Intraportal Islet Autotransplantation Independently Improves Quality of Life After Total Pancreatectomy in Patients With Chronic Refractory Pancreatitis.

OBJECTIVE: To determine if islet autotransplantation (IAT) independently improves the quality of life (QoL) in patients after total pancreatectomy and islet autotransplantation (TP-IAT). BACKGROUND: TP-IAT is increasingly being used for intractable chronic pancreatitis. However, the impact of IAT on long-term islet function and QoL is unclear. METHODS: TP-IAT patients at our center >1 year after TP-IAT with ≥1 Short Form-36 QoL measure were included. Patients were classified as insulin-independent or insulin-dependent, and as having islet graft function or failure by C-peptide. The associations of insulin use and islet graft function with QoL measures were analyzed by using a linear mixed model, accounting for time since transplant and within-person correlation. RESULTS: Among 817 islet autograft recipients, 564 patients [median (interquartile range) age: 34 (20, 45) years, 71% female] and 2161 total QoL surveys were included. QoL data were available for >5 years after TP-IAT for 42.7% and for >10 years for 17.3%. Insulin-independent patients exhibited higher QoL in 7 of 8 subscale domains and for Physical Component Summary and Mental Component Summary scores ( P <0.05 for all). Physical Component Summary was 2.91 (SE=0.57) higher in insulin-independent patients ( P <0.001). No differences in QoL were observed between those with and without graft function, but islet graft failure was rare (15% of patients). However, glycosylated hemoglobin was much higher with islet graft failure. CONCLUSIONS: QoL is significantly improved when insulin independence is present, and glycosylated hemoglobin is lower with a functioning islet graft. These data support offering IAT, rather than just performing total pancreatectomy and treating with exogenous insulin.

Progress in individualizing autologous islet isolation techniques for pediatric islet autotransplantation after total pancreatectomy in children for chronic pancreatitis.

Total pancreatectomy with islet autotransplantation is performed to treat chronic pancreatitis in children. Successful islet isolation must address the challenges of severe pancreatic fibrosis and young donor age. We have progressively introduced modifications to optimize enzymatic and mechanical dissociation of the pancreas during islet isolation. We evaluated 2 islet isolation metrics in 138 children-digest islet equivalents per gram pancreas tissue (IEQ/g) and digest IEQ per kilogram body weight (IEQ/kg), using multiple regression to adjust for key disease and patient features. Islet yield at digest had an average 4569 (standard deviation 2949) islet equivalent (IEQ)/g and 4946 (4009) IEQ/kg, with 59.1% embedded in exocrine tissue. Cases with very low yield (<2000 IEQ/g or IEQ/kg) have decreased substantially over time, 6.8% and 9.1%, respectively, in the most recent tertile of time compared to 19.2% and 23.4% in the middle and 34.1% and 36.4% in the oldest tertile. IEQ/g and IEQ/kg adjusted for patient and disease factors improved in consistency and yield in the modern era. Minimal mechanical disruption during digestion, warm enzymatic digestion using enzyme collagenase:NP activity ratio < 10:1, coupled with extended distension and trimming time during islet isolation of younger and fibrotic pediatric pancreases, gave increased islet yield with improved patient outcomes.

Total Pancreatectomy With Intraportal Islet Autotransplantation as a Treatment of Chronic Pancreatitis in Patients With CFTR Mutations.

OBJECTIVES: Chronic pancreatitis (CP) is an infrequent but debilitating complication associated with CFTR mutations. Total pancreatectomy with islet autotransplantation (TPIAT) is a treatment option for CP that provides pain relief and preserves ß-cell mass, thereby minimizing the complication of diabetes mellitus. We compared outcomes after TPIAT for CP associated with CFTR mutations to CP without CTFR mutations. METHODS: All TPIATs performed between 2002 and 2014 were retrospectively reviewed: identifying 20 CFTR homozygotes (cystic fibrosis [CF] patients), 19 CFTR heterozygotes, and 20 age-/sex-matched controls without CFTR mutations. Analysis of variance and χ tests were used to compare groups. RESULTS: Baseline demographics were not different between groups. Postoperative glycosylated hemoglobin and C-peptide levels were similar between groups, as were islet yield and rate of postoperative complications. At 1 year, 40% of CF patients, 22% of CFTR heterozygotes, and 35% of control patients were insulin independent. CONCLUSION: Total pancreatectomy with islet autotransplantation is a safe, effective treatment option for CF patients with CP, giving similar outcomes for those with other CP etiologies.

