Nation's first face transplant done in Cleveland

By MARILYNN MARCHIONE

CLEVELAND, 17 dec 2008 – A woman so horribly disfigured she was willing to risk her life to do something about it has undergone the nation's first near-total face transplant, the Cleveland Clinic announced Tuesday. Reconstructive surgeon Dr. Maria Siemionow and a team of other specialists replaced 80 percent of the woman's face with that of a female cadaver a couple of weeks ago in a bold and controversial operation certain to stoke the debate over the ethics of such surgery.

The patient's name and age were not released, and the hospital said her family wanted the reason for her transplant to remain confidential. The hospital plans a news conference Wednesday and would not give details until then.

The transplant was the fourth worldwide; two have been done in France, and one was performed in China.

Surgeons not connected to the Cleveland case reacted cautiously since little is known about the circumstances, but generally praised the operation.

"There are patients who can benefit tremendously from this. It's great that it happened," said Dr. Bohdan Pomahac, a surgeon at Harvard-affiliated Brigham and Women's Hospital in Boston who plans to offer face transplants, too.

Dr. Laurent Lantieri, a plastic surgeon at Henri Mondor-Albert Chenevier Hospital, near Paris, who did a face transplant on a man disfigured by a rare genetic disease, said: "This is very good news for all of us that doctors in the U.S. have done this."

Unlike operations involving vital organs like hearts and livers, transplants of faces or hands are done to improve quality of life — not extend it. Recipients run the risk of deadly complications and must take immune-suppressing drugs for the rest of their lives to prevent organ rejection, raising their odds of cancer and many other problems.

Arthur Caplan, a leading bioethicist who has expressed grave concerns in the past about such surgery, withheld judgment on the Cleveland case but said the woman's doctors should give her the option of assisted suicide if they wind up making her life worse.

"The biggest ethical problem is dealing with failure — if your face rejects. It would be a living hell," said Caplan, bioethics chief at the University of Pennsylvania. "If your face is falling off and you can't eat and you can't breathe and you're suffering in a terrible manner that can't be reversed, you need to put on the table assistance in dying."

Siemionow's long and careful preparation should help prevent such a horrific outcome, those familiar with her said. Siemionow, (pronounced SIM-en-now), 58, a noted hand microsurgeon, has been testing the surgical approach and ways to temper the immune system's response in experiments for more than a decade.

She has considered dozens of potential candidates over the past four years, ever since the clinic's internal review board gave permission for her to attempt the operation, and has said she would choose someone severely disfigured as her first case.

"She's a leader in this field. She's been investigating this for a long time. She has done the most amount of research in small animals looking at this," said Dr. Warren Breidenbach, a surgeon at Jewish Hospital in Louisville, Ky., who did the nation's first hand transplant, in 1999. Siemionow trained with him in Louisville.

The world's first partial face transplant was performed in France in 2005 on a 38-year-old woman who had been mauled by her dog. Isabelle Dinoire received a new nose, chin and lips from a brain-dead donor. She has done so astoundingly well that surgeons have become more comfortable with a radical operation considered unthinkable a decade ago.

Two others have received partial face transplants since then — a Chinese farmer attacked by a bear and a European man disfigured by a genetic condition. Both are believed to be doing well, though details, especially of the Chinese case, have been scant.

In the Cleveland case, "it is very important what kind of recipient they selected," and how great the need was, Pomahac (POE-ma-hawk) said. "Hopefully it will open the door both to the public and to other centers" wanting to do these operations.

Details of the Cleveland surgery are not known, but surgeons generally transplant skin, facial nerves and muscle, and often other deep tissue. That is done so the new face will actually function and not just be a mask.

In an interview at the Cleveland Clinic in 2005, Siemionow spoke of the terrible need she saw in people horribly disfigured, and how badly it scarred their social and emotional lives, not just their bodies.

"There are no really good alternative therapies for the severely burned or patients with a facial injury or damage," she said.

Her task now is to prevent organ rejection while managing the risk of infection from taking strong immune-suppressing drugs.

Rejection is a possibility whenever someone receives an organ or cells from someone else because the body regards this as foreign tissue. Two types of problems can result.

