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K Yanaga

Publications and source records attributed to K Yanaga.

At least 37 records · Page 2Linked to original sources
PubMed2000

A novel auxiliary partial orthotopic liver transplantation model in rats.

BACKGROUND: Although auxiliary partial orthotopic liver transplantation (APOLT) has become a well-accepted procedure recently, a practical experiment model in APOLT using small animals has yet to be developed. METHODS: Male Lewis rats were used for both donors and recipients. An auxiliary partial graft was obtained by ex vivo resection of the donor right and caudate lobes, and was transplanted orthotopically into the recipient after resection of the recipient medial and left hepatic lobes. Portal vein and hepatic duct reconstructions were by the cuff technique, and supra- and intrahepatic vena cava were sutured continuously. Operative outcomes, serum chemistry, liver tissue blood flow, angiographic and histopathological findings were then examined. Conventional orthotopic liver transplantation (OLT) procedures were also undertaken as a control. RESULTS: One-day, 1-week and 1-month survival rate of APOLT group was 100, 85 and 85%, respectively. AST in the APOLT group on the 1st postoperative day was significantly higher than in the OLT group. No significant differences were recognized in serum albumin and total bilirubin levels between the two groups. Although the portogram of an APOLT rat showed slight narrowing at the cuff anastomosis site, both the graft and the native liver were opacified similarly. The liver tissue blood flow on the 5th postoperative day in the native liver and the graft returned to as high as 95 and 74% of the values on laparotomy, respectively. Histological examinations of the auxiliary graft 1 month after transplantation showed mild ductular proliferation and mononuclear cell infiltration around the portal triads. CONCLUSION: This novel APOLT model in rats allows practical and reproducible results, and may be of value in the basic study of APOLT procedures.

Angiography↗
PubMed2000

[Efficacy of UFT in the treatment of para-aortic lymph node metastasis following gastric cancer surgery: case report].

The patient was a 68-year-old man who underwent pyloric gastrectomy for advanced stomach cancer on December 6, 1996. The histopathological diagnosis was poorly differentiated adenocarcinoma, ss, ly3, v1, n2 (+), and stage IIIa. Postoperative adjuvant chemotherapy consisted of short-term intravenous infusion of 5-FU, 320 mg/m2/day (= 480 mg/body) for 5 days beginning on postoperative day (POD) 1, and oral 5-FU, 200 mg/day, for 1 year beginning on POD 14. The preoperative CEA value was 316.2 ng, but it fluctuated below 10 ng postoperatively. About one year after the operation, the patient began to complain of epigastric pain, loss of appetite, and general malaise. CT of the upper abdomen revealed a 1.5-cm para-aortic lymph node, and the CEA value of 319.0 ng was abnormally high. 5-FU was stopped, oral UFT at 300 mg/day was started, and the patient's course was followed. Three months after the start of UFT, the lymph node had shrunk on CT (shrinkage rate: 66.7%), and the CEA value had decreased to 14.3 ng. As though corresponding to these changes there was a gradual decrease in the epigastric pain, general malaise, etc., and the patient's appetite also returned. There were no subsequent elevations in the CEA values or increases in the size of the para-aortic lymph nodes, and the patient's general condition was favorably maintained. UFT appeared to be effective against the lymph node metastasis around the aorta in this case.

Adenocarcinoma↗
PubMed1999

Effects of deletion variant of hepatocyte growth factor on reduced-size liver transplantation in rats.

