Pancreas transplantation.

PURPOSE OF REVIEW: To define recent changes and future directions in the practice of pancreas transplantation (PT). Two major events have occurred in the past 18 months: COVID-19 pandemic, and the first world consensus conference on PT. Several innovative studies were published after the consensus conference. RECENT FINDINGS: During COVID-19 pandemic PT activity decreased. COVID-19 in transplant recipients increases mortality rates, but data from kidney transplantation show that mortality might be higher in waitlisted patients.The world consensus conference provided 49 jury deliberations on the impact of PT on management of diabetic patients and 110 practice recommendations.Recent evidence demonstrates that PT alone is safe and effective, that results of simultaneous pancreas and kidney (SPK) remain excellent despite older recipient age and higher prevalence of type 2 diabetes, that use of hepatitis C virus (HCV)-positive donors into HCV-negative recipients is associated with good outcomes, and that use of sirolimus as primary immunosuppressant and costimulation blockade does not improve results of SPK. SUMMARY: COVID-19 pandemic and the first world consensus conference on PT were major events. Although COVID-19 pandemic should not reduce PT activity in the future, a major positive impact on both volume and outcomes of PT is awaited from the proceedings of the world consensus conference.

Using Geographic Catchment Areas to Measure Population-based Access to Kidney Transplant in the United States.

BACKGROUND: Monitoring efforts to improve access to transplantation requires a definition of the population attributable to a transplant center. Previously, assessment of variation in transplant care has focused on differences between administrative units-such as states-rather than units derived from observed care patterns. We defined catchment areas (transplant referral regions [TRRs]) from transplant center care patterns for population-based assessment of transplant access. METHODS: We used US adult transplant listings (2006-2016) and Dartmouth Atlas catchment areas to assess the optimal method of defining TRRs. We used US Renal Data System and Scientific Registry of Transplant Recipient data to compare waitlist- and population-based kidney transplant rates. RESULTS: We identified 110 kidney, 67 liver, 85 pancreas, 68 heart, and 43 lung TRRs. Most patients were listed in their assigned TRR (kidney: 76%; liver: 75%; pancreas: 75%; heart: 74%; lung: 72%), although the proportion varied by organ (interquartile range for kidney, 65.7%-82.5%; liver, 58.2%-78.8%; pancreas, 58.4%-81.1%; heart, 63.1%-80.9%; lung, 61.6%-76.3%). Patterns of population- and waitlist-based kidney transplant rates differed, most notably in the Northeast and Midwest. CONCLUSIONS: Patterns of TRR-based kidney transplant rates differ from waitlist-based rates, indicating that current metrics may not reflect transplant access in the broader population. TRRs define populations served by transplant centers and could enable future studies of how transplant centers can improve access for patients in their communities.

Effects of simultaneous pancreas-kidney transplantation and kidney transplantation alone on the outcome of peripheral vascular diseases.

BACKGROUND: The effects of Simultaneous Pancreas Kidney Transplantation (SPKT) on Peripheral Vascular Disease (PVD) warrants additional study and more target focus, since little is known about the mid- and long-term effects on the progression of PVD after transplantation. METHODS: 101 SPKT and 26 Kidney Transplantation Alone (KTA) recipients with insulin-dependent diabetes mellitus (IDDM) were retrospectively evaluated with regard to graft and metabolic outcome. Special subgroup analysis was directed towards the development and progression of peripheral vascular complications (PVC) (amputation, ischemic ulceration, lower extremity angioplasty/ bypass surgery) after transplantation. RESULTS: The 10-year patient survival was significantly higher in the SPKT group (SPKT: 82% versus KTA 40%; P < 0.001). KTA recipients had a higher prevalence of atherosclerotic risk factors, including coronary artery disease (P < 0.001), higher serum triglyceride levels (P = 0.049), higher systolic (P = 0.03) and diastolic (P = 0.02) blood pressure levels. The incidence of PVD before transplantation was comparable between both groups (P = 0.114). Risk factor adjusted multivariate analysis revealed that patients with SPKT had a significant lower amount (32%) of PVCs (32 PVCs in 21 out of 101 SPKT; P < 0.001) when compared to the KTA patients who developed a significant increase in PVCs to 69% of cases (18 PVCs in 11 out of 26 KTA; P < 0.001). In line mean values of HbA1c (P < 0.01) and serum triglycerides (P < 0.01) were significantly lower in patients with SPKT > 8 years after transplantation. CONCLUSION: SPKT favorably slows down development and progression of PVD by maintaining a superior metabolic vascular risk profile in patients with IDDM1.

