Daisuke Morioka

Outcomes of adult-to-adult living donor liver transplantation : a single institution's experience with 335 consecutive cases

Objective:To determine outcomes for both donors and recipients of adult-to-adult living donor liver transplantation (AALDLT) and independent factors impacting those outcomes. Summary Background Data:Deceased donors for organ transplantation remain extremely rare, making living donor liver transplantation (LDLT) practically the sole therapeutic modality for patients with end-stage liver disease in Japan. Methods:Retrospective analysis of initial LDLT for 335 consecutive adult (≥18 years) patients performed between November 1994 and December 2003. Results:Of the 335 recipients, 275 received right-liver grafts and the remaining 60 recipients received non-right-liver grafts. Three of the 335 liver grafts were domino-splitting livers. Sixty of the 332 donors other than the domino-donors showed major postoperative complications. Multivariate analysis indicated that accumulation of case experience significantly and advantageously affected the surgical outcomes of these living liver donors, and right-liver donation and prolonged donor operation time were shown to be independent risk factors of major complications in the donors. Post-transplant patient and graft survival estimates were 73.1% and 72.5% at 1 year, 67.7% and 66.3% at 4 years, and 64.7% and 61.9% at 7 years, respectively. Obvious pretransplant encephalopathy, a higher (≥31) modified Model for End-stage Liver Disease score (including points for persistent ascites and low serum sodium) and higher donor age (≥50 years) were indicated as independent factors predictive of graft failure (graft loss or death) in the multivariate analysis. Conclusions:Graft type and degree of experience exerted a significant impact on the surgical outcomes of AALDLT donors but did not significantly affect the survival outcomes of AALDLT recipients. Better pretransplant conditions and younger age (<50 years) among the living donors appeared to be advantageous in terms of gaining better survival outcomes of patients undergoing AALDLT.

Current role of liver transplantation for the treatment of urea cycle disorders: A review of the worldwide English literature and 13 cases at Kyoto University

To address the current role of liver transplantation (LT) for urea cycle disorders (UCDs), we reviewed the worldwide English literature on the outcomes of LT for UCD as well as 13 of our own cases of living donor liver transplantation (LDLT) for UCD. The total number of cases was 51, including our 13 cases. The overall cumulative patient survival rate is presumed to be more than 90% at 5 years. Most of the surviving patients under consideration are currently doing well with satisfactory quality of life. One advantage of LDLT over deceased donor liver transplantation (DDLT) is the opportunity to schedule surgery, which beneficially affects neurological consequences. Auxiliary partial orthotopic liver transplantation (APOLT) is no longer considered significant for the establishment of gene therapies or hepatocyte transplantation but plays a significant role in improving living liver donor safety; this is achieved by reducing the extent of the hepatectomy, which avoids right liver donation. Employing heterozygous carriers of the UCDs as donors in LDLT was generally acceptable. However, male hemizygotes with ornithine transcarbamylase deficiency (OTCD) must be excluded from donor candidacy because of the potential risk of sudden‐onset fatal hyperammonemia. Given this possibility as well as the necessity of identifying heterozygotes for other disorders, enzymatic and/or genetic assays of the liver tissues in cases of UCDs are essential to elucidate the impact of using heterozygous carrier donors on the risk or safety of LDLT donor‐recipient pairs. In conclusion, LT should be considered to be the definitive treatment for UCDs at this stage, although some issues remain unresolved. (Liver Transpl 2005;11:1332–1342.)

