BACKGROUND/AIMS: We compared the recurrence of hepatocellular carcinoma (HCC) and the survival of patients who received radiofrequency ablation (RFA) after transarterial chemoembolization (TACE) with patients treated with TACE or RFA alone. METHODS: This study included 201 patients with HCC, who were consecutively enrolled at Seoul St. Mary's Hospital between December 2004 and February 2010. Inclusion criteria were a single HCC < or = 5.0 cm or up to three HCCs < or = 3.0 cm. We used a propensity score model to compare HCC patients (n = 87) who received RFA after TACE (TACE + RFA) with those who received TACE (n = 71) or RFA alone (n = 43). RESULTS: The median follow-up period was 33.3 months (range, 6.8 to 80.9). The TACE + RFA group showed significantly lower local recurrence than the RFA or TACE groups (hazard ratio [HR], 0.309; 95% confidence interval [CI], 0.130 to 0.736; p = 0.008; and HR, 0.352; 95% CI, 0.158 to 0.787; p = 0.011, respectively). The overall survival was significantly better in the TACE + RFA group compared to the RFA group (HR, 0.422; 95% CI, 0.185 to 0.964; p = 0.041). However, the survival benefit was not different between the TACE + RFA and TACE groups (p = 0.124). Subgroup analysis showed that among patients with a tumor size < 3 cm, the TACE + RFA group had significantly better long-term survival than those in the TACE or RFA groups (p = 0.017, p = 0.004, respectively). CONCLUSIONS: TACE + RFA combination treatment showed favorable local recurrence and better overall survival rates in early-stage HCC patients. Patients with tumors < 3 cm are likely to benefit more from TACE + RFA combination treatment. Additional studies are needed for the selection of suitable HCC patients for TACE + RFA treatment.
Adult ; Aged ; Aged, 80 and over ; Carcinoma, Hepatocellular/mortality/pathology/*therapy ; *Catheter Ablation/adverse effects/mortality ; *Chemoembolization, Therapeutic/adverse effects/mortality ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Liver Neoplasms/mortality/pathology/*therapy ; Male ; Middle Aged ; *Neoadjuvant Therapy/adverse effects/mortality ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Patient Selection ; Proportional Hazards Models ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Time Factors ; Treatment Outcome ; Tumor Burden ; Young Adult

Pretransplant alpha-fetoprotein (AFP) is a useful tumor marker predicting recurrence of hepatocellular carcinoma (HCC). Little is known, however, about the relationship between changes in AFP concentration and prognosis. This study investigated the clinical significance of change in peri-transplant AFP level as a predictor of HCC recurrence. Data from 125 HCC patients with elevated pretransplant AFP level who underwent liver transplantation (LT) between February 2000 and December 2010 were retrospectively reviewed. Patients with AFP normalization within 1 month after LT were classified into the rapid normalization group (n = 97), with all other patients classified into the non-rapid normalization group (n = 28). Tumor recurrence was observed in 17 of the 97 patients (17.5%) with rapid normalization; of these, 11 patients had high AFP levels and six had normal levels at recurrence. In contrast, tumor recurrence was observed in 24 of the 28 patients (85.7%) without rapid normalization, with all 24 having high AFP levels at recurrence. Multivariate analysis showed that non-rapid normalization (harzard ratio [HR], 4.41, P < 0.001), sex (HR, 3.26, P = 0.03), tumor size (HR, 1.15, P = 0.001), and microvascular invasion (HR, 2.65, P = 0.005) were independent risk factors for recurrence. In conclusion, rapid normalization of post-LT AFP level at 1 month is a useful clinical marker for HCC recurrence. Therefore, an adjuvant strategy and/or intensive screening are needed for patients who do not show rapid normalization.
Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Carcinoma, Hepatocellular/blood/mortality/*pathology/therapy ; Female ; Humans ; Kaplan-Meier Estimate ; Liver Neoplasms/blood/mortality/*pathology/therapy ; *Liver Transplantation ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Recurrence, Local ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Severity of Illness Index ; alpha-Fetoproteins/analysis

