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Postoperative recurrence of liver cancer is the main obstacle to improving the survival rate of patients with liver cancer. We established an mRNA-based model to predict the risk of recurrence after hepatectomy for liver cancer and explored the relationship between immune infiltration and the risk of recurrence after hepatectomy for liver cancer. We performed a series of bioinformatics analyses on the gene expression profiles of patients with liver cancer, and selected 18 mRNAs as biomarkers for predicting the risk of recurrence of liver cancer using a machine learning method. At the same time, we evaluated the immune infiltration of the samples and conducted a joint analysis of the recurrence risk of liver cancer and found that B cell, B cell naive, T cell CD4+ memory resting, and T cell CD4+ were significantly correlated with the risk of postoperative recurrence of liver cancer. These results are helpful for early detection, intervention, and the individualized treatment of patients with liver cancer after surgical resection, and help to reveal the potential mechanism of liver cancer recurrence. [ABSTRACT FROM AUTHOR]

Detecting deep tumors inside living subject is still challenging for Cerenkov luminescence imaging (CLI). In this study, a high-sensitivity endoscopic CLI (ECLI) system was developed with a dual-mode deep cooling approach to improve the imaging sensitivity. System was characterized through a series of ex vivo studies. Furthermore, subcutaneous and orthotropic human hepatocellular carcinoma (HCC) mouse models were established for ECLI guided tumor resection in vivo. The results showed that the ECLI system had spatial resolution (62.5 μm) and imaging sensitivity (6.29 × 10−2 kBq/μl 18F-FDG). The in vivo experimental data from the HCC mouse models demonstrated that the system was effective to intraoperatively guide the surgery of deep tumors such as liver cancer. Overall, the developed system exhibits promising potential for the applications of tumor precise resection and novel nanoprobe based optical imaging. Intraoperative guidance by optical imaging significantly promotes the achievement of precise tumor surgery. A high-sensitivity imaging system was developed for endoscopic Cerenkov luminescence imaging (ECLI). By employing the clinical radiopharmaceutical and clinical device, the deep liver tumors were detected and visualized intraoperatively. Clear ECLI optical signals were observed in the tumor location where the radiopharmaceutical was aggregated. Tumor boundaries were also delineated clearly. In vivo ECLI technique showed high potential for clinical translation and believed promising for intraoperative imaging with novel nanoprobes. Unlabelled Image [ABSTRACT FROM AUTHOR]

Background/Aim: Liver transplantation is a well-recognized treatment for non-resectable hepatocellular carcinoma (HCC); however, the overall survival and waiting list removal rates for hepatitis C virus (HCV)-related HCC have not been assessed. Methods: The present study included 11,146 patients with HCC and 64,788 patients without HCC, listed for liver transplantation on the Scientific Registry of Transplant Recipients database between 2003 and 2010. Results: In a multivariate analysis, HCV infection was an independent predictor of being transplanted or remaining on the waiting list in HCC candidates (HR 0.65, 95 % CI 0.60-0.71, p < 0.001). However, patients in the advanced status (model for end-stage liver disease score over 20, tumor stage exceed tumor-node-metastasis stage II, or alpha fetoprotein lover 400 ng/ml) but without HCV had better post-transplant survival than patients in the advanced status and with HCV (64 vs. 47 % at 5 years, p < 0.001), and comparable survival to patients with HCV but not in the advanced status (62 %, p = 0.461). Conclusions: HCC candidates with HCV infection are more likely to be transplanted, remain on the waiting list for longer, and have worse post-transplant survival. Patients in the advanced status but without HCV also could share a similar post-transplant survival to those not in the advanced status but with HCV. [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: 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]

