Background Diabetes is associated with increased morbidity and mortality in patients with cystic fibrosis (CF). While liver transplantation is well established for CF-related liver disease (CFLD), the role of simultaneous liver–pancreas transplantation is less understood. Methods We polled 81 pediatric transplantation centers to identify and characterize subjects who had undergone simultaneous liver–pancreas transplantation and obtain opinions about this procedure in CFLD. Results Fifty (61.7%) polled transplant centers responded and 94% reported that they would consider simultaneous liver–pancreas transplantation for CFLD and diabetes. A total of 8 patients with simultaneous liver–pancreas transplantation were identified with median follow up of 38 months. All patients had pre-existing diabetes. Exocrine and endocrine pancreatic function was initially restored in all patients with later functional loss in one patient. Body mass index Z-score increased between one year pre-transplantation and one year post-transplantation (P = 0.029). Conclusions Patients with CFLD undergoing initial assessment for liver transplantation may benefit from consideration of simultaneous liver–pancreas transplantation.

Renal impairment is frequently compromised in patients with end-stage liver disease and is associated with increased long-term mortality post-LT. In contrast to CNI, basiliximab is an immunosuppressive agent with minimal nephrotoxic potential. This study reviews the experience of a single pediatric liver transplant center's renal-sparing approach with the use of basiliximab and MMF to compensate for delayed entry of CNI in children with renal impairment at the time of organ availability. There were no differences in renal function between pediatric patients with and without pre-LT renal impairment within the first year (cGFR: 135mL/min/1.73m(2) vs. 144mL/min/1.73m(2); p=0.56) or at 5-8yr following LT, (129mL/min/1.73m(2) vs. 130mL/min/1.73m(2); p=0.97). In addition, there was no difference in ACR rates (50% vs. 43%, p=0.62) between patients in the basiliximab group and those patients receiving standard CNI and steroid strategies. The utilization of a renal-sparing approach with basiliximab alongside delayed entry and lower early target trough levels of CNI in children with renal impairment at the time of LT is safe and maintains excellent long-term kidney function.

Though robust clinical data are available within transplantation, these data are not used for broad-based, multicentered quality improvement initiates. This article describes a targeted quality improvement initiative within the Studies of Pediatric Liver Transplantation (SPLIT) Registry. Using standard statistical techniques and clinical expertise to adjust for data and statistical reliability, we identified the pediatric liver transplant centers in North America with the lowest hepatic artery thrombosis rate and biliary complication rates. A survey was completed to establish current practices within the entire SPLIT group. Surgeons from the highest performing centers presented a detailed, technically oriented overview of their current practices. The presentations and discussion that followed were recorded and form the basis of the best practices described herein. We frame this work as a unique six-step approach roadmap that may serve as an efficient and cost effective model for novel broad-based quality improvement initiatives within transplantation.

We examined serum IL-6 and IgE assays as adjuncts to VL monitoring for PTLD. Paediatric solid organ transplant recipients were followed with VL monitoring. VL, IL-6, and IgE assays were compared between PTLD cases and non-cases at <3, 3-6 and >6 months after transplantation. Median IL-6 levels in PTLD cases were 15.5 (2.0-87.1) and 23.3 (2.1-276) pg/mL compared with 3.25 (0.92-114) and 3.5 (0.75-199.25) pg/mL in non-cases at 3-6 and >6 months, respectively (p = 0.006 and p = 0.005). At >6 months, IL-6 levels correlated with VL and PTLD occurrence (Spearman's coefficients = 0.40; p = 0.001 and 0.32; p = 0.003) in univariate analyses. No benefit was derived from performance of IgE levels. The sensitivity and specificity of high VL as a test of PTLD were 76.3% and 92.5%, while the negative predictive value and PPV of VL were 94.9% and 68.4%, respectively. Combining elevated IL-6 with high VL increased the PPV and specificity to 80% and 96.2%, respectively, and improved the receiver operating characteristic curve. Serum IL-6 levels can improve the clinician's ability to identify PTLD, among patients with elevated EBV viral loads.

