Metabolic measures before surgery and long-term diabetes outcomes in recipients of total pancreatectomy and islet autotransplantation

In this single-center, retrospective cohort study, we aimed to elucidate simple metabolic markers or surrogate indices of β-cell function that best predict long-term insulin independence and goal glycemic HbA1c control (HbA1c ≤ 6.5%) after total pancreatectomy with islet autotransplantation (TP-IAT). Patients who underwent TP-IAT (n = 371) were reviewed for metabolic measures before TP-IAT and for insulin independence and glycemic control at 1, 3, and 5 years after TP-IAT. Insulin independence and goal glycemic control were achieved in 33% and 68% at 1 year, respectively. Although the groups who were insulin independent and dependent overlap substantially on baseline measures, an individual who has abnormal glycemia (prediabetes HbA1c or fasting glucose) or estimated IEQs/kg < 2500 has a very high likelihood of remaining insulin dependent after surgery. In multivariate logistic regression modelling, metabolic measures correctly predicted insulin independence in about 70% of patients at 1, 3, and 5 years after TP-IAT. In conclusion, metabolic testing measures before surgery are highly associated with diabetes outcomes after TP-IAT at a population level and correctly predict outcomes in approximately two out of three patients. These findings may aid in prognostic counseling for chronic pancreatitis patients who are likely to eventually need TP-IAT.     

Three-Dimensional Computed Tomographic Volumetric Changes in Pancreas Before and After Living Donor Surgery for Pancreas Transplantation: Effect of Volume on Glucose Metabolism

In the present study, we aimed to compare the pancreas volumetric changes before and after living donor surgery for pancreas transplantation, using three-dimensional (3D) computed tomography (CT) and glucose metabolism. Pancreatic volume (PV) measurement using 3D CT was performed in 13 consecutive donors who underwent distal pancreatectomy for simultaneous living donor pancreas and kidney transplantation. PV was measured using a workstation before and 3 months after living donor operation. As the parameters of glucose metabolism, hemoglobin A1c (HbA1c) level, fasting plasma glucose (FPG) level, body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR), and insulinogenic index (IGI) were examined simultaneously with the PV measurement. The preoperative and postoperative PVs of pancreas was 30 ± 5 mL and 42 ± 9 mL, respectively. The postoperative PV was significantly higher than the preoperative PV (P < .01) and increased by approximately 40% at 3 months after surgery. The postoperative FPG and HbA1c levels were significantly higher than the preoperative values (P < .01). BMI decreased significantly after surgery (P < .01). No differences in HOMA-IR and IGI were noted between before and after surgery. Diabetes mellitus was not observed any of the 13 living donors during this period. Distal pancreatectomy for living donors caused an increase in the PV and maintained insulin resistance, but it was not sufficient to maintain glucose metabolism at the preoperative state.     

Islet damage during isolation as assessed by miRNAs and the correlation of miRNA levels with posttransplantation outcome in islet autotransplantation

High‐quality pancreatic islets are essential for better posttransplantation endocrine function in total pancreatectomy with islet autotransplantation (TPIAT), yet stress during the isolation process affects quality and yield. We analyzed islet‐enriched microRNAs (miRNAs) ‐375 and ‐200c released during isolation to assess damage and correlated the data with posttransplantation endocrine function. The absolute concentration of miR‐375, miR‐200c, and C‐peptide was measured in various islet isolation steps, including digestion, dilution, recombination, purification, and bagging, in 12 cases of TPIAT. Posttransplantation glycemic control was monitored through C‐peptide, hemoglobin A_1c, insulin requirement, and SUITO index. The amount of miR‐375 released was significantly higher during enzymatic digestion followed by the islet bagging (P < .001). Mir‐200c mirrored these changes, albeit at lower concentrations. In contrast, the C‐peptide amount was significantly higher in the purification and bagging steps (P < .001). Lower amounts of miR‐375 were associated with a lower 6‐month insulin requirement (P = .01) and lower hemoglobin A_1c (P = .04). Measurement of the absolute quantity of miRNA‐375 and ‐200c released during islet isolation is a useful tool to assess islet damage. The quantity of released miRNA is indicative of posttransplantation endocrine function in TPIAT patients.     

