Geographic Disparities in Access to Simultaneous Pancreas and Kidney Transplant in the Pre- and Post-Pancreas Allocation System Eras.

BACKGROUND: The 2014 pancreas allocation system (PAS) intended to decrease geographic variability in listing practices for simultaneous pancreas and kidney (SPK) transplant and define eligibility criteria for those with type 2 diabetes mellitus (T2DM). Our primary aims were to evaluate geographic disparities in access to SPK and assess T2DM SPK listings in the pre- and post-PAS eras. METHODS: Adult listings for SPK and kidney transplant (pre-PAS, January 2010 to October 29, 2014; post-PAS, October 30, 2014, to June 2, 2017) were identified in the Scientific Registry of Transplant Recipients. Multivariable logistic regression models tested associations of geography and/or diabetes mellitus type on the likelihood of SPK versus kidney transplant listing pre- and post-PAS. Competing risk models tested the likelihood of SPK transplantation within 2 years of listing for SPK. RESULTS: Among 41 205 listings (27 393 pre-PAS; 24 439 T2DM), univariate analysis showed reduced percentages for SPK post-PAS (22.1%-20.8%; P = 0.003). After adjusting for patient and center characteristics, geographic disparities declined slightly but persisted post-PAS (era by region interaction P < 0.001). The era by type of diabetes mellitus interaction effect was statistically significant (P = 0.039), reflecting that the proportions of SPK listings for T2DM increased in the post-PAS era (3.4%-3.9%; univariate P = 0.038), while those for type 1 diabetes mellitus remained statistically stable (47.9%-48.4%; univariate P = 0.571). Among people listed for SPK, geographic disparities in the cumulative incidence of transplantation within 2 years declined and the overall likelihood of transplantation increased in the post-PAS era (both P < 0.001). CONCLUSIONS: Geographic disparities in access to SPK declined slightly but persisted post-PAS. With new allocation change proposals and elimination of listing criteria for T2DM, further monitoring is warranted.

Robotic pancreas transplantation: the state of the art.

PURPOSE OF REVIEW: Robotic pancreas transplantation is a novel procedure that aims to reduce surgical invasiveness, and thereby limit complications related to the surgical access. Given that few centers are providing robotic transplantation, this review serves as a state of the science article to outline early experiences and highlight areas for future research. RECENT FINDINGS: Pancreas transplantation results in relatively high rates of wound and other surgical complications that are known to deleteriously impact outcomes. The minimally invasive, robotic-assisted approach decreases wound complications. Because of the obesity epidemic, overweight and obese status is encountered in an increasing number of transplant candidates. These candidates are subject to increased wound-related complications and most benefit from a robotic approach. The first clinical reports on laparoscopic, robotic-assisted kidney and pancreas transplantation indicate a significant decrease in wound complications and excellent outcomes in obese patients otherwise denied access to transplantation. SUMMARY: With excellent results achieved in surgically challenging patients and further accumulation of experience, laparoscopic, robotic-assisted pancreas and kidney transplantation may evolve to a new standard approach.

Defining outcomes for beta cell replacement therapy: a work in progress.

Defined outcomes for beta cell replacement therapy in the treatment of diabetes are critically needed. Progress towards the clinical acceptance of pancreas and islet transplantation has been hampered by the lack of clear definitions of functional and efficacy outcomes, as well as a lack of consistently applied glycaemic control metrics, together with poor alignment with the field of artificial insulin delivery/artificial pancreas development. To address this problem, the International Pancreas & Islet Transplant Association (IPITA) collaborated with the European Pancreas and Islet Transplant Association (EPITA) to develop a consensus for a joint statement on the definition of function and failure of beta cell replacement therapies, which is summarised in this commentary.

Diabetic Foot Complications Despite Successful Pancreas Transplantation.

BACKGROUND: It is known that successful pancreas transplantation enables patients with diabetes to maintain a normal glucose level without insulin and reduces diabetes-related complications. However, we have little information about the foot-specific morbidity in patients who have undergone successful pancreas transplantation. The purpose of this study was to investigate the prevalence and predisposing factors for foot complications after successful pancreas transplantation. METHODS: This retrospective study included 218 patients (91 males, 127 females) who had undergone pancreas transplantation for diabetes. The mean age was 40.7 (range, 15-76) years. Diabetes type, transplantation type, body mass index, and diabetes duration before transplantation were confirmed. After pancreas transplantation, the occurrence and duration of foot and ankle complications were assessed. RESULTS: Twenty-two patients (10.1%) had diabetic foot complications. Fifteen patients (6.9%) had diabetic foot ulcer and 7 patients (3.2%) had Charcot arthropathy. Three patients had both diabetic foot ulcer and Charcot arthropathy. Three insufficiency fractures (1.4%) were included. Mean time of complications after transplantation was 18.5 (range, 2-77) months. Creatinine level 1 year after surgery was higher in the complication group rather than the noncomplication group ( P = .02). CONCLUSION: Complications of the foot and ankle still occurred following pancreas transplantation in patients with diabetes. LEVEL OF EVIDENCE: Level III, comparative study.

