个。通过功能富集发现，这些基因主要集中在化学物致癌作用、药物代谢-细胞色素P450系统、细胞色素P450对异生物质的代谢影响以及视黄醇代谢通路。经单因素Cox回归、R软件“survival”包生存曲线分析显示，UCN2、CST1、PROS1、SLC35E4、PEMT五个基因对ICC患者预后存在显著性影响。通过多因素Cox回归分析，CST1、PEMT、PROS1构建的风险模型对ICC患者预后具有判断作用。结论 UCN2、CST1、PROS1、SLC35E4、PEMT基因可能成为ICC预后判断指标，为后续临床试验提供数据支持。