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PubMed1995

Randomized study of chemoembolization as an adjuvant therapy for primary liver carcinoma after hepatectomy.

From April 1990 to December 1993, 140 patients were recruited to a randomized study to evaluate transcatheter hepatic arterial chemoembolization (TACE) as an adjuvant therapy for primary liver carcinoma after hepatectomy. This study investigated the principle, techniques and results of TACE. The results showed that the intrahepatic recurrence rate was 48.9% in the patients who underwent radical resection only, but only 21.3% in the patients who also underwent TACE 3-4 weeks after hepatectomy (P < 0.01). The 1-, 2-, 3-, and 4-year survival rates were 72.3%, 52.7%, 35.1%, and 35.1% respectively for the patients who underwent radical resection only, and were 97.9%, 85.5%, 69.5%, and 56.9% for the patients who also underwent TACE 3-4 weeks after radical resection (P < 0.001). The 1-, 2-, 3-, and 4-year survival rates were 38.9%, 0%, 0%, and 0% for the patients who underwent palliative resection only, and were 68.3%, 32.3%, 21.5%, and 21.5% respectively for the patients undergoing TACE 3-4 weeks after palliative hepatectomy (P < 0.001).

Adult↗
PubMed1991

Prolactin-provoked alterations of cytosolic, membrane, and nuclear protein kinase C following partial hepatectomy.

The adenohypophyseal polypeptide hormone prolactin is a potent liver mitogen, stimulating cell cycle progression, an effect that appears coupled to increasing protein kinase C activity in membrane and nuclear fractions. Here, we examine whether hepatocyte proliferation, stimulated by partial hepatectomy, is associated with altered serum prolactin or protein kinase C activation. Within 5-15 min of liver resection, serum prolactin concentrations elevate significantly. Protein kinase C activity in hepatic cytosol decreases significantly, and membrane and nuclear PKC activity increase by 30 min. Hypophysectomy prior to partial hepatectomy abrogates any effect of liver resection on protein kinase C activation in the hepatic remnant. Based upon these data, it is suggested that the rapid increase in serum prolactin seen after partial hepatectomy may be linked to protein kinase C activation, which in turn stimulates the hepatic proliferative response that is essential for hepatic regeneration.

Animals↗
PubMed1992

Effect of total hepatectomy on coagulation and glucose homeostasis in the pig.

It has been suggested recently that patients with fulminant liver failure should be prepared for transplantation by early hepatectomy, yet the acute effects of removal of the liver upon the coagulation profile and certain hormones are not known. This study was conducted on totally hepatectomized pigs that survived up to 27 hr. Measurements were made of serum insulin, plasma glucagon (IRG and GLI), glucose, catecholamines, and the coagulation profile. The increase in serum insulin was directly related to levels of plasma glucose--there was a 100-fold increase in animals with plasma glucose levels greater than 400 mg/100 ml and none when blood glucose was less than 100 mg/100 ml. Plasma glucagon showed a sharp transient increase within 1 hr of hepatectomy and a slow rise thereafter with levels apparently unrelated to serum insulin or plasma glucose. There was a transient increase in plasma adrenaline but a sharp continuous increase in plasma norepinephrine. No changes of note occurred in the coagulation profile--even levels of fibrinogen only declined by 20% in 27 hr. The study has shown that early total hepatectomy is safe as far as changes in coagulation are concerned but changes in serum insulin and especially plasma norepinephrine may be of more significance.

Animals↗
PubMed1994

Endotoxin-induced liver injury after extended hepatectomy and the role of Kupffer cells in the rat.

