Seisuke Sakamoto

Biliary reconstruction in right lobe living-donor liver transplantation : Comparison of different techniques in 321 recipients

Objective:To assess the incidence of biliary complications after right lobe living-donor liver transplantation (LDLT) in patients undergoing duct-to-duct choledochocholedochostomy or Roux-en-Y choledochojejunostomy reconstruction. Summary Background Data:Biliary tract complications remain one of the most serious morbidities following liver transplantation. No large series has yet been carried out to compare the 2 techniques in LDLT. This study undertook a retrospective assessment of the relation between the method of biliary reconstruction used and the complications reported. Methods:Between February 1998 and June 2004, 321 patients received right lobe LDLT. Biliary reconstruction was achieved with Roux-en-Y choledochojejunostomy in 121 patients, duct-to-duct choledochocholedochostomy in 192 patients, and combined Roux-en-Y and duct-to-duct choledochocholedochostomy in 8 patients. The number of graft bile duct and anastomosis, mode of anastomosis, use of stent tube, and management of biliary complications were analyzed. Results:The overall incidence of biliary complications was 24.0%. Univariate analysis revealed that hepatic artery complications, cytomegalovirus infections, and blood type incompatibility were significant risk factors for biliary complications. The respective incidence of biliary leakage and stricture were 12.4% and 8.3% for Roux-en-Y, and 4.7% and 26.6% for duct-to-duct reconstruction. Duct-to-duct choledochocholedochostomy showed a significantly lower incidence of leakage and a higher incidence of stricture; however, 74.5% of the stricture was managed with endoscopic treatment. Conclusions:The authors found an increase in the biliary stricture rate in the duct-to-duct choledochocholedochostomy group. Because of greater physiologic bilioenteric continuity, less incidence of leakage, and easy endoscopic access, duct-to-duct reconstruction represents a feasible technique in right lobe LDLT.

Expansion of selection criteria for patients with hepatocellular carcinoma in living donor liver transplantation

In the present study, the results of living donor liver transplantation (LDLT) for 125 hepatocellular carcinoma (HCC) patients were analyzed to determine optimal criteria exceeding the Milan criteria (MC) but still with predictably good outcomes. On the basis of pretransplant imaging studies, 70 patients met the MC, and 55 patients did not. Patients who exceeded the MC but presented with ≤10 tumors all ≤5 cm in diameter (n = 30) displayed 5‐year recurrence rates (7.3%) similar to those of patients within the MC (9.7%, P = 0.8787). According to the results of multivariate analysis of risk factors for recurrence among preoperative tumor variables, we have defined the new criteria, namely ≤10 tumors all ≤5 cm in diameter and protein induced by vitamin K absence or antagonist‐II (PIVKA‐II) ≤400 mAU/mL. The 78 patients who met the new criteria showed significantly lower 5‐year recurrence rates (4.9%) than the 40 patients who exceeded them (60.5%, P < 0.0001). Similarly, 5‐year survival rates significantly differed between these groups (86.7% versus 34.4%, respectively; P < 0.0001). In conclusion, selection criteria for patients with HCC undergoing LDLT may be safely extended to ≤10 tumors all ≤5 cm in diameter and PIVKA‐II ≤400 mAU/mL with acceptable outcomes. Liver Transpl 13: 1637–1644, 2007.

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.)

Graft size assessment and analysis of donors for living donor liver transplantation using right lobe.

Background. Modality of living donor liver transplantation (LDLT) hasbeen expanded to adult cases. However, the safety of right lobectomy fromliving donors has not yet beenproven. Methods. A total of 62 cases of LDLT, using the right lobe, werereviewed. Study 1: Discrepancy between estimated graft volume and actual graftweight was evaluated. Study 2: Postoperative liver functions were analyzed inrelation to residual liver volume (RLV) or age. Residual liver volume ofdonors was defined using two indices, (RLV = estimated whole livervolume − estimated graft volume and %RLV = RLV/estimated wholeliver volume×100). Donors were divided into two groups on the basis ofeither %RLV (<40%; 40%≤) or age (<50 years old; 50 years old≤).Study 3: Right lobe donors were compared with left lobe donors (35 cases) interms of their postoperative liverfunctions. Results. Study 1: The relationship between estimated graft volumeand actual graft weight was linear (y=159.136+0.735x,R 2 =0.571, P <0.001). Study 2: %RLV ranged from23.5% to 55.8% (mean±SD: 43.2±6.0). Fifteen cases showed %RLVless than 40%. Postoperative bilirubin clearance was delayed in that group(%RLV<40%). Serum total bilirubin values on postoperative day 7 in theolder group (age ≥50) were significantly higher than those in the youngergroup (age<50). Study 3: Postoperative liver functions of right lobe donorswere significantly higher than those of left-lobe donors. Eleven donors(17.7%) had surgical complications, all of which were cured with propertreatment. Conclusions. Right lobectomy from living donors is a safe procedure withacceptable morbidity, but some care should be taken early after the operationfor donors with small residual liver and ageddonors.