Low prevalence of diabetes distress following total pancreatectomy with islet autotransplantation

Diabetes distress (DD), or psychological fatigue associated with diabetes management, is common in type 1 and 2 diabetes mellitus and is associated with poor glycemic control. Diabetes distress has never been evaluated in patients undergoing total pancreatectomy with islet autotransplant (TPIAT) for chronic pancreatitis. We analyzed DD after TPIAT in 260 patients (average age 34.3 [standard deviation 15], 75.5% F) undergoing TPIAT between 2006 and 2014. Each patient completed 1 or more diabetes distress scale (DDS) questionnaires from 1 to 7 years post‐TPIAT (631 total). We examined changes in DD over 7 years and also patient characteristics associated with DD 1 year post‐TPIAT (n = 189). One year after TPIAT, 151 of 189 (80%) reported no or low distress (DD<2). Diabetes distress increased over time by an average of 0.084 (SE 0.017) points per year, an average 0.59 point increase from years 1 to 7 (P < .0001). Insulin‐dependent patients had significantly greater DD 1 year post‐TPIAT compared to insulin‐independent patients (P < .0001). Higher DD was associated with poorer glycemic control as indicated by HbA1c (P < .0001). Prevalence of DD is low but increases over time after TPIAT. Insulin dependence and poorer glycemic control are associated with higher levels of DD.     

Purity of islet preparations and 5‐year metabolic outcome of allogenic islet transplantation

In allogenic islet transplantation (IT), high purity of islet preparations and low contamination by nonislet cells are generally favored. The aim of the present study was to analyze the relation between the purity of transplanted preparations and graft function during 5 years post‐IT. Twenty‐four patients with type 1 diabetes, followed for 5 years after IT, were enrolled. Metabolic parameters and daily insulin requirements were compared between patients who received islet preparations with a mean purity <50% (LOW purity) or ≥50% (HIGH purity). We also analyzed blood levels of carbohydrate antigen 19‐9 (CA 19‐9)—a biomarker of pancreatic ductal cells—and glucagon, before and after IT. At 5 years, mean hemoglobin A1c (HbA1c levels) (P = .01) and daily insulin requirements (P = .03) were lower in the LOW purity group. Insulin independence was more frequent in the LOW purity group (P < .05). CA19‐9 and glucagon levels increased post‐IT (P < .0001) and were inversely correlated with the degree of purity. Overall, our results suggest that nonislet cells have a beneficial effect on long‐term islet graft function, possibly through ductal‐to‐endocrine cell differentiation. ClinicalTrial.gov NCT00446264 and NCT01123187.     

Beneficial effect of recombinant rC1rC2 collagenases on human islet function: Efficacy of low‐dose enzymes on pancreas digestion and yield

A high number of human islets can be isolated by using modern purified tissue dissociation enzymes; however, this requires the use of >20 Wunsch units (WU)/g of pancreas for digestion. Attempts to reduce this dose have resulted in pancreas underdigestion and poor islet recovery but improved islet function. In this study, we achieved a high number of functional islets using a low dose of recombinant collagenase enzyme mixture (RCEM‐1200 WU rC2 and 10 million collagen‐degrading activity [CDA] U of rC1 containing about 209 mg of collagenase to digest a 100‐g pancreas). The collagenase dose used in these isolations is about 42% of the natural collagenase enzyme mixture (NCEM) dose commonly used to digest a 100‐g pancreas. Low‐dose RCEM was efficient in digesting entire pancreases to obtain higher yield (5535 ± 830 and 2582 ± 925 islet equivalent/g, P < .05) and less undigested tissue (16.7 ± 5% and 37.8 ± 3%, P < .05) compared with low‐dose NCEM (12WU/g). Additionally, low‐dose RCEM islets retained better morphology (confirmed with scanning electron microscopy) and higher in vitro basal insulin release (2391 ± 1342 and 1778 ± 978 μU/mL; P < .05) compared with standard‐dose NCEM. Nude mouse bioassay demonstrated better islet function for low‐dose RCEM (area under the curve [AUC] 24 968) compared with low‐dose (AUC–38 225) or standard‐dose NCEM (AUC–38 685), P < .05. This is the first report indicating that islet function can be improved by using low‐dose rC1rC2 (RCEM).     

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.     

