Jin Mo Yang

Comparative study between doxorubicin-eluting beads and conventional transarterial chemoembolization for treatment of hepatocellular carcinoma.

BACKGROUND & AIMS Transarterial chemoembolization (TACE) is a widely used treatment for hepatocellular carcinoma. In order to maximize its therapeutic efficacy, doxorubicin-loaded drug-eluting beads have been developed to deliver higher doses of the chemotherapeutic agent and to prolong contact time with the tumor. The purpose of this study was to evaluate the efficacy and safety of drug-eluting bead (DC bead®) TACE in comparison with conventional TACE (cTACE). METHODS A total of 129 patients who underwent TACE between August 2008 and February 2011 were enrolled. We compared HCC patients who underwent TACE with DC bead® (n=60) to controls who received cTACE (n=69). The primary end points were treatment response and treatment-related adverse events. The secondary end point was time to progression. RESULTS The treatment response in the DC bead® group was significantly higher than that of the cTACE group (p<0.001). The time to progression was significantly better in the DC bead® group than in the cTACE group (11.7 and 7.6months, respectively, p=0.018). Subgroup analysis showed that in intermediate-stage HCC, DC bead® treatment resulted in a significantly better treatment response and longer time to progression than cTACE (p<0.001 and 0.038, respectively). However, there was no statistically significant difference in liver toxicity between the DC bead® and cTACE group (p>0.05). CONCLUSIONS TACE with DC bead® showed better treatment response and delayed tumor progression compared with cTACE. There was no significant difference in hepatic treatment-related toxicities. DC bead® TACE thus appears to be a feasible and promising approach to the treatment of HCC.

SOX4 overexpression regulates the p53-mediated apoptosis in hepatocellular carcinoma: clinical implication and functional analysis in vitro

BACKGROUND AND AIMS The underlying molecular mechanisms of hepatocellular carcinoma (HCC) remain poorly understood due to its complex development process. The human T cell-specific transcription factor sex-determining region Y-related high-mobility group (HMG) box 4 (SOX4) has been linked to development and tumorigenesis. In this study, we characterized the roles of SOX4 in regulation of the p53 transcription activity and evaluated the expression patterns and prognostic value of the transcription factor SOX4 in HCC. METHODS The expression levels of human SOX4 were examined in HCC samples obtained from 58 patients having curative partial hepatectomy. The interaction and effects of SOX4 on the p53 pathway were assessed in HCC cell lines. Luciferase reporter assay to examine p53-mediated transcription of target genes was performed. The association of SOX4 expression level with tumor recurrence and overall survival was evaluated. RESULTS We showed that the HMG box domain of SOX4 interacted with p53, resulting in the inhibition of p53-mediated transcription by the Bax promoter. More importantly, SOX4 overexpression led to a significant repression of p53-induced Bax expression and subsequent repression of p53-mediated apoptosis induced by gamma-irradiation. In clinicopathological analysis, nuclear overexpression of SOX4 was observed in 37 out of 58 (63.8%) HCC samples, and this correlated with diminished risk of recurrence (P = 0.014) and improved overall survival time (P = 0.045) in HCC patients. CONCLUSION These results suggest that SOX4 contributes to hepatocarcinogenesis by inhibiting p53-mediated apoptosis and that its overexpression might be a useful prognostic marker for survival after surgical resection.

Long-term outcome of high-intensity focused ultrasound in advanced pancreatic cancer.

Objectives: The aim of this study was to evaluate safety and efficacy of high-intensity focused ultrasound (HIFU) for advanced pancreatic cancer (PC). Methods: Patients with PC TNM stage III or IV were included. Magnetic resonance imaging was performed 2 weeks before and after the HIFU. The ablating tumor volume was calculated by ratio of the nonperfused necrotic area of the planned area on contrast-enhanced T1-weighted image on post-HIFU magnetic resonance imaging. The ablation results were stratified into 4 ranges: 100% to 90% unenhanced area of targeting area, 90% to 50%, within 50%, and no change. Results: High-intensity focused ultrasound treatment was performed without severe adverse event in 46 patients, 49 times (male-female = 25:21; mean age, 60.7 ± 10.0; TNM stage 3-stage 4 = 18:28). Average size of the PC lesion was 4.2 ± 1.4 cm (1.6-9.3 cm). After HIFU treatment, ablating tumor volume was as follows: 90% to 100% in 38 lesions, 90% to 50% in 8, and within 50% in 3. Overall median survival (S1) from initial PC diagnosis was 12.4 months. Overall survival (S2) rates at 6, 12, and 18 months from HIFU were 52.2%, 30.4%, and 21.79%, respectively, with a median survival of 7.0 months Conclusions: High-intensity focused ultrasound is safe and effective, which induced excellent local tumor control in most patients with advanced PC.

Spontaneous regression of a large hepatocellular carcinoma with skull metastasis

Abstract  Spontaneous regression of hepatocellular carcinoma (HCC) is a rare phenomenon. This case of a 65‐year‐old Korean man with HCC and metastatic frontal bone mass that regressed after radiotherapy for frontal bone mass without any other therapeutic modalities is described. The clinical diagnosis of HCC was made because of the presence of a liver mass on abdominal computed tomography (CT) scan, high serum α‐fetoprotein value and tissue diagnosis on frontal bone biopsy. The patient refused any other recommended treatments, but accepted the radiation therapy due to a painful frontal bone mass, and ingested mushroom called Phellinus linteus for one and a half years. Ten months after radiation therapy, he experienced a reduction in size of the frontal bone mass and improvement of lesions in the liver, sternum and ribs. The patient is alive and in good condition without any symptoms or tumor aggravation in August 2002. It was concluded that a rare case of spontaneous regression of HCC had occurred.

