Small bowel transplant: an evidence-based analysis.
OBJECTIVE
The Medical Advisory Secretariat undertook a review of the evidence on the effectiveness and cost-effectiveness of small bowel transplant in the treatment of intestinal failure.
Intestinal failure is the loss of absorptive capacity of the small intestine that results in an inability to meet the nutrient and fluid requirements of the body via the enteral route. Patients with intestinal failure usually receive nutrients intravenously, a procedure known as parenteral nutrition. However, long-term parenteral nutrition is associated with complications including liver failure and loss of venous access due to recurrent infections. Small bowel transplant is the transplantation of a cadaveric intestinal allograft for the purpose of restoring intestinal function in patients with irreversible intestinal failure. The transplant may involve the small intestine alone (isolated small bowel ISB), the small intestine and the liver (SB-L) when there is irreversible liver failure, or multiple organs including the small bowel (multivisceral MV or cluster). Although living related donor transplant is being investigated at a limited number of centres, cadaveric donors have been used in most small bowel transplants. The actual transplant procedure takes approximately 12-18 hours. After intestinal transplant, the patient is generally placed on prophylactic antibiotic medication and immunosuppressive regimen that, in the majority of cases, would include tacrolimus, corticosteroids and an induction agent. Close monitoring for infection and rejection are essential for early treatment.
The Medical Advisory Secretariat undertook a review of 35 reports from 9 case series and 1 international registry. Sample size of the individual studies ranged from 9 to 155. As of May 2001, 651 patients had received small bowel transplant procedures worldwide. According to information from the Canadian Organ Replacement Register, a total of 27 small bowel transplants were performed in Canada from 1988 to 2002.
The experience in small bowel transplant is still limited. International data showed that during the last decade, patient survival and graft survival rates from SBT have improved, mainly because of improved immunosuppression therapy and earlier detection and treatment of infection and rejection. The Intestinal Transplant Registry reported 1-year actuarial patient survival rates of 69% for isolated small bowel transplant, 66% for small bowel-liver transplant, and 63% for multivisceral transplant, and a graft survival rate of 55% for ISB and 63% for SB-L and MV. The range of 1-year patient survival rates reported ranged from 33%-87%. Reported 1-year graft survival rates ranged from 46-71%. Regression analysis performed by the International Transplant Registry in 1997 indicated that centres that have performed at least 10 small bowel transplants had better patient and graft survival rates than centres that performed less than 10 transplants. However, analysis of the data up to May 2001 suggests that the critical mass of 10 transplants no longer holds true for transplants after 1995, and that good results can be achieved at any multiorgan transplant program with moderate patient volumes. The largest Centre reported an overall 1-year patient and graft survival rate of 72% and 64% respectively, and 5-year patient and graft survival of 48% and 40% respectively. The overall 1-year patient survival rate reported for Ontario pediatric small bowel transplants was 61% with the highest survival rate of 83% for ISB. The majority (70% or higher) of surviving small bowel transplant recipients was able to wean from parenteral nutrition and meet all caloric needs enterally. Some may need enteral or parenteral supplementation during periods of illness. Growth and weight gain in children after ISB were reported by two studies while two other studies reported a decrease in growth velocity with no catch-up growth. The quality of life after SBT was reported to be comparable to that of patients on home enteral nutrition. A study found that while the parents of pediatric SBT recipients reported significant limitations in the physical and psychological well being of the children compared with normal school children, the pediatric SBT recipients themselves reported a quality of life similar to other school children. Survival was found to be better in transplants performed since 1991. Patient survival was associated with the type of organ transplanted with better survival in isolated small bowel recipients.


RESULTS
Despite improvement in patient and graft survival rates, small bowel transplant is still associated with significant mortality and morbidity. Infection with subsequent sepsis is the leading cause of death (51.3%). Bacterial, fungal and viral infections have all been reported. The most common viral infections are cytomegalorvirus (18-40%) and Epstein-Barr virus. The latter often led to ß-cell post-transplant lymphoproliferative disease. Graft rejection is the second leading cause of death after SBT (10.4%) and is responsible for 57% of graft removal. Acute rejection rates ranged from 51% to 83% in the major programs. Most of the acute rejection episodes were mild and responded to steroids and OKT3. Antilymphocyte therapy was needed in up to 27% of patients. Isolated small bowel allograft and positive lymphocytotoxic cross-match were found to be risk factors for acute rejection. Post-transplant lymphoproliferative disease occurred in 21% of SBT recipients and accounted for 7% of post-transplant mortality. The frequency was higher in pediatric recipients (31%) and in adults receiving composite visceral allografts (25%). The allograft itself is often involved in post-transplant lymphoproliferative disease. The reported incidence of host versus graft disease varied widely among centers (0% - 14%). Surgical complications were reported to occur in 85% of SB-L transplants and 25% of ISB transplants. Reoperations were required in 45% - 66% of patients in a large series and the most common reason for reoperation was intra-abdominal abscess. The median cost of intestinal transplant in the US was reported to be approximately $275,000US (approximately CDN$429,000) per case. A US study concluded that based on the US cost of home parenteral nutrition, small bowel transplant could be cost-effective by the second year after the transplant.


CONCLUSIONS
There is evidence that small bowel transplant can prolong the life of some patients with irreversible intestinal failure who can no longer continue to be managed by parenteral nutrition therapy. Both patient survival and graft survival rates have improved with time. However, small bowel transplant is still associated with significant mortality and morbidity. The outcomes are inferior to those of total parenteral nutrition. Evidence suggests that this procedure should only be used when total parenteral nutrition is no longer feasible.