Solitary Pancreas Transplantation Research Articles

316.8: Early graft loss in solitary pancreas transplant recipients within Eurotransplant

316.8: Early graft loss in solitary pancreas transplant recipients within Eurotransplant

Analysis of Individual Components of Frailty in Simultaneous Pancreas and Kidney, and Solitary Pancreas Transplant Recipients.

It is not known which of the 5 components of the Fried frailty score have the most predictive value for outcomes in simultaneous pancreas-kidney transplant (SPK) and solitary pancreas transplant (SPT) recipients. In this study, we sought to investigate the association between pretransplant overall frailty and individual frailty components, with posttransplant outcomes among SPK and SPT recipients. Outcomes of interest were length of stay, kidney delayed graft function (K-DGF), readmission within 30 d after discharge, cardiovascular events, acute rejection, pancreas death-censored graft failure (DCGF), kidney DCGF, and death. Of the individual frailty components among SPK (n = 113), only slow walk time was associated with an increased risk of mortality (adjusted odds ratio [aOR]: 4.99; P = 0.03). Among SPT (n = 49), higher sum frailty scores (coefficient correlation 0.29; P = 0.04) and weight loss (coefficient correlation = 0.30; P = 0.03) were associated with prolonged length of stay. Similarly, weight loss among SPT was associated with an increased risk of DCGF (aOR: 4.34; P = 0.049). Low grip strength was strongly associated with an increased risk of early readmission (aOR: 13.08; P = 0.008). We found that not all components of frailty contribute equally to predicting outcomes. Objective measurements of slow walk time, unintentional weight loss, and low grip strength were found to be associated with less optimal outcomes in pancreas transplant recipients. Targeted interventions may improve posttransplant outcomes.

The 2022 International Pancreas Transplant Registry Report—A Review

Over the last decades, the number of pancreas transplants has increased all over the world. Since the first pancreas transplant in 1966, patient and graft survival after simultaneous pancreas and kidney as well as after solitary pancreas transplantation have improved significantly. Patient survival at 1 year is >96% in all 3 recipient categories and pancreas graft survival is >90% for simultaneous pancreas and kidney and >86% for solitary transplants. For transplants performed between 2001 and 2010, with >10 years' follow-up time, the half-life (50% graft function) was 13 years for simultaneous pancreas and kidney, almost 10 years for a pancreas after kidney transplant, and >6 years for a pancreas transplant alone. These excellent results are even more astonishing because more high-risk patients were transplanted. The main reasons for improvement in outcome were reductions in technical failures and immunologic graft losses. These decreases were due to better patient and donor selection, standardization of surgical techniques, and superior immunosuppressive protocols.

110-OR: Excellent Outcome of Solitary Pancreas Transplant Recipients with Brittle Diabetes and without Advanced Nephropathy

Introduction: In contrast to non-pancreatic transplantation, where nephrologists refer patients for kidney and hepatologists for liver transplantation, endocrinologists only rarely refer patients with brittle diabetes for solitary pancreas transplantation. While most pancreas transplants are performed in combination with a kidney graft, solitary pancreas transplants (PTA) without a previous kidney transplant accounted for only 6-7% of pancreas transplants per year although a PTA is the best treatment option to achieve long-term insulin-independence in patients with severe brittle diabetes. Methods: The change in demographics and outcome of 1,636 primary PTAs were analyzed between 20 and 2020 in 5-year intervals. Graft survival was defined as complete insulin-independence. Multivariate analysis was performed to assess factors that impacted outcome and the potential need for a subsequent kidney transplant. Results: Over time, recipient age increased, but donor age and preservation time decreased significantly. Most recipients received induction therapy and maintenance immunosuppression. These changes resulted in significant improvement in patient and pancreas graft survival. Three-year patient survival increased from 92% in 2001-to 96% in 2016-20. Three-year pancreas graft survival improved from 60% in 2001-to 77% in 2016-20 (p<0.0001) . The most influential factors for this decrease were older recipient age and better immunosuppression. The rate of a subsequent kidney transplant declined significantly. It was primarily contingent on native graft function at the time of transplant. If the GFR was as >70ml/min only 1% of patients required a kidney graft. Conclusion: The results of PTA have significantly improved over the past 20 years. A PTA should be strongly considered in brittle diabetic patients before the development of advanced nephropathy. Disclosure A.Gruessner: None.

