Elevated Risk of Cancer Following Solid Organ Transplant in Childhood: A Population-based Cohort Study

Background Cancer risk is elevated among adult transplant recipients, but there is limited data regarding long-term cancer risk and mortality in pediatric recipients. Methods We conducted a population-based retrospective cohort study in Ontario, Canada. We included pediatric recipients of solid organ transplants at the Hospital for Sick Children, Toronto from 1991 to 2014, and compared rates of new cancers and cancer-specific mortality to nontransplanted Ontario children born in the same year. We constructed standard and time-dependent Cox proportional hazards models accounting for competing risk of death. Results A total of 951 recipients (kidney n=400, liver n=283, heart n=218, lung n=36, multiorgan/small bowel n=14) were compared to 5.3 million general population children. Mean (SD) age was 8.2 (6.4) years; 50% were male. Over a mean (SD) follow-up of 10.8 (7.1) years, cumulative incidence of cancer was 20% in recipients and 1.2% in the general population (incidence rate ratio 32.9; 95% CI 26.6-40.8). Risk was highest in the first year posttransplant (aHR 176; 95% CI 117-264), but remained elevated beyond 10 years (aHR 10.8; 95% CI 6.3-18.6). Lymphoproliferative disorders were predominant (77%); however, solid cancers (renal, sarcomas, genital, thyroid) were seen. Recipients of lung or multiorgan transplants were at highest risk. Cancer-specific mortality was also higher among recipients (HR 93.1; 95% CI 59.6-145.2). Conclusions Childhood transplant recipients have a 30-times greater cancer incidence versus the general population. Further investigation is needed to guide screening strategies in this at-risk population. *Corresponding Author Contact Information: Rulan S. Parekh, MD, MS., FRCPC, Nephrologist, Division of Nephrology, Associate Chief, Clinical Research, Scientist, Child Health Evaluative Sciences, Research Institute, Professor, Faculty of Medicine, Institute of Medical Sciences and Dalla Lana School of Public Health, University of Toronto, Peter Gilgan Centre for Research & Learning, The Hospital for Sick Children (SickKids), 686 Bay Street, Child Health Evaluative Sciences, 11th floor, Toronto, ON, Canada, M5G 0A4, Phone: 416-813-7654 ext. 328042, Fax: 416-813-5979. Email: rulan.parekh@sickkids.ca AUTHORSHIP A.K., S.D., S.J.K., P.C.N., and R.S.P participated in the study design. A.K., S.D., S.G., and P.C.N. participated in the data analysis. A.K., S.D., J.S.D., P.C.N., and R.S.P drafted the manuscript. All authors read and approved the final manuscript. DISCLOSURES The authors declare no conflicts of interest. FUNDING Dr. Rulan S. Parekh received funding from the Transplant & Regenerative Medicine Centre (TRMC) Catalyst Grant at The Hospital for Sick Children, Ashley's Angels Catwalk and the Canadian Institutes of Health Research (CIHR) for the completion of this study. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Regional Variation in Utilization and Outcomes of Liver Allografts from Donors with High Body-Mass Index and Graft Macrosteatosis: A Role for Liver Biopsy

Background Obesity, defined as a body mass index ≥30 kg/m2 (hBMI), is a growing epidemic worldwide and is associated with multiple comorbidities. hBMI individuals account for an increasing portion of potential liver donors. Here we evaluate trends in the utilization and outcomes of hBMI donors on a national and regional level and the potential role of liver biopsy in donor evaluation. Methods UNOS STAR database was evaluated for deceased donor liver transplants between 2006 and 2016 across 11 OPTN regions. hBMI donors were compared to lower BMI counterparts and evaluated for biopsy rates, utilization rates and allograft outcomes. Univariate and multivariable analyses were performed. Results 77 050 potential donors were identified and 60 200 transplants were evaluated. Utilization rates for hBMI donors was 66.1% versus 78.1% for lower BMI donors (p

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Renal Revival; the Hidden Benefit of Antirejection Medications

No abstract available

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Reduced Risk of BK Polyomavirus Infection in HLA-B51 Positive Kidney Transplant Recipients

Background Identification of specific HLA alleles and T cell epitopes that influence the course of BK polyomavirus (BKPyV) infection after kidney transplantation (KTx), including development of BKPyV-associated nephropathy (BKPyVAN), can be useful for patient risk stratification and possibly vaccine development. Methods In a retrospective cohort of 407 living kidney donor-recipient pairs, donor and recipient HLA class I and II status were correlated with the occurrence of recipient BKPyV viremia and BKPyVAN in the first year after KTx. Relevant HLA alleles were systematically analyzed for candidate peptide epitopes in silico. Results While none of the 78 HLA alleles analyzed increased the risk of BKPyV viremia and BKPyVAN, a considerable reduction of BKPyV viremia and BKPyVAN cases was observed in HLA-B51 positive KTx recipients. Multivariate analysis showed that HLA-B51-positivity, found in 36 recipients (9%), reduced the risk of viremia approximately five-fold (HR 0.18, 95% CI: 0.04 – 0.73, p = 0.017). Four HLA-B51-restricted putative cytotoxic T lymphocyte epitopes were identified, including a previously described HLA-B supermotif-containing peptide (LPLMRKAYL), encoded by 2 relevant T-antigens (Small T and Large T) and previously shown to be highly immunogenic. Conclusions In conclusion, HLA-B51-positive kidney transplant recipients were less susceptible to BKPyV infection, which might be explained by efficient presentation of a particular BKPyV-derived immunogenic peptide. Authorship The author's specific contributions are as follows: HFW and MCWF initiated the study. HFW, ACMK, JWdF, JIR, FHJC and MCWF designed the study. HFW, CSdB, GWH and JIR collected the samples and gathered the data. CSdB performed the serological tests and the PCR assays. HFW analysed the data. EWvZ and GWH provided statistical support. HFW, ACMK, JWdF, JIR, FHJC, and MCWF interpreted the data. HFW and MCWF drafted the manuscript, and designed the figures and tables. All authors reviewed and approved the final report. Disclosure The authors declare no conflicts of interest Funding This study was supported by the Dutch Kidney Foundation, grant 13A1D302. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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The Impact of Deceased Donor Liver Extraction Time on Early Allograft Function in Adult Liver Transplant Recipients

