Exploring definitions of graft pancreatitis following pancreas transplantation: A scoping review.

Despite the clinical relevance of graft pancreatitis (GP) after pancreas transplantation (PT), a universally accepted definition is lacking. Aim of this scoping review was to provide a systematic overview of GP definitions reported in the literature. MEDLINE, Web of Science and Embase were searched for relevant articles. Prospective/retrospective studies reporting a GP definition were included. The included series (n = 20) used four main criteria (clinical, biochemical, radiological and pathological) to define GP. Overall, 9 studies defined GP using a single criterion (n = 8 biochemical, n = 1 pathological), 7 series using two criteria (n = 3 clinical + biochemical, n = 3 biochemical + radiological, n = 1 clinical + radiological), 3 series using three criteria (n = 3 clinical + biochemical + radiological), and 1 series using four criteria. Overall, 20 definitions of GP were found. GP rate was reported by 19 series and ranged between 0% and 87%. This scoping review confirms that a universally accepted definition of GP is absent, and there is no consensus on the criteria on which it should be grounded. Future research should focus on developing a validated definition of GP.

Donor Blood Tests do Not Predict Pancreas Graft Survival After Simultaneous Pancreas Kidney Transplantation; a National Cohort Study.

Simultaneous pancreas-kidney (SPK) transplantation improves quality of life and limits progression of diabetic complications. There is reluctance to accept pancreata from donors with abnormal blood tests, due to concern of inferior outcomes. We investigated whether donor amylase and liver blood tests (markers of visceral ischaemic injury) predict pancreas graft outcome using the UK Transplant Registry (2016-2021). 857 SPK recipients were included (619 following brainstem death, 238 following circulatory death). Peak donor amylase ranged from 8 to 3300 U/L (median = 70), and this had no impact on pancreas graft survival when adjusting for multiple confounders (aHR = 0.944, 95% CI = 0.754-1.81). Peak alanine transaminases also did not influence pancreas graft survival in multivariable models (aHR = 0.967, 95% CI = 0.848-1.102). Restricted cubic splines were used to assess associations between donor blood tests and pancreas graft survival without assuming linear relationships; these confirmed neither amylase, nor transaminases, significantly impact pancreas transplant outcome. This is the largest, most statistically robust study evaluating donor blood tests and transplant outcome. Provided other factors are acceptable, pancreata from donors with mild or moderately raised amylase and transaminases can be accepted with confidence. The use of pancreas grafts from such donors is therefore a safe, immediate, and simple approach to expand the donor pool to reach increasing demands.

The role of donor hypertension and angiotensin II in the occurrence of early pancreas allograft thrombosis.

Background: About 10-20% of pancreas allografts are still lost in the early postoperative period despite the identification of numerous detrimental risk factors that correlate with graft thrombosis. Methods: We conducted a multicenter study including 899 pancreas transplant recipients between 2000 and 2018. Early pancreas failure due to complete thrombosis, long-term pancreas, kidney and patient survivals were analyzed and adjusted to donor, recipient and perioperative variables using a multivariate cause-specific Cox model stratified to transplant centers. Results: Pancreas from donors with history of hypertension (6.7%), as well as with high body mass index (BMI), were independently associated with an increased risk of pancreas failure within the first 30 post-operative days (respectively, HR= 2.57, 95% CI from 1.35 to 4.89 and HR= 1.11, 95% CI from 1.04 to 1.19). Interaction term between hypertension and BMI was negative. Donor hypertension also impacted long-term pancreas survival (HR= 1.88, 95% CI from 1.13 to 3.12). However, when pancreas survival was calculated after the postoperative day 30, donor hypertension was no longer a significant risk factor (HR= 1.22, 95% CI from 0.47 to 3.15). A lower pancreas survival was observed in patients receiving a pancreas from a hypertensive donor without RAAS (Renin Angiotensin Aldosterone System) blockers compared to others (50% vs 14%, p < 0.001). Pancreas survival was similar among non-hypertensive donors and hypertensive ones under RAAS blockers. Conclusion: Donor hypertension was a significant and independent risk factor of pancreas failure. The well-known pathogenic role of renin-angiotensin-aldosterone system seems to be involved in the genesis of this immediate graft failure.

