Leida Zhang

Transarterial Chemoembolization (TACE) plus Sorafenib Versus TACE for Intermediate or Advanced Stage Hepatocellular Carcinoma: A Meta-Analysis

Background Sorafenib is used in patients with intermediate or advanced stage hepatocellular carcinoma (HCC) before or after of transarterial chemoembolization (TACE). However, the survival outcomes of TACE combined with sorafenib versus TACE alone remain controversial. Thus, we conducted a meta-analysis to evaluate the efficacy and safety of the combination therapy of TACE plus sorafenib in patients with intermediate or advanced stage of HCC. Methods Pubmed and Embase databases were systematically reviewed for studies published up to November 2013, that compared TACE alone or in combination with sorafenib. Pooled hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated for overall survival (OS), time to progression (TTP), objective response rate (ORR), and progression free survival (PFS) using random-effects or fixed-effects model, depending on the heterogeneity between the included studies. Results Six studies published from 2011 to 2013, with a total of 1254 patients, were included in this meta-analysis. The pooled results showed that TACE combined with sorafenib significantly improved OS (HR = 0.65; 95% CI: 0.47–0.89, P = 0.007), TTP (HR = 0.68; 95% CI: 0.52–0.87, P = 0.003), ORR (HR = 1.06; 95% CI: 1.01–1.12, P = 0.021), but did not affect PFS (HR = 0.84; 95% CI: 0.62–1.14, P = 0.267). The incidence of grade III/IV adverse reaction was higher in the TACE plus sorafenib group than in the TACE group. Conclusions The meta-analysis confirmed that the combination therapy of TACE plus sorafenib in patients with intermediate or advanced stage of HCC, can improve the OS, TTP, and ORR. This combination therapy was also associated with a significantly increased risk of adverse reactions.

Apigenin potentiates the growth inhibitory effects by IKK-β-mediated NF-κB activation in pancreatic cancer cells.

Apigenin is a potential chemopreventive agent for cancer prevention. Because of the central role of transcription factor nuclear factor-κB (NF-κB) in pancreatic cancer, we investigated the roles of NF-κB in apigenin-induced growth inhibition in pancreatic cancer cells. It showed that apigenin reduced cell growth and induced apoptosis in the cells. Apigenin treatment down-regulated not only basal but also TNF-α-induced NF-κB DNA binding activity, NF-κB transcription activity, inhibitor of κB (IκB)-α phosphorylation together with translocation of p65 and p50, and it accompanied with the blockade of IκB kinase (IKK)-β activity. Moreover, IKK blockage potentiated the anticancer efficacy of apigenin and IKK-β overexpression attenuated the apigenin-induced cell growth inhibition. Additionally, apigenin (30 mg/kg) administration suppressed pancreatic cancer growth and IKK-β activation in nude mice xenograft. These results indicated that apigenin had a potential to inhibit IKK-β-mediated NF-κB activation, and was a valuable agent for the pancreatic cancer treatment.

Pancreaticoduodenectomy combined with vascular resection and reconstruction for patients with locally advanced pancreatic cancer: a multicenter, retrospective analysis.

Objective The aim of this study was to present the therapeutic outcome of patients with locally advanced pancreatic cancer treated with pancreatoduodenectomy combined with vascular resection and reconstruction in addition to highlighting the mortality/morbidity and main prognostic factors associated with this treatment. Materials and Methods We retrospectively analyzed the clinical and pathological data of a total of 566 pancreatic cancer patients who were treated with PD from five teaching hospitals during the period of December 2006–December 2011. This study included 119 (21.0%) patients treated with PD combined with vascular resection and reconstruction. We performed a detailed statistical analysis of various factors, including postoperative complications, operative mortality, survival rate, operative time, pathological type, and lymph node metastasis. Results The median survival time of the 119 cases that received PD combined with vascular resection was 13.3 months, and the 1-, 2-, and 3-year survival rates were 30.3%, 14.1%, and 8.1%, respectively. The postoperative complication incidence was 23.5%, and the mortality rate was 6.7%. For the combined vascular resection group, complications occurred in 28 cases (23.5%). For the group without vascular resection, complications occurred in 37 cases (8.2%). There was significant difference between the two groups (p = 0.001). The degree of tumor differentiation and the occurrence of complications after surgery were independent prognostic factors that determined the patients’ long-term survival. Conclusions Compared with PD without vascular resection, PD combined with vascular resection and reconstruction increased the incidence of postoperative complications. However, PD combined with vascular resection and reconstruction could achieve the complete removal of tumors without significantly increasing the mortality rate, and the median survival time was higher than that of patients who underwent palliative treatment. In addition, the two independent factors affecting the postoperative survival time were the degree of tumor differentiation and the presence or absence of postoperative complications.

Role of integrin αvβ6 in the pathogenesis of ischemia-related biliary fibrosis after liver transplantation.

