Peng Zhu

Randomized clinical trial comparing infrahepatic inferior vena cava clamping with low central venous pressure in complex liver resections involving the Pringle manoeuvre.

Control of bleeding remains key to successful hepatic resection. The present randomized clinical trial compared infrahepatic inferior vena cava (IVC) clamping with low central venous pressure (CVP) during complex hepatectomy using portal triad clamping (PTC).

Nuclear SIPA1 activates integrin β1 promoter and promotes invasion of breast cancer cells.

SIPA1 (signal-induced proliferation-associated protein 1) is a GTPase activation protein that can catalyze the hydrolysis of Rap1 bound GTP to GDP. Recently attention has been paid to a potential role for SIPA1 in cancer metastasis; however, the underlying mechanism of how changes in SIPA1 levels may lead to increased metastasis remains poorly understood. In this study, we showed that SIPA1 was mainly localized to the nuclei in highly invasive breast cancer tumor tissue and MDA-MB-231 cells. Knockdown of SIPA1 in MDA-MB-231 altered cell morphology and cell proliferation ability. Furthermore, this study is the first to establish that nuclear SIPA1 can interact with the integrin β1 promoter and activate its transcription; this interaction appears to be important for SIPA1-dependent MDA-MB-231 cell adhesion and invasion. We also demonstrated that the phosphorylation of FAK, Akt and the expression of MMP9, downstream signaling molecules of integrin β1, were decreased upon SIPA1 knockdown, and MDA-MB-231 cell invasion was impaired. Taken together, these results suggest nuclear SIPA1 contributes to breast cancer cell invasion through the regulation of integrin β1 signaling.

Surgical Treatment of Giant Liver Hemangioma Larger Than 10 cm: A Single Center's Experience With 86 Patients

AbstractThe ideal surgical treatment of giant liver hemangioma is still controversial. This study aims to compare the outcomes of enucleation with those of resection for liver hemangioma larger than 10 cm in different locations of the liver and establish the preoperative predictors of increased intraoperative blood loss.Eighty-six patients underwent enucleation or liver resection for liver hemangioma larger than 10 cm was retrospectively reviewed. Patient demographic, tumor characteristics, surgical indications, the outcomes of both surgical treatment, and the clinicopathological parameters influencing intraoperative blood loss were analyzed.Forty-six patients received enucleation and 40 patients received liver resection. Mean tumor size was 14.1 cm with a range of 10–35 cm. Blood loss, blood product usage, operative time, hepatic vascular occlusion time and frequency, complications and postsurgical hospital stay were similar between liver resections and enucleation for right-liver and left-liver hemangiomas. There was no surgery-related mortality in either group. Bleeding was more related to adjacency of major vascular structures than the size of hemangioma. Adjacency to major vascular structures and right or bilateral liver hemangiomas were independently associated with blood loss >550 mL (P = 0.000 and 0.042, respectively).Both enucleation and liver resection are safe and effective surgical treatments for liver hemangiomas larger than 10 cm. The risk of intraoperative blood loss is related to adjacency to major vascular structures and the location of hemangioma.

Novel EDA p.Ile260Ser Mutation Linked to Non-syndromic Hypodontia

Hypodontia, a tooth developmental disease, can affect chewing and pronunciation. Mutations in the ectodysplasin-A (EDA) gene can lead to both X-linked hypohidrotic ectodermal dysplasia (XLHED) and non-syndromic hypodontia (NSH). However, the mechanism by which these 2 related but different disorders are caused by the distinct mutations in EDA is unknown. In this study, we identified a novel missense mutation (c.779 T>G) in a Chinese family with NSH via a direct sequencing approach. This mutation results in an Ile260Ser substitution in the tumor necrosis factor (TNF) homology domain. Homology modeling suggests that this alteration may induce a conformational change in the hydrophobic center of the TNF homology domain. Furthermore, by exploring systematic 3D conformation analysis and calculation of residue relative solvent accessibility (RSA) for all the reported mutated amino acid sites on EDA’s TNF homology domain, we found that the site mutations at the interior may be linked to XLHED, while those at the surface are more likely to be associated with NSH. These findings may aid in the discovery of unidentified functionally significant mutation sites in the EDA gene and provide a new way to clarify the mechanisms by which the XLHED and NSH phenotypes arise from mutations in the same gene.

