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PubMed1985

Course of hepatic regeneration after 80% to 90% resection of normal rat liver. Comparison with two-lobe and one-lobe hepatectomy.

After subtotal (80% to 90%) hepatectomy of the normal rat liver, thymidine kinase activity began to increase after 24 hours and reached a maximum at 36 hours. This persisted for another 60 hours before it declined to reach the baseline by 7 to 8 days. The maximal increase was 30- to 50-fold. After two-lobe (67% to 78%) hepatectomy, the maximal increase was similar, but the onset and the maximum each occurred 12 hours earlier, and the maximum only persisted for another 24 hours. The important first peak of ornithine decarboxylase activity occurred earlier and rose higher after 67% to 78% hepatectomy. The distributions with time of histologic mitosis counts were similar to the distributions of thymidine kinase activity (reflects DNA synthesis) at each of the three levels of hepatectomy, 80% to 90%, 67% to 78% and 37% +/- 0.5%. Thus the initiation of regeneration was delayed after subtotal resection, but the regenerative response as reflected by DNA synthesis and cell multiplication was prolonged.

Alanine Transaminase↗
PubMed1985

Hepatectomy for metastatic liver tumor.

Hepatectomy for liver metastasis from the colo-rectum and other organs was performed in 77 cases at the National Cancer Center Hospital. The operative procedures included every variety of hepatectomy from extended resection as trisegmentectomy to small resection as partial resection. The operative mortality rate was 3.9% (3/77). The overall cumulative 5-year survival rate was 26.7 +/- 13.9% (survival rate +/- Greenwood's 5% standard error). The long-term survival of the patients with unilobular metastasis (H1) was better than that of bilobular (H2) and disseminated (H3 metastasis). When H1 was divided into solitary unilobular metastasis (H1 solitary) and multiple unilobular metastasis (H1 multiple), the prognosis for the former was better than for the latter after hepatectomy. The long-term survival of patients with H1 multiple was the same as that of patients with H2 and H3; that means that one of the factors affecting prognosis after hepatectomy is whether the tumor is solitary or multiple.

Adolescent↗
PubMed1985

[Systemic hemodynamics and oxygen metabolism after hepatectomy--effect of hyperdynamic systemic circulatory support on postoperative prognosis].

This study was undertaken to evaluate inotropic effect of dobutamine (DOB) on systemic and hepatic hemodynamics after hepatectomy. Systemic hemodynamics after 70% hepatectomy using mongrel dogs was depressed and oxygen metabolism was disturbed. Whereas in the dogs administrated DOB after hepatectomy, systemic circulation was improved and oxygen metabolism was maintained in a favorable state. In these hepatectomized dogs, hepatic blood flow was increased after administration of DOB. Systemic hemodynamics after hepatectomy in 37 cases of cirrhotic hepatoma was studied. In 15 cases, 3 micrograms/kg/min of DOB was infused i.v.d. after operation, and remaining 22 cases were assessed without DOB as control group. In controls, systemic circulation was depressed and increase of peripheral oxygen demand was compensated by increase of oxygen extraction ratio. Whereas in DOB group, oxygen delivery increased according to hyperdynamic systemic circulation and was followed by increase of oxygen consumption. These favorable hemodynamic results in DOB group reflected on the postoperative prognosis of these patients; 5 of 22 in control group, whereas only 1 of 15 in DOB group died of hepatic failure postoperatively. It is concluded administration of DOB in cirrhotic hepatectomized patients maintained systemic circulation in a hyperdynamic state and this resulted in improvement of postoperative prognosis.

Adult↗
PubMed1977

Isozymic changes of acid phosphatase and esterase in regenerating rat liver after partial hepatectomy in relation to cell differentiation.

Activities and isozyme patterns of acid phosphatase and esterase were studied in rat liver at different intervals after partial hepatectomy to clarify the grade of immaturity of normal regenerating liver cells as a control for the unlimited proliferation of hepatoma cells. Acid phosphatase and esterase activities in the liver were elevated during a 12-hr period after hepatectomy, while their isozyme patterns did not change from those of immature liver. Similar findings were also observed in the liver of sham-operated rats. Eighteen hours after the operation, at the S phase before cell division, the isozyme pattern of these enzymes began to shift from an adult liver-type to an immature one resembling those of the infant liver 3 weeks after birth rather than those of newborn or fetal liver. Two or three days after partial hepatectomy, the isozymes characteristic of an immature liver type were more apparent. Although enzyme activities mostly returned to the normal adult level one week after the operation, the isozyme patterns did not completely return to those of an adult liver. These results indicate that despite the rapid proliferation of liver cells, the grade of cell differentiation of the regenerating liver after partial hepatectomy is much nearer to that of the normal adult liver rather than that of the fetal liver.

