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[Effect of hormones and partial hepatectomy on incorporation of labeled precursor in nuclear proteins of mouse liver].

Partial hepatectomy altered the nuclear protein synthesis, most distinct for H1 histones, within 1,5-3 hrs after the operation. Laparotomy, administration of hormones and dibutyryl-cAMP did not affect the cell nuclear apparatus throughout similar to partial hepatectomy. The cell response to partial hepatectomy appears to develop involving a number of factors between which unspecific stress reactions and hormones carry out a definite role.

Animals↗

Prediction of the safe limits of hepatectomy by combined volumetric and functional measurements in patients with impaired hepatic function.

By use of computed tomography measurements, preoperative estimations of the safe limits of hepatic resection have been attempted in 38 patients with primary hepatocellular carcinoma who underwent hepatectomies of varying degrees. Twenty eight (73.7%) of these 38 patients had cirrhosis. Preoperative computed tomography estimations of volume of liver and hepatocellular carcinoma have been compared with measured volume of the resected specimens. The average differences between the estimated and actual volumes of resected liver and hepatocellular carcinoma were within 10% and 7%, respectively. To quantify the extent of hepatectomy, the "parenchymal hepatic resection rate" (formula: see text) was provided. As an indicator of functional impairment of the liver, the retention rate 15 minutes after an intravenous injection of indocyanine green dye (ICG) at 0.5 mg/kg (ICG R15) was used. A close correlation was observed between the parenchymal hepatic resection rate and ICG R15 relative to the patients' outcome, indicating their potential use in the prediction of the safe limits of hepatectomy and the probable development of posthepatectomy liver failure.

Carcinoma, Hepatocellular↗

[Electron microscopic study of the chromatin in hepatocyte nuclei in the 1st hours after a partial hepatectomy. IV. Increased sensitivity of active chromatin to EDTA exposure].

In the period of increasing the guinea-pig hepatocyte chromatin template activity, 2.5 hours after partial hepatectomy, an increased susceptibility of condensed chromatin to the bleaching action of EDTA in the Bernard reaction has been found. The condensed chromatin of the activated by partial hepatectomy guinea-pig hepatocytes, studied on ultrathin sections, is bleached under the action of EDTA more intensely compared to the chromatin of the control (non-activated) cells. Five hours after partial hepatectomy, when hepatocyte chromatin, according to its physico-chemical properties and functional activity, is the same as that of the control (non-operated) animals, its capacity of being bleached by EDTA also returns to the control level. In one nucleus studied on ultrathin sections the perinucleolar chromatin was found to be more sensitive to EDTA than the chromatin of other parts of the nucleus. It is suggested that the treatment with EDTA under given conditions can be used for revealing the functional state of chromatin on ultrathin sections.

Animals↗

Effects of partial hepatectomy on transplanted hepatocytes.

When hepatocytes are injected into the fat pads of syngeneic rats, they behave like clonogenic units and proliferate to form nodules at the site of transplantation. The probability of formation of nodules was quantitated by use of the serial dilution assay. When hepatocytes are injected into hepatectomized hosts, the probability of formation of nodules is enhanced 8-fold. There is slight decrease in the initial rate of disappearance of hepatocytes transplanted into hepatectomized hosts, but the percentage of hepatocytes that remain at the site of injection after 6 days is the same for both recipient types. Hepatectomy in the recipient animals is accompanied by a parallel increase in DNA synthesis and mitosis in the hepatocytes at the transplantation site. The probability of clone formation was found to be inversely proportional to the time between host hepatectomy and hepatocyte transplantation. The implication of these findings for the mode of action and the nature of the hepatectomy stimulus is discussed.

Adipose Tissue↗

Variations in blood ammonia and glutamine levels after hepatectomy and/or abdominal evisceration in the rat.

