Pancreas Transplantation Research Articles

Subclinical Pancreas Rejection on Protocol Biopsy Within the First Year of Simultaneous Pancreas Kidney Transplant.

This single-center retrospective study investigated subclinical rejection prevalence and significance in simultaneous pancreas and kidney transplant (SPKT) recipients. We analyzed 352 SPKT recipients from July 2003 to April 2022. Our protocol included pancreas allograft surveillance biopsies at 1, 4, and 12months post-transplant. After excluding 153 patients unable to undergo pancreas biopsy, our study cohort comprised 199 recipients. Among the 199 patients with protocol pancreas biopsies, 107 had multiple protocol pancreas biopsies in the first year, totaling 323. Subclinical rejection was identified in 132 episodes (41%). Of these, 72% were Grade 1, 20% were indeterminate, and 8% were Banff Grade 2 or higher. All episodes of subclinical rejection were treated. Rates of pancreas graft loss (10%vs. 7%) and clinical rejection (21%vs. 20%) at 3 years were similar between those with and without subclinical rejection. Subclinical rejection Banff Grade 2 or more was associated with poor pancreas graft survival HR of 5.5 (95% CI: 1.24-24.37, p = 0.025). Of 236 simultaneous protocol kidney and pancreas biopsies, 102 (43%) showed pancreas subclinical rejection, while only 17% had concurrent kidney subclinical rejection. Our findings suggest limited predictive value of pancreatic enzymes and euglycemia in detecting pancreas rejection. Furthermore, poor concordance existed between pancreas and kidney subclinical rejection.

S4823 Pregnancy Outcomes Following Triple Organ (Small Bowel, Liver, and Pancreas) Transplantation

S4823 Pregnancy Outcomes Following Triple Organ (Small Bowel, Liver, and Pancreas) Transplantation

Transplantation for type 1 diabetes: radiologist's primer on islet, pancreas and pancreas-kidney transplantation imaging.

Whole-organ pancreas, pancreatic-kidney and islet transplantation are surgical therapeutic options for the treatment of type 1 diabetes. They can enable effective glycemic control, improve quality of life and delay/reduce the secondary complications of type 1 diabetes mellitus. Radiologists are integral members of the multidisciplinary transplantation team involved in these procedures, with multimodality imaging serving as the mainstay for early recognition and management of transplant related complications. This review highlights the transplantation procedures available for patients with type 1 Diabetes Mellitus with a focus on the imaging appearance of transplantation-related complications.

Pretransplant Hypoalbuminemia Is Not Associated with Worse Outcomes among Simultaneous Pancreas and Kidney Transplant Recipients

Pretransplant Hypoalbuminemia Is Not Associated with Worse Outcomes among Simultaneous Pancreas and Kidney Transplant Recipients

Objetivos del tratamiento de la diabetes mellitus tipo 1

There are three ways to assess blood glucose control in type 1 diabetes (DM1): glycated hemoglobin (HbA1c, general target less than or equal to 7%), time in the 70–180mg/dl range (general target 70% or higher), and capillary blood glucose. Diabetes education is a fundamental element in achieving self-management of the disease. It is based on three fundamental pillars: nutrition, insulin therapy, and management of diabetes technology (sensors, insulin pumps, smart insulin pens, and mobile applications). Drug treatment for DM1 consists of intensive insulin therapy using multiple dose injection (MDI) or continuous subcutaneous insulin infusion (CSII). The choice of treatment regimen should be based on patient characteristics and other clinical considerations (e.g., pregnancy, presence of undetected hypoglycemia, or variable insulin requirements). There are currently no other insulin adjuvant therapies approved for use in DM1, although DM2 drugs such as GLP-1 analogs or SGLT2 inhibitors that may provide benefits in blood glucose control or weight loss have been used. Kidney-pancreas or pancreatic islet transplantation is considered a final option in patients with end-stage chronic kidney disease together with or following renal transplantation or in individuals with undetected or severe recurrent hypoglycemia that does not respond to optimized management.

Delayed Graft Function among Simultaneous Pancreas-Kidney Transplant Recipients Is Associated with an Increased Risk of Urinary Tract Infections and Kidney Rejections

Delayed Graft Function among Simultaneous Pancreas-Kidney Transplant Recipients Is Associated with an Increased Risk of Urinary Tract Infections and Kidney Rejections

Prolonged Cold Ischemia Time in Pancreas Transplantation Yields Similar Outcomes Compared with Standard of Care Outcomes: Single-Center Experience, a Call to Action to Decrease Nonuse Rates

Prolonged Cold Ischemia Time in Pancreas Transplantation Yields Similar Outcomes Compared with Standard of Care Outcomes: Single-Center Experience, a Call to Action to Decrease Nonuse Rates

Experience from 100 consecutive pancreas transplants amidst low national transplant activity: a retrospective study at a single center in Korea.

