Joong-Won Park

National Cancer Center Korea, Kōyō, Gyeonggi-do, South Korea

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Publications (88)381.95 Total impact

  • Hee-Won Kwak · Joong-Won Park · Young Hwan Koh · Ju Hee Lee · Ami Yu · Byung-Ho Nam
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    ABSTRACT: Objectives: Chronic hepatitis B virus (HBV) infection is the most common cause of hepatocellular carcinoma (HCC) in South Korea, but a high prevalence of metabolic diseases may result in increases in the incidence of cryptogenic HCC (cHCC). We studied characteristics of the cHCC in a single-center cohort. Methods: A cohort of 1,784 HCC patients newly diagnosed and treated at the National Cancer Center, Korea, between 2004 and 2009 was reviewed and analyzed. Results: The cause of HCC was categorized as cHCC, HBV, hepatitis C virus (HCV), or alcohol. Overall, 162 (9.1%) patients of the HCC cohort had cHCC, and their mean age was 61.9 years. The median survival of cHCC patients was 24.7 months, which was the second shortest among the four groups after HBV HCC. cHCC patients had the largest tumor size (mean 7.4 cm) and the second highest proportion of poor prognostic factors such as the proportion of poorly defined tumors and extrahepatic spread in imaging studies. cHCC patients had better survival than HBV HCC patients according to multivariate analysis. Among cHCC patients, 137 (84.6%) had anti-HBc IgG antibodies, but this sub-group had different clinical features to those of HBV HCC patients. The body mass index (BMI) and hyperglycemia and hypercholesterolemia levels in cHCC patients were similar to those in HCV and alcoholic HCC patients. Conclusions: Anti-HBc IgG antibodies were present in most cHCC patients, but cHCC patients had better survival than HBV HCC patients on multivariate analysis. However, cHCC patients had a larger mean tumor size and more aggressive tumor characteristics than HCV HCC or alcoholic HCC patients did. It is hoped that this study will contribute to a better understanding of cHCC in HBV-endemic areas.
    No preview · Article · Dec 2015
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    ABSTRACT: To identify prognostic indicators in patients treated with radiotherapy (RT) for metastases from hepatocellular carcinoma (HCC) in abdominal lymph nodes (LNs). RT was used to treat 65 patients for metastases from HCC in abdominal LNs. Total radiation dose was 30-60 Gy (median 52.8 Gy), with fraction size 1.8-3 Gy. RT was administered five times per week to an equivalent dose in 2-Gy fractions (EQD2; Gy10) of 32.5-65 Gy10 (median 54 Gy10) and an α/βratio for tumor and acute effects of normal tissue of 10. Median overall survival (OS) in all patients was 8.1 months. LN responders had significantly higher median OS than nonresponders (14.5 vs. 3.7 months, p < 0.05). Multivariate analysis showed that Child-Pugh classification, status of intrahepatic tumor, number of metastatic LNs, and LN response were independently predictive of OS (p < 0.05 each). Based on results of multivariate analysis, patients were prognostically stratified according to pretreatment risk factors, including Child-Pugh classification, intrahepatic tumor status, and number of metastatic LNs; with the expected median OS in patients with ≥ 2, 1, and 0 risk factors being 2.9, 9.8, and 27.6 months, respectively (p < 0.05). Our data showed that LN response to RT was an independent prognostic factor for OS in advanced HCC patients with abdominal LN metastases, and suggested that RT for metastatic LNs might improve OS in these patients. In addition, our data suggest that Child-Pugh classification, intrahepatic tumor status, and number of metastatic LNs may be useful prognostic and therapeutic indicators for selecting treatment strategies.