Pancreas Transplantation From Pediatric Donors: A United Network for Organ Sharing Registry Analysis.

BACKGROUND: Pancreas grafts from pediatric donors are still considered "not ideal." Perceived concerns are related to low islet mass and potential for graft thrombosis. METHODS: The study evaluated all pancreas transplants from January 2000 to May 2015 using the Organ Procurement and Transplant Network database. Comparative analysis of recipient and graft survival was performed between pediatric (≤18 years) and adult donors. In the pediatric group, the outcomes were stratified based on donor age (≤6, 7-12, and 13-18 years) and weight (<30, 30-95, and >95 kg). RESULTS: In the selected era, 18 430 pancreas transplants were performed from 4915 pediatric donors (27%). Short-term graft and patient survivals were comparable between pediatric and adult donors. Ten-year patient and graft survivals were higher in the pediatric donor group: (70% and 54% vs 68% and 51%, P = 0.001). However, very-low-weight pediatric donors (<30 kg) resulted in worse graft survival in the long term (44% at 10 years, P = 0.006). CONCLUSIONS: Pediatric donor pancreas transplants had comparable patient and graft survival to the adult donor transplants. However, the islet mass of very small donors could influence long-term graft survival if the weights of donors and recipients are not properly matched. Usage of "very small" pediatric donors was not associated with higher incidence of technical complications or early graft loss.

Validation of the Pancreas Donor Risk Index for use in a UK population.

Pancreas graft failure rates remain substantial. The PDRI can be used at the time of organ offering, to predict one-year graft survival. This study aimed to validate the PDRI for a UK population. Data for 1021 pancreas transplants were retrieved from a national database for all pancreas transplants. Cases were categorized by PDRI quartile and compared for death-censored graft survival. Significant differences were observed between the UK and US cohorts. The PDRI accurately discriminated graft survival for SPK and was associated with a hazard ratio of 1.52 (P = 0.009) in this group. However, in the PTA and PAK groups, no association between PDRI quartile and graft survival was observed. This is the largest study to validate the PDRI in a European cohort and has shown for the first time that the PDRI can be used as a tool to predict graft survival in SPK transplantation, but not PTA or PAK transplantation.

Summary of the British Transplantation Society guidelines for transplantation from donors after deceased circulatory death.

The second edition of the British Transplantation Society Guidelines for Transplantation from Donors after Deceased Circulatory Death was published in June 2013. The guideline has been extensively revised since the previous edition in 2004 and has used the GRADE system to rate the strength of evidence and recommendations. This article summarizes the Statements of Recommendation contained in the guideline, which provide a framework for transplantation after deceased circulatory death in the U.K. and may be of wide international interest. It is recommended that the full guideline document is consulted for details of the relevant references and evidence base. This may be accessed at: http://www.bts.org.uk/MBR/Clinical/Guidelines/Current/Member/Clinical/Current_Guidelines.aspx.

Optimizing the program-specific reporting of pancreas transplant outcomes.

The Scientific Registry of Transplant Recipients is charged with providing program-specific reports for organ transplant programs in the United States. Monitoring graft survival for pancreas transplant programs has been problematic as there are three different pancreas transplant procedures that may have different outcomes, and analyzing them separately reduces events and statistical power. We combined two consecutive 2.5-year cohorts of transplant recipients to develop Cox proportional hazards models predicting outcomes, and tested these models in the second 2.5-year cohort. We used separate models for 1- and 3-year graft and patient survival for each transplant type: simultaneous pancreas-kidney (SPK), pancreas after kidney (PAK) and pancreas transplant alone (PTA). We first built a predictive model for each pancreas transplant type, and then pooled the transplant types within centers to compare total observed events with total predicted events. Models for 1-year pancreas graft and patient survival yielded C statistics of 0.65 (95% confidence interval, 0.63-0.68) and 0.66 (0.61-0.72), respectively, comparable to C statistics for 1-year patient and graft survival for other organ transplants. Model calibration (Hosmer-Lemeshow method) was also acceptable. We conclude that pooling the results of SPK, PAK and PTA can produce potentially useful models for reporting program-specific pancreas transplant outcomes.

