Pancreas Allograft Research Articles

Predictors of 10-Year Pancreas Allograft Survival After Simultaneous Pancreas and Kidney Transplantation

This study aimed to identify the preoperative, perioperative, and postoperative factors affecting 10-year pancreas allograft survival after simultaneous pancreas and kidney (SPK) transplantation. Analysis was performed on a prospectively maintained database of 56 SPK transplants consecutively performed between January 1992 and October 2002. The definition cutoff points of specific variables were obtained by the receiver operating characteristic curve and multiple logistic regression analyses that were performed to determine the predictors of pancreas allograft survival after 10 years. In total, 44 (79%) patients had an overall survival of more than 10 years, and the overall 10-year pancreas allograft survival rate was 57% (n = 32/56). The significant predictors for pancreas allograft failure in 10 years and above were kidney allograft failure (P = 0.04), serum creatinine 1 year postoperatively (P = 0.002), and serum hemoglobin A1c (HbA1c) level 2 years postoperatively (P = 0.003). A serum creatinine cutoff value of more than 129 μmol/L at 1 year was 87.5% sensitive and 70% specific for predicting pancreas allograft failure at 10 years. Serum HbA1c of more than 5.6% at 2 years was 85.7% sensitive and 62.5% specific for predicting pancreas allograft failure at 10 years. On multivariate analysis, 129 μmol/L and above of serum creatinine and more than 5.6% of serum HbA1c were the independent predictors of pancreas allograft failure at 10 years. These findings may provide important information for identifying patients at risk for long-term pancreas allograft failure after SPK transplantation.

Kidney Delayed Graft Function Is Associated With Early Pancreas Allograft Failure in Simultaneous Pancreas Kidney Transplant Recipients.

We found in a single center study that kidney delayed graft function (DGF) in simultaneous pancreas kidney (SPK) recipients was associated with poor pancreas allograft outcomes. We investigated the association of DGF with SPK outcomes using OPTN data. 14,636 patients received a primary SPK between March 1994 and March 2013. A total of 1,112 (8%) recipients had DGF. Those with DGF were younger, had a higher mean BMI, were more likely to be male, non-Caucasian, less likely to receive a pre-emptive kidney transplant and had donors who were older and had a higher mean BMI. 3219 pancreas allografts failed over a median follow-up of 4.3 years. DGF was associated with early (<30 day) pancreas allograft failure (N=980) (Figure 1A).Figure: No Caption available.DGF remained associated with early pancreas allograft failure after adjustment for recipient and donor age, gender, ethnicity, BMI, pre-transplant dialysis, DCD, infection, leak and pancreatitis (HR=2.35); (Table 1).Table: No Caption available.DGF was not significantly associated with pancreas allograft failure after 30 days (n=2239) in adjusted analysis (HR=1.09). Furthermore, DGF was significantly associated with kidney allograft failure and patient death within 30 days (HR=18.5 and HR=3.15 respectively) and beyond 30 days (HR=1.42 and HR=1.44 respectively) in unadjusted and adjusted analyses (Figure 1B and 1C, Table 1). Kidney DGF is an important risk factor for early pancreas allograft failure in SPK recipients and is also significantly associated with early and longer-term kidney loss and decreased patient survival.

Surgical Salvage of Partial Pancreatic Allograft Thrombosis Presenting as Ruptured Pancreatic Cyst: A Case Report

IntroductionVascular thrombosis is an important cause of pancreatic graft loss, and the vast majority is managed using graft pancreatectomy. There are limited reports and case series of successful salvage of the pancreas allograft. We describe a case of partial pancreatic allograft thrombosis presenting as ruptured pancreatic cyst successfully salvaged using a graft distal pancreatectomy. MethodsWe used descriptive retrospective analysis. ResultsA 29-year-old patient with type 1 diabetes and end-stage renal failure underwent a simultaneous pancreas kidney transplantation with immediate graft function. The cadaveric pancreas allograft was placed head up in the right iliac fossa with enteric exocrine drainage and standard vascular anastomosis. He presented with compressive symptoms on his bladder 5 months later, and a computed tomography (CT) showed a 4-cm cystic lesion in the body and tail of the pancreas allograft. Spontaneous rupture of the cyst occurred 3 weeks after the initial onset of symptoms with generalized abdominal pain. He underwent graft distal pancreatectomy with good recovery. He remains euglycemic, insulin-free with a normal renal function. Histology of the resected unhealthy graft showed an arterial thrombus with xanthogranulomatous inflammation and necrosis. ConclusionSurgical salvage with graft distal pancreatectomy is feasible for partial pancreatic allograft thrombosis. Cystic lesion in the pancreas is a possible presentation of vascular thrombosis.