Liver injury by endotoxin given during regeneration following a 70% hepatectomy was examined in Wistar rats. The intravenous administration of endotoxin caused an elevation of the serum GPT level, and severe damage of the remnant liver showing centrilobular necrosis with microthrombi. The highest mortality was induced by the administration of endotoxin to rats 24 h after hepatectomy. Kupffer cells in the regenerative phase of the liver showed an augmented in vitro production of both tumor necrosis factor (TNF) and interleukin-1 (IL-1). The simultaneous administration of heparin and prostagladin E1 (PGE1), which is known to suppress the production of TNF and IL-1, reduced the magnitude of liver injury and the mortality of these rats. The absence of any direct cytotoxic effect of TNF and IL-1 against liver cells suggested that the cytokines, produced by Kupffer cells, play an important but indirect role in the remnant liver injury induced by endotoxin after hepatectomy.

Animals↗
PubMed1989

Estradiol and testosterone levels in patients undergoing partial hepatectomy. A possible signal for hepatic regeneration?

In five adult male patients undergoing a 40-60% partial hepatectomy, serum sex hormone levels before and after hepatic resection were determined. Blood was drawn immediately prior to each surgical procedure and at specified time points postoperatively. Compared to hormone levels found prior to surgery, following major hepatic resection, estradiol levels increase at 24 and 48 hr, while testosterone levels decline, being significantly reduced at 96 and 144 hr. These data demonstrate that adult males who undergo a 40-60% partial hepatectomy experience alterations in their sex hormone levels similar to those observed in male rats following a 70% hepatectomy. These changes in sex hormone levels have been associated in animals with an alteration of the sex hormone receptor status of the liver that is thought to participate in the initiation of the regenerative response. These studies suggest, but do not prove, that in man, as in the case of the rat, sex hormones may participate in the initiation of or at least modulate in part the regenerative response that occurs following a major hepatic resection.

Adult↗
PubMed1996

Pathophysiological effect of hepatic ischemia and reperfusion after hepatectomy in dogs with obstructive jaundice, focusing on the effect of coenzyme Q10 and styrene-co-maleic acid superoxide dismutase.

The purpose of the present study was to elucidate the effect of hepatic reflow following ischemia on the remnant liver after hepatectomy with occluded hepatic blood inflow in dogs with obstructive jaundice. When 40% hepatectomy was performed with 10-min occlusion of hepatic blood inflow in dogs with obstructive jaundice, the lipid peroxide content in the remnant liver increased significantly, together with a reduction in superoxide dismutase (SOD)-like activity. The levels of endotoxin and beta-N-acetyl hexosaminase (NAH) in peripheral blood also increased. The phagocytic index increased transiently after 30 min, followed by a marked decrease after 3h. Histologically, degeneration and necrosis of the hepatic parenchymal cells were demonstrated, and survival rate at 7 days was only 23.1%. With the administration of coenzyme Q10 (CoQ10) or styrene-co-maleic acid SOD (SM-SOD), these phenomena were significantly inhibited, and the survival rate improved. After hepatectomy, Kupffer cells in the remnant liver were activated by increased endotoxin levels in the portal vein, inducing the production of free radicals, which, in turn, damaged the Kupffer cells by reducing endotoxin clearance. Finally, the impaired functional reserve in the remnant liver provoked liver failure. The administration of CoQ10 or SM-SOD prevented the occurrence of these phenomena triggered by the free radicals generated by Kupffer cells, stimulated by endotoxin in the portal vein.

Animals↗
PubMed1996

Identification of homeobox genes expressed during the process of rat liver regeneration after partial hepatectomy.

Homeobox (HBox) genes are well-known to be involved in development and differentiation. To ascertain a role of HBox genes in the process of liver regeneration, we identified HBox genes expressed at various times after partial hepatectomy in rats (at 0 hr, 1 hr, 2 days, and 4 days) by using reverse transcription-polymerase chain reaction (RT-PCR), cloning, and sequencing techniques. By the competitive RT-PCR method using generic primers, expression levels of HBox genes in regenerating livers were estimated at as low as only 0.4-2% of that in 14-day embryonic liver; however, we identified multiple HBox genes at different stages. Comparing sets of HBox genes identified at different stages, we could find two candidates of stage specifically expressed HBox genes (one rat caudal-related gene, RCdx-3, stimulated at 1 hr, and one rat Hox gene, RHoxB5, repressed after hepatectomy) and continuous expression of five Hox genes (RHoxA1, A4, A5, B2, and B3) before and after hepatectomy. These HBox genes are considered to correlate with the process of liver regeneration.