Beta-cell therapies for type 1 diabetes: Transplants and bionics.

Research continues toward the goal of treating type 1 diabetes by replacing insulin-producing beta cells. Ideally, such treatment would be safe and long-lasting and would eliminate the need for subcutaneous insulin replacement. This article reviews the current state of beta-cell replacement through transplant of the whole pancreas or of islet cells. It also looks at the "bionic" pancreas and other future challenges.

Pneumocystis jiroveci pneumonia in kidney and simultaneous pancreas kidney transplant recipients in the present era of routine post-transplant prophylaxis: risk factors and outcomes.

BACKGROUND: The goal of this study was to identify predictors for development of Pneumocystis jirovecii pneumonia (PJP) in kidney and simultaneous kidney and pancreas transplant recipients in the present era of universal primary prophylaxis. METHODS: We reviewed adult recipients of kidney transplant or simultaneous pancreas and kidney transplant at the University of Wisconsin between January 1, 1994 and December 31, 2016. Patients diagnosed with PJP during this time frame were included. Controls were randomly selected from among those whose post-transplant course was not complicated by PJP, matched on time since transplant through incidence density sampling with a 3:1 ratio. RESULTS: 28 (0.45%) of 6270 recipients developed PJP between 1994 and 2016. Median time since transplant was 4.6 years (interquartile range (IQR): 1.4-9.6 years). Affected recipients were older, had more HLA mismatches, and were more likely to have had BK viremia, CMV viremia and invasive fungal infections than matched controls. CMV viremia remained the only significant risk factor in multivariate analysis, and was a strong predictor (OR 6.27; p = 0.002). Ninety percent of the cases with prior CMV viremia had been diagnosed in the year preceding the diagnosis of PJP; among these, median time from diagnosis of CMV to diagnosis of PJP was 3.4 months (IQR: 1.74-11.5 months) and median peak CMV viral load prior to diagnosis of PJP was 3684.5 IU/mL (IQR: 1034-93,300 IU/mL). Additionally, 88.9% of patients with CMV in the preceding year had active infection at time of PJP diagnosis. Patient and graft survival were significantly worse at 2 years in recipients with PJP than our control group (42.4% vs. 88.5, and 37.9% vs. 79.9%; p < 0.001). CONCLUSIONS: Despite the low overall incidence of PJP in the era of universal prophylaxis, outcomes are poor. We suggest extending or re-initiating PJP prophylaxis for at least 6 months in the setting of CMV viremia due to the relatively low risk of therapy and potential significant impact on disease prevention.

[Machine perfusion: new opportunities in abdominal organ transplantation]. / Szervkonzerválás gépi perfúzióval: új lehetoségek a hasi szervek transzplantációjában.

Machine perfusion of marginal grafts might be a possible solution to organ shortage and a promising tool for reducing waiting list morbidity and mortality. In recent years, optimizing the circumstances of organ preservation prior to implantation via machine perfusion has become a hot topic of research. Machine perfusion offers a platform for organ reconditioning, assessment of cell viability and function, pharmacological preconditioning, prolongation of preservation time (ischemia time) and finally reducing graft injury. The objective of the new technology is to increase the pool of transplantable organs safely. Multicentric prospective studies have been evaluating the short and long term outcomes of different methods, however, several questions still remain unanswered. This review summarizes the recent advances in the field of machine perfusion, focusing on preclinical and clinical results. Machine perfusion seems to be a new milestone in the modern era of solid organ transplantation. Orv Hetil. 2018; 159(46): 1882-1890.

[The first five years of Hungary's Eurotransplant membership]. / Az Eurotransplant-csatlakozás elso öt éve Magyarországon.

The author concludes lessons learned from Hungary joining Eurotransplant five years ago through the more than half a century history of the Hungarian organ transplantation. The result of the stepwise evolution is that today's transplantation activity can be measured by a European benchmark. In comparison to the era before the membership, there are 40% more transplantations in the country. First the numbers of the living donor kidney transplantations significantly raised, followed by the organs transplanted from brain-dead donors: kidney, heart, pancreas, then liver and finally also lung. The ratio of the multiorgan donors changed from about 40% to more than 70%. A reassuring solution was found for the high urgent cases, for the paediatric transplants and for the highly immunized patients, who would have been in a desperate situation without Eurotransplant, but now every Hungarian end-stage organ failure patient has similar chances for getting a potential life-saving organ as their former luckier West-European counterparts. Orv Hetil. 2018; 159(42): 1695-1699.