In order to specify the role of peripheral muscular tissue in ammonia metabolism, we studied, in rats, the variations of ammonia and glutamine levels in arterial and femoral venous blood after hepatectomy and abdominal evisceration with nephrectomy. In non-fasting rats this operation was immediately followed by an important hyperammonemia which was due to ammonia muscular release; glutamine blood levels increased only slightly without any modification in their arterio-femoral venous differences. The hyperammonemia induced by hepatectomy-evisceration was greatly reduced in animals which had been fasting for 48 hours but was not modified by a 72hrs preoperative sucrose feeding. These nutritional conditions did not change the blood glutamine variations which were first related to the abdominal evisceration. Indeed, in abdominal eviscerated rats without hepatectomy there was an important hyperglutaminemia with only a slight increase in blood ammonia. These results indicate that in rat 1) the liver plays an important part in skeletal muscle ammonia metabolism, 2) this metabolism is related to food ingestion, 3) the gastrointestinal tissue intervenes in glutamine metabolism.

Ammonia↗

Endotoxin and interleukin-1 related hepatic inflammatory response promotes liver failure after partial hepatectomy.

Impairment of various functions of the liver and concomitantly increased levels of parameters of liver damage, a clinical entity termed liver failure, is commonly seen after partial hepatectomy. We investigated in a rat model whether damage of the remnant liver was due to local inflammatory responses, and related to endotoxin or interleukin-1 (IL-1). To address this question, the effects of partial hepatectomy on infiltration of immunocompetent cells and expression of major histocompatibility complex (MHC) class II antigen of macrophages in the remnant liver was studied using immunohistochemical techniques. Specific intervention with recombinant N-terminal bactericidal/permeability-increasing protein (rBPI23) to neutralize endotoxin and with IL-1 receptor antagonist (IL-1ra) to block IL-1 activity was used to examine the respective roles of endotoxin and IL-1. After partial hepatectomy, we found an influx of neutrophils, an increased expression of MHC class II antigens, and morphologic changes of Kupffer cells consistent with activation. These inflammatory events coincided with increased serum levels of markers of liver damage (aspartate aminotransferase, alanine aminotransferase, ammonia). Both neutralization of endotoxin and blocking of IL-1 activity reduced hepatic inflammation and reduced serum levels of aminotransferases and ammonia. In addition, liver cell proliferation as assessed by staining for proliferating cell nuclear antigen (PCNA) expression was significantly enhanced when either endotoxin or IL-1 effects were blocked. Thus, our results suggest that local hepatic inflammatory responses inhibit liver cell proliferation and promote liver failure, presumably by affecting the functional capacity of the remnant liver.

Animals↗

[Influence of enteral nutrition on hepatic regeneration and small intestinal epithelium after hepatectomy in rat-comparative assessment with TPN].

The influence of enteral nutrition on hepatic regeneration and small intestinal mucosa was examined after 70% hepatectomy in rats. The rats were divided into two groups, enteral nutrition group (EN group) and total parenteral nutrition group (TPN group). The study was carried out for 3 days (72 hours) after hepatectomy. Both groups were received almost the same energy. Rats were sacrificed at 72 hours later. Hepatic regeneration rate, nutritional parameters, small intestinal mucosa, and BrdU labelling index (LI) were compared. The hepatic regeneration rate of each group was as follows: TPN; 95.0%, EN; 99.3%. The hepatic protein content of each liver: TPN; 166.88 mg/g, EN; 175.9 mg/g. EN group was better nutritional condition than TPN group 3 days after hepatectomy. The status of small intestinal mucosa was microscopically observed in each group. EN group was also better than TPN group. BrdU LI of hepatic cell was a measured at 24 hours after and 72 hours after. LI of EN group decreased faster than that of TPN group, and it was considered that hepatic regeneration had been achieved faster by EN than TPN. The observation indicates that EN is effective for hepatic regeneration.

Animals↗

Alteration in levels of human hepatocyte growth factor following hepatectomy.