The first is graft-versus-host disease, which could happen if the new facial tissue were to attack the recipient's body. The second is if the patient's body were to attack the transplanted face, causing inflammation and other problems at the site of the new tissue.

Either of these can be life-threatening. They can come on suddenly, within days or weeks of the operation, or set in slowly.

French Patient Calls Partial Face Transplant Very Satisfactory

Michael Smith
LYON, France, Dec. 12 -- Eighteen months after a partial face transplant, the patient is doing well and is "very satisfied" with the results of the surgery, researchers here said.Isabelle Dinoire now has "an almost normal appearance" and nearly complete function, according to Jean-Michel Dubernard, M.D., Ph.D., of the University of Lyon, and colleagues.
Action Points --->
Explain to interested patients that French surgeons performed a partial face transplant in 2005 on a woman who had been disfigured by a dog.
Note that this study says that results 18 months after the surgery were good and the patient is satisfied, but add that side effects were occasionally severe.
"The patient says she is not afraid of walking in the street or meeting people at a party, and she is very satisfied with the aesthetic and functional results," Dr. Dubernard and colleagues reported in the Dec. 13 issue of the New England Journal of Medicine.
A video posted with the report shows her speaking clearly in French, contracting the muscles of the transplant, and smiling.
The transplant was regarded a technical tour-de-force when it was performed in 2005, although questions were raised about the ethics of the surgery.But "the encouraging 18-month outcomes of face transplantation in our patient suggest that this procedure can offer hope for some patients with severe disfigurement," Dr. Dubernard and colleagues concluded.
The patients had two episodes of rejection, at 18 and 214 days after the surgery, characterized by the gradual development of erythema and edema.
The first was controlled with increases in the doses of oral prednisone, tacrolimus, and mycophenolate mofetil, as well as clobetasol ointment and prednisone mouthwashes, coupled with three 1,000-mg intravenous boluses of methylprednisolone.
The second was met with three 750-mg boluses of intravenous methylprednisolone, combined with prednisone mouthwashes and local applications of clobetasol and tacrolimus ointments. The oral corticosteroid dose was increased to 50 mg daily and tapered to 5 mg a day over eight weeks.
Dinoire had a progressive decrease in renal function, which her physicians attributed to the tacrolimus. When the drug was replaced with sirolimus, her renal function gradually improved, they said.
The surgery provided "a reasonable functional outcome," commented transplant specialist Maria Siemionow, M.D., Ph.D., D.Sc., of the Cleveland Clinic, but with "quite severe side effects," including two episodes of rejection and a decrease in renal function.
Because of the potential side effects, Dr. Siemionow said, she still considers such surgery should be a "last chance" that is considered only when all other options are exhausted.
Two other partial face transplants have been performed -- one in March 2006 in China and the other in January 2007 in France -- but no reports have been published on those cases, the researchers said.
"It should be almost a life-saving procedure" that allows a patient to resume a place in society, Dr. Siemionow said.
"You cannot walk on the street without a face," Dr. Siemionow said, and for that reason there are "patients who have severe deformity or after severe trauma who will be candidates."
But the selection of such patients has to be done "very carefully," she said.
Dinoire became a candidate for the surgery after her dog chewed her face, amputating the distal portion of her nose, both lips, chin, and adjacent parts of the cheeks.
Her doctors concluded at the time that conventional plastic surgery techniques would not work.
The donor was a brain-dead 46-year-old woman who had the same blood group as Dinoire. The two women also shared five HLA antigens.
Dinoire was able to eat and drink almost normally a week after surgery, the researchers reported, and sensation on the transplanted part of her face was normal by six months.
Functional recovery was slower, however. Dinoire started to regain control of the upper lip by 12 weeks after surgery and the lower lip by the end of the fourth month. She was able to close the lips by six months.
After a year, she could contract the chin muscles and the nose pyramidal muscles. Her smile was asymmetric for the first 10 months, but was "nearly normal at 14 months and normal at 18 months," the researchers said.
The study was supported by the university hospitals of Amiens and Lyon. The researchers reported no potential conflicts.
Primary source: New England Journal of MedicineSource reference:Dubernard J-M, et al "Outcomes 18 Months after the first human partial face transplantation" N Engl J Med 2007; 357: 2451-60.