Significant arterial complications after pancreas transplantation-A single-center experience and review of literature.

Arterial fistulas and pseudoaneurysms are rarely described significant arterial complications associated with pancreas transplantation that sometimes present with herald or catastrophic bleeding. We herein describe our institutional case series with a focus on management and outcomes. Of 2256 pancreas transplants, 24 arterial complications were identified in 23 recipients. Chart review was performed to describe the clinical characteristics, treatments, and outcomes of the complications (pseudoaneurysm, arterial enteric/cystic/ureteric fistula, or arteriovenous fistula). Of these 23 patients, 57% had a failed allograft at the time of the complication. Nine patients underwent primary surgical repair of 10 complications, 13 were treated by endovascular methods, and one patient by medical management. In total, 3 embolized patients rebled, 2 of which had failed allografts prior to treatment. Of those with graft function that were treated by embolization alone, all retained graft function. Diagnosis of arterial complications requires a high degree of suspicion and should involve early systemic angiography to evaluate the pancreatic vasculature. Management can be endovascular or surgical and should be individualized. We report our center's evolution from a predominantly surgical to endovascular approach as a definitive vs stabilizing therapy, with selective coiling mostly reserved for well-defined peripheral lesions in patients with a functioning allograft.

Optimizing outcomes in pancreas transplantation: Impact of organ preservation time.

Recent changes to pancreas graft allocation policy have increased the number of organs available for regional and distant sharing, which results in a corresponding increase in preservation time. We sought to systematically assess the impact of cold ischemia time (CIT) on outcomes post-transplant. A retrospective review of 1253 pancreas transplants performed at a single transplant center was performed to correlate CIT to transplant outcomes. The rate of technical failure (TF) increased with 20+ hours of CIT, with a 2.7-fold to 6.2-fold increased rate of TF for pancreas after kidney (PAK), simultaneous pancreas and kidney (SPK), and pancreas transplants overall. Long-term graft survival was best with <12 hours of CIT; graft failure increased 1.2-fold to 1.4-fold with 12-24 hours of CIT and 2.2-fold with 24+ hours. CIT had less influence on the pancreas transplant alone category than either SPK or PAK and had markedly more influence on grafts from older (age >25 years) and overweight (body mass index >25) donors. In the final analysis, grafts with <12 hours of CIT performed the best overall, and strategies that reduce CIT (such as early allocation, pre-recovery cross-matching, and chartered flights for organs) should be considered whenever possible.

Total Pancreatectomy With Islet Autotransplantation Resolves Pain in Young Children With Severe Chronic Pancreatitis.