Objectives: To determine the safety and immunogenicity of the conjugate pneumococcal vaccine (PCV7) in pediatric solid organ transplant recipients.Patients and Methods: Pediatric solid organ transplant recipients were prospectively enrolled at >= 4 months following transplantation. Eligible pneumococcal vaccine-naive subjects received 3 doses of PCV7 at 8 week intervals, followed 8 weeks later by a dose of the 23-valent vaccine (PV23). Serology was done at baseline, 8 weeks following doses 2 and 3 of PCV7 and 8-12 weeks after PV23. Repeated measures analyses were done using SAS 9.Results: Eighty-one recipient, commenced immunization at a median age of 7.8 (0.6-17.5) years and a median time from transplantation to immunization of 1.3 (0.3-6.0) years. There were 31 heart, 18 liver, 5 lung, and 27 kidney recipients. Reported adverse events following vaccine doses included local reactions (PCV7: PV23 = 19%:16%) and fever (PCV7: PV23 = 3.8%;4.9%) and there were no serious reactions. Two doses of PCV7 induced >= 2 fold increases in geometric mean concentrations (GMCs) in all organ groups. Cardiac and lung recipients demonstrated additional benefit from a third dose of PCV7. The cardiac recipients showed most benefit from boosting with PV23 with significant increases in GMC's (P <= 0.008). The time of initiation of the vaccine strategy posttransplantation predicted seroprotection.Conclusion: PCV7 was safe and immunogenic in solid organ recipients. Three doses of this vaccine appear beneficial for selected organ groups. PV23 when administered at >= 1 year posttransplantation was useful in boosting antibody responses in patient groups demonstrating lower rates of responsiveness.

We aimed to describe the long-term changes in the imaging and clinical features of PHALT in children. A retrospective review was undertaken of consecutive children undergoing their first liver transplant between 1993 and 2003. Details of clinical progress and ultrasound imaging were recorded at one-yr post-transplantation and at last follow-up. Data were extracted on 83 children (median age at transplant 1.7 yr, range one month to 17.5 yr, 44 girls) who underwent 89 transplants. Four of these children died at a mean 5.6 yr (range 3.8-6.9 yr) after transplantation. Of the survivors, follow-up at one yr (n = 83) and at last follow-up (n = 71, median 4.3 yr post-transplant) revealed imaging evidence of splenomegaly in 46% and 44%, ascites in 6% and 4%, and portal systemic collaterals in 12% and 14%, respectively. Gastrointestinal hemorrhage associated with portal hypertension had occurred in no children at one yr and in four (6%) at latest follow-up. Features of portal hypertension on ultrasound scan are common in children before liver transplantation. An important minority of children will suffer clinically significant complications of PHALT during long-term follow-up, caused by both vascular and parenchymal disease.

Diamond, I1; Ahmed, B2; Thomas, K2; Hoppe, E1; Connolly, B2; Grant, D1; Ng, V1; Wales, P1; Fecteau, A1 Author Information

To examine outcomes and identify prognostic factors affecting survival after pediatric liver transplantation, data from 246 children who underwent a second liver transplantation (rLT) between 1996 and 2004 were analyzed from the SPLIT registry, a multi-center database currently comprised of 45 North American pediatric liver transplant programs. The main causes for loss of primary graft necessitating rLT were primary nonfunction, vascular complications, chronic rejection and biliary complications. Three-month, 1- and 2-year patient survival rates were inferior after rLT (74%, 67% and 65%) compared with primary LT (92%, 88% and 85%, respectively). Multivariate analysis of pretransplant variables revealed donor age less than 1 year, use of a technical variant allograft and INR at time of rLT as independent predictive factors for survival after rLT. Survival of patients who underwent early rLT (ErLT, <30 days after LT) was poorer than those who received rLT >30 days after LT (late rLT, LrLT): 3-month, 1- and 2-year patient survival rates 66%, 59%, and 56% versus 80%, 74% and 61%, respectively, log-rank p = 0.0141. Liver retransplantation in children is associated with decreased survival compared with primary LT, particularly, in the clinical settings of those patients requiring ErLT.