    No preview · Article · Jul 2015 · Strahlentherapie und Onkologie
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    ABSTRACT: Reliable biomarkers are required to predict the response to sorafenib. We investigated genomic variations associated with responsiveness to sorafenib for patients with unresectable hepatocellular carcinoma (HCC). Blood samples from 2 extreme, 2 strong and 3 poor responders to sorafenib were subjected to whole-genome analysis. Then, we validated candidate genomic variations with another 174 HCC patients, and performed in vitro functional analysis and in silico analyses. Genomic data of >96 gigabases/sample was generated at average of ~34X sequencing depth. In total, 1813 genomic variations were matched to sorafenib responses in clinical data; 708 were located within regions for sorafenib-target genes or drug absorption, distribution, metabolism, and excretion (ADME)-related genes. From them, 36 variants were within the coding regions and 6 identified as non-synonymous single-nucleotide variants from 4 ADME-related genes (ABCB1, FMO3, MUSK, and SLC15A2). Validation genotyping confirmed sequencing results and revealed patients genotype for rs2257212 in SLC15A2 showed longer progression-free survival (HR = 2.18). In vitro study displayed different response to sorafenib depending on the genotype of SLC15A2. Structural prediction analysis revealed changes of the phosphorylation levels in protein, potentially affecting sorafenib-associated enzymatic activity. Our finding using extreme responder seems to generate robust biomarker to predict the response of sorafenib treatment for HCC. INTRODUCTION Hepatocellular carcinoma (HCC) is one of the most common types of cancers (with the highest prevalence in the Asia-Pacific region) and the third leading cause of cancer death worldwide. [1] Because this disease is mostly diagnosed at an advance stage, potentially curative therapies are effective in less than 30–40% of HCC patients. [2, 3] While systemic therapies are indicated for advanced HCC, no effective systemic therapy for patients
    Full-text · Article · Apr 2015 · Oncotarget
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    ABSTRACT: Discoidin domain receptors (DDRs) have been identified as tyrosine kinase receptors for collagen, and the overexpression of DDR1 was correlated with hepatocellular carcinoma (HCC) progression in vitro. Little is known about DDR2 on HCC cells, and we investigated the expression and function of DDR2 in human HCC cells. Expression of DDR2 in human HCC cell lines and patient HCC tissues was observed. The suppression of DDR2 by siRNA against DDR2 was performed in vitro and in vivo study. All of HCC cell lines expressed DDR2 mRNA, and all HCC tissues from the ten patients with HCC demonstrated DDR2 mRNA expression. Transfection of DDR2 siRNA significantly inhibits cell growth compared to cells with nontarget siRNA transfection in vitro (P < 0.001). In SNU182, Hep3B, and HeLa cell xenograft models, there was a significant difference in average tumor volumes after 12 days of the DDR2 siRNA injection (P < 0.05) in SNU182 xenograft mice. DDR2 siRNA injection decreased the mean tumor volume by 65.6 % compared to that of the control. The apoptosis analysis demonstrated that DDR2 siRNA treatment significantly increased apoptotic cells (P < 0.01). Cell migration (P < 0.05) and cell invasion (P < 0.01) were significantly decreased by DDR2 siRNA treatment. The inhibition of DDR2 by RNA interference suppressed in vivo and in vitro growth of human HCC cells. Our results may support that the use of DDR2 as a novel target of HCC treatment through control of tumor apoptosis, migration, and invasion.
    No preview · Article · Apr 2015 · Journal of Cancer Research and Clinical Oncology

  • No preview · Article · Mar 2015 · Acta oncologica (Stockholm, Sweden)
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    ABSTRACT: Current guidelines recommend surgical resection as the primary treatment for a single hepatocellular cancer (HCC) with Child's A cirrhosis, normal serum bilirubin and no clinically-significant portal hypertension. We determined how frequently guidelines were followed and whether straying from them impacted survival. BRIDGE is a multiregional cohort study including HCC patients diagnosed between January 1, 2005 and June 30, 2011. 8,656 patients from 20 sites were classified into four groups: (A) 718 ideal resection candidates who were resected, (B) 144 ideal resection candidates who were not resected, (C) 1,624 non-ideal resection candidates who were resected, and (D) 6,170 non-ideal resection candidates who were not resected. Median follow-up was 27 months. Log rank and Cox regression analyses were conducted to determine differences between groups and variables associated with survival. Multivariate analysis of all ideal candidates for resection (A+B) revealed a higher risk of mortality with treatments other than resection. For all resected patients (A+C), portal hypertension and bilirubin >1mg/dl were not associated with mortality. For all patients who were not ideal candidates for resection (C+D), resection was associated with better survival compared to embolization and "other" treatments but was inferior to ablation and transplantation. Conclusions: The majority of patients undergoing resection would not be considered ideal candidates based on current guidelines. Not resecting ideal candidates was associated with higher mortality. The study suggests that selection criteria for resection may be modestly expanded without compromising outcomes and that some non-ideal candidates may still potentially benefit from resection over other treatment modalities. This article is protected by copyright. All rights reserved. © 2015 by the American Association for the Study of Liver Diseases.
