title: Long-term outcomes of clinical transplantation of pancreatic islets with uncontrolled donors after cardiac death: a multicenter experience in Japan.
abstract: BACKGROUND
  Pancreatic islet transplantation has emerged as an effective treatment for type 1 diabetes mellitus, but its use is limited due to an insufficient supply of cadaveric pancreata. In Japan, uncontrolled donors after cardiac death (DCD) are not deemed to be suitable for whole-organ pancreatic transplantation, and can provide a source of pancreas for islet transplantation. However, the long-term outcomes and utility of uncontrolled DCD in the clinical setting remain controversial. Here, we summarize the long-term outcomes of islet transplantation employing uncontrolled DCD as reported to the Japan Islet Transplantation Registry.
  
  
  METHODS
  Sixty-four isolations and 34 transplantations of pancreatic islets were conducted in 18 subjects with type 1 diabetes mellitus under the cover of immunosuppression with basiliximab, sirolimus, and tacrolimus. All donors were uncontrolled DCD at the time of harvesting. The mean follow-up time was 76 months.
  
  
  RESULTS
  Of the 18 recipients, 8, 4, and 6 recipients received 1, 2, and 3 islet infusions, respectively. Overall graft survivals (defined as a C-peptide level ≥0.3 ng/mL) were 72.2%, 44.4%, and 22.2% at 1, 2, and 5 years, respectively, whereas the corresponding graft survivals after multiple infusions were 90.0%, 70.0%, and 30.0%, respectively. Three of these recipients achieved insulin independence in 14, 79, and 215 days. HbA1c levels and the requirement of exogenous insulin were improved before loss of graft function. All recipients became free of severe hypoglycemia unawareness, however, at least 5 of 14 patients who had graft failure experienced recurrence of severe hypoglycemia after the loss of graft function.
  
  
  CONCLUSIONS
  Islet transplantation from DCD can relieve glucose instability and problems with hypoglycemia when the graft is functioning. However, islets from uncontrolled DCD may be associated with reduced long-term graft survival. Further improvements in the clinical outcome by modification of islet isolation/transplantation protocols are necessary to establish islet transplantation using DCD.
authors.affiliation: Department of Regenerative Surgery, Japan Islet Transplant Registry, Fukushima Medical University, Fukushima, Japan. Electronic address: anazawa@fmu.ac.jp.
authors.forename: T
authors.initials: T
authors.lastname: Anazawa
authors.affiliation: Department of Regenerative Surgery, Japan Islet Transplant Registry, Fukushima Medical University, Fukushima, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Saito
authors.affiliation: Division of Advanced Surgical Science and Technology, Tohoku University, Sendai, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Goto
authors.affiliation: Department of Transplant Surgery, Fujita Health University, School of Medicine, Toyoake, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kenmochi
authors.affiliation: Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Uemoto
authors.affiliation: Complementary and Alternative Medicine, Gastroenterologic Surgery, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Itoh
authors.affiliation: Department of Regenerative Medicine and Transplantation, Fukuoka University, Fukuoka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yasunami
authors.affiliation: Department of Regenerative Surgery, Japan Islet Transplant Registry, Fukushima Medical University, Fukushima, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kenjo
authors.affiliation: Department of Regenerative Surgery, Japan Islet Transplant Registry, Fukushima Medical University, Fukushima, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Department of Regenerative Surgery, Japan Islet Transplant Registry, Fukushima Medical University, Fukushima, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ise
authors.affiliation: Department of Regenerative Surgery, Japan Islet Transplant Registry, Fukushima Medical University, Fukushima, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tsuchiya
authors.affiliation: Department of Regenerative Surgery, Japan Islet Transplant Registry, Fukushima Medical University, Fukushima, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Gotoh
mesh_terms: D000328:Adult; D000368:Aged; D002096:C-Peptide / Q000097:blood; D016757:Death, Sudden, Cardiac; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000378:metabolism; D006085:Graft Survival; D006801:Humans; D016381:Islets of Langerhans Transplantation; D007564:Japan; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D002096:C-Peptide; D006442:Glycated Hemoglobin