Comparison of Ablation Area and Change in Functional Liver Reserve after Radiofrequency Ablation for Hepatocellular Carcinoma Using the arfa® and VIVA® Systems

Radiofrequency ablation (RFA) is recommended in Japan for patients with hepatocellular carcinomas (HCCs) one to three in number and ≤3 cm in size. The arfa® and VIVA® RFA systems are widely used for patients with HCC and this retrospective observational study aims to compare their performances. The study included 365 patients with HCCs one to three in number and ≤3 cm in size who underwent RFA using the arfa® system (arfa® group) or the VIVA® system (VIVA® group). The total bilirubin (T-Bil) level after RFA was higher in the arfa® group than in the VIVA® group. With a 3-cm electrode needle, the longest diameter (Dmax) and the shortest diameter were analyzed and found to be greater in the arfa® group than in the VIVA® group. Furthermore, Dmax with the 2.5-cm electrode needle was greater in the arfa® group than in the VIVA® group. Statistically significant differences in the ablation area and in the T-Bil value after RFA were observed between the groups; however, these differences are not considered clinical problems because the difference in the ablation area was only slight and the Child–Pugh score was the same between the groups. Thus, hepatologists can use either of the RFA systems based on their preference.

Structural Analysis of SMYD3 Lysine Methyltransferase for the Development of Competitive and Specific Enzyme Inhibitors

Lysine methylation is among the key posttranslational modifications to histones that contribute to epigenetic regulation. SMYD3 is a lysine methyltransferase that is essential for the proliferation of a range of tumorigenic cells. The findings that SMYD3 is significantly upregulated in most colorectal carcinomas, hepatocellular carcinomas, and breast cell carcinomas support a model in which its aberrant expression modifies established patterns of gene expression, ultimately driving unrestrained proliferation. Herein, we dissect the unique structural features of SMYD3 relative to other SET enzymes, with an emphasis on the implications for selective design of therapeutics for the clinical management of cancer. Further, we illustrate the ability of inhibitors targeting the SET domain of SMYD3 to reduce the viability of colorectal and lung carcinoma cells.

A Combination of Blood Lymphocytes and AST Levels Distinguish Patients with Small Hepatocellular Carcinomas from Non Cancer Patients.

PurposeHCC patients typically present at an advanced tumor stage, in which surgical therapies cannot be used. Screening ultrasound exams can increase the numbers of patients diagnosed with small tumors, but are often not used in patients at risk for HCC. We evaluated clinically-available and cheap potential blood tests as biomarkers for screening patients at risk for HCC.MethodsA comparison was made of commonly used blood count and liver function parameters in a group of patients (n=101) with small HCCs (<3cm) or without HCC (n=275), who presented for liver transplantation in our institute. ResultsSignificant differences were found for blood lymphocytes and AST levels. This 2-parameter combination was found to be significantly different between patients with small HCCs versus no HCC. Using the combination of lymphocytes and AST levels to dichotomize the HCC patients, only blood levels of alpha-fetoprotein amongst the tumor characteristics, were found to be significantly different amongst the 2 HCC groups, as well as levels of blood total bilirubin, ALKP and PLR ratio. The results were confirmed using a separate smaller cohort of non-transplanted small size HCC patients.ConclusionThe combination of elevated blood levels of lymphocyte counts and AST levels holds promise for screening of patients with chronic liver disease who are at risk for HCC.

Hormonally Induced Hepatocellular Carcinoma in Diabetic Wild Type and Carbohydrate Responsive Element Binding Protein Knockout Mice

Objective: In the rat, the pancreatic islet transplantation model is an established method to induce hepatocellular carcinomas (HCC), due to insulin-mediated metabolic and molecular alterations like increased glycolysis and de novo lipogenesis and the oncogenic AKT/mTOR pathway including upregulation of the transcription factor Carbohydrate-response element-binding protein (ChREBP). ChREBP could therefore represent an essential oncogenic co-factor during hormonally induced hepatocarcinogenesis. Methods: Pancreatic islet transplantation was implemented in diabetic C57Bl/6J (wild type, WT) and ChREBP-knockout (KO) mice for 6 and 12 months. Liver tissue was examined using histology, immunohistochemistry, electron microscopy and Western blot analysis. Finally, we performed NGS-based transcriptome analysis between WT and KO liver tumor tissues. Results: Three hepatocellular carcinomas were detectable after 6 and 12 months in diabetic transplanted WT mice, but only one in a KO mouse after 12 months. Pre-neoplastic clear cell foci (CCF) were also present in liver acini downstream of the islets in WT and KO mice. In KO tumors, glycolysis, de novo lipogenesis and AKT/mTOR signalling were strongly downregulated compared to WT lesions. Extrafocal liver tissue of diabetic, transplanted KO mice revealed less glycogen storage and proliferative activity than WT mice. From transcriptome analysis, we identified a set of transcripts pertaining to metabolic, oncogenic and immunogenic pathways that are differentially expressed between tumors of WT and KO mice. Of 315 metabolism-associated genes, we observed 199 genes that displayed upregulation in the tumor of WT mice, whereas 116 transcripts showed their downregulated expression in KO mice tumor. Conclusions: The pancreatic islet transplantation model is a suitable method to study hormonally induced hepatocarcinogenesis also in mice, allowing combination with gene knockout models. Our data indicate that deletion of ChREBP delays insulin-induced hepatocarcinogenesis, suggesting a combined oncogenic and lipogenic function of ChREBP along AKT/mTOR-mediated proliferation of hepatocytes and induction of hepatocellular carcinoma.

Prognostic CT Features and Prediction Model of Patients With Primary Hepatocellular Carcinomas Undergoing Partial Hepatectomy

Background: Hepatocellular carcinoma (HCC) is the most common primary malignant tumor in the liver. Partial hepatectomy is one of the most effective therapies for HCC but suffer from the high recurrence rate. At present, the studies of association between clinical outcomes and CT features of patients with HCCs undergoing partial hepatectomy are still limited. The purpose of this study is to determine the predictive CT features and establish a model for predicting relapse or metastasis in patients with primary hepatocellular carcinomas (HCCs) undergoing partial hepatectomy.Methods: The clinical data and CT features of 112 patients with histopathologically confirmed primary HCCs were retrospectively reviewed. The clinical outcomes were categorized into two groups according to whether relapse or metastasis occurred within 2 years after partial hepatectomy. The association between clinical outcomes and CT features including tumour size, margin, shape, vascular invasion (VI), arterial phase hyperenhancement, washout appearance, capsule appearance, satellite lesion, involvement segment, cirrhosis, peritumoral enhancement and necrosis was analyzed using univariate analysis and binary logistic regression. Then establish logistic regression model, followed by receiver operating characteristic (ROC) curve analysis.Results: CT features including tumor size, margin, shape, VI, washout appearance, satellite lesion, involvement segment, peritumoral enhancement and necrosis were associated with clinical outcomes, as determined by univariate analysis (P<0.05). Only tumor margin and VI remained independent risk factors in binary logistic regression analysis (OR=6.41 and 10.92 respectively). The logistic regression model was logit(p)=-1.55+1.86 margin +2.39 VI. ROC curve analysis showed that the area under curve of the obtained logistic regression model was 0.887(95% CI：0.827-0.947).Conclusion: Patients with ill-defined margin or VI of HCCs were independent risk predictors of poor clinical outcome after partial hepatectomy. The model as logit(p)= -1.55+1.86 margin +2.39 VI was a good predictor of the clinical outcomes.