The Presence of Donor-specific Antibodies Around the Time of Pancreas Graft Biopsy With Rejection Is Associated With an Increased Risk of Graft Failure.

Donor-specific antibodies (DSA) against HLA are an important biomarker predicting graft injury, rejection (Rej), and failure in various solid-organ transplant recipients. However, the impact of DSA with or without histopathological evidence of rejection among pancreas transplant recipients (PTRs) is unknown. In this study, we included all PTRs at our center between 2005 and 2020, with pancreas allograft biopsy before March 31, 2021, and with DSA checked within 15 d of the biopsy. PTRs were divided into 4 groups based on the biopsy findings on the index biopsy and DSA status as Rej-/DSA-, Rej+/DSA-, Rej-/DSA+, and Rej+/DSA+. Two hundred two PTRs had a pancreas allograft biopsy during the study period. Thirty-nine were in Rej-/DSA-, 84 Rej+/DSA-, 24 Rej-/DSA+, and 55 Rej+/DSA+. The mean interval from transplant to index biopsy was not statistically different between the 4 groups. The most common type of rejection was T cell-mediated rejection; however, antibody-mediated rejection was more prevalent in the Rej+/DSA+ group. At 5 y postbiopsy, the rate of death-censored graft failure (DCGF) for Rej-/DSA- was 18%, 24% in Rej+/DSA-; 17% in Rej-/DSA+ and 36% in Rej+/DSA+ (P = 0.14). In univariate analysis, mixed rejection (hazard ratio [HR], 3.0; 95% confidence intervals [CI], 1.22-7.39; P = 0.02) along with solitary pancreas transplantation and Rej+/DSA+ were associated with DCGF. In multivariate analysis, compared with Rej-/DSA-, Rej+/DSA+ was significantly associated with DCGF (HR, 2.32; 95% CI, 1.03-5.20; P = 0.04); however, Rej+/DSA- was not (HR, 1.06; 95% CI, 0.32-3.56; P = 0.92). PTRs with pancreas allograft rejection and concomitant DSA have an increased risk of DCGF.

Pancreas transplantation from donors after cardiac death – The US experience

IntroductionSince the beginning of pancreas transplantation, the rate of donation after cardiac (or circulatory) death (DCD) accounts for only 3% of all transplants in the US. This is the result of perceived higher complication rates and overall worse outcome with DCD donors. Such misconceptions and an increased demand for deceased donor (DD) organs warrant a systematic review of the use of DCD compared with donation after brain death (DBD) pancreata to objectively assess DCD outcome after pancreas transplantation in the US. MethodsAll 22,160 DD pancreas transplants performed in diabetic patients between 1/1/2001 and 12/31/2020 were included in this analysis. To assess changes in outcomes, patient and graft survival was computed using the Kaplan-Meier method in 5-year intervals. Comprehensive univariate and multivariable comparisons of posttransplant complications and patient and pancreas and kidney graft survival between DCD and DBD pancreas transplants were performed to assess the donor impact. ResultsIn the US over the past 20 years most DCD donors were used for simultaneous pancreas and kidney (SPK) transplants and less often for solitary pancreas transplants. DCD transplants never accounted for more than 4% per year of all pancreas transplants. A comparison of the pancreas donor risk index (pDRI) between DCD and DBD pancreata showed that the only distinguishing factor was DCD donation. SPK patient, pancreas, and kidney graft survival for DCD donors did not change significantly over time. One- and 3 -year DCD patient survival reached 96% and 93%, pancreas graft survival 90% and 84%, and kidney graft survival 96% and 91%, respectively. For the last decade, no differences in patient and graft survival between DCD and DBD donors were detected (P > 0.67). The relative risk for the use of a DCD donor was not increased (P > 0.6). Influential risk factors were older donor and recipient age as well as longer preservation times. Larger transplant center accepted DCD donors more frequently and showed better outcome. While the rate of early pancreas complications was the same for DCD vs. DBD transplants, delayed kidney graft function was significantly higher in DCD kidneys secondary to more long-distance shipping across the country. The multivariable analysis showed a 4-times higher rate in delayed graft function. Longer cold preservation time and older donor age further increased the risk of graft failure. The use of machine perfusion of the kidney graft reduced the relative risk of delayed graft function by 50%. SummaryThe use of DCD donor organs in pancreas transplantation is not associated with higher failure or complication rates in the US. A pancreas offer from a DCD donor should not be the sole reason to decline the organ for transplantation. Careful selection of specific donor and recipient factors, as well as advanced preservation techniques are essential for good outcome.

