New aspects in the liver regeneration following partial hepatectomy

We demonstrated the new two concepts for the liver regeneration after partial hepatectomy (PHx). The first is immunological findings in the regenerating liver. Th1 type T cells, which produce IFN gamma, and extrathymic T cells may play an important role in immunological control system of liver regeneration after PHx on the basis of the cellular immunity restricted by MHC class I and II molecules. The second is the mechanism of "on and off" on liver regeneration after PHx. Portal pressure, which reflecting wall shear stress of sinusoid, may trigger the liver regeneration and control the liver volume after PHx. There are two type of intrahepatic leukocytes; one type would tend to stay associated with SEC, while the other would not. Therefore shear stress may have a great influence on the leukocytes-sinusoidal endothelial cells (SEC) adhesion immediately after partial hepatectomy.     

Isozyme selective alterations of the expression of cytochrome P450 during regeneration of male rat liver following partial hepatectomy

1. During liver regeneration in the male rat, the metabolic activities of imipramine were differentially affected depending on the specific metabolic pathways. Imipramine N-demethylation was markedly reduced whereas 2-hydroxylation showed only a moderate reduction following partial hepatectomy. 2. A slight decline was observed in the hepatic microsomal content of CYP2D apoprotein, whereas a substantial decrease occurred in CYP2C11 content during liver regeneration. Since imipramine 2-hydroxylation and N-demethylation are mediated by CYP2D and 2C11 respectively, metabolic pathway-specific alterations in the activities of imipramine metabolism are explained by the isozyme selective alteration in the levels of CYPs in regenerating liver. 3. No significant effect of regeneration was observed on expression of CYP2B1 and 2E1 apoproteins. CYP3A2 apoprotein, one of the male-specific CYP isoforms, was significantly suppressed in regenerating liver showing a similar pattern of alteration to the levels of CYP2C11. The alteration pattern of the CYP1A1 level was different to the above with a moderate decline at the first day post-operation and a marked rebound thereafter. 4. In the partially hepatectomized male rate, no significant increase in androstenedione 5-alpha reductase activity, an activity predominant in the female rat, was detected. It is concluded that the pattern of alterations of hepatic oxidative metabolism during liver regeneration was not related to the functional feminization of the liver.     

Laparoscopic partial hepatectomy

This article describes the surgical techniques and indications of laparoscopic partial hepatectomy, which is not as widely available as laparoscopic cholecystectomy. Three patients with hepatocellular carcinoma and associated severe liver cirrhosis were candidates for this technique from July 1993 to August 1994. The tumor size was 4 cm or less and all the tumors were located in segment 5 or 8 which had grown nodularly and protruded from the liver surface. A microwave tissue coagulator was used for parenchymal dissection under ultrasonographic guidance in a gas-less method with or without low-pressure pneumoperitoteum of 4 mmHg. The principle of dissection consists of tissue coagulation and fragmentation with dissecting forceps. Three hepatectomies were performed uneventfully without blood transfusion and the patients rapidly returned to their preoperative conditions. The laparoscopic partial hepatectomy can be an option of treatment in selected cases where the tumor can be removed by minor, superficial resection.     

Effect of ischemia and reperfusion on hepatic regeneration following partial hepatectomy in cirrhotic rat liver

BACKGROUND: Several cutaneous tumors are characteristically associated with considerable and sometimes incapacitating pain. OBJECTIVE: A review of the histologic features of these tumors, subjective characteristics of the pain, hypotheses proposed to explain the mechanism of pain production by the tumor, and treatments that have been effective in abolishing or relieving the patient's perception of the stimulus. METHODS: Review of case reports as well as studies that have proposed mechanisms of pain production based on histologic, electron microscopic, and pharmacologic studies. RESULTS: Several hypotheses may be equally valid in explaining the cause of pain of a single tumor type, while no apparent cause is found in other types of tumors. There is variability in the success of a treatment between patients. CONCLUSION: Our understanding of the mechanism of pain production by cutaneous tumors is limited by the small number of studies (and sample size) addressing the issue as well as by our incomplete general understanding of pain production.     