Background Biliary fibrosis has been referred to as the “final common pathway” of acute and chronic bile duct injury after orthotopic liver transplantation (OLT). We studied the role of integrin &agr;v&bgr;6 in the pathogenesis of ischemia-related biliary fibrosis after OLT. Methods The mouse nonarterialized OLT model with prolonged cold ischemia time was used in this study. A total of 54 FVB/N mice were divided into three groups: sham-operated group (sham, n=18), OLT group that was given the blocking antibody to integrin &agr;v&bgr;6 (OLT+antibody, n=18), and OLT group that was given the isotype control immunoglobulin G (OLT+vehicle, n=18). The expression of &agr;v&bgr;6 and major fibrosis-related genes were studied by real-time polymerase chain reaction and immunohistochemistry. Serum and bile were collected and analyzed biochemically. The histopathologic evaluation was performed to determine the severity of biliary fibrosis and bile duct injury. Results Integrin &agr;v&bgr;6 was highly expressed on newly formed bile ducts because of cholangiocyte proliferation and was gradually upregulated with the progression of biliary fibrosis after liver transplantation. &agr;v&bgr;6 transcripts closely correlated with fibrosis stages but not bile duct injury severity. Inhibition of &agr;v&bgr;6 attenuated peribiliary collagen deposition remarkably, induced significant downregulation of fibrogenic genes, and improved hepatic function. Conclusions Integrin &agr;v&bgr;6 is strongly induced de novo in newly formed bile ducts because of cholangiocyte proliferation during ischemia-related biliary fibrogenesis after liver transplantation. Inhibition of &agr;v&bgr;6 could retard the progression of biliary fibrosis of liver allograft significantly, suggesting that &agr;v&bgr;6 is a potential target for the treatment of ischemic biliary complications.

Pancreas-sparing duodenectomy with regional lymphadenectomy for pTis and pT1 ampullary carcinoma

BACKGROUND The role of pancreas-sparing duodenectomy (PSD) in the treatment of ampullary carcinoma (Amp Ca) with local lymph node metastasis remains controversial. The aim of this study was to investigate the feasibility, safety, and long-term prognosis of PSD with regional lymphadenectomy in the treatment of early-stage (pTis/pT1) Amp Ca with or without regional lymph node metastasis. METHODS Between May 2005 and November 2009, 31 consecutive patients with Amp Ca were enrolled in this study; 25 underwent PSD. A retrospective control group of 28 patients who underwent pancreatoduodenectomy (PD) for Amp Ca during the same period was established. These 2 groups were matched in terms of demographic data, tumor size, and TNM classification. RESULTS In the PSD group, 9 patients (36%) had regional lymph node metastasis, and 23 patients (92%) had R0 resection. Patients who underwent PSD achieved favorable results in intraoperative blood loss, duration of hospital stay, and morbidity rate. The 3-year overall and disease-free survival in PSD group were 72% and 61%, respectively. There were no differences in hospital mortality and long-term survival between the 2 groups, even for patients with lymph node metastasis (N1). CONCLUSION PSD with regional lymphadenectomy is feasible and safe in the treatment of pTis/pT1 Amp Ca with or without regional lymph node metastasis. Long-term survival and morbidity rates are also favorable. PSD can be performed as an alternative of PD in selected patients with Amp Ca.

Roles of ApoB-100 Gene Polymorphisms and the Risks of Gallstones and Gallbladder Cancer: A Meta-Analysis

Background Gallstones (GS) is the major manifestation of gallbladder disease, and is the most common risk factor for gallbladder cancer (GBC). Previous studies investigating the association between ApoB-100 gene polymorphisms and the risks of GS and GBC have yielded conflicting results. Therefore, we performed a meta-analysis to clarify the effects of ApoB-100 gene polymorphisms on the risks of GS and GBC. Methods A computerized literature search was conducted to identify the relevant studies from PubMed and Embase. Fixed or random effects model was selected based on heterogeneity test. Publication bias was estimated using Begg’s funnel plots and Egger’s regression test. Results A total of 10, 3, and 3 studies were included in the analyses of the association between ApoB-100 XbaI, EcoRI, or insertion/deletion (ID) polymorphisms and the GS risks, respectively, while 3 studies were included in the analysis for the association between XbaI polymorphism and GBC risk. The combined results showed a significant association in Chinese (X+ vs. X−, OR = 2.37, 95%CI 1.52–3.70; X+X+/X+X- vs. X+X+, OR = 2.47, 95%CI 1.55–3.92), but not in Indians or Caucasians. Null association was observed between EcoRI or ID polymorphisms and GS risks. With regard to the association between XbaI polymorphism and GBC risk, a significant association was detected when GBC patients were compared with healthy persons and when GBC patients were compared with GS patients. A significant association was still detected when GBC patients (with GS) were compared with the GS patients (X+X+ vs. X-X−, OR = 0.33, 95%CI 0.12–0.90). Conclusion The results of this meta-analysis suggest that the ApoB-100 X+ allele might be associated with increased risk of GS in Chinese but not in other populations, while the ApoB-100 X+X+ genotype might be associated with reduced risk of GBC. Further studies with larger sample sizes are needed to confirm these results.

Refractory Gastroesophageal Variceal Bleeding Secondary to Neuroendocrine Carcinoma in the Pancreatic Tail

The main cause of gastroesophageal variceal bleeding (GEVB) is portal hypertension (PH) due to liver cirrhosis. Here, we report a case of regional PH and refractory GEVB secondary to neuroendocrine carcinoma (NC) in the pancreatic tail. This condition was treated using a pancreatic tail resection, splenectomy, and portal azygous devascularization. Regional PH caused by a pancreatic NC is rare and is usually presented as isolated gastric varices. This case report of regional PH details simultaneous esophageal and gastric varices that were caused by a pancreatic NC, which is a rare occurrence. Therefore, after excluding liver cirrhosis, unusual causes should be considered in cases of refractory GEVB with PH.