Hand Transplantation Remains Controversial

Hand transplantation remains a controversial issue, but recent developments and promising results with 24 worldwide hand transplants demonstrate that there may be a larger place for hand transplantation in the near future.

Two American hand transplant patients and others around the world have demonstrated excellent short- to medium-term graft survival and functional return similar to replants, according to Warren C. Breidenbach, MD, FRCS(C), of Louisville, Ky. the lead surgeon on the two American hand transplants.

In addition, researchers have found no chronic rejections. “By this point – 5 years – you normally see 50% of kidneys are starting to show some level of chronic rejection,” Breidenbach said at the American Society for Surgery of the Hand (ASSH) annual meeting. “Why we are not seeing it, we do not know. We are a bit surprised.”

But some hand surgeons and ASSH itself, as indicated by a position statement on the organization’s Web site, believe that the procedure has not proven its superiority to other techniques, nor that it is safe enough to perform at this time.

“Before we can in good faith really advocate hand transplantation, we need to get our arms around what the true functional benefits are from the patient’s perspective – beyond the fact that they may like having a hand again or they feel a stronger sense of self-esteem,” said Matthew M. Tomaino, MD, chief of the division of hand, shoulder and elbow surgery, University of Rochester Medical Center in Rochester N.Y.

Fine motor motion

Breidenbach presented updated results on the two American hand transplant patients – one at 7 years postop and the other at 5 years postop. Both patients continued to show improvement in intrinsic muscle strength, range of motion, sensation and 2-point discrimination (2-PD).

The patient, who is 7 years postoperative, is the recipient of the longest surviving hand transplant in the world. He has demonstrated the ability to perform fine motor motion, “which is something that was thought would not be possible,” Breidenbach said.

This patient also had a Carroll score of 72 out of 99 possible points and is now able to perform finer tasks such as picking up small ball bearings. However, he still cannot button his shirt or easily use cutlery.

Since 6-year follow-up, the researchers have seen a significant improvement in the patient’s sensation on Semmes-Weinstein Monofilament testing at the fingertips – now 2.83 in all fingertips, according to the study abstract.

Static 2-PD improved in all the patient’s fingers, but moving 2-PD has not changed and remains at about 10 mm, Breidenbach said.

“The second patient does not have return to 2-PD at 5 years,” Breidenbach said. “[But] he has more active thumb motion than the first patient. He worked as a gutter installer in roofing and has returned to his job.”

In the second patient, researchers observed motor and sensory return at different time points than in the first patient. This patient’s Carroll score is 49. Using Semmes-Weinstein Monofilament testing the researchers found a loss of protective sensation at the patient’s fingertips.

Hand surgeons connect the bone of a donor hand transplant to the second American transplant recipient’s arm Warren C. Breidenbach, MD, FRCS(C) prepares the donor limb with a fellow hand surgeon
Hand surgeons connect the bone of a donor hand transplant to the second American transplant recipient’s arm (left). Lead hand surgeon on the two American hand transplantations, Warren C. Breidenbach, MD, FRCS(C), prepares the donor limb with a fellow hand surgeon (right).
Photos: Lair J, courtesy of Jewish Hospital; Kleinert, Kutz and Associates Hand Care Center; and the University of Louisville.

Risk-benefit balance

Although patients clearly benefit from receiving a hand transplant, a risk-benefit balance remains, said W.P. Andrew Lee, MD, of the University of Pittsburgh School of Medicine.

When patients receive a hand transplant, they also pay a price: immunosuppressant medication, which protects against rejection of the hand, but lowers the patients’ ability to fight infection and disease.

In addition to infections, long-term immunosuppression can cause organ failures, including kidney and liver failure or diabetes. Surgeons have also seen rejection episodes in these patients that exceed those of kidney transplants, but the hand transplant-related episodes are easily controlled, Breidenbach said.

