Since May 1990, 240 patients have received 259 transplants involving the small intestine at the University of Pittsburgh, representing the largest clinical experience of any center in the world, reports Geoffrey Bond, M.D., assistant professor of surgery at the Starzl Transplantation Institute and the University of Pittsburgh School of Medicine.
While overall, the one-year patient survival for the entire experience is 80 percent, one-year survival for patients transplanted within the last five years improved to 90 percent, compared to 72 percent in both 1990 and 1995. The overall five-year patient survival is 60 percent and 10-year patient survival is 39 percent. An adult and child who were transplanted more than 13 years ago at the University of Pittsburgh are the world's longest surviving recipients of a liver-intestine transplant.
"The improvements we have seen in survival rates are clearly related to changes we've made with respect to immunosuppression. As we have better come to understand the rejection process and the unique characteristics of the small intestine, we have been able to make important refinements to therapy. This evolution of care has had a real impact on our patients, and the entire field has benefited as well," noted Dr. Bond.
While in 1990 the availability of the drug tacrolimus made successful transplants of the intestine feasible for the first time, infection and rejection problems still plagued the field.
Over the years, additional advancements have been made and improved survival rates have been achieved. One approach that has had an impact on results at the University of Pittsburgh is its unique clinical protocol that involves far fewer drugs and much lower doses of immuno- suppressive agents than conventional therapies.
"We're seeing less infection and fewer adverse side effects and complications that are usually associated with high doses of anti-rejection drugs," said Dr. Bond.
The approach has many of the patients transplanted in the last year or so taking a single anti-rejection drug as few as one to three times a week.
In 1990, the rate of opportunistic infection was between 45 and 55 percent. Now infection occurs in about 9 percent of cases. Rates of rejection have also improved. In 1990, the rate was 88 percent. Today it is 40 percent, a remarkable improvement for an organ that is particularly prone to immune system attack.
Of the 259 transplants performed at the University of Pittsburgh, 102, or 44 percent, were of the small intestine alone, performed in 74 adults and 41 children. While combined liver and intestine transplants accounted for 36 percent of the transplants, more were performed in children -- 67 compared to 27 in adults. Multivisceral transplants, which include the small intestine, liver, stomach, pancreas and duodenum, were performed in 25 adults and 12 children, and modified multivisceral transplants without the liver were performed in nine adults and four children.
"The shortage of organs remains a limiting factor to successful intestine transplantation, particularly for very young children, for whom size-matched organs are in short supply. To overcome this problem, we have been utilizing larger donors and subsequently reducing the graft size prior to transplantation," stated Dr. Bond.
In a separate presentation, the Pittsburgh team reports the use of a combination of techniques they have developed that have allowed organs from larger donors to be used. Sixteen children underwent transplants of the intestine alone or in combination with the liver using organs donated by larger individuals that were reduced in size to fit the recipients. The novel surgical approaches have permitted proper healing of the abdominal wall and all patients remain alive, well and free from total parenteral nutrition (TPN).
Patients with intestinal failure require intravenous nutrition with TPN, which can cause life-threatening complications such as liver failure and line infections. As such, intestinal transplantation is considered a life-saving procedure that can also have a profound effect on quality of life. More than 80 percent of the patients transplanted at the University of Pittsburgh no longer require TPN and are able to return to a completely normal diet.
Intestinal transplants are not experimental. Since April 2001, Medicare has approved transplants of the small intestine for patients with specific TPN-related complications at centers that perform a minimum of 10 transplants each year and have a minimum one-year patient survival rate of 65 percent. The national coverage decision by the Centers for Medicare and Medicaid Services was made based on an appeal by the University of Pittsburgh.
Patients with acute irreversible intestinal failure that cannot be repaired surgically or are at risk of rapidly developing liver complications should also be considered for early intestine transplantation, suggests the Pittsburgh team's clinical experience with nine patients who are all doing well. Transplantation to replace organs acutely and irreversibly injured before complications arise represents a possible future direction for the field.