CAUSES OF MORTALITY BEYOND 1 YEAR AFTER PRIMARY PEDIATRIC LIVER TRANSPLANT UNDER TACROLIMUS

Background. Success of pediatric liver transplantation has improved significantly. Most posttransplant deaths occur early and are related to surgical complications or recipient status at the time of transplantation. The causes of mortality beyond the first year have not been well described. Methods. Three hundred twenty-six pediatric liver transplants were performed between November 1989 and April 1998 using tacrolimus-based immunosuppression. Patients were followed until March 2002. Mean follow-up was 9.2؎2.4 years. Results. At 1 year, 279 patients (85.5%) were alive. In the subsequent 12.5 years, 10 of the remaining children died (3.58%) at a mean interval of 3.68؎1.69 years after transplant. The mean age at transplant was 5.62؎6.3 years. Six patients had infections as a major contributor to mortality, including two patients with posttransplant lymphoproliferative disorder (PTLD) and one patient that died after retransplantation for hepatitis. Two patients had recurrent malignancy. Other deaths were attributable to chronic rejection, liver failure after being lost to follow-up, and complications of cystic fibrosis. Conclusions. Pediatric liver transplantation using tacrolimus-based immunosuppression has demonstrated excellent success, with 1-and 10-year survival rates of 85.5% and 82.9%, respectively. Late mortality after pediatric liver transplantation overall remains low, with a rate of 0.32% per year. The most common cause of death was infection (60%), including PTLDrelated disease (20%). However, in the recent cohort of patients who underwent transplantation after September 1995, there were no fatal cases of Epstein-Barr virus or PTLD or late mortality thus far, suggesting a benefit from improved infectious disease surveillance using currently available modalities. Mortality from chronic rejection and noncompliance under tacrolimus has been exceedingly rare

Review of outcomes of primary liver cancers in children: Our institutional experience with resection and transplantation

Background: Operative intervention plays an important role in the management of primary liver cancers in children. Recent improvements in diagnostic modalities, pre- and postoperative chemotherapy, and operative technique have all led to improved survival in these patients. Both hepatic resection and orthotopic liver transplantation are effective operations for pediatric liver tumors; which intervention is pursued is based on preoperative extent of disease. This is a review of our institution\u27s experience with operative management of pediatric liver cancer over an 18-year period. Methods: A retrospective chart review from 1990 to 2007 identified patients who were ≤18 years old who underwent operative intervention for primary liver cancer. Demographics, type of operation, intraoperative details, pre- and postoperative management, as well as outcomes were recorded for all patients. Results: Fifty-four patients underwent 57 operations for primary liver cancer, 30 of whom underwent resection; the remaining 27 underwent orthotopic liver transplantation. The mean age at diagnosis was 41 months. Twenty patients had stage 1 or 2 disease and 34 patients had stage 3 or 4 disease. Forty-eight (89%) patients received preoperative chemotherapy. Postoperative chemotherapy was given to 92% of patients. Mean overall and intensive care unit duration of stay were 18 and 6 days, respectively. About 45% of patients had a postoperative complication, including hepatic artery thrombosis (n = 8), line sepsis (n = 6), mild acute rejection (n = 3), biliary stricture (n = 2), pneumothorax (n = 2), incarcerated omentum (n = 1), Horner\u27s syndrome (n = 1), and urosepsis (n = 1). Only 6 patients had a recurrence of their cancer, 5 after liver resection, 3 of whom later received a transplant. There was only 1 recurrence after liver transplantation. There was 1 perioperative mortality from cardiac arrest. Overall survival was 93%. Conclusion: Operative intervention plays a critical role in the management of primary liver cancer in the pediatric population. Neoadjuvant chemotherapy can be given if the tumor seems unresectable at diagnosis. If chemotherapy is unable to sufficiently downstage the tumor, orthotopic liver transplantation becomes the patient\u27s best option. Our institution has had considerable experience with both resection and liver transplantation in the treatment of pediatric primary liver cancer, with good long-term outcomes. © 2010 Mosby, Inc. All rights reserved