Maximizing Utilization in Pancreas Transplantation: Phenotypic Characteristics Differentiating Aggressive From Nonaggressive Transplant Centers.

BACKGROUND: Maximizing pancreas utilization requires a balance between judicious donor selection and transplant center aggressiveness. We sought to determine how such aggressiveness affects transplant outcomes. METHODS: Using the Scientific Registry of Transplant Recipients, we studied 28 487 deceased-donor adult pancreas transplants. Donor and recipient demographic factors indicative of aggressiveness were used to score center aggressiveness. We compared outcomes of low (> 1 SD below mean), medium (± 1 SD from mean), and high (> 1 SD above mean) aggressiveness centers using bivariate and multivariable regressions. RESULTS: Donor and recipient aggressiveness demonstrated a roughly linear relationship (R = 0.20). Center volume correlated moderately with donor (rs = 0.433) and recipient (rs = 0.270) aggressiveness. In bivariate analysis, there was little impact of donor selection aggressiveness on graft survival. Further, for simultaneous pancreas and kidney transplants, centers with greater recipient aggressiveness selection had better graft survival. High-volume centers had better graft survival than low-volume centers. In multivariable analysis, donor aggressiveness did not have an effect on graft survival, whereas graft survival for medium (hazard ratio [HR], 0.66, 95% confidence interval [95% CI], 0.53-0.83) and high (HR, 0.67; CI, 0.51-0.86) recipient aggressiveness performed better than low-aggressiveness centers. There was a clear volume effect, with high-volume centers (>20 transplants/year; HR, 0.69; CI, 0.61-0.79) performing better than low-volume centers. CONCLUSIONS: Center practice patterns using higher-risk donors and recipients did not negatively affect outcomes. This effect is likely mediated through efficiencies gained with the increased transplant volumes at these centers.

Pancreas Transplantation for Patients with Type 1 and Type 2 Diabetes Mellitus in the United States: A Registry Report.

Successful pancreas transplantation is still the only method to restore short-term and long-term insulin independence and good metabolic control for patients with diabetes. Since the first transplant in 1966, tremendous progress in outcome was made; however, transplant numbers have declined since 2004. This article describes the development and risk factors of pancreas transplantation with or without a kidney graft between 2001 and 2016. Patient survival and graft function improved significantly owing to careful recipient and donor selection, which reduced technical failure and immunologic graft loss rates.

Desarrollo y resultados de un nuevo programa de trasplante de páncreas en España: la visión del cirujano / Development and results of a novel pancreas transplant program in Spain: the surgeon's point of view

INTRODUCCIÓN: El trasplante simultáneo de páncreas-riñón se encuentra indicado para pacientes con diabetes tipo 1 y enfermedad renal terminal. Los resultados son excelentes aunque el número de procedimientos parece ser un factor que afecta a la supervivencia de paciente e injerto estando en relación con la morbilidad quirúrgica, derivada de complicaciones pancreáticas. el objetivo del estudio es describir el desarrollo de un nuevo programa y exponer los resultados en un centro con un volumen bajo de trasplantes. MÉTODOS: Analizamos 53 trasplantes simultáneos de páncreas-riñón, en un período de 7 años (2009-2016), con una mediana de seguimiento de 39 meses. RESULTADOS: Dos pacientes han fallecido, uno tras parada cardíaca en postoperatorio y otro tras accidente de tráfico complicado con una neumonía. Entre los 51 pacientes vivos se han perdido 2 injertos, uno por un rechazo crónico tras cuatro años del trasplante y otro por trombosis arterial a los 20 días del mismo, motivo, este último, de la única trasplantectomía realizada. En diez pacientes se han realizado una o más reintervenciones: pancreatitis (n=3), oclusión intestinal (n=4), trombosis arterial (n=1), fístula con peritonitis (n=1) y hemoperitoneo (n=1). La supervivencia del paciente y del injerto a 1, 3, y 5 años fue del 98, 95 y 95% y del 96, 93 y 89%, respectivamente. Conclusiones Los resultados muestran que un nuevo programa de trasplante pancreático puede conseguir resultados similares a los de grupos con mayor volumen y experiencia. Una adecuada selección de donantes y receptores, una técnica homogénea y el aprendizaje con grupos expertos garantizan estos resultados

