Validation of Kinki Criteria, a Modified Substaging System, in Patients with Intermediate Stage Hepatocellular Carcinoma.

Background: The standard treatment option that is available for patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) is transarterial chemoembolization (TACE). However, the condition of the patients with BCLC stage B disease is heterogeneous showing different tumor statuses and Child-Pugh scores; treatment strategies other than TACE are frequently employed for the patients in this stage. Based on the subclassification system proposed by Bolondi et al.

Survival Benefit of Locoregional Treatment for Hepatocellular Carcinoma with Advanced Liver Cirrhosis.

Background & Aims: Hepatocellular carcinoma (HCC) with decompensated liver cirrhosis (LC) is a life-threatening condition, which is amenable to liver transplantation (LT) as the standard first-line treatment. However, the application of LT can be limited due to a shortage of donor livers. This study aimed to clarify the effect of non-surgical therapy on the survival of patients with HCC and decompensated LC.

Phase I/II Study of Sorafenib in Combination with Hepatic Arterial Infusion Chemotherapy Using Low-Dose Cisplatin and 5-Fluorouracil.

We conducted a phase I/II study in patients with advanced hepatocellular carcinoma (HCC) to determine the recommended dose, as well as the safety and efficacy, of combination therapy of sorafenib with hepatic arterial infusion chemotherapy (HAIC) using low dose cisplatin (CDDP) and 5-fluorouracil (5FU). Cohorts consisting of 3-6 patients with HCC received an escalated dose of CDDP and 5-FU until a maximum-tolerated dose was achieved. The treatment regimen was as follows: oral administration of sorafenib (400 mg twice daily for 28 days) combined with HAIC using CDDP (14-20 mg/m(2), on days 1 and 8) and 5-FU (170-330 mg/m(2), continuously on days 1-5 and 8-12) via an implanted catheter system).

Effectiveness of Sorafenib in Patients with Transcatheter Arterial Chemoembolization (TACE) Refractory and Intermediate-Stage Hepatocellular Carcinoma.

Background And Aims: Patients with intermediate-stage hepatocellular carcinoma (HCC) refractory to transcatheter arterial chemoembolization (TACE) are considered to be candidates for sorafenib. The aim of this study was to evaluate the superiority of conversion of treatment to sorafenib on overall survival (OS) for cases refractory to TACE.

Methods: This was a retrospective cohort study carried out on 497 patients with HCC who were treated with TACE therapy at our hospital between January 2008 and December 2013.

Validation of a Modified Substaging System (Kinki Criteria) for Patients with Intermediate-Stage Hepatocellular Carcinoma.

Introduction: Barcelona Clinic Liver Cancer (BCLC) stage B, an intermediate stage, includes various conditions of hepatocellular carcinoma (HCC). This heterogeneity of the patients with intermediate-stage HCC makes it difficult to predict their survival rates. In the present study, we examined the validity of the modified Bolondi classification (Kinki criteria) as a subclassification of patients with BCLC stage B HCC.

Balloon-Occluded Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma: A Single-Center Experience.

Objective: To investigate whether balloon-occluded transcatheter arterial chemoembolization (b-TACE) can produce a more dense accumulation of iodized oil in various stages of hepatocellular carcinoma (HCC), from single to uncountable, to overcome inferior local control.

Materials And Methods: We studied 27 patients with HCC, including single to uncountable multiple lesions, who underwent b-TACE between August 2013 and April 2015. Dynamic CT was performed at baseline and 1-3 months after b-TACE.

Evaluation of ART Scores for Repeated Transarterial Chemoembolization in Japanese Patients with Hepatocellular Carcinoma.

Objective: Transarterial chemoembolization (TACE) is recommended as a first-line therapy for hepatocellular carcinoma (HCC) patients ineligible for curative therapy and without portal invasion. The Assessment for Retreatment with TACE (ART) scoring system was recently proposed for identifying patients who would not show sufficient survival benefit from repeated TACE. We reevaluated the performance of ART in HCC patients treated in Japan, where selective TACE is commonly used.

Hepatic DNA Methylation Is Affected by Hepatocellular Carcinoma Risk in Patients with and without Hepatitis Virus.

Objectives: Several studies revealed that the proportion of hepatocellular carcinoma (HCC) without hepatitis virus infection (NBNC-HCC) is increasing. On the other hand, epigenetic alterations are reportedly responsible for HCC development. Here, we identified HCC risk factors that are associated with DNA methylation in the background liver tissue of NBNC-HCC patients.

Real-Life Clinical Practice with Sorafenib in Advanced Hepatocellular Carcinoma: A Single-Center Experience Second Analysis.