Accurate identification of tumor tissues and their margins are still challenging for conventional clinical imaging methods during liver cancer surgery. In this study, dual-band confocal laser endomicroscopy (CLE) combined with image mosaic was used to guide liver cancer surgery. In the experiments with mice bearing orthotropic liver tumor, CLE can accurately detect the tumors and identify their margins with two excitation wavelengths of 488 nm and 660 nm by clinically available dyes fluorescein sodium (FS) or indocyanine green (ICG). The mosaic CLE images enlarged the imaging field and detected the liver tumor margins more accurately. Normal liver tissues fluorescence intensity of CLE images was significantly higher than that of tumor tissues in the same tumor-bearing mice (P < 0.0001). Overall, dual-band CLE imaging demonstrates to be a promising method to identify liver tumor tissues and margins, which has the prospect of clinical application and helps to achieve intraoperative radical resection. Accurate identification of tumor tissues and margins are still challenging for conventional clinical imaging methods during liver cancer operation. Confocal laser endomicroscopy (CLE) is a new type of microscopic optical imaging technique that can visualize the cellular and subcellular structures of the tissue with 1000 × magnification. CLE imaging can accuracy detect and identify the tumor tissue margins at the excitation wavelength of 488 nm and 660 nm by clinically available dyes fluorescein sodium (FS) or indocyanine green (ICG). Image mosaic and fluorescence quantification of CLE images are both helpful to distinguish liver tumor tissue. In vivo Dual-band CLE imaging technique showed high potential for clinical translation and helps to achieve intraoperative radical resection. Unlabelled Image [ABSTRACT FROM AUTHOR]

In early studies, it was shown that HINT2, which sensitizes cells to mitochondrial apoptosis, is down-regulated in hepatocellular carcinoma (HCC) cells (Martin et al., 2006). However, the molecular mechanism of this effect is unknown. Immunohistochemistry revealed that HINT2 expression is relatively low in pancreatic cancer tissues, compared to that in adjacent tissues (P < 0.05). Furthermore, its expression was related to pathological grade and lymph node metastasis (P = 0.0161 and 0.0108, respectively); in addition, down-regulation of HINT2 was found to be associated with relatively poor prognosis in pancreatic cancer patients. Up-regulation of HINT2 was shown to trigger pancreatic cancer cell apoptosis, decrease mitochondrial membrane potential (ΔΨm), promote intracellular reactive oxygen species (ROS) production, and elevate mitochondrial Ca2+ levels. However, co-treatment of HINT2 overexpressing BxPC-3 cells with ruthenium red partially inhibited HINT2-induced apoptosis, which was associated with a reduction in ΔΨm and an increase in intracellular ROS and mitochondrial Ca2+. According to our results, mitochondrial calcium uptake1 and 2 (MICU1 and MICU2) were down-regulated and the essential MCU regulator (EMRE) was up-regulated in cells transduced with Adv-HINT2. Therefore, we deduced that HINT2 triggers apoptosis in pancreatic cancer cells by regulating mitochondrial Ca2+ influx through the mitochondrial calcium uniporter (MCU). In addition, we found that HINT2 can sensitize BxPC-3 and L3.6pl cells to gemcitabine-induced apoptosis and that gemcitabine up-regulates HINT2 expression. This indicates that gemcitabine-induced apoptosis is related to HINT2 levels. [ABSTRACT FROM AUTHOR]

Abstract: Hepatocellular carcinoma (HCC) is a highly aggressive malignancy. Nanosecond pulsed electric field (nsPEF) is a new technology destroying tumor cells with a non-thermal high voltage electric field using ultra-short pulses. The study’s aim was to evaluate the ablation efficacy of nsPEFs with human HCC cell lines and a highly metastatic potential HCC xenograft model on BALB/c nude mice. The in vivo study showed nsPEFs induced HCC cell death in a dose dependent manner. On the high metastatic hepatocellular carcinoma cell line (HCCLM3) xenograft mice model, tumor growth was inhibited significantly in nsPEF-treated- groups (single dose and multi-fractionated dose). Besides a local effect, the nsPEF treatment reduced pulmonary metastases. The nsPEFs also enhanced HCC cell phagocytosis by human macrophage cell (THP1) in vitro. The nsPEF is efficient in controlling HCC progression and reducing its metastasis. NsPEF treatment may elicit a host immune response against tumor cells. This study suggests nsPEF therapy could be used as a potential locoregional therapy for hepatocellular carcinoma. [Copyright &y& Elsevier]