Amino Acid Sequence↗
PubMed1989

The influence of liver dysfunction on cyclosporine pharmacokinetics--a comparison between 70 per cent hepatectomy and complete bile duct ligation in dogs.

The influence of experimentally induced hepatic dysfunction on the pharmacokinetics of Cyclosporine A (CsA) was determined in dogs. The pharmacokinetics of oral (PO) and intravenous (IV) CsA were studied before and after 70 per cent hepatectomy or complete bile duct ligation (CBDL). Changes in liver function were monitored by serial measurements of serum bilirubin, and by the maximum removal rate (Rmax) and plasma disappearance rate (ICG-K) of indocyanine green (ICG). Concentrations of CsA in whole blood were measured by HPLC. Seventy per cent hepatectomy caused significant liver dysfunction: the ICG-Rmax decreased by 47.7 +/- 7.1 per cent (mean +/- SD) and the ICG-K decreased by 61.3 +/- 9.7 per cent during the first week after hepatectomy. At the same time, the systemic clearance (CLs) of IV-CsA decreased by 43.9 +/- 8.2 per cent, the area under the concentration curve (AUC) of IV-CsA increased by 35.4 +/- 20.8 per cent and the bioavailability of CsA decreased by 26.4 +/- 14.8 per cent. CBDL also induced significant liver dysfunction: the ICG-Rmax decreased by 39.1 +/- 12.8 per cent and the ICG-K decreased by 65.6 +/- 3.6 per cent in the second week after the operation. During the same period, the AUC of PO-CsA decreased by 69.9 +/- 10.7 per cent and the bioavailability of CsA also decreased markedly by 73.9 +/- 15.6 per cent. These data indicate that hepatic impairment significantly influences the pharmacokinetics of CsA, not only by the changes in intestinal absorption, but also by those in hepatic metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Absence of mitochondrial enhancement in the remnant liver after partial hepatectomy in cirrhotic rats.

Changes in energy metabolism after 70% partial hepatectomy were investigated in normal and carbon-tetrachloride-(CCl4)-induced-cirrhotic rats by evaluating hepatic mitochondrial ATP synthesizing activity as well as liver tissue levels of adenine nucleotides and lipid peroxide. Preoperative concentrations of ATP and total adenine nucleotides (TAN: ATP + ADP + AMP) in mumol/g dry weight (dw) and the energy charge potential (ECP) in the cirrhotic livers were 8.53 SEM 0.25, 14.73 SEM 0.54, and 0.74 SEM 0.01, respectively, and were significantly lower than those of normal livers (12.04 SEM 0.34, 15.75 SEM 0.12, and 0.86 SEM 0.01, P less than 0.01 in TAN). There was no difference in the preoperative mitochondrial phosphorylation rate (PR = x 10(-10) mol ATP/sec per mg mitochondrial protein) between normal and cirrhotic livers (21.01 SEM 0.95 and 21.55 SEM 1.03, respectively). After hepatectomy, in the normal livers these values decreased slightly after 12 h, remained low until 48 h, and returned to the preoperative value at 72 h. PR was remarkably enhanced and reached the maximum level of 32.54 SEM 2.07 at 24 h (P less than 0.001, compared to the sham-operated rats) and gradually returned to the preoperative value at 72 h. In the cirrhotic livers, ATP and ECP levels were drastically decreased at 12 h and recovered to the preoperative levels within 24 h, while TAN level remained unchanged. Enhancement of PR was not observed in any of the cirrhotic livers during the experiment. Lipid peroxidation was transiently increased postoperatively with no difference between normal and cirrhotic livers both in the sham-operated and the hepatectomized rats. These findings suggest that the energy status was more depressed in the cirrhotic livers than in normal livers both before and after hepatectomy. This depressed energy status might be attributed to the low preoperative tissue levels of adenine nucleotides and ECP level in the cirrhotic livers as well as to the absence of the enhancement of PR in the remnant livers.