ABCB1 Variation and Treatment Response in AIDS Patients: Initial Results of the Henan Cohort

HIV/AIDS has the highest mortality among infectious diseases in China. In ongoing efforts to alleviate this crisis, the national government has placed great emphasis on efforts in Henan province where HIV-infected former plasma donors in the 1990s contributed to AIDS becoming a public health crisis. Concomitant with a national initiative focusing the use of phamacogenetics for the better prediction of treatment response, we studied genetic variants with known pharmacokinetic phenotypes in a set of 298 HAART-treated (highly active antiretroviral therapy) patients infected with HIV from the Henan cohort. We measured the association of response to treatment, assessed as changes in CD4+ T cell counts after antiretroviral therapy, of five polymorphisms in four genes (CYP2B6, ABCB1/MDR1, ABCG2, and ABCC4) in which variation has been suggested to affect the pharmacokinetics of drugs commonly employed to treat HIV/AIDS. We show that genotyping for ABCB1 variations (rs1045642 and rs2032582) may help predict HIV treatment response. We found variations in this gene have a significant association with outcome as measured by CD4+ T cell counts in a discovery subset (N = 197; odds ratio (OR) = 1.58; 95% CI 1.02–2.45), these results were confirmed in a validation subset of the cohort (N = 78; OR = 2.81; 95% CI 1.32–5.96). Exploratory analysis suggests that this effect may be specific to NVP (nevirapine) or 3TC (lamivudine) response. This publication represents the first genetic analysis in a continuing effort to study and assist the patients in a very large, unique, and historically significant HIV-AIDS cohort. Genotyping of AIDS patients for ABCB1 variation may help predict outcome and potentially could help guide treatment strategies.

Perioperative antiviral therapy improves safety in patients with hepatitis B related HCC following hepatectomy

INTRODUCTION Hepatectomies may exacerbate chronic hepatitis B in patients with high hepatitis B viral (HBV) DNA levels, and could result in hepatic insufficiency. Antiviral treatment is effective for suppressing HBV virus loads. This study investigated whether perioperative antiviral therapy is warranted for resection of hepatocellular carcinoma (HCC) with concurrent HBV infections. METHODS Patients with HBV-related HCC (n = 112) who underwent major liver resection were retrospectively divided into two groups based on treatment with perioperative antiviral therapy (antiviral group) (n = 72) or absence of antiviral treatment (control group) (n = 40). RESULTS Exacerbation of chronic hepatitis B occurred in 6 patients of the control group (15.0%). The prevalence of hepatic insufficiency in the antiviral group and control group were 1.4% (1/72) and 12.5% (5/40), respectively (p < 0.05). Five of them (4.5%) developed hepatic encephalopathy and 3 of them (2.7%) developed hepatorenal syndrome. The control group had significantly higher morbidity (75.0% vs. 34.7%, p < 0.01) than the antiviral group. The control group had significantly higher levels of postoperative alanine aminotransferase (ALT) and serum bilirubin than the antiviral group. CONCLUSION Perioperative antiviral treatment improves patient safety by decreasing morbidity and speeding recovery of postoperative liver function for HBV-related major HCC resection.

Mechanisms of Survival Prolongation of Murine Cardiac Allografts Using the Treatment of CTLA4-Ig and MR1

BACKGROUND [corrected] The present study was undertaken to determine the role of costimulatory blockade in a murine cardiac transplant model. MATERIALS AND METHODS We blocked the CD28/B7 and CD154/CD40 costimulatory pathways by transient administration of CTLA4-Ig and MR1 antibody to study the effects on allograft survival time, deviation of Th1 and Th2 cytokine secretion, and other mechanisms related to prolonged survival. RESULTS Costimulatory blockade prolonged the mean survival time (MST) of cardiac allografts to 43 days for the treated group vs 8 days for the untreated group (P < .01). The costimulatory blockade down-regulated the expression of 2 Th1 cytokines (interferon-gamma [IFN-gamma] and interleukin-2 [IL-2]) and 2 Th2 cytokines (IL-4 and IL-10), reduced the numbers of graft-infiltrating CD4+ and CD8+ lymphocytes, and inhibited the expression of both perforin/GrB and FasL in allografts. CONCLUSIONS Combined administration of CTLA4-Ig/MR1 inhibited acute rejection reactions in murine cardiac allografts, prolonging the survival of cardiac grafts through several mechanisms, including inhibition of Th1 and Th2 cytokine expression, graft infiltration by CD4+ and CD8+ T lymphocytes, and reduced both perforin/GrB and Fas-FasL.