Tacrolimus's Time Below Therapeutic Range Is Associated With Acute Pancreatic Graft Rejection and the Development of De Novo Donor-specific Antibodies.

Tacrolimus is pivotal in pancreas transplants but poses challenges in maintaining optimal levels due to recipient differences. This study aimed to explore the utility of time spent below the therapeutic range and intrapatient variability in predicting rejection and de novo donor-specific antibody (dnDSA) development in pancreas graft recipients. This retrospective unicentric study included adult pancreas transplant recipients between January 2006 and July 2020. Recorded variables included demographics, immunosuppression details, HLA matching, biopsy results, dnDSA development, and clinical parameters. Statistical analysis included ROC curves, sensitivity, specificity, and predictive values. A total of 131 patients were included. Those with biopsy-proven acute rejection (BPAR, 12.2%) had more time (39.9% ± 24% vs. 25.72% ± 21.57%, p = 0.016) and tests (41.95% ± 13.57% vs. 29.96% ± 17.33%, p = 0.009) below therapeutic range. Specific cutoffs of 31.5% for time and 34% for tests below the therapeutic range showed a high negative predictive value for BPAR (93.98% and 93.1%, respectively). Similarly, patients with more than 34% of tests below the therapeutic range were associated with dnDSA appearance (38.9% vs. 9.4%, p = 0.012; OR 6.135, 1.346-27.78). In pancreas transplantation, maintaining optimal tacrolimus levels is crucial. Suboptimal test percentages below the therapeutic range prove valuable in identifying acute graft rejection risk.

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.

Impact of a Public Health Emergency on Behavior, Stress, Anxiety and Glycemic Control in Patients With Pancreas or Islet Transplantation for Type 1 Diabetes.

A public health emergency such as the COVID-19 pandemic has behavioral, mental and physical implications in patients with type 1 diabetes (T1D). To what extent the presence of a transplant further increases this burden is not known. Therefore, we compared T1D patients with an islet or pancreas transplant (ß-cell Tx; n = 51) to control T1D patients (n = 272). Fear of coronavirus infection was higher in those with ß-cell Tx than without (Visual Analogue Scale 5.0 (3.0-7.0) vs. 3.0 (2.0-5.0), p = 0.004) and social isolation behavior was more stringent (45.8% vs. 14.0% reported not leaving the house, p < 0.001). A previous ß-cell Tx was the most important predictor of at-home isolation. Glycemic control worsened in patients with ß-cell Tx, but improved in control patients (ΔHbA1c +1.67 ± 8.74 vs. -1.72 ± 6.15 mmol/mol, p = 0.006; ΔTime-In-Range during continuous glucose monitoring -4.5% (-6.0%-1.5%) vs. +3.0% (-2.0%-6.0%), p = 0.038). Fewer patients with ß-cell Tx reported easier glycemic control during lockdown (10.4% vs. 22.6%, p = 0.015). All T1D patients, regardless of transplantation status, experienced stress (33.4%), anxiety (27.9%), decreased physical activity (42.0%), weight gain (40.5%), and increased insulin requirements (29.7%). In conclusion, T1D patients with ß-cell Tx are increasingly affected by a viral pandemic lockdown with higher fear of infection, more stringent social isolation behavior and deterioration of glycemic control. This trial has been registered in the clinicaltrials.gov registry under identifying number NCT05977205 (URL: https://clinicaltrials.gov/study/NCT05977205).

Evaluating Global and Temporal Trends in Pancreas and Islet Cell Transplantation: Public Awareness and Engagement.