Human erythrocyte polyamine levels after partial hepatectomy

BACKGROUND/AIM: There are various indices of liver regeneration, but no clinically useful index that reflects the current status of liver regeneration. We assayed human erythrocyte polyamine levels after partial hepatectomy to define the relationship between erythrocyte polyamine levels and liver regeneration. MATERIALS AND METHODS: Levels of human erythrocyte polyamines (putrescine, spermidine, and spermine) were assayed by high-pressure liquid chromatography in 91 patients after partial hepatectomy and in 13 patients after surgery other than partial hepatectomy (controls). Of the patients after partial hepatectomy, 37 underwent hepatectomy of 20% or more of the liver (group A), 27 underwent segmentectomy or subsegmentectomy of the liver amounting to less than 20% of the liver (group B), and 27 underwent an operation smaller in scale than sub-segmentectomy (group C). RESULTS: The greater the proportion of the liver resected, the greater was the percent increase. In groups A, B, and C, erythrocyte levels of spermidine and spermine increased after surgery compared with the base line, and were significantly higher at 7 or 14 days, decreasing later. The differences in spermidine among the three groups were significant. CONCLUSIONS: After partial hepatectomy, the erythrocyte polyamine levels, especially the level of spermidine, were related to the proportion of liver resected. They seemed to reflect the degree of liver regeneration.     

Haemostasis after partial hepatectomy using argon beam coagulation

The argon beam coagulator is a new device for haemostasis during and after surgery on parenchymatous organs. No data are available on its efficacy and tissue effect following hepatic resection. Blood loss, the time needed to achieve adequate haemostasis and histological findings after liver resection were assessed in 12 pigs using argon beam coagulation or suture ligation only, the mattress suture technique and tissue glue application. The treatment was randomly assigned to each of the four liver lobes in each pig. Median blood loss following argon beam coagulation was 13 (range 2-47) ml and after simple suture ligation 55 (range 2-260) ml (P < 0.02). The median time needed for adequate haemostasis following argon beam coagulation was 3 (range 2-7) min versus 14 (range 2-48) min in the control group (P < 0.005). There was no difference between argon beam coagulation and tissue glue, which were both superior to the use of mattress sutures. Argon beam coagulation resulted in less tissue damage than tissue glue or mattress suturing. The argon beam coagulator is an efficient device for achieving haemostasis following partial hepatectomy in the pig. It causes only a moderate tissue reaction.     

Mitochondrial function is differentially affected upon oxidative stress

The mechanisms that lead to mitochondrial damage under oxidative stress conditions were examined in synaptosomes treated with ascorbate/iron. A loss of membrane integrity, evaluated by electron microscopy and by LDH leakage, was observed in peroxidized synaptosomes and it was prevented by pre-incubation with vitamin E (150 microM) and idebenone (50 microM). ATP levels decreased, in synaptosomes exposed to ascorbate/iron, as compared to controls. NADH-ubiquinone oxidoreductase (Cx I) and cytochrome c oxidase (Cx IV) activities were unchanged after ascorbate/iron treatment, whereas succinate-ubiquinone oxidoreductase (Cx II), ubiquinol cytochrome c reductase (Cx III) and ATP-synthase (Cx V) activities were reduced by 55%, 40%, and 55%, respectively. The decrease of complex II and ATP-synthase activities was prevented by reduced glutathione (GSH), whereas the other antioxidants tested (vitamin E and idebenone) were ineffective. However, vitamin E, idebenone and GSH prevented the reduction of complex III activity observed in synaptosomes treated with ascorbate/iron. GSH protective effect suggests that the oxidation of protein SH-groups is involved in the inhibition of complexes II, III and V activity, whereas vitamin E and idebenone protection suggests that membrane lipid peroxidation is also involved in the reduction of complex III activity. These results may indicate that the inhibition of the mitochondrial respiratory chain enzymatic complexes, that are differentially affected by oxidative stress, can be recovered by specific antioxidants.     