208.8: Experience of 91 Pancreas Retransplants and Predictors of Outcome

Pancreas retransplantation(PRT) activity has declined in recent years mirroring the tendency of overall numbers of pancreas transplantation(PT). This study aimed to analyze our experience with PRT over a 25-year program searching for reliable predictors of outcome. Donor and recipient characteristics and outcomes data were retrospectively gathered from our databank. An in-depth analysis of PRT and previous PT was performed. Sensitization was considered either if an increase of 20% in cPRA occurred or by appearance of anti-DQs. An induction with Thymoglobulin(7mg/kg) associated to tacrolimus, mycophenolate sodic and steroids was the immunosuppression regimen for all PRT. From November/2000 to June/2021, 1,018 PT were performed, being 91 PRT(8.9%). Mean donor and recipient ages were 23.7(11–44) and 37.1(22–62) years and cause of donor death was cerebrovascular in 17(18.6%). PRT categories included Re-PAK in 79(87%) and Re-PTA in 12(13%) cases. PRTs were second PT in 83(91%) and third PT in 8(9%). Cause of previous graft loss(CPGL) was technical in 40(44%), immunological in 47(52%) and other in 4(4%). Timing of previous graft loss was early(< 3 months) in 48(53%) and late in 43(47%). The mean time interval from previous PT to PRT was 48.6 months(4–241) being significantly lower whether CPGL was technical compared to immunological(21.8 x 71.6 months, p<0.001). The technical strategy for PRT was a different approach(either for exocrine or venous drainage) in 80 cases(88%) searching for a new and more virgin surgical site. The need of previous graft transplantectomy before or during PRT differed significantly being 100% for technical CPGL and 45% for immunological CPGL(p<0.001). Mean cold ischemia time for PRT was 12.2 hours(7.1–19.1h) and reoperations were required in 21% of the patients.1-year patient survival was similar between PRT and a control cohort of 365 primary solitary PT(91.2% x 92.1%,p=0.83) and also was 1-year pancreas graft survival(69.2% x 72.9%, p=0.51). 1-year patient survival for PRT was also similar according to technical or immunological CPGL(92.5% x 89.4%,p=0.72). There was a tendency of higher pancreas graft survival after PRT for technical vs immunological CPGL(72.5% x 66%, p=0.64). When subcategorized the group with immunological CPGL for early(< 5 years) and late(>5 years) immunological loss, there was a tendency of higher 1-year pancreas graft survival for the latter(84.6%) compared to technical (72.5%) or early immunological CPGL(58.8%, p=0.20).Sensitization after primary PT determined inferior 1-year pancreas graft survival in PRT compared to non-sensitized patients(44.4% x 79.7%, p=0.002). PRT has achieved similar patient and pancreas graft survivals to primary solitary PT. Early immunological CPGL and sensitization may represent a predictor of inferior outcome after PRT.