Journal of Pediatric Gastroenterology and NutritionVolume 37, Issue 1 p. 91-94 Case Report Interstitial Granulomatous Pneumonitis associated with Sirolimus in a Child after Liver Transplantation Yaron Avitzur, Yaron Avitzur Paediatric Academic Multi-Organ Transplantation (PAMOT) Program, The Hospital for Sick Children, Toronto, Canada Division of Gastroenterology and Nutrition, The Hospital for Sick Children, Toronto, CanadaSearch for more papers by this authorCarolina Jimenez-Rivera, Carolina Jimenez-Rivera Paediatric Academic Multi-Organ Transplantation (PAMOT) Program, The Hospital for Sick Children, Toronto, Canada Division of Gastroenterology and Nutrition, The Hospital for Sick Children, Toronto, CanadaSearch for more papers by this authorAnnie Fecteau, Annie Fecteau Paediatric Academic Multi-Organ Transplantation (PAMOT) Program, The Hospital for Sick Children, Toronto, Canada Division of Pediatric General Surgery, The Hospital for Sick Children, Toronto, CanadaSearch for more papers by this authorNicola Jones, Nicola Jones Paediatric Academic Multi-Organ Transplantation (PAMOT) Program, The Hospital for Sick Children, Toronto, Canada Division of Gastroenterology and Nutrition, The Hospital for Sick Children, Toronto, CanadaSearch for more papers by this authorBo Y Ngan, Bo Y Ngan Department of Paediatric Laboratory Medicine and Division of Pathology, The Hospital for Sick Children, Toronto, CanadaSearch for more papers by this authorVicky Lee Ng, Corresponding Author Vicky Lee Ng [email protected] Paediatric Academic Multi-Organ Transplantation (PAMOT) Program, The Hospital for Sick Children, Toronto, Canada Division of Gastroenterology and Nutrition, The Hospital for Sick Children, Toronto, CanadaCorrespondence to Vicky Lee Ng, MD, FRCPC, Division of Gastroenterology and Nutrition, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8 (e-mail: [email protected]).Search for more papers by this author Yaron Avitzur, Yaron Avitzur Paediatric Academic Multi-Organ Transplantation (PAMOT) Program, The Hospital for Sick Children, Toronto, Canada Division of Gastroenterology and Nutrition, The Hospital for Sick Children, Toronto, CanadaSearch for more papers by this authorCarolina Jimenez-Rivera, Carolina Jimenez-Rivera Paediatric Academic Multi-Organ Transplantation (PAMOT) Program, The Hospital for Sick Children, Toronto, Canada Division of Gastroenterology and Nutrition, The Hospital for Sick Children, Toronto, CanadaSearch for more papers by this authorAnnie Fecteau, Annie Fecteau Paediatric Academic Multi-Organ Transplantation (PAMOT) Program, The Hospital for Sick Children, Toronto, Canada Division of Pediatric General Surgery, The Hospital for Sick Children, Toronto, CanadaSearch for more papers by this authorNicola Jones, Nicola Jones Paediatric Academic Multi-Organ Transplantation (PAMOT) Program, The Hospital for Sick Children, Toronto, Canada Division of Gastroenterology and Nutrition, The Hospital for Sick Children, Toronto, CanadaSearch for more papers by this authorBo Y Ngan, Bo Y Ngan Department of Paediatric Laboratory Medicine and Division of Pathology, The Hospital for Sick Children, Toronto, CanadaSearch for more papers by this authorVicky Lee Ng, Corresponding Author Vicky Lee Ng [email protected] Paediatric Academic Multi-Organ Transplantation (PAMOT) Program, The Hospital for Sick Children, Toronto, Canada Division of Gastroenterology and Nutrition, The Hospital for Sick Children, Toronto, CanadaCorrespondence to Vicky Lee Ng, MD, FRCPC, Division of Gastroenterology and Nutrition, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8 (e-mail: [email protected]).Search for more papers by this author First published: 01 July 2003 https://doi.org/10.1002/j.1536-4801.2003.tb08111.xCitations: 6Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat REFERENCES 1Sindhi R, Webber S, Venkataramanan R, et al. Sirolimus for rescue and primary immunosuppression in transplanted children receiving tacrolimus. Transplantation 2001; 72: 851. 10.1097/00007890-200109150-00019 CASPubMedWeb of Science®Google Scholar 2Pappas PA, Weppler D, Pinna AD, et al. Sirolimus in pediatric gastrointestinal transplantation: the use of sirolimus for pediatric transplant patients with tacrolimus-related cardiomyopathy. Pediatr Transplant 2000; 4: 45. 