Posttransplant Lymphoproliferative Disorders in Liver Transplantation: A 20-Year Experience

OBJECTIVE: To evaluate the incidence of posttransplant lymphoproliferative disease (PTLD) and the risk factors and the impact of this complication on survival outcomes in a large cohort of liver transplant recipients at a single institution. SUMMARY BACKGROUND DATA: Liver transplantation has been accepted as a therapeutic option for patients with end-stage liver disease since 1983, in large part due to the availability and reliance on the use of nonspecifically directed immunosuppression. However, as predicted and subsequently verified in 1968, an increased incidence of certain de novo malignancies has been observed, particularly with regards to lymphoid neoplasms. While many reports have confirmed and clarified the nature of PTLD, the literature is fraught with conflicting experience and outcomes with PTLD. METHODS: Four thousand consecutive patients who underwent liver transplants between February 1981 and April 1998 were included in this analysis and were followed to November 2001. The effect of recipient age at the time of transplant, recipient gender, diagnosis, baseline immunosuppression, grading of PTLD, and association with Epstein-Barr virus were compared. The causes of death were also examined. Treatment for PTLD varied over the 20-year period, but all included massive reduction or elimination of baseline immunosuppression. RESULTS: The 1-year patient survival for liver transplant patients with PTLD was 85%, while the overall patient survival for the entire cohort was 53%. The actuarial 20-year survival was estimated at 45%. The overall median time to PTLD presentation was 10 months, and children had an incidence of PTLD that was threefold higher than adults. Patient survival was better in children, in patients transplanted in the era of tacrolimus immunosuppression, in patients with polymorphic PTLD, and in those with limited disease. Interestingly, neither the presence or absence of Epstein-Barr virus nor the timing of PTLD presentation appeared to influence overall patient survival. Patients transplanted for alcohol-related liver disease had a similar incidence of PTLD but had a higher risk of mortality. CONCLUSIONS: While PTLD continues to pose problems in patients receiving liver transplants, improvements in patient survival have been observed over time. While it is too early to assess the impact of new advances in prophylaxis, diagnosis, and treatment, such approaches are based on an increased knowledge of the pathophysiology of PTLD

Analysis of national and single-center incidence and survival after liver transplantation for hepatoblastoma: New trends and future opportunities

BackgroundLiver transplantation (LTx) for hepatoblatoma appears to be increasing. Favorable tumor histology is increasingly linked to survival after surgical resection and could also determine posttransplantation outcomes.MethodsTo evaluate national trends in tumor and LTx incidence as the basis for observations at some LTx centers, and determinants of survival after LTx for hepatoblastoma, we queried the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) registry representing 9.451% of the U.S. population (1975–2007), the United Network for Organ Sharing (UNOS, 1988–2010, n = 332), and Children's Hospital of Pittsburgh database (CHP, 1987–2011, n = 35).ResultsIn the United States, hepatoblastoma cases increased 4-fold, LTx for hepatoblastoma increased 20-fold, and hepatoblastoma surpassed other unresectable liver malignancies requiring LTx by nearly 3-fold. Actuarial 5-year patient survival exceeded 75%. Recurrences in 16% were greater after segmental LTx in the total U.S. experience (P = .049). At CHP, 5 children died from recurrences (n = 4) and sepsis (n = 1). Tumors were epithelial (57%) or mixed epithelial-stromal (42%), Children's Oncology Group stage III (77%) or IV (23%). Recurrences were related to previous pulmonary metastases (P = .016), and tumor necrosis <50% (P = .013), but not to small cell undifferentiated tumor histology (P = NS). Hepatic artery thrombosis was more common after LTx for hepatoblastoma compared with nonmalignant indications (P = .0089). Thirty-three children received pre-LTx chemotherapy, 88.6% with cisplatin, and 85.7% received post-LTx chemotherapy.ConclusionOutcomes after LTx for hepatoblastoma may benefit from improved detection and treatment of pretransplantation metastases, adequate tumor lysis after chemotherapy, and perioperative antithrombotic agents but are unaffected by undifferentiated tumor histology