Koichi Kozaki

Living-donor liver transplantation for hepatocellular carcinoma.

In cadaveric liver transplantation, the Milan criteria have been accepted as the selection criteria for hepatocellular carcinoma (HCC) patients in considering organ allocation. However, the situation is different in living-donor liver transplantation (LDLT), in which the donor has a strong preference for altruism. The authors describe herein their experience with LDLT for HCC patients using their patient selection criteria. From February 1999 to March 2002, right lobe LDLT was performed in 56 patients with HCC. The authors’ exclusion criteria included only those with extrahepatic metastasis or vascular invasion detected during preoperative evaluation. Thirty patients (54%) were in tumor, node, metastases stage IVa and 25 patients (45%) did not meet the Milan criteria at the time of LDLT. The follow-up period was 1 to 39 months (median, 11 months). The overall survival rates at 1 and 3 years were 73% and 55%, respectively, and the latter was significantly lower than that of adult right lobe LDLT without HCC (71% at 3 years). Fourteen patients died because of postoperative complications without tumor recurrence. Thirty-six patients survived without recurrence and six patients had recurrence. Among the six patients with recurrence, four had survived for 11 to 36 months after LDLT. In the analysis of patients who survived longer than 3 months after transplantation, 19 of 20 within the Milan criteria survived without recurrence. However, 15 of 20 patients beyond the criteria also survived without recurrence for 3 to 33 months (median, 12 months) and three of five patients with recurrence were alive for 11 to 36 months (median, 20 months). Histopathologic grading and microscopic portal venous invasion had significant negative impact on tumor recurrence. LDLT was an effective treatment for uncontrollable hepatocellular carcinoma. Because many patients who did not meet the Milan criteria survived without tumor recurrence after transplantation, different patient selection criteria are necessary in LDLT to save those with advanced HCC.

Long-term outcomes of 600 living donor liver transplants for pediatric patients at a single center.

This report concerns the long‐term outcome of living donor liver transplantation (LDLT) for pediatric patients at a single center. Between June 1990 and December 2003, a total of 600 LDLTs, including 568 primary transplantations and 32 retransplantations, were performed for pediatric patients, who were immunosuppressed with FK506 and low‐dose corticosteroids. Patient survival at 1, 5, and 10 years were 84.6%, 82.4%, and 77.2%, respectively, and the corresponding findings for graft survivals were 84.1%, 80.9%, and 74.5%. Multivariate analysis demonstrated that fulminant hepatic failure (FHF), a graft vs. body weight (GBWR) ratio of <0.8, and ABO‐incompatible transplants were independently associated with both patient and graft survival. The retransplantation rate was 6%, and 55 patients (9.7%) have been completely weaned off immunosuppressants. Long‐term patient and graft survival after pediatric LDLT for a large cohort of children at our hospital were found to be as good as those for cadaveric liver transplantation, although this series includes 13% liver transplantations with ABO‐incompatible donors, which are obviously inferior in patient and graft survival. To obtain better outcomes for patients with FHF and for patients with ABO‐incompatible transplants, immunosuppressive therapy needs to be improved. Liver Transpl 12:1326‐1336, 2006.

Short- and long-term donor outcomes after kidney donation: analysis of 601 cases over a 35-year period at Japanese single center.

Background. The lack of deceased donors in Japan means that living-donor kidney transplantation is necessary in as many as 80% of cases. However, there are few data on perioperative complications and long-term outcome for live kidney donors. Methods. To determine associated perioperative morbidity and long-term mortality among live kidney donors, we reviewed 601 donor nephrectomies performed at our institution between 1970 and 2006 and attempted to contact all of the donors (or their families) to ascertain their present physical status. The survival rate and causes of death were compared with an age- and gender-matched cohort from the general population. Results. Although three donors (0.5%) experienced major perioperative complications, that is, femoral nerve compression, pulmonary thrombosis, and acute renal failure, all of the donors recovered and left hospital without complications. Among 481 donors (80%) for whom details were available at the time of inspection, 426 (88.5%) were still surviving. Donor survival rates at 5, 10, 20, and 30 years were 98.3%, 94.7%, 86.4%, and 66.2%, respectively. The mean interval between kidney donation and death was 183±102 (7–375) months, and the mean age at death was 70±11 years. The survival rate of kidney donors was better than the age- and gender-matched cohort from the general population, and the patterns and causes of death were similar. Conclusions. Our data suggest that continuation of living-donor kidney transplantation programs is justified in short- and long-term donor safety.