BACKGROUND: The clinical significance of changes in serum human hepatocyte growth factor (hHGF) in patients having hepatectomy remains unclear, partly because of various perioperative factors, such as underlying diseases and surgical procedures. STUDY DESIGN: Human hepatocyte growth factor was measured preoperatively and then on postoperative days 1, 3, 5, and 7. In 49 (79 percent) of 62 patients studied, serum hHGF increased postoperatively and peaked on postoperative day 1 or 3 (group 1), while in the other 13 patients (21 percent), it decreased on postoperative day 1 (group 2). RESULTS: The preoperative clinical parameters were comparable between the two groups except for indocyanine green retention rate at 15 minutes (16.6 compared with 23.4 percent; p < 0.05). Operative stress and histology of the nontumorous portion of the liver were also comparable between the two groups. Postoperatively, alanine aminotransferase was significantly higher in group 1 than in group 2 on postoperative days 1 and 3. Regeneration of the remnant liver one month after hepatectomy was significantly higher in group 1 than in group 2 (5 +/- 9 percent compared with -6 +/- 8 percent; p < 0.01). The incidence of postoperative hepatic failure was significantly higher in group 2 than in group 1 (15 compared with zero percent; p < 0.05). CONCLUSIONS: These observations led to the thesis that changes in serum hHGF levels after hepatectomy are an indicator of hepatic regeneration and also will serve as one factor to predict postoperative hepatic failure.

Adult↗

[Serum marker of the functional hepatic mass after extensive hepatectomy. The branched/aromatic amino acid ratio. Experimental and clinical studies].

During severe hepatic insufficiency, serum amino acid profile is modified with an increase of aromatic amino acids (AAA) (Tyrosine and Phenylalanine) and methionine concentrations and a decreased value of 3 branched chain amino acids (BCAA) (leucine, isoleucine and valine). These observations have been confirmed after hepatic surgery in experimental and clinical studies. In experimental models, after 10, 32, 68, 77 or 90% hepatectomy in Wistar rats, the BCAA/AAA ratio (R) is correlated with the extent of hepatectomy: r = 0.74, p < 0.001; with the post-operative interval time (8, 24, 32, 48, 168 or 240 hours): r = 0.60, p < 0.001 and with the liver weight when animals are sacrificed: r = 0.64, p < 0.001. In clinical studies, 26 patients have undergone 60 to 80% hepatectomy for primary or secondary tumors of the liver and R is determined on the immediate post-operative day and every day during the first post-operative week. Liver regeneration is followed by single photon emission computerized tomoscintigraphy on days 0, 7 and 30 with assessment of hepatic growth index (HGI) estimated by the ratio: liver mass on day 7 or 30/remnant liver mass on day 0. On post-operative day 7, R is 1.61 +/- 0.3 (normal: 3.5 +/- 0.51). Mean liver volume is 60 +/- 11% and HGI is 1.9 +/- 0.3. On this day, a correlation is found between R and HGI (r = 0.76). On post-operative day 30, HGI is 2.34 +/- 0.50, mean liver volume is 89.6 +/- 0.9% and R is 2.02 +/- 0.65.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

Changes in IL-6 and IL-8 after hepatectomy in patients with liver cirrhosis.

Changes in tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and interleukin-8 (IL-8) were investigated before and after hepatectomy in patients with or without liver cirrhosis (5 cases without liver cirrhosis and 14 cases with liver cirrhosis). Both the IL-6 and IL-8 values of the cirrhotic patients were significantly higher on the first postoperative day (POD) as compared with the non-cirrhotic patients. Overall, no significant correlation was found between peak values of IL-6 or IL-8 and blood loss or operating time. In the case of the cirrhotic patients, correlation of both IL-6 and IL-8 with operating time was significant at p < 0.05, gamma = 0.534 and 0.586, respectively. No correlation was found between blood loss and the peak value of IL-6, but significant correlation (gamma = 0.647, p < 0.05) was found between them in cirrhotic patients. There was no consistent increase in TNF-alpha and IL-1 beta following hepatectomy. These findings indicate that procedures undertaken to reduce the excessive production of these cytokines may be useful for preventing complications after hepatectomy in cirrhotic patients.

Carcinoma, Hepatocellular↗

[Ribonuclease activity following partial hepatectomy in the liver of healthy and alloxan diabetic rats and histological findings in the islets of Langerhans (author's transl)].