Dumping following partial gastrectomy

The incidence of dumping has varied from 1 to 75% in a number of reported series. The discrepancy probably depends mainly on different definitions of the dumping syndrome. In the present work, the clinical diagnostic index (CDI) first proposed by Sigstad in 1968, has been used in a follow-up study of 241 patients after gastric resection for ulcer disease. 86% of the patients were satisfied with the result of the operation. Dumping occurred daily in 14.1% and 19.5% had the symptoms occasionally. The differences in the frequency of dumping after BI and BII resection were not statistically significant, gastro-jejunal fixation (GJF) and the position of the anastomosis had no influence on the prognosis.     

Time course comparison of cell-cycle protein expression following partial hepatectomy and WY14,643-induced hepatic cell proliferation in F344 rats

During recent years, there has been an extensive research focus in the area of cell-cycle control in eukaryotes and the relationship that exists between cell proliferation and cancer. The eukaryotic cell-cycle is governed by signal transduction pathways mediated by complexes of cyclin dependent kinases (CDK) and their partner cyclin proteins. This study was performed to identify differences in cell-cycle control protein expression following physical and chemical stimuli of hepatic cell growth. Protein levels of cell cycle mediators, cyclin dependent kinases (CDK 1,2,4,5), cyclin proteins (A,B,D1-D3 and E), proliferating cell nuclear antigen (PCNA), tumor suppressor proteins (p53 and Rb), and CDK inhibitory proteins (p16Ink4, p21Waf1 and p27Kip1) were examined in F344 rats following 70% partial hepatectomy or a single dose of WY14,643 over 96- and 48-h time courses, respectively. CDK1 (p34cdc2) and PCNA protein concentrations, quantified by ELISA, were significantly increased beginning at the 24-h time point and maximal at 48 h (6.9- and 3.7-fold for partial hepatectomy and 4.2- and 3.3-fold for WY14,643, respectively). Differential effects were observed with the G1 cell-cycle mediators CDK4, CDK5, and cyclin D3, p21Waf1 and p27Kip1 CDK inhibitory protein concentrations rose in accordance with the induction of DNA synthesis and histone H1 kinase activity. In addition, there were dramatic differences in p53 protein expression patterns following partial hepatectomy versus WY14,643 dosing. Because non-genotoxic hepatocarcinogens are known to induce cellular proliferation, data generated from this study may aid in elucidating the specific hepatocarcinogenic signal transduction pathways stimulated by non-genotoxic carcinogens.     

Lysosomal enzyme beta-glucuronidase. Release from regenerating liver after partial hepatectomy

In 12 dogs, 70% hepatectomy was performed to investigate the changes in serum lysosomal enzyme beta-glucuronidase activities, and to compare them with other liver functions and with the restoration of liver mass. Three dogs died within 24 hours without recovering consciousness from anesthesia, and one died on the fourth postoperative day because of hepatic insufficiency. The other eight dogs were killed at various postoperative times up to eight weeks. Regeneration of the remaining liver occurred rapidly after operation. The peak elevation of serum glutamic oxaloacetic transaminase activity was found on the first postoperative day, with a steady return to normal within two or three weeks. To the contrary, the serum activity of beta-glucuronidase decreased during the first three days, but increased substantially between the seventh and 14th postoperative day, when regeneration was considered to be maximum. The results seem to indicate that serial determinations of lysosomal enzyme activities in the blood can be a beneficial biochemical index for detection of progressing liver regeneration following partial hepatectomy.     

Synthesis of pteroylpolyglutamates in rat liver during regeneration after partial hepatectomy

The liver content of higher polyglutamate forms of folic acid, which in partially hepatectomized rats is markedly lower as compared with sham operated animals, is normalized by the vitamin administration. The greater availability of folic acid and consequently of the tetrahydrofolates, promotes the synthesis of actual coenzymic forms; so their content, in regenerating liver, is maintained at normal values in spite of a higher requirement caused by the exaltation of biosynthetic processes.     

