Fumitaka Oike

Changes in portal venous pressure in the early phase after living donor liver transplantation: pathogenesis and clinical implications.

Background. Although living-donor liver transplantation (LDLT) has been accepted for adult populations, the occurrence and pathogenesis of small-for-size syndrome remain highly controversial. Methods. Portal venous pressure (PVP) was measured in 79 cases of LDLT from anhepatic phase to day 14. PVP was monitored through a catheter inserted via the inferior mesenteric vein. In a separate series of seven cases of adult LDLT, the splenic artery was ligated following arterial reperfusion. Results. For days 2 to 4 and 9 to 11, recipients of small-for-size graft (<0.8% of body weight) displayed significantly higher PVP than recipients of larger grafts. The 13 patients with elevated mean PVP (≥20 mm Hg) early in the first week (days 0–4) demonstrated significantly worse survival (84.5% vs. 38.5% at 6 months;P < 0.01), but this was not applicable to elevated mean PVP late in the first week (days 5–7). Elevated PVP early in the first week was also associated with higher incidence of bacteremia, cholestasis, prolonged prothrombin time, and ascites. Splenic artery ligation (SAL) immediately reduced PVP from 10 to 20 mm Hg (median, 16 mm Hg) to 9 to 13 mm Hg (median, 11 mm Hg;P = 0.02). Posttransplant PVP was significantly lower in SAL patients than in non-SAL patients from days 2 to 7 despite small graft size. Early PVP in SAL patients was consistently below 20 mm Hg, and survival was significantly better than in non-SAL patients with high early PVP (P < 0.01). Conclusion. Elevated PVP in the early phase is strongly associated with poor patient survival attributable, at least in part, to small-for-size graft. Further elucidation of the pathogenesis behind this phenomenon and efforts to modify PVP will be key to improving results.

Anatomical variations and surgical strategies in right lobe living donor liver transplantation: lessons from 120 cases.

Background. Anatomical variations in right liver lobe are common. However, clinical implications and surgical management of these variations in living donor liver transplantation have not been analyzed systematically. Methods. Surgical anatomy of vascular and biliary structures in 120 right lobe grafts were reevaluated by reviewing the results of preoperative (computerized tomography and Doppler ultrasonography) and intraoperative (cholangiography) imaging as well as surgical findings. The data were analyzed in relation to surgical management of anatomical variations. Results. The incidence of variants leading to multiple portal vein anastomoses was 7.5%. The incidence of dual right hepatic veins was 0.8%; 30% of the grafts had significant accessory hepatic veins (>5 mm) and 13.9% of these were multiple. All of them were successfully reconstructed with technical modifications including venoplasty and venous grafts, except for two cases with multiple intraparenchymal portal vein branches to the anterior segment. The incidence of dual hepatic arteries was 1.7%, but only one of them was reconstructed without negative sequelae. The incidence of variants potentially leading to multiple bile duct anastomoses was 35.0%, and eventually 39.2% of the grafts had multiple orifices. With a variety of techniques including ductoplasty, hepaticohepaticostomy, and biliary stent, total incidence of leakage and stenosis was 10.8% and 9.2%, respectively. Although ductoplasty, internal stent or no stenting, seemed to be associated with increased risk of complications, anatomical variants, multiple bile ducts, and duct-to-duct reconstruction did not bear a significant risk. Conclusions. Anatomical variations of vascular and biliary structures in right lobe grafts are common. However, most can be managed safely with technical modifications. Only cases with intraparenchymal origin of the anterior portal vein(s) may form a relative contraindication, especially when combined with similar biliary variants. Otherwise, intraoperative assessment of biliary anatomy was enough for successful management. Detailed and precise assessment of vascular and biliary anatomy is vital for appropriate surgical management.

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.

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.

