Liver Transplantation for Hepatocellular Carcinoma With Bile Duct Tumor-Associated Thrombi: A Systematic Review and Pooled Analysis
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SUBMITTER: Kim S
PROVIDER: S-EPMC11235349 | biostudies-literature | 2022 Jan
REPOSITORIES: biostudies-literature
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Project description:Bile duct tumor thrombosis (BDTT) is a complication mostly observed in patients with advanced hepatocellular carcinoma (HCC), causing jaundice and associated with poor clinical outcome. However, its underlying molecular mechanism is unclear. Here, we develop spontaneous preclinical HCC animal models with BDTT to identify the role of BMI1 expressing tumor initiating cells (BMI1high TICs) in inducing BDTT. BMI1 overexpression transforms liver progenitor cells into BMI1high TICs, which possess strong tumorigenicity and increased trans-intrahepatic biliary epithelial migration ability by secreting lysosomal cathepsin B (CTSB). Orthotopic liver implantation of BMI1high TICs into mice generates tumors and triggers CTSB mediated bile duct invasion to form tumor thrombus, while CTSB inhibitor treatment prohibits BDTT and extends mouse survival. Clinically, the elevated serum CTSB level determines BDTT incidence in HCC patients. Mechanistically, BMI1 epigenetically up-regulates CTSB secretion in TICs by repressing miR-218-1-3p expression. These findings identify a potential diagnostic and therapeutic target for HCC patients with BDTT.
| S-EPMC10624910 | biostudies-literature
Project description:BackgroundHepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) in the clinic is rare, and surgical treatment is currently considered the most effective treatment. However, the influence of BDTT on the prognosis of HCC patients who underwent surgery remains controversial in previous studies. Therefore, this paper uses meta-analysis method to elucidate this controversy.MethodsIn this study, we conducted a literature search on databases PubMed, Embase and Web of Science from inception until September 2016. Each study was evaluated with Newcastle-Ottawa Scale (NOS). The pooled effect was calculated, and the association between BDTT and overall survival (OS) or disease-free survival (DFS) was reevaluated using meta-analysis for hazard ratio (HR) and 95% confidence interval (CI).ResultsA total of 11 studies was included containing 5295 patients. The (HR) for OS and DFS was 3.21 and 1.81, 95%CI was 2.34-4.39 and 1.17-2.78 respectively.ConclusionsThe results showed that HCC patients with BDTT had a worse prognosis than those without BDTT after hepatic resection or liver transplantation (LT).
| S-EPMC5417567 | biostudies-literature
Project description:Hepatocellular carcinoma with bile duct tumor thrombus (BDTT) is a malignant disease. The most commonly used diagnosis methods for BDTT are MRCP/ERCP, ultrasonic diagnosis or CT scan. However, BDTT is often misdiagnosed as other bile duct diseases, such as extrahepatic cholangiocarcinoma (EHCC), choledochal cyst (Cyst) and common bile duct stone (Stone). Diagnostic methods, which are more accurate and less destructive, are urgently needed. In this paper, we analyzed the small molecule metabolites in the serum of BDTT, Stone, Cyst and EHCC patients and normal people using untargeted GC-MS, and identified 21 metabolites that show different levels among different samples. Using targeted UHPLC-QQQ-MS analysis, we found that several metabolites are significantly changed. ROC curve analysis revealed two metabolites, L-citrulline and D-aspartic acid, as potential biomarkers that can distinguish BDTT from other bile duct diseases.
| S-EPMC5818651 | biostudies-literature
Project description:BackgroundHepatocellular carcinoma (HCC) associated with bile duct tumor thrombus (BDTT) is uncommon in clinical practice. Surgical resection can achieve better survival than non-operative palliative treatments. However, there is great controversy regarding the optimal surgical modality, particularly regarding the approach to remove BDTT in patients with HCC with macroscopic BDTT.MethodsData from consecutive patients who underwent radical surgery for HCC and macroscopic BDTT at the Eastern Hepatobiliary Surgery Hospital and Fujian Provincial Hospital from January 2009 to December 2016 were retrospectively reviewed. The survival outcomes of patients who underwent hepatectomy combined with extrahepatic bile duct resection (the EBDR group) were compared with those of patients undergoing liver resection plus thrombectomy (the thrombectomy group) using propensity score matching (PSM). Univariate and multivariate Cox analyses were performed to identify independent prognostic factors for overall survival (OS) and recurrence-free survival (RFS).Results217 patients included in this study were divided into two groups: the EBDR group (n=30) and the thrombectomy group (n=187). A total of 90 patients were matched by PSM with a 1:2 ratio. Before PSM, the OS and RFS rates were comparable between the two groups (for OS, P=0.517; for RFS, P=0.211). After PSM, the OS rates did not differ statistically significantly between the EBDR and thrombectomy groups (P=0.134). Nevertheless, the RFS rate of the EBDR group was significantly higher compared to that of the thrombectomy group (P=0.020). Multivariate analysis demonstrated that some traditional risk factors, such as tumor size and microscopic resection margin, were more important prognostic factors than the BDTT type.ConclusionsFor patients with HCC and macroscopic BDTT, hepatectomy combined with extrahepatic bile duct resection is associated with a reduced recurrence rate in comparison with concurrent thrombectomy. Further large-scale, prospective studies are warranted to evaluate the impact of different surgical modalities on these patients' survival.