Donor risk factors, retrieval technique, preservation and ischemia/reperfusion injury in pancreas transplantation.

PURPOSE OF REVIEW: Pancreas transplantation is still hampered by a high incidence of early graft loss, and organ quality concerns result in high nonrecovery/discard rates. Demographic donor characteristics, surgical retrieval strategy, preservation fluid and ischemia time are crucial factors in the process of organ selection and are discussed in this review. RECENT FINDINGS: The donor shortage is driving an increasing utilization of nonideal organs which would previously have been identified as unsuitable. Recent literature suggests that organs from extended criteria donors - older (>45 years), BMI >30  kg/m(2), and donation after cardiac death (DCD) - can achieve the same graft and patient survival as those from standard criteria donors, with the proviso that the accumulation of risk factors and long ischemic times should be avoided. Visual assessment of the pancreas is advisable before declining/accepting a pancreas. University of Wisconsin represents the gold standard solution; however, histidine-tryptophan-ketoglutarate and Celsior result in equal outcomes if cold ischemia time (CIT) is less than 12  h. Currently in pancreas transplantation, there is no proven effective ischemia/reperfusion injury prophylaxis than trying to keep CIT as short as possible. SUMMARY: Demographic risk factors, inspection of the pancreas by an experienced surgeon and predicted CIT are crucial factors in deciding whether to accept a pancreas for transplantation. However, there is a need for an improved evidence base to determine where to set the 'cut-off' for unsuitable pancreatic grafts.

Prevention and management of graft thrombosis in pancreatic transplant.

Pancreatic transplant effectively cures type 1 diabetes mellitus and maintains consistent long-term euglycemia. However, technical failure, and in particular graft thrombosis, accounts for the vast majority of transplants lost in the early postoperative period. The pancreas' inherently low microvascular flow state makes it vulnerable to vascular complications, as does the hypercoagulable blood of diabetic patients. Ultimately, the phenomenon is most definitely multifactorial. Prevention, as opposed to treatment, is key and should focus on reducing these multiple risk factors. This will involve tactical donor selection, optimal surgical technique and some form of anticoagulation. Close monitoring and early intervention will be crucial when treating thrombosis once preventative methods have failed. This may be achieved by further anticoagulation, graft salvage, or pancreatectomy with retransplant. This article will explore the multiple factors contributing to graft thrombus formation and the ways in which they may be addressed to firstly prevent, or more likely, reduce thrombosis. Secondly, we will consider the management strategies which can be implemented once thrombosis has occurred.

Results of pancreas transplantation alone with special attention to native kidney function and proteinuria in type 1 diabetes patients.

We report on our single-center experience with pancreas transplantation alone (PTA) in 71 patients with type 1 diabetes, and a 4-year follow-up. Portal insulin delivery was used in 73.2% of cases and enteric drainage of exocrine secretion in 100%. Immunosuppression consisted of basiliximab (76%), or thymoglobulin (24%), followed by mycophenolate mofetil, tacrolimus, and low-dose steroids. Actuarial patient and pancreas survival at 4 years were 98.4% and 76.7%, respectively. Relaparatomy was needed in 18.3% of patients. Restored endogenous insulin secretion resulted in sustained normalization of fasting plasma glucose levels and HbA1c concentration in all technically successful transplantations. Protenuria (24-hour) improved significantly after PTA. Renal function declined only in recipients with pretransplant glomerular filtration rate (GFR) greater than 90 ml/min, possibly as a result of correction of hyperfiltration following normalization of glucose metabolism. Further improvements were recorded in several cardiovascular risk factors, retinopathy, and neuropathy. We conclude that PTA was an effective and reasonably safe procedure in this single-center experience.

Improvement in short-term pancreas transplant outcome by targeted antimicrobial therapy and refined donor selection.

Graft thrombosis and infectious complications are the main early causes of pancreatic allograft loss in recipients of whole vascularized pancreas transplants, resulting in loss rates up to 10 per cent in the first post transplant week. In this study we sought to determine if initiation of a standardized selection criteria and posttransplant chemoprophylaxis regimen could reduce the rate of early allograft loss; we compared the rate of early allograft loss after introduction of these changes. Of the 61 diabetic recipients who underwent these protocols, 50.8 per cent were female. Average age was 42.9 ± 7.4 years of age, average length of stay was 12.7 ± 8.7 days, with all transplants performed heterotopic to the right lower quadrant with venous drainage to the proximal external or common iliac vein. Organ donors were 21.4 ± 4.8 years of age, body mass index was 23.9 ± 2.8 kg/m(2), with a length of stay of 3.7 ± 1.6 days. One-week pancreatic allograft survival for the protocolized versus nonprotocolized patients was 100 per cent versus 96.7 per cent, 1 month was 98.4 per cent versus 93.4 per cent, and 1 year was 96.7 per cent versus 88.5 per cent, respectively. In the protocolized group there were two graft losses due to infectious complications and none due to thrombosis. Before initiation of the protocols patient survival at 1 year was 91.8 per cent and after was 100 per cent. Pancreas transplantation is arguably the most technically demanding organ transplant from a complication and loss standpoint. However, highly successful outcomes can be obtained with standardized protocols beginning pretransplant to reduce the incidence of posttransplant complications.