208.1: The Presence of Donor-specific Antibodies Around the Time of Pancreas Graft Biopsy With Rejection Is Associated With an Increased Risk of Graft Failure

Introduction: Donor-specific antibodies (DSA) against human leukocyte antigen (HLA) are an important biomarker predicting graft injury, rejection (Rej), and failure in various solid organ transplant recipients. However, the impact of DSA with or without Rej among pancreas transplant recipients (PTRs) is unknown. Method: In this study, we included all PTRs who had undergone either simultaneous pancreas-kidney or solitary pancreas transplant at our center between 2005 and 2020, with pancreas allograft biopsy before 03/2021, and with DSA checked within 15 days of the biopsy. Among PTRs with multiple biopsies during the study period, the first index biopsy was used to analyze the data. Pancreas biopsies at the time of implant or explant were excluded, as were biopsies with no pancreas tissue present. PTRs were divided into four groups based on the biopsy findings on the index biopsy and DSA status as Rej-/DSA-; Rej+/DSA-; Rej-/DSA+ and Rej+/DSA+. Results: A total of 352 pancreas allograft biopsies were performed in 203 PTRs during the study period. Of these, 203 PTRs, 41 were in Rej-/DSA-; 87 Rej+/DSA-; 24 Rej-/DSA+; and 51 Rej+/DSA+. Most of the baseline characteristics were similar between the groups, except PTRs in Rej-/DSA+ and Rej+/DSA+ were relatively younger, with a mean age of 39 compared to 43 for the other two groups. The mean interval from transplant to index biopsy was not statistically different between the four groups. The most common rejection was TCMR, however, AMR was more prevalent in the Rej+/DSA+ group. In addition, DSA against class II HLA was more prevalent in the DSA+/Rej + group. There was no statistical difference in the mean post index biopsy follow-up. At last follow up, the rate of death censored graft failure (DCGF) for Rej-/DSA- was 22%, 29% in Rej+/DSA-; 17% in Rej-/DSA+ and 39% in Rej+/DSA+. Although not statistically significant, there was a trend towards inferior pancreas graft survival in Rej+/DSA+ group by unadjusted K-M survival analysis (Figure 1).In multivariable analysis compared to Rej-/DSA-, Rej+/DSA+ was significantly associated with DCGF (HR: 2.25, 95% CI: 1.02 to 4.97; p=0.04), however Rej+/DSA- was not (HR: 1.40; 95% CI: 0.65 to 3.0; p=0.39). Conclusions: PTRs with pancreas allograft rejection in the presence of DSA have an increased risk of DCGF, and may warrant particularly aggressive management.

P.151: A Comparative Analysis of IGL-1 Versus HTK Solution in Pancreas Transplantation