| S-EPMC8039701 | biostudies-literature
Project description:BackgroundThe long-term prognosis after surgery of patients with hepatocellular carcinoma (HCC) and extrahepatic bile duct tumor thrombus (Ex-BDTT) remains unknown. We aimed to identify the surgical outcomes of patients with HCC and Ex-BDTT.MethodsA total of 138 patients with Ex-BDTT who underwent hepatectomy with preservation of the extrahepatic bile duct from five large hospitals in China between January 2009 and December 2017 were included. The Cox proportional hazards model was used to analyze overall survival (OS) and recurrence-free survival (RFS).ResultsWith a median follow-up of 60 months (range, 1-127.8 months), the median OS and RFS of the patients were 28.6 and 8.9 months, respectively. The 1-, 3-, and 5-year OS rates of HCC patients with Ex-BDTT were 71.7%, 41.2%, and 33.5%, respectively, and the corresponding RFS rates were 43.5%, 21.7%, and 20.0%, respectively. Multivariate analysis identified that major hepatectomy, R0 resection, and major vascular invasion were independent prognostic factors for OS and RFS. In addition, preoperative serum total bilirubin ≥ 4.2 mg/dL was an independent prognostic factor for RFS.ConclusionMajor hepatectomy with preservation of the extrahepatic bile duct can provide favorable long-term survival for HCC patients with Ex-BDTT.
| S-EPMC10726108 | biostudies-literature
Project description:BackgroundThe optimal surgical modality for hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) remains controversial, especially regarding deciding whether to perform concurrent bile duct resection (BDR).MethodsPubMed, EMBASE, Cochrane Library, Web of Science and Scopus databases were systematically searched from inception to February 2020, in order to compare overall survival (OS) and recurrence-free survival (RFS) rates of HCC patients with BDTT who had either received hepatectomy with extrahepatic bile duct resection (BDR group) or hepatectomy without bile duct resection (NBDR group). Relevant outcomes were extracted by two investigators.ResultsA total of 12 studies involving 355 patients was included. The 1-, 3- and 5-year OS rates were similar in the BDR and NBDR groups (OR =0.58, 95% CI: 0.31-1.09, P=0.09; OR =0.74, 95% CI: 0.43-1.28, P=0.28; OR =0.63, 95% CI: 0.36-1.11, P=0.11, respectively). However, the BDR group had better 1-, 3- and 5-year RFS rates than the NBDR group (OR =0.38, 95% CI: 0.22-0.65, P<0.01; OR =0.40, 95% CI: 0.22-0.72, P<0.01; OR =0.37, 95% CI: 0.19-0.71, P<0.01, respectively).ConclusionsConcomitant bile duct resection results in decreased postoperative recurrence in HCC patients with BDTT. However, the OS rates were similar whether or not patients underwent bile duct resection.
