Biomedical subjects

R Kanashima

Publications and source records attributed to R Kanashima.

17 recordsLinked to original sources

PubMed1989

Famotidine does not inhibit liver regeneration.

The H2-blockers, cimetidine and ranitidine, are reported to inhibit liver regeneration. In this work, the effects of a new powerful H2-receptor antagonist, famotidine, on liver regeneration were studied in rats. The animals were divided into three groups: group I in which a standard two-thirds hepatectomy was performed, group II in which the rats were treated with famotidine (intramuscular dose of 0.8 mg/kg body weight) on the day of operation and 24 and 48 h after hepatectomy, and group III in which the animals were intramuscularly injected with a larger dose of famotidine (1.2 mg/kg body weight) in the same way as group II. The histology and mitotic index of remnant livers and serum levels of aminotransferase and albumin were examined from 24 h to 10 days after the operation. The treatment with famotidine (groups II and III) did not inhibit hepatocyte mitosis but, on the contrary, raised the index on day 3 after hepatectomy when compared with the controls (group I). The albumin synthesis was well preserved in the famotidine-treated animals. The noninhibitory effects of famotidine on liver regeneration are discussed.

Alanine Transaminase↗

PubMed1985

Ranitidine as an inhibitor of liver regeneration.

The effects of ranitidine, a new H2-receptor antagonist, on liver regeneration were investigated using a protocol described previously. The animals in Group I had standard two-thirds hepatectomy. In Group II, the rats received an 8 mg/kg intramuscular dose of ranitidine immediately and 24 and 48 hours after two-thirds hepatectomy. In Group III, the rats had the same amounts of ranitidine after a sham operation. Mortality rate, liver weight restoration, mitotic activities of the residual livers, and serum levels of aminotransferases were examined from 24 hours to 14 days after operation. The mortality was very high in Group II (45 percent), whereas no rats died in Group I, and only 1 of 35 animals died in Group III. Administration of ranitidine after hepatectomy resulted in suppression not only of liver restoration, but also of the mitotic activities of hepatocytes. The serum aminotransferase levels in Group II had a tendency to increase after hepatectomy, compared with the levels in Group I. Using light microscopy, we detected that the hepatectomized group treated with ranitidine (Group II) underwent profound liver steatosis and marked dilatation of sinusoidal spaces. The present and previous observations by us indicate that ranitidine also inhibits, like cimetidine, liver regeneration after hepatectomy. The causes of the inhibitory effects of both cimetidine and ranitidine on hepatocyte cell division have also been discussed herein.

Animals↗

PubMed1984

The natural history of hepatocellular carcinoma. A study of 100 untreated cases.

The natural course of hepatocellular carcinoma (HCC) was evaluated in 100 untreated patients who were seen during recent 13 years. There were 80 males and 20 females. The macroscopic type of tumor was massive in 58, nodular in 35, and diffuse in 7 cases. Liver cirrhosis was associated with in 80% of patients. The mean survival time of overall patients was 4 months from the onset of initial symptoms to death and 2 months from admission to death. Occult and cirrhotic types of HCC showed a longer survival than frank and febrile types that had a mean survival time of all patients. The prognosis of icteric and metastatic types was poorest. Sex, tumor type, or associated cirrhosis did not substantially affect the natural course of HCC. The tumor stage and clinical stage were grossly correlated to the prognosis. In terms of symptoms, severe jaundice and ascites were the most dismal prognostic signs.

Adult↗

PubMed1983

Inhibitory effect of cimetidine on liver regeneration after two-thirds hepatectomy in rats.

