[Intestinal transplantation from the laboratory to the clinic]

The short bowel syndrome is caused by the anatomical or functional loss of more than 75% of the small bowel. These patients are currently dependent upon long-term total parenteral nutrition (TPN), a treatment that has made much progress, but which is not devoid of complications and which alters the quality of life. Transplantation of a new bowel is the only curative treatment for this disease. But intestinal transplantation (Itx) is not yet considered as an alternative to TPN. Itx is rendered difficult by the immunological obstacles, in particular a vigorous rejection response and the capacity of the bowel graft to induce a graft-versus-host disease (GVHD). Currently only profound and chronic immunosuppression is capable of controling this alloimmune response, but this is at the cost of infection, lymphoma and direct drug toxicity. For this reason Itx is currently rarely performed and usually seen as a "last chance" treatment for terminal patients with life-threatening complications of TPN. The last 10 years, there has been much research performed on Itx. Rejection and GVHD have been better characterized in small and large animal models. Some mechanisms of this alloimmune response have been delineated. Reproducible surgical techniques have been developed in large animal models. Immunomodulatory strategies have been developed that can help to control rejection and reduce the need for immunosuppression. The lessons learned from these experiments--in particular the surgical models that were developed and the immunomodulatory strategies that were designed--were applied in a clinical Itx programme. In October 2000 and in June 2002, 2 Itx were performed in patients with a short bowel syndrome and life-threatening liver failure caused by TPN. Both patients are doing well and have developed no episode of rejection or GVHD so far. This is despite the fact that they are receiving extremely low immunosupppression for this type of transplant. Currently those 2 patients are physically completely rehabilitated and can eat normally again.