Pediatric intestinal transplantation.

The field of intestinal transplantation has experienced dramatic growth since the first reported cases 3 decades ago. Improvements in operative technique, donor assessment and immunosuppressive protocols have afforded children who suffer from life-threatening complications of intestinal failure a chance at long-term survival. As experience has grown, newer diseases, with more systemic manifestations have arisen as potential indications for transplant. After discussing the historical developments of intestinal transplant as a backdrop, this review focuses on the specific pre-operative indications for transplant as well as the great success that intestinal rehabilitation has witnessed over the past decade. A detailed discussion of evolution of immunosuppressive strategies is followed a general review of the common infectious complications experienced by children after intestinal transplant as well as the current long- and short-term results, including a section on new research on the quality of life in this challenging population of patients.

Pediatric liver transplantation for hepatocellular cancer and rare liver malignancies: US multicenter and single-center experience (1981-2015).

A tenth of all pediatric liver transplantations (LTs) are performed for unresectable liver malignancies, especially the more common hepatoblastoma (HBL). Less understood are outcomes after LT for the rare hepatocellular carcinoma, nonhepatoblastoma embryonal tumors (EMBs), and slow growing metastatic neuroendocrine tumors of childhood. Pediatric LT is increasingly performed for rare unresectable liver malignancies other than HBL. We performed a retrospective review of outcomes after LT for malignancy in the multicenter US Scientific Registry of Transplant Recipients (SRTR; n = 677; 1987-2015). We then reviewed the Children's Hospital of Pittsburgh (CHP; n = 74; 1981-2014) experience focusing on LT for unresectable hepatocellular cancer (HCC), EMBs, and metastatic liver tumors (METS). HBL was included to provide reference statistics. In the SRTR database, LT for HCC and HBL increased over time (P < 0.001). Compared with other malignancies, the 149 HCC cases received fewer segmental grafts (P < 0.001) and also experienced 10-year patient survival similar to 15,710 adult HCC LT recipients (51.6% versus 49.6%; P = 0.848, not significant [NS], log-rank test). For 22 of 149 cases with incidental HCC, 10-year patient survival was higher than 127 primary HCC cases (85% [95% confidence interval (CI), 70.6%-100%] versus 48.3% [95% CI, 38%-61%]; P = 0.168, NS) and similar to 3392 biliary atresia cases (89.9%; 95% CI, 88.7%-91%). Actuarial 10-year patient survival for 17 EMBs, 10 METS, and 6 leiomyosarcoma patients exceeded 60%. These survival outcomes were similar to those seen for HBL. At CHP, posttransplant recurrence-free and overall survival among 25 HCC, 17 (68%) of whom had preexisting liver disease, was 16/25 or 64%, and 9/25 or 36%, respectively. All 10 patients with incidental HCC and tumor-node-metastasis stage I and II HCC survived recurrence-free. Only vascular invasion predicted poor survival in multivariate analysis (P < 0.0001). A total of 4 of 5 EMB patients (80%) and all patients with METS (neuroendocrine-2, pseudopapillary pancreatic-1) also survived recurrence-free. Among children, LT can be curative for unresectable HCC confined to the liver and without vascular invasion, incidental HCC, embryonal tumors, and metastatic neuroendocrine tumors. Liver Transplantation 23 1577-1588 2017 AASLD.

Liver transplantation at the University of Pittsburgh.

As with other programs across the country, at the University of Pittsburgh liver transplantation continues to evolve after three decades. The shortage of organs represents the biggest problem in the field, and in response there has been an increase in the number of expanded-criteria-donor transplants and other methods to expand the donor pool such as live-donor, domino, and split-liver transplants. As the program has matured, we have seen an increasing number of recipients needing re-transplantation because--unlike with kidney transplants--recurrence of disease represents a significantly greater problem than immunologic graft failure. Modern immunosuppression, especially with agents such as tacrolimus, have significantly reduced the immunologic problems associated with liver transplantation. But as survival rates have improved and patients are living longer after transplant, the problems associated with long-term immunosuppression have become increasingly important. Our program, along with others, continues to look at methods to minimize the overall amount of long-term immunosuppression to which patients are exposed.

