[Right hepatectomy, extensive right hepatectomy or trisegmentectomy? Surgical applications related to in intrahepatic anatomy (author's transl)].
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Hepatectomy↗
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The mechanism of impaired coagulation after partial hepatectomy in the dog.
Coagulation mechanisms were examined in the dog after a 70 per cent hepatectomy and the additional effect of varying periods of ischemia on the liver remnant. Dogs were submitted to a 70 per cent partial hepatectomy, and the liver remnant was rendered ischemic by occluding the vascular inflow. Portal decompression during ischemia was accomplished by allowing portal venous flow through the lobes subsequently resected. Dogs in the control group, those undergoing hepatectomy alone and those undergoing hepatectomy together with 60 minutes of ischemia time exhibited a fall in hemoglobin and hematocrit values, a transient leukocytosis, a small increase in kaolincephalin clotting time and a decline in platelet count but no significant thrombocytopenia. Prothrombin time was changed in dogs undergoing hepatectomy, but this was not affected by ischemia. The characteristic rise in plasma fibrinogen postoperatively was abolished, and fibrinogen levels were lower in dogs undergoing hepatectomy alone and fell significantly in dogs subjected to 30 to 60 minutes of ischemia of the liver remnant. Factors V and VII were decreased after hepatectomy, and Factor V was more severely reduced after 30 to 60 minutes of ischemia. There was no overt bleeding tendency. In ten dogs, the liver remnant was subjected to ischemia for 75 minutes. Four of these died within three days of operation, two with severe hypoglycemia and two with postoperative bleeding. All six surviving dogs exhibited gross coagulation defects. Prothrombin time rose, kaolin-cephalin clotting time increased and platelets fell to a greater degree than in any of the other dogs. Plasma fibrinogen level showed a profound fall, as did Factor V, the magnitude of these changes being greater than after a shorter period of ischemia. Factor VII was also decreased, but this did not appear to be related to the ischemic interval. In the clinical situation in which intrinsic coagulation mechanisms are shown to be impaired, treatment with Factor V and VII concentrates may be the best way of correcting the coagulation defect.
Animals↗
Effect of 5-fluorouracil on liver regeneration and metabolism after partial hepatectomy in the rat.
The effects of 5-fluorouracil (5-FU) on regenerating liver were studied after two thirds hepatectomy in rats. In Group I, 68% hepatectomy was performed. In Group II, 5-FU in a dose of 20 mg/kg was administered intravenously immediately after, 24 and 48 hours after the same hepatectomy. In Group III, the same amount of 5-FU was given after sham-operation. The mortality rates were 4.5% in Group I, 28.0% in Group II, and 0% in Group III. The treatment with 5-FU following hepatectomy caused not only suppression but delay of liver cell division. Histologic changes such as cellular degeneration, liver steatosis and dilatation of the sinusoidal space were marked and prolonged in the hepatectomy-5-FU group. The metabolic abnormalities in albumin, cholesterol, triglycedides, and phospholipids were further more profound in Group II compared to those in Group I. In Group III, moderate derangements in albumin, triglycerides and phospholipids were observed. The results may indicate that adjuvant chemotherapy with 5-FU or similar drugs immediately after partial hepatectomy in hepatoma patients should be performed with great care if necessary. Otherwise, it should not be carried out until hepatic regneration is almost completed.
Animals↗
[Coagulation disturbances after subtotal or total hepatectomy in the dog (author's transl)].
The authors relate 15 cases of blood coagulation disturbances among three groups of animals after 80%, 90% or total hepatectomy. Animals in group I, after 80% hepatectomy, were sacrified between the 10th and 30th postoperative days. Group II animals, with 90% hepatectomy, survived for periods ranging from 18 to 24 hours. In group III, after total hepatectomy, survival varied between 30 and 40 hours. The coagulation disturbances which were observed following 80% hepatectomy were spontaneously compatible with the survival of the animals. Following 90% and total hepatectomy the resulting disturbances were constantly severe enough to limit survival time. Supportive procoagulant therapy associated with sequential heparin administration seems justified by the insufficient biosynthesis of clotting factors and their unavoidable consumption as a result of localized then disseminated intravascular coagulation and secondary fibrinolysis.
