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Background: De novo malignancies occur after liver transplantation because of immunosuppression and improved long-term survival. But the spectrums and associated risk factors remain unclear. Aims: To describe the overall pattern of de novo cancers in liver transplant recipients. Methods: Data from Scientific Registry of Transplant Recipients from October 1987 to December 2009 were analyzed. The spectrum of de novo cancer was analyzed and logistic-regression was used to identify predictors of do novo malignancies. Results: Among 89,036 liver transplant recipients, 6,834 recipients developed 9,717 post-transplant malignancies. We focused on non-skin malignancies. A total of 3,845 recipients suffered from 4,854 de novo non-skin malignancies, including 1,098 de novo hematological malignancies, 38 donor-related cases, and 3,718 de novo solid-organ malignancies. Liver transplant recipients had more than 11 times elevated cancer risk compared with the general population. The long-term overall survival was better for recipients without de novo cancer. Multivariate analysis indicated that HCV, alcoholic liver disease, autoimmune liver disease, nonalcoholic steatohepatitis, re-transplantation, combined transplantation, hepatocellular carcinoma, immunosuppression regime of cellcept, cyclosporine, sirolimus, steroids and tacrolimus were independent predictors for the development of solid malignancies after liver transplantation. Conclusions: De novo cancer risk was elevated in liver transplant recipients. Multiple factors including age, gender, underlying liver disease and immunosuppression were associated with the development of de novo cancer. This is useful in guiding recipient selection as well as post-transplant surveillance and prevention. [ABSTRACT FROM AUTHOR]

Background: Standard-volume polyethylene glycol (PEG) gut lavage solutions are safe and effective, but they require the consumption of large volumes of fluid. A new lower-volume solution of PEG plus ascorbic acid has been used recently as a preparation for colonoscopy. Aim: A meta-analysis was performed to compare the performance of low-volume PEG plus ascorbic acid with standard-volume PEG as bowel preparation for colonoscopy. Study: Electronic and manual searches were performed to identify randomized controlled trials (RCTs) that compared the performance of low-volume PEG plus ascorbic acid with standard-volume PEG as bowel preparation for colonoscopy. After a methodological quality assessment and data extraction, the pooled estimates of bowel preparation efficacy during bowel cleansing, compliance with preparation, willingness to repeat the same preparation, and the side effects were calculated. We calculated pooled estimates of odds ratios (OR) by fixed- and/or random-effects models. We also assessed heterogeneity among studies and the publication bias. Results: Eleven RCTs were identified for analysis. The pooled OR for preparation efficacy during bowel cleansing and for compliance with preparation for low-volume PEG plus ascorbic acid were 1.08 (95% CI = 0.98–1.28, P = 0.34) and 2.23 (95% CI = 1.67–2.98, P<0.00001), respectively, compared with those for standard-volume PEG. The side effects of vomiting and nausea for low-volume PEG plus ascorbic acid were reduced relative to standard-volume PEG. There was no significant publication bias, according to a funnel plot. Conclusions: Low-volume PEG plus ascorbic acid gut lavage achieved non-inferior efficacy for bowel cleansing, is more acceptable to patients, and has fewer side effects than standard-volume PEG as a bowel preparation method for colonoscopy. [ABSTRACT FROM AUTHOR]

Background: The enhanced liver fibrosis test (ELF) has been shown to accurately predict significant liver fibrosis in several liver diseases. Aims: To perform a meta-analysis to assess the performance of the ELF test for the assessment of liver fibrosis. Study: Electronic and manual searches were performed to identify studies of the ELF test. After methodological quality assessment and data extraction, pooled estimates of the sensitivity, specificity, area under the receiver operating characteristic curve (AUROC), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and summary receiver operating characteristics (sROC) were assessed systematically. The extent of heterogeneity and reasons for it were assessed. Results: Nine studies were identified for analysis. The pooled sensitivity, specificity, positive LR, negative LR, and DOR values of ELF test, for assessment of significant liver fibrosis, were 83% (95% CI = 0.80–0.86), 73% (95% CI = 0.69–0.77), 4.00 (95% CI = 2.50–6.39), 0.24 (95% CI = 0.17–0.34), and 16.10 (95% CI = 8.27–31.34), respectively; and, for evaluation of severe liver fibrosis, were 78% (95% CI = 0.74–0.81), 76% (95% CI = 0.73–0.78), 4.39 (95% CI = 2.76–6.97), 0.27 (95% CI = 0.16–0.46), and 16.01 (95% CI: 7.15–35.82), respectively; and, for estimation of cirrhosis, were 80% (95% CI = 0.75–0.85), 71% (95% CI = 0.68–0.74), 3.13 (95% CI = 2.01–4.87), 0.29 (95% CI = 0.19–0.44), and 14.09 (95% CI: 5.43–36.59), respectively. Conclusions: The ELF test shows good performance and considerable diagnostic value for the prediction of histological fibrosis stage. [ABSTRACT FROM AUTHOR]

