Bile: miRNA pattern and protein-based biomarkers may predict acute cellular rejection after liver transplantation.

Context: Bile rather than blood depicts the local inflammation in the liver and may improve prediction and diagnosis of acute cellular rejection (ACR) after liver transplantation (OLT).

Methods: Secretome and miRNAs were analyzed during the first two weeks and on clinical suspicion of ACR in the bile of 45 OLT recipients.

Results: Levels of CD44, CXCL9, miR-122, miR-133a, miR-148a and miR-194 were significantly higher in bile of patients who developed ACR within the first 6 months after OLT and during ACR.

CD44 and CXCL9 serum protein levels predict the risk of clinically significant allograft rejection after liver transplantation.

The diagnosis of acute cellular rejection (ACR) after liver transplantation is based on histological analysis of biopsies because noninvasive biomarkers for allograft rejection are not yet established for clinical routines. CD31, CD44, and chemokine (C-X-C motif) ligand (CXCL) 9 have previously been described as biomarkers for cross-organ allograft rejection. Here, we assessed the predictive and diagnostic value of these proteins as serum biomarkers for clinically significant ACR in the first 6 months after liver transplantation in a prospective study.

Cytoreductive Surgery for Pancreatic Cancer Improves Overall Outcome of Gemcitabine-Based Chemotherapy.

Objectives: Pancreatoduodenectomy is feasible also in patients with locally advanced pancreatic adenocarcinoma (PA) nowadays. Data on risk and survival analysis of palliative pancreatic resections followed by gemcitabine-based chemotherapy (Cx) are limited.

Methods: Between 2000 and 2009, a total of 45 patients had primary cytoreductive surgery (cS) (pancreaticoduodenectomy or total pancreatectomy) followed by gemcitabine-based Cx (cS + Cx) for advanced PA.

Hedgehog pathway as a potential treatment target in human cholangiocarcinoma.

Background: Innovative treatment concepts targeting essential signaling pathways may offer new chances for patients suffering from cholangiocarcinoma (CCC). For that, we performed a systematic molecular genetic analysis concerning the Hedgehog activity in human CCC samples and analyzed the effect of Hh inhibition on CCC cells in vitro and in vivo.

Methods: Activation of the Hh pathway was analyzed in 50 human CCC samples using quantitative polymerase chain reaction (qPCR).

Genetic variants of STAT-4 affect the development of graft fibrosis after liver transplantation for HCV-induced liver disease.

Background: Hepatitis C virus (HCV) reinfection after liver transplantation may lead to recirrhosis and seems to be influenced by genetic factors. The aim of our study was to evaluate the role of STAT-4-polymorphisms in the development of HCV-related graft disease based on protocol biopsies.

Methods: One hundred sixty transplant patients with HCV recurrence were genotyped for STAT-4 (rs7574865) by polymerase chain reaction.

YKL-40-gene polymorphism affects acute cellular rejection and fibrosis progression after transplantation for hepatitis C virus-induced liver disease.

Background And Aim: The development of end-stage graft disease is suspected to be partially determined by an individual genetic background. The aim of our study was to determine the prevalence of YKL-40-gene polymorphism in hepatitis C virus (HCV)-positive patients and its impact on the incidence of acute cellular rejection (ACR), graft fibrosis and antiviral treatment response.

Methods: A total of 149 patients, who underwent liver transplantation for HCV-induced liver disease, were genotyped for YKL-40 (rs4950928; G/C) by TaqMan Genotyping Assay.

Safety and efficacy of new integrated bipolar and ultrasonic scissors compared to conventional laparoscopic 5-mm sealing and cutting instruments.

Background: Hemostasis is a central issue in laparoscopic surgery. Ultrasonic scissors and bipolar clamps are commonly used, with known advantages with each technique.

Methods: The prototype of new surgical scissors, delivering ultrasonically generated frictional heat energy and bipolar heat energy simultaneously (THUNDERBEAT(®) [TB]), was compared to ultrasonic scissors (Harmonic ACE(®) [HA]) and an advanced bipolar device (LigaSure(®) [LS]) using a pig model.

Role of IL28B polymorphism in the development of hepatitis C virus-induced hepatocellular carcinoma, graft fibrosis, and posttransplant antiviral therapy.

Background: The development of liver graft disease is partially determined by individual genetic background. Interleukin 28B (IL28B) is strongly suspected to be involved in susceptibility for hepatitis C virus (HCV) infection, inflammation, and antiviral treatment response before and after liver transplantation (LT). Currently, the role of IL28B polymorphism (rs12979860) in the development of hepatocellular carcinoma (HCC) is unclear, and only limited data are available on the course of HCV recurrence.

Transforming growth factor-β1-gene polymorphism in the development of kidney disease after liver transplantation.

Background: The development of kidney dysfunction is one of the most important after liver transplantation (LT). Genetic variants of pathogenetically relevant cytokines may influence the development and course of the disease. The aim of our study was to evaluate the role of transforming growth factor-β1 (TGF-β1) polymorphism in this context.