10.1034/j.1399-3046.2000.00083.x CASPubMedGoogle Scholar 3Jimenez C, Avitzur Y, Fecteau A, Jones N, Ng V. Sirolimus as immune suppressive therapy in children with malignancy after liver transplantation (abstract). J Pediatr Gastroenterol Nutr 2002; 35: 418. Google Scholar 4Nishida S, Pinna A, Verzaro R, et al. Sirolimus (rapamycin)-based rescue treatment following chronic rejection after liver transplantation. Transplant Proc 2001; 33: 1495. 10.1016/S0041-1345(00)02566-5 CASPubMedWeb of Science®Google Scholar 5Saunders RN, Metcalfe MS, Nicholson ML. Rapamycin in transplantation: a review of the evidence. Kidney Int 2001; 59: 3. 10.1046/j.1523-1755.2001.00460.x CASPubMedWeb of Science®Google Scholar 6Neuhaus P, Klupp J, Langrehr JM. mTOR inhibitors: an overview. Liver Transpl 2001; 7: 473. 10.1053/jlts.2001.24645 CASPubMedWeb of Science®Google Scholar 7Hong JC, Kahan BD. Sirolimus-induced thrombocytopenia and leukopenia in renal transplant recipients: risk factors, incidence, progression, and management. Transplantation 2000; 69: 2085. 10.1097/00007890-200005270-00019 CASPubMedWeb of Science®Google Scholar 8Kahan BD. Efficacy of sirolimus compared with azathioprine for reduction of acute renal allograft rejection: a randomised multicentre study. The Rapamune US Study Group. Lancet 2000; 356: 194. 10.1016/S0140-6736(00)02480-6 CASPubMedWeb of Science®Google Scholar 9Watson CJ, Friend PJ, Jamieson NV, et al. Sirolimus: a potent new immunosuppressant for liver transplantation. Transplantation 1999; 67: 505. 10.1097/00007890-199902270-00002 CASPubMedWeb of Science®Google Scholar 10Morelon E, Stern M, Israel-Biet D, et al. Characteristics of sirolimus-associated interstitial pneumonitis in renal transplant patients. Transplantation 2001; 72: 787. 10.1097/00007890-200109150-00008 CASPubMedWeb of Science®Google Scholar 11Morelon E, Stern M, Kreis H. Interstitial pneumonitis associated with sirolimus therapy in renal-transplant recipients. N Engl J Med 2000; 343: 225. 10.1056/NEJM200007203430317 CASPubMedWeb of Science®Google Scholar 12Singer SJ, Tiernan R, Sullivan EJ. Interstitial pneumonitis associated with sirolimus therapy in renal-transplant recipients. N Engl J Med 2000; 343: 1815. 10.1056/NEJM200012143432417 CASPubMedWeb of Science®Google Scholar 13Lennon A, Finan K, FitzGerald MX, McCormick PA. Interstitial pneumonitis associated with sirolimus (rapamycin) therapy after liver transplantation. Transplantation 2001; 72: 1166. 10.1097/00007890-200109270-00034 CASPubMedWeb of Science®Google Scholar 14Peltekian K, McAlister VC, Colohan S, et al. De novo use of low-dose tacrolimus and sirolimus in liver transplantation. Transplant Proc 2001; 33: 1341. 10.1016/S0041-1345(00)02501-X CASPubMedWeb of Science®Google Scholar 15McAlister VC, Peltekian KM, Malatjalian DA, et al. Orthotopic liver transplantation using low-dose tacrolimus and sirolimus. Liver Transpl 2001; 7: 701. 10.1053/jlts.2001.26510 CASPubMedWeb of Science®Google Scholar 16Pridohl O, Heinemann K, Hartwig T, et al. Low-dose immunosuppression with FK 506 and sirolimus after liver transplantation: 1-year results. Transplant Proc 2001; 33: 3229. 10.1016/S0041-1345(01)02373-9 CASPubMedWeb of Science®Google Scholar 17Chang GJ, Mahanty HD, Quan D, et al. Experience with the use of sirolimus in liver transplantation-use in patients for whom calcineurin inhibitors are contraindicated. Liver Transpl 2000; 6: 734. 10.1053/jlts.2000.19023 CASPubMedWeb of Science®Google Scholar 18Majewski M, Korecka M, Kossev P, et al. The immunosuppressive macrolide RAD inhibits growth of human Epstein-Barr virus-transformed B lymphocytes in vitro and in vivo: A potential approach to prevention and treatment of posttransplant lymphoproliferative disorders. Proc Natl Acad Sci U S A 2000; 97: 4285. 10.1073/pnas.080068597 CASPubMedWeb of Science®Google Scholar 19Henry MT, Newstead CG. Sirolimus: another cause of drug-induced interstitial pneumonitis. Transplantation 2001; 72: 773. CASPubMedWeb of Science®Google Scholar 20Saag KG KJ, Hunninghake GW. Interstitial lung diseases. 6th ed. Philadelphia: Lippincott-Raven Publishers, 1998. Google Scholar Citing Literature Volume37, Issue1July 2003Pages 91-94 ReferencesRelatedInformation