Interdisciplinary management of pediatric intestinal failure: a 10-year review of rehabilitation and transplantation.

Management of children with intestinal failure is optimized by interdisciplinary coordination of parenteral and enteral nutrition support, medical management of associated complications, surgical lengthening procedures, and intestinal transplantation. Three hundred eighty-nine pediatric patients have been referred to our center for interdisciplinary assessment of intestinal failure since 1996 (median age=1 year; range 1 day-28.8 years). Factors predictive of weaning from parenteral nutrition without transplantation included increased mean bowel length for patients with gastroschisis (44 vs. 23 cm, p<0.05) and atresia (35 vs. 20 cm, p<0.01) and lower mean total bilirubin for patients with NEC (6.1 vs. 12.7 mg/dL, p<0.05). Others were also more likely to survive if referred with a lower mean total bilirubin (NEC, 7.9 vs. 12.7 mg/dL, p<0.05; pseudo-obstruction, 2.3 vs. 16.3 mg/dL, p<0.01). Patients weaned from parenteral nutrition by 2.5 years after referral achieved 95% survival at 5 years vs. 52% for those not weaned. Bowel lengthening procedures were performed on 25 patients. Eight subsequently weaned from parenteral nutrition without transplantation. Aggressive medical and nutritional intervention along with early referral, intestinal lengthening procedures, and intestinal transplantation in children with intestinal failure dependent on parenteral nutrition can result in the achievement of enteral autonomy and improved survival.

Monitoring immune function during tacrolimus tapering in small bowel transplant recipients.

Long term use of immunosuppressants impacts the cardiovascular system and increases the risk of infection and malignancy. To effectively reduce immunosuppression in a transplant recipient a tool is needed to directly monitor the level of immune function. The Cylex(R) Immune Cell Function Assay, approved by the FDA for the assessment of cell-mediated immunity, shows promise as an objective measure of a transplant recipient's immune function. In a blinded retrospective study, the immune function was compared to clinical courses and histological examinations of biopsies of 20 small bowel transplant recipients during periods of immunosuppressant tapering. Eight patients with no major adverse events or changes of immunosuppressive therapy had moderate to low immune function and were categorized as immunologically and clinically stable. Twelve patients displaying strong immune responses were immunologically and clinically volatile requiring addition of steroids and or OKT3. Results validate the clinical utility of the Cylex Immune Cell Function Assay as an objective tool for assessing immune function. By evaluating immune function, physicians now can identify those patients who are candidates for minimization of immunosuppressant therapy, manage the timing and rate of immunosuppressant weaning and be forewarned of increased patient risk.

De novo malignancies after intestinal and multivisceral transplantation.

BACKGROUND: Maintenance immunosuppression required after organ transplantation creates a permissive environment in which cancer cells can proliferate because of lack of natural immunologic surveillance. With more than a decade of clinical experience, this report is the first to address the risk of de novo cancer after intestinal transplantation. METHODS: A total of 168 consecutive intestinal transplant recipients (86 children and 82 adults) were studied, of whom 52% were male and 91% were white. Surveillance, Epidemiology, and End Results data was used to count expected rates of de novo cancers in the general population matched for age, sex, and length of follow-up. RESULTS: With a mean follow-up of 47+/-41 months, 7 (4.2%) patients developed nonlymphoid de novo cancer, with a cumulative risk of 3% at 5 years and 28% at 10 years. Of these malignancies, one was donor-driven adenocarcinoma. With 0.58 being the expected rate of malignancy for the general population, the risk among intestinal recipients was 8.7 times higher (P =0.01). Such morbidity was significantly higher (50 times) among younger patients (<25 years), with a slight male preponderance. Induction immunosuppression was associated with early onset of de novo cancer. Patient survival after diagnosis of de novo cancer was 72% at 1 year, 57% at 2 years, and 29% at 5 years. CONCLUSION: With conventional immunosuppression, intestinal recipients are at a significantly higher risk of developing de novo cancer when compared with the general population. Thus, a novel tolerogenic immunosuppressive strategy has been recently implemented to reduce the lifelong need for immunosuppression.