    No preview · Article · Feb 2015 · Hepatology
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    ABSTRACT: Tenofovir disoproxil fumarate (TDF) monotherapy is a therapeutic option for chronic hepatitis B (CHB) patients infected with hepatitis B virus (HBV) variants resistant to lamivudine (LAM). We evaluated antiviral efficacy and safety of TDF alone compared to TDF plus LAM or telbivudine (LdT) combination in patients harboring HBV variants with genotypic resistance to LAM. This multicenter retrospective study included consecutive patients who had LAM-resistant HBV variants and were treated with TDF alone (monotherapy group) or TDF combined with LAM or LdT (combination therapy group) for at least 6 months. Inverse probability of treatment weighting (IPTW) for the entire cohort was applied to control for treatment selection bias. Overall, 153 patients (33 in the monotherapy group and 120 in the combination therapy group) were analyzed. The overall probability of achieving complete virologic suppression at month 12 was 91.6%: 88.6% in the monotherapy group and 92.6% in the combination therapy group. Combination therapy was not superior to monotherapy in viral suppression before and after IPTW (P=0.562 and P=0.194, respectively). Hepatitis B e antigen (HBeAg) loss, biochemical response, and virologic breakthrough did not differ between treatment groups. The probabilities of complete virologic suppression were comparable between treatment groups in the subsets according to HBeAg status and HBV DNA levels at baseline. No patient experienced any significant renal dysfunction during the treatment period. In conclusion, TDF monotherapy has comparable antiviral efficacy to TDF plus LAM or LdT combination therapy with favorable safety profile in CHB patients with LAM-resistant HBV variants. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
    Preview · Article · Nov 2014 · Antimicrobial Agents and Chemotherapy
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    ABSTRACT: Purpose: There is an unmet need for treatment options in hepatocellular carcinoma (HCC). Sorafenib is currently the only approved systemic treatment for HCC. Refametinib, an oral, allosteric MEK inhibitor, has demonstrated antitumor activity in combination with sorafenib in vitro and in vivo. A phase II study evaluated efficacy and safety of refametinib plus sorafenib in Asian patients with HCC (NCT01204177). Experimental design: Eligible patients received twice-daily refametinib 50 mg plus twice-daily sorafenib 200 mg (morning)/400 mg (evening), with dose escalation to sorafenib 400 mg twice daily from cycle 2 if no grade ≥ 2 hand-foot skin reaction, fatigue, or gastrointestinal toxicity occurred. Primary efficacy endpoint: disease control rate. Secondary endpoints: time to progression, overall survival, pharmacokinetic assessment, biomarker analysis, safety, and tolerability. Results: Of 95 enrolled patients, 70 received study treatment. Most patients had liver cirrhosis (82.9%) and hepatitis B viral infection (75.7%). Disease control rate was 44.8% (primary efficacy analysis; n = 58). Median time to progression was 122 days, median overall survival was 290 days (n = 70). Best clinical responders had RAS mutations; majority of poor responders had wild-type RAS. Most frequent drug-related adverse events were diarrhea, rash, aspartate aminotransferase elevation, vomiting, and nausea. Dose modifications due to adverse events were necessary in almost all patients. Conclusions: Refametinib plus sorafenib showed antitumor activity in patients with HCC and was tolerated at reduced doses by most patients. Frequent dose modifications due to grade 3 adverse events may have contributed to limited treatment effect. Patients with RAS mutations appear to benefit from refametinib/sorafenib combination.