Living Donor Liver Transplantation for Pediatric Patients with Inheritable Metabolic Disorders

Forty‐six pediatric patients who underwent living donor liver transplantation (LDLT) using parental liver grafts for inheritable metabolic disorders (IMD) were evaluated to determine the outcomes of the surgery, decisive factors for post‐transplant patient survival and the impact of using donors who were heterozygous for the particular disorder. Disorders included Wilson disease (WD, n = 21), ornithine transcarbamylase deficiency (OTCD, n = 6), tyrosinemia type I (TTI, n = 6), glycogen storage disease (GSD, n = 4), propionic acidemia (PPA, n = 3), methylmalonic acidemia (MMA, n = 2), Crigler‐Najjar syndrome type I (CNSI, n = 2), bile acid synthetic defect (BASD, n = 1) and erythropoietic protoporphyria (EPP, n = 1). The post‐transplant cumulative patient survival rates were 86.8 and 81.2% at 1 and 5 years, respectively. Post‐transplant patient survival and recovery of the growth retardation were significantly better in the liver‐oriented diseases (WD, OTCD, TTI, CNSI and BASD) than in the non‐liver‐oriented diseases (GSD, PPA, MMA and EPP) and pre‐transplant growth retardation disadvantageously affected post‐transplant outcomes. Although 40 of 46 donors were considered heterozygous for each disorder, neither mortality nor morbidity related to the heterozygosis has been observed. LDLT using parental donors can be recommended as an effective treatment for pediatric patients with IMD. In the non‐liver‐oriented diseases, however, satisfactory outcomes were not obtained by hepatic replacement alone.

Management of Massive Arterial Hemorrhage After Pancreatobiliary Surgery: Does Embolotherapy Contribute to Successful Outcome?

Massive arterial hemorrhage is, although unusual, a life-threatening complication of major pancreatobiliary surgery. Records of 351 patients who underwent major surgery for malignant pancreatobiliary disease were reviewed in this series. Thirteen patients (3.7%) experienced massive hemorrhage after surgery. Complete hemostasis by transcatheter arterial embolization (TAE) or re-laparotomy was achieved in five patients and one patient, respectively. However, 7 of 13 cases ended in fatality, which is a 54% mortality rate. Among six survivors, one underwent selective TAE for a pseudoaneurysm of the right hepatic artery (RHA). Three patients underwent TAE proximal to the proper hepatic artery (PHA): hepatic inflow was maintained by successful TAE of the gastroduodenal artery in two and via a well-developed subphrenic artery in one. One patient had TAE of the celiac axis for a pseudoaneurysm of the splenic artery (SPA), and hepatic inflow was maintained by the arcades around the pancreatic head. One patient who experienced a pseudoaneurysm of the RHA after left hemihepatectomy successfully underwent re-laparotomy, ligation of RHA, and creation of an ileocolic arterioportal shunt. In contrast, four of seven patients with fatal outcomes experienced hepatic infarction following TAE proximal to the PHA or injury of the common hepatic artery during angiography. One patient who underwent a major hepatectomy for hilar bile duct cancer had a recurrent hemorrhage after TAE of the gastroduodenal artery and experienced hepatic failure. In the two patients with a pseudoaneurysm of the SPA or the superior mesenteric artery, an emergency re-laparotomy was required to obtain hemostasis because of worsening clinical status. Selective TAE distal to PHA or in the SPA is usually successful. TAE proximal to PHA must be restricted to cases where collateral hepatic blood flow exists. Otherwise or for a pseudoaneurysm of the superior mesenteric artery, endovascular stenting, temporary creation of an ileocolic arterioportal shunt, or vascular reconstruction by re-laparotomy is an alternative.

Vascular reconstruction and complications in living donor liver transplantation in infants weighing less than 6 kilograms: The Kyoto experience