BACKGROUND: The deletion variant of hepatocyte growth factor (dHGF) exerts mitogenic and antifibrotic effects. The purpose of this study was to evaluate the effect of dHGF on rats that had undergone syngeneic or allogeneic reduced-size (60%) orthotopic liver transplantation (ROLT). METHODS: Starting immediately after the syngeneic (Lewis to Lewis) and allogeneic (Lewis to Brown Norway) ROLT, 500 microg/kg dHGF was administered i.v. twice a day until the day the rats were killed. Its effect on hepatic graft weight, regeneration, and biochemical parameters was evaluated. RESULTS: dHGF promoted restoration of the liver volume and liver regeneration as well as protein synthesis in the rats that underwent syngeneic ROLT. In the rats that underwent allogeneic ROLT, dHGF reduced the level of serum cytosolic enzymes related to acute cellular rejection, but a significant improvement in liver regeneration and protein synthesis was not seen. When tacrolimus was administered to prevent rejection of the allogeneic grafts, the beneficial effect of dHGF was apparent, and was as beneficial as in syngeneic ROLT. CONCLUSIONS: Administering dHGF after liver transplantation augments the regeneration and functional recovery of partial liver grafts and reduces hepatocyte injury in acute cellular rejection.

Animals↗
PubMed1999

Effect of specific neutrophil elastase inhibitor on ischemia/reperfusion injury in rat liver transplantation.

Activated neutrophils have been implicated as playing an important role in ischemia/reperfusion injury of the liver by releasing toxic mediators such as oxygen free radicals and elastases. In the present study, we evaluated the effect of a novel, specific neutrophil elastase inhibitor (ONO-5046) on cold-ischemia/reperfusion injury of the liver allograft in rodents. Livers from male Lewis rats were procured and stored cold (4 degrees C) in lactated Ringer's solution and transplanted orthotopically. Recipients were divided into three groups: Vehicle group, 5-h preservation and vehicle (n = 8); ONO-5046 group, 5-h preservation and administration of ONO-5046 (n = 8); and Control group, minimum preservation only (n = 8). Bile output after reperfusion was significantly larger in the ONO-5046 group compared to the Vehicle group (P < 0.05 or less). Sinusoidal endothelial cell function represented by the serum hyaluronic acid concentration at 120 min after reperfusion of the ONO-5046 group was significantly lower than that in the Vehicle group (17.0 +/- 7.9 vs 36.2 +/- 14.9 ng/ml, P < 0.05), whereas serum transaminase levels 120 min after reperfusion were comparable between the two groups. Liver tissue energy charge 120 min after reperfusion was significantly better in the ONO-5046 group compared to the Vehicle group (P < 0.05). Furthermore, the number of neutrophils infiltrating the allograft after reperfusion was significantly depressed in the ONO-5046 group compared to the Vehicle group (P < 0. 02). These data suggest that the neutrophil elastase might cause liver damage early after reperfusion in cold-stored liver, which can be ameliorated by the administration of a specific neutrophil elastase inhibitor, ONO-5046.

Adenine Nucleotides↗
PubMed1999

The mechanism of hepatic graft protection against reperfusion injury by prostaglandin E1.

The purpose of this study was to evaluate the effect of prostaglandin E1 (PGE1) on protecting against hepatic endothelial cell damage and increasing graft viability after cold preservation and reperfusion, using an isolated perfused rat liver (IPRL) model. The grafts were divided into three groups, according to the cold preservation time and PGE1 administration, namely: 4h preservation (group 1, n = 9), 6h preservation (group 2, n = 9), and 6h preservation followed by PGE1 infusion (group 3, n = 9). After cold storage, the grafts were put on the recirculating IPRL system, then reperfused for 120 min at 37 degrees C with oxygenated Krebs-Henseleit buffer containing hyaluronic acid (HA). To examine the function of the sinusoidal endothelial cells and hepatocytes, serial measurements of HA, tumor necrosis factor-alpha (TNFalpha), thromboxane B2 (TXB2), acid phosphatase, and conventional parameters in the perfusate were made. After perfusion, the trypan blue exclusion test was performed to assess the presence of any microscopic sinusoidal lining cell damage. In group 3, the bile output and HA clearance were significantly greater, while glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, TNFalpha, TXB2, and acid phosphatase in the perfusate were significantly lower than in group 2. Histologically, less endothelial cell damage and hepatocyte damage than in group 2 was also confirmed. These results therefore suggest that the improvement of hepatic graft viability by PGE1 administration is mainly due to sinusoidal endothelial cell protection.

Acid Phosphatase↗
PubMed1999

Deletion variant of hepatocyte growth factor prolongs allograft survival after liver transplantation in rats.