Objectives: Sorafenib has become a standard therapy for advanced hepatocellular carcinoma following the demonstration of significant increase in progression-free survival as well as overall survival (OS) in the 2-phase III trials. We examined efficacy and adverse events (AEs) in patients treated with sorafenib over a 6-year period since approval in Japan.

Methods: Two hundred and forty-one patients treated with sorafenib at the Kinki University Hospital were retrospectively analyzed clinically for the factors related to survival periods, tumor response evaluated by the Response Evaluation Criteria In Cancer of the Liver (RECICL) and AEs.

Early Viral Response Predicts the Efficacy of Antiviral Triple Therapy with Simeprevir, Peg-Interferon and Ribavirin in Patients Infected with Hepatitis C Virus Genotype 1.

Objectives: Triple therapy using peg-interferon, ribavirin and simeprevir (PEG-IFN/RBV/SMV) has reportedly resulted in high-sustained virological response (SVR) rates in patients with chronic hepatitis C (CHC), especially in naïve cases and relapsers to prior PEG-IFN/RBV therapy. Here, we retrospectively analyzed the antiviral response associated with a triple regimen, in the context of early reduction of viral load during treatment.

Methods: Forty-six CHC patients with HCV genotype 1b were treated with PEG-IFN/RBV/SMV triple therapy: 20 were naïve cases, 12 were relapsers and 14 were non-responders to prior PEG-IFN/RBV therapy.

Efficacy and safety of telaprevir-based antiviral treatment for elderly patients with hepatitis C virus.

Background: Telaprevir-based antiviral therapy has been the primary treatment for chronic hepatitis C genotype 1 at a high viral load since November 2011. On the other hand, a number of patients have been reported to require withdrawal from or reduced doses of drugs due to side effects, such as eruptions, anemia, and renal dysfunction. In addition, as hepatitis C patients are growing older, it is imperative to investigate the tolerability of triple combination therapy for elderly patients.

Treatment of hepatocellular carcinoma with Child-Pugh C cirrhosis.

Background: In most guidelines, no other interventional therapy but liver transplantation is recommended for the treatment of hepatocellular carcinoma (HCC) with Child-Pugh C cirrhosis (CP-C). However, in Japan, patients were sometimes treated with expectation of benefit.

Summary: A workshop was conducted to explore the state of treatments for CP-C HCC in Japan.

Combination guidance of contrast-enhanced US and fusion imaging in radiofrequency ablation for hepatocellular carcinoma with poor conspicuity on contrast-enhanced US/fusion imaging.

Purpose: The purpose of this study was to evaluate the usefulness of the combination guidance of contrast-enhanced US (CEUS) and fusion imaging in radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) with poor conspicuity on B-mode US and CEUS/fusion imaging.

Materials And Methods: We conducted a retrospective cohort study, which included 356 patients with 556 HCCs that were inconspicuous on B-mode US. A total of 192 patients with 344 HCCs, 123 patients with 155 HCCs, and 37 patients with 57 HCCs underwent RFA under CEUS guidance, fusion imaging guidance, and the combination of CEUS and fusion imaging guidance.

Validation of the criteria of transcatheter arterial chemoembolization failure or refractoriness in patients with advanced hepatocellular carcinoma proposed by the LCSGJ.

Background: Transcatheter arterial chemoembolization (TACE) failure or refractoriness is an indication for sorafenib therapy in patients with advanced hepatocellular carcinoma. The study evaluated the validity of the definition of TACE failure or refractoriness as proposed by the Liver Cancer Study Group of Japan (LCSGJ) through a retrospective analysis of sorafenib treatment.

Methods: Out of 265 patients with advanced hepatocellular carcinoma who were treated with sorafenib at our hospital, 45 experienced TACE failure or refractoriness and were included in this study and retrospectively analyzed.

Identification of epigenetically inactivated genes in human hepatocellular carcinoma by integrative analyses of methylation profiling and pharmacological unmasking.

Objectives: DNA methylation-dependent transcriptional inactivation of tumor suppressor genes (TSGs) is critical for the pathogenesis of hepatocellular carcinoma (HCC). This study identifies potential TSGs in HCCs using methylation profiling and pharmacological unmasking of methylated TSGs.

Methods: Methylation profiling was performed on 22 pairs of HCCs and their corresponding noncancerous liver tissues using the Infinium HumanMethylation27 BeadChip.

Decreased blood flow after sorafenib administration is an imaging biomarker to predict overall survival in patients with advanced hepatocellular carcinoma.

