Outcome of liver retransplantation in children.

Irreversible liver graft failure is a life-threatening complication. We reviewed the first 200 pediatric liver transplantations in Birmingham. Forty-one children developed primary graft failure, 9 of whom developed secondary graft failure. The main indications for graft failure were primary nonfunction (PRNF; 8 patients), vascular complications (VASC; 23 patients), and chronic rejection (CHRE; 19 patients). Thirty-two children underwent retransplantation (ReTx) (21 children received reduced grafts; 11 children, whole hepatic grafts). Patient survival was significantly worse for retransplant recipients compared with children receiving a single graft (63% v 76. 5% actuarial patient survival at 1 year; P <.05). Primary graft 1-year actuarial survival was 74% in first grafts compared with 47% for regrafts (P <.05), but improved with time. The graft 1-year survival rate was 55% for whole grafts and 45% for reduced and/or split grafts in the first 100 grafts compared with 83% and 66% in the second 100 grafts, respectively (P <.01). Emergency ReTx within a month of transplantation was associated with more complications and a worse outcome (1-year survival rate, 37%) compared with patients who underwent ReTx later (1-year survival rate, 72%; P <. 01). The incidence of primary graft failure decreased from 33% in the first 100 grafts to 16% in the second 100 grafts (P <.01), as did the incidence of PRNF, which decreased from 8% to 0% (P <.05). Although the rates of graft failure from VASC decreased from 15% to 8% (P =.2) and CHRE decreased from 11% to 8% (P =.6), neither reached statistical significance. The improved results overall are because of advances in surgical techniques, intensive care management, and graft preservation and refinements in immunosuppression. We conclude that ReTx for a child with primary graft failure is justified.

Early risk factors in pediatric renal transplantation at a single center.

BACKGROUND/PURPOSE: Renal transplantation is the preferred treatment for renal failure in childhood, but the incidence of graft failure is generally higher than that in adult recipients. A single center was studied to determine if there were any correctable factors that could contribute to graft failure. METHODS: Recipient, donor, and perioperative factors were analyzed using standard statistical tests in 59 pediatric renal transplants performed between 1992 and 1995 using standard cyclosporin-based immunosuppression. RESULTS: Three factors were found to be significantly different between those recipients with good graft function and those who either died or were returned to dialysis. Any history of donor hypotension was a detrimental factor (P < .05, chi(2) test). In addition, those with failed grafts were more likely to have received their grafts from younger donors (P = .025, Mann Whitney U test). A third risk factor was a low postoperative central venous pressure in those whose graft ultimately failed (P = .0012, Mann Whitney U test). CONCLUSIONS: With a pediatric recipient who is stable and has a low priority for a renal graft, small donors, particularly those who have experienced hypotension, should be considered not suitable for transplantation. The chances of a successful graft can be improved by good communication between surgeon, pediatrician, and anesthetist. The importance of maintaining a positive central venous pressure is emphasised.

Encouraging results of split-liver transplantation.

BACKGROUND: Liver donor shortage presently accounts for a 10 per cent waiting list mortality rate. Split-liver transplantation (SLT) can improve utilization of this scarce resource. METHODS: Twenty-four SLTs (11 left, 13 right grafts) from 13 livers were performed in 23 patients (nine adults, 14 children), comprising 4.5 per cent of all orthotopic liver transplants (14 urgent or emergency, ten elective). The left graft comprised segments II and III, whereas the right graft comprised segments V-VIII in eight cases, IV-VIII in three, and segments I, IV-VIII, and I, V-VIII in one case each. Additional arterial extension grafts were required in six of 24 cases, and portal venous interposition graft in one. RESULTS: Twenty-one grafts showed good initial function, with one primary non-function and two initial poor function. The median peak aspartate aminotransferase level was 782 (range 94-2301) and 982 (range 382-2520) units/l for left and right grafts respectively. Five patients died (all urgent recipients), all within the first 30 days after surgery. Two SLT recipients underwent subsequent retransplantation. All ten elective recipients are alive. The 1-year actuarial patient and graft survival rates at a median follow-up of 20 months were 78 and 68 per cent respectively. CONCLUSION: These encouraging results compare favourably with those of reduced-size and whole-liver transplantation and justify wider application of this technique, thereby optimizing donor resource use.

Progress in pediatric liver transplantation--the Birmingham experience.

This report describes the evolution of the Birmingham, UK experience with pediatric liver transplantation from 1983 to present. Two hundred liver grafts were placed in 168 children less than 17 years of age. The current survival rate exceeds 80%.

Unresectable hepatic tumors in childhood and the role of liver transplantation.

Liver transplantation has been performed in five children with unresectable hepatic tumors who did not have extrahepatic metastases at the time of surgery. Two of the children had hepatoblastomas, one had an infantile hemangioendothelioma, and two had a hepatoma. The two children who had hepatoblastoma are well (37 and 25 months posttransplant) and have no evidence of recurrence. The child with infantile hemangioendothelioma had a successful operation, with good quality of life, but died of tumor recurrence 41 months after transplantation. Both children with hepatomas died, one of graft failure owing to chronic rejection and the other of tumor recurrence 5 months posttransplant. These results suggest that liver transplantation may be successful in children with unresectable hepatic tumors without extrahepatic spread and should be considered particularly for the treatment of hepatoblastoma.