Combination of hedgehog signaling blockage and chemotherapy leads to tumor reduction in pancreatic adenocarcinomas.

Objectives: Activation of the hedgehog signal transduction pathway, triggered by hedgehog binding to the transmembrane receptor patched 1 (PTCH1) or by mutations in the PTCH1 gene, plays an important role in the development of various tumors.

Methods: To investigate whether the Hedgehog signaling pathway is also active in human pancreatic adenocarcinomas, we determined the expression levels of the known Hedgehog target genes PTCH1 and GLI-1 in pancreatic tumors. To determine whether alterations in the PTCH1 gene are responsible for this pathway activation, we screened pancreatic carcinomas for mutations in PTCH.

Association of mannose-binding lectin-2 gene polymorphism with the development of hepatitis C-induced hepatocellular carcinoma.

Background: Development of end-stage liver and graft disease is suspected to be partially determined by the individual genetic background. Mannose-binding lectin (MBL) is an important immunomodulatory factor, which is supposed to be involved in complement activation and oncogenesis. Genetic polymorphisms of MBL-2 alter MBL functionality.

Treatment of hepatitis C-virus-reinfection after liver transplant with silibinin in nonresponders to pegylated interferon-based therapy.

Objectives: Hepatitis C-virus-persistence after orthotopic liver transplant leads to reduced patient and graft survival compared to other indications. Current interferon-based antiviral therapy of hepatitis C-virus-infection posttransplant provides a sustained response rate of 30% to 40%. This study, performed in an hepatitis C-virus-reinfected liver transplant population, examines the antiviral effect of intravenously administered silibinin, recently reported to exhibit strong antiviral properties in the natural setting of hepatitis C-virus-related liver disease.

Relationship between the interleukin-28b gene polymorphism and the histological severity of hepatitis C virus-induced graft inflammation and the response to antiviral therapy after liver transplantation.

Up to 30% of liver transplants will develop graft cirrhosis within 5 years after liver transplantation (LT) due to recurrent HCV-infection forwarding accelerated graft damage. Genetic variants of cytokines involved in the immune response may contribute to the degree of graft inflammation, fibrosis progression, and antiviral therapy outcome. The aim of our study was to analyze biochemical and histological inflammation extent based on protocol liver biopsies and to evaluate the role of genetic variants of IL-28b in HCV-related graft disease and antiviral treatment response.

Transforming growth factor β1 polymorphisms and progression of graft fibrosis after liver transplantation for hepatitis C virus--induced liver disease.

Re-infection with the hepatitis C virus (HCV) is an important development after liver transplantation (LT); it can lead to graft fibrosis. The aim of this study was to assess the role of transforming growth factor β1 (TGF-β1) polymorphisms in the development of HCV-related graft disease by evaluating protocol liver biopsies. A total of 192 patients with a recurrence of HCV infection after LT were genotyped for TGF-β1 codon 10 (C→T) and codon 25 (G→C) using the polymerase chain reaction.

Erythropoietin reduces ischemia-reperfusion injury after liver transplantation in rats.

Human recombinant Erythropoietin (rHuEpo) has recently been shown to be a potent protector of ischemia- reperfusion injury in warm-liver ischemia. Significant enhancement of hepatic regeneration and survival after large volume partial hepatic resection has also been demonstrated. It was the aim of this study to evaluate the capacities of rHuEpo in the setting of rat liver transplantation.

Improvement of microsurgical techniques in orthotopic rat liver transplantation.

Background: Because of the limited tolerance to portal venous clamping, the model of liver transplantation in rats represents a difficult task, which requires a great proportion of experience. Since techniques that include the introduction of an artificial stent increase the risk of thrombosis, it was our goal to modify the classical vascular hand-sewn venous anastomosis technique by using a modified end-to-end knotless procedure.

Materials And Methods: Seventy-two animals were randomly assigned to 1 of 2 experimental groups, which differed by the technique for the 3 venous anastomoses (supra- and infrahepatic vena cava, portal vein).

Erythropoietin promotes hepatic regeneration after extended liver resection in rats.

Background And Aim: It has been proven in various animal studies that recombinant human erythropoietin (rHuEPO) protects renal, cardiac and neuronal, as well as hepatic, tissue from ischemia, and promotes regeneration of adult central nervous system neurons. To date, no data are available as to whether rHuEPO has the ability to stimulate liver regeneration after liver resection.

Methods: Rats undergoing 70% or 90% hepatectomy received an intraportalvenous administration (i.

Combination therapy of poly (ADP-ribose) polymerase inhibitor 3-aminobenzamide and gemcitabine shows strong antitumor activity in pancreatic cancer cells.

Background And Aim: Poly (ADP-ribose) polymerase (PARP) inhibitors such as 3-aminobenzamide (3-ABA) enhance the in vitro cytotoxicity of DNA mono-functional alkylating agents such as radiation or chemotherapeutic agents. The aim of this study was to test an approach combining the PARP inhibitor 3-ABA with standard gemcitabine therapy in human pancreatic cancer cells.

Methods: Cell viability was determined by proliferation assay (XTT).