Background: Sorafenib is a multikinase inhibitor targeting Raf and protein tyrosine kinases, which are involved in cell growth and tumor angiogenesis. Sorafenib administration induces temporary inhibition of tumor growth and a decrease in arterial blood flow in a considerable number of hepatocellular carcinoma (HCC) patients. We retrospectively evaluated the association between decreased blood flow and the overall survival (OS) of HCC patients after the initiation of sorafenib therapy.

Validation of three staging systems for hepatocellular carcinoma (JIS score, biomarker-combined JIS score and BCLC system) in 4,649 cases from a Japanese nationwide survey.

Objective: Clinical staging is very important for optimal therapeutic strategy and prognostic prediction in patients with hepatocellular carcinoma (HCC). The Barcelona Clinic Liver Cancer (BCLC) staging system is the most widely used and best-validated method for HCC. Similarly, the conventional Japan Integrated Staging (c-JIS) score and the biomarker-combined JIS (bm-JIS) score have also been reported to effectively stratify HCC patients.

Duration of stable disease is associated with overall survival in patients with advanced hepatocellular carcinoma treated with sorafenib.

Background: Sorafenib is a molecular-targeting agent showing improved overall survival (OS) for advanced hepatocellular carcinoma (HCC). Although tumor dormancy, characterized by stable tumor status or stable disease (SD) without tumor regression, is a unique feature of sorafenib treatment, the contribution of SD to OS remains debatable. This study aimed to clarify the correlation between SD periods and OS in patients with HCC treated with sorafenib.

Radiofrequency ablation for hepatocellular carcinoma measuring 2 cm or smaller: results and risk factors for local recurrence.

Objective: The purpose of this study was to evaluate the risk factors for local recurrence with radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) measuring ≤2 cm.

Methods: This study involved 234 patients with 274 HCCs measuring ≤2 cm who had undergone RFA as the initial treatment. The mean tumor diameter was 1.

Genome-wide profiling of DNA methylation and tumor progression in human hepatocellular carcinoma.

Objective: To clarify the progression pattern of abnormal DNA methylation during the development of hepatocellular carcinoma (HCC) using a comprehensive methylation assay.

Methods: We used an Infinium HumanMethylation450 BeadChip array that can analyze >485,000 CpG sites distributed throughout the genome for a comprehensive methylation study of 117 liver tissues consisting of 59 HCC and 58 noncancerous livers. Altered DNA methylation patterns during tumor progression were also analyzed.

Comparison of systems for assessment of post-therapeutic response to sorafenib for hepatocellular carcinoma.

Background: To test the hypothesis that use of the response evaluation criteria in cancer of the liver (RECICL), an improved evaluation system designed to address the limitations of the response evaluation criteria in solid tumors 1.1 (RECIST1.1) and modified RECIST (mRECIST), provides for more accurate evaluation of response of patients with hepatocellular carcinoma (HCC) to treatment with sorafenib, a molecularly targeted agent, as assessed by overall survival (OS).

Reactive oxygen species induce epigenetic instability through the formation of 8-hydroxydeoxyguanosine in human hepatocarcinogenesis.

Chronic hepatitis C (CHC) triggers oxidative stress and contributes to the emergence of hepatocellular carcinoma (HCC). We previously reported that tumor suppressor gene (TSG) methylation is a critical factor during the early stages of hepatocarcinogenesis. In this study, we clarify the association between oxidative stress and epigenetic alterations during hepatocarcinogenesis.

Unique association between global DNA hypomethylation and chromosomal alterations in human hepatocellular carcinoma.

Global DNA hypomethylation is a characteristic feature of cancer cells that closely associates with chromosomal instability (CIN). However, the association between these characteristics during hepatocarcinogenesis remains unclear. Herein, we determined the relationship between hypomethylation and CIN in human hepatocellular carcinoma (HCC) by analyzing 179 HCCs, 178 matched non-tumor livers and 23 normal liver tissues.

Quantification of tumor DNA in serum and vascular invasion of human hepatocellular carcinoma.

Objectives: Hepatocellular carcinoma (HCC) is one of the common cancers worldwide. Accurate diagnosis of tumor progression is critical for the appropriate management of HCC. Here, we established a sensitive assay to detect and quantify tumor-derived DNA in the serum of HCC patients.

Usefulness of contrast-enhanced ultrasonography to evaluate the post-treatment responses of radiofrequency ablation for hepatocellular carcinoma: comparison with dynamic CT.

Objective: Contrast-enhanced ultrasonography (CEUS) with Sonazoid® and dynamic computed tomography (CT) were used to evaluate radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). Local recurrence rate was used as the gold standard of evaluation.

Methods: From January 2007 to December 2011, 86 HCCs from 70 patients were treated with RFA.