Georges Lopez Institute(IGL-1) is a relatively new preservation solution used for static cold storage of abdominal organs. Although the use of IGL-1 in liver or kidney transplantation is more established, there are limited data regarding its use in pancreas transplantation(PT). The aim of this study was to analyze our experience with IGL-1 in PT. In a retrospective analysis, data from 186 PT performed from jan/2019 to June/2021, being 121 SPK and 65 solitary PT(S-PT) were reviewed. The use of HTK(n=104) and IGL-1(n=82) solution was stratified into two groups. The profile of donors and recipients, post-transplant(PO) pancreatic enzymes and outcomes were compared. There were no significant differences between HTK and IGL-1 groups regarding recipient race, age(34.4 x 35.7 years),gender, cerebrovascular cause of donor death(24% x 23.2%), pancreas(8.2 x 8.0h) and kidney(9.5 x 9.3h) cold ischemia time and distribution of SPK/S-PT(59.6%/40.4% x 71.9%/28.1%). Donor age(26.0 x 29.7 years,p=0.002) and use of duodenal drainage(0.96% x 47.6%,p<0.001) were significantly different between HTK and IGL-1 group, respectively. Peak Amylase(379 x 364 UI/ml) and Lipase(364 x 271UI/ml) and PO day 5 Amylase(159 x 148UI/ml) and Lipase(95 x 83UI/ml) were similar between groups. However, peak amylase from drain fluid was higher in HTK group(3869 x 2333 UI/ml, p=0.045). Mean hospital stay(7.8 x 8.0 days), time with abdominal drain(10.5 x 11.4 days) and kidney DGF(45.2% x 52.5%) for SPK were also similar between HTK and IGL-1 groups, respectively. There was a tendency of better 1-year patient survival (89% x 81.7%,p=0.167) and significant higher 1-year pancreas(82.9% x 68.3,p=0.022) and kidney(89.8% x 74.2%,p=0.026) graft survivals for the IGL-1 group. The IGL-1 group was also followed by lower rate of early reoperations (8.5% x 19.2%, p=0.04), technical failure(7.3% x 17.3%,p=0.047) and death related to technical issues(2.4% x 10.6%, p=0.031). IGL-1 seems to be superior to HTK solution for pancreas preservation and achieved better outcomes particularly regarding technical issues.

Impact of Recipient Age on Outcomes After Pancreas Transplantation

Few reports have provided the ages of pancreas transplant recipients. The aim of this study was to determine whether recipient age affects survival of pancreatic grafts after transplantation. We analyzed 73 patients who had undergone pancreas transplantation at our institution from August 2001 to March 2020 and assessed the effects of recipient age on pancreas graft survival within 5 years after pancreas transplantation. The cutoff value for recipient age established by receiver operating characteristic curve was 35 years. The pancreas graft survival rate of recipients aged 35 years or younger (1, 3, and 5 years: 72.9%, 41.7%, and 41.7%, respectively) was significantly lower than that of recipients aged over 35 years (1, 3, and 5 years: 93.2%, 88.4%, and 88.4%, respectively). Multivariate Cox hazard regression analysis showed that recipient age 35 years or younger (hazard ratio=3.60; 95% confidence interval, 1.04-12.50; P=.044) and solitary pancreas transplantation (hazard ratio=10.72; 95% confidence interval, 2.72-42.28; P < .001) were significant risk factors for pancreas graft loss within 5 years. Our data suggest that younger recipient age is a risk factor for pancreas graft loss after transplantation.

Alloimmunity in pancreas transplantation.

Despite significant improvement in pancreas allograft survival, rejection continues to be a major clinical problem. This review will focus on emerging literature related to the impact of pretransplant and de-novo DSA (dnDSA) in pancreas transplant recipients, and the diagnosis and treatment of T-cell-medicated rejection (TCMR) and antibody-mediated rejection (ABMR) in this complex group of patients. Recent data suggest that pretransplant DSA and the emergence of dnDSA in pancreas transplant recipients are both associated with increased risk of ABMR. The pancreas allograft biopsy is essential for the specific diagnosis of TCMR and/or ABMR, distinguish rejection from other causes of graft dysfunction, and to guide-targeted therapy. This distinction is important especially in the setting of solitary pancreas transplants but also in simultaneous pancreas-kidney transplants where solid evidence has now emerged demonstrating discordant biopsy findings. Treatment of rejection in a functioning pancreas can prolong allograft survival. The accurate and timely diagnosis of active alloimmune destruction in pancreas transplant recipients is paramount to preserving graft function in the long term. This review will discuss new, rapidly evolving information that is valuable for the physician caring for these patients to achieve optimal immunological outcomes.

Fence Angioplasty Prevents Narrowing of Venous Anastomosis in Solitary Pancreas Transplant.