Living donor liver transplantation as a second‐line therapeutic strategy for patients with hepatocellular carcinoma

Living donor liver transplantation (LDLT) has evolved to represent an important surgical strategy for patients with hepatocellular carcinoma (HCC). However, due to disadvantages, including donor risks and higher rates of perioperative complications, LDLT has been considered as a second‐line treatment in Japan. The present study retrospectively evaluated clinical outcomes for 93 patients with HCC who underwent LDLT at our institute, including 44 patients who exceeded Milan criteria (MC). A total of 73 patients (78%) displayed a history of previous treatment for HCC using various nontransplant methods. Median follow‐up was 24 months (range, 1–76 months). At 4 years after LDLT, overall patient survival rate was 64%, with similar rates for within‐MC and over‐MC groups (68% vs. 59%, respectively; P = 0.6548). However, cumulative recurrence rate was significantly higher in the over‐MC group than in the within‐MC group (35% vs. 15%, P = 0.0190). Regarding history of conventional treatment for HCC before LDLT, patients who had received only 1–2 previous treatments showed significantly lower recurrence rates than patients with ≥3 treatments (9% vs. 37%, P = 0.0411). In conclusion, LDLT may constitute an optional treatment with a chance of cure for patients with otherwise uncontrolled disease. However, repeated nontransplant treatments for recurrent HCC prior to LDLT may increase the risk of recurrence and impair the survival advantages conferred by LDLT. Liver Transpl 12:912–919, 2006.

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.

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.

Living Donor Liver Transplantation for Patients with HCC Exceeding the Milan Criteria: A Proposal of Expanded Criteria

Background: Optimal indications for living donor liver transplantation (LDLT) for patients with hepatocellular carcinoma (HCC) have yet not been established. The aim of the present study was to determine optimal criteria including categories outside the Milan criteria (MC) and still with a predictably good outcome. Patients and Methods: Between February 1999 and December 2007, 136 patients with HCC underwent LDLT. Based on preoperative imaging studies, 74 patients met the MC and 62 did not. Results: Overall patient survival rate at 5 years was 70%. Patients who exceeded MC but presented with ≤10 tumors and all ≤5 cm in diameter (n = 33) displayed similar 5-year recurrence rate to those within MC (7 vs. 10%). Based on the results of multivariate analysis of risk factors for recurrence, we defined new criteria as n ≤10 and all ≤5 cm and PIVKA-II ≤400 mAU/ml. The 5-year recurrence rate for the 83 patients who met the new criteria was significantly lower than for the 44 patients who exceeded them (5 vs. 61%, p < 0.0001). Similarly, patients who met the new criteria showed a significantly better 5-year survival rate (87 vs. 37%, p < 0.0001). Conclusion: The selection criteria may be safely extended up to n ≤10 and all ≤5 cm in diameter and PIVKA-II ≤400 mAU/ml with acceptable outcomes.

Maternal Microchimerism in Underlying Pathogenesis of Biliary Atresia: Quantification and Phenotypes of Maternal Cells in the Liver

OBJECTIVE. The goal was to examine whether microchimerism plays a crucial role in the pathogenesis of biliary atresia; we analyzed the localization of maternal microchimeric cells and their phenotypes. METHODS. Liver biopsy specimens from 8 male infants with biliary atresia and 6 control subjects with other liver diseases were investigated for maternal chimeric cells and their phenotypes through double-staining fluorescence in situ hybridization and immunohistochemical analyses. RESULTS. Significantly larger numbers of maternal XX+ cells were found in the portal area and sinusoids of patients with biliary atresia, in comparison with control patients. In phenotypic analyses of XX+ cells, CD8+ T cells, CD45+ cells, and cytokeratin-positive cells were found, and the numbers and proportions among total CD8+ T cells were significantly higher than those in control patients. CONCLUSIONS. Significantly more maternal chimeric CD8+ T cells in the livers of patients with biliary atresia suggest that maternal immunologic insults represent the underlying pathogenesis in biliary atresia. The findings support the recently postulated mechanisms of alloautoimmune and/or autoalloimmune responses.

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.