Downregulation and pro-apoptotic effect of hypoxia-inducible factor 2 alpha in hepatocellular carcinoma.

The role of HIF-2α in hepatocellular carcinoma (HCC) is unclear. The aim of the present study was to investigate the expression pattern and role of HIF-2α in HCC patients. Immunohistochemical staining and western blotting analyses were applied to detect the protein level of HIF-2α in 206 paired HCC and peritumoral tissues. Kaplan-Meier survival and Cox proportional hazard regression analyses were performed to identify risk factors for overall survival and recurrence-free survival in these patients. The function of HIF-2α was studied in HCC cells and in vivo models. We found that the protein levels of HIF-2α in HCC tissues were lower than in peritumoral tissues, and were negatively correlated with tumor size (P < 0.05). Kaplan-Meier survival and univariate analysis revealed that HCC patients with high HIF-2α protein levels had longer overall survival (P < 0.05). Over-expression of HIF-2α induced apoptosis in HCC cells and increased the levels of pro-apoptotic proteins, Bak, ZBP-89 and PDCD4, whereas the inhibition of HIF-2α expression achieved opposite results. The findings were confirmed in a mouse HCC xenograft model. In conclusion, our study revealed that HIF-2α was decreased and played an anti-tumorigenic role in HCC.

Distinguished prognosis after hepatectomy of HBV-related hepatocellular carcinoma with or without cirrhosis: a long-term follow-up analysis.

BACKGROUND: Conflicting results have often been observed for the prognosis of hepatocellular carcinoma (HCC) patients, but few studies have attempted to explore the reasons for the conflicting results. We aimed to distinguish the prognosis of patients with HCC with cirrhosis (HCC-C) and that of patients with HCC without cirrhosis (HCC-NC). METHODS: Patients with hepatitis B virus (HBV)-associated HCC treated by curative liver resection at a single institution between 1995 and 2013 were retrospectively evaluated. Kaplan-Meier and multivariate analyses were performed to identify risk factors, including tumor-related factors, hypoxia-inducible factor 1α expression, HBV X protein (HBx) expression, and HBx double mutations for overall survival and recurrence-free survival in these patients. RESULTS: The long-term prognosis of HCC-NC patients is better than that of HCC-C patients. Male sex, poor differentiation, preoperative serum alanine aminotransferase level greater than 80 IU/L, and α-fetoprotein level greater than 400 ng/mL were risk factors for overall survival among HCC-NC patients but not among HCC-C patients, and age greater than 50 years was associated with poor overall survival only in cirrhotic patients. HCC-C patients benefit more from antiviral therapy following curative hepatectomy than do HCC-NC patients. The clinical value of the biomarkers hypoxia-inducible factor 1α, HBx, and HBx double mutations for predicting HCC prognosis was significantly different between these two groups. CONCLUSIONS: There were differences in tumor-related prognostic factors, effectiveness of the antiviral therapy after hepatectomy, and biomarkers between HCC-C and HCC-NC patients, indicating that subgroup analysis of the prognostic factors may result in better management of HCC and that HCC patients, especially those with liver cirrhosis, should be given antiviral therapy.

Oxidized Regenerated Cellulose Reduces the Amount of Fluid Drainage after Liver Resection: A Randomized Prospective Clinical Trial.

BACKGROUND/AIMS: Oxidized regenerated cellulose (ORC) has been registered as adjuncts to stimulate hemostasis in liver surgery. However, most previous studies were primarily designed to study the intra-operative hemostatic efficacy, and the effect on prophylactic application was never studied as a primary endpoint. This randomized prospective clinical trial was undertaken to evaluate whether ORC is safe and effective when used as a prophylactic agent covering the raw cut surface during the hepatectomy to reduce the volume and duration of drainage. METHODOLOGY: Between June 2011 and August 2012, a total of 40 patients undergoing major hepatectomy were randomly assigned to ORC or control groups (20 in each group). Patient characteristics, resection-related factors, debit of drainage and postoperative complications were compared between the two groups. RESULTS: The two groups were comparable in terms of demographics, indications for surgery, extent of hepatectomy, and intraoperative blood loss. The amount of drainage after operation was significantly less in the ORC group compared with the control group (406.9 ± 308.1 vs. 627.0 ± 301.6 ml, P = 0.028). CONCLUSIONS: Application of ORC covering the raw cut surface during the hepatectomy can significantly decrease the amount of drainage.