Since 1992, over 800 pancreas transplants have been performed in Korea. However, this number is significantly lower compared to the number of kidney or liver transplants. Between 2015 and July 2023, Pusan National University Yangsan Hospital conducted 100 pancreas transplants, accounting for about 20% of all transplants performed in Korea during this period. The study comprised 27 simultaneous pancreas and kidney (SPK) transplants, 23 pancreas after kidney (PAK) transplants, and 50 pancreas transplant alone (PTA) cases. Duodenoduodenostomy was the primary surgical technique employed for exocrine drainage, along with various modifications of the venous outflow anastomosis. The availability of brain-dead donors for kidney transplants was lower compared to isolated pancreas transplants. Patients undergoing SPK transplants faced significantly longer waiting times than those receiving PTA or PAK transplants. The rate of surgical complications was acceptable, with a notably low thrombotic graft failure rate of 1.0%. In the PTA group, acute rejection of the graft pancreas occurred frequently (18.0%), though this was not statistically significant (P=0.328). The pancreas transplantation survival rates were 91.0%, 78.5%, and 75.4% at 1, 5, and 9 years, respectively. The PTA group exhibited a lower graft survival rate than the SPK and PAK groups, with marginal statistical significance (P=0.059). Graft survival rates have improved over time due to advancements in surgical techniques and immunosuppressant strategies. By sharing our experiences, we aim to enhance the activity and success of pancreas transplantation in Korea.

Various Approaches and Future Prospective for Therapies for Diabetes: A Review

The global prevalence of diabetes mellitus disease marked by increased blood glucose levels, has reached epidemic proportions. This review provides a comprehensive assessment of the current landscape of diabetes therapies and outlines future prospects for improving the management and treatment of this condition. The current scenario highlights a multifaceted approach to diabetes management, with a focus on lifestyle interventions, oral antidiabetic drugs, insulin therapy, and emerging technologies like continuous glucose monitoring and closed-loop systems. While these approaches have significantly improved the lives of people with diabetes, several challenges persist. These include medication adherence, hypoglycemia risk, and the financial burden of diabetes care. Innovative treatments that improve glucose regulation, improve cardiovascular health, and help patients lose weight—like SGLT-2 inhibitors and GLP-1 receptor agonists—have showed promise in treating these issues. The future prospects for diabetes therapies are exciting, with ongoing research into cell-based therapies, including pancreatic islet transplantation and stem cell-derived beta cells. Personalized medicine approaches, driven by genetics and artificial intelligence, hold the potential to optimize treatment regimens and predict individual responses to various therapies. Furthermore, advancements in telemedicine and digital health technologies will enhance patient self-management and remote monitoring.

Everolimus Personalized Therapy: Second Consensus Report by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology.

The Immunosuppressive Drugs Scientific Committee of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology established the second consensus report to guide Therapeutic Drug Monitoring (TDM) of everolimus (EVR) and its optimal use in clinical practice 7 years after the first version was published in 2016. This version provides information focused on new developments that have arisen in the last 7 years. For the general aspects of the pharmacology and TDM of EVR that have retained their relevance, readers can refer to the 2016 document. This edition includes new evidence from the literature, focusing on the topics updated during the last 7 years, including indirect pharmacological effects of EVR on the mammalian target of rapamycin complex 2 with the major mechanism of direct inhibition of the mammalian target of rapamycin complex 1. In addition, various concepts and technical options to monitor EVR concentrations, improve analytical performance, and increase the number of options available for immunochemical analytical methods have been included. Only limited new pharmacogenetic information regarding EVR has emerged; however, pharmacometrics and model-informed precision dosing have been constructed using physiological parameters as covariates, including pharmacogenetic information. In clinical settings, EVR is combined with a decreased dose of calcineurin inhibitors, such as tacrolimus and cyclosporine, instead of mycophenolic acid. The literature and recommendations for specific organ transplantations, such as that of the kidneys, liver, heart, and lungs, as well as for oncology and pediatrics have been updated. EVR TDM for pancreatic and islet transplantation has been added to this edition. The pharmacodynamic monitoring of EVR in organ transplantation has also been updated. These updates and additions, along with the previous version of this consensus document, will be helpful to clinicians and researchers treating patients receiving EVR.