Adenine Nucleotides↗
PubMed1994

Kupffer cell function in chronic liver injury and after partial hepatectomy.

The reticuloendothelial system (RES) plays an important role in the biological defense system. In the liver, Kupffer cells are the main constituent of the RES, and when their function is impaired postoperative complications may more often occur. By using 99mTc-labeled human serum albumin millimicrospheres (99mTc-HSA-MM) combined with assessment of single photon emission computed tomography (SPECT), we have attempted to determine the function of Kupffer cells independently of the hepatic blood flow. First, Kupffer cell function in rats with chronic liver injury caused by CCl4 was studied. The hepatic uptake rate in chronic liver injury was decreased, and a reduced phagocytic activity of the Kupffer cells was noted. The parameter concerning Kupffer cell degradation, the excretion rate (k), was markedly decreased in the early period of chronic liver injury. Changes in Kupffer cell function after 30% and 70% hepatectomy were also studied. After 30% hepatectomy, the excretion rate was decreased on the first postoperative day (POD), and it was increased beyond that found after sham operation on the 3rd POD. In contrast, slower recovery of uptake rate was demonstrated. After 70% hepatectomy, both uptake and excretion rates were markedly reduced, and recovery was prolonged beyond the 5th POD. The hepatic uptake was not parallel with the excretion rate in either experiment. These results suggest that the method that measures the hepatic excretion rate may provide a better assessment of Kupffer cell function than the current uptake measurement with radiolabeled colloid.

Animals↗
PubMed1995

Significance of aminopyrine breath test as a parameter of hepatic functional reserve in 40% partial hepatectomy of rats with CCl4-induced liver injury.

Rats with CCl4-induced liver injury underwent partial (40%) hepatectomy. The [14C]aminopyrine breath test (ABT) values in rats with CCl4-induced liver injury were reduced by 34% compared with those in rats with normal liver. Preoperative ABT values clearly discriminated between survivors and those that died following 40% partial hepatectomy in rats CCl4-induced liver injury (P < 0.05). Hepatic protein synthesis was remarkably enhanced in CCl4-induced liver injury compared with normal liver (P < 0.001), and this was inversely correlated with ABT values (P < 0.001). These data show that the enhanced hepatic protein synthesis could induce a decrease of hepatic functional reserve. ABT seems to be a useful preoperative test for predicting surgical mortality following hepatectomy.

Alanine Transaminase↗
PubMed1996

Lipid peroxidation and antioxidant activities in regenerating liver after partial hepatectomy in splenectomized rats.

Lipid peroxidation, antioxidant activities, and total fatty acids were investigated in the regenerating liver after partial hepatectomy in splenectomized male Wistar rats. The lipoperoxide levels were significantly lower in the splenectomized rats than in the non-splenectomized rats. The hepatic superoxide dismutase (SOD) activity was significantly higher in the splenectomized rats than in the controls, whereas the alpha-tocopherol content, and the activities of glutathione (GSH) peroxidase and catalase did not differ so widely between splenectomized and nonsplenectomized rats. In both groups, the fatty acid composition of the total lipids was not so different in the early stages of hepatic regeneration after partial hepatectomy, but it was noted that in the later stages of hepatic regeneration, polyunsaturated fatty acids tended to increase in the splenectomized rats. These results suggest that splenectomy attenuates lipid peroxidation, and tends to increase in polyunsaturated fatty acids in the remnant liver after partial hepatectomy, which may be attributable to high SOD activity, the maintenance of alpha-tocopherol, and the remaining activities of GSH peroxidase and catalase.