Background: Salvage liver transplantation (SLT) has recently been proposed for recurrent hepatocellular carcinoma after liver resection; however, criteria for candidate assessment in SLT have not been thoroughly evaluated. Methods and Findings: We retrospectively analyzed outcomes and factors affecting survival of 53 recipients who received SLT in the Liver Transplantation Center, The First Affiliated Hospital of Zhejiang University between 2004 and 2012. Thirty recipients fulfilled the Hangzhou criteria, of which 16 also fulfilled the Milan criteria, while the remaining 23 exceeded both criteria. The 1-year, 3-year and 5-year overall survival rates and tumor-free survival rates were both superior in patients fulfilling Milan or Hangzhou criteria compared with those exceeding the criteria. For recipients outside Milan criteria but within Hangzhou criteria, the 1-year, 3-year overall survival rates were 70.1%, 70.1%, similar to recipients within Milan criteria, with the 1-year, 3-year and 5-year overall survival of 93.8%%, 62.1% and 62.1% (P = 0.586). The tumor-free survival rates were also similar between these two subgroups, with 51.9% and 51.9% vs. 85.6%, 85.6% and 64.2% during the same time interval, respectively (P = 0.054). Cox regression analysis identified Hangzhou criteria (within vs. outside, hazard ratio (HR) 0.376) and diameter of the largest tumor (HR 3.523) to be independent predictors for overall survival. The only predictor for tumor-free survival was diameter of the largest tumor (HR 22.289). Conclusions: Hangzhou criteria safely expanded the candidate pool and are feasible in assessment of candidates for SLT. This is helpful in donor liver allocation in transplant practice. [ABSTRACT FROM AUTHOR]

Background and Aim: Recurrence and metastasis are associated with poor prognosis in hepatocellular carcinoma even in the patients who have undergone radical resection. Therefore, effective treatment is urgently needed for improvement of patients' survival. Previously, we reported that nanosecond pulse electric fields (nsPEFs) can ablate melanoma by induction of apoptosis and inhibition of angiogenesis. This study aims to investigate the in vivo ablation strategy by comparing the dose effect of nanosecond electric fields in vitro and in vivo on hepatocellular carcinoma. Materials and Methods: Four hepatocellular carcinoma cell lines HepG2, SMMC7721, Hep1-6, and HCCLM3 were pulsed to test the anti-proliferation and anti-migration ability of 100 ns nsPEFs in vitro. The animal model of human subdermal xenograft HCCLM3 cells into BALB/c nude mouse was used to test the anti-tumor growth and macrophage infiltration in vivo. Results: In vitro assays showed anti-tumor effect of nsPEFs is dose-dependant. But the in vivo study showed the strategy of low dose and multiple treatments is superior to high dose single treatment. The macrophages infiltration significantly increased in the tumors which were treated by multiple low dose nsPEFs. Conclusion: The low dose multiple nsPEFs application is more efficient than high dose single treatment in inhibiting the tumor volume in vivo, which is quite different from the dose-effect relationship in vitro. Beside the electric field strength, the macrophage involvement must be considered to account for effect variability and toxicology in vivo. [ABSTRACT FROM AUTHOR]