The immunomodulatory effect of leflunomide in rat cardiac allotransplantation.

Leflunomide, a novel immunosuppressant, has been the subject of recent preclinical studies using solid organ allo- and xenotransplantation models. The objectives of this study were to evaluate the efficacy and toxicity of leflunomide using a rat cardiac allotransplant model in two different strain combinations (DA x PVG and DA x Lew). Leflunomide, at doses ranging between 5 and 30 mg/kg, prolonged graft survival in both strain combinations as effectively as CsA and FK506 1 mg/kg (P < 0.05). A dose-dependent effect was seen only after a longer treatment course. When ongoing rejection was intercepted early (postoperative day 2), 5 mg/kg was as effective as 1 mg/kg FK506 (P > 0.05) but was inferior to CsA in the DA x PVG combination (P < 0.05). However, in the DA x Lew combination, leflunomide was equally as efficacious as 15 mg/kg CsA and 1 mg/kg FK506 (P > 0.05). If ongoing rejection was treated at postoperative day 4, 10 mg/kg leflunomide was not only as effective as 15 mg/kg CsA and 1 mg/kg FK506, but demonstrated a dose-dependent increase in graft survival in both strain combinations. The toxicity of leflunomide at doses of especially 5-20 mg/kg was minimal in comparison to therapeutic doses of CsA and FK506 using body weight and biochemical parameters of renal and liver function. These in vivo observations convincingly show leflunomide to be equally as potent an immunosuppressant as CsA and FK506 in transplant rejection. It is also well tolerated on long-term administration and, by virtue of this fact, is a potentially suitable candidate for clinical transplantation.

Rat heart-aorta cluster transplantation: a novel model to study transplant rejection.

The purpose of this study was to develop a microsurgical cluster model of heart plus entire thoracic aorta transplantation and to compare it to the isolated model of heart transplantation as a tool to study transplant rejection. Thirty-six syngeneic (DA x DA and Lew x Lew) and allogeneic (DA x PVG and DA x Lew) cluster heart-aorta transplants were compared to 43 syngeneic and allogeneic isolated heart grafts. Graft survival, recipient survival and histological data on myocardial and aortic tissues were assessed. There was no statistically significant difference in graft survival between the two models studied (P > 0.05). In the cluster transplants, the aortic component was spared the severity of acute rejection noted for the myocardial counterpart. In conclusion, the results demonstrated that the cluster model was technically feasible and highly reproducible. Additionally, it was possible to apply this model to the study of experimental allograft rejection using novel immunosuppressants. The success of the cluster model in strongly mismatched transplant strain combinations underscores its potential for application in slower rejection combinations, making it particularly suited for chronic rejection studies. The inherent capacity for sampling a broader range of vessel sizes in one animal makes the cluster model more suitable than the isolated models of aorta or heart for application to experimental protocols.

The immunomodulatory effects of a novel agent, leflunomide, in rat cardiac allotransplantation.

We assessed the immunomodulatory effect of leflunomide (LEF) in a heterotopic abdominal model of rat heart transplantation using a major histocompatibility mismatch (DA X LEW). The endpoint of this study was cardiac rejection assessed by abdominal palpation of the ventricular impulse and confirmed by laparotomy and histology. In this study, LF was investigated using four dosages (5, 10, 20 and 30 mg/kg per day orally) against cyclosporine (CsA) (15 mg/kg per day orally) and FK 506 (1 mg/kg per day orally). The ability of LEF to prevent rejection and reverse ongoing acute rejection was assessed. The results showed that untreated hearts were fully rejected by day 5 and that LEF at 5 mg/kg was significantly better than any other dose tested, was superior to FK 1 mg/kg, and was as effective as CsA 15 mg/kg in preventing rejection after a short course of treatment. After a longer course, 10 and 20 mg/kg LEF proved more effective than 5 mg/kg in controlling rejection and as efficacious as 1 mg/kg FK and 15 mg/kg CsA. In the control of ongoing established early rejection. LEF proved to be equally effective, even at lower doses (5 mg/kg), to CsA 15 mg/kg and FK 1 mg/kg. In the control of ongoing established late rejection, 20 mg/kg LEF proved to be superior to 10 mg/kg LEF and 15 mg/kg CsA, and was as effective as FK 1 mg/kg. However, when higher doses of CsA (25 mg/kg) and FK (2 mg/kg) were tested against 20 mg/kg LEF in this mode of rescue, LEF proved as effective as CsA and superior to FK. In the assessment of drug toxicity using body weight as a parameter, 20 mg/kg LEF proved safer than any other LEF dose tested, and safer than 15 mg/kg CsA and 1 mg/kg FK in both short- and long term administration. We conclude that LEF is a relatively safe and potent immunosuppressant with promising clinical potential.