ObjectiveTo determine outcome in diabetic pancreas transplant recipients according to risk factors and the surgical techniques and immunosuppressive protocols that evolved during a 33-year period at a single institution. Summary Background DataInsulin-dependent diabetes mellitus is associated with a high incidence of management problems and secondary complications. Clinical pancreas transplantation began at the University of Minnesota in 1966, initially with a high failure rate, but outcome improved in parallel with other organ transplants. The authors retrospectively analyzed the factors associated with the increased success rate of pancreas transplants. MethodsFrom December 16, 1966, to March 31, 2000, the authors performed 1,194 pancreas transplants (111 from living donors; 191 retransplants): 498 simultaneous pancreas-kidney (SPK) and 1 simultaneous pancreas-liver transplant; 404 pancreas after kidney (PAK) transplants; and 291 pancreas transplants alone (PTA). The analyses were divided into five eras: era 0, 1966 to 1973 (n ϭ 14), historical; era 1, 1978 to 1986 (n ϭ 148), transition to cyclosporine for immunosuppression, multiple duct management techniques, and only solitary (PAK and PTA) transplants; era 2, 1986 to 1994 (n ϭ 461), all categories (SPK, PAK, and PTA), predominately bladder drainage for graft duct management, and primarily triple therapy (cyclosporine, azathioprine, and prednisone) for maintenance immunosuppression; era 3, 1994 to 1998 (n ϭ 286), tacrolimus and mycophenolate mofetil used; and era 4, 1998 to 2000 (n ϭ 275), use of daclizumab for induction immunosuppression, primarily enteric drainage for SPK transplants, pretransplant immunosuppression in candidates awaiting PTA. ResultsPatient and primary cadaver pancreas graft functional (insulinindependence) survival rates at 1 year by category and era were as follows: SPK, era 2 (n ϭ 214) versus eras 3 and 4 combined (n ϭ 212), 85% and 64% versus 92% and 79%, respectively; PAK, era 1 (n ϭ 36) versus 2 (n ϭ 61) versus 3 (n ϭ 84) versus 4 (n ϭ 92), 86% and 17%, 98% and 59%, 98% and 76%, and 98% and 81%, respectively; in PTA, era 1 (n ϭ 36) versus 2 (n ϭ 72) versus 3 (n ϭ 30) versus 4 (n ϭ 40), 77% and 31%, 99% and 50%, 90% and 67%, and 100% and 88%, respectively. In eras 3 and 4 combined for primary cadaver SPK transplants, pancreas graft survival rates were significantly higher with bladder drainage (n ϭ 136) than enteric drainage (n ϭ 70), 82% versus 74% at 1 year (P ϭ .03). Increasing recipient age had an adverse effect on outcome only in SPK recipients. Vascular disease was common (in eras 3 and 4, 27% of SPK recipients had a pretransplant myocardial infarction and 40% had a coronary artery bypass); those with no vascular disease had significantly higher patient and graft survival rates in the SPK and PAK categories. Living donor segmental pancreas transplants were associated with higher technically successful graft survival rates in each era, predominately solitary (PAK and PTA) in eras 1 and 2 and SPK in eras 3 and 4. Diabetic seconda...

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ObjectiveTo review a single center's experience and outcome with living donor transplants. Summary Background DataOutcome after living donor transplants is better than after cadaver donor transplants. Since the inception of the authors' program, they have performed 2,540 living donor transplants. For the most recent cohort of recipients, improvements in patient care and immunosuppressive protocols have improved outcome. In this review, the authors analyzed outcome in relation to protocol. MethodsThe authors studied patient and graft survival by decade. For those transplanted in the 1990s, the impact of immunosuppressive protocol, donor source, diabetes, and preemptive transplantation was analyzed. The incidence of rejection, posttransplant steroid-related complications, and return to work was determined. Finally, multivariate analysis was used to study risk factors for worse 1-year graft survival and, for those with graft function at 1 year, to study risk factors for worse long-term survival. ResultsFor each decade since 1960, outcome has improved after living donor transplants. Compared with patients transplanted in the 1960s, those transplanted in the 1990s have better 8-year actuarial patient and graft survival rates. Death with function and chronic rejection have continued to be a major cause of graft loss, whereas acute rejection has become a rare cause of graft loss. Cardiovascular deaths have become a more predominant cause of patient death; infection has decreased. Donor source (e.g., ideally HLA-identical sibling) continues to be important. For living donor transplants, rejection and graft survival rates are related to donor source. The authors show that patients who had preemptive transplants or less than 1 year of dialysis have better 5-year graft survival and more frequently return to full-time employment. Readmission and complications remain problems; of patients transplanted in the 1990s, only 36% never required readmission. Similarly, steroid-related complications remain common. The authors' multivariate analysis shows that the major risk factor for worse 1-year graft survival was delayed graft function. For recipients with 1-year graft survival, risk factors for worse long-term outcome were pretransplant smoking, pretransplant peripheral vascular disease, pretransplant dialysis for more than 1 year, one or more acute rejection episodes, and donor age older than 55. ConclusionsThese data show that the outcome of living donor transplants has continued to improve. However, for living donors, donor source affects outcome. The authors also identify other major risk factors affecting both short-and long-term outcome.The first successful kidney transplants in humans were from identical twin living donors.1,2 Although transplanted before the development of chemical immunosuppression, many of these identical twin grafts had long-term survival. With recognition of the immunosuppressive effects of prednisone and azathioprine, the use of nontwin donors became possible.3,4 Considerable controversy soon follow...

The process of microbial translocation was studied using Candida albicans, Escherichia coli, or endotoxin instilled into Thiry-Vella loops of thermally injured guinea pigs and rats. Translocation of C. albicans occurred by direct penetration of enterocytes by a unique process different from classical phagocytosis. Translocation between enterocytes was not observed. Internalization was associated with a disturbance of the plasma membrane and brush border, but most internalized organisms were not surrounded by a plasma membrane. Passage of the candida into the lamina propria appeared to be associated with disruption of the basal membrane with extrusion of cytoplasm of the cell and candida. Organisms in the lamina propria were commonly phagocytized by macrophages but also were found free in lymphatics and blood vessels. Translocation of E. coli and endotoxin also occurred directly through enterocytes rather than between them, but translocated endotoxin diffused through the lamina propria and muscular wall of the bowel wall by passing between rather than through the myocytes. These descriptive phenomena provide new insight into the role of the enterocyte and intestinal immune cells in the translocation process.