Lung Transplant--Taking Risks to Save a Life : Medicine: The mother-daughter surgery illustrates the chances that doctors and family members are willing to take with experimental operations. The ultimate success will not be known for years.
The dramatic mother-to-daughter lung transplant at Stanford University Medical Center last week illustrates the risks surgeons and family members are prepared to take with potentially life-saving experimental operations.
The complex procedure, planned by doctors for the last year and a half, also demonstrates that transplant surgeons are no longer satisfied with simply prolonging a person’s life--particularly a child’s--for a year or two.
“A child that receives a transplant is going to need to grow and develop normally if you can ever consider that transplant successful,” said Dr. Vaughn A. Starnes, the chief surgeon for the operation.
Both mother and daughter, who have requested anonymity, were reported making good progress on Sunday as they continued their recovery from Thursday’s operations, which are believed to have been the first of their kind in the world.
The child suffers from a rare, invariably fatal, lung disease known as bronchopulmonary dysplasia. She also had a heart defect, which was corrected during the surgery.
But it now appears that the ultimate success of this and future living donor lung transplants will not be known for three to four years, when the girl’s health and development can be assessed.
The surgery is considered highly experimental because fewer than 20 lung transplants using cadaver donors have been performed in children worldwide and because of the potential risk to the mother.
In adults, several hundred lung transplants have been done, with a one-year survival rate of about 70% and a three-year survival rate of 50% or less, Starnes said. By comparison, heart, kidney and liver transplants are far more common and the overall results far better. Physicians suspect that one reason is that the lung may trigger stronger immunologic reactions in the body than do other organs.
Starnes, the director of Stanford’s heart-lung transplant program, has been planning living donor lung transplants since 1989. While Stanford’s results with dead unrelated donors compared favorably with many other programs, he had become frustrated by several factors.
* About a quarter of the children awaiting lung transplants were dying while they waited, because of the shortage of suitable organs. A typical child waited six to 12 months for a donor.
* Other children were surviving the operation, only to have their bodies ravaged by chronic rejection episodes--during which the breathing passages of the lungs are destroyed--and by the side effects of the powerful drugs needed to fight rejection. This was particularly true for children between the age of 3 and puberty.
“Patients are coming back to us and saying this is not such a great experience,” Starnes said. “I have had several rejection episodes. I am on chronic steroids. I am fat. I have hair everywhere. I feel like I’d rather die,” are some of the comments he has heard.
Starnes reasoned that partial lung transplants from living related donors, like the partial liver transplants from living donors that were pioneered at the University of Chicago last year, might solve some of of these problems.
Not only would there be a ready source of organs, but better tissue matching might lessen or eliminate rejection episodes. While surgeons who transplant livers or kidneys have a day or two to match the tissues of cadaver donors and recipients, this is not possible with hearts and lungs, which can only be stored for a few hours.
Armed with bits and pieces of data from research in pigs and lung transplants in adults, Starnes persuaded Stanford’s Institutional Review Board, which is charged with monitoring the safety and medical soundness of human experiments, that the time was right to proceed.
But, in an interview, Starnes acknowledged that their were many unknowns.
For example, Starnes’ experiments in pigs, which have yet to be published, demonstrated that a segment of lung transplanted from an adult pig can take over immediate lung function in a small offspring. But because the transplant lasted only 24 hours (all the animals were killed so the lung tissue could be examined), researchers do not know the long-term effectiveness of the procedure.
Starnes said he plans--but has yet to do--experiments in which segments of lungs from adult pigs are transplanted into piglets, who are then followed to see if they grow normally to maturity.
Starnes also does not know if a segment of an adult’s lung can handle the blood flow from the entire body as the child grows and how the lung tissue itself will grow. Only the girl’s right lung was removed, but little blood or oxygen will flow through her deceased left lung.
The transplanted right upper lobe of the mother’s lung is expected to expand to fill her daughter’s right chest cavity. As a result, the existing surfaces for gas exchange, known as alveoli, should become larger. But it is unlikely that new alveoli will develop, Starnes said.
Additionally, the tissues of the mother and daughter are not a perfect match. This means that the daughter is still at significant risk for rejection episodes.
Another significant issue is the potential surgical risk to lung donors. For a person with healthy lungs, the loss of one-third of one lung is unlikely to cause problems. But the surgery to obtain the lung segment is not entirely safe.
The risk is not hypothetical, said Arthur Caplan, the director of the Center for Biomedical Ethics at the University of Minnesota. “People definitely die from removing parts of solid organs.”
Stanford surgeons first discussed last week’s surgery with the family four months ago. Before final approval was given, members of the university’s review board “interviewed the mother and child separately to make sure the investigators had not unduly biased them,” Starnes said.
Review board members will conduct similar interviews before authorizing each of the additional five to 10 surgeries that are planned.
But despite this independent review, some experts in medical ethics doubt that meaningful informed consent for such surgery can truly be obtained from a parent with a dying child.
“It is a pretty coercive environment,” Caplan said. It is “hard to feel you can say no when you are talking about your own family and others will know if you say no.”
Starnes said he was sensitive to this issue, and believes that lung transplants using cadaver donors should remain the procedure of choice until his results are in.
The use of cadaver donors “only puts one person at risk. That is the bottom line,” Starnes said. If the results with living related donors “are very good three or four years out, then that will lend support to expanding the operation.”