QUESTION: What changes in the level of ribonuclease activity (RNase activity) can be observed in the regenerating liver of healthy and alloxan diabetic rats following partial hepatectomy? What coincidental alterations of the ratio A-cells to B-cells do occur in the islets of Langerhans? MATERIALS AND METHODS: 120 male Wistar rats of averagely 180 g body weight were fed a standard diet ("Rehbrücke") with drinking water ad libitum. After deprivation of food for 15 hours the animals were sacrificed by heart puncture under ether anesthesia. The caudal part of the body was rinsed free from blood by ice-cooled physiological saline via the aorta. After removal of the livers each 2 g of liver tissue were homogenized in 0.25 M saccharose or 70% ethyl alcohol. For the study of impairment of ribonuclease activity in the liver following different lesions the animals were divided into 3 test groups of 35 animals each: group 1: alloxan diabetes; group 2: liver regeneration after partial hepatectomy; group 3: alloxan diabetes in combination with liver regeneration after partial hepatectomy. From each group always 4 to 6 animals were sacrificed at the following time intervals: 2nd day and 4th day as well as after 3, 4 and 6 weeks. In 8 animals the enzymatic activity was not influenced. RNA content and dry weight of the livers of all test animals were determined. In liver homogenates with saccharose the ribonuclease activity was measured according to the method of FIERS (1961) using highly purified yeast RNA for substrate. This technique is especially suitable for raw tissue homogenates. After 30 min incubation at 37 degrees C and precipitation of the high-molecular polynucleotides as well as of protein by means of methylglycol and barium perchlorate the not precipitable low-molecular oligonucleotides which were produced by ribonuclease action, were spectrophotometrically measured in the supernatant at 260 nm. The deltaE-value was calculated for the employed quantity of RNA related to mg of protein brought into action. Demonstration and determination of the ribonuclease inhibitor was abandoned. Two different RNA substrate concentrations were used; in the higher concentration the activity was measured at pH 5.5 to 6 and 7.5, in the lower concentrations at pH 7. Protein measurement was performed after the method of LOWREY (LOWREY et al. 1951) as modified by GLASER and KLEINE (1962); blood sugar was determined in tail vein blood by means of o-toluidine technique. In the liver homogenate with ethyl alcohol the RNA extraction was modified according to the data given by OGUR and ROSEN (1950); RNA determination was done colorimetrically using orcin hydrochloric acid. For dry weight determination the same homogenate was used. Alloxan diabetes was induced by injecting the rats 175 mg/kg b.w. of alloxan after fasting for 24 hours. The 5% alloxan solution in citrate buffer (pH = 4) was prepared immediately before injection. For further experimentation only those animals with blood sugar values of greater than 300 mg/100 ml were employed...

Animals↗

Early pregnancy factor in liver regeneration after partial hepatectomy in rats: relationship with chaperonin 10.

Early pregnancy factor is not only a product of dividing embryonic and neoplastic cells, as demonstrated previously, but also of normal proliferating cells. Eight hours after partial hepatectomy in rats, early pregnancy factor was detected in serum. It rose to a peak by 48 hr. Neutralization of early pregnancy factor in vivo by passive immunization with specific antibodies, 18 hr after partial hepatectomy, resulted in a significant decrease in the uptake of [3H]thymidine by the liver remnant, measured 4 to 6 hr later. These results suggest that during liver regeneration, early pregnancy factor is essential to the sequence of events that culminates in DNA synthesis and cell division. Recently we purified early pregnancy factor from human platelets and determined by mass spectrometry a precise molecular mass of 10,843 Da. Amino acid sequencing (approximately 72% of the molecule) demonstrated that early pregnancy factor is highly homologous with chaperonin 10, a stress-inducible mitochondrial protein, and that platelet-derived early pregnancy factor and rat chaperonin 10 share similar biochemical and immunological properties. In this study we show that early pregnancy factor, purified from regenerating rat liver and from serum taken 24 hr after hepatectomy, shares these properties. In addition, antibodies to early pregnancy factor, effective in passive immunization studies, recognize chaperonin 10, whereas chaperonin 10 antibodies bind to early pregnancy factor from regenerating liver and posthepatectomy serum. We propose that early pregnancy factor/chaperonin 10 is selectively released from proliferating cells and, in an autocrine or paracrine mode (or both) is involved in DNA synthesis.