Utility of arginine stimulation testing in preoperative assessment of children undergoing total pancreatectomy with islet autotransplantation

Metabolic outcomes after total pancreatectomy with islet autotransplantation (TPIAT) are influenced by the islet mass transplanted. Preclinical and clinical studies indicate that insulin and C‐peptide levels measured after intravenous administration of the beta cell secretagogue arginine can be used to estimate the available islet mass. We sought to determine if preoperative arginine stimulation test (AST) results predicted transplanted islet mass and metabolic outcomes in pediatric patients undergoing TPIAT. We evaluated the association of preoperative C‐peptide and insulin responses to AST with islet isolation metrics using linear regression, and with postoperative insulin independence using logistic regression. Twenty‐six TPIAT patients underwent preoperative AST from 2015 to 2018. The acute C‐peptide response to arginine (ACRarg) was correlated with isolated islet equivalents (IEQ; r = 0.59, P = 0.002) and islet number (IPN; r = 0.48, P = 0.013). The acute insulin response to arginine (AIRarg) was not significantly correlated with IEQ (r = 0.38, P = 0.095) or IPN (r = 0.41, P = 0.071). Neither ACRarg nor AIRarg was associated with insulin use at 6 months postoperatively. Preoperative C‐peptide response to arginine correlates with islet mass available for transplant in pediatric TPIAT patients. AST represents an additional tool before autotransplant to provide counseling on likely islet mass and to inform quality improvements of islet isolation techniques.     

Islet transplantation as safe and efficacious method to restore glycemic control and to avoid severe hypoglycemia after donor organ failure in pancreas transplantation

The aim of this study was to assess safety and efficacy of islet transplantation after initial pancreas transplantation with subsequent organ failure. Patients undergoing islet transplantation at our institution after pancreas organ failure were compared to a control group of patients with pancreas graft failure, but without islet transplantation and to a group receiving pancreas retransplantation. Ten patients underwent islet transplantation after initial pancreas transplantation failed and were followed for a median of 51 months. The primary end point of HbA1c <7.0% and freedom of severe hypoglycemia was met by nine of 10 patients after follow‐up after islet transplantation and in all three patients in the pancreas retransplantation group, but by none of the patients in the group without retransplantation (n = 7). Insulin requirement was reduced by 50% after islet transplantation. Kidney function (eGFR) declined with a rate of ‐1.0 mL ± 1.2 mL/min/1.73 m² per year during follow‐up after islet transplantation, which tended to be slower than in the group without retransplantation (P = .07). Islet transplantation after deceased donor pancreas transplant failure is a method that can safely improve glycemic control and reduce the incidence of severe hypoglycemia and thus establish similar glycemic control as after initial pancreas transplantation, despite the need of additional exogenous insulin.     

Targeting CXCR1/2 in the first multicenter,double-blinded,randomized trial in autologous islet transplant recipients

Several cytokines and chemokines are elevated after islet infusion in patients undergoing total pancreatectomy with islet autotransplantation (TPIAT), including CXCL8 (also known as interleukin-8), leading to islet loss. We investigated whether use of reparixin for blockade of the CXCL8 pathway would improve islet engraftment and insulin independence after TPIAT. Adults without diabetes scheduled for TPIAT at nine academic centers were randomized to a continuous infusion of reparixin or placebo (double-blinded) for 7 days in the peri-transplant period. Efficacy measures included insulin independence (primary), insulin dose, hemoglobin A_1c (HbA_1c), and mixed meal tolerance testing. The intent-to-treat population included 102 participants (age 39.5 ± 12.2 years, 69% female), n = 50 reparixin-treated, n = 52 placebo-treated. The proportion insulin-independent at Day 365 was similar in reparixin and placebo: 20% vs. 21% (p = .542). Twenty-seven of 42 (64.3%) in the reparixin group and 28/45 (62.2%) in the placebo group maintained HbA_1c ≤6.5% (p = .842, Day 365). Area under the curve C-peptide from mixed meal testing was similar between groups, as were adverse events. In conclusion, reparixin infusion did not improve diabetes outcomes. CXCL8 inhibition alone may be insufficient to prevent islet damage from innate inflammation in islet autotransplantation. This first multicenter clinical trial in TPIAT highlights the potential for future multicenter collaborations.     

