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Frontiers in Endocrinology 2022Pancreas (and islet) transplantation is the only curative treatment for type 1 diabetes patients whose β-cell functions have been abolished. However, the lack of donor... (Review)
Review
Pancreas (and islet) transplantation is the only curative treatment for type 1 diabetes patients whose β-cell functions have been abolished. However, the lack of donor organs has been the major hurdle to save a large number of patients. Therefore, transplantation of animal organs is expected to be an alternative method to solve the serious shortage of donor organs. More recently, a method to generate organs from pluripotent stem cells inside the body of other species has been developed. This interspecies organ generation using blastocyst complementation (BC) is expected to be the next-generation regenerative medicine. Here, we describe the recent advances and future prospects for these two approaches.
Topics: Animals; Blastocyst; Organogenesis; Pluripotent Stem Cells; Regenerative Medicine; Transplantation, Heterologous
PubMed: 35992127
DOI: 10.3389/fendo.2022.963282 -
Current Diabetes Reports Nov 2019Beta-cell replacement is the best therapeutic option for patients with type 1 diabetes. Because of donor scarcity, more extended criteria donors are used for... (Review)
Review
PURPOSE OF REVIEW
Beta-cell replacement is the best therapeutic option for patients with type 1 diabetes. Because of donor scarcity, more extended criteria donors are used for transplantation. Donation after circulatory death donors (DCD) are not commonly used for pancreas transplantation, because of the supposed higher risk of complications. This review gives an overview on the pathophysiology, risk factors, and outcome in DCD transplantation and discusses different preservation methods.
RECENT FINDINGS
Studies on outcomes of DCD pancreata show similar results compared with those of donation after brain death (DBD), when accumulation of other risk factors is avoided. Hypothermic machine perfusion is shown to be a safe method to improve graft viability in experimental settings. DCD should not be the sole reason to decline a pancreas for transplantation. Adequate donor selection and improved preservation techniques can lead to enhanced pancreas utilization and outcome.
Topics: Death; Diabetes Mellitus, Type 1; Donor Selection; Graft Survival; Humans; Organ Preservation; Pancreas Transplantation; Retrospective Studies; Risk Factors; Tissue Donors; Treatment Outcome
PubMed: 31741132
DOI: 10.1007/s11892-019-1238-y -
Transplant International : Official... Apr 2021With a later onset of diabetes complications and thus increasing age of transplant candidates, many centers have extended upper age limits for pancreas transplantation....
With a later onset of diabetes complications and thus increasing age of transplant candidates, many centers have extended upper age limits for pancreas transplantation. This study investigates the effect of recipient and donor age on outcomes after pancreas transplantation.We retrospectively analyzed 565 pancreas transplants performed at two Eurotransplant centers. The cohort was split at a recipient and donor age of 50 and 40 years, respectively. Median recipient age in old patients (≥50 years; 27.2%) was 54 years and 40 years in young patients (<50 years). Compared to young recipients, old recipients had an inferior patient survival rate (≥50: 5yr, 82.8%; 10yr, 65.6%; <50: 5yr, 93.3%; 10yr, 82.0%; P < 0.0001). Old recipients demonstrated comparable death-censored pancreas (≥50: 1yr, 80.6%; 5yr, 70.2%; <50: 1yr, 87.3%; 5yr, 77.8%; P = 0.35) and kidney graft survival (≥50: 1yr, 97.4%; 5yr, 90.6%; <50: 1yr, 97.8%; 5yr, 90.2%; P = 0.53) compared to young recipients. Besides a lower rate of kidney rejection, similar relative risks for postoperative complications were detected in old and young patients. This study shows that despite an increased mortality in old recipients, excellent graft survival can be achieved similar to that of young patients. Age alone should not exclude patients from receiving a pancreas transplant.