Adsorption↗

Internal biliary drainage, unlike external drainage, does not suppress the regeneration of cholestatic rat liver after partial hepatectomy.

We previously showed that hepatic cells proliferate in obstructive jaundice alone without partial hepatectomy and found that external biliary drainage for obstructive jaundice markedly suppresses liver regeneration after partial hepatectomy. In this study, we produced a model system for internal biliary drainage in which bile was drained into the stomach of rat fed a liquid diet. The regeneration capacity of the liver was assessed on the basis of the induction of DNA polymerase-alpha activity, as well as the mitotic index of hepatic cells. A remarkable difference was observed in the regeneration capacities of cholestatic livers between two groups--one in which jaundice was released by the internal and one by external biliary drainage before hepatectomy. After 5 days of internal biliary drainage, the regeneration capacity remained at a level comparable to that of sham-operated control rats, in sharp contrast to the impaired regeneration after external biliary drainage. These results clearly indicate that internal biliary drainage is preferable for release of biliary obstruction before partial resection of cholestatic liver.

Animals↗

Prevention of pleural effusion after hepatectomy using fibrin sealant.

Retention of pleural effusion after hepatectomy is an important complication that may affect the postoperative course. However, there are few reports on its pathogenesis or preventive measures. We evaluated the mechanism of the development of this complication and preventive measures against it. During the past 4-year period, hepatectomy was performed in 77 patients, of whom 64 underwent liver mobilization by transecting the hepatic ligaments. A fibrin sealant was sprayed on the cut surface of the hepatic ligaments in randomly selected 25 of the 64 patients to determine whether this application can prevent postoperative retention of pleural effusion. Post-operative pleural effusion was not observed in any patient treated by fibrin sealant spraying but was observed in 13 (30%) of the other 39 patients treated with this sealant (p < 0.05). In addition, none of the 23 patients in whom the liver was not mobilized during hepatectomy showed postoperative pleural effusion. These results suggest that severance of the hepatic ligaments is a major cause of pleural effusion, and application of a fibrin sealant to the undersurface of the diaphragm around the insertion of the liver ligaments is useful for preventing this complication.

Drainage↗

Depolymerization of hepatocellular microtubules after partial hepatectomy.

Asialoglycoproteins (ASG) are internalized by hepatocytes by ASG receptor (ASGR)-mediated endocytosis. We have shown previously that when a plasmid DNA, pAlb(9-12)CAT (expressing chloramphenicol acetyltransferase driven by an albumin promoter enhancer), was complexed with an ASG-polylysine conjugate and injected intravenously in rats, 80% of the DNA was internalized by the liver. In normal recipient rats, over 95% of the internalized DNA was degraded in 4 h; the plasmid was undetectable after 48 h. In contrast, when 66% hepatectomy was performed 20 min after DNA administration, the internalized DNA persisted for several weeks in cytoplasmic vesicles (Chowdhury, N. R., Wu, C. H., Wu, B. Y., Yerneni, P. C., Bommineni, V. R., and Chowdhury, J. R. (1993) J. Biol. Chem. 268, 11265-11271). Since microtubules are required for the translocation of ligand-containing endosomes to lysosomes, the site of ligand degradation, we hypothesized that persistence of the endocytosed DNA might be related to changes in microtubular structure and function. To test this hypothesis, we examined hepatocellular microtubules by immunofluorescence confocal microscopy. Liver from untreated rats or sham-operated controls showed a network of fibrillar microtubules throughout the cytoplasm. The extent of the microtubular network was substantially reduced 3-6 h after 66% hepatectomy. By 24 h, microtubules had regenerated. Intraportal infusion of cycloheximide (250 mg/kg body weight) 15 min before 66% hepatectomy, prevented microtubular disruption, indicating that protein synthesis is required for this process. Immunotransblot analysis showed that hepatic alpha-tubulin concentration remained unchanged through microtubular disassembly and subsequent reassembly, which is consistent with conservation and reutilization of tubulin released by depolymerization of microtubules.