Acid Phosphatase↗
PubMed1983

Promotion of liver cancer development by brief exposure to dietary 2-acetylaminofluorene plus partial hepatectomy or carbon tetrachloride.

Adult male Fischer rats were exposed to a necrogenic dose (200 mg/kg) of diethylnitrosamine or to nonnecrogenic doses of N-methyl-N-nitrosourea, 1,2-dimethylhydrazine, or benzo(a)pyrene following partial hepatectomy or sham hepatectomy. This treatment by itself led to no hepatocellular carcinomas by 8 to 18 months, except in animals given N-methyl-N-nitrosourea, which showed a 30% incidence by 12 months. With each treatment regimen, exposure to dietary 2-acetylaminofluorene for 2 weeks coupled with partial hepatectomy or the administration of a necrogenic dose of CCl4, was associated with an incidence of 68 to 94% of cancer at 8, 12, or 18 months, depending upon the initiating carcinogen used. Appropriate controls showed either no hepatocellular carcinoma or a much lower incidence. It is concluded that the 2-week exposure to dietary 2-acetylaminofluorene plus partial hepatectomy or the administration of CCl4 has a strong promoting effect on liver carcinogenesis with four different chemical carcinogens.

1,2-Dimethylhydrazine↗
PubMed1984

[Flow cytometric analysis of hepatocellular regeneration after partial hepatectomy and administration of hepatotrophic factors].

Kinetics of hepatocellular regeneration after 30% and 70% hepatectomy and the effect of hepatotrophic factors on the normal liver and regenerating livers after hepatectomy were investigated by flow-cytometric analysis using adult male rats. The results were as follows: The DNA histogram of hepatocytes in the normal group had two peaks in G0G1 and G2M components; G0G1 29% S 13%, G2M 58%. In the 30% hepatectomized group, the peak of G2M slightly increased, and remarkable change was not noticed during 4 weeks. In the 70% hepatectomized group, the percentage of hepatocytes in G0G1 and G2M were markedly changed during 2 days after hepatectomy. The peak of G0G1 moved to S after 24 hours, to G2M after 36 hours and returned to G0G1 after 48 hours. Afterwards the G0G1 gradually decreased while the G2M increased and they finally reached a single peak of G2M at the 7th day. Supernatant of the intestinal homogenate after hepatectomy and EGF initiated the cell kinetics in normal and regenerating rat livers. Changes on cell kinetics was not observed after insulin and glucagon administration.

Animals↗
PubMed1984

[Indication of extended hepatectomy for liver cancer].

From the results of 95 cases of hepatectomy for liver cancer, including 67 cases of primary liver cancer, during the past 7 years in our department, the indication of extended hepatectomy for liver cancer was reviewed retrospectively, based on the pathological findings and functional reserve of the liver. 1. For curative resection, it is necessary to perform resection of larger segments than tumor existing area. 2. Morphologically, the extent of hepatectomy must be evaluated by the pathological findings such as the existence of tumor emboli in the portal vein, tumor capsule and daughter nodules, etc. 3. Functionally, resectability of the liver could be estimated preoperatively by total risk calculated from various liver function tests through multivariate analysis and the functional reserve (ICGmax) of the remnant liver. Furthermore, ICGRmax of unit liver volume is a good parameter of hepatic regeneration and long prognosis after hepatectomy.

Hepatectomy↗
PubMed1983

[Effects of cianidanol on chronic liver injury induced by carbon tetrachloride and on liver regeneration after partial hepatectomy in rats].

Effects of cianidanol on chronic liver injury induced by prolonged administration of carbon tetrachloride (CCl4) and on liver regeneration after partial hepatectomy of normal liver and CCl4 chronically injured liver were investigated by the measurement of plasma and liver biochemical parameters. Cianidanol increased the total plasma protein and 14C-Leu incorporation into plasma protein, while it reduced the contents of liver cholesterol and triglycerides. In rats with chronically injured liver or regenerating liver after partial hepatectomy of chronically injured liver, cianidanol improved the retention rate of BSP and the content of liver sugar. In rats with chronically injured liver, plasma GPT and GOT activities were reduced with the administration of cianidanol. Cianidanol had no effect on the regeneration rate after partial hepatectomy of normal liver, but it increased the regeneration rate after partial hepatectomy of chronically injured liver. These results suggest that cianidanol has the effect of improving the function of liver cells damaged by CCl4 treatment and of promoting the recovery of cell function to a normal level.

Alanine Transaminase↗
PubMed1983

[Significance of major hepatectomy for metastatic liver malignancy].