OBJECTIVE: To evaluate the safety and clinical outcomes of chemoembolization in Child-Pugh class C patients with hepatocellular carcinomas (HCC). MATERIALS AND METHODS: The study comprised 55 patients with HCC who were classified as Child-Pugh class C and who underwent initial chemoembolization between January 2003 and December 2012. Selective chemoembolization was performed in all technically feasible cases to minimize procedure-related complications. All adverse events within 30 days were recorded using the Common Terminology Criteria for Adverse Events (CTCAE). The tumor response to chemoembolization was evaluated using the modified Response Evaluation Criteria In Solid Tumors. RESULTS: Thirty (54.5%) patients were within the Milan criteria, and 25 (45.5%) were beyond. The mortality of study subjects at 30 days was 5.5%. Major complications were observed in five (9.1%) patients who were all beyond the Milan criteria: two hepatic failures, one hepatic encephalopathy, and two CTCAE grade 3 increases in aspartate aminotransferase/alanine aminotransferase abnormality. The mean length of hospitalization was 6.3 ± 8.3 days (standard deviation), and 18 (32.7%) patients were discharged on the next day after chemoembolization. The tumor responses of the patients who met the Milan criteria were significantly higher (p = 0.014) than those of the patients who did not. The overall median survival was 7.1 months (95% confidence interval: 4.4-9.8 months). CONCLUSION: Even in patients with Child-Pugh class C, chemoembolization can be performed safely with a selective technique in selected cases with a small tumor burden.
Adult ; Aged ; Alanine Transaminase/metabolism ; Aspartate Aminotransferases/metabolism ; Carcinoma, Hepatocellular/mortality/*pathology/therapy ; Chemoembolization, Therapeutic/adverse effects ; Female ; Hepatic Encephalopathy/etiology ; Humans ; Length of Stay ; Liver Neoplasms/mortality/*pathology/therapy ; Liver Transplantation ; Male ; Middle Aged ; Proportional Hazards Models ; Severity of Illness Index ; Survival Rate ; Treatment Outcome ; Tumor Burden

OBJECTIVE: To evaluate the safety and efficacy of transcatheter arterial chemoembolization (TACE) in patients with infiltrative hepatocellular carcinoma (HCC) and to identify the prognostic factors associated with patient survival. MATERIALS AND METHODS: Fifty two patients who underwent TACE for infiltrative HCC were evaluated between 2007 and 2010. The maximum diameter of the tumors ranged from 7 cm to 22 cm (median 15 cm). Of 46 infiltrative HCC patients with portal vein tumor thrombosis, 32 patients received adjuvant radiation therapy for portal vein tumor thrombosis after TACE. RESULTS: The tumor response by European Association for the Study of the Liver criteria was partial in 18%, stable in 47%, and progressive in 35% of the patients. The median survival time was 5.7 months (Kaplan-Meier analysis). The survival rates were 48% at six months, 25% at one year, and 12% at two years. In the multivariable Cox regression analysis, Child-Pugh class (p = 0.02), adjuvant radiotherapy (p = 0.003) and tumor response after TACE (p = 0.004) were significant factors associated with patient survival. Major complications occurred in nine patients. The major complication rate was significantly higher in patients with Child-Pugh B than in patients with Child-Pugh A (p = 0.049, chi2 test). CONCLUSION: Transcatheter arterial chemoembolization can be a safe treatment option in infiltrative HCC patients with Child Pugh class A. Child Pugh class A, radiotherapy for portal vein tumor thrombosis after TACE and tumor response are good prognostic factors for an increased survival after TACE in patients with infiltrative HCCs.
Adult ; Aged ; Carcinoma, Hepatocellular/mortality/pathology/*therapy ; Chemoembolization, Therapeutic/*adverse effects/methods/mortality ; Female ; Humans ; Kaplan-Meier Estimate ; Liver Neoplasms/mortality/pathology/*therapy ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Survival Rate ; Tumor Burden ; Venous Thrombosis/etiology

