Living Donor Pancreas Transplantation Research Articles

Living Donor Pancreas Transplants: Donor Selection and Risk Minimization

Purpose of Review In this study, our goal was to analyze nearly 4 decades of experience since the first living donor pancreas transplant in 1979, focusing on what constitutes optimal donor selection and ideal post donation follow-up. When combined with a living donor kidney transplant, a living donor pancreas transplant offers patients with concurrent renal failure and diabetes the option of a single procedure: a living donor simultaneous pancreas-kidney (SPK) transplant. Living donor SPK transplants not only can reduce the waiting time in areas where it is long but also, for highly sensitized patients, can electively identify a donor with a negative crossmatch.

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

BackgroundLiving 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. MethodsFifty-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. ResultsDuring 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. ConclusionLiving 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.

Single-Center Experience with Pancreas Transplantation

BackgroundRecently improved patient and graft survivals, as well as decreased of postoperative morbidity have ushered in pancreas transplantation (PT) due to technical refinements as well as better immunosuppression and postoperative management. Herein we analyzed the outcomes of PT over a 19-year experiences at a single center. MethodsAll recipients who underwent deceased donor or living donor PT from July 1992 to July 2011 were enrolled in this study. We reviewed their medical records, including operative records, as well as clinical and laboratory findings. We analyzed graft and patient survival rates using the Kaplan-Meier method. ResultsOne hundred fifty-three cases were performed between July 1992 and July 2011. The indication for PT was type I diabetes in 125 (81.7%), and type II diabetes in 28 (18.3%) patients. The pancreas donor was deceased in 139 (90.8%) and living in 14 cases (9.2%). The type of PT was simultaneous pancreas-kidney transplantation (n = 91, 59.5%), pancreas alone (n = 49; 32.0%), or pancreas after kidney (n = 13, 8.5%). Median follow-up was 43.0 months (range 0–228). At 1, 5, and 10 years overall patient survivals were 93.8%, 88.1%, and 85.1%, and graft survivals, 82.3%, 70.6%, and 64.6%, respectively. When we divided the deceased donor PT recipients into two groups according to when they underwent PT (up to 2005 [n = 54]) vs 2006 and later [n = 85]), the recent group showed significantly improved patient and graft survival rates (P < .001). With no difference between type I (n = 65) and type II (n = 20) patients (P = .159). ConclusionConsidering the improved quality of life and long-term patient survival, PT can be an effective treatment strategy in diabetic patients requiring insulin regardless of type of disorder.

Pushing the envelope

More than 160 living donor segmental pancreas/islet transplants have been done since the first in 1977, more than three-quarters at one institution. We review this three-decade experience to project future application. Initially, living donor pancreas transplants were done because the results with deceased donors were poor. As the results with deceased donors improved, the incentive to do living donor transplants declined but never disappeared. A living donor simultaneous pancreas-kidney transplant in a uremic diabetic can correct diabetes and pre-empt dialysis with one operation, obviating the high mortality rate of waiting for a deceased donor. Solitary pancreas transplant candidates with preformed human leukocyte antigen antibodies but a negative cross match to a living donor volunteer also benefit. The technical failure rate of living donor pancreas transplants was high in the initial cases (>1/3), nearly double that for deceased donors, but has since declined to nearly zero. Living donor segmental pancreatectomy has little surgical morbidity (currently done laparoscopically) with only a small risk for diabetes by strict selection criteria. living donor and deceased donor graft survival rates are equivalent. Islet allografts have been done from three living donors, the last one successfully, showing the potential for further application. The incentives for living donor transplants are to eliminate long-wait times for a deceased donor organ and to improve outcomes. With both the incentive is high, but either by itself is sufficient. As the number of pancreas transplant candidates increase, so will wait times for a deceased donor organ. For this reason, living donor pancreas/islet transplant volume will likely increase in the years to come.

