Makoto Kume

New Simple Technique for Hepatic Parenchymal Resection Using a Cavitron Ultrasonic Surgical Aspirator® and Bipolar Cautery Equipped with a Channel for Water Dripping

Abstract. We have developed a new technique to resect hepatic parenchyma without inflow occlusion by using the Cavitron Ultrasonic Surgical Aspirator (CUSA®) and bipolar cautery with a saline irrigation system. The significance of this method in hepatectomy was analyzed in comparison with historical control of hepatectomy using Pringles maneuver. An ordinary bipolar cautery was remodeled with an infusion line to bring saline droplets down the inner surface of one arm of the tweezers through an opening about 1.5 cm proximal to its tip. The optimal flow rate of saline was approximately one drop per second. The power of bipolar cautery was adjusted to 50 watts. When the tweezer blades were approximated to 1 or 2 mm, saline droplets were directed to the tip of tweezers and could be immediately evaporated. After sonicating parenchymal cells, the tissue of small branches of Glissons tree or small tributaries of the hepatic vein were coagulated by bipolar cautery. The coagulated cords were then easily cut by scissors. The impact of this technique on ordinary liver resections was evaluated by analyzing the postoperative clinical course in relation to the hepatic functional reserve necessary for major hepatectomy, duration of hepatectomy, and intraoperative blood loss. Hepatic resection without vascular occlusion using this technique could decrease the morbidity in patients who have less hepatic functional reserve. It could also decrease intraoperative blood loss. This new technique effectively decreased the surgical load of the remnant liver during parenchymal resection by avoiding ischemic stress. Consequently it extends the safety limits of major hepatectomy.

Pharmacologic stimulation of adenosine A2 receptor supplants ischemic preconditioning in providing ischemic tolerance in rat livers

BACKGROUND Ischemic preconditioning (IPC) is a promising strategy for conferring ischemic tolerance. We confirmed the acquisition of ischemic tolerance in the liver immediately after IPC and the role of adenosine kinetics in this process. METHODS Male Lewis rats were used. IPC was administered with a 10-minute ischemia followed by a 10-minute reperfusion. Ischemic tolerance was tested with a 45-minute ischemia. Changes in the adenosine concentrations in liver tissue were evaluated, and the effects of adenosine A1 or A2 receptor agonists or antagonists were examined either in place of or against IPC. RESULTS The 7-day animal survival was significantly better in the IPC group than in the control group (87% vs 53%; n = 15, P < .05). The release of liver-related enzymes during reperfusion was suppressed better in the IPC group (P < .01). Recovery of adenosine triphosphate levels was faster in the IPC group (P < .01). After IPC, adenosine concentrations in liver tissue immediately increased to 1555 +/- 299 pmol/g wet tissue and were maintained at that level during a subsequent 45-minute ischemia. The ischemic tolerance generated by IPC was mimicked by the administration of adenosine A2 receptor agonist and opposed by adenosine A2 receptor antagonist. CONCLUSIONS The ischemic tolerance of the liver immediately after IPC can be supplanted by selective pharmacologic stimulation of adenosine A2 receptors.

Changes in the fatty acid composition of the liver with the administration of N-3 polyunsaturated fatty acids and the effects on warm ischemia/reperfusion injury in the rat liver.

