Through 1997, over 10,000 pancreas transplants have been performed world-wide, with 88% being simultaneous kidney-pancreas transplants (SKPTs). Current 1-year patient survival exceeds 90% and pancreas graft survival (complete insulin independence) exceeds 80% for SKPT, 70% for sequential pancreas after kidney transplant (PAKT), and 65% for pancreas transplant alone (PTA). According to Registry data, rejection accounts for 32% of graft failures in the first year after pancreas transplantation. However, improving outcomes are expected to continue with the evolution of treatment protocols. Most pancreas transplant centres employ quadruple drug immunosuppression with anti-lymphocyte induction, using either a monoclonal or polyclonal antibody agent. In recent years, there has been an overall decline in the use of antibody-induction therapy from 90% during 1987-93, to 83% of pancreas transplants performed during 1994-97. Maintenance immunosuppression is triple therapy consisting of a calcineurin inhibitor (cyclosporine or tacrolimus), corticosteroids, and an anti-metabolite such as azathioprine (AZA) or mycophenolate mofetil (MMF). Prior to 1995, nearly all pancreas transplant recipients were managed with Sandimmune. Since 1986, tacrolimus-based therapy has been used in approximately 20% of cases, and a new microemulsion formulation of cyclosporine (Neoral) has replaced Sandimmune in contemporary post-transplant immunosuppression. In addition, MMF is replacing AZA as part of the standard immunosuppressive regimen following pancreas transplantation. At present, a number of centres are conducting various trials with new drug combinations including either Neoral or tacrolimus in combination with steroids and MMF, with or without antibody-induction therapy. From 1994 to 1997, the 1-year rates of immunologic graft loss have decreased to 2% after SKPT, 9% after PAKT, and 16% after PTA. The current array of new immunosuppressive agents are providing more effective control of rejection and permitting solitary pancreas transplantation to become an accepted treatment option in diabetic patients without advanced complications. The apparent potency of new drug combinations has also resulted in a resurgence of interest in steroid withdrawal. Immunosuppressive strategies will continue to evolve to achieve effective control of rejection while minimizing injury to the allograft and risk to the patient. In addition, new regimens must not only address the issue of specific drug toxicities, but also long-term economic, metabolic, and quality of life outcomes. Pancreas transplantation will remain an important alternative in the treatment of diabetic patients until other strategies are developed that can provide equal glycaemic control with less immunosuppression and overall morbidity.

Humans↗

PubMed1998

Mortality after vascularized pancreas transplantation.

BACKGROUND: Previous studies have questioned the safety of vascularized pancreas transplantation (PTX), particularly because diabetes is an independent risk factor for coronary artery disease and cardiac death. METHODS: A retrospective analysis of the timing and causes of death after PTX was performed. From April 1989 through December 1995, 196 PTXs were performed in 186 diabetic patients including 134 simultaneous kidney-PTXs, 59 solitary PTXs, and 3 combined liver-PTXs. All patients underwent whole organ PTX with bladder drainage, received triple or quadruple immunosuppression, and had a minimum follow-up of 1 year (mean 3.8 years). RESULTS: A total of 22 patients (12%) died at a mean of 19 months after PTX. Infection was the most common cause of early death, whereas the majority of late deaths were due to cardiac causes. In the 8 deaths caused by infection, 6 were associated with operative complications, but only 2 received excessive immunosuppression for rejection. In the 10 cardiac deaths, 6 patients were older than 40 years at the time of PTX and 4 had experienced pancreas graft loss before death. Four-year actuarial patient survival was 92% after simultaneous kidney-PTX and 87% after solitary PTX. CONCLUSIONS: In this series, the mortality rate after PTX was 12%, with infection, myocardial infarction, and sudden death accounting for over 80% of deaths. Deaths from infection most commonly occurred early and were associated with operative complications, whereas cardiac deaths usually were late and related to recipient age or preceded by pancreas graft loss. Future strategies aimed at reducing mortality after PTX should emphasize appropriate recipient selection and target prevention of operative complications.

Adult↗

PubMed1998

Experience with portal-enteric pancreas transplant at the University of Tennessee-Memphis.