BackgroundGraft thrombosis is the leading cause of early graft failure in pancreas transplants. Direct anastomosis grafting of the portal vein to the iliac vein or vena cava generally appears narrowed on postoperative computed tomography (CT) scans. However, modification of surgical techniques may prevent venous narrowing, which also prevents thrombosis-related graft failure.Material/MethodsWe performed 31 solitary pancreas transplants since 2015. Retrospective analysis of these patients was performed.ResultsFence angioplasty was applied in the final 12 cases, and no technical failures or early graft losses occurred in these cases. Three graft losses, including 2 immunologic losses and 1 patient death with functioning graft, occurred after at least postoperative 4 months. The venous anastomoses were evaluated via intraoperative Doppler ultrasound and postoperative CT scans. Intraoperative Doppler ultrasound revealed improved spectral waves of venous anastomoses in the fence group (monophasic spectral wave, 42.9% vs. 0%, p=0.017). The fence-graft applied group had no cases of narrowing, whereas the non-fence group had high narrowing rates on CT scans (84.2% vs. 0%, p<0.001). Furthermore, with less use of postoperative heparin, postoperative bleeding rates were lower in the fence group (36% vs. 0%, p=0.026).ConclusionsFence angioplasty is a definitive method for avoiding venous anastomotic stenosis and preventing graft failure due to thrombosis.

Graft dysfunction in simultaneous pancreas kidney transplantation (SPK): Results of concurrent kidney and pancreas allograft biopsies.

Simultaneous pancreas and kidney transplants offer significant therapeutic advantages but present a diagnostic approach dilemma in the diagnosis of rejection. Because both organs are from the same donor, the kidney has been treated traditionally as the "sentinel" organ to biopsy, presumably representing the status of both allografts. Truly concurrent biopsy studies, however, are needed to confirm this hypothesis. We examined 101 concurrent biopsies from 70 patients with dysfunction in either or both organs. Results showed concurrent rejection in 23 of 57 (40%) of cases with rejection; 19 of 57 (33.5%) and 15 of 57 (26.5%) showed kidney or pancreas only rejection, respectively. The degree and type of rejection differed in the majority (13 of 23, 56.5%) of cases with concurrent rejection, with the pancreas more often showing higher rejection grade. Taking into account pancreas dysfunction, a positive kidney biopsy should correctly predict pancreas rejection in 86% of the instances. However, the lack of complete concordance between the 2 organs, the discrepancies in grade and type of rejection, and the tendency for higher rejection grades in concurrent or pancreas only rejections, all support the rationale for pancreas biopsies. The latter provide additional data on the overall status of the organ, as well as information on nonrejection-related pathologies.

In-Hospital Cardiovascular Complications After Pancreas Transplantation in the United States from 2003 to 2012

Large database studies detailing the risk of perioperative cardiovascular complications after pancreas transplant has been limited, perhaps because these outcomes are not captured by transplant registries. Greater data on the incidence and risks of such outcomes could provide additional insight for referring physicians and inform potential recipients of their risk. We performed a serial, cross-sectional analysis of the National Inpatient Sample, the largest publicly available inpatient database in the United States, to assess for the risk of cardiovascular complications after pancreas transplants in the United States from 2003 to 2012 (n= 13,399). Using multivariable logistic regression models, the risk of cardiovascular outcomes after simultaneous pancreas-kidney transplants (SPK) was compared with solitary pancreas transplants (pancreas after kidney and pancreas transplant alone [PAK+ PTA]). The unadjusted prevalence of in-hospital cardiovascular complications was higher in SPK than PAK+ PTA (5.5% vs 3.7%, p <0.001). After multivariable adjustment, SPK remained associated with significantly higher odds of any cardiovascular complication (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.21 to 1.80, p= 0.01), and particularly stroke (OR 13.41, 95% CI 4.78 to 37.63, p <0.001), compared with PAK+ PTA. However, there was no difference in perioperative mortality (OR 0.78, 95% CI 0.54 to 1.12, p= 0.18). In conclusion, these findings highlight the association between uremia and stroke in pancreas transplant patients, as well as the need for improved preoperative cardiac risk assessment and perioperative management, especially in those who underwent SPK.