The impact of hepatitis B viral load on recurrence after complete necrosis in patients with hepatocellular carcinoma who receive transarterial chemolipiodolization: implications for viral suppression to reduce the risk of cancer recurrence.

Hepatocellular carcinoma (HCC) has a high tendency for recurrence after radical treatment. Apart from tumor and liver function parameters, little is known about the role of hepatitis B virus (HBV) factors in the recurrence of HCC. The objective of this study was to identify the potential relation between viral load and HCC recurrence in patients undergoing transarterial chemolipiodolization.

Comparison of Surrogate Serum Markers and Transient Elastography (Fibroscan) for Assessing Cirrhosis in Patients with Chronic Viral Hepatitis

BackgroundProgressive hepatic fibrosis with development of cirrhosis is a feature of almost all chronic liver diseases.AimsWe assessed the performance of Fibroscan in patients with chronic viral hepatitis, and in comparison with and combined with several surrogate serum markers for predicting cirrhosis.MethodsIn this prospective multicenter cohort study, a novel panel of serum markers was constructed and serum levels of surrogate markers of liver fibrosis and Fibroscan were compared with the stage of fibrosis in the liver biopsy specimens obtained from 121 subjects with chronic viral hepatitis. Another 159 patients were enrolled to validate the diagnostic accuracy of this novel panel.ResultsMultivariate analysis identified platelet count and procollagen III N-terminal peptide (PIIINP) as independent predictors of liver cirrhosis. The PP score (combining of platelet count and PIIINP) showed significantly better diagnostic accuracy (areas under the receiver operating characteristic curves, AUROC: 0.885) than that of previously reported serologic tests, including APRI, Forns fibrosis index, FIB-4 index and ELF algorithm, in the validation group (AUROC: 0.792, 0.740, 0.800, and 0.775, respectively). The AUROC of Fibroscan was 0.743 and the best performance was obtained by combining Fibroscan, platelet count and PIIINP, with an AUROC of 0.826. However, there was no significant difference among the AUROCs of Fibroscan alone, PP score, the combination of Fibroscan and PP score, and previously reported serologic tests in the estimation group.ConclusionsFibroscan and surrogate serum markers had similar accuracy for predicting cirrhosis, and combining Fibroscan and serum markers did not improve the accuracy.

Preconditioning by extracorporeal liver support (MARS) of patients with cirrhosis and severe liver failure evaluated for living donor liver transplantation -- a pilot study.

Abstract: Purpose: The aim of this prospective study was to evaluate the effectiveness of preconditioning molecular adsorbent recirculating system (MARS) treatment on patients with acute‐on‐chronic liver failure (AoCLF), who were awaiting living donor liver transplantation (LDLT).

The usefulness of liver stiffness measurement using FibroScan in chronic hepatitis C in South Korea: A multicenter, prospective study

Aim:  We investigated the accuracy of liver stiffness measurement (LSM) in chronic hepatitis C (CHC) in a multicenter, prospective study in South Korea.

Association between human leukocytes antigen alleles and chronic hepatitis C virus infection in the Korean population.

Abstract: Background/Aim: Recent data have shown that the clinical outcome of hepatitis C virus (HCV) infection may be influenced by the host genetic factor. The aim of this study was to investigate whether particular human leukocytes antigen (HLA) molecules are associated with the susceptibility to HCV infection in the Korean population.

Efficacy and Tolerability of Peginterferon Alpha Plus Ribavirin in the Routine Daily Treatment of Chronic Hepatitis C Patients in Korea: A Multi-Center, Retrospective Observational Study

Background/Aims We aimed to evaluate the efficacy and safety of peginterferon plus ribavirin for chronic hepatitis C (CHC) patients under real life setting in Korea. Methods We retrospectively analyzed the medical records of 758 CHC patients treated with peginterferon plus ribavirin between 2000 and 2008 from 14 university hospitals in the Gyeonggi-Incheon area in Korea. Results Hepatitis C virus (HCV) genotype 1 was detected in 61.2% of patients, while genotype 2 was detected in 35.5%. Baseline HCV RNA level was ≥6×105 IU/mL in 51.6% of patients. The sustained virological response (SVR) rate was 59.6% regardless of genotype; 53.6% in genotype 1 and 71.4% in genotype 2/3. On multivariate analysis, male gender (p=0.011), early virological response (p<0.001), genotype 2/3 (p<0.001), HCV RNA <6×105 IU/mL (p=0.005) and adherence to the drug >80% of the planned dose (p<0.001) were associated with SVR. The rate of premature discontinuation was 35.7%. The main reason for withdrawal was intolerance to the drug due to common adverse events or cytopenia (48.2%). Conclusions Our data suggest that the efficacy of peginterferon and ribavirin therapy in Koreans is better in Koreans than in Caucasians for the treatment of CHC, corroborating previous studies that have shown the superior therapeutic efficacy of this regimen in Asians.