Laparoscopic and robotic donor pancreatectomy for living donor pancreas and pancreas–kidney transplantation

Pancreas transplantation is a widely accepted procedure that can efficiently restore euglycemia and prevent progression of complications. In most instances, the limiting factor for deceased donor organ transplantation is the availability and quality of the available organs. Living donor pancreas transplant was introduced at the University of Minnesota in 1979. Because of the potential risks for the donor and the technical challenges in the recipient operation, this procedure has not become very popular since then. In 1999, in the attempt to decrease the morbidity associated with open distal pancreatectomy, the first laparoscopic donor distal pancreatectomy with hand-assisted technique was performed at the same institution. In 2000, the FDA approved the robotic surgical system Da Vinci for general use. Since then, the system has been extensively used at our institution to perform living donor nephrectomy. The only case reported worldwide of robotic distal pancreatectomy and nephrectomy for living donor pancreas-kidney transplantation was successfully performed by our team in 2006 at the University of Illinois at Chicago and proved as a promising technique. The application of minimally invasive techniques has allowed an increased acceptance of the procedure among potential donors and may, therefore, increase the number of donors for this life-saving transplant. The initial results are encouraging and clearly prove feasibility.

Short‐ and long‐term outcome for living pancreas donors

The advantages of living donor pancreas transplants for the recipient include good HLA matching, lower immunologic risk, less immunosuppression, lower risk of infection and of posttransplant malignancies, and shorter pancreas graft preservation time. In 2008, a total of 155 segmental pancreas transplants using living donors were reported to the International Pancreas Transplant Registry from six countries. Pancreas living donors need to undergo a thorough pretransplant endocrinologic workup in order to minimize the risk of metabolic complications. The pretransplant workup has evolved over time, after initial reports showed that up to 25% of living donors had elevated hemoglobin A(1c) levels after donation. Avoiding obesity after donation diminishes the risk of long-term metabolic complications. The risk of surgical complications for the donor (such as pancreatitis, pancreatic leak or fistula, pancreatic abscess, and pancreatic pseudocyst) is less than 5%. If both the donor and recipient operations are technically successful, the long-term graft survival rate is significantly higher for living (versus deceased) donor pancreas transplant recipients. Future long-term studies of metabolic function in living donors are warranted to determine whether living donor pancreas transplants can safely be applied more widely and whether living donors can be used for islet transplants.

Living donor pancreas transplantation in Japan

Living-donor pancreas transplants (LDPs) were introduced at Chiba-East National Hospital in 2004, and 12 LDPs have been performed at this institution to date. Based on the outcome of these 12 LDPs, the efficacy and safety of LDPs are herein discussed. Twelve diabetic patients underwent LDPs; ten had simultaneous pancreas and kidney transplants from living donors, one had pancreas transplant after a kidney transplant from a living donor, and one had a pancreas transplant alone from a living donor. The donors were parents or brothers and the ABO blood types were incompatible in three LDPs. The procedures for the donor and recipient operations were performed according to the technique established by the University of Minnesota. Bladder drainage was used in 11 recipients and enteric drainage was used in one patient. Tacrolimus, basiliximab, mycophenolate mofetil, and prednisone were used for induction and immunosuppressive treatment. A splenectomy, double-filtered plasmapheresis, and plasma exchange were added in the ABO-incompatible LDPs. No complications were observed in the donors during hospitalization. The 1-year survivals of the patients, kidney grafts, and pancreas grafts were 100, 100, and 100%, respectively. The 3-year survivals were 91.7, 90, and 91.7%, respectively. Three patients developed leakage of pancreatic juice and one patient required a surgical procedure. Cytomegalovirus antigenemia was detected in five patients (42%). Based on the excellent outcome of the LDPs at this institution, LDPs is therefore expected to become a promising option for the treatment of patients with severe diabetes.