Animals↗
Effect of a single treatment with the alkylating carcinogens dimethynitrosamine, diethylnitrosamine and methyl methanesulphonate, on liver regenerating after partial hepatectomy. I. Test for induction of liver carcinomas.
A single injection of dimethylnitrosamine (DMN), 12.0-15.6 mg-kg, given to 100 g female rats 24 h after partial hepatectomy, induced hepatocellular carcinoma. No animals receiving DMN without partial hepatectomy developed liver carcinomas. Previous evidence had suggested that the incidence of tumours was highest when DMN was administered during the wave of DNA replication which follows partial hepatectomy. The present experiments made this suggestive evidence statistically significant. A single treatment with diethylnitrosamine (DEN) induced liver cell cancer when given to intact or to partially hepatectomised rats. No tumors developed when another alkylating carcinogen, methyl methanesulphonate (MMS), was administered after partial hepatectomy. The significance of these results in relation to the mechanism of initiation of carcinogenesis is discussed.
Adenocarcinoma↗
High density lipoprotein catabolism before and after partial hepatectomy.
The serum decay and tissue distribution of iodine-labeled high density lipoprotein (HDL)-apoproteins were measured in rats 2--8 h after partial hepatectomy or sham-operation. A method was developed allowing continuous bloodsampling without using anticoagulantia or anaesthetics. The serum decay of HDL-apoproteins was biexponential. Neither the initial rapid phase (t 1/2 0.3 +/- 0.1 h), nor the slow phase (t 1/2 6.2 +/- 0.3 h) were influenced by the removal of 2/3 of the liver and consequently there was no effect on the fractional catabolic rate (F.C.R.: 2.9 +/- 0.2/day). The level of circulating HDL was decreased by partial hepatectomy but the chemical composition of HDL was unchanged. Total tissue HDL radioactivity in the control rats was 5.7, 2.8, 2.7, 1.0, 0.7, 0.2, 0.4 and 0.1% of the injected dose for skeletal muscle, adipose tissue, liver, jejunum, kidneys, spleen, lungs and heart, respectively. Only the value for liver was affected significantly by partial hepatectomy (0.6%). It is concluded that the in vivo degradation rate of HDL-apoproteins is not influenced by the removal of 2/3 of the liver and that the decrease in serum HDL concentration is due to an impaired rate of hepatic synthesis. These results indicate the possiblity of extrahepatic HDL-apoprotein catabolism or a stimulation of HDL-apoprotein degradation, induced by partial hepatectomy, in the remaining liver lobes.
Animals↗
Anabolism versus catabolism of [5-3H]uridine and its relationship to ribonucleic acid labelling in mouse liver after partial hepatectomy.
The balance between anabolism and catabolism of [5-(3)H]uridine was studied in the mouse after partial hepatectomy. Labelling of RNA and UDP-glucose was determined and evaluated in relation to changes in the specific radioactivity of UTP. The amounts of labelled catabolic products of uridine were increased several-fold in liver and blood after partial hepatectomy. The specific radioactivity of RNA decreased to about 60% of the control value at 6h and was in the same range as that of control liver at 24h after operation. Decreased labelling of RNA and UDP-glucose was attributable to decreased specific radioactivity of UTP. No changes in the size of the UTP pool or in the balance between uridine anabolism and catabolism were found that could explain the decreased specific radioactivity of UTP. Rather, the alterations in the labelling of this metabolite induced by the partial hepatectomy may be related to decreased phosphorylating capacity in the liver cells and/or dilution of the labelled precursor in an expanded uridine pool. The enhanced amounts of uridine catabolic products in liver and blood were probably a consequence of accumulation and altered incorporation of the metabolites from the blood into the liver cells. Despite the increased amounts of labelled catabolic products and the decreased labelling of RNA, the results reported here actually suggest decreased uridine catabolism and slightly increased RNA synthesis in mouse liver after partial hepatectomy. The results stress the importance of proper controls in determination of nucleic acid synthesis and in metabolic studies by use of labelled precursors.