What Is the Risk of Transmission From HBcAb Positive Donors To the Recipient in Kidney and Pancreas Transplantation?

Introduction: There is variation of practice amongst UK kidney and pancreas transplant units in implanting grafts from HBcAb +ve donors due to the perceived risk of transmission of hepatitis B (HBV). Centres transplanting such grafts have variable practice of antiviral prophylaxis with lamivudine ranging from no prophylaxis to life-long prophylaxis. The aim of this study was to assess the rate of HBV infection in HBsAg -ve recipients of renal and pancreas allografts receiving organs from HBcAb +ve, HBsAg -ve donors. Methods: We surveyed the UK kidney and pancreas transplant units regarding their practices of accepting HBcAb +ve donor grafts and the subsequent use of antiviral prophylaxis. All patients receiving a kidney (KT) and or pancreas (PT) allograft from HBcAb +ve, HBsAg -ve donors between Jan 2002 and Dec 2011 were identified retrospectively from the UK Transplant Registry. Post transplant virology data were also collected. All patients had a minimum follow-up of 2 years. Results: The survey was incomplete at the time of this analysis and hence is not presented. A total of 277 patients were identified who underwent KT (n=252) or PT (n=25) from HBcAb +ve donors. Of these 2 KT recipients were HBsAg +ve prior to transplantation and were excluded from the analysis. Of the remaining 275, seven recipients (6 KT, 1 PT) had documented evidence of HBV positive virology post transplant (2.5%). At the time of this analysis, 178 patients (159 KT, 19 PT) had documented negative virology (65%) and 98 (93 KT and 5 PT) were recorded as ‘not reported’ (35%). Of the 11 KT in our centre, no HBV transmission recorded. All received 100 day lamivudine prophylaxisConclusions: The risk of HBV transmission following kidney and pancreas transplantation from HBcAb +ve donors remains low. Use of antiviral prophylaxis can help reduce this risk further. We suggest 100-day post-transplant lamivudine prophylaxis in kidney and pancreas transplantation. There is a need for clear guidelines for the safe and effective use of HBcAb +ve grafts

The Findings of For Cause Biopsies in Pancreas Transplant Recipients and Their Impact On Transplant Outcomes.

Background: There is limited data regarding the histological findings in pancreas allografts with graft dysfunction and the predictive value of the findings for the outcomes. We sought to determine the rate and type of acute rejection and the impact on graft survival. Methods: 132 pancreas transplant recipients required a total of 214 biopsies for graft dysfunction, in the form of elevation of amylase/lipase or hyperglycemia, between April 2003 and December 2012. Biopsies were evaluated for acute T-cell-mediated rejection (ACMR) and antibody-mediated rejection (AMR). Biopsies were scored according to the applicable criteria at the time of biopsy. The rejection episodes were treated with thymoglobulin in majority of the cases. Patient and graft survival rates were assessed. Results: Transplant type was categorized as simultaneous pancreas-kidney (SPK) in 63 patients, pancreas after kidney (PAK) in 42 patients, and pancreas transplant alone (PTA) in 27 patients. The mean recipient age was 40.2±8.1 years and 68 (51.5%) were male. The incidence of biopsies with ACMR, AMR, or both was 49.2%, 4.8%, and 1.6%, respectively. Patients were followed for 48.8±42.3 months until graft failure or censoring. The overall graft failure rate following the biopsy was 42.4%. Patients with rejection were not at an increased risk of graft loss compared to those free of rejection (HR=1.43, p=0.23). In this cohort recipients of SPK had a lower risk of graft loss compared to PTA (HR 0.38, p=0.005). In addition, the unadjusted risk of graft loss in men was 49% lower than women (p=0.021). During the follow up 9.1% of the patients died. Conclusions: Our data suggest that in pancreas transplant recipients with graft dysfunction, acute rejection is a dominant finding in the biopsies. However, with proper treatment the rejection does not have a significantly negative impact on graft survival.

Systematic Study of Causes of Death and Allograft Loss After Pancreas Transplantation in the Modern Era.