Major hepatectomies for 24 metastatic liver tumors including 13 of colo-rectum origin were performed. The cumulative survival rate in 23 cases excluding one case of operative death is 67.4%, 44.3% and 29.1% for 1, 3 and 5 year, respectively. The significant difference was observed in survival rate between H1(n = 16) and H2 - 3 (n = 7). In colo-rectum origin group the survival rate of solitary H1 was better than that of multiple H1 significantly. The Japanese Colon Cancer Research Meeting reported the relative survival rate of 33 cases of H1 colo-rectum origin including 2 of hepatectomized cases. The survival rate of the present 11 hepatectomized cases in the same category is significantly better than that in the report of Colon Cancer Research Meeting, which shows utility of hepatectomy for H1 metastatic tumor. Although in H2 - 3 group 5 of 7 cases died within one year after hepatectomy, 2 particular cases survived 22 months and 57 months. The primary lesions of these two were leiomyosarcoma of the jejunum and carcinoid tumor of the lung. The indication for major hepatectomy for metastatic liver malignancy is the tumor of H1, especially solitary and the slow growing or some kind of functioning tumor.

Adult↗
PubMed1983

The effect of 5-fluorouracil on DNA synthesis in the rat liver undergoing compensatory hyperplasia after partial hepatectomy.

An investigation has been made into the effects of 5-fluorouracil (5FU) on DNA synthesis after partial hepatectomy. Animals underwent in vivo isolated liver perfusion with 5-fluorouracil followed by partial hepatectomy or Sham hepatectomy. Controls consisted of animals whose liver was perfused with 0.9% saline. Liver weight and DNA synthesis were recorded at various times following 5-fluorouracil perfusion and partial hepatectomy and control procedures. The results have shown that perfusion with large concentrations of the cytotoxic agent (5 FU) can be performed without apparent serious side effects on liver weight and with only minimal delay in liver cell proliferation.

Animals↗
PubMed1980

A comparative study of lysosomal enzyme contents in blood and liver of rats following partial hepatectomy.

Lysosomal enzyme contents (acid phosphatase and beta-glucuronidase) in blood and liver were comparatively studied with histochemical methods after 70 per cent hepatectomy in rats. The major source of these enzymes released into the circulation was investigated. The serum lysosomal enzymes were substantially increased immediately after hepatectomy (6 and 12 hours), with the simultaneous peak elevation of serum glutamic oxaloacetic transaminase (SGOT). This increment decreased thereafter. However, the second significant increment was observed between 48 and 72 hours postoperatively, when SGOT activity was almost normalized. Histochemically, lysosomes in regenerating liver were significantly increased at 6 and 12 hours, mainly in the hepatocytes, and at 36 hours exclusively in the Kupffer cells, after hepatectomy, From these observations, the initial significant increment of lysosomal enzymes in the serum, seems to be due to enzymatic leakage following surgical trauma to the remnant liver. The comparative study may indicate that the major source of lysosomal enzymes released substantially into the circulation, from 48 to 72 hours, could be the Kupffer cells which contained numerous amounts of lysosomes at 36 hours following hepatectomy. A possible mechanism for the enzymatic release in our study seems to be "reverse endocytosis".

Acid Phosphatase↗
PubMed1981

Effects of partial hepatectomy and dietary phenobarbital on liver and mammary tumorigenesis by two N-hydroxy-N-acylaminobiphenyls in female CD rats.

The objective of this study was to investigate the induction of liver tumors by arylhydroxamic acids. The potential involvement of sulfate conjugation was minimized by the administration of a N-hydroxy-4-acylaminobiphenyl to female CD rats. This experimental design provided for the exposure of a target organ that has only a low capacity for activation of hydroxamic acids by sulfate conjugation, with a carcinogen that does not induce tumors in liver that possess a high sulfotransferase activity. A single dose of the N-formyl or N-acetyl derivatives of N-hydroxy-4-aminobiphenyl was given i.p. at 0.4 mmol/kg body weight to 34-day-old animals. In attempts to amplify the hepatocarcinogenic potential of the compounds, partial hepatectomy 24 hr before the chemical injection and subsequent long-term treatment with phenobarbital in the diet were carried out. For comparative purposes, other animals were subjected to three additional partial hepatectomies subsequent to the carcinogen administration instead of the phenobarbital treatment. The experiments were terminated 64 weeks after injection. Both the N-formyl and N-acetyl derivatives of N-hydroxy-4-aminobiphenyl, in conjunction with partial hepatectomy and subsequent treatment of dietary phenobarbital, induced a high incidence of neoplastic nodules and gamma-glutamyltranspeptidase-positive foci in the liver. Only one hepatocellular carcinoma was observed in each treatment group. Repeated partial hepatectomies enhanced the yield of gamma-glutamyltranspeptidase-positive foci but were ineffective in producing neoplastic nodules. In addition to the liver lesions, mammary tumors were also induced. Importantly, an inhibitory effect of the subsequent administration of phenobarbital was observed on mammary tumor formation, possibly because of alterations in hormone metabolism resulting from the induction of microsomal enzymes by phenobarbital, which resulted in a decreased promoting effect. There was no difference in the tumorigenicity of the formyl and acetyl derivatives in these experiments.