Smaller‐size infants undergoing living‐donor liver transplantation (LDLT) are at increased risks of vascular complications because of their smaller vascular structures in addition to vascular pedicles of insufficient length for reconstruction. Out of 585 child patients transplanted between June 1990 and March 2005, 64 (10%) weighing less than 6 kg underwent 65 LDLTs. Median age and weight were 6.9 months (range: 1‐16 months) and 5 kg (range: 2.8‐5.9 kg), respectively. Forty‐five lateral segment, 12 monosegment, and 8 reduced monosegment grafts were adopted, and median graft‐to‐recipient weight ratio was 4.4% (range: 2.3‐9.7). Outflow obstruction occurred in only 1 patient (1.5%). Portal vein complication occurred in 9 (14%) including 5 with portal vein thrombosis. Hepatic artery thrombosis (HAT) occurred in 5 (7.7%). Patient and graft survivals were 73% and 72% at 1 yr, and 69% and 68% at 5 yr after LDLT, respectively. Thirteen of 22 grafts (58%) lost during the follow‐up period occurred within the first 3 months posttransplantation. Overall graft survival in patients with and without portal vein complication was 67% and 65%, respectively (P = 0.54). Overall graft survival in patients with and without HAT was 40% and 67%, respectively. HAT significantly affected graft survival (P = 0.04). In conclusion, our surgical technique for smaller‐size recipients resulted in an acceptable rate of vascular complications. Overcoming early posttransplantation complications will further improve outcomes in infantile LDLT. Liver Transpl 12:1224–1232, 2006.

Impact of Human Leukocyte Antigen Mismatching on Outcomes of Living Donor Liver Transplantation for Primary Biliary Cirrhosis

Patient selection criteria of deceased donor liver transplantation for primary biliary cirrhosis (PBC) are almost completely established. The aim of this study was to establish selection criteria for both patients and donors of living donor liver transplantation (LDLT) for PBC. We used univariate and multivariate analyses to examine patient and donor characteristics of our first 50 cases of LDLT for PBC to elucidate factors that significantly impacted patient survival or disease recurrence after LDLT in the univariate and/or multivariate analyses. Multivariate analysis demonstrated that the presence of persistent ascites before LDLT, a higher number of human leukocyte antigen (HLA)‐A, ‐B, and ‐DR mismatches between donor and recipient, and donor age ≥50 years were factors significantly associated with early posttransplant death. Independent risk factors for PBC recurrence after LDLT were a lower number of HLA mismatches between donor and recipient, and a lower average trough level of tacrolimus within 1 year after LDLT. Specifically, the lower the number of HLA‐A, ‐B, and ‐DR mismatches or the average trough level of tacrolimus within 1 year after LDLT, the higher the possibility of developing a recurrence of PBC. In conclusion, the absence of persistent ascites before LDLT, a lower number of HLA‐A, ‐B, and ‐DR mismatches between donor and recipient, and a younger donor (<50 years) are preferred for gaining acceptable survival outcomes for the transplant. However, a lower number of HLA‐A, ‐B, and ‐DR mismatches between donor and recipient may be a risk factor for PBC recurrence. Liver Transpl, 2006.

Living Donor Liver Transplantation for Noncirrhotic Inheritable Metabolic Liver Diseases: Impact of the Use of Heterozygous Donors

Background. In living donor liver transplantation (LDLT), the liver donor is almost always a blood relative; therefore, the donor is sometimes a heterozygous carrier of inheritable diseases. The use of such carriers as donors has not been validated. The aim of the present study was to evaluate the outcome of LDLT for noncirrhotic inheritable metabolic liver disease (NCIMLD) to clarify the effects of using a heterozygous carrier as a donor. Methods. Between June 1990 and December 2003, 21 patients with NCIMLD underwent LDLT at our institution. The indications for LDLT included type II citrullinemia (n = 7), ornithine transcarbamylase deficiency (n = 6), propionic acidemia (n = 3), Crigler-Najjar syndrome type I (n = 2), methylmalonic acidemia (n = 2), and familial amyloid polyneuropathy (n = 1). Of these 21 recipients, six underwent auxiliary partial orthotopic liver transplantation. Results. The cumulative survival rate of the recipients was 85.7% at both 1 and 5 years after operation. All surviving recipients are currently doing well without sequelae of the original diseases, including neurological impairments or physical growth retardation. Twelve of the 21 donors were considered to be heterozygous carriers based on the modes of inheritance of the recipients’ diseases and preoperative donor medical examinations. All donors were uneventfully discharged from the hospital and have been doing well since discharge. No mortality or morbidity related to the use of heterozygous donors was observed in donors or recipients. Conclusions. Our results suggest that the use of heterozygous donors in LDLT for NCIMLD has no negative impact on either donors or recipients, although some issues remain unsolved and should be evaluated in further studies.

