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Progress in individualizing autologous islet isolation techniques for pediatric islet autotransplantation after total pancreatectomy in children for chronic pancreatitis |
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| Authors: | Joshua J. Wilhelm Appakalai N. Balamurugan Melena D. Bellin James S. Hodges Jessica Diaz Sarah Jane Schwarzenberg Zachary A. Swanson Marie E. Cook Elissa M. Downs David E. R. Sutherland Bernhard J. Hering Srinath Chinnakotla |
| Affiliation: | 1. Schulze Diabetes Institute, University of Minnesota Medical School, Minneapolis, Minnesota, USA;2. Department of Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA;3. Schulze Diabetes Institute, University of Minnesota Medical School, Minneapolis, Minnesota, USA Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota, USA;4. Division of Biostatistics, University of Minnesota Medical School, Minneapolis, Minnesota, USA;5. Division of Transplantation, Department of Surgery, University of Minnesota Medical School, Minneapolis, Minnesota, USA;6. Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota, USA |
| Abstract: | Total pancreatectomy with islet autotransplantation is performed to treat chronic pancreatitis in children. Successful islet isolation must address the challenges of severe pancreatic fibrosis and young donor age. We have progressively introduced modifications to optimize enzymatic and mechanical dissociation of the pancreas during islet isolation. We evaluated 2 islet isolation metrics in 138 children—digest islet equivalents per gram pancreas tissue (IEQ/g) and digest IEQ per kilogram body weight (IEQ/kg), using multiple regression to adjust for key disease and patient features. Islet yield at digest had an average 4569 (standard deviation 2949) islet equivalent (IEQ)/g and 4946 (4009) IEQ/kg, with 59.1% embedded in exocrine tissue. Cases with very low yield (<2000 IEQ/g or IEQ/kg) have decreased substantially over time, 6.8% and 9.1%, respectively, in the most recent tertile of time compared to 19.2% and 23.4% in the middle and 34.1% and 36.4% in the oldest tertile. IEQ/g and IEQ/kg adjusted for patient and disease factors improved in consistency and yield in the modern era. Minimal mechanical disruption during digestion, warm enzymatic digestion using enzyme collagenase:NP activity ratio < 10:1, coupled with extended distension and trimming time during islet isolation of younger and fibrotic pediatric pancreases, gave increased islet yield with improved patient outcomes. |
| Keywords: | clinical research/ practice diabetes islet isolation pediatrics |