Animals↗

Radiation hepatology of the rat: the effects of the proliferation stimulus induced by subtotal hepatectomy.

The effect of an 80 to 90% hepatectomy in stimulating proliferation immediately after irradiation of the liver was studied. A dose of 15 Gy was not lethal for animals with intact livers, but all animals with subtotal hepatectomies exposed to this dose died from apparent liver failure 28 to 60 days after exposure. To elucidate the mechanism for this mortality, plasma aspartate aminotransferase, retention of intravenous injected rose bengal, liver weight and liver hydroxyproline content were measured 0 to 90 days after 15 Gy irradiation of the liver to determine temporal changes in necrosis, function, mass and fibrosis, respectively, in animals with either intact livers or livers with subtotal resection. Irradiation of the liver had no significant effect on these parameters in animals with intact livers. In subtotally hepatectomized animals the same radiation dose that suppressed liver mass restoration significantly increased hepatocyte necrosis within 7 days, which was followed by increased liver hydroxyproline concentration and hepatic dysfunction. This radiation-induced temporal change in hepatic dysfunction correlated with increased concentration of hydroxyproline but not with liver mass, indicating that liver fibrosis was the cause of hepatic dysfunction. Since similar sequelae are produced in intact livers after higher doses and longer intervals after irradiation, the proliferation stimulus induced by partial hepatectomy must accelerate the expression of damage and lower the radiation tolerance of the liver. However, in subtotally hepatectomized animals radiation-induced hepatocyte necrosis precedes fibrosis, whereas the reverse is normally true for animals with intact livers.

Animals↗

[The significance of portal infusion chemotherapy for prevention of recurrence in residual liver after hepatectomy for metastases from colorectal cancer].

We performed portal infusion chemotherapy using a reservoir for prevention of recurrence in residual liver after hepatectomy for metastases from colo-rectal cancer. To study the usefulness of portal infusion chemotherapy, the period from hepatectomy to recurrence in residual liver was investigated by three treatment groups for H2 cases; (a) a group of systemic chemotherapy, (b) a group of arterial infusion chemotherapy and (c) a portal infusion chemotherapy group. Treatment in (a) group was for 204 +/- 98.2 days (n = 6), in (b) group for 343.0 +/- 238.3 days (n = 8) and in (c) group for 961.0 +/- 1,172.4 days (n = 5). There was no statistically significant difference in the three groups, but (c) group had a better result in recurrence in residual liver. As for prevention of recurrence in residual liver after re-hepatectomy, there was no significant difference in the three groups, but (c) group had the longest survival.

Aged↗

[Long-term results of irregular hepatectomy for primary liver cancer at the right lobe].

From 1964 to 1990, 228 cases with primary liver cancer at the right lobe underwent irregular hepatectomy in our hospital. Of them, 47 were asymptomatic. Alpha feto-protein (AFP) was positive in 162 (71%) and 195 patients were associated with liver cirrhosis (85.6%). In 60 cases, the tumor size was less than 5cm in diameter. During operation, the following methods were used for interruption of hepatic blood flow: temporary blockage of the hepatic hilum in 117 cases, microwave coagulation of hepatic parenchyma in 77 cases, continuous mattress sutures in 29 cases, hepatic clamp in 3 cases and other methods in 2 cases. One segment resection was done in 116 patients, two segments in 67, three segments in 28 and four segments in 17. One hundred and fifty-five patients underwent radical resection and 73 patients underwent palliative resection. The operative mortality was 2.6%. The 3- and 5- year survival rates of the patients so treated were 48.3% and 38.8%, respectively. The 3- and 5- year survival rates of the patients with small tumor ( < 5cm in diameter) after hepatectomy were 59.9% and 53.3%, respectively. The medvan survival time after palliative hepatectomy was 15.7 months.

Adult↗