The Effects of Tamoxifen on Human Hepatocelluar Carcinoma Cell Proliferation and Transforming Growth Factor-beta1 Expression / 대한간학회지

BACKGROUND/AIMS: Tamoxifen has been tried in patients with hepatocellular carcinoma (HCC), however, its inhibitory mechanism remains unknown. In this study, we evaluated the effects of tamoxifen on HCC cell growth and the expression of transforming growth factor-beta1 (TGF-beta1) which had been known as an important cytokine in growth of HCC. METHODS: Hep 3B cells were cultivated in estrogen free media with 0.1 micro M, 0.5 micro M, 1 micro M, 5 micro M, and 10 micro M of tamoxifen for 6 days. Viable cells were counted daily and the TGF-beta1 concentrations in supernatant were measured by ELISA method. RESULTS: The number of viable HCC cells increased rather significantly after the treatment of tamoxifen of lower concentration (0.1 micro M) compared with that of the control (2.59x10(7) vs. 1.97x10(7); p<0.05). As the concentration of treated tamoxifen was higher, the number of viable HCC cells became gradually less, resulting in the significant decrease of it at the highest concentration (10 micro M) compared with that of the control (1.40x10(7) vs. 1.97x10(7); p<0.05). TGF-beta1 concentration in supernatant of tamoxifen-treated samples was significantly decreased compared with those of controls, regardless of the amount of treated tamoxifen. CONCLUSIONS: These results suggest that tamoxifen may suppress TGF-beta1 expression to an extent, although it has different effects on the proliferation of HCC cells, at the various concentrations of this agent in vitro. Such effects of tamoxifen on TGF-beta1 expression may inhibit the growth and progression of HCCs over-expressing TGF-beta1 in vivo.

The Clinical Usefulness of SPIO-MRI in Detection and Staging of Hepatocellular Carcinoma / 대한간학회지

BACKGROUND/AIMS: It is still unclear whether Super Paramagnetic Iron Oxide-Magnetic Resonance Imaging (SPIO-MRI) is a clinically useful imaging modality for patients with hepatocellular carcinoma (HCC). This study searched for the clinical usefulness and limitations of SPIO-MRI with respect to tumor detection capacity, false positive and negative rate, and early recurrence rate. METHODS: From December 1999 to February 2001, 218 patients who were surgical candidates by 3-phase dynamic helical CT (3dHCT) were enrolled. We reviewed the medical records and radiologic findings, retrospectively, and postulated the post-operative pathologic findings and the early recurrences within 3 months as the standards for the true positive lesion. RESULTS: The mean number of nodules detected by SPIO-MRI was significantly more numerous than that of 3dHCT (p<0.01). Modifications of treatment strategy due to the discordant findings between SPIO-MRI and 3dHCT for tumor resectability were observed in 22 (10.1%) out of 218 patients. Early recurrences were observed in 10 patients (7.8%). The false positive and negative rates of SPIO-MRI were 6.3% and 13.3%, respectively. CONCLUSIONS: We demonstrated that the tumor detection rate of SPIO-MRI was better than that of 3dHCT. Given the relatively acceptable false positive and negative rates, SPIO-MRI could be an appropriate preoperative imaging modality for patients with HCCs.

Taehan Kan Hakhoe Chi (The Korean Journal of Hepatology) and Index Medicus (Medline/PubMed) / 대한간학회지

It is our great pleasure to announce that the Taehan Kan Hakhoe Chi (The Korean Journal of Hepatology) was approved for listing, from 2002, in the Index Medicus, Medline/PubMed of the National Library of Medicine, NIH of USA. Herein, I review the searching tools employing a Medical Subject Heading (MeSH) such as liver disease and liver neoplasm or an author index for this Journal in the PubMed at a website. Of course, The Korean Journal of Hepatology should be continually striving to be upgraded. Dream comes true.