The effects of cimetidine on the regenerating liver were studied in rats after they had two-thirds hepatectomy. In Group I, standard two-thirds hepatectomy was performed. In Group II, cimetidine in a dose of 40 mg/kg was given intramuscularly immediately and 24 and 48 hours after two-thirds hepatectomy. In Group III, the same amount of cimetidine was given after a sham operation. Mortality rate, liver weight restoration, mitotic activities of remnant livers, and serum levels of aminotransferases and albumin were examined from 24 hours to 14 days after operation. The mortality rate was 11.1 percent in Group II, whereas no rats in Groups I and III died. Although there were no differences in the residual liver weights among the hepatectomized groups, treatment with cimetidine induced substantial suppression and delay of liver cell division. The serum aminotransferase levels in Group II increased significantly after hepatectomy compared with the levels in Group I. The albumin synthesis remained suppressed in Group II. Light microscopy showed prolonged liver steatosis and marked dilatation of the sinusoidal space in that group. Our results may indicate that cimetidine has an inhibitory effect on liver regeneration and that it should be administered very carefully after extensive hepatic resection if applied as prophylaxis for the life-threatening complication, stress ulcer syndrome. Otherwise, antacid therapy or other trials should be carried out.

Animals↗

PubMed1982

Effect of doxorubicin on liver regeneration and host survival after two-thirds hepatectomy in rats.

The effects of doxorubicin (Adriamycin) on regenerating liver were studied after two-thirds hepatectomy in rats. In Group I, standard two-thirds hepatectomy was performed. Doxorubicin in a dose of 2 mg/kg (Group II) and 6 mg/kg (Group III) was given intravenously immediately after the same hepatectomy. In Group IV, 6 mg/kg doxorubicin was given after sham operation. Animal survival, body weight restoration, wet weight and mitotic activity of remnant livers, and serum albumin concentrations were examined 1-14 days after operation. The survival rates were 95.5% in Group I, 76.8% in Group II, 10.3% in Group III, and 96.7% in Group IV. Although there were no differences in the residual liver weights among the hepatectomized groups, treatment with doxorubicin induced substantial, dose-dependent suppression and delay of liver cell division. Serum albumin levels dropped considerably in hepatectomized, doxorubicin-treated rats. Light microscopy showed degenerative changes with a single cell necrosis of hepatocytes in Group III. Death among rats hepatectomized and treated with doxorubicin was considered to be mainly due to the failure of residual livers since albumin synthesis was impaired and no marked changes were seen in vital organs other than the liver. For patients with hepatoma, the present results may indicate that the administration of adjuvant chemotherapy with doxorubicin, when necessary immediately after hepatectomy, should be performed with great care. In the absence of such necessity, doxorubicin should be withheld until life-sustaining liver regeneration has taken place.

Animals↗

PubMed1982

Release of lysosomal enzymes after partial hepatectomy: study of patients with and without cirrhosis of the liver.

Serum activities of lysosomal enzymes beta-glucuronidase and acid phosphatase were serially estimated in 14 patients with and without cirrhosis of the liver who underwent 40% to 80% hepatic resection. Substantial increases in enzyme activities were observed two to eight weeks after operation in ten of 11 patients who did not suffer from postoperative liver failure. Regeneration of the residual livers was almost satisfactory in all 11, as evidenced by clinical, roentgenologic, and histologic findings. In three patients with advanced cirrhosis who died of hepatic failure 21 to 39 days after extensive hepatic resection, there was neither the enzymatic reaction nor evidence of regeneration of the liver remnants. In the light of this study and our previous experimental studies, serial determination of the lysosomal enzyme activities in blood is probably a beneficial biochemical index for detection of progressive hepatic regeneration.

Acid Phosphatase↗

PubMed1982

Serum activities of lysosomal enzymes in patients with liver cell carcinoma.

Serum activities of two lysosomal enzymes, beta-glucuronidase and acid phosphatase, were estimated in 66 patients with liver cell carcinoma, 10 with secondary liver cancer, 14 with cirrhosis of the liver, and 9 normal controls. A substantial increase in the enzyme activities was found in patients with liver cell carcinoma but not in those with secondary liver cancer. The degree of the enzyme elevations paralleled the stage of hepatoma. Although the serum activities of both enzymes were also elevated in patients with liver cirrhosis, the elevations were significantly higher in hepatoma than in liver cirrhosis. Possible mechanisms for the elevation of serum lysosomal enzyme activities in hepatoma are discussed, but further studies are necessary to elucidate the biological and clinicopathological significance of estimating serum lysosomal acid hydrolases in patients with primary liver cell carcinoma.

