5Small Intestine and Combined Liver-Small Intestine Transplantation

Report

The reacquisition of bowel functions by transplantation of the small intestines was demonstrated to be technically feasible in dogs in 1966.(1). However, unlike the successful transplantation of the hearth, lung, liver, and kidney, transplantation of the small bowel in humans was unsuccessful through the 1980s, mainly because of the failure of immunosuppressive therapy to prevent graft rejections and graft versus host disease.(2-5). Typically, reports described stormy postoperative courses for small intestine graft recipients, with lengthy periods of intensive care before rejection of the grafts. The substantial lymphoid components in the small intestines are thought to contribute to making the control of immunological reactions that generally occur between graft and host more difficult in small bowel transplant than in other organ transplants. With the use of newer immunosuppressive agents, such as FK 506, transplantation of the small intestine may show improved outcomes as is currently being reported by investigators in Pittsburgh, PA.(6).

Background

The first successful small intestine transplantation was performed by Goulet et al(7). in 1989; the recipient was a 5-month-old infant. After being successfully treated for episodes of rejection, the infant was released from the hospital 10 months after surgery and was reported to be on an enteral diet and growing normally 30 months after transplantation. The only other report of successful small intestine transplantations was that by Todo et al.(6). Of the eight small intestines transplanted, one failed at 22 months and the others were reported to be surviving at 3 weeks to 5 months posttransplant. Four of the surviving recipients did not require parenteral nutrition at 2 to 5 months posttransplant, while the other three, at 1 month or less posttransplant, continued to be partially supported by parenteral nutrition.

All recipients of small intestine transplants have had short-bowel syndromes as the result of massive small bowel resections for conditions such as volvulus, enterocolitis, Crohn's disease, mesenteric vascular disease, or trauma. These patients had received total parenteral nutrition (TPN) for varying lengths of time.

Many patients receiving TPN develop complications such as severe infections caused by permanent intravenous catheters or metabolic disturbances of the liver caused by parenterally administered nutrition. Some TPN recipients with signs of liver dysfunction have received combined liver-small intestine grafts. Except for the recent success reported for small intestine transplants, recipients of these combined grafts appeared to have had better graft survival outcomes than those who received only the small intestine grafts.(8,9). The possible protective effect of the liver(10). was reminiscent of findings in animal studies showing that a simultaneous liver graft seemed to exert a protective effect that appeared to enhance the survival of other organ grafts.(11-13).

Discussion

The first successful combined liver-small intestine transplantation in a patient was reported in 1990 by Grant et al,(8). who transplanted a combined graft into a 41-year-old woman who had a short-bowel syndrome secondary to mesenteric thrombosis and had signs of liver failure as manifested by an antithrombin III deficiency. Episodes of graft rejection and transient acute graft versus host disease in the first few months posttransplant were overcome by administration of immunosuppressant agents including cyclosporine A, OKT3, steroid, and azathioprine. Two months after transplantation, the liver showed no clinical or biochemical evidence of liver rejection and was functioning to maintain liver enzyme values, bilirubin concentrations, and prothrombin times within the normal range. Since the eighth week posttransplant, the patient's entire nutrient, fluid, and electrolyte requirements were satisfied by an enteral diet. The patient was discharged from the hospital 8 months after surgery, after recovering from complications that resulted from a Hickman catheter infection, and was leading a normal lifestyle that included an unrestricted oral diet a year after grafting. In a subsequent report,(14). this patient was again noted to be in good health and on a normal diet 23 months posttransplant. This later report also described two additional liver-small intestine transplant recipients, one of whom died 9 weeks posttransplant with biopsy-proved cytomegalovirus enteritis. The other recipient was reported to be surviving and on a normal diet 11 months posttransplant.

In Pittsburgh, eight patients underwent combined liver-small intestine transplantation in 1990-1991.(6). All recipients (two adults and six children) had advanced hepatic disease with elevated serum total bilirubin concentrations and had been receiving TPN because of shortgut syndrome. An infant recipient died 23 days posttransplant of sepsis and graft versus host disease. The remaining seven recipients were reported to be well, at home, and consuming normal oral diets 7-20 months posttransplant. Except for very brief notations that liver-rejection episodes occurring in some of the patients were treated successfully and that the livers resumed normal function before the grafted intestine,(15). none of the reports presented any data to evaluate functional status of the transplanted livers in these patients.

Recently a report from Wisconsin(16). described a 14-month-old child with short-gut syndrome, cirrhosis, and variceal bleeding, who received a combined liver-small intestine transplant. The child's postoperative course was apparently satisfactory, and biopsy showed that the intestines were histologically normal and viable. However, severe coagulopathy and renal failure developed, and the patient died on the 52nd postoperative day.

Summary

Recent published accounts of experiences with either small intestine or combined liver-small intestine transplants indicate that both types of transplantations may be feasible, with some expectation of successful outcome in terms of graft survival and benefit to the patient. Clinical and outcome data for recipients of small intestine transplants are presented in Table 1, and data for recipients of combined liver-small intestine grafts are presented in Table 2. Only the Pittsburgh group has reported successful transplantations and survival of recipients of small intestine (eight patients, one graft failure) and combined liver-small intestine transplants (eight patients, one death).(6). Aside from these patients, there have been reports of a few other recipients with generally poorer outcomes at other transplant centers. In Ontario, Canada, two of three patients who received combined liver-small intestine grafts were reported to be surviving, and the only recipient of a small intestine transplant died 10 weeks after surgery.(14). In Paris, France, of five patients who received small intestine grafts, only one child is surviving with a functioning graft.(17). An unsuccessful combined liver-small intestine transplantation was done at one other center,(16). and unsuccessful small intestine transplantations were attempted at three other centers. (18-21). The total experience reported in the literature numbers 18 small intestine transplantations with eight surviving, functioning grafts. Twelve combined liver-small intestine transplantations have been done, with nine recipients surviving with functional grafts. Perhaps with improvements in immunosuppressive therapy, satisfactory long-term outcomes might be expected. Although the results with the use of FK 506 reported from Pittsburgh are encouraging, the small number of cases so far, the short period of follow-up, and the lack of similar successful transplantation experiences at other transplant centers preclude the ascertainment of whether transplantation of the small intestine or the combined liver-small intestine is a generally beneficial treatment procedure at this time. The short period of follow-up is of concern in view of the reported failure of one of the grafts after 17 months and another after 22 months.

Table

Table 1. Small intestine transplantation.

Table

Table 2. Combined liver-small intestine transplantation.

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AHCPR Pub. No. 93-0067