| S-EPMC7791268 | biostudies-literature
Project description:BackgroundThe effect of bile duct tumor thrombus (BDTT) on the postoperative long-term prognosis of hepatocellular carcinoma (HCC) patients is still under debate.MethodsThe PubMed, Embase, Cochrane Library, Web of Science databases were systematically searched to collect the clinicopathologic characteristics, perioperative indices, and postoperative survival outcomes in the BDTT and non-BDTT groups of HCC patients from inception to February 1, 2020. The study outcomes were extracted by two independent investigators.ResultsA total of 15 studies involving 6,484 patients were included. The meta-analysis revealed that the levels of serum total bilirubin and alkaline phosphatase were notably higher in patients with HCC and BDTT than those without BDTT. Meanwhile, HCC patients with BDTT had more aggressive biological characteristics, such as poor tumor differentiation, macrovascular invasion, and lymph node metastasis, as compared to patients without BDTT. The 1-year [odds ratio (OR) 0.39, 95% confidence interval (CI): 0.31-0.48, P<0.01], 3-year (OR 0.33, 95% CI: 0.22-0.51, P<0.01) and 5-year overall survival (OS) rates (OR 0.31, 95% CI: 0.20-0.49, P<0.01) of the BDTT group were significantly worse than those of the non-BDTT group. The hazard ratio of HCC with BDTT was 4.27 (95% CI: 3.47-5.26, P<0.01) within 5 years after hepatectomy.ConclusionsHCC patients with BDTT had worse OS compared to patients free of BDTT after surgery. BDTT may be a potential prognostic factor for HCC patients.
| S-EPMC7812187 | biostudies-literature
Project description:Hepatocellular carcinoma invading the bile duct (bile duct tumor thrombus) is an unfavorable condition. Although overall survival following surgical resection among patients with hepatocellular carcinoma with bile duct tumor thrombus is significantly better than that among those treated with transarterial chemoembolization or chemotherapy, surgical resection can be indicated for selected patients. Additionally, systemic therapy is indicated only for patients with Child-Pugh class A. Therefore, transarterial therapy plays an essential role in the treatment of bile duct tumor thrombus. Transarterial chemoembolization with iodized oil and gelatin sponge particles is an established first-line transarterial treatment that can necrotize most bile duct tumor thrombi. However, we should pay attention to symptoms caused by intraductal hemorrhage during transarterial chemoembolization and the sloughing of necrotized bile duct tumor thrombi.
| S-EPMC10957244 | biostudies-literature
Project description:BackgroundBile duct injury (BDI) after cholecystectomy is a serious complication. In a small subset of patients with BDI, failure of surgical or non-surgical management might lead to acute or chronic liver failure. The aim of this study was to review the indications and outcome of liver transplantation (LT) for BDI after open and laparoscopic cholecystectomy.MethodsPatients with BDI after cholecystectomy who were on the waiting list for LT between January 1987 and December 2010 were identified from LT centres in Spain. A standardized questionnaire was sent to each unit for extraction of data on diagnosis, previous treatments, indication and outcome of LT for BDI.ResultsSome 27 patients with BDI after cholecystectomy in whom surgical and non-surgical management for BDI failed were scheduled for LT over the 24-year interval. Emergency LT for acute liver failure was indicated in seven patients, all after laparoscopic cholecystectomy. Two patients died while on the waiting list and only one patient survived more than 30 days after LT. Elective LT for secondary biliary cirrhosis after a failed hepaticojejunostomy was performed in 13 patients after open and seven after laparoscopic cholecystectomy. One patient from the elective transplantation group died within 30 days of LT. The estimated 5-year overall survival rate was 68 per cent.ConclusionEmergency LT for acute liver failure was more common in patients with BDI after laparoscopic cholecystectomy, and associated with a poor outcome.
| S-EPMC4253129 | biostudies-literature
Project description:Liver transplantation (LT) is the only potentially curative option for children with unresectable hepatocellular carcinoma (HCC). We performed a systematic review of the MEDLINE, Scopus, Cochrane Library, and Web of Science databases (end-of-search date: 31 July 2020). Our outcomes were overall survival (OS) and disease-free survival (DFS). We evaluated the effect of clinically relevant variables on outcomes using the Kaplan-Meier method and log-rank test. Sixty-seven studies reporting on 245 children undergoing LT for HCC were included. DFS data were available for 150 patients and the 1-, 3-, and 5-year DFS rates were 92.3%, 89.1%, and 84.5%, respectively. Sixty of the two hundred and thirty-eight patients (25.2%) died over a mean follow up of 46.8 ± 47.4 months. OS data were available for 222 patients and the 1-, 3-, and 5-year OS rates were 87.9%, 78.8%, and 74.3%, respectively. Although no difference was observed between children transplanted within vs. beyond Milan criteria (p = 0.15), superior OS was observed in children transplanted within vs. beyond UCSF criteria (p = 0.02). LT can yield favorable outcomes for pediatric HCC beyond Milan but not beyond UCSF criteria. Further research is required to determine appropriate LT selection criteria for pediatric HCC.
| S-EPMC8908995 | biostudies-literature