BACKGROUND: Pancreas transplantation is a crucial surgical intervention for managing diabetes, but it faces challenges such as its invasive nature, stringent patient selection criteria, organ scarcity, and centralized expertise. Despite the steadily increasing number of pancreas transplants in the United States, there is a need to understand global trends in interest to increase awareness of and participation in pancreas and islet cell transplantation. METHODS: We analyzed Google Search trends for "Pancreas Transplantation" and "Islet Cell Transplantation" from 2004 to 14 November 2023, assessing variations in search interest over time and across geographical locations. The Augmented Dickey-Fuller (ADF) test was used to determine the stationarity of the trends (p < 0.05). RESULTS: Search interest for "Pancreas Transplantation" varied from its 2004 baseline, with a general decline in peak interest over time. The lowest interest was in December 2010, with a slight increase by November 2023. Ecuador, Kuwait, and Saudi Arabia showed the highest search interest. "Islet Cell Transplantation" had its lowest interest in December 2016 and a more pronounced decline over time, with Poland, China, and South Korea having the highest search volumes. In the U.S., "Pancreas Transplantation" ranked 4th in interest, while "Islet Cell Transplantation" ranked 11th. The ADF test confirmed the stationarity of the search trends for both procedures. CONCLUSIONS: "Pancreas Transplantation" and "Islet Cell Transplantation" showed initial peaks in search interest followed by a general downtrend. The stationary search trends suggest a lack of significant fluctuations or cyclical variations. These findings highlight the need for enhanced educational initiatives to increase the understanding and awareness of these critical transplant procedures among the public and professionals.

Pancreas after kidney transplantation, is it the time to overcome the stigma?

BACKGROUND: Pancreas transplantation is the most effective treatment to improve quality of life and overcome complications in patients with end-stage renal disease and diabetes mellitus. One of the main approaches for concurrent renal disease and diabetes mellitus which has been underutilized during the past decade is a pancreas transplant after kidney transplantation. Our study aimed to quantify outcomes following pancreas after kidney transplants (PAKs) in the United States from 2001 to 2020 with an emphasis on graft and patient survival. METHODS AND MATERIALS: A retrospective registry analysis was performed by accessing the OPTN/UNOS database for PAKs that were performed in the United States from January 2001 to April 2020. The study population was divided into two subgroups: patients receiving a pancreas transplant between 2001 and 2010 and those receiving a pancreas transplant between 2011 and 2020. RESULTS: The study examined a total number of 3706 PAK recipients; patients who received a PAK from January 2001 through December 2010 (n = 2892) and those who received a PAK from January 2011 to April 2020 (n = 814). The selection process of transplant recipients did not drastically change throughout the 2001-2010 and 2011-2020 periods. Length of stay at the hospital after the transplantation improved significantly in the 2011-2020 group relative to the 2001-2010 group (8.48 vs. 10.08 days, mean, p < 0.01). Additionally, more transplantation with 4-6 human leukocyte antigen mismatch occurred in the 2011-2020 group than in the 2001-2010 group (80.6% vs. 71.4%, p < 0.01). The pancreas preservation time of 13.35 h in the 2001-2010 group decreased significantly to 11.17 h in the 2011-2020 group (p < 0.001). The mean donor's amylase and lipase also decreased significantly in the 2011-2020 cohort. Significant graft survival improvement was observed in the 2011-2020 group compared to the 2001-2010 group after a long-term follow-up (p < 0.001). The mean Calculated Pancreas Donor Risk Index was 1.08 for the 2001-2010 group and 0.99 for the 2011-2020 group with a significant difference (p < 0.001). CONCLUSION: The beneficial results and improved outcomes observed in PAK patients demonstrate the effectiveness of the operation for individuals in need of a pancreas transplant. PAKs can prove to be a meaningful solution to overcome long waiting times, decrease the donor-recipient imbalance, expand the donor pool, and overcome the current underutilization in order to improve the short- and long-term quality of life in the groups of interest.

Efficacy and Safety Evaluation of Energy Devices in Bench Surgery for Pancreas Transplantation.