    No preview · Article · Oct 2014 · Clinical Cancer Research
  • Bo Hyun Kim · Joong-Won Park

    No preview · Article · Oct 2014
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    ABSTRACT: Purpose The purpose of this study is to determine the optimal dose of proton beam therapy (PBT) in hepatocellular carcinoma (HCC) patients. Materials and Methods Inoperable HCC patients who had naïve, recurrent, or residual tumor to treatment were considered eligible for PBT. Patients received PBT with 60 GyE in 20 fractions (dose level 1; equivalent dose in 2 Gy fractions [EQD2], 65 GyE10); 66 GyE in 22 fractions (dose level 2; EQD2, 71.5 GyE10); or 72 GyE in 24 fractions (dose level 3; EQD2, 78 GyE10). Dose-limiting toxicity was determined by grade ≥ 3 acute toxicity. Results Twenty-seven patients were enrolled; eight, seven, and 12 patients were treated with dose levels 1, 2, and 3, respectively. Overall, treatment was well tolerated, with no dose-limiting toxicities. The complete response (CR) rates of primary tumors after PBT for dose levels 1, 2, and 3 were 62.5% (5/8), 57.1% (4/7), and 100% (12/12), respectively (p=0.039). The 3-and 5-year local progression-free survival (LPFS) rates among 26 patients, excluding one patient who underwent liver transplantation after PBT due to its probable significant effect on disease control, were 79.9% and 63.9%, respectively, and the 3-and 5-year overall survival rates were 56.4% and 42.3%, respectively. The 3-year LPFS rate was significantly higher in patients who achieved CR than in those who did not (90% vs. 40%, p=0.003). Conclusion PBT is safe and effective and an EQD2 ≥ 78 GyE10 should be delivered for achievement of local tumor control.
    Preview · Article · Sep 2014 · Cancer Research and Treatment
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    ABSTRACT: Assessing treatment responses in hepatocellular carcinoma (HCC) is challenging, and alternative radiologic methods of measuring treatment response are required. Modified Response Evaluation Criteria in Solid Tumors (mRECIST) for HCC and alpha-fetoprotein (AFP) levels were assessed in a post hoc analysis of a phase II study of brivanib, a selective dual inhibitor of fibroblast growth factor and vascular endothelial growth factor signaling. HCC patients were treated with first-line (cohort A; n = 55) or second-line (cohort B; n = 46) brivanib alaninate 800 mg once daily. Outcomes were compared between World Health Organization (WHO) criteria and (retrospectively by) mRECIST by independent review. The relationship between on-study AFP changes and outcome was analyzed in patients with elevated AFP at baseline. Response rates were higher with mRECIST versus WHO criteria in cohorts A (25.5% vs. 7.3%) and B (10.9% vs. 4.3%). Progressive disease (PD) as assessed by mRECIST was associated with a very short median overall survival (OS; cohort A, 2.8 months; cohort B, 5.3 months); PD as assessed by WHO criteria reflected a mixed population of patients with better outcomes. mRECIST responders tended to have a>50% AFP decrease during therapy. In cohorts A and B pooled, an early AFP response (>20%or >50% decline from baseline within the first 4 weeks) was not associated with longer median OS. Tumor response as assessed by mRECIST differed from that by WHO criteria, with mRECIST possibly identifying true nonresponders with a poor prognosis. Many patients had AFP decreases correlating with tumor shrinkage, yet an association with long-term benefit was unclear. mRECIST and on-treatment AFP levels are being explored further with brivanib in HCC.
    No preview · Article · Aug 2014
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    Full-text · Article · Jun 2014 · Journal of Hepatology
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    ABSTRACT: Hepatocellular carcinoma (HCC) is classified as a poor prognostic tumor, and becomes frequently aggressive. MicroRNAs emerge as key contributors to tumor progression. This study investigated whether miR-148a dysregulation differentiates poor prognosis of HCC, exploring new targets of miR-148a. miR-148a dysregulation discriminated not only the overall survival and recurrence free survival rates of HCC, but the microvascular invasion. In the human HCC samples, ubiquitin specific protease 4 (USP4) and sphingosine 1-phosphate receptor 1 (S1P1) were up-regulated as the new targets of miR-148a. USP4 and S1P1 were up-regulated in mesenchymal-type liver-tumor cells with miR-148a dysregulation, facilitating migration and proliferation of tumor cells. The inverse relationship between miR-148a and the identified targets was verified in a tumor xenograft model. In the analysis of human samples, the expression of USP4, but not S1P1, correlated with the decrease of miR-148a. In a heterotropic patient-derived HCC xenograft model, USP4 was also overexpressed in G1 and G2 tumors when miR-148a was dysregulated, reflecting the closer link between miR-148a and USP4 for a shift in the expansion phase of tumorgraft. In conclusion, miR-148a dysregulation affects the poor prognosis of HCC. Of the identified targets of miR-148a, USP4 overexpression may contribute to HCC progression towards more aggressive feature.