Animals↗
Insulin requirements for hepatic regeneration following hepatectomy.
On the basis of changes in the adenine nucleotide the mitochondrial metabolism of the remnant liver, insulin requirements for hepatic regeneration were studied in diabetic rats treated with varying amounts of alloxan. Mildly diabetic rats with less than 30% inhibition in maximal portal insulin response to oral glucose load, showed a parabolic glucose tolerance pattern and could tolerate partial hepatectomy. Whereas, severely diabetic rats with more than 45% inhibition showed a linear glucose tolerance pattern and died within 24 hours after partial hepatectomy. In the former rats, the energy charge (ATP + 1/2ADP/ATP + ADP + AMP) levels of the remnant liver decrease slightly at an early period after partial hepatectomy but could be restored rapidly to normal levels with a concomitant rise of oxidative phosphorylation in remnant liver mitochondria. In contrast, the energy charge levels in the latter groups fell more markedly and could not be restored, because of insufficient enhancement of mitochondrial oxidative phosphorylation. It is suggested that an enhancement in mitochondrial phosphorylative activity of the remnant liver following partial hepatectomy is inhibited in proportion to the severity of impaired insulin secretion, resulting in a decrease of the potential functional capacity of liver.
Adenine Nucleotides↗
Effect of double partial hepatectomies at various intervals on [3H]thymidine incorporation into rat liver DNA.
At various intervals after a 34% hepatectomy, another 34% (50% of the remnant) hepatectomy was performed on rats, and the [3H]thymidine incorporation into the DNA of remaining liver cells was measured 24 hr after the first operation. The values of [3H]thymidine incorporation into liver DNA of rats hepatectomized doubly (34% and 34%) at 6, 8 and 10 hr intervals were greater than the sum of the value of rats which received a single 34% hepatectomy at the start and those of rats which received a single 68% hepatectomy at 6, 8 and 10 hr, respectively.
Animals↗
[Hepatic suppurations requiring segmented or atypical hepatectomies].
Following studies of cases with hepatic suppurations the authors indicate the necessity for regular or atypic hepatectomies. The extension of the suppurative process in the liver made necessary the ligature of the great sagital vein and the authors show, on the basis of anatomic and topographical data (hepatic segmentation), that it is necessary to extend the hepatectomy to the IV-th para-median segment. The authors also present the indications for bi-segmental right hepatectomy in segments VII-VI as well as of the total left regulated hepatectomy.
Adolescent↗
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↗
Interrelations between uptake of [14C]orotic acid and labeling of UTP and RNA in rat and mouse liver after partial hepatectomy.
The uptake and utilization of [6-14C]orotic acid for UTP and RNA synthesis were studied in rat and mouse liver at 24 h after partial hepatectomy. Rat liver concentrated radioactivity relative to blood several-fold better than did mouse liver after both sham-operation and partial hepatectomy. The results showed that in mouse liver, contrary to rat liver, the orotic acid uptake was not increased after the partial hepatectomy. In rat liver, the precursor uptake and the labeling of UTP increased by about 75% whereas the specific radioactivity of RNA increased 2 to 3-fold after the operation, thus indicating an increased RNA synthesis. Mouse liver showed no increased [14C]orotic acid uptake or labeling of UTP or RNA at 24 h after partial hepatectomy.
Animals↗
The effects of prolonged hepatic ischaemia before 70 per cent partial hepatectomy in the dog.
The effect of prolonged normothermic ischaemia before partial hepatectomy was assessed in 10 dogs. During the period of ischaemia, portal decompression was maintained. The survival rate for animals undergoing 75 minutes of total liver ischaemia was 60 per cent and 2 of the dogs died as a result of hypoglycaemia. High levels of alkaline phosphatase and transaminases in the survivors indicated a severe degree of hepatocyte damage. However, complete restoration of liver mass was noted 6 weeks after partial hepatectomy and was not impaired by the prolonged ischaemia. This study confirms the resistance of the dog liver to ischaemia before partial hepatectomy. The critical period beyond which ischaemia is followed by an increasing number of deaths and severe metabolic upset is in the region of 1 hours.