BACKGROUND/AIMS: The most commonly used immunosuppressant therapy after liver transplantation (LT) is a combination of tacrolimus and steroid. Basiliximab induction has recently been introduced; however, the most appropriate immunosuppression for hepatocellular carcinoma (HCC) patients after LT is still debated. METHODS: Ninety-three LT recipients with HCC who took tacrolimus and steroids as major immunosuppressants were included. Induction with basiliximab was implemented in 43 patients (46.2%). Mycophenolate mofetil (MMF) was added to reduce the tacrolimus dosage (n=28, 30.1%). The 1-year tacrolimus exposure level was 7.2 +/- 1.3 ng/mL (mean +/- SD). RESULTS: The 1- and 3-year recurrence rates of HCC were 12.9% and 19.4%, respectively. Tacrolimus exposure, cumulative steroid dosages, and MMF dosages had no impact on HCC recurrence. Induction therapy with basiliximab, high alpha fetoprotein (AFP; >400 ng/mL) and protein induced by vitamin K absence/antagonist-II (PIVKA-II; >100 mAU/mL) levels, and microvascular invasion were significant risk factors for 1-year recurrence (P<0.05). High AFP and PIVKA-II levels, and positive 18fluoro-2-deoxy-d-glucose positron-emission tomography findings were significantly associated with 3-year recurrence (P<0.05). CONCLUSIONS: Induction therapy with basiliximab, a strong immunosuppressant, may have a negative impact with respect to early HCC recurrence (i.e., within 1 year) in high-risk patients.
Adult ; Aged ; Biological Markers/analysis ; Carcinoma, Hepatocellular/mortality/pathology/*therapy ; Female ; Humans ; Immunosuppressive Agents/*therapeutic use ; Liver Neoplasms/mortality/pathology/*therapy ; *Liver Transplantation ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Positron-Emission Tomography ; Protein Precursors/analysis ; Prothrombin/analysis ; Regression Analysis ; Risk Factors ; Severity of Illness Index ; Survival Rate ; alpha-Fetoproteins/analysis

PURPOSE: For locally unresectable hepatocellular carcinoma (HCC) patients, concurrent chemoradiotherapy (CCRT) has been applied as a loco-regional treatment. After shrinkage of tumors in selected patients, surgical resection is performed. The aim of this study was to evaluate prognostic factors and long-term survivors in such patients. MATERIALS AND METHODS: From January 2000 to January 2009, 264 patients with HCC were treated with CCRT (45 Gy with fractional dose of 1.8 Gy), and intra-arterial chemotherapy was administered during radiotherapy. Eighteen of these patients (6.8%) underwent hepatic resection after showing a response to CCRT. Cases were considered resectable when tumor-free margins and sufficient remnant volumes were obtained without extrahepatic metastasis. Prior to operation, there were six patients with complete remission, 11 with partial remission, and six with stable disease according to modified Response Evaluation Criteria in Solid Tumors. RESULTS: In pathologic review, four patients (22.2%) showed total necrosis and seven patients (38.9%) showed 70-99% necrosis. A high level of necrosis (> or =80%) was correlated with low risk for extrahepatic metastasis and long-term survival. In univariate analyses, vessel invasion and capsular infiltration were significantly correlated with disease free survival (DFS) (p=0.017 and 0.013, respectively), and vessel invasion was significantly correlated with overall survival (OS) (p=0.013). In multivariate analyses, capsule infiltration was a significant factor for DFS (p=0.016) and vessel invasion was significant for OS (p=0.015). CONCLUSION: CCRT showed favorable responses and locally advanced HCC converted into resectable tumor after CCRT in selected patients. Long-term survivors showed the pathological features of near total necrosis, as well as negative capsule and vessel invasion.
Adult ; Aged ; Antimetabolites, Antineoplastic/administration & dosage ; Antineoplastic Agents/administration & dosage ; Carcinoma, Hepatocellular/mortality/pathology/*therapy ; Chemoradiotherapy/*methods ; Cisplatin/administration & dosage ; Disease-Free Survival ; Female ; Fluorouracil/administration & dosage ; Humans ; Liver Neoplasms/mortality/pathology/*therapy ; Male ; Middle Aged ; Prognosis ; Radiotherapy, Conformal ; Remission Induction ; Republic of Korea/epidemiology ; *Salvage Therapy ; Survival Rate ; Treatment Outcome ; Tumor Burden

OBJECTIVETo explore the efficacy and safty of sorafenib in Child-Pugh class B to class C hepatocellular carcinoma (HCC).