INTRODUCTION: Bench surgery for the preparation of deceased donor pancreatic grafts is labor-intensive and time-consuming. We hypothesized that energy devices could be used during bench surgery to decrease the bench surgery time. However, because bench surgery has two unique characteristics, wet conditions and no blood flow in the vessels, it is necessary to verify the safety and efficacy under such conditions. METHODS: In an animal tissue model, we validated both ultrasonic and bipolar energy devices: Harmonic Shears and the LigaSure (LS) vessel-sealing device by evaluating heat spread and pressure resistance under bench surgery conditions. In a clinical evaluation of the LS, we compared the outcomes of 22 patients in two different bench surgery groups: with and without the use of the LS. RESULTS: Clinically, the bench surgery time was significantly shorter in the LS group than that in the conventional group (P < 0.001). In the animal tissue experiments, the highest temperature in bench surgery conditions was 60.4°C after 1 s at a 5-mm distance in the LS group. Pressure resistance of ≥ 750 mmHg was achieved in almost all trials in both veins and arteries, with no difference between Harmonic Shears and LS. There was more surgical smoke visually in bench conditions versus in dry conditions and under half bite versus full bite conditions. CONCLUSIONS: The encouraging results of our exploratory clinical and animal studies of the energy devices suggest that they may be useful in the setting of bench surgery.

Generating strategies for a national comeback in pancreas transplantation: A Delphi survey and US conference report.

In the United States, potential transplant candidates with insulin-dependent diabetes mellitus are inconsistently offered pancreas transplantation (PTx), contributing to a dramatic decline in pancreas allograft utilization over the past 2 decades. The American Society of Transplantation organized a workshop to identify barriers inhibiting PTx and to develop strategies for a national comeback. The 2-day workshop focused on 4 main topics: (1) referral/candidate selection, (2) organ recovery/utilization, (3) program performance/patient outcomes, and (4) enhanced education/research. Topics were explored through expert presentations, patient testimonials, breakout sessions, and strategic planning, including the identification of tasks for immediate focus. Additionally, a modified-Delphi survey was conducted among workshop members to develop and rate the importance of barriers, and the impact and feasibility of workgroup-identified improvement strategies. The panelists identified 16 barriers to progress and 44 strategies for consideration. The steps for a national comeback in PTx involve greater emphasis on efficient referral and candidate selection, better donor pancreas utilization practices, eliminating financial barriers to procurement and transplant, improving collaboration between transplant and diabetes societies and professionals, and increasing focus on PTx training, education, and research. Partnership between national societies, patient advocacy groups, and professionals will be essential to realizing this critical agenda.

Infection-Related Hospitalizations After Simultaneous Pancreas-Kidney Transplantation Compared to Kidney Transplantation Alone.

The total burden of infections after transplantation has not been compared in detail between recipients of simultaneous pancreas-kidney transplantation (SPK) and kidney transplantation alone (KTA). We compared infection-related hospitalizations and bacteremias after transplantation during 1- and 5-year follow-up among 162 patients undergoing SPK. The control group consisted of 153 type 1 diabetics undergoing KTA with the inclusion criteria of donor and recipient age < 60, and BMI < 30. During the first year, SPK patients had more infection-related hospitalizations (0.54 vs. 0.31 PPY, IRR 1.76, p = <0.001) and bacteremias (0.11 vs. 0.01 PPY, IRR 17.12, p = <0.001) compared to KTA patients. The first infection-related hospitalizations and bacteremias occurred later during follow-up in KTA patients. SPK was an independent risk factor for infection-related hospitalization and bacteremia during the first year after transplantation, but not during the 5-year follow-up. Patient survival did not differ between groups, however, KTA patients had inferior kidney graft survival. SPK patients are at greater risk for infection-related hospitalizations and bacteremias during the first year after transplantation compared to KTA patients, however, at the end of the follow-up the risk of infection was similar between groups.

Evaluation and post-transplant management of children after multi-organ-with-kidney transplantation.

Multi-organ transplantation involves the transplant of two or more organs from a single donor into a single recipient; in most cases, one of these organs is a kidney. Multi-organ transplantation is uncommon in pediatric transplantation but can be life-saving or significantly life-improving for children with rare diseases, including primary heart, liver, pancreas, or intestinal failure with secondary kidney failure, metabolic disorders, and genetic conditions causing multi-organ dysfunction. This manuscript reviews the current state of pediatric multi-organ transplantation that includes a kidney, with a focus on indications, evaluation, and key differences in management compared to kidney-alone transplantation. Guidelines and consensus statements for pediatric multi-organ transplantation are nonexistent; this review condenses reported statistics and peer-reviewed expert opinion while highlighting areas in need of further research.