Background: The aim of the study is to identify specific causes of mortality and pancreas allograft loss of the three pancreas transplantation (PT) types in the modern era with ATG induction and tacrolimus based triple immunosuppression. Methods: We performed a retrospective review of 262 adult patients who received PT at our institution from 01/01/1998 to 12/31/2009. The causes of death and graft loss were determined by reviewing clinical and histologic information. Results:89 recipients from the cohort died during the median follow-up of 8 years (IQR 4.1 to 11.2 years). The most common causes of death were infection/sepsis (20%) and cardio/cerebrovascular disease (25 %). Among patients that died, the cause of death was not different among the three PT types (p=0.50). 133 of 279 (48%) grafts were lost, and 10 recipients (4%) lost more than one allograft. Graft losses due to death with a functioning graft (DWF)(37%) and graft thrombosis (17% early and 7% late) were the most common causes. Within the first year post PT, early thrombosis was the most common cause of all graft loss (53%). Immunologic factors became most common causes censoring for death beyond one year post PT (50%). Graft survival was higher in Simultaneous Pancreas Kidney transplantation (SPK) than that in Pancreas transplantation alone (PTA) or Pancreas after kidney transplantation (PAK) recipients, most likely because of the relative low incidence of DWF and graft loss due to immunologic factors in SPK recipients. Conclusion: PT may not change the distribution of underlying causes of death in patients with long-standing diabetes. Early thrombosis and rejection remain the main targets in our efforts to improve long term pancreas allograft survival.

Histological Evidence of Recurrent Type 1 DM or De-Novo Type 2 DM in Whole Pancreas Transplants With Late Loss of Function: Report of 4 Cases.

The most common indication for pancreas transplantation is Type 1 diabetes mellitus(DM). Recurrence of this disorder with selective T-cell mediated destruction of β cells has been reported. Changes consistent with Type 2 DM (amyloid deposition) have occurred in rare cases of islet transplantation. A proportion of recipients develop hyperglycemia despite receiving a technically successful graft. Occasionally progressive hyperglycemia develops after several years of excellent graft function. Management of pancreas allografts is based mostly on clinical findings (and renal biopsy in SPKs) with histological evaluation of the pancreas itself done only rarely. Thus, histological correlates of hyperglycemia and overall graft failure, are often unavailable. We retrospectively performed Congo red stain for amyloid, and Insulin and Glucagon stains for β and α islet cells, respectively in samples from patients with hyperglycemia received between 2000 and 2013 (152 pancreas biopsies and 33 pancreatectomies). Islet pathology that could explain the graft failure (independent of acute or chronic rejection) was identified in 2 biopsies and 2 pancreatectomies from 4 patients summarized in table 1. There was no fibrosis/parenchymal atrophy.Table: No Caption available.Primary islet disease may represent the main cause of graft loss in pancreas transplantation. The incidence of recurrent Type 1 DM is considered to be low but this has not been studied systematically. Similarly, the occurrence of de-novo Type 2 DM changes, described here for the first time in whole pancreas transplants has not been studied. Systematic evaluation of histological samples is necessary for accurate determination of the cause of graft loss in pancreas transplants.

Damage to the Deceased Donor Pancreas Allograft During Procurement - A Registry Analysis.

Damage to the Deceased Donor Pancreas Allograft During Procurement - A Registry Analysis.

Immune Responses to Tissue Restricted Non-HLA Self-Antigens in Simultaneous Kidney Pancreas Transplant Recipients Are Associated With Rejection.

Background: Antibodies (Abs) to tissue restricted self-antigens (SA) have been associated with rejection following solid organ transplantation. In this study we measured antibodies to the kidney self antigens (KSAg) Collagen-IV (Col-IV) and Fibronectin (FN) and to pancreas self-antigens (PSAg) including insulin autoantibodies (IAA),islet cell antibodies (ICA), Glutamic acid decarboxylase (GAD) and pancreas-associated protein-1 (PAP1) in simultaneous pancreas kidney (SPK) recipients with and without rejection. Materials and Methods Antibodies against Col-IV, FN, insulin, islet cell, GAD and PAP were measured by ELISA in 28 SPK post-transplant using ELISA. Abs were additionally measured on stored pre-transplant sera. Biopsy-proven acute rejection episodes of the kidney and/or pancreas allograft occurred in 11 patients (Group A). This group included 6 patients with combined rejection, 2 with kidney-alone and 3 with pancreas-alone rejections. Group B had 17 SPK recipients who remained rejection free were enrolled as normal controls. Results Abs to KSAg Col IV was significantly higher in post-transplant in SPK with rejection (Table 1) (p Value 0.0387). There was additionally a non-significant increase in FN Abs both pre-transplant and post-transplant in SPK with rejection. Antibodies to PSAg (IAA, ICA, GAD and PAP) were not associated with rejection after SPK.Table: No Caption available.Conclusion The development of Abs to KSAg is associated with rejection after SPK. No association with antibodies to pancreatic self-antigens and rejection was observed.