Alanine Transaminase↗
Effect of partial hepatectomy on the interrenal tissues of Xenopus laevis (Daudin).
Partial hepatectomy was carried out on Xenopus laevis to investigate its influence on the endocrine system. In addition to other endocrine effects, a marked hypertrophy and stimulation of the interrenal gland was observed. Activated cells contain mitochondria with extended and irregularly coiled tubules embedded in a low electron dense matrix. Hepatectomy induces two phases of proliferation [3 and 35 days postoperative (p.o.)]. After 106 days p.o. giant mitochondria possessing narrow and closely packed, parallel tubules surrounded by an electron dense matrix indicate a phase of inactivation. The smooth endoplasmic reticulum and the Golgi apparatus proliferate after hepatectomy. During activation the high lipid content seen in controls in decreased significantly.
Adrenal Glands↗
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↗
Effects of the liver homogenate obtained following partial hepatectomy on cirrhosis of the liver.
The authors studied the influence of liver homogenates as a whole and collected at various intervals after partial hepatectomy on cirrhosis of the liver. The lyophilized homogenates were administered over a period of 6 weeks to various groups of albino rats pretreated with CCl4 for a period of 6 months. The normal liver homogenate did not influence the histological and biochemical picture of the hepatocirrhosis. The material collected 48 hours after partial hepatectomy causes a moderate stimulation of the mechanisms of parenchymatous regeneration. 7 days after partial hepatectomy (in the postmitotic period) the hepatic regenerate shows a biological effect with lysis of collagen fibres and protection of parenchymatous cells.
Alanine Transaminase↗
Repeated partial hepatectomy as a promoting stimulus for carcinogenic response of liver to nitrosamines in rats.
Partial hepatectomy 24 h before a single i.p. dose of dimethylnitrosamine, diethylnitrosamine or ethylmethylnitrosamine increased the carcinogenic response in the liver of rats as determined by the number of tumours and the number of "focal proliferations" produced. Secondly, in rats given a single i.p. dose of diethylnitrosamine, 3 partial hepatectomies 5, 10 and 15 weeks after dosing the animals increased the carcinogenic response in the liver. The stimulus of repeated partial hepatectomy therefore appears to act as a "promoting agent" for liver carcinogenesis, that is if the single dose of diethylnitrosamine is regarded as an "initiating agent" in the terms of the two-stage hypothesis.
Animals↗
Induction of pinocytosis in rat hepatocytes by partial hepatectomy.
Rat hepatocytes, normally not highly pinocytic cells, becomes so after partial hepatectomy when about two-thirds of the liver is removed. Droplets, up to 20 mum in diameter, develop, initially by addition to smaller pinocytic structures and later by fusion with lysosomes. The droplets contain a material with an electron microscope periodicity characteristic of fibrin; they are periodic acid Schiff-positive as is plasma. It is therefore reasonable to consider plasma glycoproteins to be major components of the droplets. The droplets are at all times membrane delimited, an observation possible only after perfusion fixation. The droplets are positive for three lysosomal hydrolases identified cytochemically: acid phosphatase, N-acetyl-beta-glucosaminidase, and beta-glucuronidase. From light and electron microscopy it is evident that these activities are acquired by fusion with lysosomes, mostly autophagic vacuoles and residual bodies both of which become very numerous after partial hepatectomy. Pinocytic structures are seen relatively infrequently in the hepatocytes of normal rats but a great many are present after partial hepatectomy. They are most easily observed if horseradish peroxidase (HRP) is intravenously injected before sacrifice and sections are incubated for HRP cytochemistry. The low dose of HRP employed (10 mg/100 g body weight) does not induce pinocytosis in controls, either untreated rats or rats subjected to laparotomy, including palpation of the liver. However, in partially hepatectomized rats even a much smaller dose of intravenous HRP (3.3 mg/100 g) visualizes the pinocytic structures in hepatocytes (coated vesicles, channels, cuplike bodies, and droplets). Kupffer cells pinocytose much HRP in both control and partially hepatectomized rats.
Acetylglucosaminidase↗