Baihe Zhang

Distal Bile Duct Carcinoma: Prognostic Factors After Curative Surgery. A Series of 112 Cases

BackgroundThe identification of independent prognostic indicators in distal bile duct carcinomas (DBDCs) has been limited by the small number of tumors and a lack of molecular prognostic markers. Markers assessed in combination may perform better than those considered individually. We conducted this study to identify prognostic predictors of patients with DBDC with special focus on combination of expression of p53 protein and clinicopathological predictors.MethodsBetween December 1996 and 2002, 112 consecutive patients undergoing pancreaticoduodenectomy in the Eastern Hepatobiliary Surgery Hospital for distal bile duct carcinomas were identified in a prospectively collected database. The survival of patients was comparable with respect to patient characteristics, clinicopathological factors and degree of p53 protein expression followed by a univariate and multivariate analysis.ResultsActual 1, 3, and 5-year survival rates were 85.7, 50.9, and 25.0%, respectively. By Cox proportional hazards survival analysis, the most powerful predictors of survival rate were p53 expression [relative risk (RR) 5.2, 95% CI 4.8–5.6], pancreatic invasion (RR 5.6, 95% CI 4.3–6.9), lymph nodes metastasis (RR 3.9, 95% CI 3.3–4.5), and operative time (RR 1.8, 95% CI 1.5–2.1).ConclusionsOverexpression of p53 in DBDC is strongly associated with significantly reduced survival, independently of clinicopathological prognostic factors. The resection margin status provides little independent prognostic information. Longer operative time may have unfavorable effect on prognosis of patients with DBDC.

Resection with total caudate lobectomy confers survival benefit in hilar cholangiocarcinoma of Bismuth type III and IV

PURPOSE To identify prognostic predictors for overall survival of patients with hilar cholangiocarcinoma of Bismuth type III and IV (HCBT34), and to determine survival benefit and safety of total caudate lobectomy (TCL) in a Chinese centre. METHODS From January 2001 to December 2010, 171 patients with the diagnosis of HCBT34, who underwent a potentially curative resection, were included in this study. Cox proportional hazards regression models were used to determine the association between possible prognostic variables and survival time. Curative resectability rate, morbidity and mortality were investigated also. RESULTS Resection with TCL was significantly associated with more opportunity to achieve curative resection (p < 0.01), did not accompany with more morbidity (p = 0.39) and mortality (p = 0.67). Cox regression analysis demonstrated positive resection margins [Relative Risk (RR) 3.6, 95% CI 3.5-3.7], not well differentiation (RR 2.9, 95% CI 2.7-3.1), higher preoperative serum peak CA19-9 level (RR 1.6, 95% CI 1.5-1.7) and regional lymph nodes involvement (RR 1.5, 95% CI 1.4-1.6) as independent adverse prognostic variables. CONCLUSIONS Resection with TCL offers a long-term survival opportunity for HCBT34, with high curative resectability rates and an acceptable safety profile.

Sorafenib extends the survival time of patients with multiple recurrences of hepatocellular carcinoma after liver transplantation

Aim:To determine the efficacy and toxicities of sorafenib in the treatment of patients with multiple recurrences of hepatocellular carcinoma (HCC) after liver transplantation in a Chinese population.Methods:Twenty patients with multiple recurrences of HCC after liver transplantation were retrospectively studied. They received either transarterial chemoembolization (TACE) or TACE combined with sorafenib.Results:The median survival times (MST) after multiple recurrences was 14 months (TACE+sorafenib group) and 6 months (TACE only group). The difference was significant in MST between the two groups (P=0.005). The TACE + sorafenib group had more stable disease (SD) patients than the TACE group. The most frequent adverse events of sorafenib were hand–foot skin reaction and diarrhea. In the univariate analysis, preoperative bilirubin and CHILD grade are found to be significantly associated with tumor-free survival time, the survival time after multiple recurrences and overall survival time. TACE+sorafenib group showed a better outcome than single TACE treatment group. In the multivariate COX regression modeling, the preoperative high CHILD grade was found to be a risk factor of tumor-free survival time. In addition, the preoperative high bilirubin grade was also found to be a risk factor of survival time after recurrence and overall survival time. Furthermore, survival time after recurrence and overall survival time were also associated with therapeutic schedule, which was indicated by the GROUP.Conclusion:Treatment with TACE and sorafenib is worthy of further study and may have more extensive application prospects.