OBJECTIVES: Fear of diabetes and major surgery may prohibit referral of young children severely affected by pancreatitis for total pancreatectomy with islet autotransplant (TPIAT). We evaluated outcomes in our youngest TPIAT recipients, 3 to 8 years of age at surgery. METHODS: Medical records were reviewed for 17 children (9 girls) ages 8 years or younger undergoing TPIAT from 2000 to 2014. Most (14/17) had genetic risk factors for pancreatitis. Since 2006, TPIAT recipients were followed prospectively with health questionnaires including assessments of pain and narcotic use, and scheduled hemoglobin A1c (HbA1c) and mixed-meal tolerance tests (6 mL/kg Boost HP) before surgery, and at regular intervals after. Patients are 1 to 11 years post-TPIAT (median 2.2 years). Data are reported as median (25th, 75th percentile). RESULTS: All had relief of pain, with all 17 patients off narcotics at most recent follow-up. Hospitalization rates decreased from 5.0 hospitalization episodes per person-year of follow-up before TPIAT, to 0.35 episodes per person-year of follow-up after TPIAT. Fourteen (82%) discontinued insulin, higher than the observed insulin independence rate of 41% in 399 patients older than 8 years of age undergoing TPIAT over the same interval (P = 0.004). Median post-TPIAT HbA1c was 5.9% (5.6%, 6.3%), and within patient post-TPIAT mean HbA1c was ≤6.5% for all but 2 patients. CONCLUSIONS: Young children with severe refractory chronic pancreatitis may be good candidates for TPIAT, with high rates of pain relief and insulin independence, and excellent glycemic control in the majority.

Long-Term Glycemic Control in Adult Patients Undergoing Remote vs. Local Total Pancreatectomy With Islet Autotransplantation.

OBJECTIVES: Total pancreatectomy with islet autotransplantation (TPIAT) is increasingly performed with remote islet cell processing and preparation, i.e., with islet cell isolation performed remotely from the primary surgical site at an appropriately equipped islet isolation facility. We aimed to determine whether TPIAT using remote islet isolation results in comparable long-term glycemic outcomes compared with TPIAT performed with standard local isolation. METHODS: We performed a retrospective cohort study of adult patients who underwent TPIAT at three tertiary care centers from 2010 to 2013. Two centers performed remote isolation and one performed local isolation. Explanted pancreata in the remote cohort were transported ∼130 miles to and from islet isolation facilities. The primary outcome was insulin independence 1 year following transplant. RESULTS: Baseline characteristics were similar between groups except the remote cohort had higher preoperative hemoglobin A1c (HbA1c; 5.43 vs. 5.25, P=0.02) and there were more females in the local cohort (58% vs. 76%, P=0.049). At 1 year, 27% of remote and 32% of local patients were insulin independent (P=0.48). Remote patients experienced a greater drop in fasting c-peptide (-1.66 vs. -0.64, P=0.006) and a greater rise in HbA1c (1.65 vs. 0.99, P=0.014) at 1-year follow-up. A preoperative c-peptide >2.7 (odds ratio (OR) 4.4, 95% confidence interval (CI) 1.6-14.3) and >3,000 islet equivalents/kg (OR 11.0, 95% CI 3.2-37.3) were associated with one-year insulin independence in the local group. CONCLUSIONS: At 1 year after TPIAT, patients undergoing remote surgery have equivalent rates of long-term insulin independence compared with patients undergoing TPIAT locally, but metabolic control is superior with local isolation.

Evolution of Living Donor Nephrectomy at a Single Center: Long-term Outcomes With 4 Different Techniques in Greater Than 4000 Donors Over 50 Years.

BACKGROUND: The development of minimally invasive surgical approaches to donor nephrectomy (DN) has been driven by the potential advantages for the donor, with questions remaining about long-term outcomes. METHODS: All living DN performed from June 1963 through December 2014 at the University of Minnesota were reviewed. Outcomes were compared among 4 DN techniques. RESULTS: We performed 4286 DNs: 2759 open DN (ODNs), 1190 hand-assisted (HA) laparoscopic DNs (LDNs), 203 pure LDN (P-LDNs), and 97 robot-assisted-LDN. Laparoscopic DN was associated with an older (P < 0.001) and heavier (P < 0.001) donor population. Laparoscopic DN was associated with a higher probability of left kidney procurement (P < 0.001). All 3 LDN modalities required a longer operative time (P < 0.001); robot-assisted-LDN took significantly longer than HA-LDN or P-LDN. Laparoscopic DN decreased the need for intraoperative blood transfusion (P < 0.001) and reduced the incidence of intraoperative complications (P < 0.001) and hospital length of stay (P < 0.001). However, LDN led to a significantly higher rate of readmissions, both short-term (<30 day, P < 0.001) and long-term (>30 day, P < 0.001). Undergoing HA-LDN was associated with a higher rate of an incisional hernia compared with all other modalities (P < 0.001). For recipients, LDN seemed to be associated with lower rates of graft failure at 1 year compared with ODN (P = 0.002). The odds of delayed graft function increased for kidneys with multiple arteries procured via P-LDN compared with HA-LDN (OR 3 [1,10]) and ODN (OR 5 [2, 15]). CONCLUSIONS: In our experience, LDN was associated with decreased donor intraoperative complications and hospital length of stay but higher rates of readmission and long-term complications.