METHODSIn this three-center open-label study from November 2011 to May 2013, we randomly assigned 189 patients with advanced Child-Pugh class B or C HCC patients into two groups, one group with 95 patient to receive sorafenib (400 mg a time, twice a day) and the other group with 94 patients to receive best supportive care. The primary end points were progression-free survival and overall survival.

RESULTSThe median progression-free survival was 2.2 months and 1.9 months in the sorafenib group and best supportive care group respectively (Hazard ratio in the sorafenib group, 0.55; 95% confidence interval, 0.40-0.75; P=0.002). The median overall survival was 4.0 months and 3.5 months in the sorafenib group and best supportive care group respectively (Hazard ratio in the sorafenib group, 0.48; 95% confidence interval, 0.35-0.68; P<0.001). The main adverse effect of sorafenib was rash and acne of the skin (in 51.7% patients). The incidences of severe rash, diarrhea, and dry skin were 5.6%, 5.6%, and 2.2% in the sorafenib group. One patient reached partial response in the sorafenib group.

CONCLUSIONSSorafenib is safe in patients with liver function impaired advanced HCC. It is effective in terms of progression-free survival and overall survival compared with best supportive care. Liver functions are the important predictive factors.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents ; administration & dosage ; adverse effects ; therapeutic use ; Carcinoma, Hepatocellular ; drug therapy ; mortality ; pathology ; Cross-Over Studies ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Liver Function Tests ; Liver Neoplasms ; drug therapy ; mortality ; pathology ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Niacinamide ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use ; Phenylurea Compounds ; administration & dosage ; adverse effects ; therapeutic use ; Treatment Outcome ; Young Adult

Although continuous low-dose (metronomic [MET]) therapy exerts anti-cancer efficacy in various cancer models, the effect of long-term MET therapy for hepatocellular carcinoma (HCC) remains unknown. This study assessed the long-term efficacy of MET on suppression of tumor growth and spontaneous metastasis in a rat model of HCC induced by administration of diethylnitrosamine for 16 wk. The rats were divided into 3 groups: MTD group received intraperitoneal (i.p.) injections of 40 mg/kg cyclophosphamide on days 1, 3, and 5 of a 21-day cycle; Control and MET groups received i.p. injections of saline and 20 mg/kg cyclophosphamide twice a week, respectively. Anti-tumor and anti-angiogenic effects and anti-metastatic mechanisms including matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) were evaluated. Twelve wk of MET therapy resulted in a significant reduction in intrahepatic tumors than control or MTD therapy. The MET group had fewer proliferating cell nuclear antigen-positive cells and decreased hypoxia-inducible factor-1alpha levels and microvessel density. Lung metastases were detected in 100%, 80%, and 42.9% in the control, MTD, and MET groups, respectively. MET therapy significantly decreased expression of TIMP-1, MMP-2 and -9. For mediators of pro-MMP-2 activation, MET therapy induced significant suppression in the TIMP-2 and MMP-14 level. The survival in the MET group was significantly prolonged compared to the control and MTD groups. Long-term MET scheduling suppresses tumor growth and metastasis via its potent anti-angiogenic properties and a decrease in MMPs and TIMPs activities. These results provide a rationale for long-term MET dosing in future clinical trials of HCC treatment.
Animals ; Antineoplastic Agents/*administration & dosage/*pharmacology ; Carcinoma, Hepatocellular/chemically induced/*drug therapy/mortality/pathology ; Cell Proliferation/drug effects ; Cyclophosphamide/*administration & dosage/*pharmacology ; Diethylnitrosamine ; Disease Models, Animal ; Gene Expression Regulation, Neoplastic/*drug effects ; Liver Cirrhosis/chemically induced ; Liver Neoplasms/chemically induced/*drug therapy/mortality/pathology ; Lung Neoplasms/drug therapy/pathology/secondary ; Male ; Matrix Metalloproteinases/metabolism ; Neovascularization, Pathologic/enzymology/physiopathology ; Rats ; Rats, Sprague-Dawley ; Survival Analysis ; Tissue Inhibitor of Metalloproteinases/metabolism ; Tumor Burden/drug effects