The Correlation of Child-Pugh Score, PGA Index and MELD Score in the Patient with Liver Cirrhosis and Hepatocellular Carcinoma According to the Cause of Alcohol and Hepatitis B Virus / 대한간학회지

BACKGROUND/AIMS: To determine the treatment modalities and the prognosis of a patient with liver cirrhosis, quantitative estimation of liver function is important. We assessed the Child-Pugh score (CPS), the common method as a severity index for the cirrhosis, the Promthombin, gamma GT, and Apolipoprotein A1 (PGA) index and model for end-stage liver disease (MELD) score. The purpose of this study was to evaluate the correlation between these indices in the patients with cirrhosis only and hepatocellular carcinoma (PHC), according to underlying causes (HBV and alcohol). METHODS: We reviewed medical records of 339 cirrhotic patients with/without hepatocellular carcinoma and divided patient groups by disease and underlying cause: cirrhosis caused by alcohol; LC-Al, cirrhosis caused by HBV; LC-B, hepatocellular carcinoma with cirrhosis caused by alcohol; HCC-Al, hepatocellular carcinoma with cirrhosis caused by HBV; HCC-B. We assessed the CPS, PGA index and MELD score and calculated the correlation coefficient between these scores. RESULTS: Among the total of 339 patients, 201 patients were diagnosed on the liver cirrhosis only, and 138 patients on the hepatocellular carcinoma with cirrhosis. In each groups, mean score values were not significantly different in CPS, PGA index and MELD score. The correlation of CPS, PGA index and MELD score in all groups, except for the correlation of PGA index and MELD score in HCC-Al group, was significantly positive (p<0.05). Compared to correlation coefficients between three indices, the patients with cirrhosis only had higher tendencies than the patients with hepatocellular carcinoma. The patients by HBV had higher tendencies than by alcohol. CONCLUSIONS: The correlations between CPS, PGA index and MELD score showed significantly positive correlations in the patients with liver cirrhosis only and hepatocellular carcinoma with cirrhosis (except in HCC-Al group). The patients with cirrhosis only had higher correlation coefficients than the patients with PHC and the patients by HBV had higher than by alcohol.

Early Diagnosis and Improved Survival with Screening for Hepatocellular Carcinoma / 대한간학회지

BACKGROUND/AIMS: Screening for hepatocellular carcinoma (HCC) is a common practice in the endemic countries but its exact role has not been fully investigated. The purpose of this study was to determine whether screening can achieve early diagnosis and survival benefits. METHODS: All HCC patients diagnosed at our hospital (September 1994~April 2000) were enrolled; They were divided into two groups; a surveilled group screened with alpha-fetoprotein (AFP) and ultrasound (US) for longer than 6 months before diagnosis and a non-surveilled group. We compared the tumor size, portal vein thrombosis, and stage at initial diagnosis and survival rate between the two groups. RESULTS: A total of 247 patients were enrolled. 64 were in the surveilled group and 183 were in the non-surveilled group. The tumor size at initial diagnosis in the surveilled group was smaller than in the non-surveilled group (2.6+/-2.0 cm vs. 5.7+/-4.1 cm, p<0.05). The percentages of patients with stage I, II, III, and IV were 42.2%, 20.3%, 14.1%, 23.4% in the surveilled group and 8.7%, 19.7%, 36.6%, 35.0% in the non-surveilled group. A significantly higher proportion in the surveilled group had earlier stage compared with the non-surveilled group (p<0.05). Portal vein thrombosis in the surveilled group was noticed as significantly less than in the non-surveilled group (9.4% vs. 26.8%, p<0.05). Among Child-Pugh A patients, the cumulative survival rate in the surveilled group was significantly higher than in the non-surveilled group (1 year; 91.4% vs. 70.7%, 2 year; 71.5% vs. 59.9%, p<0.05). CONCLUSIONS: Screening with AFP and US is a useful tool for early diagnosis of HCC, especially with improved survival in Child-Pugh A patients.