Topics: Graft Rejection; Graft Survival; Humans; Kidney Transplantation; Middle Aged; Pancreas Transplantation; Retrospective Studies; Tissue Donors; Treatment Outcome
PubMed: 33570795
DOI: 10.1111/tri.13845 -
Transplant International : Official... 2022Ethnic disparities in the outcomes after simultaneous pancreas kidney (SPK) transplantation still exist. The influence of ethnicity on the outcomes of pancreas...
Ethnic disparities in the outcomes after simultaneous pancreas kidney (SPK) transplantation still exist. The influence of ethnicity on the outcomes of pancreas transplantation in the UK has not been reported and hence we aimed to investigate our cohort. A retrospective analysis of all pancreas transplant recipients ( = 171; Caucasians = 118/Black Asian Ethnic Minorities, BAME = 53) from 2006 to 2020 was done. The median follow-up was 80 months. Patient & pancreas graft survival, rejection rate, steroid free maintenance rate, HbA1c, weight gain, and the incidence of secondary diabetic complications post-transplant were compared between the groups. < 0.003 was considered significant (corrected for multiple hypothesis testing). Immunosuppression consisted of alemtuzumab induction and steroid free maintenance with tacrolimus and mycophenolate mofetil. Pancreas graft & patient survival were equivalent in both the groups. BAME recipients had a higher prevalence of type-2 diabetes mellitus pre-transplant (BAME = 30.19% vs. Caucasians = 0.85%, < 0.0001), and waited for a similar time to transplantation once waitlisted, although pre-emptive SPK transplantation rate was higher for Caucasian recipients (Caucasians = 78.5% vs. BAME = 0.85%, < 0.0001). Despite equivalent rejections & steroid usage, BAME recipients gained more weight (BAME = 7.7% vs. Caucasians = 1.8%, = 0.001), but had similar HbA1c (functioning grafts) at 3-,12-, 36-, and 60-months post-transplant.
Topics: Ethnicity; Glycated Hemoglobin; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Pancreas Transplantation; Retrospective Studies; Steroids; United Kingdom
PubMed: 35781938
DOI: 10.3389/ti.2022.10490 -
American Journal of Kidney Diseases :... Sep 2021Optimal glycemic control in kidney transplant recipients with diabetes is associated with improved morbidity and better patient and allograft survival. Transplant... (Review)
Review
Optimal glycemic control in kidney transplant recipients with diabetes is associated with improved morbidity and better patient and allograft survival. Transplant options for patients with diabetes requiring insulin therapy and chronic kidney disease who are suitable candidates for kidney transplantation should include consideration of β-cell replacement therapy: pancreas or islet transplantation. International variation related to national regulatory policies exists in offering one or both options to suitable candidates and is further affected by pancreas/islet allocation policies and transplant waiting list dynamics. The selection of appropriate candidates depends on patient age, coexistent morbidities, the timing of referral to the transplant center (predialysis versus on dialysis) and availability of living kidney donors. Therefore, early referral (estimated glomerular filtration rate < 30 mL/min/1.73 m) is of the utmost importance to ensure adequate time for informed decision making and thorough pretransplant evaluation. Obesity, cardiovascular disease, peripheral vascular disease, smoking, and frailty are some of the conditions that need to be addressed before acceptance on the transplant list, and ideally before dialysis becoming imminent. This review offers insights into selection of pancreas/islet transplant candidates by transplant centers and an update on posttransplant outcomes, which may have practice implications for referring nephrologists.
