BACKGROUND/AIMS: Silibinin, the main component of silymarin, is used as a hepatoprotectant and exhibits anticancer effects against various cancer cells. This study evaluated the effects of a combination of silibinin with either gefitinib or sorafenib on hepatocellular carcinoma (HCC) cells. METHODS: Several different human HCC cell lines were used to test the growth-inhibiting effects and cell toxicity of silibinin both alone and in combination with either gefitinib or sorafenib. The cell viability and growth inhibition were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, trypan blue staining, and a colony-forming assay. Furthermore, changes in epidermal growth factor receptor (EGFR)-related signals were evaluated by Western blot analysis. RESULTS: Gefitinib, sorafenib, and silibinin individually exhibited dose-dependent antiproliferative effects on HCC cells. Combined treatment with silibinin enhanced the gefitinib-induced growth-inhibiting effects in some HCC cell lines. The combination effect of gefitinib and silibinin was synergistic in the SNU761 cell line, but was only additive in the Huh-BAT cell line. The combination effect may be attributable to inhibition of EGFR-dependent Akt signaling. Enhanced growth-inhibiting effects were also observed in HCC cells treated with a combination of sorafenib and silibinin. CONCLUSIONS: Combined treatment with silibinin enhanced the growth-inhibiting effects of both gefitinib and sorafenib. Therefore, the combination of silibinin with either sorafenib or gefitinib could be a useful treatment approach for HCC in the future.
Antineoplastic Agents/*pharmacology ; Carcinoma, Hepatocellular/metabolism/pathology ; Cell Line, Tumor ; Cell Proliferation/*drug effects ; Cell Survival/drug effects ; Down-Regulation/drug effects ; Drug Screening Assays, Antitumor ; Drug Synergism ; Humans ; Liver Neoplasms/metabolism/pathology ; Niacinamide/*analogs & derivatives/pharmacology ; Phenylurea Compounds/*pharmacology ; Proto-Oncogene Proteins c-akt/metabolism ; Quinazolines/*pharmacology ; Receptor, Epidermal Growth Factor/metabolism ; Signal Transduction/drug effects ; Silymarin/*pharmacology

BACKGROUND/AIMS: This study evaluated the prevalence and location of colonic adenomatous polyps in asymptomatic adults. METHODS: A total of 2,849 asymptomatic adults underwent colonscopic screening as a part of health evaluation from January 2003 to September 2005. Completed questionnaires as well as the colonoscopic and pathologic findings were analyzed. RESULTS: There were 406 (14.3%) subjects with adenomatous polyps including 78 (2.7%) with advanced polyps. There was a trend toward an increased prevalence of adenomatous polyps with age. The relative risk of a proximal polyp according to the distal findings was 5.7 (95% CI 4.3 ~ 7.4) for adenoma, 4.9 (95% CI 3.0 ~ 7.7) for advanced adenoma compared with that for no adenomatous polyp. There were no index polyps at the distal colon in 30% of the 406 subjects. CONCLUSIONS: Though distal polyps are associated with the proximal polyps, 30% of asymptomatic adults with proximal polyps are not associated with any distal index polyps. For those without any contraindication to the procedure, colonoscopy performed by experienced colonoscopists as a screening test is feasible for detecting those patients with colorectal polyps.
Adenoma ; Adenomatous Polyps ; Adult* ; Colon* ; Colonic Neoplasms* ; Colonoscopy* ; Humans ; Mass Screening* ; Polyps ; Prevalence ; Surveys and Questionnaires