BACKGROUND: Despite continued progress in the development of immunosuppressive agents, allograft rejection remains an important cause of morbidity and mortality after liver transplantation. We examined the effect of the deletion variant of hepatocyte growth factor (dHGF) on allograft rejection after liver transplantation. METHODS: Male Dark Agouti rats (RT1a) were selected as donors and male Lewis rats (RT1l) as recipients for a rejection model. The recipients were divided into 2 groups after orthotopic liver transplantation (OLTx): in the dHGF group dHGF was given intravenously twice a day (1 mg/kg/day) after OLTx, whereas in the control group vehicle buffer was given intravenously daily twice after OLTx. The survival period, serum chemistry studies, and histopathologic findings were then compared between the 2 groups. RESULTS: The mean survival period after OLTx in the dHGF group was significantly longer than that in the control group (21.4 +/- 1.3 days vs 11.8 +/- 0.4 days, P < .001). On the 10th posttransplant day the serum albumin level significantly improved in the dHGF group (P < .01), and the serum total bilirubin and aspartate aminotransferase levels were significantly lower in the dHGF group (P < .01 and P < .05, respectively). On the 10th posttransplant day a histologic examination revealed no apparent difference in the severity of rejection between the 2 groups. The number of proliferating cell nuclear antigen-positive hepatocytes in the dHGF group significantly increased (P < .01), whereas the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling-positive hepatocytes were significantly reduced in the dHGF group (P < .01) in comparison with those in the control group. CONCLUSION: dHGF has an antiapoptotic property as well as a proliferative and protective effect on hepatocytes under allograft rejection. dHGF might serve as a novel agent for reducing the harmful effects of hepatic allograft rejection in rats.

Amino Acid Sequence↗
PubMed1999

[Effects of DAC (doxifluridine, adriamycin, cyclophosphamide) chemotherapy in advanced breast cancer patients].

Effects of DAC (doxifluridine (5'-DFUR), adriamycin (ADM), cyclophosphamide (CPA)) chemotherapy were evaluated in seven patients with advanced breast cancer. 5'-DFUR of 600 mg was orally daily, ADM of 40 mg/m2 was administered intravenously (bolus) at day 1 and CPA of 400 mg/m2 was administered intravenously (one shot) at day 1 and day 8. These were repeated as one cycle of 21 days. Two complete responses, three partial responses and two progressive diseases were obtained, and the response rate was 71% (95% confidence interval: 29-96%). The side-effects of more than grade 3 were observed in leucocytopenia (4/7), neutrocytopenia (6/7), anorexia (2/7), nausea or vomiting (2/7) and alopecia (6/7). These results suggest that DAC chemotherapy is a novel, attractive regimen for treatment of advanced breast cancer. The randomized clinical trial is required to elucidate the efficacy of 5-fluorouracil (5-FU) or its analogues and the significance of methods for their administration in management of patients with advanced breast cancer.

Administration, Oral↗
PubMed1998

A thoracoabdominal hepatectomy and a transdiaphragmatic hepatectomy for patients with cirrhosis and hepatocellular carcinoma.