Topics: Diabetes Mellitus, Type 1; Global Health; Graft Survival; Humans; Kidney Diseases; Kidney Transplantation; Living Donors; Morbidity; Postoperative Complications; Transplantation, Homologous
PubMed: 33992729
DOI: 10.1053/j.ajkd.2021.02.339 -
World Journal of Transplantation Jan 2021To describe the main aspects of back-table surgery in pancreatic graft and the problems arising from poor technique. Back-table surgery for pancreatic graft is a... (Review)
Review
To describe the main aspects of back-table surgery in pancreatic graft and the problems arising from poor technique. Back-table surgery for pancreatic graft is a complex, meticulous and laborious technique on which the success of implant surgery and perioperative results depends. The technique can be described in the following steps: Preparation of the sterile table, inspection of the pancreas-spleen block, management of the duodenum, identification of the bile duct, preparation of the portal vein, preparation of the own graft arteries and anastomosis to the arterial graft, spleen management and graft preservation prior to implantation in the recipient. A careful inspection of the pancreas-spleen block should be performed. It is important to identify the stump of the main bile duct, the portal vein cuff, and the arrangement of the superior mesenteric artery and splenic artery. The redundant duodenum must be removed. The availability of a good venous cuff facilitates the portal vein anastomosis and the positioning of the graft, two key points to prevent thrombosis. The section line of the arteries must be clean, without atherosclerosis, to prevent arterial thrombosis. The superior and splenic mesenteric arteries are generally separated by dense fibrolymphatic tissue. The artery can be reconstructed by interposing a "Y" graft from the donor iliac artery; or with an end-to-end anastomosis between the splenic artery and the superior mesenteric artery. An exquisite technique of bench work helps to prevent the most feared complications of pancreas transplantation: Thrombosis and graft pancreatitis.
PubMed: 33552938
DOI: 10.5500/wjt.v11.i1.1 -
Journal of Diabetes Investigation Oct 2023It is crucial to develop practical and noninvasive methods to assess the functional beta-cell mass in a donor pancreas, in which monitoring and precise evaluation is...
It is crucial to develop practical and noninvasive methods to assess the functional beta-cell mass in a donor pancreas, in which monitoring and precise evaluation is challenging. A patient with type 1 diabetes underwent noninvasive imaging following simultaneous kidney-pancreas transplantation with positron emission tomography/computed tomography (PET/CT) using an exendin-based probe, [ F]FB(ePEG12)12-exendin-4. Following transplantation, PET imaging with [ F]FB(ePEG12)12-exendin-4 revealed simultaneous and distinct accumulations in the donor and native pancreases. The pancreases were outlined at a reasonable distance from the surrounding organs using [ F]FB(ePEG12)12-exendin-4 whole-body maximum intensity projection and axial PET images. At 1 and 2 h after [ F]FB(ePEG12)12-exendin-4 administration, the mean standardized uptake values were 2.96 and 3.08, respectively, in the donor pancreas and 1.97 and 2.25, respectively, in the native pancreas. [ F]FB(ePEG12)12-exendin-4 positron emission tomography imaging allowed repeatable and quantitative assessment of beta-cell mass following simultaneous kidney-pancreas transplantation.
Topics: Humans; Positron Emission Tomography Computed Tomography; Exenatide; Pancrelipase; Peptides; Kidney Transplantation; Pancreas
PubMed: 37377043
DOI: 10.1111/jdi.14045 -
Transplant International : Official... 2023Thrombosis is a leading causes of pancreas graft loss after simultaneous pancreas kidney (SPK), pancreas after kidney (PAK), and pancreas transplant alone (PTA). There... (Meta-Analysis)
Meta-Analysis Review
Thrombosis is a leading causes of pancreas graft loss after simultaneous pancreas kidney (SPK), pancreas after kidney (PAK), and pancreas transplant alone (PTA). There remains no standardized thromboprophylaxis protocol. The aim of this systematic review and meta-analysis is to evaluate the impact of heparin thromboprophylaxis on the incidence of pancreas thrombosis, pancreas graft loss, bleeding, and secondary outcomes in SPK, PAK, and PTA. Following PRISMA guidelines, we systematically searched BIOSIS®, PubMed®, Cochrane Library®, EMBASE®, MEDLINE®, and Web of Science® on April 21, 2021. Primary peer-reviewed studies that met inclusion criteria were included. Two methods of quantitative synthesis were performed to account for comparative and non-comparative studies. We included 11 studies, comprising of 1,122 patients in the heparin group and 236 patients in the no-heparin group. When compared to the no-heparin control, prophylactic heparinization significantly decreased the risk of early pancreas thrombosis and pancreas loss for SPK, PAK and PTA without increasing the incidence of bleeding or acute return to the operating room. Heparin thromboprophylaxis yields an approximate two-fold reduction in both pancreas thrombosis and pancreas loss for SPK, PAK and PTA. We report the dosage, frequency, and duration of heparin administration to consolidate the available evidence.
