Masaaki Onaga

Risk factors for the local recurrence of hepatocellular carcinoma after a single session of percutaneous radiofrequency ablation.

BackgroundRadiofrequency ablation (RFA) is a new, minimally invasive treatment for hepatocellular carcinoma (HCC). However, there is little available information regarding local recurrence after a single session of RFA with a single electrode insertion.MethodsFrom February 1999 to September 2001, we treated 104 HCC tumors with an expandable needle with four hooks. Ninety-nine of the 104 tumors were successfully treated by single-session RFA with a single electrode insertion. We investigated the relationships between pretreatment factors (tumor size, tumor staining, tumor capsule, and tumor location) and local recurrence in these 99 tumors.ResultsThe mean size of the 99 tumors was 21.5 mm in diameter (range, 10 to 33 mm). The overall local recurrence rates were 9.7%, 15.4%, and 20.4%, at 1, 2, and 3 years, respectively. For small tumors (smaller than 25 mm), the local recurrence rates at 1, 2, and 3 years were 4.0%, 8.0%, and 14.6%, respectively. The local recurrence rates were 21.1% and 32.3% at 1 and 2 years, respectively, for large tumors (25 mm or larger), and at 3 years the rate was over 50% for tumors located close to the liver surface. Tumor size and tumor location relative to the liver surface were significantly associated with a higher local recurrence rate. However, other variables tested showed no significant relationship to the local recurrence rate.ConclusionsThis study demonstrated that both tumor size and location relative to the liver surface influence the local efficacy of single-session RFA with a single electrode insertion.

Osteoactivin expressed during cirrhosis development in rats fed a choline-deficient, l-amino acid-defined diet, accelerates motility of hepatoma cells

BACKGROUND/AIMS Hepatocellular carcinoma (HCC) is closely associated with chronic liver diseases, particularly cirrhosis. However, the genes involved in hepatocarcinogenesis in the context of developing cirrhosis remain unknown. This study aims to identify genes associated with early cirrhosis-associated hepatocarcinogenesis. METHODS We examined genes differentially expressed between the livers of normal rats and rats fed a choline-deficient, L-amino acid-defined (CDAA) diet using suppression subtractive hybridization. We examined both the expression in the liver and HCC tissues of osteoactivin (OA), isolated in this screen, and its effect on invasiveness and metastasis. RESULTS OA mRNA was strongly expressed in the livers of rats fed the CDAA diet for 1-3 months. Moderate expression was sustained for 18 months. OA overexpression increased the invasiveness and metastasis of rat hepatoma cells in vitro and in vivo. In humans, OA expression was not detectable in normal liver tissues. While OA transcripts were detectable in cirrhotic nontumorous liver tissues surrounding HCCs, the majority of HCC tissue samples exhibited higher levels of OA expression than the surrounding normal tissue. CONCLUSIONS These results indicate that OA is a novel factor involved in the progression of HCC via stimulation of tumor invasiveness and metastatic potential.

A case of acute hepatitis A with marked hemophagocytosis in bone marrow

A previously well 18-year-old female was referred to our hospital because of abnormalities of blood biochemistry and slight jaundice. Because serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were elevated more than 6000 IU/L, the patient was suspected to have acute viral hepatitis. The platelet count on admission was 9.7x10(4)/µl, which was decreased from the initial value of 21x10(4)/µl for 3 days. The coagulation tests revealed marked elevation of D-dimmer, fibrinogen degradation products and thrombin-antithrombin III complex suggesting increase in fibrinolysis. Serum levels of high density lipoprotein cholesterol and ferritin were markedly decreased and increased, respectively. The bone marrow smears revealed proliferation of mature histiocytes ingesting platelets and erythrocytes, these pathological findings were consistent with those of hemophagocytic syndrome (HPS). In addition, anti-hepatitis A IgM antibody in the serum and hepatitis A virus (HAV) RNA in the stool were positive. Therefore, the patient was diagnosed as having acute hepatitis A with probable HPS. Since a fulminant clinical course was suspected, glucocorticoid pulse therapy was started immediately 7 days after onset and a favorable clinical outcome resulted.

A case of hepatocellular carcinoma associated with autoimmune hepatitis

Abstract We report a case of hepatocellular carcinoma (HCC) associated with autoimmune hepatitis in an 80-year-old female. The patient exhibited the presence of a liver injury 10 years previously. However, because the etiology was not identified, she did not receive specific treatment such as glucocorticoid therapy. She was admitted to our hospital because of the presence of a mass lesion in the S 8 region of the liver detected by ultrasonography. Serum alanine and aspartate aminotransferase levels were elevated and the serum γ -globulin level was increased to more than 2.5 g/dl. Serum autoantibodies such as antinuclear antibody and anti-DNA antibody were positive. Hepatitis virus markers and their genes for hepatitis B virus (HBV) and hepatitis C virus (HCV) were negative in the serum. The biopsied specimen from the non-tumorous lesion showed a marked infiltration of chronic inflammatory cells, particularly plasma cells, and the tumorous lesion was well to moderately differentiated HCC. HBV DNA and HCV RNA were not detected in the tissue specimen from the non-tumorous lesion.

HGF-Related Proteins in Hepatocellular Carcinoma (HCC)

Hepatocyte growth factor (HGF) is secreted as a single-chain form (proHGF) from mesenchymal cells of the liver, and proHGF is converted to heterodimeric HGF (mature HGF) by serine proteases, including hepatocyte growth factor activator (HGFA), in response to tissue injury. Hepatocyte growth factor activator inhibitor type 1 (HAI-1) and type 2 (HAI-2) have recently been purified from the conditioned medium of a gastric cancer cell line, and their cDNAs have been successfully cloned. The hepatocytes of patients with chronic liver diseases including hepatocellular carcinoma (HCC) were stained with anti-HGFA. HAI-1 was detected in tumorous tissues of HCC, but not in liver tissues of patients with chronic liver diseases. Tumorous tissues in HCC were positive for HAI-1 mRNA. HAI-1 may play an important role in the development or invasiveness of HCC through the mechanism regulating HGF activation.

HBV and HCV negative hepatocellular carcinoma associated with porphyria cutanea tarda-A case report.

症例は65歳, 男性. 常習飲酒家. 15年前より露光部に色素沈着があり, 創傷が治癒しにくかった. 1995年9月, 肝内腫瘤を指摘され, 当科に入院. 日光曝露部に色素沈着を認め, 血液生化学検査では血清トランスアミナーゼの軽度上昇, 血清鉄とフェリチンの高値がみられた. 尿中ウロポルフィリンは著増し, 尿中ポルフィリン前駆体および血中・便中ポルフィリンは正常範囲内で, HBVおよびHCV関連マーカーはすべて陰性であった. 腹部USTで右葉に充実性腫瘤を認め, 同部位からの狙撃生検像は高分化型の肝細胞癌 (HCC) の所見であった. 非癌部の組織像は肝硬変の所見で, 肝細胞内には針状結晶が存在した. 肝組織中のHBV-DNA (PCR法) およびHCV-RNA (RT-PCR法) は陰性であった. 以上の検査結果より, HCCを合併した晩発性皮膚ポルフィリン症 (porphyria cutanea tarda; PCT) と診断した. HBVおよびHCVが関与していないPCTにおけるHCC合併例はこれまで本邦では報告されていないので, PCTにおける肝発癌について文献的考察を加え報告する.