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A Review of Non-operative Treatments for Hepatocellular Carcinoma with Advanced Portal Vein Tumor Thrombus.

ABSTRACT: Portal vein tumor thrombus (PVTT) frequently occurs with the progression of hepatocellular carcinoma (HCC) and is an important factor in determining the prognosis of HCC. In many cases of HCC with advanced PVTT, treatment is difficult because the tumor has considerable extension into the liver, and portal hypertension is a frequent complication. The standard therapy for unresectable HCC with advanced PVTT is sorafenib therapy in patients with good hepatic function. However, the outcomes of sorafenib therapy are not completely satisfactory, making the development of another therapy an urgent task. Therefore, this review aims to summarize non-operative treatments for HCC with advanced PVTT and discuss future perspectives based on those therapies, including therapies still being developed.

SUBMITTER: Moriguchi M

PROVIDER: S-EPMC5472939 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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A Review of Non-operative Treatments for Hepatocellular Carcinoma with Advanced Portal Vein Tumor Thrombus.

Moriguchi Michihisa M Furuta Mitsuhiro M Itoh Yoshito Y

Journal of clinical and translational hepatology 20170412 2

Portal vein tumor thrombus (PVTT) frequently occurs with the progression of hepatocellular carcinoma (HCC) and is an important factor in determining the prognosis of HCC. In many cases of HCC with advanced PVTT, treatment is difficult because the tumor has considerable extension into the liver, and portal hypertension is a frequent complication. The standard therapy for unresectable HCC with advanced PVTT is sorafenib therapy in patients with good hepatic function. However, the outcomes of soraf ...[more]

PMID: 28660156

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Project description:Background: Survival benefit of surgical resection for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) has been approved recently. However, risk factors for in-hospital mortality in these patients remain unclear. We aimed to determine risk factors and reduce the mortality of these patients. Methods: We analyzed data for 521 of all 1531 HCC patients with PVTT underwent surgery. The primary outcome measure was in-hospital mortality after surgical resection. Univariate and Multivariate cox-regression were performed to identify independent predictors of in-hospital mortality. The methods of Kaplan-Meier, bootstrap and ten-fold-cross validation were applied to validate the risk factors. Results: 521 of 1531 patients in 2004-2012 occurred for the diagnosis of HCC associated with PVTT and underwent surgical resection as a training cohort. Other 325 patients in 2013-2016 were included as a validation cohort. Overall mortality of postoperative in-patients was 3.3% (17/521) and 2.8 % (9/325), respectively. Univariate analysis of mortality revealed that frequency of hospitalization, total albumin, different types of PVTT, bleeding volume, blood transfusion, resection volume, and tumor volume were related with mortality. Therefore, the bootstrap validation reflected that the risk factors of multivariate cox regression in model1(frequency of hospitalization, bleeding volume, and tumor volume) and model 2 (frequency of hospitalization, bleeding volume and total albumin) were stable with mortality in hospital. Ten-fold cross-validation of cox regression analysis showed that the mean C-statistic with 95%CI of model1 and model2 respectively were 0.887(0.779-0.976) and 0.867(0.789-0.966) for predicting in-hospital mortality. Consistency results of models were in the training cohort and validation cohort. Conclusion: Total albumin, tumor volume, intraoperative bleeding and frequency of hospitalization were independent predictive factors for in-hospital mortality in HCC patients with PVTT under surgery. Further study is warranted to utilize these factors to lower in-hospital mortality.

Project description:The present study aims to investigate the role and underlying mechanism of microRNA (miR)-186 in patients with hepatocellular carcinoma (HCC) complicated with portal vein tumor thrombus. Blood samples from 29 HCC patients with portal vein tumor thrombus were collected between January 2014 and September 2015 in Huai'an First People's Hospital, while blood from 36 HCC patients without vein tumor thrombus was also collected in the same period. In addition, tumor thrombus specimens were collected from the HCC patients with portal vein tumor thrombus, and peritumoral tissues of the tumor thrombus were used as the control. Reverse transcription-quantitative polymerase chain reaction, ELISA and western blot analyses were applied to detect vascular endothelial growth factor (VEGF) expression at the mRNA and protein levels. Bioinformatics prediction was used to predict the target of miR-186, and then miR-186 expression was detected. Furthermore, dual-luciferase reporter assay was used to validate whether miR-186 directly targeted VEGF. Following transfection with agomiR-186, the expression levels of miR-186 and VEGF were detected, while MTT assay was used to detect EA.hy926 cell proliferation subsequent to small interfering RNA (siRNA) silencing. The results identified that VEGF was significantly increased in the tumor thrombus and blood samples of HCC patients with vein tumor thrombus at the mRNA and protein levels, while miR-186 expression was significantly decreased (P<0.05). Following silencing VEGF by siRNA transfection, the proliferation of EA.hy926 cells was inhibited. In addition, VEGF expression was significantly decreased and cell proliferation was reduced when upregulating miR-186. Dual-luciferase reporter assay demonstrated that miR-186 regulated VEGF expression through complementary binding to 3'-untranslated region. In conclusion, VEGF was significantly increased in tumor thrombus and blood samples from HCC patients with vein tumor thrombus, which may be associated with the downregulation of miR-186. Thus, miR-186 may promote the development and progression of vein tumor thrombus in HCC.

Dataset Information

A Review of Non-operative Treatments for Hepatocellular Carcinoma with Advanced Portal Vein Tumor Thrombus.

Publications

A Review of Non-operative Treatments for Hepatocellular Carcinoma with Advanced Portal Vein Tumor Thrombus.

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