    Full-text · Article · Apr 2014 · Oncotarget
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    ABSTRACT: The aim of this work was to evaluate the clinical efficacy and safety of simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) in patients with inoperable hepatocellular carcinoma (HCC). A total of 53 patients with inoperable HCC underwent SIB-IMRT using two dose-fractionation schemes, depending on the proximity of gastrointestinal structures. The 41 patients in the low dose-fractionation (LD) group, with internal target volume (ITV) < 1 cm from gastrointestinal structures, received total doses of 55 and 44 Gy in 22 fractions to planning target volume 1 (PTV1) and 2 (PTV2), respectively. The 12 patients in the high dose-fractionation (HD) group, with ITV ≥ 1 cm from gastrointestinal structures, received total doses of 66 and 55 Gy in 22 fractions to the PTV1 and PTV2, respectively. Overall, treatment was well tolerated, with no grade > 3 toxicity. The LD group had larger sized tumors (median: 6 vs. 3.4 cm) and greater frequencies of vascular invasion (80.6 vs. 16.7 %) than patients in the HD group (p < 0.05 each). The median overall survival (OS) was 25.1 mKonzept ist machbar und sicheronths and the actuarial 2-year local progression-free survival (LPFS), relapse-free survival (RFS), and OS rates were 67.3, 14.7, and 54.7 %, respectively. The HD group tended to show better tumor response (100 vs. 62.2 %, p = 0.039) and 2-year LPFS (85.7 vs. 59 %, p = 0.119), RFS (38.1 vs. 7.3 %, p = 0.063), and OS (83.3 vs. 44.3 %, p = 0.037) rates than the LD group. Multivariate analysis showed that tumor response was significantly associated with OS. SIB-IMRT is feasible and safe for patients with inoperable HCC.
    No preview · Article · Mar 2014 · Strahlentherapie und Onkologie
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    ABSTRACT: To evaluate the clinical effectiveness and safety of proton beam therapy (PBT) in advanced hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT). Twenty-seven HCC patients with PVTT underwent PBT, including 22 patients with modified International Union Against Cancer (mUICC) stage IVA,five patients with stage IVB primary tumors, and 16 with main PVTT. A median dose of 55 GyE (range, 50-66 GyE) in 20-22 fractions was delivered to a target volume encompassing both the PVTT and primary tumor. Overall, treatment was well tolerated, with no toxicity of grade ≥ 3. Median overall survival (OS) times in all patients and in stage IVA patients were 13.2 months and 16 months, respectively. Assessments of PVTT response showed complete response in 0 of 27 (0 %) patients, partial response in 15 (55.6 %), stable disease in 10 (37 %), and progressive disease in 2 (7.4 %) patients, with an objective response rate of 55.6 %. PVTT responders showed significantly higher actuarial 1-year local progression-free survival (LPFS; 85.6 % vs. 51.3 %), relapse-free survival (RFS; 20 % vs. 0 %) and OS (80 % vs. 25 %) rates than nonresponders (p < 0.05 each). Multivariate analysis showed that PVTT response and mUICC stage were independent prognostic factors for OS. Our data suggest that PBT could improve LPFS, RFS, and OS in advanced HCC patients with PVTT and it is feasible and safe for these patients.
