Functional and immunological aspects of small bowel transplantation : an experimental study in dogs

Small bowel transplantation is thought to be the ultimate therapeutic treatment for patients with an irreversible short bowel syndrome and those with intolerance to long-term total parenteral nutrition. Although the small bowel was one of the first organs to be transplanted experimentally, it is the last to be engrafted successfully in humans. The extreme immunogenicity of the small bowel graft and its compromised function after the transplantation procedure still hamper clinical small bowel transplantation as an established therapy. This thesis tries to answer several questions concerning immunological and functional aspects of intestinal transplantation in a pre-clinical animal model. The experiments were performed at the Laboratory for Experimental Surgery, Erasmus University Rotterdam. In part A of this thesis an overview of the problems encountered with the short bowel syndrome is given. In addition, the past and present experiences of experimental and clinical small bowel transplantations are extensively described. Part A ends with the scope of this study, formulating questions and objectives of investigation. In part B the general materials and methods used in the experiments are described. Part C is a compilation of adapted versions of original articles, in which the general materials and methods are omitted. These articles are a reflection of the questions raised in chapter 3. The general discussion of our experimental results is given in part D. Finally, several avenues for future experimental and clinical small bowel transplantation are proposed.

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