OBJECTIVE: To evaluate the results of a thoracoabdominal hepatectomy and a transdiaphragmatic hepatectomy for hepatocellular carcinoma in patients with impaired liver function. DESIGN: Retrospective study. SETTING: A university hospital in Japan. PATIENTS: Twenty-seven patients who from 1991 to 1996 underwent a thoracoabdominal hepatectomy for hepatocellular carcinoma located mainly in the superior portion of the liver and 20 patients who underwent a transdiaphragmatic hepatectomy for hepatocellular carcinoma located near the diaphragm. MAIN OUTCOME MEASURES: Morbidity, survival, and disease-free survival after each operation. Comparisons were then made with 183 patients who had undergone an ordinary transabdominal hepatectomy during the same period. RESULTS: In the thoracoabdominal hepatectomy group, 17 patients underwent a partial resection, 4 patients underwent a subsegmentectomy, and another 6 patients underwent either a segmentectomy or a procedure that was greater in size than a segmentectomy, whereas all of the patients in the transdiaphragmatic group underwent a partial resection. The morbidities in the thoracoabdominal group included pleural effusion in 6 patients (22%); intra-abdominal infection in 5 patients (19%); and hepatic failure in 3 patients (11%), of whom 1 died (mortality rate, 4%). In the transdiaphragmatic group, only 2 patients (10%) had non-life-threatening complications. The cumulative survival rates and the disease-free survival rates of the patients at 3 years were 51% and 24% in the thoracoabdominal hepatectomy group and 62% and 30% in the transdiaphragmatic hepatectomy group; no significant differences were observed when these findings were compared with those of patients who had undergone a transabdominal hepatectomy. CONCLUSION: The outcomes of the patients undergoing thoracoabdominal hepatectomy and those undergoing a transdiaphragmatic hepatectomy were generally satisfactory in spite of the fact that these procedures were performed on patients with cirrhosis and impaired liver function.

Aged↗
PubMed1998

Prognosis of hepatocellular carcinoma with diabetes mellitus after hepatic resection.

We evaluated the effect of diabetes mellitus on the prognosis of hepatocellular carcinoma after an elective hepatic resection. Of the 342 patients who underwent a hepatic resection between April 1985 and March 1995, 87 (25.4%) were diabetic. Postoperative morbidity was more common among diabetics than among nondiabetics (36.0% vs. 22.5%, P = .0239). The postoperative survival rate and the cancer-free survival rate were also better in patients without diabetes than in those with diabetes (P = .0333, P = .0149). The results of a multivariate analysis show diabetes mellitus to be an independent and prognostic indicator after a hepatic resection with hepatocellular carcinoma. According to the above findings, diabetes mellitus is thus considered to be a risk factor for prognosis after hepatic resection in patients with hepatocellular carcinoma.

Adult↗
PubMed1998

Risk factors linked to postoperative morbidity in patients with hepatocellular carcinoma.

BACKGROUND: The aim of this study was to clarify the risk factors for morbidity as well as to establish an optimum surgical strategy for hepatocellular carcinoma (HCC). METHODS: The risk factors linked to postoperative complications were analysed in 388 patients over a 10-year period, according to the kind of operative procedure. RESULTS: Stepwise regression analysis revealed that the most important factors related to postoperative morbidity were: age, creatinine level and the histological grade of fibrosis for the bisegmentectomy; the presence of diabetes mellitus, blood urea nitrogen level, the indocyanine green dye retention rate at 15 min and blood loss for the segmentectomy; the presence of diabetes mellitus and blood loss for subsegmentectomy; the presence of diabetes mellitus, the aspartate aminotransferase level, and the total operating time for resection less than subsegmentectomy. CONCLUSION: The most important risk factors were not always related to liver function tests, but instead to other coexisting conditions such as diabetes mellitus and operation stress including operating time and blood loss. Therefore, any future treatment strategy of hepatic resection for HCC should make every effort both to evaluate coexisting conditions carefully and to reduce operative stress as far as possible.

Age Factors↗
PubMed1998

Amelioration of liver injury by ischaemic preconditioning.

BACKGROUND: Ischaemic preconditioning, i.e. preparatory brief ischaemia before subsequent long ischaemia, can effectively protect the heart from ischaemia-reperfusion injury in animals. The purpose of this study was to demonstrate the same phenomenon in the liver. METHODS: Using warm ischaemia-reperfusion of 70 per cent of the liver followed by resection of the non-ischaemic portion in rats, livers with 10 min of ischaemic preconditioning, i.e. 10 min of warm ischaemia and reperfusion, were compared with those that had not been subjected to such a manoeuvre. RESULTS: At 120 min after reperfusion following 40 min of warm ischaemia, the livers with 10 min of ischaemic preconditioning had a significantly lower mean(s.d.) serum alanine aminotransferase level (492(217) versus 1236(695) units/l; P < 0005) and lactic dehydrogenase level (7905(4002) versus 15066(9201) units/l; P< 0.05), as well as a higher bile output (0.12(0.03) versus 0.09(0.04) ml per g liver; P < 0.05) and liver tissue adenosine 5'-triphosphate level (78(13) versus 61(11) per cent; P< 0.05) than the control livers. The necrosis rate, histologically defined as the percentage of necrotic area in given liver sections, was reduced significantly by this manoeuvre (mean(s.d.) 1.3(1.3) versus 5.3(1.7) per cent; P< 0.05). CONCLUSION: Ischaemic preconditioning exerts a protective effect on hepatic warm ischaemia-reperfusion injury. Such a manoeuvre may be useful for hepatic resection in the clinical setting.