Suppression of Tumor Formation and Induction of Natural Killer Cell Activity in BALB/c Nude Mice by Human B7-1 (CD80) Gene Transfer Subcutaneously Injected with Human Hepatocellular Carcinoma Cells (Huh-7) / 대한간학회지

BACKGROUND/AIMS: Immunogene therapy is extensively studied for a therapeutic modality of various cancers. This study was conducted to investigate the efficacy of immunogene therapy using the T-cell costimulatory molecule and human B7-1 (CD80, hB7-1) in an in vivo human hepatocellular carcinoma (HCC) model. METHODS: The stable HCC cell line expressing hB7-1 gene was established using retroviral vector (Huh-7/hB7-1). Of fourteen BALB/c nude mice, 7 were subcutaneously injected with 2 X 10(6) Huh-7/hB7-1 cells, while the other 7 were injected with 2 X 10(6) Huh-7/mock cells as a control group. After the injection, the mice were observed weekly for three months for subcutaneous tumor formation. Assay for natural killer (NK) cell cytotoxicity and serum IFN-gamma was performed at 1 and 2 weeks after inoculation. RESULTS: In BALB/c nude mice inoculated with Huh-7/hB7-1 cells, no tumor growth was observed. BALB/c nude mice inoculated with Huh-7/hB7-1 cells showed significantly increased NK cell activities of splenocytes compared with those with Huh-7/mock cells. Serum IFN-gamma was not measurable at 1 week, but significantly increased at 2 weeks after inoculation to the level of 470 pg/ml in BALB/c nude mice with Huh-7/mock cells and 521 pg/ml in BALB/c nude mice with Huh-7/hB7-1. CONCLUSIONS: Our results demonstrate the in vivo anti-tumor immunity and NK cell activation by transfer of hB7-1 gene into human HCC in xenogeneic BALB/c nude mice model. This approach may provide a tool for the development of immunogene therapies against human malignant tumors.

A Comparison of Patients With Hepatocellular Carcinoma Between A Short-term (Less Than 6 months) Survival Group and A Long-term (Over 24 Months) Survival Group After Treatment with Transcatheter Arterial Chemoembolization / 대한간학회지

BACKGROUND/AIM: Although hepatocellular carcinoma(HCC) shows poor prognosis, transcatheter hepatic arterial chemoembolization(TACE) can improve survival rate in some patient groups. This study investigated the synergy effect of the different clinical indices on the survival time in patients with HCC underwent TACE. MATERIALS AND METFODS: A retrospective study of 241 patients with HCC who underwent TACE with a mixture of lipiodol, mitomycin-C and adriamycin, alone or followed by gelfoam was conducted. Three different survival groups (A, less than 6 months; B, between between 6 and 23 months; and C, over 24 months) were compared. RESULTS: Alkaline phosphatase was lowest in group C (p=0.0001). The longer the survival, the lower (p=0.027, p=0.007) the AST and AST/ALT ratio were. Albumin was higher (p=0.032), GGT and LDH were lower (p=0.003, p=0.002) in the long-term survival group. The long-term survival group revealed an absence of both ascites(p<0.002) and portal vein thrombosis(p<0.001), and lower TNM stage (P<0.0001). The single nodular type of HCC was more frequent (P<0.0001) and the size of tumor was smaller in the long-term survival group (P<0.0001). Child-Pugh class was lower in the long-term survival group (p=0.017). The higher serum albumin and elder age, the higher albumin and the lower alkaline phosphatase or alpha-fetoprotein, represented synergic effects on a long term survival. The higher albumin and the smaller size or the lower tumor stage, the higher albumin and platelet revealed similar synergy effects. Although the age or platelet is high, low albumin showed poor prognosis. CONCLUSION: Patients with small-sized single, nodular HCC in a low Child-Pugh class without evidence of ascites and portal vein thrombosis, and the higher level of serum albumin but lower levels of alpha-fetoprotein, alkaline phosphatase, GGT, and LDH, can expect a long-term survival over 24 months by the treatment of TACE. There are meaningful synergies of the different clinical variables affecting the survival times in the patients with HCC undergoing TACE.

