Measurement of hepatic blood flow using 111In colloid.

The reduced hepatic blood flow calculated from hepatic scintigram with 198Au colloid was elucidated as the primary responsible factor for postoperative hepatic insufficiency. However 198Au colloid is no longer in use because of the high levels of radiation. Although 99mTc-phytate behaves similarly to 198Au on imaging, there were discrepancies between the hepatic blood flow index (KL) value and the severity of cirrhosis determined by laboratory data or by histology. In the measurement of hepatic blood flow using a radioactive colloid, factors like organ distribution, stability and uniformity of the colloid particles influence the values. In the present study, a 111In colloid was prepared and administered to rats to investigate the usefulness: as much as 95.4 (0.8) [Mean (+/- SD)]% of the colloid accumulated in the liver at pH 6.8. The distribution of particle diameter was within a relatively narrow range with the peak at 0.2 to 0.4 microns. Moreover, the KL values were not affected by condition of the reticuloendothelial system. The values showed a significant correlation with the measurements of the hepatic tissue blood flow obtained by the hydrogen gas clearance method (gamma = 0.83, P &#60; 0.001). Thus, the 111In colloid can be clinically used as a substitute for 198Au colloid in the preoperative examination for estimation of the limit of resection.</p

Quantitative measurement of portal blood flow by magnetic resonance phase contrast: comparative study of flow phantom and Doppler ultrasound in vivo.

A non-invasive method for measuring portal blood flow by magnetic resonance (MR) phase contrast was evaluated in a flow phantom and 20 healthy volunteers. In a flow phantom study, the flow volumes and mean flow velocities measured by MR phase contrast showed close correlations with those measured by electromagnetic flowmetry. In 20 healthy volunteers, the cross-sectional areas, flow volumes and mean flow velocities measured by MR phase contrast correlated well with those measured by the Doppler ultrasound method. Portal blood flow averaged during the imaging time could be measured under natural breathing conditions by using a large number of acquisitions without the limitations imposed on the Doppler ultrasound method. MR phase contrast is considered to be useful for the non-invasive measurement of portal blood flow.</p

Laparoscopic cholecystectomy: a multicenter study of 17 hospitals.

A study of 1,254 laparoscopic cholecystectomies performed at 17 hospitals affiliated with the Liver, Gallbladder, and Pancreas Research Group of the First Department of Surgery at Okayama University was undertaken to assess the current status and safety of this procedure. The data for 336 patients, comprising the initial 20 laparoscopic cholecystectomies performed at each institution, were compared with the data from the remaining 918 patients. Comparison of the two groups revealed the following: 1. the rates of intraoperative conversion to open cholecystectomy were 11.3% and 5.1% (P &#60; 0.05), 2. the complication rates were 5.7% and 3.4%, and 3. the rates of bile duct injury were 2.4% and 1.1%, respectively. Compared with the first group, the bile duct injuries resulting from a lack of experience decreased in the second group, however, the incidence of these injuries occurring during avulsion of the gallbladder in difficult cases increased. These results suggest that the experience acquired during the initial 20 laparoscopic cholecystectomies led to a reduction in the rate of intraoperative conversion to open cholecystectomy, but it did not reduce the rate of complications, and that the risk of bile duct injury was always present.</p

Effect of Picibanil (OK 432) on the Scavenging Effect of Free Radicals Produced during Liver Regeneration in the Rat

We administered a biological response modifier Picibanil (OK-432), attenuated Streptococcus pyogenes, via the dorsal vein of the penis after 70% hepatectomy in rats, and clarified the scavenging effect of Picibanil on free radicals generated in the regenerating liver. A group of 5 rats was intravenously administered with 25 KE/kg of OK-432 after hepatectomy, while the control group was given saline after hepatectomy. Serum levels of aspartate aminotransferase and alanine aminotransferase and the value of thiobarbituric acid-reactive substances in serum and hepatic tissue after hepatectomy were serially measured, and these values were significantly lower in Picibanil treated animals than in control animals. Free radical production in the regenerating liver was also measured by electron spin resonance spectrometry, and OK-432 injection significantly reduced free radical production. These results suggested that OK-432 reduced hepatocellular damage in regenerating liver by inhibiting lipid peroxidation.</p

Expression of Fas antigen and Bcl-2 protein in hepatocellular carcinoma.

Fas antigen (ag) is a cell surface protein known to trigger apoptosis in a variety of cells upon specific antibody binding. On the other hand, Bcl-2 protein, an oncogene product located at the mitochondrial inner surface, prolongs cell survival by blocking apoptosis. In this study we examined the expression of Fas ag and bcl-2 protein in 17 cases of hepatocellular carcinoma (HCC) to determine their role on HCC. By flow cytometric analysis, mean (SD) value of the expression of Fas ag on hepatocytes derived from normal liver, diseased liver (chronic hepatitis or liver cirrhosis) and HCC was 5.8 (4.7)%, 10.3 (6.9)%, and 24.0 (18.2)%, respectively. Fas ag expression on hepatoma cells was significantly greater than normal and diseased liver cells. The expression of Bcl-2 protein in normal liver, diseased liver and HCC was 4.3 (8.5)%, 0.8 (2.5)% and 2.1 (3.4)%, respectively, and the difference was not significant. These results suggest that induction of apoptosis may be a possible therapy against HCC.</p

31P nuclear magnetic resonance evaluation of rat liver preserved in UW solution.