Synthesis of secretory protein in regenerating liver of rat after partial hepatectomy

Albumin immunoreactivity in the liver was examined on days 2, 5 and 10 after two-thirds partial hepatectomy by light and ultrastructural immunoperoxidase methods and the ultrastructural area of the rough endoplasmic reticulum (ER) in hepatocytes was measured. Albumin immunoreactivity was seen in the rough ER and Golgi apparatus of all hepatocytes in the hepatectomized liver and ultrastructural analysis showed a significantly greater area of rough ER on day 5 than on days 2 or 10. Albumin mRNA was studied by the in situ hybridization technique using radioisotopes and their numbers were determined visually. Albumin mRNA was present as grains in all hepatocytes and the grains varied in number during regeneration of the liver, being more abundant on day 5 than on days 2 or 10. The activity of [3H]-leucine incorporated into albumin synthesis, an indicator of translational activity, was higher on days 5 and 10 than on day 2 and was highest on day 5. In conclusion, albumin synthesis varied during liver regeneration after partial hepatectomy, being reduced at the peak of cell proliferation on day 2 and being most active on day 5.     

Accelerated recovery of glycerol-induced acute renal failure in rats with previous partial hepatectomy

Recent primary prevention trials demonstrated that cardiovascular morbidity and mortality benefits are not accompanied by adverse effects on overall mortality and morbidity in cohorts representing plasma cholesterol concentrations observed in the bulk of coronary artery disease. During the past year, further analyses of the West of Scotland Coronary Prevention Study have indicated that benefit requires a 25% reduction of LDL cholesterol and that such treatment is not very expensive when focussed on selected high-risk individuals. The Air Force/Texas Coronary Artery Prevention Study indicated that benefit is seen in individuals with even lower plasma lipid concentration. Although current treatment with lifestyle and lipid modifying drug management is successful in primary prevention, the unpredictable nature of coronary artery disease and the cost of drugs mitigate against direct application of drug management in persons with relatively low risk, but selective treatment should be undertaken in very high-risk settings. Future studies need to examine more specific at risk cohorts, test better targeted lipoprotein modification, test more risk factors and also examine whether changes in vascular function or markers of inflammation will predict a better outcome.     

Effect of RES on liver regeneration and survival after 90% partial hepatectomy

In previous studies, 90% partial hepatectomy in the rat was invariably accompanied by 100% mortality within 40 hr. This paper describes the effect of enhanced reticuloendothelial system (RES) on liver regeneration after 90% partial hepatectomy. RES was activated using 5 K.E. of OK-432 injected intraperitoneally 24 hr before 90% partial hepatectomy. Ninety per cent of the liver mass was resected and rats were provided with tap water or 20% glucose orally and subcutaneously. Survival time was strikingly different. In rats provided with tap water only; 100% of rats died before 42 hr. In rats provided with 20% glucose; 44.2% of rats survived beyond 42 hr. In rats pretreated with OK-432 and provided with 20% glucose; 87.0% of rats survived beyond 42 hr. This regimen results in severe hypoglycemia and dead within 42 hr. When RES was activated before 90% partial hepatectomy, significantly higher blood glucose level was observed. BrdU labeling index was significantly higher in rats pretreated with OK-432 than in control rats. The results indicate that enhancement of RES before 90% partial hepatectomy provides acute metabolic support and enhancement of liver regeneration resulting in improved survival.     

A study of mechanism by which tumor growth was induced by partial hepatectomy

In this study, 18 BUF rats with 7316 A liver cancer burden were divided into three groups. Groups A underwent simple laparotomy, group B had 70% hepatectomy, and group C with laparotomy plus TGF-beta . Splenic adhesive cells and serum of postoperative day 5 in both group A and B were added into mixed lymphocellular culture and CCL-64 cell culture, TGF-beta was also added into MLC and 7613 A liver cancer culture. It was found that in group B and C the growth rate of tumor cells was greatly accelerated (P < 0.01); whereas MLC and CCL-64 cell proliferation was inhibited by the serum and splenic adhesive cells from group B (P < 0.05). TGF-beta also significantly inhibited MLC through it had no effect on 7316 A liver cancer cells. The authors came to the conclusion that there was the activity of TGF-beta in the serum of the rats with partial hepatectomy which inhibits the proliferation of host immune cells.