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is heterogenous in terms of its glucose metabolism. Positron emission tomography with fluorine-18-fluorodeoxyglucose (FDG-PET) shows various levels of FDG uptake for patients with HCC. This study was designed to assess the usefulness of FDG-PET for predicting the outcome of the patients with HCC. METHODS: FDG-PET was performed for 27 patients with HCC. The standardized uptake value (SUV) and SUV ratio (defined as the tumor-to-nontumor ratio of SUV) was calculated for each patient. The clinical factors of the outcome were analyzed by regression analysis using Cox's multivariate proportional hazard model. The survival rate was calculated by the Kaplan-Meier method. RESULTS: Among the analyzed clinical factors including tumor size, number of tumors, AFP, involvement of major vessels, presence of systemic metastases, Child-Pugh class the SUV and SUV ratio, only the SUV was the only significant independent prognostic factor (p=0.001). On the basis of the SUV, the patients were divided into two groups of roughly equal size: group A, SUV of <7; group B, SUV >or=7. The cumulative survival rate was significantly lower for group B than for group A, and the median survival time was significantly different (4 months vs 15 months, respectively) (p=0.003). CONCLUSIONS: These results suggest that FDG-PET is useful to predict the outcome for patients with hepatocellular carcinoma.
Adult ; Aged ; Carcinoma, Hepatocellular/mortality/*radionuclide imaging ; English Abstract ; Female ; Fluorodeoxyglucose F18/*diagnostic use ; Humans ; Liver Neoplasms/mortality/*radionuclide imaging ; Male ; Middle Aged ; *Positron-Emission Tomography ; Prognosis ; Radiopharmaceuticals/*diagnostic use ; Survival Rate

BACKGROUND/AIMS: [18F]FDG-PET is a functional imaging modality reflecting cellular glucose metabolism. In most malignant cells, accumulation and trapping of [18F]FDG allows the visualization of increased uptake compared with normal cells. The aim of this study was to assess the value of PET in differentiating benign from malignant hepatic lesions and to determine in which types of hepatic tumors PET can help evaluate stage, monitor response to therapy, and detect recurrence. METHODS: Eighty patients with liver lesions were enrolled (hepatocellular carcinoma 34, cholangiocarcinoma 8, metastatic liver cancer 25, hemangioma 6, liver abscess 7). Liver metastases were 22 adenocarcinoma, 2 lymphoma, 2 squamous cell carcinoma. The PET images of these patients were analyzed. SUV and lesion-to-normal liver background SUV ratio were obtained and compared among the disease groups. RESULTS: All liver metastases and all cholangiocarcinomas had increased uptake value, with SUV ratios greater than 2. Hepatocellular carcinoma had SUV ratios greater than 2 in 20 of 34 patients (59%). All hemangiomas had poor uptake, a SUV ratio of less than 2. All liver abscesses showed definite uptake. CONCLUSIONS: The PET technique using FDG static imaging was useful in differentiating malignant from benign lesions of the liver in limited situations. Limitations included false negative results in some patients with hepatocellular carcinoma. Liver abscesses raised problems in differential diagnosis from malignant liver tumors. The findings of this study suggest that the PET technique might be applied in tumor staging and the detection of recurrence, as well as monitoring responses to therapy for all adenocarcinomas and some hepatocelluar carcinomas.
Adult ; Aged ; Diagnosis, Differential ; English Abstract ; Female ; Fludeoxyglucose F 18/diagnostic use ; Human ; Liver Diseases/*radionuclide imaging ; Liver Neoplasms/radionuclide imaging ; Male ; Middle Aged ; Radiopharmaceuticals/diagnostic use ; *Tomography, Emission-Computed

BACKGROUND/AIMS: Angiogenesis occurs in response to tissue damage, and is of vital importance for tumor growth and metastasis. Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) are potent angiogenic factors, and have been suggested to be useful diagnostic markers in certain hypervascular tumors. However, little is known of serum bFGF and VEGF in patients with hepatocellular carcinoma (HCC). We attempted to measure serum bFGF and VEGF in patients with chronic liver diseases (CLD) and HCC to assess their pathogenetic role and usability as tumor markers. METHODS: Serum bFGF and VEGF were measured in 8 patients with chronic hepatitis (CH), 15 patients with liver cirrhosis (LC), and 49 patients with HCC. bFGF was measured in 33, and VEGF was measured in 50, healthy blood donors. RESULTS: Serum bFGF was 3.8+/-1.9, 2.0+/-1.4, 4.2+/-6.0, 17.4+/-30.0 pg/mL in normal control, CH, LC, HCC, respectively. The serum bFGF level was significantly increased in patients with HCC when compared with normal control or patients with CLD. No difference, however, was observed in serum VEGF levels among the four groups. The serum levels of bFGF and VEGF were not significantly different in patients with HCC according to tumor type, size and stage. Serum bFGF showed good sensitivity (90%), specificity (87%), and positive predictive value (94%) in differentiating patients with HCC from those with CLD at the cut-off value of 4.6 pg/mL. CONCLUSIONS: bFGF might play a role in the growth of HCC and its serum level might be used as a tumor marker. On the other hand, serum VEGF does not seem to be an adequate tumor marker.
Angiogenesis Inducing Agents ; Blood Donors ; Carcinoma, Hepatocellular* ; Fibroblast Growth Factor 2* ; Hand ; Hepatitis, Chronic ; Humans ; Liver Cirrhosis ; Liver Diseases* ; Liver* ; Neoplasm Metastasis ; Sensitivity and Specificity ; Biomarkers, Tumor ; Vascular Endothelial Growth Factor A*