Animals↗
PubMed1996

Reduction of hepatic acute phase response after partial hepatectomy in elderly patients.

The hepatic capacity for acute phase protein synthesis after partial hepatectomy in the elderly patients was prospectively studied. Forty-one patients who consecutively underwent a partial hepatectomy were grouped according to age of greater or less than 70 years; 12 were in the older group and 29 in the younger. The changes in the levels of serum interleukin-6, alpha 1-antitrypsin, alpha 1-acid glycoprotein, haptoglobin, and plasma fibrinogen were measured after surgery. The postoperative changes in standard liver function tests were also measured. The incidence of postoperative infected complications was 25% in the older group and 7% in the younger (P = 0.28). Although postoperative levels of serum interleukin-6 were similar between the two groups, those of serum alpha 1-antitrypsin, alpha 1-acid glycoprotein, and haptoglobin were significantly lower in the elderly (P < 0.05). Postoperative levels of serum alpha 1-antitrypsin and plasma fibrinogen showed an increase of about 30% compared with the preoperative values (P < 0.05) in the younger group, but no significant increase in the older. Postoperative deterioration of serum albumin levels and hepaplastin test values was also significantly more severe in the older group (P < 0.05). We conclude that in the older patients, a reduction of acute phase protein synthesis occurs after partial hepatectomy as a result of a global deterioration of liver function, and may render patients liable to infection.

Acute-Phase Proteins↗
PubMed1979

Inhibited autophagic degradation of cytoplasm during compensatory growth of liver cells after partial hepatectomy.

The livers from 56 sham-operated and 56 partially hepatectomized male albino rats killed 4--81 h after operation were investigated by electron microscopic morphometry. Following partial hepatectomy, the principal changes in volume fractions in the hepatocellular cytoplasm were: decrease of glycogen and, to a lesser extent, of mitochondria together with considerable increase of fat droplets. The volume fraction of microbodies (= peroxisomes) showed no significant difference between control and regenerating liver. By evaluating large test fields of about 40,000 micrometers 2 sectioned cytoplasm per animal it could be demonstrated that the volume fraction and the numerical density of autophagic vacuoles (AV's) were significantly reduced after partial hepatectomy. The extent of this reduction depended on the postoperative time interval. AV's were reduced by 75% at day 0 (4--17 h p.o.), by 98% at day I (19--33 h p-o.), by 75% at day II (43--57 h p.o.), and still by 50% at day III (67--81 h p.o.). The different types of AV's, defined on the basis of the different cytoplasmic components enclosed, were reduced to similar extent during the respective time periods. The reduction of AV's seems to be specific for the regenerating organ since no significant differences in the volume fraction of AV's could be found in the proximal tubular cells of the kidney of partially hepatectomized animals when compared with those of sham-operated controls. The inhibition of intracellular autophagic degradation in regenerating liver has its biochemical equivalent, i.e. inhibited protein catabolism, and is interpreted as an important and adequate mechanism in effecting the shift from the physiological steady state between anabolism and catabolism to the positive balance which is required for the compensatory growth of the liver after partial hepatectomy.

Animals↗
PubMed1984

Suppression and acceleration of DNA synthesis in megakaryocytes after partial hepatectomy.

3H-thymidine labelling indices of megakaryocytes were determined in the spleen and bone marrow of normal, sham-operated and partially hepatectomized rats. Compared with controls, the labelling indices were much lower in megakaryocytes but much higher in other cells such as erythroid cells or proliferating duodenal mucosal cells when measured in rats from 12 to 36 h after partial hepatectomy. From 48 to 72 h after hepatectomy the labelling indices of megakaryocytes became higher than control values. On the other hand the labelling indices of megakaryocytes from 12 to 36 h after sham operation were higher than controls. The accelerated DNA synthesis of megakaryocytes after sham operation was considered to reflect the additional DNA synthesis in this cell line which leads to an increase of the average ploidy level. The initial decrease in labelling indices of megakaryocytes after partial hepatectomy did not occur if serum from normal or thrombocytopenic rats was injected. These findings suggest that the liver may produce a humoral factor which influences the so-called endomitosis of megakaryocytes.