Prognostic significance of the number of positive lymph nodes in gallbladder cancer

The aim of this study was to assess the prognostic impact of the number of lymph node metastases. The medical records of 33 patients with node-positive gallbladder cancer (GBC) treated at our institution from January 1985 through December 2002 were reviewed. There were 10 cases with a single node metastasis. The sites were as follows: the cystic duct node, the pericholedochal node, the retroportal node, the hilar node, the lymph node around the common hepatic artery, and the paraaortic node. According to the International Union Against Cancer (UICC) 5th edition, 5-year survival rates for the patients with pN1, pN2, and greater than pN2 were 19.2%, 10%, and 0%, respectively (not significant). Patients with a single node metastasis had a higher 5-year survival rate (33%) than patients with two or more lymph node metastases (0%; P<0.05). There were no lymph node recurrences in patients with a single node metastasis. Number of positive nodes and liver metastasis were factors predictive of significantly worse survival. Rather than using the topographic classification, or even simply classifying whether nodal involvement is positive or negative, classification according to the number of positive nodes will contribute to establishing a more practically useful staging system.

Usefulness of Absorbable Sutures in Preventing Surgical Site Infection in Hepatectomy

We evaluated the usefulness of synthetic absorbable sutures (Vicryl) in preventing surgical site infection (SSI) after hepatectomy. A rat model of 60% partial hepatectomy was used. Bleeding from the cut surface of the liver was controlled by using two suture types: silk and Vicryl. In the Vicryl group, the lesser omentum was slightly adherent to the cut surface of the liver, while in the silk group, the suture remained, and severe adhesions were found. The number of Staphylococcus aureus was significantly larger in the silk group. We compared a group of patients (n = 125) who underwent hepatectomy using silk with one (n = 188) using Vicryl. The respective incidences of SSI and infection on the cut surface of the liver in the Vicryl group (3.2, 1.6%) were significantly lower than in the silk group (11.2, 8.8%). In accordance with the results of multivariate analysis, duration of operation, use of silk sutures and the complication of bile leakage were selected as independent factors. The risk of SSI in the silk group was 3.4 times that in the Vicryl group. The use of synthetic absorbable sutures, instead of silk sutures, in all the procedures of hepatectomy contributed significantly to the prevention of SSI.

Efficacy of Hepatic Resection for Hepatocellular Carcinomas Larger than 10 cm

The objective of this study were to evaluate the efficacy of hepatic resection for large hepatocellular carcinomas (HCCs) and examine clinicopathologic factors influencing overall survival after resection of a large HCC. The pre-, intra-, and postoperative factors and long-term outcome of 26 patients with HCCs >10 cm who underwent hepatic resection (group A) were compared with the those of 143 patients with HCCs ≤10 cm (group B). Hepatic resection for large HCCs can be performed with a mortality rate of 3.8%, which was similar to the rate for group B (2.1%). The overall cumulative survival results for group A (1 year 41.0%, 3 years 29.3%, 5 years 29.3%; median survival 10.1 months) were markedly worse than those for group B (1 year 93.1%, 3 years 74.5%, 5 years 44.7%; median survival 53.4 months) (p < 0.0001). Multivariate analysis identified venous invasion as an independent risk factor of survival of patients with a large HCC. The overall cumulative survival results in patients with venous invasion (1 year 28.0%, 3 years 0%; median survival 6.4 months) were markedly worse than in patients without venous invasion (1 year 64.8%, 3.5 years 64.8%; median survival, 51.8 months) (p < 0.0066). We concluded that hepatic resection can be performed safely for HCCs >10 cm with a low mortality rate. It appears reasonable to believe that hepatic resection is the treatment of choice for large HCCs without venous invasion.