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Abstract: Hepatocellular carcinoma (HCC) is a hypervascular cancer characterized by rapid progression as well as resistance to conventional chemotherapy. It has been shown that microRNAs play critical roles in pathogenesis of HCC. MicroRNA-122 (miR-122) is a liver-specific microRNA and is frequently downregulated in HCC. In the present study, we investigated whether restoration of miR-122 in HCC cells could render cells sensitive to chemotherapeutic agents adriamycin (ADM) or vincristine (VCR). Our data showed that overexpression of miR-122 in HCC cells induced by adenovirus expressing miR-122 could render cell sensitive to ADM or VCR. Analysis of cell cycle distribution showed that the anti-proliferative effect of miR-122 is associated with increase of cell number in the G2/M phase. Moreover, treatment with Ad-miR122 and ADM or VCR resulted in high accumulation of HCC cells in G2/M phase. We further demonstrated that overexpression of miR-122 could modulate the sensitivity of the HCC cells to chemotherapeutic drugs through downregulating MDR related genes MDR-1, GST-π, and MRP, antiapoptotic gene Bcl-w and cell cycle related gene cyclin B1. Taken together, our findings demonstrated that combination of Ad-miR122 with chemotherapeutic agents inhibited HCC cell growth by inducing G2/M arrest and that this arrest is associated, at least in part, with reduced expression of MDR related genes and Cyclin B1. [Copyright &y& Elsevier]

: BackgroundResection of a large hepatocellular carcinoma in the right liver or a small tumor located at the superior and posterior part of the right liver requires extensive hepatic mobilization. A thoracoabdominal approach might facilitate hepatic resection in such situations, but the safety and benefits of this approach remain unclear.: Study designA retrospective study based on a prospectively collected database of 488 patients was performed to evaluate the perioperative outcomes of right-sided hepatic resection for hepatocellular carcinoma using the thoracoabdominal approach (n = 92) in comparison with the conventional abdominal approach (n = 396).: ResultsThe two groups were comparable in age, comorbid illnesses, liver function, tumor size, and underlying cirrhosis. There were more extended right hepatectomies in the thoracoabdominal approach group than in the abdominal approach group, but the difference was not significant (33.7% versus 26.0%, p = 0.14). A significantly higher proportion of patients in the thoracoabdominal approach group did not require blood transfusion compared with the abdominal approach group (66.3% versus 54.8%, p = 0.04). The operating time for the former group was longer (median 450 min versus 360 min, p < 0.001). There were no significant differences in hospital stay (median 12.5 days versus 13.0 days, p = 0.82), overall morbidity (41.3% versus 38.6%, p = 0.64), or hospital mortality (4.3% versus 7.3%, p = 0.37) between the two groups.: ConclusionsThe thoracoabdominal approach is a safe operative approach that can facilitate resection of massive tumors in the right liver or tumors involving segments 7 and 8 without increased morbidity. [Copyright &y& Elsevier]

Background The aim of this study was to determine the effect of anatomic resection (AR) versus non-anatomic resection (NAR) on recurrence rates in patients with hepatocellular carcinoma (HCC). Methods Eligible patients were randomized to AR or NAR from January 2006 to July 2007 at a single center. The primary outcome was the 2-year recurrence-free survival (RFS). Secondary outcomes were postoperative complications, time to first recurrence, 1-, 3-, and 5-year RFS, and overall survival (OS). Results Fifty-three (51%) and 52 (50%) patients underwent NAR and AR, respectively. A larger proportion of patients achieved margins ≥20 mm in the AR group (52% vs. 30%; P = 0.023). Complications (blood loss, transfusion requirement, and hospital stay) were similar between the two groups. Median follow-up was 33 (range, 2–77) months. Incidence of local recurrence at 2 years was 30% and 59% in the AR and NAR groups, respectively. Median time to first local recurrence in the AR group was significantly longer than in the NAR group (53 vs. 10 months, P = 0.010). There was no difference in overall RFS between the two groups (P = 0.290). Discussion AR decreased the 2-year local recurrence rate and increased the time to first local recurrence compared to NAR in patients with HCC. [ABSTRACT FROM AUTHOR]

Highlights: [•] HDAC inhibitors suppress cell growth and self-renewal of liver CSCs. [•] HDAC3 is selectively expressed in liver CSCs and participates in self-renewal of liver CSCs. [•] HDAC3 regulates expression of pluripotency factors through histone modification. [•] Overexpression of HDAC3 is associated with poor outcome of liver cancer. [•] HDAC inhibitors render liver CSCs sensitive to sorafenib. [Copyright &y& Elsevier]

Background & Aims: The aim of this study was to compare the efficacy of radiofrequency ablation (RFA) with surgical resection (RES) in the treatment of small hepatocellular carcinoma (HCC). Methods: A total of 168 patients with small HCC with nodular diameters of less than 4cm and up to two nodules were randomly divided into RES (n=84) and RFA groups (n=84). Outcomes were carefully monitored and evaluated during the 3-year follow-up period. Results: The 1-, 2-, and 3-year survival rates for the RES and RFA groups were 96.0%, 87.6%, 74.8% and 93.1%, 83.1%, 67.2%, respectively. The corresponding recurrence-free survival rates for the two groups were 90.6%, 76.7%, 61.1% and 86.2%, 66.6%, 49.6%, respectively. There were no statistically significant differences between the two groups in overall survival rate (p =0.342) or recurrence-free survival rate (p =0.122). Multivariate analysis demonstrated that the independent risk factors associated with survival were multiple occurrences of tumors at different hepatic locations (relative risk of 2.696; 95% CI: 1.189–6.117; p =0.018) and preoperative indocyanine green retention rate at 15min (ICG-15) (relative risk of 3.853; 95% CI: 1.647–9.015; p =0.002). Conclusions: In patients with small hepatocellular carcinomas, percutaneous RFA may provide therapeutic effects similar to those of RES. However, percutaneous RFA is more likely to be incomplete for the treatment of small HCCs located at specific sites of the liver, and open or laparoscopic surgery may be the better choice. [Copyright &y& Elsevier]