Clinical Efficacy of Serum PIVKA-II in the Diagnosis and Follow up after Treatment of Hepatocellular Carcinoma / 대한간학회지

BACKGROUND/AIMS: Protein induced by vitamin K absence or antagonist II (PIVKA-II) appears to be a useful tumor marker for the evaluation of patients with hepatocellular carcinoma (HCC). But the usefulness of PIVKA-II was not yet clear in Korea where hepatitis B-virus is endemic. We investigated the usefulness of PIVKA-II in the diagnosis and follow-up after treatment of HCC. METHODS: We studied patients with HCC which was pathologically confirmed. PIVKA-II was measured by enzyme immunoassay. PIVKA-II levels before and after treatment, in correlation with imaging studies, were analyzed for the comparison of treatment responses. Kappa index was obtained. RESULTS: A total of 129 patients were included. 93 patients (72%) were HBsAg positive. 86 patients (67%) were PIVKA-II >40 mAU/mL. 52 patients (40%) were AFP >20 ng/mL and 77 patients (60%) were AFP 40 mAU/mL. 68 of 129 patients were evaluated treatment response. On the basis of radiologic response, CR was 33, PR 17, SD 12, and PD 6. Of the 33 radiologic CR patients, 30 patients were CR and 3 patients were PR by means of PIVKA-II response. Of the 17 radiologic PR patients, 6 patients were CR and 7 patients were PR. Therefore, tumor responses by radiologic and PIVKA-II were well correlated (Kappa index was 0.59). CONCLUSIONS: PIVKA-II can be used as a useful tumor marker for patients with HCC, especially those with low levels of AFP, before and after treatment in Korea.

Evaluation of Various Hepatic Lesions with Positron Emission Tomography / 대한간학회지

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.

A Case of Hepatocellular Carcinoma with Metastasis to Gingival Mucosa / 대한간학회지

Hepatocellular carcinoma is one of the most common causes of death in Koreans. Most cases of hepatocellular carcinoma are beyond the stage of curative resection at the time of diagnosis due to extrahepatic metastasis as well as wide distribution of tumor in the liver. The lung is the most common site of extrahepatic metastasis but metastasis to gingiva is very rare in hepatocellular carcinoma. We report a case hepatecellular carcinoma with gingival methststasis in a 59 year old male patient.

Hepatocellular Carcinoma with Fatty Metamorphosis / 대한간학회지

No abstract available.

Expression Patterns of E-cadherin and beta-catenin According to Clinicopathological Characteristics of Hepatocellular Carcinoma / 대한간학회지

BACKGROUND/AIMS: E-cadherin is involved in intercellular binding and cellular polarity formation. beta-catenin plays a fundamental role in regulation of the E-cadherin cell adhesion complex. The abnormalities of the components of the complex may disrupt this adhesive function. We investigated the expression patterns of E-cadherin and beta-catenin to determine the clinical significance of these proteins in hepatocellular carcinoma. MATERIALS/METHODS: Thirty-six hepaticellular carcinoma tissues and adjacent non-tumor specimens were analyzed. Subcellular distribution of E-cadherin and beta-catenin was examined by immunohistochemistry staining. We evaluated the patterns of the expression, and investigated the relationship with the cause of HCC; level of AFP; TNM stage; tumor size; growth types; metastasis; differentiation grade of HCC; and presence of portal vein thrombosis. RESULTS: Immunohistochemistry showed that all non-tumor tissues had membranous type staining of E-cadherin. All non-tumor tissues showed cytoplasmic type staining of beta-catenin, but no beta-catenin accumulation in nuclei was found. 58% (21/36) of HCC showed positive expression of E-cadherin in cytoplasmic membrane. The cytoplasmic expression of beta-catenin in HCC was 83% (30/36); nuclear expression in 14% (5/36); and no staining in 3% (1/36). Nuclear beta-catenin expression was observed in none (0/4) of the well-differentiated HCC; 17%(3/9) of moderate-differentiated HCC; and 17%(2/6) of poorly-differentiated HCC. There were no relationships between E-cadherin and beta-catenin expression with other clinicopathologic factors. CONCLUSIONS: Loss of cytoplasmic staining of E-cadherin and nuclear accumulation of beta-catenin were observed in HCC. Nuclear accumulation of beta-catenin was not found in well differentiated HCC but was found in poorly differentiated HCC.