Background. Initiated in 1995, the Studies of Pediatric Liver Transplantation (SPLIT) registry database is a cooperative research network of pediatric transplantation centers in the United States and Canada. The primary objectives are to characterize and follow trends in transplant indications, transplantation techniques, and outcomes (e.g., patient/graft survival, rejection, growth parameters, and immunosuppressive therapy.)Methods. As of June 15, 2000, 29 centers registered 1144 patients, 640 of whom received their first liver-only transplant while registered in SPLIT. Patients are followed every 6 months for 2 years and yearly thereafter. Data are submitted to a central coordinating center.Results. One/two-year patient survival and graft loss estimates are 0.85/0.82 and 0.77/0.72, respectively. Risk factors for death include: in ICU at transplant (relative risk (RR) = 2.63, P < 0.05) and height/weight deficits of two or more standard deviations (RR = 1.67, P < 0.05). Risk factors for graft loss include: in ICU at transplant (RR = 1.77, P < 0.05) and receiving a cadaveric split organ compared with a whole organ (RR = 2.3, P < 0.05). The percentage of patients diagnosed with hepatic a. and portal v. thrombosis were 9.7% and 7%, respectively; 15% had biliary complications within 30 days. At least one re-operation was required in 45%. One/two-year rejection probability estimates are 0.60/0.66. Tacrolimus, as primary therapy posttransplant, reduces first rejection risk (RR = 0.70, P < 0.05). Eighty-nine percent of school-aged children are in school full-time, 18 months posttransplant.Conclusions. This report provides one of the first descriptions of characteristics and clinical courses of a multicenter pediatric transplant population. Observations are subject to patient selection biases but are useful for generating hypothesis for future studies.

PURPOSE:The mortality rate for pediatric patients on the waiting list for transplantation has a major impact on the overall effectiveness of pediatric small bowel transplantation. This review was undertaken to determine the fate of Canadian children assessed for small bowel transplant and the outcome of those who undergo transplant in the tacrolimus era.METHODS:The authors reviewed retrospectively all of the pediatric small bowel patients listed since 1988 through the Canadian Organ Replacement Register and all the children referred to our program in its first year. All children who received a small bowel transplant between January 1993 and December 1999 also were reviewed.RESULTS:The mortality rate for pediatric patients on the small bowel transplant list was 53% after an average of 105 days on the list compared with 212 days for those who underwent transplant. Patients who died while on the list were younger and had signs of advanced liver disease at the time of listing. Thirteen Canadian children have received a small bowel transplant with an overall 1-year patient and graft survival rate of 61% and 53%, respectively. Survivors are all independent from total parenteral nutrition.CONCLUSION:Many Canadian children miss their opportunity for a successful small bowel transplant because of late referrals and a shortage of donor organs.