Duct-to-Duct Biliary Reconstruction in Living Donor Liver Transplantation Utilizing Right Lobe Graft

ObjectiveTo assess the feasibility and safety of duct-to-duct biliary anastomosis for living donor liver transplantation (LDLT) utilizing the right lobe. Summary Background DataBiliary tract complications remain one of the most serious problems after liver transplantation. Roux-en-Y hepaticojejunostomy has been a standard procedure for biliary reconstruction in LDLT with a partial hepatic graft. However, end-to-end choledochocholedochostomy is the technique of choice for biliary reconstruction and yields a more physiologic bilioenteric continuity than can be achieved with Roux-en-Y hepaticojejunostomy. The authors performed right lobe LDLT with end-to-end duct-to-duct biliary anastomosis, and this study assessed retrospectively the relation between the manner of reconstruction and complications. MethodsBetween July 1999 and December 2000, 51 patients (11–67 years of age) underwent 52 right lobe LDLTs with duct-to-duct biliary reconstruction and remained alive more than 1 month after their transplantation. Interrupted biliary anastomosis was performed for 24 transplants and the continuous procedure was used for 28. A biliary tube was inserted downward into the common bile ducts through the recipient’s cystic duct in 16 transplants (cystic drainage), or a biliary stent tube was pushed upward into the anastomosis through the cystic duct in four transplants (cystic stent), or upward into the anastomosis through the wall of the common bile duct in 31 transplants (external stent). ResultsBiliary anastomotic procedures consisted of 34 single end-to-end anastomoses, 11 double end-to-end anastomoses, and 7 single anastomoses for double hepatic ducts. Overall, 5 patients developed leakage (9.6%) and 12 patients suffered stricture (23.0%). For biliary anastomosis with interrupted suture, the incidence of stricture was significantly higher in the cystic drainage group (53.3%, 8/15) than in the stent group consisting of cystic stent and external stent (0%, 0/8). While the respective incidences of leakage and stricture were 20% and 53.3% for intermittent suture with a cystic drainage tube (n = 15), they were 7.7% and 15.4% for a continuous suture with an external stent (n = 26). There was a significant difference in the incidence of stricture. ConclusionsDuct-to-duct reconstruction with continuous suture combined with an external stent represents a useful technique for LDLT utilizing the right lobe, but biliary complications remain significant.

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.

Impact of recipient age on outcome of ABO-incompatible living-donor liver transplantation.

Background. Transplantation of hepatic grafts from ABO-incompatible donors is controversial because of the risk of hyperacute rejection mediated by preformed anti-ABO antibodies. The aim of the present study was to evaluate the outcome of liver transplants performed with ABO-incompatible living-donor livers and to detect risk factors for development of complications. Methods. From June 1990 to February 2000, 66 patients, 10 months to 55 years old (median, 2 years old), received 68 ABO-incompatible living-donor liver grafts. The antibody titer and clinical course were followed prospectively during a period ranging from 3 to 11 years. Results. The 5-year patient survival was 59%, 76%, and 80% for ABO-incompatible, ABO-compatible, and ABO-identical grafts, respectively (P <0.01). In patients <1 year old, ≥1 to <8, ≥8 to <16, and and ≥16 years old, 5-year survival was 76%, 68%, 53%, and 22%, respectively. The incidence of intrahepatic biliary complications and hepatic necrosis in ABO-incompatible living-related grafts (18% and 8%, respectively) was significantly (P <0.0001) greater than in ABO-compatible and ABO-identical grafts (both 0.6% and 0%, respectively). Predictive risk factors for increased mortality and morbidity were age greater than 1 year and elevated anti-ABO titers before transplantation. Conclusions. ABO-incompatible liver transplantation was carried out with relative safety in infants <1 year old but was not satisfactory in children >1 year in long-term follow-up. Patients aged >8 years remain at considerable risk of early fatal outcome because of hepatic necrosis, and new strategies to prevent antibody-mediated rejection are required.