Microbial contamination of transplant solutions during pancreatic islet autotransplants is not associated with clinical infection in a pediatric population.

BACKGROUND/OBJECTIVES: Total pancreatectomy and islet autotransplant (TP-IAT) is a potential treatment for children with severe refractory chronic pancreatitis. Cultures from the resected pancreas and final islet preparation are frequently positive for microbes. It is unknown whether positive cultures are associated with adverse outcomes in pediatric patients. METHODS: We reviewed the medical records of children (n = 86) who underwent TP-IAT from May 2006-March 2015 with emphasis on demographics, previous pancreatic interventions, culture results, islet yield, hospital days, posttransplant islet function, and posttransplant infections. We compared outcomes in patients with positive (n = 57) and negative (n = 29) cultures. RESULTS: Patients with positive cultures had higher rates of previous pancreas surgery (P = 0.007) and endoscopic retrograde cholangiopancreatography (P < 0.0001). Positive cultures were not associated with posttransplant infections (P = 1.00) or prolonged hospital length of stay (P = 0.29). Patients with positive final islet preparation culture showed increased rates of graft failure at 2 years posttransplant (P = 0.041), but not when adjusted for islet mass transplanted (P = 0.39). CONCLUSIONS: Positive cultures during pediatric TP-IATs do not increase the risk of posttransplant infections or prolong hospital length of stay. Endocrine function depends on islet mass transplanted.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Total Pancreatectomy With Islet Autotransplantation Improves Quality of Life in Patients With Refractory Recurrent Acute Pancreatitis.

BACKGROUND & AIMS: Therapeutic options are limited for patients with recurrent acute pancreatitis who have intractable symptoms despite maximal endoscopic and medical treatment, but equivocal or no morphologic or functional evidence of chronic pancreatitis. We performed a prospective observational cohort study to determine the efficacy of total pancreatectomy with islet autotransplantation (TPIAT) for these patients. METHODS: We collected data from all patients undergoing TPIAT at the University of Minnesota from 2007 through 2013; 49 patients (42 female; mean age, 32.8 ± 7.8 years) had a diagnosis of recurrent acute pancreatitis not provoked by intervention, with negative or equivocal findings from nondiagnostic imaging or pancreatic function tests for chronic pancreatitis, and intractable pain between episodes. Data on insulin use, narcotic requirements, pain scores, and health-related quality of life were collected before TPIAT; 3 months, 6 months, and 1 year afterward; and then yearly. RESULTS: All 49 patients studied required narcotics before TPIAT (45 daily users and 4 intermittent users); 2 had insulin-treated diabetes. At 1 year after TPIAT, 22 out of 48 patients (46%) reported no use of narcotic pain medications (P < .001 vs baseline). Health-related quality of life score, measured by the physical and mental component summary score, increased by approximately 1 standard deviation from the population mean (P < .001 for the physical component summary; P = .019 for the mental component summary). At 1 year after TPIAT, 21 out of 48 patients (45%) were insulin independent; their mean percent glycosylated hemoglobin A1c at 1 year after TPIAT was 6.0% ± 0.9% (5.2% ± 0.6% pre-TPIAT). CONCLUSIONS: Patients with recurrent acute pancreatitis but lacking clear chronic pancreatitis benefit from TPIAT, with outcomes similar to those previously described for patients with chronic pancreatitis (improved quality of life and reduced narcotic use). For these patients who have otherwise limited surgical treatment options, TPIAT can be considered when medical and endoscopic therapies have failed.