Expanding the Pancreas Donor Pool

Currently underutilized and in somewhat short supply, the pancreas allograft is a relatively scarce resource. Despite factors such as increased demand, positive changes in organ donation rates, and the liberalization of ‘organ-acceptable’ criteria, there has been a decline in the number of deceased donor pancreas transplants performed in the US. Concomitantly, there has been an increase in similar transplants performed in other countries. While it is understandable that there are a multiplicity of factors to be considered in the evaluation of the potential pancreas allograft donor in an attempt to minimize graft loss and morbidity, it is a simple truth that as a result there are unused transplantable organs. This paper will deal with the multifaceted problem of pancreas underutilization and will discuss strategies that could lead to the expansion of the pancreas donor pool.

Donation After Circulatory Death

Organ donation after circulatory death (DCD) has been endorsed by the World Health Organization and is practiced worldwide. This overview examines current DCD practices, identifies problems and challenges, and suggests clinical strategies for possible improvement. Although there is uniform agreement on DCD donor candidacy (ventilator-dependent individuals with nonrecoverable or irreversible neurologic injury not meeting brain death criteria), there are variations in all aspects of DCD practice. Utilization of DCD organs is limited by hypoxia, hypotension, reduced--then absent--organ perfusion, and ischemia/reperfusion syndrome. Nevertheless, DCD kidneys exhibit comparable function and survival to donors with brain death kidneys, although they have higher rates of primary graft nonfunction, delayed graft function, discard, and retrieval associated injury. Concern over ischemic organ injury underscores the reluctance to recover extrarenal DCD organs since lack of medical therapy to support inadequate allograft function limits their acceptability. Nevertheless, limited results with DCD pancreas, liver, and lung allografts (but not heart) are now approaching that of donors with brain death organs. Pretransplant machine perfusion of DCD kidneys (vs. static storage) may reduce delayed graft function but has no effect on long-term organ function and survival. Normothermic regional perfusion used during DCD abdominal organ retrieval may reduce ischemic organ injury and increase the number of usable organs, although critical confirmative studies have yet to be done. Minor increases in usable DCD kidneys could accrue from increased use of pediatric DCD kidneys and from selective use of DCD/ECD kidneys, whereas a modest increase could result through utilization of donors declared dead beyond 1 hr from withdrawal of life support therapy. A significant increase in transplantable kidneys could be achieved by extension of the concept of living kidney donation in relation to imminent death of potential DCD donors. Progress in research to identify, prevent, and repair DCD-associated organ retrieval injury should improve utilization of DCD organs. Recent results using ex situ pretransplant organ perfusion of DCD organs has been encouraging in this regard.

The allocation of pancreas allografts on donor age and duration of intensive care unit stay: the experience of the North Italy Transplant program

Starting in 2011, the North Italy Transplant program (NITp) has based on the allocation of pancreas allografts on donor age and duration of intensive care unit (ICU) stay, but not on donor weight or BMI. We analyzed the detailed allocation protocols of all NITp pancreas donors (2011-2012; n = 433). Outcome measures included donor characteristics and pancreas loss reasons during the allocation process. Twenty-three percent of the 433 pancreases offered for allocation were transplanted. Younger age, shorter ICU stay, traumatic brain death, and higher eGFR were predictors of pancreas transplant, either as vascularized organ or as islets. Among pancreas allografts offered to vascularized organ programs, 35% were indeed transplanted, and younger donor age was the only predictor of transplant. The most common reasons for pancreas withdrawal from the allocation process were donor-related factors. Among pancreas offered to islet programs, 48% were processed, but only 14.2% were indeed transplanted, with unsuccessful isolation being the most common reason for pancreas loss. Younger donor age and higher BMI were predictors of islet allograft transplant. The current allocation strategy has allowed an equal distribution of pancreas allografts between programs for either vascularized organ or islet transplant. The high rate of discarded organs remained an unresolved issue.