Evolving Trends in the Management of Duodenal Leaks After Pancreas Transplantation: A Single-Centre Experience.

Duodenal leaks (DL) contribute to most graft losses following pancreas transplantation. However, there is a paucity of literature comparing graft preservation approach versus upfront graft pancreatectomy in these patients. We reviewed all pancreas transplants performed in our institution between 2000 and 2020 and identified the recipients developing DL to compare based on their management: percutaneous drainage vs. operative graft preservation vs. upfront pancreatectomy. Of the 595 patients undergoing pancreas transplantation, 74 (12.4%) developed a duodenal leak with a median follow up of 108months. Forty-five (61%) were managed by graft preservation strategies, with the rest being treated with upfront graft pancreatectomy. DL managed by graft preservation strategies had similar graft survival rates at 1 and 5-year compared to the matched cohort of population without DL (95% and 59% vs. 91% and 62%; p = 0.78). Multivariate analysis identified male recipient (OR: OR: 6.18; CI95%: 1.26-41.09; p = 0.04) to have higher odds of undergoing an upfront graft pancreatectomy. In appropriately selected recipients with DL, graft preservation strategies utilizing either interventional radiology guided percutaneous drainage or laparotomy with/without repair of leak can achieve comparable long-term graft survival rates compared to recipients without DL.

Lantidra: Cell Therapy for Treatment of Type 1 Diabetes Mellitus

The more recent cell treatment for type 1 Diabetes is called lantidra. Lantidra has recently received approval to treat type 1 Diabetes mellitus. The first allogeneic (deceased donor) pancreatic islet cell therapy, lantidra (donislecel), was approved by the FDA Centre for Biologics Evaluation and Research (CBER) on June 28, 2023. It is intended to treat adults with type 1 diabetes who, despite current management, do not achieve target glycosylated hemoglobin levels due to recurrent episodes of severe hypoglycemia. The editorial’s goal is to draw attention to the growing impact of type 1 diabetes on the world’s health, discuss earlier attempts at pancreatic transplant techniques, and announces the first regulatory approval of a revolutionary transplant strategy called allogeneic pancreatic islet beta cell infusion.

Analysis of Rejection, Infection and Surgical Outcomes in Type I Versus Type II Diabetic Recipients After Simultaneous Pancreas-Kidney Transplantation.

Given the increasing frequency of simultaneous pancreas-kidney transplants performed in recipients with Type II diabetes and CKD, we sought to evaluate possible differences in the rates of allograft rejection, infection, and surgical complications in 298 Type I (T1D) versus 47 Type II (T2D) diabetic recipients of simultaneous pancreas-kidney transplants between 2006-2017. There were no significant differences in patient or graft survival. The risk of biopsy-proven rejection of both grafts was not significantly different between T2D and T1D recipients (HRpancreas = 1.04, p = 0.93; HRkidney = 0.96; p = 0.93). Rejection-free survival in both grafts were also not different between the two diabetes types (ppancreas = 0.57; pkidney = 0.41). T2D had a significantly lower incidence of de novo DSA at 1year (21% vs. 39%, p = 0.02). There was no difference in T2D vs. T1D recipients regarding readmissions (HR = 0.77, p = 0.25), infections (HR = 0.77, p = 0.18), major surgical complications (HR = 0.89, p = 0.79) and thrombosis (HR = 0.92, p = 0.90). In conclusion, rejection, infections, and surgical complications after simultaneous pancreas-kidney transplant are not statistically significantly different in T2D compared to T1D recipients.

Expansion of the Pancreas Transplant Recipient Pool: Appropriate for Most or Are There Limits?

Expansion of the Pancreas Transplant Recipient Pool: Appropriate for Most or Are There Limits?

Adipose Tissue Can Have a Protective Effect on Outcome After Simultaneous Pancreas-Kidney Transplantation in Non-Obese Recipients.