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is a drug-resistant tumor. The expression of a multidrug resistant gene, P-glycoprotein (P-gp) is a major mechanism of drug resistance. The aims of our study were, firstly, to observe the expression rate of P-gp in HCC tissue obtained by percutaneous fine needle aspiration (PCNA) from stage IV HCC patients; secondly to examine the association between P-gp and chemotherapeutic response; and finally to investigate the correlation between p53 protein expression and P-gp expression. Subjects and METHODS: We studied 29 cases of stage IV HCC treated by systemic chemotherapy. Expression of P-gp and p53 were evaluated by immunohistochemical staining of HCC tissue with human monoclonal antibody, JSB-1 (Anti P-gp) and DO-7 (Anti p53), respectively. We analyzed the results of immunohistochemical staining of HCC tissues of the patients in relation to chemotherapeutic response and other clinical characteristics. RESULTS: The expression rate of P-gp was 27.6%. Partial response to anti-cancer chemotherapy was observed in 16.7% of the patients. Although we could not see a statistically significant association between P-gp expression and chemotherapeutic response, none of the responsive patients showed P-gp expression. p53 protein expression was found in 45% of the patients. There was no significant correlation between p53 protein expression and P-gp expression. CONCLUSIONS: Although the number of our study subjects was small, chemotherapy- responsive patients didn't show P-gp expression. P-gp expression might be used as a predictor of response to potentially toxic anti-cancer chemotherapy in HCC patients. Further study is warranted to confirm our results.
Biopsy, Fine-Needle ; Carcinoma, Hepatocellular* ; Drug Resistance ; Drug Therapy* ; Humans ; P-Glycoprotein*

BACKGROUND/AIMS: About 15% of Korean hepatocellular carcinoma (HCC) are negative both of Hepatitis B surface antigen (HBsAg) and anti-hepatitis C virus (anti-HCV) in their sera. They can be classified as a non-B, non-C hepatocellular carcinoma group (NBNC group). The aims of our study were, firstly, to describe the clinical characteristics of Korean NBNC HCC and compare them with those of HBsAg-positive HCC (HBV group) and anti-HCV-positive HCC (HCV group). Secondly we wanted to assess the frequency of viremia of HBV, HCV and transfusion-transmitted virus (TTV) in NBNC HCC patients. METHODS: We prospectively collected clinical data and sera from 113 NBNC HCC patients and performed PCR for HBV DNA, HCV RNA and TTV DNA. We also collected clinical data from 125 HBsAg-positive HCC patients and 61 anti-HCV-positive HCC patients during a similar period. RESULTS: The mean age of the NBNC HCC group was 59 years, in-between that of the HBV and the HCV groups. A History of heavy alcohol drinking was found in 48% of the NBNC HCC group. This was significantly higher than that of the HBV group, but similar to that of the HCV group. Serum alphaFP level in the NBNC HCC group was more frequently in the normal range compared to that in the HBV and HCV groups. The detection rates of HBV DNA, HCV RNA and TTV DNA in the NBNC HCC group were 17%, 13%, and 67% respectively. CONCLUSIONS: The NBNC HCC patients seemed to comprise a heterogeneous group of various etiologies and clinical presentations. About one third of these patients displayed evidence of viremia of HBV or HCV.
Alcohol Drinking ; Carcinoma, Hepatocellular* ; DNA ; Epidemiology ; Hepacivirus ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Humans ; Polymerase Chain Reaction ; Prospective Studies ; Reference Values ; RNA ; Torque teno virus ; Viremia*

