Larynxes Successfully Transplanted in Dogs : Medicine: The technique has eluded researchers for 30 years. The UCLA team says it is a major step toward accomplishing the procedure in humans.

UCLA researchers have capped a 30-year quest by successfully transplanting larynxes in dogs, a major step, they say, toward accomplishing the procedure in humans.

The technique has eluded researchers for so long because of their inability to achieve a functioning larynx by reactivating nerve endings that connect the larynx, or voice box, to the brain stem.

Dr. Gerald Berke, a UCLA surgeon, said Wednesday that his team achieved success by attaching the laryngeal nerves at a different site than had previously been used. “It’s a very simple thing that could have been done years ago,” he said.

About 12,500 Americans have their larynxes removed every year because of throat cancer. Although the procedure is not life-threatening, those who have had the larynx removed are no longer able to smell or taste food or breathe or speak normally.

Berke predicted that the procedure could be used in humans in as little as four years, but noted that several ethical and economic problems must be solved first. In particular, the drugs needed to suppress the immune system’s attack on the foreign larynx might put the recipient at an unacceptably high risk for a cancer recurrence.

“But there are certain types of trauma (that do not involve cancer) in which the procedure could be ethically used now,” said Dr. Lawrence Hoover, am otolaryngologist at the University of Kansas Medical Center in Kansas City. “And when we get to the point where transplant rejection can be suppressed without interfering with the body’s ability to fight cancer, Dr. Berke’s innovation . . . will make it possible to proceed immediately.”

“This is a very strong piece of work,” added Dr. Roger L. Crumley, an otolaryngologist at the UC Irvine Medical Center. But he added that his estimate of human application was more along the line of five to 10 years.

The larynx, located at the top of the trachea, is an organ made of muscle and cartilage lined with mucous membrane. It is the center of voice production and is involved in functions such as swallowing and coughing. It also serves as a valve to keep fluids out of the lungs.

Survival without the larynx is possible but it produces “tremendous changes” in lifestyle, Berke said. Such patients typically speak with an artificial voice box that has an often weak and unexpressive sound. Furthermore, because the patient no longer breathes through the mouth and nose but through a hole in the throat, the sense of taste and smell is lost. Patients generally cannot swim because of the risk of drowning, and even showers can be hazardous.

Surgeons have attempted to transplant larynxes in both humans and animals for at least 30 years, but the procedures have failed because of the difficulty of reattaching nerves in the larynx to the central nervous system, a process called reinnervation. If these connections are not made properly, the larynx will be lifeless and dysfunctional.

Most researchers have tried to connect a bundle of nerve endings outside the larynx to the brain stem, but this has not worked. Berke focused instead on a site inside the larynx where the bundle of nerve tissues has branched into two pathways, one that controls opening and one that controls closing of the larynx.

In his first studies, he performed surgery on dogs--whose larynxes are similar to humans’--to sever the nerves beyond the junction site inside the larynx, then he sutured them back together. He observed that the function of the larynxes was retained after this procedure, whereas it was not if the nerves were severed outside the larynx.

He then used the new technique to transplant larynxes into five dogs. All the procedures were successful and, “for all practical purposes, they functioned totally normally,” including producing barks, he said.

Berke and his colleagues are now attempting to refine the procedure so that less immunosuppression is necessary, or so that it can be more selective, allowing a recipient’s immune system to fight off any residual cancer cells.

He also noted that in humans, the required immune suppression is quite expensive, about $15,000 per year. Insurance companies may balk at such a high cost for a transplant that is not necessary to preserve life.

“That brings up a philosophical question,” he said. “Is our goal just to cure illness at all costs, or are we obliged to try to improve the quality of life for patients during their lifetimes? That’s a question we are going to have to answer soon.”