Animals↗
PubMedDate not supplied

Effects of total parenteral nutrition enriched with branched chain amino acid infusion on liver function and serum amino acid pattern in dogs undergoing hepatectomy.

In order to study effects of different total parenteral nutritional regimens on the recovery of liver function and on plasma amino acid pattern after major hepatectomy, twelve healthy mongrel dogs were submitted to 70% liver resection and randomly divided into three different groups: group I (control group) received only 10% glucose; group II received 10% glucose plus 8.5% Freamine; group III received 10% glucose plus 100% branched chain amino acid (BCAA) solution. Blood samples were analyzed for determining biochemical parameters, including plasma amino acid levels, before surgery and on 3rd and 7th postoperative day. The 'BCAA group', compared to other groups, showed higher values of plasma proteins (p less than 0.01) and prothrombin activity (p less than 0.05) on the 3rd postoperative day. The total concentration of plasma amino acids decreased after hepatectomy. Gluconeogenetic amino acids alanine and glutamine were markedly decreased in groups II and III, likely due to their increased consumption during gluconeogenesis. Aromatic amino acids were increased in all groups, due to the transient liver insufficiency. BCAA markedly increased in group III on 3rd postoperative day and returned to basal values on 7th postoperative day; possible explanations of such alterations are discussed. Our findings suggest that BCAA may represent a first choice substrate in the early phase after hepatectomy.

Amino Acids↗
PubMed1990

Effect of medium-chain triglycerides (MCT) as an energy substrate after hepatectomy in rats with streptozotocin-induced diabetes.

The suitability of energy substrates used by the remnant liver after a 70% partial hepatectomy was studied in relation to the hepatic energy status in diabetic rats. Rats with streptozotocin-induced diabetes mellitus underwent 70% hepatectomy, and were divided into three groups receiving total parenteral nutrition (TPN) for 24h. One group received standard TPN without fat, while two other groups received standard TPN with medium-chain triglycerides (MCTs) or long-chain triglycerides (LCTs) as a 10% lipid emulsion. All rats of the TPN group without fat died within 24h. Blood ketone body ratios (aceto-acetate/beta-hydroxybutyrate), energy charge levels of the remnant liver, and cumulative amounts of 14CO2 in the expired breath during the 6h following 14C-labeled fat emulsion administration (MCT or LCT) were all significantly higher in the MCT group than in the LCT group 24h after hepatectomy. These findings suggest that medium-chain fatty acids (MCFAs) as an energy substrate are superior to long-chain fatty acids (LCFAs) during the immediate posthepatectomy phase in diabetics.

Animals↗
PubMed2001

Histologic factors affecting prognosis following hepatectomy for intrahepatic cholangiocarcinoma.

Long-term survival following hepatectomy for intrahepatic cholangiocarcinoma has been poor, and specific factors influencing survival are unclear. In a retrospective study we sought to determine prognostic factors related to survival in these patients. In 28 patients who underwent hepatic resection for intrahepatic cholangiocarcinoma, we investigated the relations of several histologic factors to patient survival by univariate and multivariate analyses. No deaths occurred during the first 30 days. Median and mean survival times following hepatectomy were 409 and 935 days, respectively. The respective survival rates at 1, 3, and 5 years were 57%, 27%, and 27%. Resection margin status, intrahepatic metastasis, lymph node involvement, and lymphatic invasion were significant predictors of outcome. In a multivariate analysis using the Cox proportional hazards model, only lymphatic invasion independently predicted survival. Curative resection with clear margins was found to prolong survival after surgery. Hepatectomy for intrahepatic cholangiocarcinoma without lymphatic invasion offers hope for long-term survival.

Adult↗