Evolution of Islet Transplantation for the Last 30 Years.

In this article, we will review the changes that have occurred in islet transplantation at the birth of Pancreas 30 years ago. The first attempts at ß-cell replacement in humans, pancreas and islet transplantation, were performed in the 1960s and 1970s. Although pancreas transplantation has been an accepted treatment for severe labile diabetes predating the emergence of the journal, allogeneic islet transplantation remains experimental. Current investigations within islet transplantation focus to improve islet function after transplantation. Improving islet viability during isolation, exploring ways to increase engraftment, and protection from the host immune system are some of the goals of these investigative efforts. The major barriers to clinical islet transplantation are shortage of human pancreas, the need for immunosuppression, and the inadequacy of the islet isolation process. It is generally accepted that islet encapsulation is an immunoisolation tool with good potential to address the first 2 of those barriers. We have therefore devoted a major part of this review to the critical factors needed to make it a clinical reality. With improved islet isolation techniques and determination of the best site of engraftment as well as improved encapsulation techniques, we hope that islet transplantation could someday achieve routine clinical use.

Factors Predicting Outcomes After a Total Pancreatectomy and Islet Autotransplantation Lessons Learned From Over 500 Cases.

OBJECTIVE: Our objective was to analyze factors predicting outcomes after a total pancreatectomy and islet autotransplantation (TP-IAT). BACKGROUND: Chronic pancreatitis (CP) is increasingly treated by a TP-IAT. Postoperative outcomes are generally favorable, but a minority of patients fare poorly. METHODS: In our single-centered study, we analyzed the records of 581 patients with CP who underwent a TP-IAT. Endpoints included persistent postoperative "pancreatic pain" similar to preoperative levels, narcotic use for any reason, and islet graft failure at 1 year. RESULTS: In our patients, the duration (mean ±â€ŠSD) of CP before their TP-IAT was 7.1 ±â€Š0.3 years and narcotic usage of 3.3 ±â€Š0.2 years. Pediatric patients had better postoperative outcomes. Among adult patients, the odds of narcotic use at 1 year were increased by previous endoscopic retrograde cholangiopancreatography (ERCP) and stent placement, and a high number of previous stents (>3). Independent risk factors for pancreatic pain at 1 year were pancreas divisum, previous body mass index >30, and a high number of previous stents (>3). The strongest independent risk factor for islet graft failure was a low islet yield-in islet equivalents (IEQ)-per kilogram of body weight. We noted a strong dose-response relationship between the lowest-yield category (<2000 IEQ) and the highest (≥5000 IEQ or more). Islet graft failure was 25-fold more likely in the lowest-yield category. CONCLUSIONS: This article represents the largest study of factors predicting outcomes after a TP-IAT. Preoperatively, the patient subgroups we identified warrant further attention.

Islet Oxygen Consumption Rate (OCR) Dose Predicts Insulin Independence in Clinical Islet Autotransplantation.

BACKGROUND: Reliable in vitro islet quality assessment assays that can be performed routinely, prospectively, and are able to predict clinical transplant outcomes are needed. In this paper we present data on the utility of an assay based on cellular oxygen consumption rate (OCR) in predicting clinical islet autotransplant (IAT) insulin independence (II). IAT is an attractive model for evaluating characterization assays regarding their utility in predicting II due to an absence of confounding factors such as immune rejection and immunosuppressant toxicity. METHODS: Membrane integrity staining (FDA/PI), OCR normalized to DNA (OCR/DNA), islet equivalent (IE) and OCR (viable IE) normalized to recipient body weight (IE dose and OCR dose), and OCR/DNA normalized to islet size index (ISI) were used to characterize autoislet preparations (n = 35). Correlation between pre-IAT islet product characteristics and II was determined using receiver operating characteristic analysis. RESULTS: Preparations that resulted in II had significantly higher OCR dose and IE dose (p<0.001). These islet characterization methods were highly correlated with II at 6-12 months post-IAT (area-under-the-curve (AUC) = 0.94 for IE dose and 0.96 for OCR dose). FDA/PI (AUC = 0.49) and OCR/DNA (AUC = 0.58) did not correlate with II. OCR/DNA/ISI may have some utility in predicting outcome (AUC = 0.72). CONCLUSIONS: Commonly used assays to determine whether a clinical islet preparation is of high quality prior to transplantation are greatly lacking in sensitivity and specificity. While IE dose is highly predictive, it does not take into account islet cell quality. OCR dose, which takes into consideration both islet cell quality and quantity, may enable a more accurate and prospective evaluation of clinical islet preparations.

