[Combination of transcatheter arterial infusion of SMANCS and embolization on hepatocellular carcinoma].
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Biomedical subjects
Publications and source records attributed to K Kumada.
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OBJECTIVE: Abnormally elevated central venous pressure is considered to be an etiological factor in the onset of acute hepatic failure following modified Fontan operation. This paper hypothesises that an increase in inferior vena cava pressure (IVCP) after such an operation has adverse effects on hepatic energy status. DESIGN: Various degrees of venous hypertension were produced in 10 mongrel dogs by clamping the thoracic IVC with an active veno-venous shunt and varying its flow rate from 60-2.5 ml/min/kg. Arterial ketone body ratio (KBR), reflecting the hepatic mitochondrial redox state, was measured as an index of hepatic energy status. MEASUREMENTS AND RESULTS: The lower the flow rates of the shunt, the higher the pressures of IVC and portal vein, while systolic blood pressure was maintained above 100 mmHg. CO significantly decreased when the pump speed was less than 30 ml/min/kg. KBR showed a negative correlation to IVCP as well as a positive correlation to portal blood flow (p < 0.05). CONCLUSION: From the simple regression line obtained between IVCP and KBR, it was determined that an upper safety limit of IVCP may lie at about 27 cmH2O (20.5 mmHg), and that a IVCP of 35 cmH2O (26.6 mmHg) seems to be the critical level for maintaining liver viability.
The effect of low-molecular-weight heparin (LMWH) on hepatic mithocondrial metabolism was compared with that of unfractionated heparin (UH) after the intravenous administration of these two kinds of heparin to normal rabbits. The magnitude of decrease in blood triglyceride levels 5 min after administration of UH (200 U/kg) was significantly greater than after LMWH (200 U/kg). Free fatty acid levels in the blood were significantly higher after this dose of UH than after LMWH. Blood total ketone body levels (acetoacetate + 3-hydroxybutyrate) 15 min after injection of 50 U/kg of UH were significantly higher than those after a dose of 50 U/kg of LMWH, and levels after 200 U/kg of UH were significantly higher than those after 200 U/kg of LMWH at 15, 30, 45 and 60 min. Enhanced ketogenesis was not noted after LMWH at any of the doses, or after UH at 3 U/kg. Arterial ketone body ratio (AKBR; acetoacetate/3-hydroxybutyrate), which reflects the hepatic mitochondrial oxidation-reduction state (NAD+/NADH), was maintained above 1.0 in all groups except in the U-200 group, while AKBR in that group was significantly decreased to 0.99 +/- 0.14 at 30 min, and further decreased to 0.80 +/- 0.08 at 60 min. These results indicate that LMWH has less effect on lipolysis than UH and does not enhance ketogenesis, resulting in less deterioration of mitochondrial redox state.
We reviewed 37 living related liver transplantations (LRLT) performed by our department during the last 27 months on children with end-stage liver disease. The patients were 15 boys and 22 girls aged 7 months to 15 years with biliary atresia (27), cryptogenic cirrhosis (3), Budd-Chiari syndrome (2), progressive intrahepatic cholestasis (2), protoporphyria (1), Wilson's disease (1), and fulminant hepatitis (1). The donors were 14 fathers and 23 mothers. Grafts were made from the left lateral segment (19), left lateral segment with partial S4 (11), left lobe (6), and right lobe (1). After graft harvesting all donors resumed normal liver function and normal life. The recipient underwent total hepatectomy with preservation of the inferior vena cava. FK506 and low-dose steroids were used for immunosuppression. The survival rate was 90% (27/30) in elective cases and 57% (4/7) in emergency cases. Six recipients had functioning grafts but died of extrahepatic complications. Hepatic vein stenosis occurred in 3 cases at 3 months after LRLT and was successfully treated by balloon dilatation. Portal vein stenosis occurred in 1 case at 8 months after LRLT and was also safely dilated. We incurred no hepatic artery thrombosis after introducing microsurgery techniques. Among 12 viral, 5 bacterial, and 3 fungal postoperative infections, 1 Candida pneumonia and 1 EBV-associated lymphoma were lethal. Three patients with ABO-blood group compatible grafts and one with an incompatible graft developed acute rejection, which was controlled in evey case by steroid bolus and/or increasing the dose of FK506. There were no definite episodes of rejection in ABO-identical cases. Children with moderate growth retardation (> or = -1.5 SD of normal growth) caught up in growth soon after LRLT, but those with severe retardation (<-1.5 SD) were slow to attain age-normal height. Appropriate timing, meticulous surgical procedures, and comprehensive management of complications are crucial for successful outcome with LRLT. LRLT is a promising option for alleviating the shortage of livers for pediatric transplantation and may be regarded as an independent modality to supplement cadaver donation.