Acid Phosphatase↗

PubMed1981

Alteration in plasma amino acid concentrations following subtotal hepatectomy in dogs.

Plasma amino acid concentrations were serially estimated after 82.5% resection of the liver in dogs. Slight to moderate decreases were found in valine, leucine, isoleucine, threonine and methionine concentrations for the first 12 hours. The first three branched chain amino acids thereafter increased up to 180%. Between 24 and 72 hours, threonine and methionine increased markedly in four surviving dogs but not in two which died in hepatic coma. Significant increases were found in phenylalanine and lysine concentrations but there was no substantial change in tryptophan levels throughout the experiment. Among the non essential amino acids, the most striking increase was seen in tyrosine and serine concentrations with their peak at 48 to 72 hours. Arginine and aspartate transiently decreased within 12 hours but most of other amino acids increased more or less during the observation. Although the molar ratios of the branched chain to the aromatic amino acids dropped dramatically, it was difficult to draw definitive remarks on the relationship between the molar ratio and the grade of hepatic coma in each animal. A further study is necessary to determine whether the correction of plasma amino acid alterations is beneficial or not following critical liver resection.

Amino Acids↗

PubMed1980

Serum alpha-fetoprotein in patients following partial hepatectomy.

Serum alpha-fetoprotein (AFP) concentrations were estimated postoperatively at weekly intervals with the radioimmunoassay in eight adult patients. Seven patients underwent partial hepatectomies of up to 80% of the liver. Surgical drainage was carried out in one individual who had a huge pyogenic abscess in the right hepatic lobe. Despite evidence of clinical and biochemical recovery associated with normal liver regeneration, none of the sera were positive for AFP during the period 4-12 weeks after operation. This study does not support the hypothesis that the elevation of serum AFP in benign liver diseases reflects the extent of liver regeneration.

Aged↗

PubMed1980

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

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

Acid Phosphatase↗

PubMed1979

Remnant liver function during surgery for extensive hepatic resection.

True functional reserve of remnant liver should be determined at the same condition that contemplated hepatectomy has been performed, and this condition can be achieved before resection by temporary clamping of the inflow vessels of hepatic lobes to be removed. Using indocyanine green (ICG), the remnant liver function (RLF) was evaluated whether or not the method can be a useful indicator for or against hepatomy. In the study of healthy dogs, the RLF proved to be a reliable indicator to prospect hepatic failure which may occur after extensive resection of the liver. Then, the method was employed in nine patients who underwent 40 to 70 per cent hepatectomy. The results indicated that the RLF with ICG during surgery, if performed under stable hemodynamics, is a beneficial tool to decide the resectability in equivocal cases.

Adult↗

PubMed1979

Treatment of hepatocellular carcinoma with associated cirrhosis.

During the recent 10 years, 105 patients with hepatocellular carcinoma were admitted to our clinic. Seventy of them had an associated cirrhosis of the liver. The therapeutic results of these 70 patients were analyzed according to the mode of treatment. The mean survival periods after admission were as follows; No cancer treatment group (12 patients) 79 days, Chemotherapy group regardless of the mode of administration (25 patients) 97 days, Hepatic artery ligation with chemotherapy group (16 patients) 197 days. Hepatic resection was carried out in 17 patients; partial hepatectomy in 5, left lateral segmentectomy in 1, left lobectomy in 3, and right lobectomy in 8. The 50% survival period of all the hepatectomized patients was 8.5 months. Seven patients are living 5 months to 3 years after operation. Five patients died of recurrence of hepatoma between 4 months and 3 years and 2 months postoperatively. Five individuals died of causes related to the operation; two hepatic failure, two fatal infection, and one massive haemorrhage from acute duodenal ulcer. The results indicated that hepatic resection, from partial to extensive, might be possible even in patients with associated cirrhosis but more exact criteria are mandatory in selecting patients for major hepatic resection. Hepatic artery ligation with chemotherapy should be the first choice for those with nonresectable hepatoma. Continuous infusion of oncolytic agents into the hepatic artery may be considered for those in whom arterial ligation is contraindicated.

