Long-term outcomes of clinical transplantation of pancreatic islets with uncontrolled donors after cardiac death: A multicenter experience in japan

T. Anazawa, T. Saito, M. Goto, Takashi Kenmochi, S. Uemoto, T. Itoh, Y. Yasunami, A. Kenjo, T. Kimura, K. Ise, T. Tsuchiya, M. Gotoh

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1980-1984
Number of pages5
JournalTransplantation Proceedings
Volume46
Issue number6
DOIs
Publication statusPublished - 01-01-2014

Fingerprint

Islets of Langerhans Transplantation
Japan
Tissue Donors
Graft Survival
Hypoglycemia
Transplants
Type 1 Diabetes Mellitus
Insulin
Pancreas Transplantation
C-Peptide
Tacrolimus
Organ Transplantation
Sirolimus
Immunosuppression
Registries
Pancreas
Glucose
Recurrence

All Science Journal Classification (ASJC) codes

  • Surgery
  • Transplantation

Cite this

Anazawa, T. ; Saito, T. ; Goto, M. ; Kenmochi, Takashi ; Uemoto, S. ; Itoh, T. ; Yasunami, Y. ; Kenjo, A. ; Kimura, T. ; Ise, K. ; Tsuchiya, T. ; Gotoh, M. / Long-term outcomes of clinical transplantation of pancreatic islets with uncontrolled donors after cardiac death : A multicenter experience in japan. In: Transplantation Proceedings. 2014 ; Vol. 46, No. 6. pp. 1980-1984.
@article{f4fc61bf12ef4d70b860c9a389c75f5e,
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.",
author = "T. Anazawa and T. Saito and M. Goto and Takashi Kenmochi and S. Uemoto and T. Itoh and Y. Yasunami and A. Kenjo and T. Kimura and K. Ise and T. Tsuchiya and M. Gotoh",
year = "2014",
month = "1",
day = "1",
doi = "10.1016/j.transproceed.2014.06.006",
language = "English",
volume = "46",
pages = "1980--1984",
journal = "Transplantation Proceedings",
issn = "0041-1345",
publisher = "Elsevier USA",
number = "6",

}

Anazawa, T, Saito, T, Goto, M, Kenmochi, T, Uemoto, S, Itoh, T, Yasunami, Y, Kenjo, A, Kimura, T, Ise, K, Tsuchiya, T & Gotoh, M 2014, 'Long-term outcomes of clinical transplantation of pancreatic islets with uncontrolled donors after cardiac death: A multicenter experience in japan', Transplantation Proceedings, vol. 46, no. 6, pp. 1980-1984. https://doi.org/10.1016/j.transproceed.2014.06.006

Long-term outcomes of clinical transplantation of pancreatic islets with uncontrolled donors after cardiac death : A multicenter experience in japan. / Anazawa, T.; Saito, T.; Goto, M.; Kenmochi, Takashi; Uemoto, S.; Itoh, T.; Yasunami, Y.; Kenjo, A.; Kimura, T.; Ise, K.; Tsuchiya, T.; Gotoh, M.

In: Transplantation Proceedings, Vol. 46, No. 6, 01.01.2014, p. 1980-1984.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Long-term outcomes of clinical transplantation of pancreatic islets with uncontrolled donors after cardiac death

T2 - A multicenter experience in japan

AU - Anazawa, T.

AU - Saito, T.

AU - Goto, M.

AU - Kenmochi, Takashi

AU - Uemoto, S.

AU - Itoh, T.

AU - Yasunami, Y.

AU - Kenjo, A.

AU - Kimura, T.

AU - Ise, K.

AU - Tsuchiya, T.

AU - Gotoh, M.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84906085180&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84906085180&partnerID=8YFLogxK

U2 - 10.1016/j.transproceed.2014.06.006

DO - 10.1016/j.transproceed.2014.06.006

M3 - Article

C2 - 25131088

AN - SCOPUS:84906085180

VL - 46

SP - 1980

EP - 1984

JO - Transplantation Proceedings

JF - Transplantation Proceedings

SN - 0041-1345

IS - 6

ER -