Clinical features of hepatocellular carcinoma with reference to ages in Korean patients / 대한내과학회지

BACKGROUND: Hepatocellular carcinoma(HCC) has characteristic differences in both viral profiles and the most frequently occurring age in each country. It also has clinically distinct features between adult patients of the age under 65 and senile patients over 65 years. Herein we investigate differences in clinical features of the patients with HCC of the three different age groups : young patients (group 1) below 45 years of age; most frequently occurring age (45 - 65 year) (group 2); and elderly patients (group 3) above 65 years of age. METHODS: The 371 HCC patients hospitalized and followed-up from 1986 to February 1997 have been analyzed. At the time of diagnosis there was no significant difference among the three groups in alcohol intake, cigarette smoking, sex, family history of liver disease, mean values of aminotransferases, Child-Pugh class, tumor location, TNM stage, tumor size, varix grade, metastasis, abdominal pain, ascites, encephalopathy, fever, or jaundice. RESULTS: In the younger group HCC showed (1) a high incidence of HBsAg positivity (group 1, 95.3%; group 2, 78.6%; group 3, 25%; p400 ng/mL) showed no differences among the three age groups (p=0.23766). (6) The overall survival rates did not differ statistically among the three groups (mean survival: group 1, 12 months; group 2, 18 months; group 3, 15 months; p=0.4635, log rank test). CONCLUSION: These data support the younger patients with HCC are the most frequently associated with HBV contrarily to the elderly patients the more frequently associated with HCV or NBNC rather than HBV. This suggests, in turn, that the onset of HCC occurs one or two decades later in those with adult-acquired HCV than it does in lifelong HBV patients after neonatal vertical infection.

Stereological Analysis of gamma-Glutamyl Transpeptidase Positive Foci in Diethylnitrosamine-Induced Hepatocarcinogenesis of Sprague-Dawley Rats / 대한간학회지

BACKGROUND/AIMS: Hepatocarcinogenesis of microscopically altered foci could be shown to be progressed into a trabecular pattern of hepatocellular carcinoma. And it is reported that down-regulation of TGF beta II receptor and up-regulation of TGF alpha and c-myc reveal the progression of diethylnitrosamine-induced foci into liver cell cancer. Up-regulation of TGF beta II receptor, however, causes apoptosis of foci. To determine characteristic morphology and growth kinetics of putatively precancerous y glutamyl transpeptidase (GGT) positive foci and hyperplastic nodules, a stereological quantification was attempted in the Peraino's neonatal rat model initiated by diethylnitrosamine and promoted by phenobarbital. MATERIALS/METHODS: Fifteen Sprague-Dawley rats were I.p. injected with 0.15 pmole/g of body weight of diethylnitrosamine mixed in corn oil at one day after birth. From weaning at 4 weeks of life, the rats were continuously fed 0.035% phenobarbital in drinking water and sacrified 5 rats at each time point of 8 weeks, 16 weeks, and 32 weeks. Teklad standard diet was fed after weaning. The livers obtained were fixed in freshly prepared, cold ethanol-acetic acid (99:1 vo1%). For the GGT histochemical staining, Rutenberg's method was modified, and counterstained with H & E or toluidine blue. For the stereological analysis GGT positive foci and nodules were traced in 200 consecutive tissue sections and quantified the 3 dimensional volumes by computer assisted planimetry. Either spheroidal or non-spheroidal morphology was determined by parabola 2nd degree equation ' y=ax+bx+c (sphere a=-P,). RESULTS: Thirty nine (55.71%) out of 70 representative lesions were nonspheroidal. Especially at 8 weeks, the 28 out of 40 GGT positive foci were irregular, nonspheroidal shape. Later times, however, GGT positive foci and reprogrammed nodular lesions were become spheroidal. Lilliefors probabilities test for spheroidal frequency was statistically significant (p<0.05). CONCLUSION: Stereologically non-spheroidal characteristics of the early GGT positive foci limit growth kinetic estimation by 3 dimensional volume quantitation but permit in later times in spheroidal, GGT positive foci and reprogrammed nodules showing fade-out of GGT activity. In other words, GGT positive foci may be clonally selected for growing into hyperplastic nodules and hepatocellular carcinoma or regressed by apoptosis.

Changes of Epidermal Growth Factor in Sera among the Patients with Chronic Hepatitis, Cirrhosis and Hepatocellular Carcinoma / 대한간학회지

BACKGROUND/AIMS: Epidermal growth factors (EGF) is known to activate mitogen activated protein kinase (MAP kinase) in hepatocytes by the route of both Raf-dependent and Raf-indefendent pathways. And this is likely to play important role in normal liver cell growth and regeneration. EGF is also reported as a potent mitogen and one of the angiogenic factors. To elucidate the dynamic changes of the serum concentration of epidermal growth factor in chronic liver disease and its correlation with role of EGF and mechanism of tumor development, this study is intended to employ an ELISA in 38 biopsy-proven cases. METHODS: Sera taken out of 5 patients with chronic persistent hepatitis. 4 patients with chronic active hepatitis, 19 patients with liver cirrhosis, 10 patients with hepato-cellular carcinoma that pathological diagnosis was proven later were tested for EGF employing Quantikine ELISA Kits (R & D Systems Inc. Minneapolis, MN). The statistical analysis was evaluated by student's t-test. RESULTS: EGF concentration was 253.33+ 69.5pg/ml(Mean+ SE) in hepatocellular carcinoma, 246.60+ 91.19pg/ml(Mean+ SE) in chronic active hepatitis, 222.71+ 115.97pg/ml (Mean+ SE) in chronic persistent hepatitis, 141.15+ 23.12pg/ml(Mean+ SE) in liver cirrhosis in orders. Serum EGF concentration in hepatocellular carcinoma was significantly higher than that in liver cirrhosis(p value=0.021695). However, comparing to the remaining other groups, no significant difference was found. CONCLUSION: These results support that the reconstruction of the capillary networks in liver cirrhosis resplts in down-regulation of the EGF in comparison to chronic hepatitis. But it is suggested that revaluation of EGF stimulates MAP kinase activity eventually playing in tumorigenesis of the liver with neoangiogenesis.