Preface to topic “Living donor pancreas transplantation”

Pancreas transplantation is an established treatment for type 1 diabetic patients. The outcome of pancreas transplantation has rapidly improved in association with improvements in the surgical procedure and a newly developed immunosuppressive regimen. The pancreas was the first extra-renal organ to be transplanted successfully from living donors, at the University of Minnesota in 1979 [1]. A simultaneous pancreas and kidney transplantation from a living donor was first successfully performed for a diabetic patient with end-stage renal disease at the same institution in 1994 [2]. In Japan, only seventy-four pancreas transplantations from deceased donors have been performed since the first pancreas transplantation was performed by Fukao et al. in 1984 [3]. Unfortunately, twenty-three diabetic patients on the waiting list to undergo pancreas transplantation in the Japan Organ Transplant Network died during the 10-year period from 1999 to 2008 [4]. Based on a severe shortage of deceased donors in this country and the poor prognosis of diabetic patients, especially those with end-stage renal disease, the first simultaneous pancreas and kidney transplant from a living related donor was successfully introduced in Japan by Kenmochi et al., on 7 January 2004 [5]. Seventeen living donor pancreas transplants have since been performed in this country, with an excellent outcome (unpublished data). The concept of living donor organ transplantation presents ethical, legal, medical, social, and psychological challenges. In addition, the most important issue in living donor pancreas transplantation must be to protect the donor against the development of diabetes by ensuring the preservation of the donor’s endocrine function after the distal pancreatectomy. The donors of pancreas transplants may develop insufficient glucose tolerance after surgery because the pancreas lacks the ability to regenerate. This problem remains unsolved. This topic was selected to clarify the current status of living donor pancreas transplantation both worldwide and in Japan. All three authors are clinical doctors actively at work in the field of living donor pancreas transplantation. I hope this topic may provide some helpful information for the treatment of severe diabetic patients.

Evaluation of Segmental Pancreatic Function Using 11C-Methionine Positron Emission Tomography for Safe Operation of Living Donor Pancreas Transplantation

For the safe operation of living donor pancreas transplantation, we investigated the utility of 11C-methionine positron emission tomography (PET) to examine the function of the residual pancreatic head in patients with pancreatic disease undergoing distal pancreatectomy and in living donors of pancreas transplantation. After 6 hours of fasting, we intravenously injected 370 to 740 MBq 11C-methionine. PET was scanned 30 minutes after injection. 11C-methionine PET uptake by the pancreatic head versus body/tail was expressed as a standardized uptake value (SUV). The SUVs of the pancreatic head were compared before versus after surgery. The SUVs of the pancreatic head in patients before and after distal pancreatectomy were 15.3 ± 6.0 and 18.2 ± 2.4, respectively. The SUVs of the pancreatic head in donors before and after distal pancreatectomy were 16.1 ± 1.0 and 14.7 ± 1.4, respectively. Both patients and donors showed no significant difference in SUVs of the pancreatic head before and after surgery. However, the SUVs of the residual pancreatic head were elevated after distal pancreatectomy in 80% of patients and 50% of donors. These data indicated that the function of the pancreatic head may be maintained or improved after distal pancreatectomy. 11C-methionine PET may become a potent modality to evaluate segmental pancreatic function for a safe living donor operation.

Living Donor Pancreas Transplantation

The pancreas was the first extrarenal organ to be successfully transplanted with use of a living donor. The goal at that time, in the azathioprine and cyclosporine eras, was to improve graft survival rates after solitary pancreas transplants. But today, in the tacrolimus era, most living donor pancreas transplants are with a simultaneous living donor kidney transplant because of the cadaver kidney donor shortage. The evolution of stringent selection criteria for living pancreas donors has significantly reduced the incidence of surgical complications and adverse metabolic changes. In contrast to kidney and liver transplants with use of living donors, the donor mortality rate after more than 140 living donor pancreas transplants has remained 0%. The introduction of laparoscopic donor hemipancreatectomy, with its rapid recovery time, makes living pancreas donation more attractive. Patient and graft survival rates for living donor pancreas recipients are now greater than 85%. Living donor pancreas (with or without a simultaneous living donor kidney) transplants decrease the number of deaths of diabetic patients on dialysis and on the waiting list, help overcome the organ shortage, reduce morbidity, and improve the quality of life for patients formerly on dialysis or with debilitating side effects of diabetes. Meticulous donor workup remains key to a low metabolic and surgical complication rate.