The UT-Memphis Group has made a number of important contributions to the field of PTX including: 1. Pioneering studies on the effects of PTX on autonomic neuropathy;(15, 16) 2. Comprehensive reports dealing with quality of life after PTX;(17, 18, 38) 3. Seminal studies on the metabolic effects of PTX with portal venous delivery of insulin;(33,34) 4. Refining and perfecting a novel technique of PTX with portal venous drainage of insulin and primary enteric drainage of the exocrine secretions;(2,6,11,19) 5. Describing a percutaneous technique of pancreas biopsy;(20) and 6. Pioneering the use of glucose tolerance for rejection surveillance.(24) The P-E technique has the potential to become the standard of care in the near future because it is more physiologic, normalizes carbohydrate and lipid metabolism, and minimizes complications attributed to the transplant procedure. In addition, we have been actively involved in studying new immunosuppressive regimens in order to improve and simplify the care of the PTX recipient. We believe that PTX will remain an important option in the treatment of IDDM until other strategies are developed that can provide equal glycemic control with less or no immunosuppression or less overall morbidity.

Adult↗

PubMed1997

Analysis of hospital charges after simultaneous pancreas-kidney transplantation in the era of managed care.

BACKGROUND: The purpose of this study was to analyze and compare hospital charges in simultaneous pancreas-kidney transplant (SPKT) recipients before and after implementation of managed care principles. METHODS: Two groups were compared: 14 consecutive SPKT patients transplanted in 1991 vs. 15 consecutive SPKT patients transplanted in 1995. All patients underwent whole organ pancreas transplantation with bladder drainage and received quadruple immunosuppression with OKT3 induction. The two groups were well-matched; outliers were excluded (four in 1991 and five in 1995), and no attempt was made to convert 1991 to 1995 dollars. Patient and graft survival rates were 100%, and no major early complications occurred. All SPKTs were performed in a single hospital setting, and all inpatient charges for the initial hospitalization were analyzed retrospectively and itemized by service. RESULTS: Pharmacy, organ acquisition, and clinical laboratory services accounted for nearly 80% of charges in each group. For the initial transplant hospitalization, the 1995 group experienced significant reductions in: (1) length of stay (16.3+/-1.4-135+/-3.5 days, P=0.03); (2) total number of laboratory tests (392+/-15-224+/-60, P<10(-3)); (3) clinical laboratory charges ($23,623+/-$1,780-$11,165+/-$3,091, P<10(-6)); and (4) total inpatient charges with organ acquisition charges excluded ($87,815+/-$8,678-$75,152+/-$16,871, P=0.049). However, these potential savings were offset by a nearly 47% increase in organ acquisition charges and a 38% increase in medical/surgical supplies. Consequently, total hospital charges for SPKT were no different in 1991 and 1995. CONCLUSIONS: Despite the rising costs of medical care, we have implemented managed care principles after SPKT that were successful in stabilizing hospital charges by decreasing length of stay and clinical laboratory tests during the study period. However, escalating charges related to organ acquisition and medical/surgical supplies remain a problem.

Adult↗

PubMed1997

Retransplantation in the diabetic patient with a pancreas allograft.

BACKGROUND: Retransplantation has been considered a risk factor for both postoperative complications and diminished graft survival, especially in diabetic patients. METHODS: A retrospective survey was performed of a consecutive case series of 196 pancreas transplants in 186 diabetic patients. All patients underwent whole organ pancreas transplantation with bladder drainage. RESULTS: A total of 33 pancreas transplants (17%) in 30 patients were performed after previous transplant. The mean interval between transplants was 3.9 years. At the time of retransplantation, 16 patients had concomitant procedures. Venous extension grafts were used in 10 patients. The mean length of initial hospital stay was 19.5 days, and mean hospital charges were approximately $125,000. The incidences of rejection, infection, and operative complications were 61%, 67%, and 45%, respectively. Patient survival was 90%, kidney graft survival was 82%, and pancreas graft survival was 61% after a mean follow-up of 29 months. Complete rehabilitation was achieved in 73% of cases. CONCLUSIONS: Pancreas transplantation after previous transplant is a challenging but safe treatment that often requires concomitant procedures, the use of vascular extension grafts, and atypical placement of the allograft. However, the good results justify an aggressive policy of retransplantation in the diabetic patient either with a failed allograft or functioning kidney transplant.

Adult↗

PubMed1997