INTRODUCTION: Simultaneous kidney-pancreas transplantation for patients with type 1 diabetes and end-stage chronic renal disease is widely performed. However, the rate of surgical morbidity from pancreatic complications remains high. The aim of this study was to describe the development and results of a new program, from the point of view of the pancreatic surgeon. METHODS: We analyzed 53 simultaneous kidney-pancreas transplantations performed over a period of seven years (2009-2016), with a median follow up of 39 months (range: 1-86 months). RESULTS: Out of the total of this series, two patients died: one patient because of cardiac arrest immediately after surgery; and another patient due to traffic accident, complicated by pneumonia. Among the 51 living patients, two grafts were lost: one due to chronic rejection four years after transplantation; and the other due to arterial thrombosis 20 days after transplantation (the only case requiring transplantectomy). In ten patients, one or more re-operations were necessary due to the following: graft pancreatitis (n=4), small intestinal obstruction (n=4), arterial thrombosis (n=1), fistula (n=1) and hemoperitoneum (n=1). Overall patient and graft survival rates after 1, 3 and 5 years were 98, 95 and 95% and 96, 93 and 89%, respectively. CONCLUSIONS: This study has shown that the results of a new pancreas transplant program, which relies on the previous experience of other groups, do not demonstrate a learning curve. Adequate surgeon education and training, as well as the proper use of standardized techniques, should ensure optimal results

Pancreas transplantation.

The treatment of patients with diabetes mellitus (DM) presents many challenges to care providers and represents a major proportion of healthcare expenditure worldwide. Successful pancreas transplantation provides durable glycemic control and improves survival for patients with diabetes. Progress in the field has mainly been based on large single center studies and the cumulative analyses of registry data from the United Network for Organ Sharing (UNOS) and the International Pancreas Transplant Registry. This review focuses on the outcomes of pancreas transplantation for patients with and without end stage renal disease. It describes the current state of pancreas transplantation, gaps in knowledge, and future studies needed to enable more patients to benefit from this treatment. A common theme that emerges is the need for multicenter randomized trials in pancreas transplantation to define clearly the efficacy, risks, and long term benefits.

Pancreas Transplantation of US and Non-US Cases from 2005 to 2014 as Reported to the United Network for Organ Sharing (UNOS) and the International Pancreas Transplant Registry (IPTR).

This report is an update of pancreas and kidney transplant activities in the US and non-US region in two periods, 2005-2009 and 2010-2014. The aim of the report was to analyze transplant progress and success in the US compared to non-US countries, and to compare trends between the two periods. Between 2005-2009 and 2010-2014, the number of US pancreas transplants declined by over 20%, while the overall number of pancreas transplants performed outside the US has increased. The decline in US numbers is predominantly due to the decline in primary and secondary pancreas after kidney transplants (PAK). During the time period studied, the number of PAK transplants dropped by 50%. In contrast, the number of simultaneous pancreas/kidney transplants (SPK) declined by only 10%, and the number of pancreas transplants alone (PTA) by 20%. Over 90% of pancreas transplants worldwide were performed, with a simultaneous kidney transplant and excellent results. Transplant outcomes in SPK improved significantly because of a decrease in the rates of technical and immunologic graft loss. In 2010-2014 vs. 2005-2009, US SPK transplant patient survival at 1 year post-transplant increased from 95.7% to 97.4%, pancreas graft function from 88.3% to 91.3%, and kidney function from 93.6% to 95.5%. A significant improvement was also noted in PAK transplants. One-year patient survival increased from 96.4% to 97.9% and pancreas graft function from 81.0% to 86.0%. PTA 1-year patient survival remained constant at 97%, and pancreas 1-year graft survival improved from 81.0% to 85.7%. With the decline in the number of transplants, a change towards better pancreas donor selection was observed. In solitary transplants, the donors were primarily young trauma victims, and the pancreas preservation time was relatively short. A general tendency towards transplanting older recipients was noted. In 2010-2014 vs. 2005-2009, PTA recipients 50 years of age or older accounted for 32% vs. 22%, PAK for 28% vs. 22%, and SPK for 22% vs. 20%. This may be due to a relatively lower immunologic graft loss rate, especially in solitary transplants, which historically has been high in young recipients. The number of pancreas transplants in patients with type 2 diabetes and end-stage renal disease has increased, and accounted for 9% of all SPK recipients in 2010-2014.