Pediatric Autologous Islet Transplantation.

A total pancreatectomy and islet autotransplant (TPIAT) offers substantial pain relief and improved quality of life for children who are severely affected by chronic or recurrent acute pancreatitis and for whom the usual medical and endoscopic therapies have failed. The pancreas is entirely resected, and the pancreatic islets are isolated from the pancreas and infused back into the patient's liver. Because this is an autologous transplant, no immunosuppression is required. Over several months, the islets engraft in the liver; the patient is then slowly weaned off insulin therapy. Slightly more than 40 % of patients become and remain insulin independent, yet even among patients who remain on insulin, most have some islet function, permitting easier diabetes control. The majority of patients experience pain relief, with significant improvements in health-related quality of life. A TPIAT should be considered for children who are significantly disabled by chronic pancreatitis.

Positive sterility cultures of transplant solutions during pancreatic islet autotransplantation are associated infrequently with clinical infection.

BACKGROUND: Chronic pancreatitis is a painful and often debilitating disease. Total pancreatectomy with intra-portal islet autotransplantation (TP-IAT) is a treatment option that allows for pain relief and preservation of beta-cell mass, thereby minimizing the complication of diabetes mellitus. Cultures of harvested islets are often positive for bacteria, possibly due to frequent procedures prior to TP-IAT, such as endoscopic retrograde cholangiopancreatography (ERCP), stenting, or other operative drainage procedures. It is unclear if these positive cultures contribute to post-operative infections. HYPOTHESIS: We hypothesized that positive cultures of transplant solutions will not be associated with increased infection risk. METHODS: We reviewed retrospectively the sterility cultures from both the pancreas preservation solution used to transport the pancreas and the final islet preparation for intra-portal infusion of patients who underwent TP-IAT between April 2006 and November 2012. Two hundred fifty-one patients underwent total, near-total, or completion pancreatectomy with IAT and had complete sterility cultures. All patients received prophylactic peri-operative antibiotics. Patients with positive pancreas preservation solution or islet sterility cultures received further antibiotics for 5-7 d. Patients' medical records were reviewed for post-operative infections and causative organisms. RESULTS: Of the 251 patients included, 151 (61%) had one or more positive bacterial cultures from the pancreas preservation solution or final islet product. Seventy-three of the 251 patients (29%) had an infectious complication. Thirty-four of the 73 (22%) patients with a post-operative infectious complication also had positive cultures. Only seven of 151 patients with positive cultures (4.7%) had an infectious complication caused by the same organism as that isolated from their pancreas or islet cell preparation. CONCLUSIONS: In autologous islet preparations, isolation solutions frequently have positive cultures, but this finding is associated infrequently with clinical infection.

Outcomes of pancreas retransplantation.