    No preview · Article · Mar 2014 · Strahlentherapie und Onkologie
  • Hwi Young Kim · Joong-Won Park
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    ABSTRACT: Sorafenib, a multikinase inhibitor that targets angiogenesis in hepatocellular carcinoma (HCC), has become a standard treatment for advanced-stage HCC and has shown survival benefits in recent clinical trials. Transarterial chemoembolization (TACE) and sorafenib are currently standard treatments for intermediate and advanced-stage HCC, respectively. Combined locoregional therapy, including TACE and molecular targeted therapies such as sorafenib, is an issue under active investigation in an attempt to improve the outcomes of patients with unresectable HCC. Various clinical trials of these combined strategies have been conducted; however, the designs of these studies are diverse in terms of treatment modalities and schedules; comparisons with controls, baseline tumor stages, and hepatic functional reserves; and outcome measures. This article reviews heterogeneity in the design of recent clinical trials of combined locoregional and molecular targeted therapies and briefly addresses future study directions.
    No preview · Article · Mar 2014
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    ABSTRACT: A standard treatment for unresectable advanced-stage intrahepatic cholangiocarcinoma (IHCC) has not yet been established. Although neoadjuvant concurrent chemoradiotherapy (CCRT) and liver transplantation are associated with long-term survival in select patients, the outcomes of CCRT for advanced-stage unresectable IHCC remain unclear. The aim of our study was to evaluate the outcomes of CCRT in patients with unresectable advanced-stage IHCC. We retrospectively reviewed the records of all patients with unresectable advanced stage (stage IVa or IVb) IHCC who were pathologically diagnosed and treated at National Cancer Center, Korea, from June 2001 to March 2012. Of the total of 92 patients, 25 (27.1%) received capecitabine plus cisplatin (XP) chemotherapy with external radiotherapy (RT) (XP-CCRT group) and 67 (72.8%) received XP chemotherapy alone (XP group). The clinical characteristics and outcomes of the 2 groups were compared. The 92 patients comprised 72 male and 20 female patients, with a median age of 58 years (range 26-78 years). The baseline clinical characteristics of the 2 groups were similar. Patients in the XP-CCRT group received a mean 44.7 Gy of RT and a mean 5.6 cycles of XP chemotherapy, whereas patients in the XP group received a mean 4.0 cycles. The disease control rate was higher in the XP-CCRT group than in the XP group, but the difference was not statistically significant (56.0% vs. 41.5%, p = 0.217). Although neutropenia was significantly more frequent in the XP-CCRT than in the XP group (48% vs. 9%, p < 0.001), the rates of other toxicities and > grade 3 toxicities did not differ. At a median follow-up of 5.3 months, PFS (4.3 vs. 1.9 months, p = 0.001) and OS (9.3 vs. 6.2 months, p = 0.048) were significantly longer in the XP-CCRT than in the XP group. XP-CCRT was well tolerated and was associated with longer PFS and OS than XP chemotherapy alone in patients with unresectable advanced IHCC. Controlled randomized trials are required to determine whether XP-CCRT is a primary treatment option for patients with unresectable advanced IHCC.
    Full-text · Article · Dec 2013 · Radiation Oncology
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    ABSTRACT: To evaluate the clinical outcomes of patients with hepatocellular carcinoma (HCC) and compare the findings with that of a previous cohort. Overall, 1972 HCC patients diagnosed and treated at the National Cancer Center, Korea between 2004 and 2009 were enrolled. The data of this cohort were compared with those of a previous cohort (2000-2003) from the same institution. In all (mean age, 56.4 years; 1642 men), 74.6% was hepatitis B virus (HBV) positive, 81.6% were Child-Pugh (CP) class A, and 64.4% was Barcelona Clinic Liver Cancer (BCLC) stage C. The modified Union for International Cancer Control (mUICC) stage I, II, III, IVa, and IVb was found in 8.9%, 29.6%, 24.8%, 23.1%, and 13.6% patients, respectively. The most common initial treatment was transarterial chemotherapy (58.3%), followed by resection (18.6%). The 5-year survival rate of BCLC stage 0, A, B, and C were 79.6%, 67.2%, 33.9%, and 17.1%, respectively. The performance status, BCLC stage, mUICC stage, CP class, model for end-stage liver disease score, tumor characteristics, portal vein tumor invasion, and serum alpha-fetoprotein level proved to be independent prognostic variables. Overall survival in the present cohort was better than that in the previous cohort (hazard ratio, 0.829; 95% confidence interval, 0.754-0.912), especially for advanced HCC patients with HBV-positive status. This cohort study provides valuable insights into the characteristics of HCC in Korean patients. Our findings may help develop clinical trials, treatment strategies, and prognosis systems for HCC patients in HBV-endemic areas.