Aminobiphenyl Compounds↗
PubMed1981

Plasma amino acid patterns in experimental acute hepatic failure: comparison between hepatectomy and liver devascularization in pigs.

To clarify the physiopathologic mechanism leading to a marked increase in aromatic amino acids (AAA) in acute hepatic failure (AHF), we compared two experimental models of AHF. Ten pigs were submitted to one-stage hepatic devascularization (group A); in eight other pigs total hepatectomy was performed (group B). The animals were maintained under constant glucose infusion. The mean survival time in group A was 23 +/- 2 hours; after hepatectomy it was 30 +/- 4 hours. Hepatic coma progressively deepened from 8 +/- 3 hours in Group A animals and was delayed until 17 +/- 5 hours in the anhepatic pigs. AAA, methionine, and tryptophan immediately increased markedly in pigs with liver ischemia. In group B animals, AAA showed a slight increase only 18 hours after hepatectomy, whereas there were no significant differences in methionine and tryptophan. The different amino acid patterns in the two groups of animals demonstrate that hepatocyte necrosis is a major source of plasma amino acids after liver devascularization. The slight increase in AAA after total hepatectomy suggests that a release mechanism from muscular mass is involved in the later stages of the experiment. The onset of coma is related to the increase in AAA rather than to alterations in blood ammonia that did not differ in either group of animals.

Amino Acids↗
PubMed1995

[Effects of angiogenesis inhibitor TNP-470 to suppress the recurrence in the liver remnant after partial hepatectomy for liver metastases in rabbits].

We investigated the effects of an angiogenesis inhibitor, TNP-470, in suppressing the recurrence in the liver remnant after partial hepatectomy for VX2 liver metastases model of rabbits. After inoculation of 1 x 10(6) VX2 tumor cells via the portal vein, the medial lobe of the liver was resected. Then, TNP-470 (7 mg/body/day) was infused (Group 1), or distilled water (Group 2), continuously via the mesenteric vein for a week. The control group received only infused distilled water via the mesenteric vein. Fourteen days after the tumor inoculation, there were 66.0 +/- 20.2 (mean +/- SD) metastatic colonies on the liver surface of control group, against 23.3 +/- 24.0 and 123.7 +/- 47.9 colonies in Group 1 and Group 2, respectively. There were significant differences between control group and Group 2, and between Group 1 and Group 2. We consider that the liver regeneration following hepatectomy might provoke tumor growth of occult metastases in the liver remnants. TNP-470 suppressed these growth by its anti-neovascular activity. And this effect reduced the number of metastatic colonies. Fourteen days after hepatectomy, the weights of the liver were no different among 3 groups. The BrdU Labeling Index was also no different between Group 1 and Group 2. TNP-470 did not suppress the regeneration of the liver remnant. We consider that the systemic side effects of TNP-470 might be made minimal, because this agent affects only on endothelial cells. These results suggest that the angiogenesis inhibitor TNP-470 is beneficial to suppress hepatic recurrence after partial hepatectomy for liver metastases without suppression of liver regeneration.

Animals↗
PubMed1995

Effect of vitamin A deficiency on the integrity of hepatocytes after partial hepatectomy.

The effect of vitamin A deficiency on hepatic regeneration in male and female rats was studied after partial hepatectomy. A fourfold increase in the number of positive dUTP end-labeled nuclei was observed in the deficient animals as early as 30 minutes after partial hepatectomy and their number reached a peak by 8 hours after the operation. The bile duct cells were both morphologically and biochemically intact at all time points. Administration of retinyl palmitate 1 hour before partial hepatectomy significantly reduced the number of positive nuclei, and treatment with retinyl palmitate 24 or 48 hours before the operation reduced the number of positive cells to the level observed in control vitamin A-supplemented rats. The level of transcripts for c-jun, c-fos, c-myc, and transforming growth factor-beta 1 were increased for an extended period of time in livers of deficient animals, whereas the expression of both p53 and max were unchanged. Immunocytochemistry demonstrated the presence of latent transforming growth factor-beta 1 in cells showing evident apoptotic or necrotic changes in their nuclei. This study demonstrates the importance of vitamin A for the survival of hepatocytes both in intact vitamin A-deficient liver and after partial hepatectomy, whereas the ductal cells appear to be less sensitive to vitamin A deficiency.