BACKGROUNDS/AIMS: The fine-needle aspiration (FNA) is a useful method for diagnosis of hepatocellular carcinoma (HCC). The aims of our study are to assess diagnostic accuracy of FNA, to define proper indications of FNA for diagnosis of HCC, and to evaluate the complications of FNA. SUBJECTS AND METHODS: To assess diagnostic accuracy we compared the results of preoperative FNA with postoperative pathology in 38 resected cases with primary liver cancer. To define proper indications and complications of FNA, we prospectively followed 138 patients received FNA for their liver tumors which were suspicious of primary liver tumor. RESULTS: The sensitivity, specificity, positive and negative predictive values of FNA were 100%, 97%, 100% and 66% respectively. All patients with serum alpha-fetoprotein (AFP) level over 1000 ng/ml were having HCC on FNA result. Among 36 patients with AFP level ranged 15-1000 ng/ml and hypervascular mass on angiography, 96% were having HCC. Among 50 patients with normal AFP level and hypervascular mass on angiography, 92% were having HCC. The major complications after FNA such as hemoperitoneum, pneumothorax, and iatrogenic arterioportal shunt developed in 2%, 2%, and 7% of subjects, respectively. We did not find any case of needle-tract seeding of cancer during a mean 4.7 months of follow-up. CONCLUSIONS: Although the FNA is an accurate method for diagnosis of HCC, FNA was usually not indicated for patients with serum AFP level over 1000 ng/ml or patients with hypervascular mass on angiography when they were suspected of having primary liver cancer. Major complications were hemoperitoneum, pneumothorax and iatrogenic arterioportal shunt. Iatrogenic arterioportal shunt may influence the efficacy of subsequent transcatheter arterial embolization.
alpha-Fetoproteins ; Angiography ; Biopsy, Fine-Needle* ; Carcinoma, Hepatocellular* ; Diagnosis* ; Follow-Up Studies ; Hemoperitoneum ; Humans ; Liver ; Liver Neoplasms ; Pathology ; Pneumothorax ; Prospective Studies ; Sensitivity and Specificity

BACKGROUND/AIMS: The incidence of hepatocellular carcinoma has been universally lower in female than in male. The aims of our study are to define whether there are any difference between female and male patients with hepatocellular carcinoma in terms of clinical characteristics and results of treatment. METHODS: Retrospective analyses of medical history, physical findings, laboratory results, etiological factors, characteristics of tumor, and therapeutic results were performed in 80 female patients with hepatocellular carcinoma compared to 160 male patients. RESULTS: Asymptomatic presentation and family history of liver disease were found more frequently in female patients than in male patients. A history of smoking and alcohol drinking were found less frequently in female patients than in male patients. The detection rate of spider angioma was significantly lower in female patients than in male patients. There was no difference in laboratory results, characteristics of tumor, and therapeutic results between female and male patients. CONCLUSIONS: Environmental factors such as smoking and alcohol drinking could contribute the sexual difference of hepatocarcinogenesis. However, clinical characteristics at the time of diagnosis and therapeutic results were not significantly different between female and male patients with hepatocellular carcinoma.
Alcohol Drinking ; Carcinoma, Hepatocellular* ; Diagnosis ; Female* ; Hemangioma ; Humans ; Incidence ; Liver Diseases ; Male ; Retrospective Studies ; Smoke ; Smoking ; Spiders

Transcatheter arterial chemoembolization (TACE) is a therapeutic option for unresectable hepatocellular carcinoma. Supraumbilical skin rash is a rare complication of TACE caused by patent hepatic falciform artery. We report herein two cases of supraumbilical skin rash developed after TACE for hepatocellular carcinoma, with discussion on the pathogenesis, prophylaxis, and treatment.
Arteries ; Carcinoma, Hepatocellular* ; Exanthema* ; Humans ; Skin*