A persistent problem in orthotopic liver transplantation is primary nonfunction (PNF) of the hepatic allograft. In an attempt to reduce the incidence of graft failure, the feasibility of pretransplant assessment of graft viability was investigated by 31P nuclear magnetic resonance (NMR) spectroscopy. The level of adenosine triphosphate (ATP) was measured as an indicator of liver function by 31P NMR spectroscopy after a 30 min normothermic reperfusion following cold-storage in University of Wisconsin (UW) solution. The mean +/- SD beta-ATP/Pi ratio after preservation for 0, 12, 24 or 48 h was 1.40 +/- 0.34, 0.85 +/- 0.27, 0.64 +/- 0.14 and 0.38 +/- 0.09, respectively. Significance was observed between 12h and 24h and between 12h and 48h of preservation. These results correlated well with the morphological changes in endothelial cells and sinusoidal lining cells examined by transmission electron microscopy. It is suggested strongly that microcirculatory disturbances due to endothelial cell injury impairs the recovery of ATP levels after reperfusion, and that ATP determination by 31P NMR spectroscopy, as a non-invasive modality, may help in the prediction of PNF after liver transplantation.</p

Lipid peroxidation in hepatocellular carcinoma.

In this study, we measured free radicals and thiobarbituric acid-reactive substances (TBARS) in hepatocellular carcinoma and in non-cancerous liver parenchyma. There was a higher concentration of free radicals in malignant tissue than in non-cancerous tissue. In contrast, the level of TBARS was significantly (P &#60; 0.01) lower than non-cancerous liver parenchyma. These paradoxical results suggested that antioxidative enzyme activity and/or inhibition of lipid peroxidation were higher in hepatocellular carcinoma.</p

A case of necrosis of hepatocellular carcinoma and tumor thrombus in the portal vein induced by transcatheter arterial lipiodol chemoembolization.

A case of hepatocellular carcinoma is reported in which the main tumor, intrahepatic metastases and a tumor thrombus in the portal vein were necrotized completely after Lipiodol chemoembolization. In this case, the tumor thrombus seemed to act as a portal embolus. This phenomenon is interesting because Lipiodol chemoembolization alone usually can not necrotize intra- or extra-capsular invasion, intrahepatic metastasis or tumor thrombus in the portal vein. This case is considered to be suggestive of a possible therapy for hepatocellular carcinoma.</p

Primary cultures of human livers and their albumin-producing capacity.

Primary cultures of surgically obtained noncancerous portions of human liver tissues were made. Liver tissues were poorly dissociated with collagenase, but well dissociated with dispase. The yield and viability of cells were improved somewhat when dissociated with collagenase followed by dispase. The mean cell yield was 1.1 X 10(6) cells/g liver. The epithelial-like morphology of the dissociated liver cells was maintained for about one week, but thereafter degenerative alteration of cells was observed. In liver explant culture, an active outgrowth of cells was observed for more than one month. Albumin production in culture fluids from dissociated livers was detectable for about 2 weeks, but later became undetectable, while that from explant culture was detectable for at least one month. These data demonstrate that adult human hepatocytes can be isolated from noncancerous portions of livers with relatively high yield, and that albumin production of the dissociated cells is detectable for several days.</p

Comparison of cellular characteristics between human hepatoma cell lines with wild-type p53 and those with mutant-type p53 gene

Characteristics of human hepatoma cell lines with the wild-type p53 were compared with those of human hepatoma cell lines with the mutant-type p53. The p21 protein located downstream of p53 was expressed in cell lines with the wild-type p53 but was not expressed in cell lines with the mutant-type p53. As to other tumor suppressor genes such as p16 and p27, there was no difference in their expression between both types of cell lines. In addition, no marked difference was observed in the activities of CDK2 and CDK4 between cell lines with the wild-type and the mutant-type p53. Phosphorylated Rb protein was detected in all cell lines except the HLE line, indicating that this cell line may have a deletion of and/or a mutation of the Rb gene. These results indicate that abnormalities of tumor suppressor genes other than p53, p16, p27, and Rb may be involved in hepatocarcinogenesis. The population doubling time of the wild-type p53 cells was significantly longer than that of the mutant p53 cells. Neither type of cell line showed a specific chromosome distribution which would indicate karyotype instability. The cell lines expressing the wild-type p53 produced tumors at lower frequency than those with the mutant p53 gene. Although there was no significant difference in effects of TGF-&#946;1, EGF, cholera toxin, and db-cAMP on cell growth between the two types of cells, all three cell lines with the wild-type p53 were resistant to cytotoxicity of TNF-&#945;, while two of the three with the mutant p53 were very sensitive to its cytotoxic effects.</p