[A study on the serum levels of insulin-like growth factor-I (IGF-I) in patients with various chronic liver diseases].
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Biomedical subjects
Publications and source records attributed to M Unoura.
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A 65-year-old Japanese woman had primary biliary cirrhosis (PBC) and chronic pancreatitis associated with ulcerative colitis. The association of PBC and ulcerative colitis may prove to be valid.
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The effect of interferon (IFN) on hepatitis B virus infection in patients with chronic active hepatitis is discussed. We can expect disappearance of DNA polymerase and HBeAG from serum by IFN administration. There seems to be no difference between IFN-alpha and IFN-beta in the effect on chronic hepatitis B virus infection. Female and those who with low pretreatment DNA polymerase activity are more susceptible to IFN treatment. With IFN alone, it is hard to expect a persistent disappearance of HBsAg. IFN therapy combined with other agents, such as adenine arabinoside, prednisolone, etc. must be considered in the future.
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The value of various screening methods in the detection of early hepatocellular carcinoma was investigated in 95 patients with cirrhosis. Infusion hepatic angiography and computed tomography with angiography were performed yearly, ultrasound every 3 months, and determination of serum alpha-fetoprotein levels every 2 months. "Space-occupying lesions" suspicious for hepatocellular carcinoma were found in 13 of the 95 cases (13.7%). Detection rates of "space-occupying lesions" were 77% for infusion hepatic angiography, 77% for computed tomography with angiography and 54% for ultrasonography, respectively. In 8 of the 13 cases, "space-occupying lesions" were subsequently confirmed as hepatocellular carcinoma by operative findings or clinical course. Serum alpha-fetoprotein levels were negative in 3 of the 8 hepatocellular carcinoma-confirmed cases, and 3 of the remaining 5 cases demonstrated levels above 400 ng per ml at the time of diagnosis. A radical resection of hepatocellular carcinoma was successfully performed in two cases. Although it was difficult to differentiate hepatocellular carcinoma from other lesions in the case of "space-occupying lesions" smaller than 2 cm in diameter, the results suggest that regularly scheduled screening may be useful to detect early hepatocellular carcinoma.
A new cell line derived from a woodchuck hepatocellular carcinoma serially transplanted in athymic nude mice has been established and named WH257GE10. The original tumor in the nude mouse system produces woodchuck hepatitis surface antigen and albumin. In addition, woodchuck hepatitis virus DNA is integrated into cellular DNA. Adaptation of the cells to the in vitro culture condition was completed after 15 months with the doubling time of 40 hr. The morphologic features of the cell by light microscopy are of an epithelial type. The modal chromosome number is 36 and the karyotype is mainly metacentric, similar to that observed in normal woodchuck liver cells. Ornithine and tyrosine aminotransferase activities were detected. Production of albumin was demonstrated in the cytoplasm by indirect immunofluorescence. Integration of woodchuck hepatitis virus DNA was shown by Southern blot analysis, although the secretion of woodchuck hepatitis surface antigen was not detected. This cell line provides an excellent in vitro model to study human hepatocellular carcinoma related to hepatitis B virus.
We report a cirrhotic patient with complete occlusion of the portal vein with marked cavernous transformation due to chronic thrombosis in whom a transjugular intrahepatic portosystemic shunt (TIPS) was successfully created after direct minilaparotomy mesenteric vein catheterization, lysis and aspiration of the thrombus, and stenting in the portal vein. The methods used, we believe, provide a new technique for performing TIPS in chronically thrombosed portal veins in which previously no effective surgical therapeutic options were available.
Magnetic resonance imaging was performed in four patients with biopsy proven idiopathic portal hypertension (IPH). The MR images show proximity of medium-sized intrahepatic vessels to each other and to the liver surface in all patients. Small vessels running parallel to the second order branches of the intrahepatic portal vein are commonly seen as collateral pathways of portal flow in IPH and were seen in two patients. These findings were clearly demonstrated on gradient-recalled echo images. Intrahepatic periportal abnormal high intensity was seen in all patients on T2-weighted images and may reflect abnormalities in the portal tracts such as fibrous enlargement and increase in the number of vascular channels. Tiny low-intensity nodules sometimes observed in liver cirrhosis were not seen in any patient. Magnetic resonance was a useful noninvasive method in the differentiation of IPH from liver cirrhosis.
To evaluate the efficacy of methotrexate (MTX)-5-fluorouracil (5-FU), cisplatin (CDDP), and interferon-alpha-2b(IFN alpha-2b) combination therapy, we conducted a clinical pilot study in patients with locally advanced hepatocellular carcinoma (HCC). Sixteen patients, who had received no prior treatment for the HCC, with portal tumor thrombosis in the main trunk or in the major branch were enrolled in the study. IFN alpha-2b (3 x 10(6) units) was injected subcutaneously 3 times per week. After a bolus administration of MTX (30 mg/m2), CDDP (75 mg/m2) and thereafter 5-FU (750 mg/m2) were given weekly by intrahepatic arterial infusion. In 15 eligible patients, there were 1 complete response (CR) and 6 partial responses (PR) with a response rate of 46.7%. Median survival of the 15 patients was 7 months, and the 2-year survival rate of CR and PR patients was 57.1%. There was severe transient hematologic toxicity. More than grade 2 nausea/vomiting was noted in > 50%. In conclusion, the IFN alpha-2b combination chemotherapy demonstrated good response in patients with locally advanced HCC. This treatment should be tried in a controlled study.
The purpose of this study was to examine the correlations among enhancement of apoptosis, cell proliferation and expression of oncogenes in gastric carcinomas induced by preoperative oral administration of 5-fluorouracil (5-FU). The occurrence of spontaneous apoptotic cell death in 42 patients with gastric carcinoma was analyzed in the biopsy specimens preoperatively. p53 status was examined by polymerase chain reaction-single strand confirmation polymorphism and sequencing. Fourteen patients received oral administration of 5-FU at 300 mg/body/day for 7 days preoperatively. For detection of apoptotic cells, apoptotic incidences (AIs) were examined by the terminal deoxynucleotidyl transferase-mediated deoxy-uridine triphosphate biotin nick end labeling method, on gastric carcinoma lesions based on the endoscopic findings before administration in the biopsy and resected tissues. Expressions of p53, Bcl-2, Bax gene and proliferating cell nuclear antigen (PCNA) were also examined by immunohistochemical staining. On preoperative biopsy, p53 point mutation was observed in 14 of the 42 tumors. The immunohistochemical staining status and point mutation of p53 gene (positive or negative) were identical in 32 of the 42 tumors (76.2%). The average AIs of the biopsy specimens were 1.58+/-1.26% on p53-negative staining (n=19) and 1.14+/-1.02% on p53-positive staining (n=23), a significant association was not recognized between p53 expression and AI. In the preoperative administration group, the PCNA labeling index was significantly higher in the biopsy specimens than in the resected tissues (43. 6+/-12.8% vs. 35.3+/-8.8%, p<0.01). In addition, postoperatively, the rate of AI was significantly more accelerated in p53-negative staining (n=6) than in p53-positive staining (n=8) (0.89+/-0. 65%right curved arrow 4.18+/-3.26%, p<0.05 vs. 1.20+/-0.60%right curved arrow 2.60+/-2.60%, NS). There was no significant correlation between AI and Bcl-2 or Bax staining. Immunohistochemical analysis of p53 and PCNA stainings in biopsy specimens appears to be a well-characterized indicator of sensitivity of chemotherapy in gastric carcinomas.