Liver Abscess Formation in Non-Tumorous Parenchyma after Transcatheter Arterial Chemoembolization (TACE) for the Treatment of Hepatocellular Carcinoma Associated with Pneumobilia / 대한간학회지

Transcatheter arterial chemoembolization (TACE) is widely used to treat inoperable hepatocellular carcinoma and metastatic tumor of the liver. Among the complications occurring after TACE, liver abscess formation in HCC is a fatal complication. The reported incidence of this complication ranges from 0% to 3.3%. Moreover, liver abscess formation in non-tumorous parenchyma is very rare. The pathogenic mechanism of this complication has been linked to several factors but retrograde enteric bacterial contamination of the biliary tract appears to be the most commonly implicated cause. The major risk factors of the biliary tract infection are pneumobilia, portal vein thrombosis, bilo-enteric anastomosis and biliary obstruction. We report a rare case of liver abscess formation in non-tumorous liver parenchyma after TACE for the treatment of hepatocellular carcinoma in a patient with pneumobilia.

Combined Hepatocellular and Cholangiocarcinoma, Separate Type: A Case Report / 대한간학회지

Combined hepatocellular and cholangiocarcinoma (cHCC-CC) is an uncommon form of primary liver cancer having features of both hepatocellular and billiary epithelial differentiation. We reptitis B virus. A 36-year-old woman was diagnosed by ultrasonography with an asymptomatic tumor inort a case of cHCC-CC that separately developed in a patient who was serologically positive for hepa the left lobe of the liver. Based on radiologic and serologic findings of elevated serum alpha-fetoprotein (AFP) level, a preoperative diagnosis of hepatocellular carcinoma was made. A left lobectomy of the liver was done. On histological examination, the resected tumor was shown to consist of two separated masses. One was hepatocellular carcinoma that showed immunoreactivity for AFP. The other was cholangio- carcinoma that showed immunoreactivity for cytokeratin-19 (CK-19) in a separate form.

Inferior Vena Cava Invasion of Hepatocellular Carcinoma / 대한간학회지

No abstract availalbe

Implications of Serum Levels of Basic Fibroblast Growth Factor and Vascular Endothelial Growth Factor in Chronic Liver Diseases and Hepatocellular Carcinoma / 대한간학회지

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.

Efficacy of Repeated Arterial Infusion of Cisplatin and 5-Fluorouracil via a Percutaneously Implantable Port System in Advanced Hepatocellular Carcinoma / 대한간학회지

BACKGROUND/AIMS: A prospective study was performed to evaluate the efficacy of low dose administration of cisplatin (CDDP) and 5-fluorouracil (5-FU) by repeated arterial infusion via a percutaneously implantable port system (PIPS) for advanced hepatocellular carcinoma (phase II trial). METHODS: Ten patients with hepatocellular carcinoma belonging to TNM stage IV, but without extrahepatic spread, were enrolled. Nine patients had main portal vein thrombosis. All the patients were positive for HBsAg. Patients were repeatedly treated with an arterial infusion of CDDP and 5-FU (10 mg and 250 mg, respectively, for 5 hours on days 1-5) via a PIPS at four week intervals. The response was assessed by dynamic CT after two courses of chemotherapy. RESULTS: Insertion of PIPS was successful in 8 of 10 patients. Two patients could not receive a second course of chemotherapy because one died of progressive hepatic failure and the other developed local infection and pseudoaneurysm formation. All the remaining 6 patients exhibited tumor progression after two courses of chemotherapy. The median survival time was 89 days (range, 59-204). The causes of death were progressive hepatic failure in one patient and uncontrolled esophageal variceal bleeding in one patient. CONCLUSIONS: Arterial infusion chemotherapy with CDDP and 5-FU via a PIPS was not an effective treatment for patients with advanced hepatocellular carcinoma.

Multicentric Occurrences of Hepatocellular Carcinoma / 대한간학회지

No abstract availalbe.

Bile Duct Invasion of Hepatocellular Carcinoma / 대한간학회지

No abstract availalbe.

Clinical Characteristics of Non-B, Non-C Hepatocellular Carcinoma and Detection of HBV, HCV and TTV Viremia / 대한간학회지

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.