Treatment of isolated pancreatic islets to reverse pancreatectomy-induced and insulin-dependent type I diabetes in humans: a 6-year experience.
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Publications and source records attributed to C Rastellini.
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The advent of small bowel transplantation has provided selected patients with chronic intestinal irreversible failure with a physiologic alternative to total parenteral nutrition. Recently a standardized technique for living related small bowel transplantation (LR-SBTx) has been developed. Three patients with short bowel syndrome underwent LR-SBTx at our institution. All donors were ABO compatible with a good human leukocyte antigen match. A segment of 180 to 200 cm of ileum was harvested and transplanted with its vascular pedicle constituted by the ileocolic artery and vein. The grafts were transplanted with a short cold and warm ischemia time. The immunosuppression regimen consisted of oral FK-506, prednisone, and intravenous induction with atgam. Serial biopsies of the intestinal grafts were performed to evaluate rejection or viral infections. The postoperative course was uneventful for all donors. All of the recipients are currently alive and well. Two of three patients are off total parenteral nutrition and tolerating an oral diet with no limitations on daily activity. In the third patient, the graft was removed 6 weeks after transplantation. At the time of enterectomy, no technical or immunologic complications were documented. Absorption tests for D-xylose and fecal fat studies were performed showing functional adaptation of the segmental graft. All biopsies were negative for acute rejection. A well-matched segmental ileal graft from a living donor can provide complete rehabilitation for patients with short bowel syndrome. Our initial experience suggests that the risk of acute rejection and infection is greatly reduced compared to cadaveric bowel transplantation. Further clinical application of this procedure is warranted.
Pyruvate has been shown to prevent intestinal mucosal injury after ischemia-reperfusion. The aim of the present study was to determine whether pyruvate can (1) prevent postreperfusion mucosal injury occurring after intestinal preservation and subsequent transplantation and (2) exert a protective effect on the intestinal graft mucosa during acute rejection. Preservation mucosal injury was evaluated, after 2 hours of reperfusion, by comparing grafts transplanted in a rat syngeneic combination (ACI to ACI) after 2 hours of cold preservation using pyruvate (n = 6) or placebo (n = 6). Mucosal parameters obtained during acute rejection (allogeneic combination: ACI to Lewis) were compared between placebo-treated (n = 6) and pyruvate-treated (n &equals 6) animals. Tissue injury was evaluated by histopathologic examination, oxygen free radical production by luminol-enhanced chemiluminescence, and degree of neutrophil infiltration by myeloperoxidase staining. After reperfusion of the preserved grafts and during acute rejection, mucosal oxygen free radical levels and the number of infiltrating neutrophils were significantly (P <0.05) increased in the untreated grafts, whereas there was a statistically significant inhibition of these parameters in those treated with pyruvate. Mucosal injury, seen after reperfusion of the preserved grafts, was prevented by pyruvate. The histopathologic abnormalities observed in the untreated grafts during rejection were also significantly reduced by pyruvate. Treatment with pyruvate before cold preservation of intestinal grafts, in this rat model, reduced reperfusion mucosal injury, neutrophil infiltration, and oxygen free radical production. Oxygen free radicals were produced in the mucosa of the graft during acute rejection and their production was reduced by pyruvate, which exerted a protective effect on the rejecting allograft mucosa.
We have tested the effect of donor bone marrow cell (DBMC) infusion on the survival of pancreatic islet allografts in the rat, without the use of cytoablative recipient conditioning. Lewis and diabetic Brown Norway rats were used as donors and recipients, respectively. Donor islets were placed beneath the left renal capsule. Infusion of DBMC and temporary immunosuppression followed by delayed islet transplantation resulted in indefinite survival of all islet grafts (MST > 180 days). Control animals demonstrated recurrent hyperglycemia (islet allografts rejection). Donor bone marrow derived cells were detected in the spleen and cervical lymph nodes of BN recipients of LEW bone marrow but not in the recipients of islet transplants alone. Second set full thickness skin grafts were performed in normal BN and in recipients of a previously successful ITX. Donor specific skin grafts were accepted in the animals that had received DBMC 40 days before the islet allograft, while animals receiving DBMC at the time of the islet allograft rejected the donor specific skin graft similarly to the controls. However, these animals did not reject a second set donor-specific islet transplant. The results indicate that radiation conditioning of the recipients was not necessary to induce microchimerism and graft acceptance in this rodent model of islet allotransplantation.
Pancreatic transplantation recently became a routine treatment for Type I diabetic patients with uremia or for those who previously received a kidney transplant with 1 year graft and patient survival of over 80% and 90%, respectively. Despite the life-long need for immunosuppression, this is clearly acceptable when compared to the need for dialysis and insulin therapy, and it reduces the evolution of diabetic complications. Isolated pancreatic transplant is less commonly applied because of the need for immunosuppression and the high rate of complications. However, this can still be an acceptable option for individual patients with brittle diabetes and hypoglycemic unawareness. Despite the fact that pancreas transplantation is an effective treatment for selected Type I diabetics, it remains a difficult surgical procedure with many potential complications and with several issues still subject to debate. In this article, the authors describe the procedure in all of its aspects and variations, and offer, through a review of the recent literature, insights on the current status of this transplant