BACKGROUNDTransarterial chemoembolization (TACE) is the most widely used primary treatment for unresectable hepatocellular carcinoma (HCC) due to its survival benefit, though its clinical effect is still far from satisfactory. Jiedufang (JDF) granule preparation is a commonly used Chinese herbal medicine formula for HCC. The aim of this study was to evaluate the effect of combined therapy with TACE and JDF granule preparation in treatment of unresectable HCC on survival.

METHODSA retrospective study of TACE was performed in 165 patients with unresectable HCC who were admitted between January 2002 and December 2007 in Changhai Hospital, Shanghai, China. Of the 165 patients, 80 patients (study group) received combined therapy consisting of TACE and a long-term maintenance treatment with oral JDF granule preparation, and the remaining 85 patients (control group) received TACE alone. The survival rates of both groups were calculated by the Kaplan-Meier method. Factors possibly affecting survival were assessed by multivariate analysis in the Cox proportional hazard model, such as maximum tumor size, number of lesions, portal vein invasion, and etc.

RESULTSThe median overall survival was 9.2 months (95% CI: 6.94 - 11.46) in the study group versus 5.87 months (95% CI: 4.21 - 7.52) in the control group. In the study group,survival rates of the 1-, 2- and 3-year follow-up were 41.2%, 18.4%, and 9.6%, respectively. Significant independent prognostic factors identified by the Cox regression analysis were as follows: serum hepatitis B surface antigen (HBsAg) (P = 0.014), maximum tumor size (P = 0.027), number of lesions (P < 0.001), portal vein invasion (P < 0.001), and the therapy model (P = 0.006).

CONCLUSIONCombination therapy of TACE and JDF granule preparation may significantly prolong survival of patients with unresectable HCC.

Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Carcinoma, Hepatocellular ; drug therapy ; mortality ; pathology ; therapy ; Chemoembolization, Therapeutic ; methods ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Liver Neoplasms ; drug therapy ; mortality ; pathology ; therapy ; Male ; Middle Aged ; Retrospective Studies ; Survival Rate ; Treatment Outcome

OBJECTIVETo evaluate the efficacy of percutaneous laser ablation (LA) in the treatment for portal vein tumor thrombus (PVTT) of hepatocellular carcinoma (HCC).

METHODSThe PVTT of HCC patients were treated through percutaneous transhepatic laser ablation (PTLA). The survival rate, thrombus size, blood flow of embolized portal vein by thrombus, liver function, ascites and clinical presentation were observed.

RESULTSThe 6-month, 1-year and 2-year survival rate of these 93 patients were 82.8%, 53.0% and 34.1%, respectively. In 11 patients with partially occluded portal vein by PVTT, the cut-surface of the PVTT diminished significantly 6 months after LA. The color blood stream signal was seen again one day after LA in all of the other 82 patients with totally occluded portal vein by thrombus, and it could still be seen in 67 of those one month later, 57 (of 71) 3 months later, 40 (of 57) 6 months later, 27 (of 32) 1 year and 4 (of 6) 2 years later after LA. In the 38 patients who survived over 1 year, PVTT was gradually atrophied and disappeared eventually in 14, PVTT was atrophied and the portal vein changed into honeycomb-like appearance in 14. In the remaining 10 patients, PVTT continued to grow and made the portal vein enlarged. It was also observed that liver function, clinical symptom and ascites were improved in various degree after LA.

CONCLUSIONPercutaneous laser ablation might be an effective and safe treatment method for controlling portal vein tumor thrombus of hepatocellular carcinoma.

Adult ; Aged ; Carcinoma, Hepatocellular ; mortality ; pathology ; surgery ; Female ; Humans ; Laser Therapy ; methods ; Liver Neoplasms ; mortality ; pathology ; surgery ; Male ; Middle Aged ; Neoplastic Cells, Circulating ; pathology ; Portal Vein ; pathology ; surgery ; Survival Analysis ; Survival Rate