Topics: Humans; Heparin; Anticoagulants; Kidney Transplantation; Venous Thromboembolism; Pancreas Transplantation; Pancreas; Thrombosis; Graft Survival
PubMed: 36819126
DOI: 10.3389/ti.2023.10442 -
American Journal of Transplantation :... Feb 2023The number of pancreas transplants in the United States was largely unchanged in 2021 at 963 transplants compared with 962 in 2020, showing that recovery from the...
The number of pancreas transplants in the United States was largely unchanged in 2021 at 963 transplants compared with 962 in 2020, showing that recovery from the COVID-19 pandemic was not as pronounced in pancreas transplantation as in other organs. The number of simultaneous pancreas-kidney transplants (SPKs) decreased from 827 to 820, whereas the number of pancreas-after-kidney transplants and pancreas transplants alone increased marginally to compensate. The proportion of patients with type 2 diabetes on the waiting list increased to 22.9% in 2021, compared with 20.1% in 2020. Consequently, the proportion of transplants in patients with type 2 diabetes increased from 21.3% in 2020 to 25.9% in 2021. The proportion of transplants in older recipients (aged 55 years or older) also increased to 13.5% in 2021 from 11.7% in 2020. Outcomes after SPK continue to be the best of the three categories of pancreas transplants: 1-year graft failure for kidney at 5.7% and pancreas at 10.5% for transplants performed in 2020. The proportion of pancreas transplants performed by medium-volume centers (11-24 transplants per year) increased sharply to 48.3% in 2021 from 35.1% in 2020, with a corresponding decrease in transplants in large-volume centers (25 or more transplants per year) to 15.9% in 2021 from 25.7% in 2020.
Topics: Humans; United States; Aged; Tissue and Organ Procurement; Diabetes Mellitus, Type 2; Graft Survival; COVID-19; Pancreas Transplantation; Pancreas
PubMed: 37132349
DOI: 10.1016/j.ajt.2023.02.005 -
Transplantation Direct Jun 2024For patients with complicated type 1 diabetes having, for example, hypoglycemia unawareness and end-stage renal disease because of diabetic nephropathy, combined...
BACKGROUND
For patients with complicated type 1 diabetes having, for example, hypoglycemia unawareness and end-stage renal disease because of diabetic nephropathy, combined pancreas and kidney transplantation (PKT) is the therapy of choice. However, the shortage of available grafts and complex impact of risk factors call for individualized, impartial predictions of PKT and pancreas transplantation (PT) outcomes to support physicians in graft acceptance decisions.
METHODS
Based on a large European cohort with 3060 PKT and PT performed between 2006 and 2021, the 3 primary patient outcomes time to patient mortality, pancreas graft loss, and kidney graft loss were visualized using Kaplan-Meier survival curves. Multivariable Cox proportional hazards models were developed for 5- and 10-y prediction of outcomes based on 26 risk factors.
RESULTS
Risk factors associated with increased mortality included previous kidney transplants, rescue allocations, longer waiting times, and simultaneous transplants of other organs. Increased pancreas graft loss was positively associated with higher recipient body mass index and donor age and negatively associated with simultaneous transplants of kidneys and other organs. Donor age was also associated with increased kidney graft losses. The multivariable Cox models reported median C-index values were 63% for patient mortality, 62% for pancreas loss, and 55% for kidney loss.
CONCLUSIONS
This study provides an online risk tool at https://riskcalc.org/ptop for individual 5- and 10-y post-PKT and PT patient outcomes based on parameters available at the time of graft offer to support critical organ acceptance decisions and encourage external validation in independent populations.
PubMed: 38757051
DOI: 10.1097/TXD.0000000000001632