Small bowel transplantation
Over 30 years ago Richard Lillehei and colleagues from Minneapolis carried out experiments demonstrating that, from a technical point of view, transplantation of the gut was feasible'. However, it rapidly became clear that compared with other forms of organ grafting there were major difficulties in achieving successful allogeneic small bowel transplantation. The small bowel has a substantial lymphoid component in the mesenteric lymph nodes, Peyer's patches and lamina propria. Therefore, in addition to recipient cells invading the graft to cause rejection, graft cells are capable of migrating to recipient tissues to cause graft uersus host disease (GVHD). Controlling these competing immunological forces presents a considerable problem.
Early clinical attempts at small bowel transplantation were all carried out in desperate cases where the patient had no other hope of survival. Although some patients lived for a few weeks, most succumbed within days of the procedure. It is now clear that systemic sepsis was the cause of death in these cases. Recent studies on immunocompromised patients receiving chemotherapy have demonstrated that in this situation bacteria can translocate across the bowel wall into the bloodstream and cause life-threatening infection. In transplanted bowel the effects of ischaemic injury following organ harvesting, combined with damage induced by early rejection, may compromise the mucosal barrier, with the rapid development of septicaemia.
In the 1980s the advent of cyclosporin, with its specific effect on T lymphocytes, rekindled interest in the possibility of small bowel transplantation. In experimental animal models cyclosporin was capable of completely subverting the rejection response. One of the fascinating observations has been that in long-surviving grafts the majority of the lymphoid tissue of the bowel is replaced by host cells2. Recent evidence indicates that a similar repopulation with recipient cells also occurs after human small bowel transplantation3. In other organ grafts such cellular infiltration is associated with rejection, but in a small bowel transplant the invading host lymphocytes clearly have a symbiotic relationship with the graft.
The development of potent new immunosuppressive agents bringing the possibility of successful human small bowel transplantation begs the question of whether there is a real clinical need for the procedure. From studies of patients currently on long-term total parenteral nutrition (TPN) it would appear that there are between two and three patients per million of population per year who develop irreversible small bowel failure4. These patients are children and adults who have had massive small bowel resection for conditions such as volvulus, enterocolitis, Crohn's disease, radiation enteritis and mesenteric vascular disease. If successful programmes could be established there would also be the possibility of offering treatment of infants with congenital problems, such as microvillus atrophy, which at the present time are uniformly fatal.
A number of isolated small bowel transplants were performed in Paris and Keil, Germany in the late 1980s, and two patients still retain functioning grafts more than 2 years after operation. In 1989 Grant and colleagues in London, Ontario performed a combined liver and small bowel graft with long-term success5 and have now carried out two further procedures of this kind. At the Second International Symposium on Small Bowel Transplantation held in Canada in October 1991, Starzl reported successful results from Pittsburgh, USA, where there is now an eight-case series of liver plus small bowel grafts immunosuppressed with FK506. Although the mechanism remains obscure, it is known from animal models that a liver graft has a protective effect and can enhance the survival of other organ grafts6.
Those patients surviving with small bowel transplants have all had stormy postoperative courses with lengthy periods in intensive care. Although transplantation is now a possibility for patients with intestinal failure there are still a number of important problems to solve. Only short-term preservation of the bowel is available at present, limiting the possibility of achieving good immunological matching of donor and recipient in cadaveric grafting. Despite the potency of the newer immunosuppressive agents, GVHD remains a potential problem which they may not adequately control. In the first liver plus small bowel case of Grant et al. there was