Perspectives on Abdominal Organ Preservation Solutions: A Comparative Literature Review

Various preservation solutions are used for kidney, liver, pancreas, small intestine, and multiorgan recoveries and transplants. The effectiveness of these solutions, primarily measured by ability to preserve the organ and graft survival, was analyzed. The 2 most common solutions used for intra-abdominal organs are University of Wisconsin Solution (UW)/Viaspan and Histidine-tryptophan-ketoglutarate (HTK)/Custodiol solution. Outcomes for liver, pancreas, and kidney allografts preserved with these 2 solutions are similar. Although HTK solution shows conflicting results with respect to pancreatic cellular edema, researchers in several studies have noted that HTK solution may be more protective than UW solution against biliary complications in liver transplant. In kidney recoveries, HTK solution may be associated with higher graft loss and increased delayed graft function in marginal deceased donors but had lower incidence of delayed graft function in living donors when compared with UW. UW remains the reference standard for use during multiorgan recoveries but is experiencing strong competition from HTK and other alternative solutions. Some researchers suggest that Celsior's comparable results in abdominal organs and viability for thoracic organs makes it a strong competitor, especially in multiorgan recoveries. Each solution has benefits accompanied by disadvantages. Although it may not be feasible, when considering single-organ recoveries, consideration of alternative solutions may be warranted.

Acute Cellular and Antibody-Mediated Rejection of the Pancreas Allograft: Incidence, Risk Factors and Outcomes

Antibody-mediated rejection (AMR) after pancreas transplantation is a recently identified entity. We describe the incidence of, risk factors for, and outcomes after AMR, and the correlation of C4d immunostaining and donor-specific antibody (DSA) in the diagnosis of AMR. We retrospectively analyzed 162 pancreas transplants in 159 patients who underwent 94 pancreas allograft biopsies between 2006 and 2009. Univariate and multivariate analyses were performed to evaluate risk factors for pancreas graft AMR. One-year rejection rates and survival after rejection were calculated by Kaplan-Meier methods. AMR occurred in 10% of patients by 1-year posttransplant. Multivariate risk factors identified for AMR include nonprimary simultaneous pancreas-kidney (SPK) transplant, primary solitary pancreas (PAN) transplant and race mismatch. After pancreas rejection, patient survival was 100% but 20% (8 of 41) of pancreas grafts failed within 1 year. Graft survival after acute cellular rejection (ACR), AMR and mixed rejection was similar. Of biopsies that stained >5% C4d, 80% were associated with increased Class I DSA. In summary, AMR occurs at a measurable rate after pancreas transplantation, and the diagnosis should be actively sought using C4d staining and DSA levels in patients with graft dysfunction, especially after nonprimary SPK and primary PAN transplantation.

Intercellular Adhesion Molecular-1, Fas, and Fas Ligand as Diagnostic Biomarkers for Acute Allograft Rejection of Pancreaticoduodenal Transplantation in Pigs

The early diagnosis of pancreas allograft dysfunction is crucial for the management and long-term survival of transplanted pancreases. We investigated whether intercellular adhesion molecular-1 (ICAM-1), Fas, and Fas ligand (FasL) can be used as novel biomarkers of acute pancreaticoduodenal allograft dysfunction in pigs. Forty outbred landraces were randomly divided into three groups. In the control group (8 pigs), a sham operation was performed but no drugs were administered. In groups 1 and 2 (8 pairs each), pancreaticoduodenal transplantation was performed, with the latter administered immunosuppressive drugs and the former not administered drugs. The expression of ICAM-1, Fas, and FasL mRNA in the peripheral vein blood was assessed by flow cytometry and RT-PCR, pre-transplant and on days 1, 3, 5, and 7 after transplantation. Simultaneously, the levels of glucose, insulin, and glucagon in the serum of the recipients were evaluated. The allograft pancreas tissue was obtained to assess the pathological damage and the expression of Fas and FasL by immunohistochemistry. On the first 7 days after transplantation, ICAM-1, Fas, and FasL mRNA expression in the blood leukocytes of the recipient increased significantly in groups 1 and 2 compared with the control group (P < 0.01). However, the levels in group 2 were significantly lower than those in group 1 (P < 0.05). Interestingly, the FasL expression increased but the Fas expression decreased gradually in the graft pancreas tissue during the first week after transplantation in both groups 1 and 2 compared with the control group (P < 0.05). The levels of serous glucose, insulin, and glucagon in groups 1 and 2 obviously changed on day 1 after transplantation but returned to normal on day 2. The recipient's pancreas pathological sections did not exhibit any rejection changes on days 1 and 3 after transplantation but showed rejection damage on days 5 and 7. ICAM-1, Fas, and FasL were found to be sensitive biomarkers of acute pancreas allograft dysfunction after pancreaticoduodenal transplantation in pigs, and their monitoring could be used to evaluate the effectiveness of the immunosuppression therapy.