Ten-year outcomes of islet transplantation in patients with type 1 diabetes: Data from the Swiss-French GRAGIL network

To describe the 10-year outcomes of islet transplantation within the Swiss-French GRAGIL Network, in patients with type 1 diabetes experiencing high glucose variability associated with severe hypoglycemia and/or with functional kidney graft. We conducted a retrospective analysis of all subjects transplanted in the GRAGIL-1c and GARGIL-2 islet transplantation trials and analyzed components of metabolic control, graft function and safety outcomes over the 10-year period of follow-up. Forty-four patients were included between September 2003 and April 2010. Thirty-one patients completed a 10-year follow-up. Ten years after islet transplantation, median HbA1c was 7.2% (6.2–8.0) (55 mmol/mol [44–64]) versus 8.0% (7.1–9.1) (64 mmol/mol [54–76]) before transplantation (p < .001). Seventeen of 23 (73.9%) recipients were free of severe hypoglycemia, 1/21 patients (4.8%) was insulin-independent and median C-peptide was 0.6 ng/ml (0.2–1.2). Insulin requirements (UI/kg/day) were 0.3 (0.1–0.5) versus 0.5 (0.4–0.6) before transplantation (p < .001). Median (IQR) β-score was 1 (0–4) (p < .05 when comparing with pre-transplantation values) and 51.9% recipients had a functional islet graft at 10 years. With a 10-year follow-up in a multicentric network, islet transplantation provided sustained improvement of glycemic control and was efficient to prevent severe hypoglycemia in almost 75% of the recipients.     

The impact of surgical complications on the outcome of total pancreatectomy with islet autotransplantation

Total pancreatectomy with islet autotransplantation is a promising treatment for refractory chronic pancreatitis. We analyzed postoperative complications in 83 TPIAT patients and their impact on islet graft function. We examined patient demographics, preoperative risk factors, intraoperative variables, and 30- and 90-day postoperative morbidity and mortality. Daily insulin requirement, HbA1c, C-peptide levels, and narcotic requirements were analyzed before and after surgery. Adverse events were recorded, with postoperative complications graded according to the Clavien-Dindo classification. There was no mortality in this patient group. Postoperative complications occurred in 38 patients (45.7%). Patients with postoperative complications were readmitted significantly more often within 30 days (p = 0.01) and 90 days posttransplant (p < 0.0003) and had a significantly longer hospital stay (p = 0.004) and intensive care unit stay (p = 0.001). Insulin dependence and graft function assessed by HbA1c, C-Peptide and insulin requirements did not differ significantly by these complications. Postoperative complications after TPIAT are associated with longer hospital and intensive care unit stay and with readmission; however, the surgical complications do not affect islet graft function.     

Modeling the Iatrogenic Pancreatic Cancer Risk After Islet Autotransplantation in Mouse

Iatrogenic pancreatic cancer metastasis after islet infusion is a potential risk of islet autotransplantation performed after pancreatectomy. To model this risk, islets and/or pancreatic exocrine clusters obtained from a genetically engineered mouse model for pancreatic ductal adenocarcinoma (the LSL‐Kras^G12D/+;LSL‐Trp53^R172H/+;Pdx‐1‐Cre, termed KPC mouse) were transplanted via the portal vein in syngeneic wild type (WT) severely diabetic recipients in the following treatment groups: group A (n = 11) received KPC exocrine clusters in volume equal to 250 islet equivalents (IEQs); group B (n = 12) received 250 WT IEQs mixed with KPC exocrine clusters (1:1 volume ratio); group C (n = 5) received 250 KPC IEQs, and group D (n = 7) received 250 WT IEQs. The incidence of hepatic metastasis was assessed by magnetic resonance imaging and histology over the 13 months of follow‐up. Overall survival was not different in the four groups. No mice developed liver metastases during the follow‐up. Two mice developed spontaneous tumors: a liver hepatocellular tumor in group A and a malignant lymphoma in group D. Islets and/or exocrine clusters obtained by KPC mouse, a model that develops pancreatic cancer with 100% penetrance, do not retain the same risk of tumor development when transplanted via the portal vein in a syngeneic diabetic recipient.     