Single center experience of 39 patients with preoperative portal vein thrombosis among 404 adult living donor liver transplantations.

Living donor liver transplantation (LDLT) for patients with portal vein thrombosis (PVT) involves technical difficulty. The aim of this research was to analyze their preoperative diagnosis of PVT, operative procedures, and postoperative courses of patients with preoperative PVT. Thirty‐nine patients of 404 adult patients (9.7%) undergoing LDLT in our hospital from 1996 June to 2004 December had PVT at their transplantation. Twenty‐nine patients had intractable ascites, 21 had gastrointestinal bleeding, and 18 had encephalopathy. The thrombus was located in the portal trunk in 23, in the portal trunk and superior mesenteric vein (SMV) in 7, and developed into the SMV and the splenic vein in 8. The occlusive grade was partial in 29, and complete in 10 patients. The thrombus was removed by a simple technique, and eversion and/or incision technique, or total removal of the portal vein (PV). The PV was reconstructed with the thrombectomized native PV, with an interposed vein graft, or porto‐caval hemitransposition. Advanced PVT had a significant impact on blood loss and hospital mortality. Three out of 10 patients with residual PVT required radiological and/or surgical intervention after transplantation. In conclusion, thorough planning is essential for a successful LDLT outcome for patients with preexisting PVT. Liver Transpl 12:1512–1518, 2006.

Auxiliary Partial Orthotopic Living Donor Liver Transplantation: Kyoto University Experience

Auxiliary partial orthotopic liver transplantation (APOLT) was initially indicated as a potentially reversible fulminant hepatic failure and non‐cirrhotic metabolic liver disease to compensate for enzyme deficiency without complete removal of the native liver. We expand our indication of APOLT for small‐for‐size grafts to support the function of implanted grafts during the early post‐operative period, and for ABO‐incompatibility to sustain a patients life if the patient has a graft failure.

Therapeutic strategy and the role of apheresis therapy for ABO incompatible living donor liver transplantation.

Abstract:  Although in Japan, transplant organs obtained from brain‐dead donors (BDD) has been allowed since October 1997, to date only 27 liver grafts from BDD have been obtained. The severe shortage of transplantable organs is a big problem, not only in liver transplantation but also other organ transplants. Liver transplantation is a fundamental treatment for end‐stage liver disease. In order to perform living‐donor liver transplantation (LDLT) in a safer manner, apheresis (plasmapheresis) plays a major role in Japan because of the prevalence of LDLT wherein later re‐transplantation is difficult. Therefore, because of a limited donor supply and because the need of patients with end‐stage liver disease is critical, use of grafts from ABO‐incompatible donors may be the only available option.

Outcomes for pediatric liver retransplantation from living donors.

Background. The only therapeutic option for patients with a failing allograft is retransplantation. Living donor liver transplantation (LDLT) is a well-accepted therapeutic option for end-stage liver disease, but retransplantation from a living donor (Re-LDLT) has not previously been discussed. Methods. A total of 547 LDLTs were performed in 519 children (<18 years old) at Kyoto University Hospital from June 1990 to October 2002. During the same study period, a total of 28 Re-LDLTs were performed in 27 recipients (Re-LDLT performed twice in 1 patient). Patient survival was analyzed with respect to various preoperative factors, such as functional status, pretransplantation apheresis, cause of primary graft failure, interval from primary to subsequent transplants, and laboratory values of total bilirubin and creatinine. Results. Kaplan-Meier survival rate from the date of Re-LDLT to 1 year was 47.6%. Functional status, pretransplantation apheresis, interval to Re-LDLT, and bilirubin and creatinine levels all exerted an adverse impact on survival after Re-LDLT. Pathologically proven major causes of primary graft failure were chronic rejection (n=10, 35.7%), chronic cholangitis (n=6, 21.4%), and vascular complications (n=7, 25.0%). Among these causes, vascular complications displayed the strongest adverse impact on survival, compared with chronic cholangitis and chronic rejection (1-year survival was 35.7% in vascular complications; 66.7% in chronic cholangitis; and 60.0% in chronic rejection). Conclusions. Re-LDLT can save patients with a failing allograft. To achieve better results after Re-LDLT, further investigations are necessary to understand the factors leading to poor outcome after Re-LDLT.