In the two American hand transplant recipients, researchers found rejection episodes and pneumonia, as well as persistent hypertension, avascular necrosis of the hip and transient diabetes in the second patient.

“The second patient had more rejection episodes [and] was a little harder to control,” Breidenbach said. This patient also required a hip replacement on one side.

Internationally, two hand transplant recipients have undergone removal of their transplants, Lee said.

One was a French patient who did not comply with his immunosuppressant medication regime and eventually underwent removal for severe skin necrosis.

The other was a Chinese patient who either had rejection or vascular thrombosis, according to Lee who studied 11 of the hand transplant recipients around the world as a Sterling Bunnell traveling fellow for the American Society for Surgery of the Hand in 2003.

Despite these risks, “we have a 92% worldwide allograft survival,” Breidenbach said. “And in reality we may even have a 100% survival if [all patients] take their medication … No mortalities, no serious infections, no tumors and no major criticism in the major ethical centers … and no chronic rejection.”

Through Lee’s testing of these patients, he found that they were all pain free, they had an aesthetics score of 93.8 and had an overall functional score of 76.9. “The benefit is there if we can lower the risk and tilt the balance,” Lee said.

A Chinese patient’s transplanted right hand A Chinese patient’s transplanted right hand
A Chinese patient’s transplanted right hand, which he uses to hold chopsticks and play mahjong. He can unbutton, but not button, his shirt.
Photos: Lee WPA

Composite tissue transplant

Researchers may well be on their way to tilting that balance. To date, surgeons have completed more than 50 worldwide composite tissue transplantations, including faces, larynx and abdominal walls.

Lee, Breidenbach and others are studying new developments in transplant immunology that will contribute to not only hand transplantation, but all composite tissue transplantation. Lee and his colleagues are seeing promising results in kidney transplants using a new induction agent, alemtuzumab (Campath-1H, Berlex Inc.), followed by a low dose of the traditional immunosuppressant tacrolimus or FK-506 (Prograf, Fujisawa). Using Campath-1H subjects patients to fewer and less toxic drugs, while accepting their transplanted organ or tissues.

Advances in the laboratory include a chimerism protocol that involves infusing the marrow cells from a donor into the recipient before transplantation to create a mixed chimera, essentially making it easier to perform the transplant.

Breidenbach and his colleagues are using mixed allogenic chimerisms in hearts and kidneys. “If we establish the model there, we will immediately apply it to the hand,” he said.

“We cannot predict the future, but I do not think we are that far away from being able to achieve composite tissue transplant with much lower side effects than what the patients are currently subject to,” Lee said.

Tomaino believes researchers need to evaluate more objective metrics, compare outcomes between hand transplantation and prostheses, and evaluate the procedure’s cost of care.

“I think it is a tremendous accomplishment technically and medically … but it does not mean it is advisable,” he said. “Until we actually look at the tremendous functional gains that can be obtained by prosthetic fitting and compare that to these transplanted patients, we are really dealing with an incomplete picture.”

Even with all the developments, surgeons are slow to perform more hand transplantations because of insurance coverage issues and the fact that many amputees do not want hand transplantation, Breidenbach said.

Finding donors is another obstacle. “I have had a patient on the list now for 3 years and we have not had a donor from the family come forward,” Breidenbach said. He believes, however, that hand surgeons should not discourage patients from hand transplantation. Their responsibility to the patient is to deliver the facts.

For more information:

  • Breidenbach WC, Gonzalez RN, Gorantla VS, et al. The two American hand transplantations: Seven-year follow-up of the first recipient and four-year follow-up of the second recipient. #38.
  • Lee WPA. The future of hand surgery/robotics in the upper extremity: The future of transplantation. Symposium 2. Both presented at the American Society for Surgery of the Hand 61st Annual Meeting. Sept. 7-9, 2006. Washington.

Tina DiMarcantonio is a correspondent who primarily writes for O&P Business News’ sister publication, Orthopedics Today. This article originally appeared in Orthopedics Today.

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