Current outcomes in islet versus solid organ pancreas transplant for β-cell replacement in type 1 diabetes.

With continued optimization of islet isolation and immunosuppression protocols, the medium-term rates of insulin independence following islet transplantation have improved significantly. This review evaluates the most up-to-date outcomes data for both solid organ pancreas and islet transplantation to develop an algorithm for selection of β-cell replacement in type 1 diabetes patients. Solid organ pancreas and islet transplantation have both displayed improved rates of 5-year insulin independence, largely attributable to improvements in immunosuppressive regimens. The medium-term rates of insulin independence following islet transplantation in highly selected type 1 nonuremic diabetic recipients is beginning to approach the success rates observed following solitary pancreas transplantation. Although pancreas transplantation has historically been favored for β-cell replacement, current outcomes following islet transplantation justify the use of this minimally invasive therapy in carefully selected patients. Pancreas transplant remains the procedure of choice for β-cell replacement in uremic patients. Islet transplantation should be considered in nonuremic patients with low BMI and low insulin requirements, patients lacking the cardiovascular reserve to undergo open abdominal surgery, or patients who elect to forego the risks of a major operation in exchange for an increased risk of islet graft failure.

Pancreas transplantation in older patients is safe, but patient selection is paramount.

Pancreas transplant outcomes have progressively improved. Despite this, some centers have continued to employ historical age limits for pancreas transplant candidates. We sought to determine the importance of chronological age in determining patient and graft survival rates after pancreas transplantation. A single-center, retrospective study of adult, deceased donor simultaneous pancreas and kidney (SPK) and solitary pancreas transplants (SP, including pancreas transplant alone and pancreas after kidney transplants) in recipients ≥55years (55+), occurring between July 1, 1999, and June 30, 2012, was performed. Seven-hundred and forty patients underwent pancreas transplantation, of which 28 patients were 55+. Patient survival was comparable for younger and older pancreas transplant recipients. Both non-death-censored and death-censored pancreatic graft survival rates were similar in younger and in older patients. Patients aged 45-54 and those aged 55+ had more frequent cardiovascular events than younger pancreas transplant recipients. There was no difference in renal graft survival for SPK patients when compared with diabetic kidney transplant alone recipients aged 55years and older. Older pancreas transplant recipients had acceptable long-term patient and graft survival rates, although complications may occur. Chronological age alone should not exclude a patient for pancreas transplant candidacy.

Long-term Outcomes for Living Pancreas Donors in the Modern Era.

Living donor segmental pancreas transplants (LDSPTx) have been performed selectively to offer a preemptive transplant option for simultaneous pancreas-kidney recipients and to perform a single operation decreasing the cost of pancreas after kidney transplant. For solitary pancreas transplants, this option historically provided a better immunologic match. Although short-term donor outcomes have been documented, there are no long-term studies. We studied postdonation outcomes in 46 segmental pancreas living donors. Surgical complications, risk factors (RF) for development of diabetes mellitus (DM) and quality of life were studied. A risk stratification model (RSM) for DM was created using predonation and postdonation RFs. Recipient outcomes were analyzed. Between January 1, 1994 and May 1, 2013, 46 LDSPTx were performed. Intraoperatively, 5 (11%) donors received transfusion. Overall, 9 (20%) donors underwent splenectomy. Postoperative complications included: 6 (13%) peripancreatic fluid collections and 2 (4%) pancreatitis episodes. Postdonation, DM requiring oral hypoglycemics was diagnosed in 7 (15%) donors and insulin-dependent DM in 5 (11%) donors. RSM with three predonation RFs (oral glucose tolerance test, basal insulin, fasting plasma glucose) and 1 postdonation RF, greater than 15% increase in body mass index from preoperative (Δ body mass index >15), predicted 12 (100%) donors that developed postdonation DM. Quality of life was not significantly affected by donation. Mean graft survival was 9.5 (±4.4) years from donors without and 9.6 (±5.4) years from donors with postdonation DM. LDSPTx can be performed with good recipient outcomes. The donation is associated with donor morbidity including impaired glucose control. Donor morbidity can be minimized by using RSM and predonation counseling on life style modifications postdonation.

