By PAM LOWNEY

On Feb. 28 -- exactly one year after she was born -- Jackie Seki received a new small intestine and liver. Her doctors in Hawaii had not expected her to survive her first 48 hours, said her mom Liann Seki.

Born with neuronal dysplasia, Jackie's small intestine lacked sufficient ganglion cells, special nerve cells that receive signals from the brain telling intestinal muscles to contract and move food through the bowel. Joining the Intestinal Transplant Program at Lucile Packard Children's Hospital when she was 3 months old, Jackie was unable to eat, surviving her first year on continuous intravenous feeding. Like others dependent on this therapy, her liver soon began to fail.

Launched in 2001, the transplant program provides a last resort for children with intestinal failure who are unable to stay on intravenous feeding, said Ricardo Castillo, MD, professor of pediatrics and program director. Congenital abnormalities, traumatic injury and a number of diseases that attack the bowel can lead to end-stage intestinal failure.

Just a decade ago, small intestine transplant surgery was little more than an experimental procedure. Major advancements in surgical techniques and immunosuppressive drugs have since turned it into a viable, life-saving therapy.

Jackie Seki gets a kiss from her mother, Liann. The 1-year-old girl was among the first patients at Packard Children's Hospital to receive a rare small intestine transplant. The native of Hawaii was unable to eat food normally before the procedure and her liver was starting to fail. With the surgery behind her and the risk of organ rejection fading, she is now eating her way toward recovery. Photo: Pam Lowney

Drawing on its close association with the School of Medicine, the transplant program has contributed to this transformation. "We've had very good success," said Castillo, "easily equal to the major centers that have been doing this longer."

Of the 40 children referred to the program, half have been eligible for transplantation and wait-listed for donor organs. To date, nine children have undergone surgery, seven of whom survived and are doing well today.

Because program services go well beyond the scope of surgery, Castillo encourages early patient referral. The program brings together a pediatrician, nutritionist, transplant surgeon, child-development specialist and social worker to evaluate and stabilize each patient during the wait for an appropriate donor.

In some cases, the team has rehabilitated liver function to where the child no longer required both a liver and a small intestine transplant. Other children have recovered sufficient intestinal function to avoid surgery altogether.

Research at the School of Medicine laid an early foundation for the success of the clinical program. In 1998, Randall Morris, MD, professor (research) of cardiothoracic surgery, led a team in developing Rapamycin, a drug therapy now widely used as a lifelong immunosuppressant to prevent organ rejection, a particularly acute problem for intestinal transplant patients.

"The bowel is a barrier to infection so it is chock-full of immune-fighting mechanisms," explained Castillo. "When you put a native immune-fighting mechanism into a different body with its own immune-fighting mechanism, it is a set-up for rejection."

Minimizing this clash during surgery and recovery requires a high-dose mix of three aggressive immunosuppressant agents. Once the new bowel begins to function, the child is moved to the less toxic Rapamycin for lifelong therapy.

Rapamycin prevents "chronic" rejection, a progressive deterioration of the transplanted organ that occurs in most patients who survive the first few months after surgery. Unlike other suppressants, though, Rapamycin does not debilitate a child's ability to ward off infection.

Though initially focused on the clinical program at Lucile Packard Children's Hospital, Castillo said he is now eager to create a research counterpart at the School of Medicine to investigate the common issues faced by his patients.

In collaboration with Alan Pratt, MD, a pediatric fellow at the hospital, Castillo has already developed an effective animal model for testing new therapies. In July he will present his work at the World Congress of Gastroenterology in Paris.

"The fact that we have already established an animal model for small intestinal transplant gives us a huge leg up in terms of progress," said Castillo, who sees great potential for collaboration with school immunologists and infectious disease specialists.

Initial research, he said, will focus on improving immunosuppression, using the GLP2 growth factor to enhance the function of the transplanted intestine and treating cytomegalovirus and other infections common to transplant patients.

In addition to training fellows in pediatric gastroenterology and intestinal transplantation, the transplant program offers residents and medical students an opportunity to learn about dehydration, diarrhea, oral aversion and other fundamental gastrointestinal concepts.

"It is like learning a lot of really basic stuff from a very unusual situation," said Castillo. Jackie's mom affirms the educational value of the program. "We have been here since June and the residents have seen Jackie's progress. They see what can be done with kids," said Seki. "So when they go out into the world and into other hospitals, they'll have higher expectations. These residents will raise the bar."

Today, Jackie continues to inspire those working with her about the possibilities of medicine. Not only is she accepting her new intestine and liver but for the first time in her life, she is eating orally.