Liver resection versus intensity-modulated radiation therapy for treatment of hepatocellular carcinoma with hepatic vein tumor thrombus: a propensity score matching analysis.

BACKGROUND: The presence of hepatic vein tumor thrombus (HVTT) is a major determinant of survival outcomes in hepatocellular carcinoma (HCC) patients. This study compared survival outcomes between liver resection (LR) and intensity-modulated radiation therapy (IMRT) in HCC patients with HVTT. METHODS: Data from patients who underwent LR or IMRT for HCC with HVTT at the Eastern Hepatobiliary Surgery Hospital were retrospectively analyzed. Their survival outcomes were compared before and after propensity score matching (PSM). RESULTS: Three hundred and seven HCC patients with HVTT who underwent either LR (n=140) or IMRT (n=167) were enrolled. PSM matched 82 pairs of patients. The overall survival (OS) and recurrence-free survival (RFS) rates were significantly higher for patients in the LR group than those in the IMRT group. On subgroup analysis, significantly better survival outcomes were obtained after LR than IMRT in patients with peripheral type of HVTT (pHVTT) and major type of HVTT (mHVTT). However, similar survival outcomes were obtained after LR and IMRT when the HVTT had developed into inferior vena cava tumor thrombus (IVCTT). CONCLUSIONS: LR resulted in significantly better survival outcomes in HCC patients with HVTT when compared to IMRT. Once the HVTT had developed IVCTT, LR and IMRT resulted in similarly bad survival outcomes.

NET1 promotes HCC growth and metastasis in vitro and in vivo via activating the Akt signaling pathway.

Neuroepithelial cell transforming gene 1 (NET1), a member of the guanine nucleotide exchange factor family, is involved in various cancers, including gastric cancer, breast cancer and glioma. However, the role of NET1 in hepatocellular carcinoma (HCC) remains largely uncovered. In this study, we found that NET1 expression was upregulated in HCC, and that upregulated NET1 expression was closely associated with poor prognosis and some clinical characteristics in HCC patients. Whilst forced expression of NET1 in HCC cells was observed to significantly promote cell growth and metastasis in vitro and in vivo; downregulation of NET1 was shown to exhibit an opposite inhibitory effect. RNA-seq analysis and gene set enrichment analysis demonstrated that knockdown of NET1 significantly suppressed the level of Akt phosphorylation level and the expression of Akt downstream genes in HCC cells. Moreover, MK2206, a potent Akt inhibitor was shown to block the NET1-induced effects in HCC. Taken together, this study demonstrated that, through the Akt signaling pathway, NET1 plays an oncogenic role in HCC progression and metastasis. Hence, NET1 may potentially be used as a potential therapeutic target and prognostic marker of HCC.

A new classification for hepatocellular carcinoma with hepatic vein tumor thrombus.

BACKGROUND: Hepatic vein tumor thrombus (HVTT) is a significant poor risk factor for survival outcomes in hepatocellular carcinoma (HCC) patients. Currently, the widely used international staging systems for HCC are not refined enough to evaluate prognosis for these patients. A new classification for macroscopic HVTT was established, aiming to better predict prognosis. METHODS: This study included 437 consecutive HCC patients with HVTT who underwent different treatments. Overall survival (OS) and time-dependent receiver operating characteristic (ROC) curve area analysis were used to determine the prognostic capacities of the new classification when compared with the different currently used staging systems. RESULTS: The new HVTT classification was defined as: type I, tumor thrombosis involving hepatic vein (HV), including microvascular invasion; type II, tumor thrombosis involving the retrohepatic segment of inferior vena cava; and type III, tumor thrombosis involving the supradiaphragmatic segment of inferior vena cava. The numbers (percentages) of patients with types I, II, and III HVTT in the new classification were 146 (33.4%), 143 (32.7%), and 148 (33.9%), respectively. The 1-, 2-, and 3-year OS rates for types I to III HVTT were 79.5%, 58.6%, and 29.1%; 54.8%, 23.3%, and 13.8%; and 24.0%, 10.0%, and 2.1%, respectively. The time-dependent-ROC curve area analysis demonstrated that the predicting capacity of the new HVTT classification was significantly better than any other staging systems. CONCLUSIONS: A new HVTT classification was established to predict prognosis of HCC patients with HVTT who underwent different treatments. This classification was superior to, and it may serve as a supplement to, the commonly used staging systems.