Adult↗

PubMed1979

Effect of purified beta glucuronidase infusion in normal dogs and dogs with acidosis.

The effects of systemic infusion of purified beta glucuronidase, lactic acid and a combination of these were studied in normal dogs from the viewpoints of hemodynamics and blood coagulation. In none of the groups was an obvious deterioration in arterial blood pressure, pulse rate, central venous pressure, portal venous pressure and electrocardiogram observed after the infusions. On the other hand, beta glucuronidase infusion with preceding acidosis caused substantial thrombocytopenia accompanied by a decrease in fibrinogen levels and abnormal thromboelastogram. A similar trend was found by the infusion of beta glucuronidase only. An intermediate abnormality was found by the infusion of lactic acid alone. Histologically, fibrin clots in the pulmonary arteries were often observed in the dogs of all groups, but the quantitative difference among the groups was difficult to evaluate. In the present investigation, shock could not be produced, but other data seemed to indicate that increased levels of acid hydrolases in the blood are concerned with deterioration and irreversibility of shock, especially in an acidotic condition.

Acidosis↗

PubMed1979

Deleterious effect of pharmacological doses of corticosteroids after partial hepatectomy in rats.

The aim of the present investigation was to determine whether pharmacological doses of corticosteroid can be used safely in the treatment of haemorrhagic shock during major hepatic resection. Following two-thirds hepatectomy in the rat the administration of dexamethasone, 4 mg/kg of body weight, produced higher morbidity and mortality compared with that in the control groups. This was considered to be mainly due to substantial suppression and retardation of liver regeneration. In addition, the steroid therapy exaggerated the degree and time of liver steatosis with marked elevation of serum fatty acid, triglyceride, phospholipid, and cholesterol concentrations. It appears therefore that it would be very hazardous to treat haemorrhagic shock as a result of major hepatic resection with pharmacological doses of corticosteroids.

Animals↗

PubMed1978

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↗

PubMed1978

Platelet aggregability after splenectomy in patients with normosplenism and hypersplenism.

The relationship between platelet count and aggregability was serially evaluated after splenectomy in patients with normosplenism and hypersplenism, and the results were compared with those found in patients undergoing only upper abdominal surgery. The preoperative count and aggregability of platelets were significantly suppressed in patients with cirrhosis of the liver, idiopathic portal hypertension, and prehepatic portal obstruction. However, the platelet aggregability of these patients markedly increased in accordance with the platelet counts after splenectomy. In the patients with normal splenic function preoperatively, splenectomy caused a simultaneous increase in platelet count and aggregability. The platelet function was not always reflected by the count in the patients with idiopathic thrombocytopenic purpura. On the other hand, in the control patients undergoing only laparatomy the platelet count substantially increased two weeks after operation, but platelet aggregability did not differ from the preoperative value. The present results suggest that additional factors for thromboembolism such as hypotension, acidosis, or stagnant blood flow should be avoided during the peak period of reactive thrombocytosis after splenectomy, and that an appropriate use of anticoagulants or inhibitors of platelet aggregation is recommended if and when necessary.

Adenosine Diphosphate↗

PubMed1977

Tumor embolism in the right atrium after hepatic artery ligation for hepatoma.

A case of tumor embolism in the right atrium after hepatic artery ligation for hepatoma was reported. Patient was a 55 year old male complaining of upper abdominal pain. Preoperative angiogram and scintigram revealed multinodular hepatomas in the right and middle his condition gradually deteriorated thereafter and sudden hypotension occurred on the 22nd postoperative day with a fatal sequela. At autopsy, the orifice of the right atrium was impacted by a tumor embolus. The cause of death seemed to be attributable to this embolus liberated from the hepatic veins. Accordingly, we emphasize the necessity of careful angiographic evaluation not only of the hepatic inflow but of the outflow tract in performing hepatic artery ligation as a treatment of nonresectable hepatoma.

Carcinoma, Hepatocellular↗