Background In liver transplantation, both cold- and warm ischemia time are known to impact early graft function. The extraction time is a period during the initial phase of organ cooling which occurs during deceased donor procurement. During this time, the organ is at risk of suboptimal cooling. Whether donor extraction time, the time from donor aortic cross-clamp to removal of the donor organ from the body cavity has an effect on early graft function is not known. Methods We investigated the effect of donor extraction time on early graft function in 292 recipients of liver grafts procured locally and transplanted at our center between June 2012 and December 2016. Early graft function was assessed using the model of early allograft function score in a multivariable regression model including donor extraction time, cold ischemia time, warm ischemia time and the donor risk index. Results Donor extraction time had an independent effect on early graft function measured by the model of early allograft function score. (Coefficient 0.018, 95%CI 0.004 to 0.03, P = 0.012; for each minute increase of donor extraction time). Besides donor extraction time, cold ischemia time, warm ischemia time and donor risk index had a significant effect on early graft function. Conclusions We demonstrate an independent effect of donor extraction time on graft function after liver transplantation. Efforts to minimize donor extraction time could improve early graft function in liver transplantation. Correspondence information: Dieter Adelmann, MD, PhD, Department of Anesthesia & Perioperative Care, University of California, San Francisco, 521 Parnassus Avenue, San Francisco, CA 94143, USA, dieter.adelmann@ucsf.edu Authorship: D.A., G.R.R., and C.U.N. drafted the study protocol. C.U.N. obtained Institutional Review Board approval D.A., M.T. and R.P.K. collected patients' data D.A. performed the statistical analysis D.A., G.R.R., S.S., L.J.B, R.P.K. and C.U.N. prepared the manuscript. Disclosures: The authors declare no conflicts of interest Funding: This study was supported by departmental funds. (Department of Anesthesia and Perioperative Care San Francisco, University of California, San Francisco, CA) Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Cell Spray Transplantation of Stem Cells for Ischemic Cardiomyopathy – How effective are dispersed droplets?

No abstract available

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Cell Spray Transplantation of Adipose-Derived Mesenchymal Stem Cell Recovers Ischemic Cardiomyopathy in a Porcine Model

Background Allogeneic adipose-derived mesenchymal stem cells (ADSC) are promising cell sources for cell therapy to treat ischemic cardiomyopathy (ICM). We hypothesized that ADSC transplantation via the new cell spray method may be a feasible, safe, and effective treatment for ICM. Methods Human ADSCs were acquired from white adipose tissue. Porcine ICM models were established by constriction of the left anterior descending coronary artery. ADSCs were spread over the surface of the heart via cell spray in fibrinogen and thrombin solutions. The cardiac function was compared to that of the control group. Results ADSCs were successfully transplanted forming a graft-like gel film covering the infarct myocardium. Premature ventricular contractions were rarely detected in the first 3 days after transplantation. Echocardiography and magnetic resonance imaging revealed improved cardiac performance of the ADSC group at 4 and 8 weeks after transplantation. Systolic and diastolic parameters were significantly greater in the ADSC group at 8 weeks after transplantation. Histological examination showed significantly attenuated left ventricular remodeling and a greater vascular density in the infarct border area in the ADSC group. Moreover, the coronary flow reserve was maintained, and expression levels of angiogenesis-related factors in the infarct border and remote areas were significantly increased. Conclusion Spray method implantation of allogenic ADSCs can improve recovery of cardiac function in a porcine infarction model. This new allogenic cell delivery system may help to resolve current limitations of invasiveness and cost in stem cell therapy. Corresponding author: Yoshiki Sawa, MD, PhD, Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan, E-mail: sawa-p@surg1.med.osaka-u.ac.jp, TEL: +81-6-6879-3154/FAX: +81-6-6879-3163 Author contributions D.M. participated in research design performance of research, analyzed data, and wrote the article. S.Y., K.K., H.K., and H.N. performed research and analyzed data. K.I. and J.H. participated in performing PET.(helped with some experiments) S.S., S.F., T.U., and K.T. reviewed all data and article. S.M. and Y.S.participated in research design, writing of the article and reviewed all data and article. All authors have met the following criteria: drafting the work or revising it critically for important intellectual content; final approval of the version to be published; agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Disclosure This study was supported by Rohto Pharmaceutical Co., Ltd. Dr. Sawa serves as an advisor for the sponsor. Dr. Sawa and Dr. Miyagawa received a speaking fee from the sponsor. Ms. Kawai, Mr. Kurata, and Mr. Nishida receive a salary from the sponsor where they are employees. The sponsor had no control over the interpretation, writing, or publication of this work. The terms of this arrangement have been reviewed and approved by Osaka University in accordance with its policy on objectivity in research. Funding This work was supported by the Department of Advanced Stem Cell Therapy (Rohto Pharmaceutical Co. Ltd.). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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