Adenosine Triphosphate↗
PubMed1998

Prognostic factors after repeat hepatectomy for recurrent hepatocellular carcinoma.

OBJECTIVE: The aims of this study were to identify prognostic factors in patients who developed recurrent hepatocellular carcinoma (HCC) after repeat hepatectomy and to elucidate the role of multicentric occurrence in the second tumor after a first hepatectomy. SUMMARY BACKGROUND DATA: A repeat hepatectomy for recurrent HCC has been established as the most effective treatment modality, whenever it is possible. However, the prognostic factors for recurrent HCC after repeat hepatectomy have yet to be clarified. METHODS: Forty-one patients who underwent a curative repeat hepatectomy were retrospectively studied. Patient survival and disease-free survival after recurrence were univariately and multivariately analyzed using 38 clinicopathologic variables. The histologic grade of HCC at repeat hepatectomy was also compared with that at first hepatectomy. RESULTS: Patient survival after repeat hepatectomy did not differ substantially from that in 312 patients undergoing primary hepatectomy. However, the disease-free survival after repeat hepatectomy was significantly lower than that in patients with only a primary hepatectomy (p < 0.05). Multivariate analysis revealed only portal vein invasion in the first hepatectomy to be an independent and significantly poor prognostic factor. Regarding multicentric occurrence at repeat hepatectomy, only 6 of 40 patients (15%) whose specimens could be evaluated histologically were determined to be Edmondson and Steiner's Grade 1. CONCLUSIONS: The only prognostic factor identified in patients with recurrent HCC after repeat hepatectomy was portal vein invasion in the first hepatectomy. Most second tumors after the first hepatectomy are considered to be caused by metastatic recurrence, not by multicentric occurrence.

Algorithms↗
PubMed1998

Effect of thromboxane synthetase inhibitor on non-heart-beating donors in rat orthotopic liver transplantation.

BACKGROUND: The use of non-heart-beating donors could relieve donor organ shortage provided that the outcome of the recipients is not jeopardized. METHODS: In this study we evaluated the effect of thromboxane synthetase inhibitor (OKY-046) on non-heart-beating donors in orthotopic liver transplantation in rodents. OKY-046 (OKY group, n = 8) or vehicle (control group, n = 8) was given to the donor animals for 60 minutes before the induction of 30 minutes of warm ischemia to the liver before transplantation and survival, and several parameters were compared between the two groups. RESULTS: All recipients in the control group died within 2 days, whereas 67% of those of the OKY group had a 2-day survival and 44% had a 2-week survival (p < 0.01). Bile output from the allograft for 2 hours after reperfusion was significantly larger in the OKY group at all time points (p < 0.05). Furthermore, serum transaminase levels 10 minutes after reperfusion were significantly lower in the OKY group (p < 0.05), although those 120 minutes after reperfusion were comparable between the two groups. The thromboxane B2 level in liver tissue 10 and 120 minutes after reperfusion was significantly lower in the OKY group compared with the control group (p < 0.02 and p < 0.05, respectively). CONCLUSIONS: These results indicate that OKY-046 given to the donor before the induction of warm ischemia could ameliorate ischemia/reperfusion injury of the hepatic allograft by reducing thromboxane A2 production after reperfusion.

Alanine Transaminase↗
PubMed1997

Indications for palliative reduction surgery in advanced hepatocellular carcinoma. The use of a remnant tumor index.