Surgical techniques for pancreas transplantation.

PURPOSE OF REVIEW: Pancreas transplantation reproducibly induces insulin independence in beta-cell penic diabetic patients. The difference between full insulin independence, partial graft function, and graft loss, mostly results from technical failure, graft rejection, and patient death with function graft. The purpose of this review is to examine recent surgical advances and discuss their contribution to improved graft function. RECENT FINDINGS: Few actual surgical innovations were described in the period reviewed. Duodenoduodenostomy is an interesting option for drainage of digestive secretions, when the pancreas is placed behind the right colon and is oriented cephalad. The main advantage of this technique is easy endoscopic assessment of donor duodenum but, when allograft pancreatectomy is necessary, repair of native duodenum may be troublesome. Selective revascularization of the gastroduodenal artery, at the back-table, possibly improves blood supply to the head of the pancreas graft and duodenal segment. There is no proof that this additional maneuver is always beneficial, although it can be graft saving in case of poor segmental graft perfusion. SUMMARY: Transplant surgeons should be familiar with all techniques for pancreas transplantation. Long-term graft function is possible only after technically successful pancreas transplantation. There is clearly a need for more objective assessment and standardization of surgical techniques for pancreas transplantation.

ASTS recommended practice guidelines for controlled donation after cardiac death organ procurement and transplantation.

The American Society of Transplant Surgeons (ASTS) champions efforts to increase organ donation. Controlled donation after cardiac death (DCD) offers the family and the patient with a hopeless prognosis the option to donate when brain death criteria will not be met. Although DCD is increasing, this endeavor is still in the midst of development. DCD protocols, recovery techniques and organ acceptance criteria vary among organ procurement organizations and transplant centers. Growing enthusiasm for DCD has been tempered by the decreased yield of transplantable organs and less favorable posttransplant outcomes compared with donation after brain death. Logistics and ethics relevant to DCD engender discussion and debate among lay and medical communities. Regulatory oversight of the mandate to increase DCD and a recent lawsuit involving professional behavior during an attempted DCD have fueled scrutiny of this activity. Within this setting, the ASTS Council sought best-practice guidelines for controlled DCD organ donation and transplantation. The proposed guidelines are evidence based when possible. They cover many aspects of DCD kidney, liver and pancreas transplantation, including donor characteristics, consent, withdrawal of ventilatory support, operative technique, ischemia times, machine perfusion, recipient considerations and biliary issues. DCD organ transplantation involves unique challenges that these recommendations seek to address.

Second annual analysis of the collaborative islet transplant registry.

In September 2001, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) founded the Collaborative Islet Transplant Registry (CITR). Each year, CITR produces a complete set of analyses available to the public. In its second year, CITR represents the efforts of 19 North American islet transplant programs reporting information on 138 islet transplant recipients (1999-2004), 256 processed pancreata that led to infusion, and 266 infusion procedures. This analysis focuses on recipients of islet-alone procedures. Median age of the recipient is 41.6 years (range, 23.1-64.4 years), duration of diabetes is 29 years (range, 4-50 years), and over 66% are female. Median weight of the recipient is 65 kg (range, 47-97 kg) and median body mass index (BMI) is 23.1 kg/m(2) (range, 18.8-31.6). Examining outcomes at 6 months following the recipient's last infusion, 67.0% are insulin independent, and at 12 months this percentage decreases to 58.0%. There is a striking decrease in the occurrence of severe hypoglycemic events subsequent to the first infusion. Over 82% of all recipients experience one or more severe hypoglycemic events in the year prior to their first infusion. However, only two recipients (2%) experience one or more severe hypoglycemic events between 30 days and 12 months postinfusion, but both of these recipients were on insulin replacement therapy and one had experienced a complete islet graft failure. The information provided in this analysis and subsequent analyses of CITR provides current and comprehensive information on outcome measures in islet transplantation.