Effects of simultaneous pancreas and kidney transplantation in Japanese individuals with type 1 diabetes and end-stage kidney disease.

This single-center observational cohort study aimed to assess the potential benefits of simultaneous pancreas and kidney transplantation (SPK) in terms of mortality and kidney graft outcomes in Japanese individuals with type 1 diabetes (T1D) and end-stage kidney disease (ESKD). We first compared all-cause mortality rates between 78 SPK recipients and 108 non-transplanted individuals with T1D and ESKD. To mitigate the bias stemming from immortal time before receiving SPK, we utilized Cox regression models treating SPK as a time-dependent covariate. Next, we compared all-cause mortality rates and kidney graft loss rates between 65 SPK recipients and 58 kidney transplantation alone (KTA) recipients. Multivariate Cox hazard models and Fine and Gray competing-risk models were employed. SPK recipients experienced significantly lower all-cause mortality rates than non-transplanted individuals, even after accounting for immortal time bias (p = 0.015 by log-rank test, hazard ratio [HR] = 0.334, p = 0.025). When comparing SPK and KTA recipients, no statistically significant difference was observed in mortality rates (HR = 0.627, p = 0.588 by Cox model; HR = 0.385, p = 0.412 by Fine and Gray model) or kidney graft loss rates (HR = 0.612, p = 0.436 by Cox model; HR = 0.639, p = 0.376 by Fine and Gray model). Dysglycemia-associated mortality were observed in non-transplanted individuals and KTA recipients, but not in SPK recipients. These findings highlight the potential life-saving impact of SPK compared with intensive insulin therapy and dialysis. Additionally, this study suggests that both SPK and KTA may offer comparable outcomes. These findings have significant implications for clinical decision-making in the context of organ transplantation for individuals with T1D and ESKD.

The impact of time to death in donors after circulatory death on recipient outcome in simultaneous pancreas-kidney transplantation.

The time to arrest donors after circulatory death is unpredictable and can vary. This leads to variable periods of warm ischemic damage prior to pancreas transplantation. There is little evidence supporting procurement team stand-down times based on donor time to death (TTD). We examined what impact TTD had on pancreas graft outcomes following donors after circulatory death (DCD) simultaneous pancreas-kidney transplantation. Data were extracted from the UK transplant registry from 2014 to 2022. Predictors of graft loss were evaluated using a Cox proportional hazards model. Adjusted restricted cubic spline models were generated to further delineate the relationship between TTD and outcome. Three-hundred-and-seventy-five DCD simultaneous kidney-pancreas transplant recipients were included. Increasing TTD was not associated with graft survival (adjusted hazard ratio HR 0.98, 95% confidence interval 0.68-1.41, P = .901). Increasing asystolic time worsened graft survival (adjusted hazard ratio 2.51, 95% confidence interval 1.16-5.43, P = .020). Restricted cubic spline modeling revealed a nonlinear relationship between asystolic time and graft survival and no relationship between TTD and graft survival. We found no evidence that TTD impacts pancreas graft survival after DCD simultaneous pancreas-kidney transplantation; however, increasing asystolic time was a significant predictor of graft loss. Procurement teams should attempt to minimize asystolic time to optimize pancreas graft survival rather than focus on the duration of TTD.

Safety of Biologic and Small Molecule Therapy for Inflammatory Bowel Disease Among Solid Organ Transplant Recipients: Systematic Review and Meta-Analysis.