BACKGROUND: Pancreas retransplantation is associated with increased rates of technical failure and rejection compared to other organ transplants. As such, it is not routinely done, and outcomes are mostly known through registry data. Here we analyze the outcomes of primary versus retransplant for all pancreas transplants done in our program over nearly 35 years. METHODS: Donor and recipient characteristics and outcomes data were prospectively gathered and recorded in our institutional database. Outcomes of primary and retransplants were reported overall, and then subgrouped by number (second, third, fourth). An in-depth analysis of transplants done after 2003 was included. Rates of technical failure, 1 year acute rejection, graft survival, and patient survival were compared. RESULTS: Two thousand one hundred forty-five pancreas transplants were performed at our institution between 1978 and 2012. Four hundred fifteen of these were retransplants. Improvements were seen in technical failure rates and graft survival for both primary and retransplants over time. There were no significant differences in technical failure or patient survival for primary versus retransplants overall, or by transplant number (second, third, fourth). Modern era retransplants had more acute rejection in the first year after transplantation. Retransplants (vs primary) had decreased mid-term death censored graft survival. Transplant type continues to be an important driver of outcome. CONCLUSIONS: Retransplant outcomes have improved over time, yet increased rejection and immunologic graft loss rates remain associated with pancreas retransplantation. In contrast, risk of technical failure and patient death for primary versus retransplants are similar. Therefore, pancreas retransplantation in highly selected candidates should be considered in experienced centers.

Assessment of ß-cell mass and α- and ß-cell survival and function by arginine stimulation in human autologous islet recipients.

We used intravenous arginine with measurements of insulin, C-peptide, and glucagon to examine ß-cell and α-cell survival and function in a group of 10 chronic pancreatitis recipients 1-8 years after total pancreatectomy and autoislet transplantation. Insulin and C-peptide responses correlated robustly with the number of islets transplanted (correlation coefficients range 0.81-0.91; P < 0.01-0.001). Since a wide range of islets were transplanted, we normalized the insulin and C-peptide responses to the number of islets transplanted in each recipient for comparison with responses in normal subjects. No significant differences were observed in terms of magnitude and timing of hormone release in the two groups. Three recipients had a portion of the autoislets placed within their peritoneal cavities, which appeared to be functioning normally up to 7 years posttransplant. Glucagon responses to arginine were normally timed and normally suppressed by intravenous glucose infusion. These findings indicate that arginine stimulation testing may be a means of assessing the numbers of native islets available in autologous islet transplant candidates and is a means of following posttransplant α- and ß-cell function and survival.

Temperature profiles of different cooling methods in porcine pancreas procurement.

Porcine islet xenotransplantation is a promising alternative to human islet allotransplantation. Porcine pancreas cooling needs to be optimized to reduce the warm ischemia time (WIT) following donation after cardiac death, which is associated with poorer islet isolation outcomes. This study examines the effect of four different cooling Methods on core porcine pancreas temperature (n = 24) and histopathology (n = 16). All Methods involved surface cooling with crushed ice and chilled irrigation. Method A, which is the standard for porcine pancreas procurement, used only surface cooling. Method B involved an intravascular flush with cold solution through the pancreas arterial system. Method C involved an intraductal infusion with cold solution through the major pancreatic duct, and Method D combined all three cooling Methods. Surface cooling alone (Method A) gradually decreased core pancreas temperature to <10 °C after 30 min. Using an intravascular flush (Method B) improved cooling during the entire duration of procurement, but incorporating an intraductal infusion (Method C) rapidly reduced core temperature 15-20 °C within the first 2 min of cooling. Combining all methods (Method D) was the most effective at rapidly reducing temperature and providing sustained cooling throughout the duration of procurement, although the recorded WIT was not different between Methods (P = 0.36). Histological scores were different between the cooling Methods (P = 0.02) and the worst with Method A. There were differences in histological scores between Methods A and C (P = 0.02) and Methods A and D (P = 0.02), but not between Methods C and D (P = 0.95), which may highlight the importance of early cooling using an intraductal infusion. In conclusion, surface cooling alone cannot rapidly cool large (porcine or human) pancreata. Additional cooling with an intravascular flush and intraductal infusion results in improved core porcine pancreas temperature profiles during procurement and histopathology scores. These data may also have implications on human pancreas procurement as use of an intraductal infusion is not common practice.