Combined heterotopic liver–pancreas transplantation as a curative treatment for liver cirrhosis and diabetes mellitus in cystic fibrosis

Cystic fibrosis (CF) is an inherited disease with a defect in epithelial chloride transport that results in a multisystem disease. Although pulmonary disease remains the primary cause of morbidity and mortality, focal biliary cirrhosis and portal hypertension may develop in up to 8% of these patients. Liver transplantation (TX) is an accepted therapy and shows good results. We report on a patient with cystic fibrosis homozygous for the most common CFTR mutation delta F 508 who received a combined heterotopic liver and pancreas transplantation at the age of 18 yr. He suffered from CFRD, which untypically required high doses of insulin. In addition, the patient had pulmonary complications, was chronically colonized with multiresistant Pseudomonas aeruginosa (MBL) and had an allergic bronchopulmonary aspergillosis (ABPA). The patient remained in stable health for 54 months post-TX and was able to live a nearly normal life. With a follow-up of five yr, the function of the liver and pancreas allografts was excellent. However, and sadly, his pulmonary function continued to deteriorate from progression of his CF, and he died of respiratory failure due to a severe pneumonia and septicemia at the age of 23 yr and five months.

Alemtuzumab induction in simultaneous pancreas and kidney transplantation

Alemtuzumab (AZ) is a monoclonal anti-CD52 antibody used as an induction agent in organ transplantation. Few studies have analyzed this agent in the context of simultaneous kidney-pancreas transplantation (SPKT). We examined US registry data of SPKT recipient outcomes from January 2002 to October 2009 stratified by induction agent including AZ, other T-cell-depleting agents combined (T cell), IL2 receptor blockade (IL-2RAb), and no induction (none). Of 6860 SPKT recipients, induction therapy was AZ in 10%, T cell in 49%, IL-2RAb in 18%, and none in 22%. On multivariate analysis, there were no significant differences in overall patient survival, pancreas or renal allograft survival, or delayed renal graft function for the three induction groups compared with no induction. Rehospitalization within six months of transplantation occurred more often with AZ (51%) T cell (52%), and IL-2RAB (45%) compared with none (41%; p < 0.0001). On multivariate analysis, there was a significant higher odds of six-month rehospitalization with AZ (aOR 1.40, 95%CI 1.14-1.71), IL-2RAb (aOR 1.20, 95%CI 1.01-1.42-1.20), and other T-cell-depleting agents (aOR 1.50, 95%CI 1.31-1.73) compared with none. Median length of stay was significantly shorter in the AZ (8 d) compared with the IL-2RAb (9 d), T cell (10 d), and none (10 d) groups (p < 0.0001). There are no differences in patient, pancreas or renal allograft survival using AZ induction. AZ may confer an advantage in the perioperative period as evidenced by a decreased hospital length of stay. However, this benefit may be lost due to more frequent rehospitalizations.