    No preview · Article · Dec 2013 · Journal of Gastroenterology and Hepatology
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    ABSTRACT: Objective: Radiation-induced hemorrhagic gastroduodenal vascular ectasia (GDVE) is rare but difficult to manage. Argon plasma coagulation (APC) has not yet been evaluated in the treatment of radiation-induced hemorrhagic GDVE. The efficacy of APC in patients with radiation-induced hemorrhagic GDVE has been investigated in this article. Material and methods: Eighteen patients with upper gastrointestinal (GI) bleeding caused by radiation-induced GDVE, including 13 with hepatocellular carcinoma, 3 with pancreatic cancer, and 2 with cholangiocarcinoma, were treated with APC. The efficacy of APC was retrospectively evaluated, based on cessation of macroscopic GI bleeding, resolution or stabilization of anemia and transfusion dependence, endoscopic ablation of almost all vascular lesions, complications, and recurrence. Results: Mean patient age was 59 years (range 42-80 years). The median time from radiation to GDVE diagnosis was 4.6 months (range 3.3-21.5 months). The median number of APC sessions per patient was 2.4 (range 1-4). All 18 patients showed an endoscopic response to APC treatment, with sustained increases in mean hemoglobin level, from 6.6 g/dL (range 2.9-9.5 g/dL) to 9.7 g/dL (range 7.1-12.7 g/dL) (p < 0.001), and decreased dependence on transfusion, from 9.1 (range 0-30) to 4.1 (range 0-15) units of packed red blood cells per patient (p = 0.038) after last endoscopic eradication by APC treatment. There were no major procedure-related adverse events or deaths. At a median follow up of 4.7 months (range 0.6-24.5 months), none of the patients experienced recurrence of GDVE. Conclusions: APC showed short-term effectiveness and safety in the treatment of radiation-induced hemorrhagic GDVE.
    No preview · Article · Nov 2013 · Scandinavian Journal of Gastroenterology
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    Bo Hyun Kim · Joong-Won Park
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    ABSTRACT: Sorafenib, as the first approved molecularly targeted agent for hepatocellular carcinoma (HCC), has changed the treatment paradigm for patients with advanced HCC. Although a significant survival advantage has been achieved with sorafenib, the prolongation of survival is modest, even in the cases of Child-Pugh class A. Because of primary resistance and secondary resistance, the anti-tumor effects of sorafenib are limited in a portion of HCC patients. To overcome these limitations of sorafenib, various molecularly targeted therapies have been studied alone or in combination with each other, and also adjuvant to other modalities. The role of sorafenib as an adjuvant or neo-adjuvant therapy needs to be evaluated before and after surgery and locoregional therapies. Because patients with HCC are a highly heterogeneous population in terms of molecular pathogenesis and in terms of the natural course of their disease, development of biomarkers of a response before or during sorafenib treatment and development of other molecularly targeted therapies is imperative for selecting prospective good responders. New agents under development target and block VEGF, VEGFR, PDGFR, FGF, FGFR, EGFR, PI3K/Akt/mTOR, IGFR, MEK, c-MET, glypican-3, JAK2, PD1, CTLA-4, etc. The advent of targeted systemic therapies for advanced HCC may have important implications for the future management of patients with advanced HCC, including a need for improved assessment of disease progression, reliable biomarkers for patient selection, and the use of a multidisciplinary approach.
    Preview · Article · Nov 2013 · Journal of the Korean Medical Association

Publication Stats

2k Citations
381.95 Total Impact Points


  • 2003-2015
    • National Cancer Center Korea
      • • Colorectal Cancer Branch
      • • Liver and Pancreatobiliary Cancer Branch
      Kōyō, Gyeonggi-do, South Korea
  • 2013
    • University of Liverpool
      Liverpool, England, United Kingdom
    • Icahn School of Medicine at Mount Sinai
      Borough of Manhattan, New York, United States
  • 2009
    • University of Ulsan
      • Department of Radiology
      Ulsan, Ulsan, South Korea