Prostanoids play a pivotal role among the inflammatory mediators associated with I/R injury. The aim of this study was to determine the effects of oral supplementation of n-3 polyunsaturated fatty acids (PUFA)-rich oil on inflammatory reactions and microcirculatory disorders caused by a hepatic warm I/R in rats. The rats were orally supplemented with n-3 PUFA-rich oil, n-6 PUFA-rich oil, or the same volume of water for 7 days. The PUFA concentration in the blood and liver tissues were evaluated, and the effects on I/R injury of the liver were assessed. The n-3 PUFA supplementation elevated the n-3/n-6 ratio in the blood and liver tissues. After reperfusion, thromboxane B2 in the blood and prostaglandin E2 in the liver were significantly suppressed in the n-3 PUFA-treated rats. Hepatic microcirculation was well maintained from the early phase (30 min) of reperfusion, and the serum concentrations of TNF-&agr; and IL-6 were significantly lower in this group. The transaminase blood levels were also suppressed in the n-3 PUFA-treated rats. Expression of COX-2 mRNA was increased in all groups at 2 h after reperfusion but there were no differences among three groups. In conclusion, preoperative n-3/n-6 ratio augmentation in the blood and in the liver can result in a successful alleviation of hepatic I/R injury.ABBREVIATIONS-AA-arachidonic acid; &agr;-LA-&agr;-linolenic acid; ALT-alanine aminotransferase; AST-aspartate aminotransferase; COX-cyclooxygenase; DHA-docosahexaenoic acid; DPA-docosapentaenoic acid; ELISA-enzyme-linked immunosorbent assay; EPA-eicosapentaenoic acid; ICU-intensive care unit; LA-linoleic acid; LDH-lactic dehydrogenase; MPO-myeloperoxidase; PG-prostaglandin; PUFA-polyunsaturated fatty acids; TX-thromboxane

Implications of Heat Shock Proteins During Liver Surgery and Liver Perfusion

Cells primed by sublethal stress transiently overproduce heat shock proteins (HSPs) and thereby develop tolerance to the next lethal stress. This response in organisms is called the stress response and involves the induction of HSPs. To assist the liver in developing tolerance for warm ischemia-reperfusion injury, which sometimes jeopardizes the patients after extended surgery for malignancies with vascular invasion in the liver, basic experiments to activate the stress response using stress preconditioning were performed. Heat shock preconditioning in rat livers has been shown to induce tolerance against warm ischemia-reperfusion injury in normal, fibrotic, and steatotic livers. Ischemic preconditioning using short-term Pringles maneuver and pharmacological preconditioning using doxorubicin were also effective. In rats, heat shock preconditioning protected livers from free radical injury induced by the oral administration of carbon tetrachloride. The above data were supported by animal survival, suppression of serum transaminase levels, and improved energy status of the liver after intervention. Increased production of HSP72 was observed after preconditioning. In addition, the significance of HSP production as a stress parameter was demonstrated during the reperfusion of congested portal blood to the ischemic liver. The ill effect of congested portal blood could not be detected by conventional parameters but was detected by observing the increase in HSP72 production. Stress preconditioning seems to be a promising strategy to counter the damaging effect of hepatic warm ischemia during liver surgery and liver perfusion.

Induction of Heat Shock Response: Effect on the Rat Liver with Carbon Tetrachloride-induced Fibrosis from Ischemia-reperfusion Injury

AbstractThe role of heat shock pretreatment in the induction of tolerance for ischemia-reperfusion injury was investigated in rat livers with fibrosis produced by carbon tetrachloride (CCl4) injected subcutaneously. The control group (group C, n= 56) received no pretreatment except anesthesia, and the heat shock group (group HS,n= 56) were exposed to heat shock (42°C) for 15 minutes. After a 48-hour recovery all rats were subjected to 30 minutes of warm ischemia. Western blotting analysis was employed for heat shock protein (HSP) 72 detection. The adenine nucleotide levels in liver tissue and the liver enzyme levels in serum were measured before and after ischemic intervention (seven animals were used at each of six time point measurements in both groups). HSP72 was induced in group HS at greater intensity than in group C. The survival rate on postoperative day 7 in group C (3/14) was significantly poorer than that in group HS (14/14) (p < 0.01). The higher survival rate in group HS was accompanied by more rapid recovery of the adenosine triphosphate level and lower serum levels of liver enzymes after reperfusion (p < 0.01 vs. group C). Heat shock preconditioning induces HSP72 in the rat liver with fibrosis and provides significantly increased tolerance of warm-ischemia reperfusion injury.

The augmentative effect of repeated heat shock preconditioning on the production of heat shock protein 72 and on ischemic tolerance in rat liver tissue.

