Small bowel transplantation in infants and children

Multivisceral transplantation, combined liver-intestine transplantation, and isolated small bowel transplantation are very similar procedures that were first developed in the 1950s. If the viscera can be conceptualized as a cluster of grapes hanging from its arterial stems, the three procedures are characterized by virtually identical vascular anastomoses, with exclusion or inclusion of as many viscera (grapes) as necessary; however, these procedures languished for nearly four decades because of the imperfect immunosuppressive regimens of the 1960s, 1970s, and 1980s. Finally, after the development of FK506, pediatric patients may undergo intestinal transplantation with the hope for long-term survival. These procedures are reserved for TPN-dependent children with permanent intestinal insufficiency. Candidacy for transplantation is also predicated on development of potentially fatal TPN complications such as cholestasis, recurrent sepsis, or thrombosis of access sites. Since 1990, 32 pediatric patients have undergone intestinal transplantation at the University of Pittsburgh, with an overall survival of 65%. Immunosuppression has been accomplished with a combination of corticosteroids, FK506, and prostaglandin E1. Although GVHD has not been a major problem, most patients have experienced rejection episodes requiring intensification of immunosuppression with a steroid bolus, a steroid recycle, an increase in FK506 dosage, or addition of OKT3. CMV has caused little morbidity, but EBV-related PTLD has affected 20% of all patients. It has not been possible to discontinue immunosuppression in the face of PTLD without engendering severe small intestinal rejection. Other problems have included recurrent sepsis, intestinal dysmotility, and persistent food avoidance. Future therapeutic trends are likely to include the performance of combined bone marrow-visceral transplant to induce a chimeric tolerogenic state and to lessen the need for long-term immunosuppression.