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.

Adult↗

PubMedDate not supplied

Preservation injury and acute rejection of rat intestinal grafts: protection afforded by pyruvate.

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.

Acute Disease↗

PubMedDate not supplied

Pyruvate in organ transplantation.

Pyruvate (PY) is a 3-carbon compound present in human tissues and physiologically used by cells as an energetic substrate in anaerobic conditions. In the last few years, we have successfully used PY to protect small bowel (SB), liver, and kidneys from ischemia/reperfusion injury in several experimental models. Although the mechanism of protection is not fully clarified, we have shown increased tissue levels of adenosine triphosphate (ATP) during ischemia. This suggests that providing supra-physiologic concentrations of PY during anaerobic glycolysis might enable the cells to remain viable during prolonged hypoxia. Furthermore, mechanisms such as direct inhibition of oxygen free radical formation, abrogation of neutrophilic infiltration and reduced up-regulation of adhesion molecules have also been documented in these studies. In light of these findings, we evaluated the efficacy of PY in organ preservation and transplantation. We demonstrated a protective effect on intestinal preservation injury and during acute rejection. Oral PY treatment induced immunologic changes in rejecting allograft, inhibiting perforin and granzyme-b expression and leukocytic infiltration. Protection was also documented on livers after prolonged hypothermic preservation using a PY based preservation solution. Additionally, isolated pancreatic islets were cultured in PY enriched media and maintained viable for up to 120 days followed by in vitro testing and transplantation revealing a well preserved function. All these findings suggest that PY is a potentially beneficial nutrient in patients undergoing organ transplantation and that future clinical application of PY in this field should be encouraged.

Acute Disease↗

PubMedDate not supplied

A new technique for isolating and culturing human hepatocytes from whole or split livers not used for transplantation.

Large numbers of human hepatocytes were obtained from split and whole livers by using an adaptive form of the collagenase perfusion technique employed in rodent and human biopsies. In order to guarantee a homogenous distribution of the perfusate within the whole specimen, major hepatic veins were cannulated with large bore catheters. This technique allowed for the isolation of human hepatocytes on a large scale (up to 18.5 x 10(9) in one case) from normal and diseased liver specimens. The yield of isolated normal viable hepatocytes is inversely proportional to the donor age. In addition, it was noted that a short time between declared death and organ harvest (cross clamp time) results in higher viability of hepatocytes. In contrast, the time of cold organ preservation did not correlate with the viability or the yield of isolated hepatocytes. We conclude that the technique presented here allows isolation of large numbers of human hepatocytes from specimens unsuitable for transplantation but very valuable for biomedical research.

Animals↗

PubMedDate not supplied

Pancreatic transplantation: a review.

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

Diabetes Mellitus, Type 1↗