Objective : Heat shock pretreatment induces heat shock protein (HSP)72 strongly in rat livers and provides the tolerance against subsequent ischemia-reperfusion injury. In this study, the effects of repeated heat shock pretreatment on the production of HSP72 in rat livers and on subsequent ischemic tolerance were investigated. Methods : Rats pretreated with repeated heat shock were compared with those that received a single heat shock pretreatment. The production of HSP72 was analysed using Western-blotting and densitometer. At 48h after heat shock pretreatment, all rats were subjected to warm liver ischemia for 30 or 45min and then reperfused. Survival rate of the animals and liver functions during reperfusion were analysed. Results : The production of HSP72 increased in the repeated heat shock group more than in the single heat shock group. Although there were no significant differences in animal survival or in liver functions after a 30-min ischemia between the single heat shock group and the repeated heat shock group, animal survival and liver functions after a 45-min ischemia were significantly better in the repeated heat shock group. Conclusion : In rats, repetition of heat shock pretreatment augmented the production of HSP72 in liver tissue and protected the liver from ischemia-reperfusion injury.

Transfection of naked nuclear factor-κB decoy oligodeoxynucleotides into liver by rapid portal vein infusion in rats: its effect on ischemia-reperfusion injury of liver.

This study was aimed at examining whether rapid portal vein infusion (RPVI) of a small volume of naked oligodeoxynucleotides (ODNs) could be used to transfect sufficient amounts of nuclear factor-κB (NF-κB) decoy ODN into the liver to suppress NF-κB activation during liver ischemia-reperfusion (I/R) injury, in which NF-κB plays a central role in regulating the production of inflammatory cytokines. One milliliter of naked NF-κB decoy ODN solution was administered into the portal vein for a few seconds. Transfection efficacy was examined by labeling the ODN with a fluorescent tag. Activation of NF-κB was investigated by electrophoretic mobility shift assay. Levels of serum liver enzymes and cytokines were measured during liver I/R injury. NF-κB decoy ODN was preferentially incorporated into Kupffer cells and sinusoidal endothelial cells, but not hepatocytes, in the rat liver. Transfected NF-κB decoy ODN suppressed the function of NF-κB in both Kupffer cells and sinusoidal endothelial cells during liver I/R injury, causing significant decreases in serum tumor necrosis factor-α and interleukin-6 levels 3 hr after reperfusion. Although the decrease in serum liver enzymes was not significant, naked NF-κB decoy ODN was successfully incorporated into Kupffer cells and sinusoidal endothelial cells by rapid portal vein infusion, inhibited NF-κB activation in both cells, and suppressed the production of inflammatory cytokines during the early phase of liver I/R injury.

Pigmentary complication of the peristomal skin in colorectal cancer patients under systemic chemotherapy using S-1: report of cases.

PURPOSE: This study describes hyperpigmentation at the epidermis around a colostomy during and after systemic chemotherapy with S-1 (a compound of tegaful, gimestat, and potassium oxonate). SUBJECTS AND SETTING: Thirty-one colorectal cancer patients (male 17, female 14) visited the stoma-care clinic, akita university hospital between april 2003 and march 2006. fourteen patients (male 8, female 6) had been observed continuously for more than 3 months. METHODS: Results of 5 male patients who received systemic chemotherapy using S-1 were compared to those of 9 male and female patients who did not receive S-1. the shades of epidermal pigmentation at the peristomal area were graded on a 3-point likert scale, where grade 2 indicated very dark pigmentation, grade 1 indicated moderately dark pigmentation, and grade 0 indicated no pigmentation of the peristomal skin. RESULTS: Pigmentation scores in patients receiving S-1 were significantly higher than scores in patients who did not receive S-1 systemic chemotherapy. CONCLUSIONS: Rapid and excessive pigmentation of the peristomal skin may occur in patients receiving S-1 systemic chemotherapy because it indicates an adverse event related with systemic chemotherapy and leads to peristomal skin problems.