Beta-cell replacement therapy: current outcomes and future landscape.

This article provides a summary of the current outcomes of β-cell replacement strategies, an algorithm for choosing a specific modality while highlighting associated advantages and disadvantages, and outlines remaining challenges and areas of active investigation in β-cell replacement therapy. The most recent reports of islet cell allotransplantation have shown improvements over previous eras and now rival some outcomes of pancreas alone transplantation. Active areas of investigation are focused on improving techniques for islet isolation, graft monitoring, and managing challenges posed by the innate and alloimmune systems. Patients with insulin-dependent diabetes who continue to experience life threatening hypoglycemia despite maximal medical management can benefit from β-cell replacement. Emerging nontransplant technologies have not provided a physiologic euglycemic state to the extent offered by transplantation. Islet transplantation eliminates hypoglycemic episodes/unawareness, facilitates normalization of hemoglobin A1c (HbA1c), decreases microvascular disease progression, and improves quality of life for patients with problematic diabetes. Mid- and long-term outcomes of islet transplantation performed at expert centers approximate those of registry reports of solitary pancreas transplant, whereas the complication profile is quite favorable.

Solitary pancreas transplantation: a review of the UK experience over a period of 10 yr.

The aim of this study was to see whether lessons could be learned from the prospectively maintained nationwide database on solitary pancreas transplantation (SPTx) performed in the UK. Two hundred and forty-five SPTx were utilized from the 2004-2013 period (113 pancreas transplant alone and 132 pancreas after kidney). The statistical analysis included donor, recipient, transplant variables, and the effect of a rejection episode on graft survival. Cold ischemia time (CIT), CIT > 12 h, donor body mass index (BMI) > 30, and non-lymphocyte-depleting induction immunosuppression achieved p-value <0.05 in the unadjusted univariate hazard model analysis. In a multivariate analysis, variables that persisted in demonstrating increased independent risk included CIT > 12 h (hazard ratio [HR] 1.94, p = 0.035) and the use of non-depleting induction immunosuppression (HR 1.95, p = 0.002). Factors such as bladder-drained grafts and donor variables including age, BMI, and donation after cardiac death (DCD) vs. donation after brain-stem death did not attain significance. Rejection reduces the overall graft survival by approximately 1000 d (1841 ± 114 d vs. 915 ± 119 d, p = 0.001). Cold ischemia time <12 h and the use of depleting antibodies as induction immunosuppression have a positive effect on pancreas allograft survival. Other factors such as bladder-drained grafts and donor variables such as age, BMI, and DCD status did not attain significance in a multivariate analysis.

Simultaneous transplantation of the living donor kidney and deceased donor pancreas and other transplant options for diabetic and uremic patients.

Solitary deceased donor kidney and simultaneous pancreas and kidney (SPK) transplantation are the two most common transplant procedures performed for patients with diabetes and uremia, vastly outnumbering all other organ replacement options. Given the improvement in outcomes for solitary pancreas transplantation, the higher mortality for diabetic patients on the waiting list, and the growing shortage of organs (particularly kidneys) for transplantation, the use of living donors for this complex patient population should be more common. Yet, despite some clear advantages, sequential pancreas after live donor kidney transplant and especially the combined procedure, simultaneous pancreas (from a deceased donor) and living donor kidney transplantation are relatively uncommon. Possible reasons for the infrequent use of these options and methods for increasing the use of living donor kidneys for the diabetic and uremic patient are presented.