Diabetes‐free survival after extended distal pancreatectomy and islet auto transplantation for benign or borderline/malignant lesions of the pancreas

Islet autotransplant is particularly attractive to prevent diabetes after extended pancreatectomy for benign or borderline/malignant pancreas disease. Between 2008 and 2018, 25 patients underwent left extended pancreatectomy (>60%) and islet autotransplant for a neoplasm located in the pancreatic neck or proximal body. Overall, disease‐free and diabetes‐free survivals were estimated and compared with those observed in 68 nondiabetic patients who underwent distal pancreatectomy for pancreatic neoplasms without islet autotransplant. Median follow‐up was 4 years. We observed no deaths and a low morbidity (nonserious procedure‐related complications in 2 of 25 patients). Patient and insulin‐independent survival rates at 4 years were 100% and 96%, respectively. Glucose homeostasis remained within a nondiabetic range at all times for 19 (73%) of 25 patients. Preoperative glycemic level and insulin resistance were major predictors of diabetes development in these patients. Patients undergoing islet autotransplant had a longer diabetes‐free survival than did patients without islet autotransplant (P = .04). In conclusion, islet autotransplant after extended pancreatic resection for neoplasms is a safe and successful procedure for preventing diabetes.     

全胰腺切除术联合自体胰岛细胞移植治疗慢性胰腺炎的新进展

全胰腺切除术联合自体胰岛细胞移植(TP-IAT)治疗慢性胰腺炎可以较好地缓解慢性疼痛以减少对镇痛药物的依赖,同时又保持了一部分胰岛功能从而减少了胰岛素的使用。TP-IAT已逐渐成为了慢性胰腺炎的一种理想的治疗方式,尤其是对于终末期患者。笔者就近年来TP-IAT治疗慢性胰腺炎的研究进展进行综述。     

Evaluation of Glucose Metabolism After Distal Pancreatectomy According to the Donor Criteria of the Living Donor Pancreas Transplantation Guidelines Proposed by the Japanese Pancreas and Islet Transplantation Association

Background

Living donor pancreas transplantation (LDPT) reduces the number of deaths of diabetic patients on dialysis and of candidates on the waiting lists and helps to overcome the organ shortage. Stringent criteria must be applied to minimize the risk of metabolic complications for living donors. The Japanese Pancreas and Islet Transplantation Association (JPITA) proposed LDPT guidelines in 2010. In this study, we retrospectively evaluated glucose metabolism of the patients who underwent distal pancreatectomy (DP) according to the donor criteria of the LDPT guidelines proposed by the JPITA.

Methods

Fifty-two nondiabetic patients who underwent DP were divided into 2 groups according to the donor criteria: indication group (IG, n = 14) who had age ≤ 65, hemoglobin A1c (HbA1c) < 5.9%, and body mass index (BMI) < 25 kg/m². The other patients were placed in the no indication group (NG, n = 38). Clinical data and percent resected volume (PRV) of each pancreas as determined by multi–detector row computed tomography volumetry were compared between the 2 groups.

Results

During the follow-up period (median 12 months), 14 patients (27%) developed new-onset diabetes within a median onset time of 10 months (range 3–24 months) postoperatively. No patient in the IG developed new-onset diabetes. On the other hand, 37% of the patients in the NG developed new-onset diabetes. There were significant between-group differences in changes in preoperative serum fasting glucose and HbA1c levels, whereas there were no significant between-group differences in preoperative serum albumin or body weight. Multivariate analysis identified preoperative HbA1c (odds ratio 51.6, P = .002) and PRV (odds ratio 2.07, P = .033) as independent risk factors for new-onset diabetes.

Conclusion

Living donor criteria in the LDPT guidelines proposed by the JPITA are appropriate for prevention of glucose metabolic complications in donors. Further long-term follow-up studies of living donors' metabolic function are needed to clarify the safety of the donor.     

In‐hospital and 90‐day outcomes after total pancreatectomy with islet autotransplantation for pediatric chronic and acute recurrent pancreatitis

Total pancreatectomy with islet autotransplantation (TPIAT) is used to treat debilitating chronic pancreatitis (CP) and acute recurrent pancreatitis (ARP) that has failed medical and endoscopic therapy. We performed a retrospective review of TPIAT patients at a free‐standing children's hospital to evaluate perioperative outcomes. Twenty patients (median age 13, 65% female) underwent TPIAT (2015 through 2017). Of the 20 patients, 95% had CP and 1 patient (5%) had ARP alone. Seventy‐five percent of the patients had a pancreatitis‐associated genetic mutation; 40% had pancreas divisum. The median surgical time was 757 (IQR 657 to 835) minutes. Median islet equivalents per kg of body weight (IEQ/kg) were 6404 (IQR 5018 to 7554). At 90 days postoperatively vs preoperatively, significantly fewer patients were receiving parenteral nutrition (0% vs 25%, P = .006) and opioids (45% vs 75%, P = .01). Short Form 36‐Item Health Survey (SF‐36) physical health module scores and total scores improved (34.0 preoperatively vs 54.6 at 90 days, P = .008, and 47.1 vs 65.3, P = .007, respectively); SF‐10 physical health scores also improved (13.4 vs 33.1, P = .02). Insulin requirement decreased from 0.5 unit/kg/day to 0.4 unit/kg/day between discharge and 90 days (P = .02). TPIAT is an effective option when debilitating disease persists despite maximal medical and endoscopic therapy. Opioid, parenteral nutrition, and exogenous insulin use can successfully be weaned within 90 days after TPIAT, with gains in health‐related quality of life.     

