Experimental and Clinical Intestinal Transplantation

Abstract

Before 1972 several attempts were made to perform small intestinal transplantation in man for the treatment of diseases leading to major losses of the small intestine. No patient had survived for more than 76 days despite intensive conventional immunosuppressants, Small intestinal allotransplantation has been investigated, experimentally, since 1959. Lillehei initially reported the results of allotransplantation of various lengths of small intestine in the canine model. Surgical techniques for successful allogeneic small intestinal transplantation as well as the methods for graft preservation, were clarified. Autotransplants of the total small bowel in dogs survived indefinitely. However, in dogs receiving total small intestinal allotransplants the mean survival period was 8–15 days. Both rejection and graft-versus-host disease have been implicated in the short survival of experimental animals.

With the advent of cyclosporine and its known action against both rejection and graft-versus-host disease, we studied the results of parenteral cyclosporine on the survival of dogs following total small intestinal allotransplantation. Cyclosporine greatly prolongs survival to a mean of 103 days, following transplantation of the small bowel, compared to only 12 days in dogs not receiving any immunosuppressive agent. Two of the treated dogs lived for longer than 200 days and one dog lived for more than 400 days.

Following this, we have developed a method of histological monitoring of the allograft by making two exterior isolated pouches of the allograft, representing the histological events leading to rejection of the in-continuity bowel. By doing so, we have demonstrated that mucosal pouch biopsies truly reflect histological changes leading to rejection of the in-continuity bowel and provide a means of histological monitoring of rejection. in addition, we have also shown that instillation of 14-carbon-labelled glucose into the isolated pouches is severely impaired in dogs undergoing a rejection process and these results correlate with histological signs of rejection as well as with lower cyclosporine levels.

Overall, with the use of cyclosporine, survival in experimental animals has increased significantly. in addition, histological means of establishing and monitoring rejection as well as physiological monitors of rejection have been developed to the point where we now feel that in certain selected patients who are unable to be placed on a home TPN programme or patients who fail on this programme, intestinal transplantation may become a viable alternative.