BACKGROUND Obesity is suggested to impair the outcome after simultaneous pancreas-kidney transplantation, which affects survival, but the quantity and distribution of adipose tissue is not yet considered in obesity assessment. We aimed to evaluate the impact of body composition on outcome after simultaneous pancreas-kidney transplantation. MATERIAL AND METHODS We retrospectively analyzed data from 40 patients who underwent simultaneous pancreas-kidney transplantation due to type 1 diabetes mellitus with consecutive end-stage renal disease. Uni- and multivariate analyses, including donor's characteristics, were performed. RESULTS Only 6 (15%) recipients were obese. The incidence of postoperative complications was correlated with lower body fat proportion (p=0.03). This correlation remained significant in the multivariate analysis (p=0.015). Nevertheless, obesity was significantly associated with worse overall survival (p<0.001). Visceral tissue proportion was correlated with a higher level of glycated hemoglobin in long-term follow-up (p=0.003). CONCLUSIONS Fat quantity and distribution should be included in the assessment of obesity. A protective effect of adipose tissue was detected on outcome after simultaneous pancreas-kidney transplantation in normosthenic recipients, but obesity still appears to have a negative effect on outcome after transplantation. Visceral fat distribution can promote de novo diabetes mellitus.

Selection Bias in Reporting of Median Waiting Times in Organ Transplantation

Median organ waiting times published by transplant organizations may be biased when not appropriately accounting for censoring, death, and competing events. This can lead to overly optimistic waiting times for all transplant programs and, consequently, may deceive patients on the waiting list, transplant physicians, and health care policymakers. To apply competing-risk multistate models to calculate probabilities for transplantation and adverse outcomes on the Swiss national transplant waiting list. The WAIT (Waitlist Analysis in Transplantation) study was a retrospective cohort study of all transplant candidates in Switzerland listed from January 1, 2018, or later and observed until December 31, 2023. Transplant candidates were listed in 1 of the 6 transplant centers (Basel, Bern, Geneva, Lausanne, St Gallen, and Zurich) for heart, liver, lungs, kidney, or pancreas and/or islet transplant. A total of 4352 candidates were listed during the study period, of whom 709 (16.3%) were excluded due to living-donor transplant (691 in the kidney program and 18 in the liver program). Waiting for organ transplant. Time to transplantation, death, or delisting. Competing-risk multistate models were used to analyze time-to-event data from the national organ waiting list with the Aalen-Johansen estimator to compute probabilities for both transplant and adverse outcomes. Results were compared with the sample median among only those undergoing transplant and the Kaplan-Meier method with censoring of competing events. Data from 3643 transplant candidates (2428 [66.6%] male; median age, 56 [range, 0-79] years) were included in the analysis. The median time to transplantation (MTT) was 0.91 (95% CI, 0.83-1.07) years for heart, 3.10 (95% CI, 2.57-3.77) years for kidney, 1.32 (95% CI, 0.76-1.55) years for liver, 0.80 (95% CI, 0.37-1.12) years for lung, and 1.62 (95% CI, 0.91-2.17) years for pancreas and/or islet programs. Alternative estimation methods introduced bias to varying degrees: the sample median among only persons undergoing transplantation underestimated the waiting time by 38% to 61% and the Kaplan-Meier method by 2% to 12% compared with the MTT. In this cohort study of transplant candidates in Switzerland, the MTT, the duration at which the transplant probability is 0.50, was used as a measure of average waiting time. Suboptimal methods led to biased and overly optimistic waiting time estimations; thus, applying appropriate competing-risk methods to address censoring and competing events is crucial.

SP6.9 - Assessing European Pancreas Transplant Practices to Optimize Patient Outcomes

Abstract Purpose Practise variability exists in pancreas transplantation, but the extent across the EU is unknown. We surveyed pancreas transplant surgeons to assess current practices. Methods A 40-question survey was sent to 84 surgeons at 17 centres in 8 EU countries. Validity and reliability were analysed. Variability was evaluated using descriptive statistics and random effects modelling. Results The response rate was 92% (78/84). The survey demonstrated good validity and reliability (Cronbach’s alpha 0.82). Substantial variability existed in donor selection criteria such as acceptable BMI (range &amp;lt;10 to 35) and age (&amp;lt;30 to &amp;gt;60 years). Back-bench preparation also varied, including arterial reconstruction (52% continuous vs. 48% interrupted sutures) and duodenal closure (66% always buried staple line, 34% not). Systemic portal venous drainage was most common (70%), but 22% used portal drainage. Post-operative anticoagulation varied from 1 week to 3 months in duration. Random effects modelling found significant variability attributable to individual surgeons, centres, and case factors. Conclusions This rigorous survey identified modifiable targets to improve the quality and consistency of pancreas transplantation across the EU. Standardised best practise guidelines should focus on reducing variability in donor selection, back-bench preparation, surgical techniques, and post-operative management. Volume of Pancreas Transplants Performed Annually per CenterNumber of Transplants PerformedRespondents, n (%)&amp;lt;1036 (46%)11-2016 (21%)21-4013 (17%)41-608 (10%)605 (6%) Surgical Experience of RespondentsNumber of PancreasTransplants Performed AnnuallyRespondents, n (%)&amp;lt;24 (5%)2-528 (36%)6-817 (22%)8-129 (12%)1520 (26%)

Harnessing cellular therapeutics for type 1 diabetes mellitus: progress, challenges, and the road ahead.