Early control of short hepatic portal veins in isolated or combined hepatic caudate lobectomy

BACKGROUND Caudate lobectomy has long been considered technically difficult. This study aimed to elaborate the significance of early control of short hepatic portal veins (SHPVs) in isolated hepatic caudate lobectomy or in hepatic caudate lobectomy combined with major partial hepatectomy, and to describe the anatomical characteristics of SHPVs. METHODS The data of 117 patients who underwent either isolated or combined caudate lobectomy by the same team of surgeons from 2005 to 2009 were retrospectively analyzed. From 2005 to 2007 (group A, n=55), we carried out early control of short hepatic veins (SHVs) only; from 2008 to 2009 (group B, n=62), we carried out early control of both SHVs and SHPVs. The two groups were compared to evaluate which surgical procedure was better. A detailed anatomical study was then carried out on the last 25 consecutive patients in group B to study the number and distribution of SHPVs during surgery. RESULTS Patients in group B had less intra-operative blood loss, less impairment of liver function, shorter postoperative hospital stay, fewer postoperative complications and required less blood transfusion (P<0.05). The number of SHPVs in the 25 patients was 183, with 7.3+/-2.7 per patient. The diameters of SHPVs were 1 to 4 mm. On average, 3.4 SHPVs/patient came from the left portal vein, 2.2 from the bifurcation, 1.4 from the right portal vein, and 0.3 from the main portal vein. On average, 3.3 SHPVs/patient supplied segment I of the liver, 0.4 for segment II, 2.1 for segment IV, 1.4 for segment V and 0.1 for segment VI. CONCLUSION Early control of SHPVs in isolated or combined hepatic caudate lobectomy may be a useful method to decrease surgical risk and improve postoperative recovery.

Lentiviral vector-mediated RNA interference of HBs gene inhibits replication of HBV: Lentiviral vector-mediated RNA interference of HBs gene inhibits replication of HBV

Objective:To construct a lentiviral vector(LV) of RNA interference(RNAi) targeting HBs gene and to observe its effect on the replication of HBV and expression of antigens.Methods: The effective sequence of siRNA targeting HBs gene was confirmed in our previous study.The complementary DNA containing both sense and antisense Oligo DNA of the targeting sequence was designed,synthesized and cloned into the lentivirus vector(pGCLM-GFP).The resulting lentivirus vector containing HBs shRNA was named LVshHBs,and it was confirmed by PCR and sequencing.293T cells were cotransfected with lentivirus vector pGCLM-GFP,pHelper 1.0 and pHelper 2.0.All virus stocks were produced by calcium phosphate-mediated transfection.The titer of virus was tested according to the expression level of GFP.HepG2.2.15 cells were infected with LVshHBs and the supernatant of the cells was subjected to ELISA,Western blotting analysis and HBV DNA quantitative analysis.Results: PCR and DNA sequencing demonstrated that the LVshHBs-producing HBs shRNA was successfully constructed.The titer of concentrated virus was 5×108-2×109 TU /ml.The inhibitory effect was efficient and the corresponding viral transcript and expression of antigens were decreased after infection.The inhibitory effect was observed 4 days after infection and peaked 9 days after the initial treatment with RNAi.Secreted HBsAg was reduced by 70% in cell culture compared with the negative control,which is also confirmed by Western blotting and real-time PCR.After quantification of HBV DNA,the level of DNA relative to the controls was also significantly reduced after RNAi treatment(P0.05).Conclusion: The lentivirus RNAi vector of HBs has been successfully constructed.The lentiviral microRNA-based RNAi targeting HBs can specifically mediate the down-regulation of HBs expression,inhibiting HBV replication and antigen expression.