Portal pressure <15 mm Hg is a key for successful adult living donor liver transplantation utilizing smaller grafts than before

To prevent small‐for‐size syndrome in adult‐to‐adult living donor liver transplantation (A‐LDLT), larger grafts (ie, right lobe grafts) have been selected in many transplant centers. However, some centers are investigating the benefits of portal pressure modulation. Five hundred sixty‐six A‐LDLT procedures using right or left lobe grafts were performed between 1998 and 2008. In 2006, we introduced intentional portal pressure control, and we changed the graft selection criteria to include a graft/recipient weight ratio >0.7% instead of the original value of >0.8%. All recipients were divided into period I (1998‐2006, the era of unintentional portal pressure control; n = 432) and period II (2006‐2008, the era of intentional portal pressure control; n = 134). The selection of small‐for‐size grafts increased from 7.8% to 23.9%, and the selection of left lobe grafts increased from 4.9% to 32.1%. Despite the increase in the number of smaller grafts in period II, 1‐year patient survival was significantly improved (87.9% versus 76.2%). In 129 recipients in period II, portal pressure was monitored. Patients with a portal pressure <15 mm Hg demonstrated better 2‐year survival (n = 86, 93.0%) than patients with a portal pressure ≥15 mm Hg (n = 43, 66.3%). The recovery from hyperbilirubinemia and coagulopathy after transplantation was significantly better in patients with a portal pressure <15 mm Hg. In conclusion, our strategy for A‐LDLT has changed from larger graft–based A‐LDLT to controlled portal pressure–based A‐LDLT with smaller grafts. A portal pressure <15 mm Hg seems to be a key for successful A‐LDLT. Liver Transpl 16:718‐728, 2010.

Surgery-related morbidity in living donors of right-lobe liver graft: lessons from the first 200 cases.

Background. Living‐donor liver transplantation (LDLT) using the left lateral segment or left‐lobe graft has been widely accepted, but currently, right‐lobe grafts are more commonly used in many LDLT programs with yet unknown risks for donors. Methods. We investigated our initial 200 donors of righ‐lobe grafts to focus on the incidence and variety of surgery‐related morbidity. Changes in liver function tests were also analyzed to clarify the relation with donor age, steatosis of the liver, and residual liver volume (RLV). Complications were surveyed for a median period of 28.7 months. Results. In all the donors, liver enzymes and bilirubin were normalized within 1 month. Enzymes on day 1 were significantly higher in donors with older age, macrovesicular steatosis, and larger RLV. Bilirubin on day 1 was significantly higher in donors with smaller RLV. Biliary enzyme was not normalized in the majority at 1 month after donation. Seventy‐five complications occurred in 69 donors. Biliary complications were most common, which consisted of 26 bile leakages (13%) and 3 biliary strictures (1.5%) in 27 donors. No significant dependence of the incidence was observed either for donor age (≥50 years), body mass index (BMI) (≥25 kg/m2), estimated RLV (<40%), or medical history. None of the complications led either to mortality or to long‐term sequelae. Conclusions. Complications occurred in a significant proportion of right‐lobe donors irrespective of donor age, BMI, estimated RLV, and medical history. Living‐liver donor surgery requires more care in right‐lobe transplants.

Surgery-related morbidity in living donors for liver transplantation.

Introduction. Complications occur in a considerable proportion of living donors for liver transplantation. In this study, the surgery-related morbidity in living donors for more than 1000 liver transplantations was investigated. Methods. The donor morbidity between June 1990 and August 2007 was analyzed retrospectively and classified by the graft type and time period. The complication severity was graded using the Clavien scoring system. Results. During the study period, 1262 living donors underwent donor operations for liver transplantation. The donors were divided into two groups by the graft type: group RG (n=500), comprising right and extended right lobe grafts, and group LG (n=762), comprising non-right lobe grafts. The overall complication rate was significantly higher in group RG than that in group LG (44.2% vs. 18.8%, P<0.05). The complication severity was worse in group RG than in group LG. Although biliary complications were the most common complications in both the groups, the frequencies differed significantly (RG: 12.2% vs. LG: 4.9%; P<0.05). Short-term complications (within 4 weeks after the donor operation) occurred in 308 donors (24.4% of all donors). Complications after 4 weeks occurred in only 17 donors. Donor age, right lobe donation, and prolonged operation time were found to be independent risk factors for complications by multivariate analyses. Conclusions. Biliary complications were the most common and feared complications in living donors. There were more frequent and severe complications for right and extended right lobe donation than for non-right lobe donation. The possible risks of donor morbidity for different graft types should be understood and carefully considered.