Type 1 diabetes mellitus (T1DM) is a growing global health concern that affects approximately 8.5 million individuals worldwide. T1DM is characterized by an autoimmune destruction of pancreatic β cells, leading to a disruption in glucose homeostasis. Therapeutic intervention for T1DM requires a complex regimen of glycaemic monitoring and the administration of exogenous insulin to regulate blood glucose levels. Advances in continuous glucose monitoring and algorithm-driven insulin delivery devices have improved the quality of life of patients. Despite this, mimicking islet function and complex physiological feedback remains challenging. Pancreatic islet transplantation represents a potential functional cure for T1DM but is hindered by donor scarcity, variability in harvested cells, aggressive immunosuppressive regimens and suboptimal clinical outcomes. Current research is directed towards generating alternative cell sources, improving transplantation methods, and enhancing cell survival without chronic immunosuppression. This Review maps the progress in cell replacement therapies for T1DM and outlines the remaining challenges and future directions. We explore the state-of-the-art strategies for generating replenishable β cells, cell delivery technologies and local targeted immune modulation. Finally, we highlight relevant animal models and the regulatory aspects for advancing these technologies towards clinical deployment.

Measuring the Impact of Postsimultaneous Pancreas-Kidney Transplantation Complications: Comparing the Comprehensive Complication Index and Clavien-Dindo Classification.

The Clavien-Dindo classification (CDC) is commonly used for assessing postoperative complications; however, it may not be comprehensive. A comprehensive complication index (CCI) was introduced to address this limitation. This study aimed to compare the effectiveness of the CCI and CDC in evaluating the complications after simultaneous pancreas-kidney (SPK) transplantation. Data were collected from patients who underwent SPK transplantation at our center between February 2018 and February 2021. Complications encountered during hospitalization were assessed using both the CDC and CCI. Linear regression analyses were performed to identify the factors related to postoperative length of stay (PLOS). Overall, 125 patients were included, with an average age of 46.87 years. Type 2 diabetes was present in 79% of the recipients. Among them, 117 patients experienced postoperative complications of CDC grades I (2.4%), II (57.6%), IIIa (8.0%), IIIb (9.6%), IVa (14.4%), IVb (0.8%), and V (0.8%) postoperative complications. The median CCI for the entire cohort was 37.2. Spearman's correlation analysis revealed significant associations between the CDC and PLOS and the CCI and PLOS. Notably, CCI exhibited a stronger correlation with PLOS (CCI: ρ=0.698vs. CDC: ρ=0.524; p=0.024). The CCI demonstrated a stronger correlation with PLOS than CDC. Our finding suggests that the CCI may be a useful tool for comprehensively assessing complications following SPK transplantation.

Four Decades of Research Productivity and Hot Spots in Pancreas Transplantation.

Background: The field of pancreas transplantation has undergone transformative phases, progressing from its promising inception in 1966 to becoming a standard treatment for patients with insulin-dependent diabetes. This bibliometric analysis explores the progression of pancreas transplantation research over a period of four decades, mapping milestones, contributors, and emerging trends. Methods: Our bibliometric analysis utilizes the comprehensive Scopus database, which includes publication titles, author information, affiliations, abstracts, keywords, and journal details. The search strategy was centered on research related to pancreas and pancreas-kidney transplantation. The analysis encompasses the time frame spanning from 1983 to 2023, with the data extraction taking place on October 7th, 2023. Results: The analysis of 4,897 articles uncovered unique trends in the field of pancreas transplantation research. The years 1989, 1996, and 2021 saw significant increases in the number of publications, which corresponded to the responses to clinical challenges and advancements. Contributions by authors from the United States of America were the most numerous, with 1,905 publications and 49,949 citations. The research topics were highlighted by keywords such as "graft survival," "graft rejection," and" Immunosuppressive treatment." Conclusion: The fluctuations in publication trends that have been identified indicate dynamic reactions to changing priorities and challenges. Although it has limitations, this analysis provides valuable insights for researchers, clinicians, and policymakers who are dealing with the complex field of pancreas transplantation literature. Further bibliometric research may advance our knowledge and direct future initiatives in this developing field.