The secretion function of intestinal graft is one of the most important factors for successful intestinal transplantation. Cystic fibrosis transmembrane conductance regulator (CFTR) mediates HCO3- and Cl- secretions in intestinal epithelial cells. In this study, we made investigation on the expression and function of CFTR in an experimental model of murine small intestinal transplantation. Heterotopic intestinal transplantations were performed in syngeneic mice. The mRNA and protein expressions of CFTR were analyzed by real time PCR and western blot. Murine intestinal mucosal HCO3- and Cl- secretions were examined in vitro in Ussing chambers by the pH stat and short circuit current (Isc) techniques. The results showed that forskolin, an activator of CFTR, stimulated jejunal mucosal epithelial HCO3- and Cl- secretions in mice, but forskolin-stimulated HCO3- and Cl- secretions in donor and recipient jejunal mucosae of mice after heterotopic jejunal transplantation were markedly decreased, compared with controls (P<0.001). The mRNA and protein expression levels of CFTR in donor and recipient jejunal mucosae of mice were also markedly lower than those in controls (P<0.001), and the mRNA and protein expression levels of tumor necrosis factor α (TNFα) were markedly increased in donor jejunal mucosae of mice (P<0.001), compared with controls. Further experiments showed that TNFα down-regulated the expression of CFTR mRNA in murine jejunal mucosa. In conclusion, after intestinal transplantation, the function of CFTR was impaired, and its mRNA and protein expressions were down-regulated, which may be induced by TNFα. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) and hepatitis C virus (HCV)-HCC are the main indications for liver transplantation. We compared differences in survival outcomes between these two conditions. Methods and Findings: The China Liver Transplant Registry (CLTR) contains data collated from all transplants performed in 86 liver transplantation centers across China. We analyzed CLTR data from January 1999 to December 2010. In all, 7,658 patients (7,162 with HBV-HCC and 496 with HCV-HCC) were included in this study. Clinical characteristics were compared between the HBV-HCC and HCV-HCC groups; Kaplan–Meier analysis was used to calculate the overall, tumor-free and hepatitis-free survival rates. The 1-year, 3-year and 5-year overall survival was significantly higher in HBV-HCC recipients than in HCV-HCC recipients (76.65%, 56.61% and 49.10% vs. 64.59%, 42.78% and 39.20%, respectively; P<0.001). The corresponding tumor-free survival rates (63.55%, 47.37%, 40.99% vs. 56.84%, 38.04%, 35.66%, respectively) and hepatitis-free survival rates (75.49%, 54.84%, 47.34% vs. 63.87%, 42.15%, 39.33%, respectively) were both superior in HBV-HCC recipients (both P<0.001). Multivariate analyses identified hepatitis, preoperative alpha-fetoprotein (AFP) level, size of largest tumor, number of tumor nodules, TNM stage, vascular invasion and preoperative model for end-stage liver disease (MELD) score as independent predictors of overall, tumor-free and hepatitis-free survival. Conclusions: Survival outcomes after liver transplantation were significantly better in HBV-HCC patients than in HCV-HCC patients. This finding may be used to guide donor liver allocation in transplantation programs. [ABSTRACT FROM AUTHOR]

Background and Aim: Recurrence and metastasis are associated with poor prognosis in hepatocellular carcinoma even in the patients who have undergone radical resection. Therefore, effective treatment is urgently needed for improvement of patients' survival. Previously, we reported that nanosecond pulse electric fields (nsPEFs) can ablate melanoma by induction of apoptosis and inhibition of angiogenesis. This study aims to investigate the in vivo ablation strategy by comparing the dose effect of nanosecond electric fields in vitro and in vivo on hepatocellular carcinoma. Materials and Methods: Four hepatocellular carcinoma cell lines HepG2, SMMC7721, Hep1-6, and HCCLM3 were pulsed to test the anti-proliferation and anti-migration ability of 100 ns nsPEFs in vitro. The animal model of human subdermal xenograft HCCLM3 cells into BALB/c nude mouse was used to test the anti-tumor growth and macrophage infiltration in vivo. Results: In vitro assays showed anti-tumor effect of nsPEFs is dose-dependant. But the in vivo study showed the strategy of low dose and multiple treatments is superior to high dose single treatment. The macrophages infiltration significantly increased in the tumors which were treated by multiple low dose nsPEFs. Conclusion: The low dose multiple nsPEFs application is more efficient than high dose single treatment in inhibiting the tumor volume in vivo, which is quite different from the dose-effect relationship in vitro. Beside the electric field strength, the macrophage involvement must be considered to account for effect variability and toxicology in vivo. [ABSTRACT FROM AUTHOR]