Improved outcome after intestinal transplantation at a single institution over 12 years.

PURPOSE: To evaluate the outcomes of patients undergoing intestinal transplantation (IT). METHODS: Retrospective review was undertaken using existing medical records and database. RESULTS: Between November 1991 and May 2003, 114 patients were referred for consideration for IT, of which 33 patients received 37 intestinal allografts. All patients had intestinal failure and all patients had significant complications from total parenteral nutrition (TPN). TPN was the predominant cause of liver failure (63%). Combined liver intestinal grafts were used in the majority of patients. Overall 1- and 3-year patient survival is 77% and 52% with patients transplanted since 1999 having a 1- and 3-year survival of 94% and 73%, respectively. The most common cause of death was sepsis. No graft or patient was lost to cytomegalovirus or Epstein-Barr virus disease. Twenty-seven percent of allografts were lost to rejection. Long-term TPN independence is 82% for grafts more than 30 days after IT. Statistical analysis revealed several important factors impacting outcome. CONCLUSIONS: Successful IT defined as prolonged patient and graft survival and TPN independence can be readily achieved in select patients with IF and complications related to TPN therapy. Outcomes have improved with experience gained and control of viral infections and rejection.

Application of combined liver-intestinal transplantation as a staged procedure.

Liver-intestinal transplantation is a complex surgical procedure that historically has required prolonged operative periods. This report is the first series where liver-intestinal transplantation was performed as a staged procedure. Specifically, allograft reperfusion was followed by resuscitation and stabilization in an intensive care unit before completion of the transplant procedure. Triage of recipients to the intensive care unit following allograft reperfusion was determined at the time of operation and was based upon the clinical condition of the recipient including hemodynamic stability, evidence of coagulopathy, and assessment of early liver function. Medical stabilization was followed by completion of the transplant procedure and definitive abdominal closure within 72 hours. The application of combined liver-intestinal transplantation as a staged procedure demonstrated no effect upon early graft function, incidence of complications, or ability to perform a definitive abdominal closure.

Induction therapy with interleukin-2 receptor antagonist after intestinal transplantation is associated with reduced acute cellular rejection and improved renal function.

PURPOSE: To determine the effectiveness of induction immunotherapy with interleukin-2 receptor antagonists (IL2RA) after intestinal transplantation (IT). METHODS: A single-center, retrospective study was undertaken of all patients undergoing IT using existing medical records and database. Immunotherapy was either triple (standard maintenance triple therapy [SMTT]) or IL2RA [induction IL2RA plus SMTTx] or OKT3 [induction antilymphocyte preparations plus SMTTx]). Data was collected for the first 175 postoperative days. Outcomes included pretransplant renal function, posttransplant serum creatinine normalized to age (nl-sCR), rejection (ACR), and survival. Standard statistical analysis was undertaken. RESULTS: There were no significant differences in the groups: triple (n = 10, median age 3.5 years, cGFR 106 +/- 44 mL/min), IL2RA (n = 13, median age 3.2 years, cGFR 101 +/- 61 mL/min), OKT3 (n = 4, median age 7.7 years, cGFR 104 +/- 27 mL/min). nl-sCR was significantly (P <.01) lower in IL2RA at most postoperative weeks. IL2RA had significantly fewer rejection and infectious episodes than the other two groups. Three-year patient survival was 92% in IL2RA versus 50% triple and OKT3. CONCLUSIONS: IL2RA immunotherapy after IT is associated with a lower incidence of renal dysfunction as compared with historical controls. Furthermore, IL2RA therapy resulted in a lower incidence of rejection and improved survival. IL2RA should be considered in select patients undergoing IT.

Intraperitoneal sensitization and the transplanted mouse heart.

Intradermal or skin-graft sensitization always results in accelerated rejection of subsequent MHC-disparate mouse heart transplants; intravenous or intrasplenic sensitization almost always results in prolonged survival. The survival time after intraperitoneal sensitization is unpredictable: hyperacute or accelerated rejection, as well as normal or prolonged survival, occurs suggestive of a delicate balance between suppressive and rejecting immune responses. We have observed a positive correlation between transplant survival and the distribution of 51Cr-labeled antigenic cells early after i.v., i.d., i.p., and intrasplenic injection. Label recovery from the viscera was already high 2 hr after i.v. injection, while after i.d. injection virtually all label was still confined to the carcass, even at the end of a 24-hr period. After i.p. injection label recovery varied significantly from mouse to mouse, from very low to a level approximating that seen after i.v. injection. This close correlation suggests that the fate of a subsequent transplant is decided within a few hours after antigen deposition, well before placement of the transplant itself.

Hyperacute rejection of the transplanted mouse heart.

Mouse hearts transplanted heterotopically to MHC-disparate recipients can be hyperacutely rejected (HAR) after a single or 3 sequential donor type skin grafts, or a single intradermal injection of lymphoid cells. In the combinations tested, not all hearts are HAR; most of them are rejected in accelerated fashion. Our results with transplanted rat hearts are similar, even in a genetic combination for which HAR of all hearts has been reported. However, in rats, HAR tends to occur more rapidly and to be associated with more-intense vascular changes. Transfer of serum from mice or rats sensitized by 3 sequential skin grafts likewise resulted in occasional hyperacute but never accelerated rejection. Transfer of lymph node cells from mice sensitized with a single skin graft always resulted in accelerated but never in hyperacute rejection; transfer of cells after 3 sequential skin grafts caused neither accelerated nor hyperacute rejection.

Effect of ibuprofen and interleukin 2 on transfusion-induced suppression of cell-mediated immunity.

Transfusion-induced immunosuppression has been associated with excessive production of prostaglandin E and decreased interleukin 2 (IL-2) production. In the present study, allogeneic blood-transfused mice were tested for cell-mediated immunity with the use of a delayed-type hypersensitivity assay. In vivo administration of a cyclo-oxygenase inhibitor, ibuprofen, and murine recombinant IL-2 was initiated on day 0 and continued daily throughout the delayed-type hypersensitivity assay. The results indicate that prostaglandin E may play a primary role in allogeneic blood transfusion-induced suppression, as manifest by normal responses in ibuprofen-treated mice. Supplementation of transfused mice with recombinant IL-2 also preserved immune response, indicating inadequate IL-2 production after transfusion, while receptor expression appears to remain intact.