Extended pancreas donor program – the EXPAND study rationale and study protocol

BackgroundSimultaneous pancreas kidney transplantation (SPK), pancreas transplantation alone (PTA) or pancreas transplantation after kidney (PAK) are the only curative treatment options for patients with type 1 (juvenile) diabetes mellitus with or without impaired renal function. Unfortunately, transplant waiting lists for this indication are increasing because the current organ acceptability criteria are restrictive; morbidity and mortality significantly increase with time on the waitlist. Currently, only pancreas organs from donors younger than 50 years of age and with a body mass index (BMI) less than 30 are allocated for transplantation in the Eurotransplant (ET) area. To address this issue we designed a study to increase the available donor pool for these patients.Methods/DesignThis study is a prospective, multicenter (20 German centers), single blinded, non-randomized, two armed trial comparing outcome after SPK, PTA or PAK between organs with the currently allowed donor criteria versus selected organs from donors with extended criteria. Extended donor criteria are defined as organs procured from donors with a BMI of 30 to 34 or a donor age between 50 and 60 years. Immunosuppression is generally standardized using induction therapy with Myfortic, tacrolimus and low dose steroids. In principle, all patients on the waitlist for primary SPK, PTA or PAK are eligible for the clinical trial when they consent to possibly receiving an extended donor criteria organ. Patients receiving an organ meeting the current standard criteria for pancreas allocation (control arm) are compared to those receiving extended criteria organ (study arm); patients are blinded for a follow-up period of one year. The combined primary endpoint is survival of the pancreas allograft and pancreas allograft function after three months, as an early relevant outcome parameter for pancreas transplantation.DiscussionThe EXPAND Study has been initiated to investigate the hypothesis that locally allocated extended criteria organs can be transplanted with similar results compared to the currently allowed standard ET organ allocation. If our study shows a favorable comparison to standard organ allocation criteria, the morbidity and mortality for patients waiting for transplantation could be reduced in the future.Trial registrationTrial registered at: NCT01384006

Clinically Significant Peripancreatic Fluid Collections After Simultaneous Pancreas-Kidney Transplantation

Peripancreatic fluid collections (PPFC) are a serious complication after simultaneous pancreas-kidney transplantation (SPKTx). Retrospective study for all 223 SPKTx performed from December 8, 1996, to October 10, 2011, to evaluate the risk factors (RF) and impact of PPFCs on outcomes was conducted. Clinically significant PPFCs were seen in 36 (16%) cases, all within 3 months after transplantation. Radiologic drainage resolved 2 (6%) cases, and 34 required laparotomy (mean [SD], 4 [7]). Compared with the non-PPFC group (n=186), the PPFC group had similar patient and total kidney graft survivals but significantly lower total pancreas survival (68% vs. 85%) and greater incidence of infections (75% vs. 46%, all P<0.05) at 5 years. PPFCs were associated with early graft pancreatitis in 18 (50%), pancreatic fistula in 20 (56%, 9 with obvious duodenal stump leak) and infection in the collection in 20 (56%) cases. Comparison of PPFCs with pancreas graft loss to the PPFCs with surviving grafts showed that the incidence of pancreatic fistula was greater in the former (90% pancreas graft loss vs. 42% pancreas graft survival, P<0.01). Binary logistic regression analysis of RF for developing PPFC showed a donor age >30 years to be significant (P=0.03; odds ratio, 3.4; confidence interval, 1.1-10.5) and a trend of association with donor body mass index >30 and pancreas cold ischemia time greater than 12 hr. PPFCs are associated with significant reduction in pancreas allograft survival and impact resource use. Donor age >30 years is a significant RF for their development. PPFCs associated with pancreatic fistula carry a greater risk for pancreas graft loss.

Acute Pancreas Allograft Rejection Is Associated With Increased Risk of Graft Failure in Pancreas Transplantation

The effect of acute allograft rejection (AR) on long-term pancreas allograft function is unclear. We retrospectively studied 227 consecutive pancreas transplants performed at our institution between January 1, 998 and December 31, 2009 including: 56 simultaneous pancreas and kidney (SPK), 69 pancreas transplantation alone (PTA); and 102 pancreas after kidney (PAK) transplants. With a median follow-up of 6.1 (IQR 3-9) years, 57 patients developed 79 episodes of AR, and 19 experienced more than one episode. The cumulative incidence for AR was 14.7%, 19.7%, 26.6% and 29.1% at 1, 2, 5 and 10 years. PTA transplant (hazards ratio [HR]=2.28, p=0.001) and donor age (per 10 years) (HR=1.34, p=0.006) were associated with higher risk for AR. The first AR episode after 3 months post PT was associated with increased risk for complete loss (CL) (HR 3.79, p<0.001), and the first AR episode occurring during 3- to 12-month and 12- to 24-month periods after PT were associated with significantly increased risk for at least partial loss (PL) (HR 2.84, p=0.014; and HR 6.25, p<0.001, respectively). We conclude that AR is associated with increased risk for CL and at least PL. The time that the first AR is observed may influence subsequent graft failure.