OBJECTIVES: To clarify the indications for and the significance of palliative reduction surgery in the multidisciplinary treatment of advanced hepatocellular carcinoma (HCC) and to propose the use of a remnant tumor index (RTI) as a simplified criterion for palliative reduction surgery in cases of advanced HCC. DESIGN: A comparison of survival based on the RTI. SETTING: A large university hospital in Japan. PATIENTS: Twenty-five patients with advanced HCC who underwent palliative reduction surgery were divided into 3 groups as follows: group 1 (n = 9), the remnant tumor after operation existed only in the liver and the RTI was less than 5.0; group 2 (n = 11), the remnant tumor after operation existed only in the liver and the RTI was greater than 5.0; and group 3 (n = 5), extrahepatic metastatic tumor existed after operation. MAIN OUTCOME MEASURES: Pathological findings and survival rate after surgery. RESULTS: There was no significant difference in the degree of macroscopic intrahepatic metastases among the 3 groups; however, both the portal vein invasion and the histological grade tended to be more severe in groups 2 and 3. The respective 1-year and 3-year survival rates for group 1 were 67% and 33%, and those for group 2 were 21% and 0%. There were no survivors in group 3 at 1 year after surgery. Significant differences were found in the survival rates between groups 1 and 2 (P < .05), and between groups 1 and 3 (P < .05). CONCLUSION: Palliative reduction surgery for advanced HCC is only considered effective for patients with both an RTI of less than 5.0 and no extrahepatic metastasis.

Aged↗
PubMed1997

Reduction of rewarming injury of the hepatic graft by a heat insulator.

BACKGROUND: The deleterious effect of rewarming in orthotopic liver transplantation is recognized. This study examined the significance of rewarming the hepatic allograft, and the possibility of using a heat insulator to reduce rewarming injury. METHODS: After total hepatectomy in rats with in situ perfusion by chilled (4 degrees C) lactated Ringer's solution, the livers were divided into four groups of ten each: group 1, 4-h preservation in chilled Ringer's solution and 15 min of rewarming; group 2, 6-h preservation in chilled Ringer's solution; group 3, 6-h preservation in chilled Ringer's solution and 15 min of rewarming; group 4, 6-h preservation in chilled Ringer's solution and 15 min of rewarming with a heat insulator. Glutamic-pyruvic transaminase (GPT) and N-acetyl-beta-glucosaminidase (NAG) concentrations in the final graft effluent, and the amount of adenosine 5'-triphosphate (ATP) in liver tissue after preservation, were measured. RESULTS: GPT and NAG concentrations in the final graft effluent of group 3 were higher than those of group 2 (P < 0.01), whereas values in group 4 were lower than those of group 3 (P < 0.05). The final ATP concentration in group 3 was significantly lower than that in group 2 (P < 0.01), whereas the value in group 4 was significantly higher than that of group 3 (P < 0.01). CONCLUSION: Rewarming diminishes the viability of a liver graft with degradation of ATP, and a heat insulator reduces rewarming injury.

Acetylglucosaminidase↗
PubMed1997

Significance of liver size in hepatic surgery.

The purpose of this study was to evaluate the significance of liver volumetry as a parameter for hepatic functional reserve in cirrhotic patients with hepatocellular carcinoma. Liver volume was calculated from preoperative computed tomograms of 44 cirrhotic patients who underwent elective hepatic resections for hepatocellular carcinoma. The liver volume per body weight of non-alcoholic cirrhotics was significantly smaller than that of alcoholic cirrhotics (20.9 vs. 26.7 cc/kg; p = 0.03). The values for alcoholic cirrhotics was comparable with normal values. The liver volume per body weight of the cirrhotic patients demonstrated correlation with the preoperative serum albumin (p < 0.01) and indocyanine green clearance (p = 0.02). We conclude that the determination of hepatic atrophy by volumetry can serve as a parameter for the assessment of hepatic reserve but not as a predictor of postoperative complications in elective liver surgery for cirrhotic patients.

Atrophy↗