BACKGROUND: Patients undergoing organ transplantation are often on immunosuppressing medications to prevent rejection of the transplant. The data on use of concomitant immunosuppression for inflammatory bowel disease (IBD) and organ transplant management are limited. This study sought to evaluate the safety of biologic and small molecule therapy for the treatment of IBD among solid organ transplant recipients. METHODS: Medline, Embase, and Web of Science databases were systematically searched for studies reporting on safety outcomes associated with the use of biologic and small molecule therapy (infliximab, adalimumab, certolizumab, golimumab, vedolizumab, ustekinumab, and tofacitinib) in patients with IBD postsolid organ transplant (eg, liver, kidney, heart, lung, pancreas). The primary outcome was infectious complications. Secondary outcomes included serious infections, colectomy, and discontinuation of biologic therapy. RESULTS: Seven hundred ninety-seven articles were identified for screening, yielding 16 articles for the meta-analyses with information on 163 patients. Antitumor necrosis factor α (Anti-TNFs; infliximab and adalimumab) were used in 8 studies, vedolizumab in 6 studies, and a combination of ustekinumab or vedolizumab and anti-TNFs in 2 studies. Two studies reported outcomes after kidney and cardiac transplant respectively, whereas the rest of the studies included patients with liver transplants. The rates of all infections and serious infections were 20.09 per 100 person-years (100-PY; 95% CI, 12.23-32.99 per 100-PY, I2 = 54%) and 17.39 per 100-PY (95% CI, 11.73-25.78 per 100-PY, I2 = 21%), respectively. The rates of colectomy and biologic medication discontinuation were 12.62 per 100-PY (95% CI, 6.34-25.11 per 100-PY, I2 = 34%) and 19.68 per 100-PY (95% CI, 9.97-38.84 per 100-PY, I2 = 74%), respectively. No cases of venous thromboembolism or death attributable to biologic use were reported. CONCLUSION: Biologic therapy is overall well tolerated in patients with solid organ transplant. Long-term studies are needed to better define the role of specific agents in this patient population.

Banff 2022 pancreas transplantation multidisciplinary report: Refinement of guidelines for T cell-mediated rejection, antibody-mediated rejection and islet pathology. Assessment of duodenal cuff biopsies and noninvasive diagnostic methods.

The Banff pancreas working schema for diagnosis and grading of rejection is widely used for treatment guidance and risk stratification in centers that perform pancreas allograft biopsies. Since the last update, various studies have provided additional insight regarding the application of the schema and enhanced our understanding of additional clinicopathologic entities. This update aims to clarify terminology and lesion description for T cell-mediated and antibody-mediated allograft rejections, in both active and chronic forms. In addition, morphologic and immunohistochemical tools are described to help distinguish rejection from nonrejection pathologies. For the first time, a clinicopathologic approach to islet pathology in the early and late posttransplant periods is discussed. This update also includes a discussion and recommendations on the utilization of endoscopic duodenal donor cuff biopsies as surrogates for pancreas biopsies in various clinical settings. Finally, an analysis and recommendations on the use of donor-derived cell-free DNA for monitoring pancreas graft recipients are provided. This multidisciplinary effort assesses the current role of pancreas allograft biopsies and offers practical guidelines that can be helpful to pancreas transplant practitioners as well as experienced pathologists and pathologists in training.

Incidental appendicectomy in pancreas transplantation: A single-center study.

BACKGROUND: Appendicitis in pancreatic transplant recipients can be challenging to diagnose and manage. Incidental appendicectomy (IA) during pancreas transplantation obviates the risk of appendicitis but potentially at the cost of increased operating time or early post-operative complications. This study reviewed the value of IA at a single center. METHODS: This was a retrospective study of patients who underwent a pancreas transplant in our unit from January 1st, 2012 to December 31st, 2020, with end of follow-up on May 21st, 2023; recipients were grouped by whether or not an IA was performed during pancreas transplantation. Donor, recipient, operative, and graft outcomes were compared between the two groups. Post-transplant complications related to appendiceal pathology (or IA) were recorded and classified. RESULTS: Two hundred forty-three patients underwent a pancreas transplant; 227 (93%) patients had an appendix in situ at transplantation, and of these 53 (23%) underwent an IA and 174 (77%) did not. There were no statistically significant differences in operative time (p = .06) or hospital stay (p = .50) between the two groups. In the IA cohort, there were no Clavien-Dindo Grade III-V complications relating to the appendicectomy. In those that did not undergo an IA, two patients (1%) subsequently required appendicectomy due to appendicitis. Comparison of pancreatic graft survival showed no statistically significant difference between the groups (p = .44). CONCLUSIONS: This study suggests that IA is effective at reducing risks of post-transplant appendiceal complications without significantly prolonging inpatient stay or impairing graft survival. These data support the consideration of undertaking an IA for all patients undergoing a pancreas transplant.