Survival has greatly improved over time as management strategies evolved. The current results clearly justify elevating the procedure level to that of other abdominal organs with the privilege to permanently reside in a respected place in the surgical armamentarium. Meanwhile, innovative tactics are still required to conquer long-term hazards of chronic rejection of liver-free allografts and infection of multivisceral recipients.
The survival rates after intestinal transplantation have cumulatively improved during the past decade. With the management strategies currently under evaluation, intestinal transplant procedures have the potential to become the standard of care for patients with end-stage intestinal failure.
Summary
Introduction of new innovative immunosuppressive strategies has been the milestone of the recent evolution of intestinal and multivisceral transplantation. With new insights into the mechanisms of organ engraftment and acquired tolerance, the Pittsburgh tolerogenic protocol was recently introduced and consisted of two main therapeutic principles: recipient pretreatment with lymphoid ablating antibodies and minimal post‐transplant immunosuppression with tacrolimus monotherapy. The reported herein improved survival and the striking ability to wean immunosuppression among the intestinal and multivisceral recipients pretreated with a single‐dose of Thymoglobulin (rATG) or Campath‐1H (alemtuzumab) supports our working hypothesis with successful induction of variable tolerance. It is important, however, that careful monitoring of subtle histologic changes in serial endoscopic‐guided mucosal biopsies be carried out for early diagnosis of allograft immune activation with prompt restoration of the baseline immunosuppressive therapy. Future scientific discoveries with better understanding of the mechanisms of immune tolerance and clinical introduction of reliable assays will increase the chance and safety of achieving complete tolerance among the intestinal and other solid organ recipients. This review will focus on the historic evolution of the immunosuppressive and other management strategies utilized for the intestinal and multivisceral recipients at the University of Pittsburgh with special reference to allograft immunity and the successful achievement of partial tolerance.
Most acute-rejection episodes are mild and do not lead to clinically significant architectural sequelae. When tested prospectively under real-life and -time conditions, the Banff schema can be used to identify those few patients who are potentially at risk for more significant problems. Creation, capture, and integration of non-free text, or "digital," pathology data can be used to prospectively conduct outcomes-based research in transplantation.
Despite pretransplant lymphoid depletion, preemptive antiviral therapy and minimization of posttransplant immunosuppression significantly reduced PTLD morbidity (P=0.0001) and mortality (P=0.001) with no impact on NLC. Patient survival was also improved (P=0.0001) with 91% at 1 year and 75% at 5 years.
Background/Aims-Deficient biliary epithelial cell (BEC) expression of small proline rich protein (SPRR) 2A in IL-6-/-mice is associated with defective biliary barrier function after bile duct ligation. And numerous gene array expression studies show SPRR2A to commonly be among the most highly upregulated genes in many non-squamous, stressed and remodeling barrier epithelia. Since the function of SPRR in these circumstances is unknown, we tested the exploratory hypothesis that BEC SPRR2A expression contributes to BEC barrier function and wound repair.
The role of NF-κB, the rapid-response transcription factor for multiple genes, in cold ischemia-reperfusion (I/R) injury was examined after syngeneic transplantation of liver grafts. Lewis rat recipients were killed 1–48 h after reperfusion of three different liver grafts: 1) uninfected control, 2) infected ex vivo with control adenoviral vector (AdEGFP), and 3) infected ex vivo with AdIκB. In uninfected control livers, NF-κB was activated biphasically at 1–3 and 12 h after reperfusion with aspartate transaminase (AST) levels of 4,244 ± 691 IU/l. The first peak of NF-κB activation associated with an increase of mRNA for TNF-α, IL-1β, and IL-10. AdEGFP transfection resulted in similar outcomes. Interestingly, AdIκB-transfected liver grafts suffered more severe I/R injury (AST >9,000 IU/l). Transfected IκB was detected in transplanted livers as early as 6 h, and this correlated with the abrogation of the second, but not the first, peak of NF-κB activation at 12–48 h and increased apoptosis. Thus inhibition of the second wave of NF-κB activation in IκB-transfected livers resulted in an increase of liver injury, suggesting that NF-κB may have a dual role during liver I/R injury.
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