Small bowel transplantationBMJ 1996; 312 doi: https://doi.org/10.1136/bmj.312.7026.261 (Published 03 February 1996) Cite this as: BMJ 1996;312:261
- Nicole Brousse,
- Olivier Goulet
- Professor of pathology Professor of paediatrics Department of Pathology and Gastroenterology and Nutrition (Pr C.Ricour), Hopital Necker-Enfants Malades, 75743 Paris, Cedex 15, France
Unique problems but now standard treatment for small bowel insufficiency Intestinal transplantation is the logical alternative to definitive parenteral nutrition in patients with chronic intestinal failure after conditions such as necrotising enterocolitis or midgut volvulus. Long term parenteral nutrition is associated with complications such as liver impairment and local and systemic infections. But since its introduction in the late 1960s, parenteral nutrition has improved greatly, especially with the development of long term home parenteral nutrition, and, as a result, interest in small bowel transplantation has waned. The evolution of the procedure, first reported in experimental animals by Alexis Carrel in 1902,1 has therefore taken longer than that of other solid organ transplants. However, recent advances in immunosuppression and the monitoring of rejection have brought small bowel transplantation into the realms of standard treatment for certain conditions.
Several features of the small bowel make it unique among transplantable organs: the large amount of lymphoid tissue contained in the mesenteric lymph nodes, Peyer's patches, and lamina propria; its heavy colonisation with microorganisms; and the expression of great quantities of class II antigens on the surface of epithelial cells. These features may contribute respectively to graft versus host disease, graft rejection, and sepsis.
Difficulties in transplanting small bowel in humans were first perceived in the 1960s. Seven adults who had undergone massive small bowel resection and subsequent small bowel transplantation were treated with antilymphoglobulins, corticosteroids, and azathioprine, but none survived more than 76 days after the operation.2 The limitations of parenteral nutrition and reports of long term survival in animals treated with the new immunosuppressive drug cyclosporin have revived interest in the procedure.3 However, among the 20 recipients treated with cyclosporin after small bowel transplantation between 1985 and 1990, only two patients, one adult and one child, were able to resume normal oral nutrition; most of the grafts failed because of rejection or infection but surprisingly not as the result of graft versus host disease.
Data on long term patient and graft survival are now available from the intestinal transplant registry (D Grant, IVth International Symposium on Small Bowel Transplantation, Pittsburgh, October 1995). Currently more than 170 patients have received small bowel transplants; 38% of them isolated, 46% combined with liver transplantation, and 16% as part of a multivisceral transplantation. Two thirds of the recipients were children or adolescents. With the immunosuppressive drug tacrolimus, actuarial graft survival rates at one year and three years were 65% and 29% for isolated small bowel transplantation, 64% and 38% for the combined procedure, and 51% and 37% for multivisceral transplantation. Eighty per cent of the 86 survivors no longer require parenteral nutrition and are totally orally fed.
Two recent advances have made small bowel transplantation a promising option for the treatment of end stage intestinal failure: combination with liver transplantation, and the development of tacrolimus. In 1990 Grant et al reported the successful outcome after combined small bowel and liver transplantation in an adult treated with cyclosporin.4 This result has opened the procedure to patients who have developed end stage liver disease as a complication of parenteral nutrition and has raised the possibility that liver transplantation from the same donor may induce tolerance to the small bowel graft. With regard to this last possibility, experimental models5 6 and clinical results (D Grant, IVth International Symposium on Small Bowel Transplantation)7 have given conflicting evidence. A large series showed no advantage in long term survival of small bowel grafts when the procedure was combined with liver transplantation.7 Currently there is no indication to transplant the liver unless the patient has end stage cirrhosis.
Early diagnosis of rejection is essential
The second advance has been the introduction by Starzl et al of a new macrolide immunosuppressive drug, tacrolimus (FK506).8 This drug has produced two year graft survival rates after isolated small bowel transplantation of 40% compared with 11% with cyclosporin (D Grant, IVth International Symposium on Small Bowel Transplantation), and it may prove as useful in small bowel transplantation as cyclosporin has been in liver and heart transplantation.
Monitoring for intestinal rejection is vital after small bowel transplantation since graft rejection is the main complication of the procedure and early diagnosis and treatment of graft rejection is an absolute necessity. Macroscopic changes of mucosal injury and clinical symptoms of graft rejection appear late after the first signs of histological damage. It seems that the combination of conventional histology with haematein eosin staining and immunohistochemistry on repeated mucosal biopsies provides not only early and rapid diagnosis but information on mechanisms of mucosal injury.9 10 Patients receive a major histocompatibility class incompatible small bowel cadaveric allograft. The distal part of this is left as an enterostomy for at least the first three months, allowing close histological and immunohistochemical follow up by sequential biopsy.
Human allograft rejection is the consequence of a succession of non-specific events, amplifying the immune reaction triggered by allogenic T cells. This is probably due to the abundant lymphoid population within the intestine and explains the main difficulty of controlling the rejection process once it has started. The destructive effect of the cytokines released by this inflammatory cascade emphasises the importance of prevention by active immunosuppression and early detection of rejection with appropriate immunohistochemical monitoring. Other complications of intestinal transplantation include rare cases of graft versus host disease, cases of lymphoproliferative disorders related to small bowel transplantation, and the usual complications of immunosuppression such as viral and fungal infections.
Finally, despite dramatic improvements in clinical outcome, indications for small bowel transplantation will always be rarer than for other solid organ transplants such as kidney, heart, or liver. In Britain an estimated two patients per million population, with an equal number of adults and children, are estimated to require small bowel transplantation each year.11 The procedure should be offered to patients with small intestine insufficiency due to anatomical abnormalities (short bowel syndrome) or functional disorders (intractable diarrhoea of infancy or chronic intestinal pseudo-obstruction syndrome). In the treatment of intestinal failure, however, small bowel transplantation can only become standard when it can offer greater safety and better quality of life than long term home parenteral nutrition.