The relationship between portal hemodynamics and the energy metabolism of the liver with acute hepatic venous occlusion (HVO) was investigated by assessing the changes in the hepatic blood flow, arterial blood ketone body ratio (AKBR) and adenylate energy charge potential (ECP) of the liver tissue in canine model. Acute HVO was induced by the ligation of both the supra- and infrahepatic inferior vena cava (IVC) over the protruding ends of a heparin-coated polyethylene cannula inserted into the IVC. All dogs with only HVO (n = 5) died within 30 min. HVO dogs with additional mesocaval (MC) shunt (n = 10) survived longer than 7 days, during which time their AKBR were maintained in the normal range (over 1.0). ECP was also maintained above the normal level (over 0.850) during the 28-day period. Along with increasing portal pressure caused by the narrowing of the shunt anastomosis, the hepatic blood flow decrease gradually, resulting in a sudden decrease in AKBR and ECP when the portal pressure increased over 11 mm Hg. It is suggested that the normalization of portal pressure is one of the most important factors for maintaining the hepatic energy metabolism and that MC shunt is an effective therapy for maintaining the function of the liver with HVO, as long as portal pressure can be kept within normal range.
The influence of deteriorated liver function on the healing process of arterial anastomosis was investigated in rats who underwent arterial reconstruction by the microscopic surgical techniques of conventional sutured vascular anastomosis (CSVA) and laser-assisted vascular anastomosis (LAVA). After 70% hepatectomy, the arterial ketone body ratio, reflecting the hepatic mitochondrial redox state, and the adenylate energy charges of the platelets, polymorphonuclear leukocytes and mononuclear cells, which play an important role in wound healing, were significantly lower in hepatectomized rats than in control. Tensile strength and bursting pressure with CSVA at the abdominal aortic anastomosis were also significantly lower in hepatectomized rats than in control. While CSVA was superior to LAVA in tensile strength, bursting pressure and incidence of aneurysm formation in nonhepatectomized rats, LAVA tended to show a lower degree of disadvantage in hepatectomized rats than CSVA, especially in the incidence of calcification at the anastomotic site. It was concluded that LAVA would be a useful option in vascular anastomosis, even during extended hepatectomy.
We describe a method for detecting virus-specific RNA sequences using a nonradioactive enzyme system, and analyze coxsackie B4 virus (cox.B4) RNA sequences in infected mouse kidney with pathological changes. Diffuse mesangial proliferation was observed transiently 24 h after inoculation of cox.B4 virus in glomeruli. OCT-treated thin sections of the same tissue were hybridized in situ using a digoxigenin-labeled oligonucleotide probe. The strongest signal was observed in the mesangial sample. These findings suggest that the transient proliferative mesangial changes were caused by direct injury following virus infection without immune complex.
OBJECTIVE: To evaluate the results of the treatment of lymphoedema by intra-arterial infusion of autologous lymphocytes. DESIGN: Open study. SETTING: University Hospital. SUBJECTS: 13 patients with refractory lymphoedema. INTERVENTIONS: Lymphocytes were separated from the patient's own blood using a blood cell separator; about 100 cc of lymphocyte dominant blood separated from this blood was immediately infused into the proximal artery of the affected limb. Infusion was practiced once a week, and repeated 4 to 6 times. MAIN OUTCOME MEASURES: Change in size of the affected limb (defined as the difference between the affected limb and the normal limb after treatment), and softening of the edema (measured with a tension gauge). RESULTS: In all 13 patients there was softening of the affected hard limb followed by a reduction in the size of the limb (mean 64%), and the ache and sensation of heat in the limb lessened. The reduction in size was maintained in 9 of the 13 patients for three months, despite returning to their normal activities. CONCLUSION: Intra-arterial infusion of autologous lymphocytes is a promising treatment for refractory lymphoedema.
The size of segmental liver grafts assessed by preoperative computed tomography (CT) volumetry was evaluated in relation to surgical outcome in 14 living related partial liver transplantations (LRLTs). The aim was to show that graft size can be accurately assessed before operation and to estimate the lower safety limit of graft size in assessing subsequent graft function and survival. The relationship between calculated CT volume and weight of the liver was linear in the recipient (r = 0.97) and donor (r = 0.98). The mean(s.e.m.) modified liver weight ratio (MLWR; ratio of graft weight to recipient's expected liver weight based on body-weight) was 0.59(0.07) (range 0.27-1.09). Surgical complications related to an oversized graft and primary graft failure caused by a small-for-size graft were not observed. The lowest MLWR of any survivor was 0.27. These results suggest that a partial liver graft reduced to about 30 per cent of the recipient's expected liver weight can tolerate LRLT well.