Institutional indications for islet transplantation after total pancreatectomy

BACKGROUND/PURPOSE: This study was designed to establish institutional indications for pancreatic islet transplantation by examining patients with total pancreatectomy as candidates for islet allotransplantation. METHODS: In 12 patients who underwent total pancreatectomy, we compared pre-and postoperative plasma glucose level, body mass index, HbA1c, and daily insulin use; we examined candidacy for islet allotransplantation based on the guidelines of Japan's islet transplantation registry. RESULTS: Eight of the 12 patients with total pancreatectomy were operated for intraductal papillary mucinous neoplasm. At our institution, the 5-year survival of patients with intraductal papillary mucinous neoplasm was far better (76.3%) than that of patients with pancreatic cancer. Postoperatively, plasma glucose level, HbA1c, and daily insulin use were increased in all patients with total pancreatectomy. Of the 12 patients treated with total pancreatectomy, 4 (intraductal papillary mucinous neoplasm, n = 2; islet cell tumor, n = 1; and acute pancreatitis due to arteriovenous malformation, n = 1) showed deteriorated diabetic control and therefore were considered to be candidates for islet allotransplantation according to the guidelines. CONCLUSIONS: Islet allotransplantation could be indicated for patients with favorable postoperative survival who have had a total pancreatectomy for either benign or neoplastic disease.     

Islet alloautotransplantation: Allogeneic pancreas transplantation followed by transplant pancreatectomy and islet transplantation

Simultaneous pancreas–kidney (SPK) transplantation is an important treatment option for patients with type 1 diabetes (T1D) and end‐stage renal disease (ESRD). Due to complications, in up to 10% of patients, allograft pancreatectomy is necessary shortly after transplantation. Usually the donor pancreas is discarded. Here, we report on a novel procedure to rescue endocrine tissue after allograft pancreatectomy. A 39‐year‐old woman with T1D and ESRD who had undergone SPK transplantation required emergency allograft pancreatectomy due to bleeding at the vascular anastomosis. Islets were isolated from the removed pancreas allograft, and almost 480 000 islet equivalents were infused into the portal vein. The patient recovered fully. After 3 months, near‐normal mixed meal test (fasting glucose 7.0 mmol/L, 2‐hour glucose 7.5 mmol/L, maximal stimulated C‐peptide 3.25 nmol/L, without insulin use in the preceding 36 hours) was achieved. Glycated hemoglobin while taking a low dose of long‐acting insulin was 32.7 mmol/mol hemoglobin (5.3%). When a donor pancreas is lost after transplantation, rescue β cell therapy by islet alloautotransplantation enables optimal use of scarce donor pancreata to optimize glycemic control without additional HLA alloantigen exposure.     

Clinical use of donation after circulatory death pancreas for islet transplantation

Due to a shortage of donation after brain death (DBD) organs, donation after circulatory death (DCD) is increasingly performed. In the field of islet transplantation, there is uncertainty regarding the suitability of DCD pancreas in terms of islet yield and function after islet isolation. The aim of this study was to investigate the potential use of DCD pancreas for islet transplantation. Islet isolation procedures from 126 category 3 DCD and 258 DBD pancreas were performed in a 9-year period. Islet yield after isolation was significantly lower for DCD compared to DBD pancreas (395 515 islet equivalents [IEQ] and 480 017 IEQ, respectively; p = .003). The decrease in IEQ during 2 days of culture was not different between the two groups. Warm ischemia time was not related to DCD islet yield. In vitro insulin secretion after a glucose challenge was similar between DCD and DBD islets. After islet transplantation, DCD islet graft recipients had similar graft function (AUC C-peptide) during mixed meal tolerance tests and Igls score compared to DBD graft recipients. In conclusion, DCD islets can be considered for clinical islet transplantation.