The Role of Apheresis Therapy for ABO Incompatible Living Donor Liver Transplantation: The Kyoto University Experience

Abstract:  Liver transplantation is a radical surgical therapy for end‐stage liver disease. Although in Japan organ transplantation from brain‐dead donors (BDD) has been allowed since October 1997, to date, only 29 liver grafts from BDD have been obtained. Thus, most of the liver transplantations carried out use living‐donor liver transplantation (LDLT), and BDD liver transplantation is only used in rare cases. In order to carry out LDLT more safely, apheresis (plasmapheresis: PE) plays a major role in our country because of the prevalence of LDLT wherein later re‐transplantation is difficult. Thus, because of a limited donor supply and because the needs of patients with end‐stage liver disease is critical, use of grafts from ABO‐incompatible (ABO‐I) donors might be the only available option. From June 1990 to November 2005, 1100 patients underwent 1151 LDLT cases at Kyoto University Hospital. Additionally, 159 LDLT cases (13.8%) received ABO‐I living‐donor liver grafts. The role of apheresis in ABO‐I LDLT is the reduction of antibody titers such as anti‐A or anti‐B antibody. We carry out preoperative PE as a general rule for ABO‐I cases, and the recipient’s antibody level against the donor’s blood type is decreased to one eighth of the baseline value before LDLT. Until now, baseline immunosuppressive agents included steroids, tacrolimus and cyclophosphamide. At first, splenectomy was carried out during surgery to suppress antibody production, and intraportal (PV) infusion therapy was carried out to control local disseminated intravascular coagulation (DIC) occurring in ABO‐I grafts. At that time, three drugs‐methylprednisolone, prostaglandin E1 (PGE1), and gabexate mesylate (FOY) were infused continuously for 3 weeks after LDLT. At present, instead of PV infusion therapy, hepatic artery infusion therapy without splenectomy is adopted because of portal thrombosis, and two drugs— methylprednisolone and PGE1‐ are infused continuously for 3 weeks following LDLT. Recently, we introduced anti‐CD20 monoclonal antibody (Rituximab) instead of splenectomy for B cell deletion before ABO‐I LDLT. In the present article, we describe the role of apheresis around ABO‐I LDLT based on our recent experiences.

Successful surgical ligation under intraoperative portal vein pressure monitoring of a large portosystemic shunt presenting as an intrapulmonary shunt: report of a case.

We report a rare case of patent ductus venosus (PDV) with collapsed intrahepatic portal branches and an intrapulmonary shunt. Excellent improvement of the intrahepatic portal vein flow was achieved by ligating the large ductus venosus under intraoperative portal vein pressure (PVP) monitoring. A 3-year-old boy being followed up for hypergalactosemia at a local hospital was found to have mild lip cyanosis, exertional dyspnea, clubbed fingers, and mild liver dysfunction with high levels of transaminase and ammonia. Cardiac catheterization indicated an intrapulmonary shunt with a ratio of 33%. Abdominal ultrasonography and computed tomography showed remarkable communication between the portal vein and the inferior vena cava. We performed laparotomy and successfully ligated the PDV under PVP monitoring. The PVP did not increase until the catheter was removed 7 days postoperatively. The patient’s liver function test results returned to normal within 2 weeks. His serum galactose level was 0 mg/dl after drinking milk, and his SpO2 in room air and exertional dyspnea also improved. He was discharged 18 days after his operation, without any complications. We propose that ligation of a PDV under PVP monitoring could be a treatment of choice, bearing in mind that PDV is associated with collapsed intrahepatic portal branches.

Monosegmental living donor liver transplantation

BACKGROUND Living donor liver transplant (LDLT) program has been started from 1990 in Japan, and is still major form of liver transplantation because of the scarcity of cadaveric donor organs. In small infants, implantation of left lateral segment grafts can be a problem because of a large-for-size graft. Until November 2002, we performed 867 transplants for 828 patients (561 children and 306 adults), and 14 cases received monosegment grafts from living donors. METHODS Fifteen patients, median age 211 days, median weights 5.95 kg, received monosegmental LDLT. The indication for using this technique was infants with an estimated graft-to-recipient weight ratio of over 4.0%. RESULTS Graft and patient survival is 85.7%. There were no differences in donor operation time and blood loss between monosegmentectomy and left lateral segmentectomy. Segment III grafts were indicated in 13 cases. Two vascular complications were observed (one hepatic artery thrombosis and one portal vein thrombosis). CONCLUSIONS Monosegental living donor liver transplantation is a feasible option with satisfactory graft survival in small babies with liver failure.