PCNA is known as a cell cycle-related nuclear antigen. We stained PCNA immunohistochemically, and examined whether or not PCNA expressive rate could be applied clinically for a biological parameter of the histopathological effects in preoperative chemotherapy. PCNA was stained in proliferating cell by measuring nuclear DNA simultaneously. The most suitable fixation time in PCNA expression was 24 hours. On the examination of fixation fluid, ethanol was considered to be more suitable than buffer formaldehyde because PCNA expressive rate in ethanol correlated to BrdU labeling index with statistical significance. We examined PCNA expressive rate in gastric carcinomas. In the group whose histopathological effects of preoperative chemotherapy was recognized to be positive, PCNA expressive rate was significantly lower than in the group of negative effect. We measured thymidylate synthetase inhibition rate (TSIR) in the cases of preoperative oral administration of 5-FU, and the significantly negative correlation was seen between TSIR and PCNA expressive rate in the cases of differentiated adenocarcinoma (p < 0.05). The proliferating activity was recognized to be lower in the cases of higher inhibitional effect for DNA synthesis. PCNA expressive rate was considered to be a more effective and objective biological parameter on the evaluation of malignant potential in gastric carcinoma.
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Hepatic vascular exclusion with double venovenous bypass using a centrifugal force pump was used in major hepatic resections in eight patients with hepatocellular carcinoma combined with cirrhosis, and results were compared with those in four patients with hepatocellular carcinoma without cirrhosis and eight with metastatic tumors without cirrhosis among 521 patients undergoing liver resection. Concomitant resection of the retrohepatic inferior vena cava was performed in three of eight patients with cirrhosis and five of 12 patients without cirrhosis. All patients, except one with cirrhosis, tolerated major resection without any hemodynamic impairment, which is often observed in hepatic vascular exclusion without venovenous bypass. One patient, whose complete inflow occlusion period was 70 minutes, died of liver failure. In this patient, the recovery of the arterial ketone body ratio above 1.0 was delayed until 3 days after recirculation, whereas the ratio in the others recovered promptly. Postoperative complications such as increased bilirubin level, pleural effusion, and gastrointestinal tract bleeding were observed in seven of eight patients with cirrhosis compared with six of 12 without cirrhosis. Hepatic vascular exclusion is feasible even in cirrhotics as long as it is applied with venovenous bypass and is kept within the time limit of 60 minutes.
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To investigate the pathophysiology of warm ischemia (WI) of the liver, the changes in hemodynamics and energy metabolism were studied during and after 60-min complete WI induced by total hepatic vascular exclusion (HVE) in the canine model. Hepatic arterial blood flow after WI was maintained at 76% of the pre-ischemic level, while portal blood flow was only 27% of the pre-ischemic level associated with increased portal vein pressure, which was twice the pre-ischemic level, resulting in a decrease of total hepatic blood flow to 46% of the pre-ischemic level. Concentration of tissue lipid peroxide increased after WI. Arterial blood ketone body ratio (AKBR), which reflects the hepatic mitochondrial redox state, could not recover to the pre-ischemic level after termination of WI. However, when 100 mg/kg of allopurinol (xanthine oxidase inhibitor) was administered intravenously 10 min prior to initiating WI, AKBR was restored to the pre-ischemic level at 30 min after WI in spite of the fact that allopurinol administration to one group produced no remarkable changes in the hepatic hemodynamics compared with the group without allopurinol treatment. Concentration of adenine nucleotides was significantly higher for the treated group at the end of and after WI than for the group without allopurinol treatment and was maintained at a higher level even after WI. Lipid peroxide production was suppressed. Electron microscopic examination revealed that allopurinol treatment could not prevent mitochondrial swelling. It is suggested that WI causes injury primarily to the portal sinusoidal circulation, resulting in portal congestion concomitant with high portal pressure after the release of WI. Allopurinol could prevent the deterioration of mitochondrial ATP metabolism, and was able to inhibit lipid peroxide production, resulting in the rapid recovery of mitochondrial redox state in spite of the fact that it produced no amelioration of hepatic hemodynamics and morphological alterations.