Animals↗
PubMedDate not supplied

[The effect of covalently and noncovalently bound complexes of albumin with bilirubin on DNA and protein synthesis in liver and spleen of rats subjected to splenectomy and partial hepatectomy].

Noncovalently bound complexes of albumin and bilirubin were found to stimulate DNA and protein synthesis in partially hepatectomized regenerating rat liver tissue, while the covalently bound complex inhibited both these synthesis types in liver tissue after partial hepatectomy. Splenectomy of intact rats caused an induction of DNA and protein synthesis in liver tissue but partial hepatectomy decreased drastically the synthesis rate in spleen, thus suggesting that humoral factors stimulating the proliferation response in liver and spleen tissues were developed after spleen- and hepatectomies. The covalently bound albumin and bilirubin complex did not affect the rate of DNA and protein synthesis in liver tissue of splenectomized rats, while the complex with noncovalent bonds restored the rate of DNA and protein synthesis in the spleen of rats with partial hepatectomy. Only the noncovalently bound complex of albumin and bilirubin exhibited the properties inherent in hepatotropic growing factor whereas albumin administration was not effective. Possible structure and action of the noncovalently bound albumin and bilirubin complex are discussed.

Animals↗
PubMed1995

Catalase-negative peroxisomes: transient appearance in rat hepatocytes during liver regeneration after partial hepatectomy.

Using light microscopy enzyme cytochemistry to localize catalase activity in peroxisomes, a population of peroxisome-negative hepatocytes was detected in livers of rats during liver regeneration induced by two-thirds partial hepatectomy. However, examination by electron microscopy revealed that this population of hepatocytes contained peroxisomes with a delimiting membrane and a nucleoid, but no cytochemically demonstrable catalase activity within their matrix. Regenerating livers 6, 18, 24, 36, 48 and 72 hours, and 1 week after partial hepatectomy showed hepatocytes without catalase activity. However, their numbers varied, with the most numerous appearing at 24 hours after partial hepatectomy. Mitosis of catalase-negative hepatocytes were seen along with mitosis of hepatocytes containing the normal complement of catalase-positive peroxisomes. The catalase-negative hepatocytes did not show evidence of apoptosis or necrotic cell death. Lysosomal acid phosphatase activity and bile canalicular ATPase activity were present in hepatocytes with catalase-negative peroxisomes. Another population of hepatocytes with a small number of catalase-positive peroxisomes appeared and were more numerous at 36 hours after partial hepatectomy; ultrastructurally, these hepatocytes contained both catalase-negative peroxisomes, which appeared to undergo dissolution, and catalase-positive peroxisomes, which were smaller in size. After complete restoration of the liver, all hepatocytes displayed essentially uniform numbers of catalase-positive peroxisomes. These studies indicated that during liver regeneration there is a transient loss of catalase in peroxisomes of some hepatocytes. These cells proliferate and with time acquire new catalase-positive peroxisomes. The observations are discussed in relation to peroxisome biogenesis, hepatocellular carcinogenesis, and oxidative stress during liver regeneration.

Animals↗
PubMed1994

Indications for major hepatectomy in cirrhotic liver.

In an investigation of the indications for major hepatic resection of the cirrhotic liver, the records of 152 consecutive patients who had undergone a right hepatic resection between April 1985 and January 1991 were reviewed. A comparison of right hepatic lobectomy and right partial hepatectomy of the liver with no cirrhotic changes, revealed that postoperative values of serum glutamic pyruvic transaminase were significantly higher after right partial hepatectomy than after right lobectomy, despite the fact that there were no significant differences with respect to preoperative laboratory data, and there was a greater blood loss and total weight of the resected liver in patients receiving a right lobectomy as compared with those undergoing partial hepatectomy. These results suggest that in order to enable a more favorable recovery from hepatic resection, it is essential to avoid both mechanical damage and ischemic injury to the residual liver during hepatic surgery. A total of 77 patients underwent a partial hepatectomy of a cirrhotic liver, and among these patients, 16 patients had values of the indocyanine green test of less than 20%, as well as a portal pressure of less than 200 mm saline. Compared with these 16 cirrhotic patients and those patients who underwent right lobectomy, there were no significant differences with regard to the pre-operative laboratory data and portal pressure. These results therefore suggest that major hepatic lobectomy could be performed on selected patients with cirrhotic livers.

Adult↗