Abstract | HYPOTHESIS: DESIGN: Prospective before-after cohort study. SETTING: Tertiary referral center. PATIENTS: INTERVENTIONS: Thirty human pancreata were retrieved from local multiorgan donors and consecutively processed with intraductal collagenase perfusion, continuous digestion, and density gradient purification (group 1, n = 9) or similarly processed but impure tissue fractions cultured in vitro and then repurified to retrieve additional islets (group 2, n = 21). Islets were implanted by percutaneous portal embolization, providing more than 10 000 islet equivalents (IE) per kilogram of body weight (infusions from 1-3 donors per patient) under cover of antithymocyte globulin, sirolimus, or mycophenolate mofetil and tacrolimus. MAIN OUTCOME MEASURES: RESULTS: For group 1 vs group 2, no differences were observed in pancreas age (43 vs 44 years), cold storage (5 vs 4 hours), or weight (73 vs 82 g). Group 2 yielded 453 690 IE vs 214 109 IE in group 1 (P = .002). Grafts contained 50% or more endocrine cells in both groups. No difference occurred in cell viability or insulin secretion. Islets from 90% of group 2 pancreata met release criteria for transplantation. C-peptide secretion was detected in all recipients and persisted with a median follow-up to 12 months (range, 6-21 months) after full islet transplantation. Daily insulin dependence was reversed in all patients for at least 3 months. Five patients resumed small insulin doses. Compared with the best care program, all patients had improved metabolic stability. The mean +/- SE HbA(1c) level at entry into the study was 7.8% +/- 0.5%, and this decreased to 6.9% +/- 0.2% after best care (P = .38) and further to 6.2% +/- 0.2% at 6 months after transplantation (P = .002 vs entry; P = .15 vs best care; analysis of variance). CONCLUSIONS: Local pancreas donor retrieval with islet isolation and culture conditioning enabled an offer of islets for transplantation for 90% of consecutively processed pancreata. Isolated islets secreted insulin during prolonged follow-up after implantation into patients, yielding metabolic control comparable with that achieved by best medical therapy.
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Authors | Garth L Warnock, R Mark Meloche, David Thompson, R Jean Shapiro, Michelle Fung, Ziliang Ao, Stephen Ho, Zehua He, Long-Jun Dai, Linnea Young, Lorraine Blackburn, Sharon Kozak, Peter T W Kim, David Al-Adra, James D Johnson, Yu-Huan Theresa Liao, Tom Elliott, C Bruce Verchere |
Journal | Archives of surgery (Chicago, Ill. : 1960)
(Arch Surg)
Vol. 140
Issue 8
Pg. 735-44
(Aug 2005)
ISSN: 0004-0010 [Print] United States |
PMID | 16103282
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
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Topics |
- Adult
- Analysis of Variance
- Blood Glucose
(analysis)
- Cohort Studies
- Diabetes Mellitus, Type 1
(diagnosis, drug therapy, surgery)
- Female
- Follow-Up Studies
- Graft Rejection
- Graft Survival
- Humans
- Insulin
(therapeutic use)
- Islets of Langerhans
(cytology)
- Islets of Langerhans Transplantation
(adverse effects, methods)
- Male
- Middle Aged
- Monitoring, Physiologic
(methods)
- Probability
- Prospective Studies
- Risk Assessment
- Severity of Illness Index
- Tissue and Organ Harvesting
- Transplantation Immunology
(physiology)
- Treatment Outcome
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