Surgical treatment of hepato-pancreato-biliary disease in China: the Tongji experience

Hepato-pancreato-biliary (HPB) tumors are common in China. However, these tumors are often diagnosed at intermediate/ advanced stages because of the lack of a systemic surveillance program in China. This situation creates many technical challenges for surgeons and increases the incidence of postoperative complications. Therefore, Dr. Xiao-Ping Chen has made many important technical improvements, such as Chen’s hepatic portal occlusion method, the anterior approach for liver resection of large HCC tumors, the modified technique of Belghiti’s liver-hanging maneuver, inserting biliary-enteric anastomosis technique, and invaginated pancreaticojujunostomy with transpancreatic U-sutures. These techniques are simple, practical, and easy to learn. Owing to these advantages, complicated surgical procedures can be simplified, and the curative effects are greatly improved. These improved techniques have been widely applied in China and will benefit many additional patients. In this review, we introduce our experience of surgically treating intermediate/advanced hepatocellular carcinoma (HCC), hilar cholangiocarcinoma (HC), and pancreatic carcinoma, mainly focusing on technical innovations established by Dr. Chen in HPB surgery.

Selective Inflow Occlusion Technique Versus Intermittent Pringle Maneuver in Hepatectomy for Large Hepatocellular Carcinoma: A Retrospective Study.

AbstractSelective inflow occlusion (SIO) maneuver preserved inflow of nontumorous liver and was supposed to protect liver function. This study aims to evaluate whether SIO maneuver is superior to Pringle maneuver in patients undergoing partial hepatectomy with large hepatocellular carcinomas (HCCs).Between January 2008 and May 2012, 656 patients underwent large HCC resections and were divided into 2 groups: intermittent Pringle maneuver (IP) group (n = 336) and SIO group (n = 320). Operative parameters, postoperative laboratory tests, and morbidity and mortality were analyzed.In comparison to the IP maneuver, the SIO maneuver significantly decreased intraoperative blood loss (473 vs 691 mL, P = 0.001) and transfusion rates (11.3% vs 28.6%, P = 0.006). The rate of major complication between the 2 groups was comparable (22.6% vs 18.8%, P = 0.541). Patients with moderate/severe cirrhosis, total bilirubin > 17 &mgr;mol/L, or HBV DNA> = 104 copy/mL in SIO group resulted in lower major complication rates.The SIO maneuver is a safe and effective technique for large HCC resections. In patients with moderate/severe cirrhosis, total bilirubin > 17 &mgr;mol/L, or HBV DNA> = 104 copy/mL, the SIO technique is preferentially recommended.

Analysis of Social and Genetic Factors Influencing Heterosexual Transmission of HIV within Serodiscordant Couples in the Henan Cohort

There is considerable variability between individuals in susceptibility to infection by human immunodeficiency virus (HIV). Many social, clinical and genetic factors are known to contribute to the likelihood of HIV transmission, but there is little consensus on the relative importance and potential interaction of these factors. Additionally, recent studies of several variants in chemokine receptors have identified alleles that may be predictive of HIV transmission and disease progression; however the strengths and directions of the associations of these genetic markers with HIV transmission have markedly varied between studies. To better identify factors that predict HIV transmission in a Chinese population, 180 cohabiting serodiscordant couples were enrolled for study by the Henan Center for Disease Prevention and Control, and transmission and progression of HIV infection were regularly measured. We found that anti-retroviral therapy, education level, and condom use were the most significant factors in determining likelihood of HIV transmission in this study. We also assessed ten variants in three genes (CXCL12, CCR2, and CCR5) that have been shown to influence HIV transmission. We found two tightly linked variants in CCR2 and CCR5, rs1799864 and rs1800024, have a significant positive association with transmission as recessive models (OR>10, P value=0.011). Mixed effects models showed that these genetic variants both retained significance when assessed with either treatment or condom use. These markers of transmission susceptibility may therefore serve to help stratify individuals by risk for HIV transmission.