Beta-Cell Replacement: Pancreas and Islet Cell Transplantation.

Pancreas and islet transplantation are 2 types of beta-cell replacement therapies for type 1 diabetes mellitus. Since 1966, when pancreas transplantation was first performed, it has evolved to become a highly efficient procedure with high success rates, thanks to advances in surgical technique and immunosuppression. Pancreas transplantation is mostly performed as simultaneous pancreas-kidney transplantation in patients with end-stage nephropathy secondary to diabetes. In spite of its efficiency, pancreas transplantation is still a major surgical procedure burdened by high morbidity, which called for the development of less invasive and hazardous ways of replacing beta-cell function in the past. Islet transplantation was developed in the 1970s as a minimally invasive procedure with initially poor outcomes. However, since the report of the 'Edmonton protocol' in 2000, the functional results of islet transplantation have substantially and constantly improved and are about to match those of whole pancreas transplantation. Islet transplantation is primarily performed alone in nonuremic patients with severe hypoglycemia. Both pancreas transplantation and islet transplantation are able to abolish hypoglycemia and to prevent or slow down the development of secondary complications of diabetes. Pancreas transplantation and islet transplantation should be seen as two complementary, rather than competing, therapeutic approaches for beta-cell replacement that are able to optimize organ donor use and patient care.

Thirty Years of Pancreas Transplantation at Leiden University Medical Center: Long-term Follow-up in a Large Eurotransplant Center.

BACKGROUND: An overview of 30 years of pancreas transplantation at a high volume center. Analysis of patient survival- and graft survival-associated risk factors. METHODS: All pancreas transplantations performed in our center from January 1, 1984, till December 31, 2012, were evaluated. Covariates influencing pancreas graft survival were analyzed using both univariate and multivariate analysis and Kaplan-Meier analysis. RESULTS: In the study period, 349 pancreas transplantations were performed. With the introduction of modern induction therapy in 1999, 5-year patient survival improved to 92.0% (P = 0.003). Five-year pancreas graft survival improved to 80.3% (P = 0.026). Pancreas graft survival was influenced by left or right donor kidney, transplant type, local origin of procurement team, pancreas cold ischemia time, recipient cerebrovascular disease. Pancreas donor risk index increased to 1.39 over the years and pancreas donor risk index 1.24 or higher is a risk factor for graft survival (P = 0.007). CONCLUSIONS: This study has shown excellent results in patient and pancreas graft survivals after 30 years of pancreas transplantation in a high volume center. Different donor, transplant, and recipient related risk factors influence pancreas graft survival. Even with higher risk pancreas donors, good results can be achieved.

Simultaneous pancreas and kidney transplantation: current trends and future directions.

PURPOSE OF REVIEW: Important trends are being observed in pancreas transplantation in the USA. We will describe recent trends in simultaneous pancreas kidney (SPK) transplantation related to immunosuppression, treatment of rejection, and transplantation for patients of advanced age and C-peptide positive diabetes. RECENT FINDINGS: Rates of pancreas transplantation have declined, despite improved pancreatic graft outcomes. Regarding immunosuppression, trends in SPK transplantation include T-cell depletion induction therapy, waning mammalian target of rapamycin inhibitor use and steroid use in greater than 50% of pancreas transplant recipients with few patients undergoing late steroid weaning. Rejection of the pancreas may be discordant with the kidney after SPK and there is a greater appreciation of antibody-mediated rejection of the pancreas allograft. De-novo donor-specific antibody without graft dysfunction remains an active area of study, and the treatment for this condition is unclear. SPKs are being performed with greater frequency in type 2 diabetes mellitus patients and in patients of advanced age, with exemplary results. SUMMARY: The current state of the art in SPK transplantation is yielding superb and improving results.

Controversies in pancreas transplantation.

Pancreas transplants are now highly effective for patients with diabetes mellitus. Improvements in outcomes have primarily been due to significant reductions in technical failures and immunological graft loss. In this short review we discuss three areas of controversy in the field of pancreas transplantation. Notwithstanding the controversies we have highlighted, in line with the American Diabetic Association position statement, simultaneous pancreas-kidney transplants and pancreas after kidney transplants should be routine for diabetic kidney recipients, and a pancreas transplant alone is appropriate for non-uremic labile diabetic patients.