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Publications (4)11.06 Total impact

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    ABSTRACT: To assess feasibility and success of venous recanalization in patients with short gut syndrome who have lost their traditional central venous access and required intestinal or multivisceral transplantation. Twelve patients between the ages of 7 and 55 years with short gut syndrome and long-standing total parenteral nutrition (TPN) dependency and/or hypercoagulability were treated. All had extensive chronic central venous occlusions and survival was dependent on restoration of access and planned transplantation. Central venous recanalizations were obtained via sharp needle recanalization techniques, venous reconstructions with stents, and/or extraanatomic access to the central venous system for placement of central venous tunneled catheters. Central venous access was restored in all patients without operative-related mortality. Three major hemodynamic perioperative technical complications were recorded and successfully treated. There were three self-limited early infectious complications. With a mean follow-up of 22 months, eight of the 12 patients were alive with successful small bowel or multivisceral transplantation; six of those became independent of TPN. The remaining four patients died of complications related to TPN (n = 3) or transplantation (n = 1). With a mean follow-up of 20 months, all but two of the recanalized venous accesses were maintained, for a success rate of 83%. Recanalizations of extensive chronic vein occlusions are feasible but associated with high risk. The technique is life-saving for TPN-dependent patients and can restore candidacy for intestinal and multivisceral transplantation. This approach is likely to be increasingly requested because of the current clinical availability of the transplant procedure.
    Journal of Vascular and Interventional Radiology 10/2005; 16(9):1203-13. · 2.00 Impact Factor
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    ABSTRACT: A highly selected subject group comprising pediatric recipients of liver (n = 36) and small intestine alone (n = 1) or multivisceral graft (n = 2) were converted to sirolimus maintenance therapy for tacrolimus-related side effects (n = 32) or by primary intent (n = 7). Indications were nephrotoxicity (n = 14), primary intent (n = 7), post-transplant lymphoproliferative disorder (n = 6), seizures (n = 4), recurrent acute rejection (n = 2), and cardiomyopathy (n = 1). Thirty subjects (78%) experienced successful conversion, with one subject requiring atorvastatin for hypercholesterolemia and hypertriglyceridemia. Nine subjects (22%) were converted back to tacrolimus for serious adverse events including acute rejection (n = 2), elevated liver function tests (n = 1), severe leucopenia (n = 1), non-compliance (n = 2), recurrent malignancy/death (n = 1), steatohepatitis (n = 1), and thrombocytopenic thrombotic purpura (n = 1). Among subjects with nephrotoxicity, significant benefit was seen only in those subjects with shorter time to rescue after transplantation (n = 8 of 14 subjects). Additional benefits included a significant decrease in mean serum creatinine from pretransplant values for the entire population, and elimination of antihypertensive treatment in all five subjects receiving it prior to conversion. Hemoglobin, serum cholesterol and triglycerides, white cell counts and platelets remained within normal limits for the duration of follow-up (36 month). Conversion from tacrolimus to sirolimus is successful in selected pediatric liver and intestine recipients. Chronic nephrotoxicity may be ameliorated by early conversion. Improvement in renal function and hypertension management, and absence of sirolimus-related adverse events argue for prospective evaluation of regimens in which mTOR inhibitors are used without calcineurin inhibitors in children.
    Pediatric Transplantation 07/2005; 9(3):391-7. · 1.50 Impact Factor
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    ABSTRACT: Although the outcome of liver transplantation has improved significantly during the past two decades, graft loss caused by chronic rejection after liver transplantation still occurs in 2% to 20% of recipients. The overall incidence of chronic rejection is also reported to be low in adult recipients, and risk factors have been identified. Chronic rejection is associated with the inability to maintain baseline immunosuppression. Additionally, the diagnoses of primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis, hepatitis B virus, and hepatitis C virus, common indications for liver transplantation in adults, are associated with a higher incidence of chronic rejection. Fortunately, these diagnoses are rarely seen in children. Little is known about chronic rejection in long-term pediatric liver transplant survivors. The purpose of this longitudinal study was to examine the incidence of biopsy-proven chronic rejection in long-term survivors of primary pediatric liver transplantation under tacrolimus-based immunosuppression. From October 1989 to December 1992, 166 children (boys=95, girls=71; mean age=5.0+/-2.9 years) received a primary liver transplant. These patients were followed until March 2000 with a mean follow-up of 9+/-0.8 (range, 7.4-10.4) years. All liver biopsy specimens and explanted grafts were evaluated for evidence of chronic rejection using the International Banff Criteria. The mortality rate during the follow-up period was 15% (n=25). Retransplantation was required in 11% (n=18) of recipients. Actuarial patient and graft survival rates at 10 years were 84.9% and 80.1%, respectively. There were 535 liver biopsy samples available for evaluation, including the 18 explanted allografts. Biopsy specimens of three other functioning allografts showed evidence of chronic rejection. Immunosuppression had been discontinued or drastically reduced in these recipients because of life-threatening infections, noncompliance, or both. On restoring baseline immunosuppression, all three children had normalized liver function and the allografts were maintained; the liver transplant patients who are alive currently have normal liver functions. The findings of this study suggest that chronic rejection does not occur in pediatric liver transplant recipients receiving tacrolimus-based immunosuppression, provided baseline immunosuppression is maintained.
    Transplantation 05/2003; 75(7):1020-5. · 3.78 Impact Factor
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    ABSTRACT: Aims. The role of sirolimus (SRL) as a rescue agent (n=42) and as a component of primary immunosuppression (n=8) was evaluated in a mixed population of 50 transplanted children receiving tacrolimus (liver: 26, heart: 5, intestinal: 5, liver-intestine: 9, lung: 1, bone marrow: 1, liver-kidney: 1, multivisceral: 1). Rescue indications for tacrolimus (TAC) failure were recurrent acute rejection and acute rejection complicating withdrawal of immunosuppression in posttransplant lymphoproliferative disorder (PTLD). Rescue indications for TAC toxicity were nephrotoxicity, pancreatitis, seizures, hypertrophic cardiomyopathy, and graft-versus-host disease. Results. Mean age at rescue was 11.5 years and mean follow-up was 204 (range 18-800) days. As primary immunosuppression, SRL+TAC prevented early acute rejection in 7/8 children. The indication for rescue resolved in 33/42 children. In children with TAC toxicity, this was associated with decrease in TAC doses by 50%, significant improvements in renal function, and continuing decline in Epstein-Barr virus (EBV) viral load in PTLD patients. Serious adverse events led to discontinuation of SRL in 9/42 rescue patients, 3 of them also experienced acute rejection. Three additional children also experienced acute rejection on SRL therapy (overall incidence 6/50, 12%). Pharmacokinetic analysis in the first week of SRL administration suggested a short half-life (11.8±5.5 hr, n=21). Conclusions. SRL and reduced-dose TAC may achieve adequate immunosuppression without compromising renal function or enhancing EBV viremia significantly.
    Transplantation 09/2001; 72(5):851-855. · 3.78 Impact Factor