First Double Hand Transplant: A Newsmaker Interview With Nadey S. Hakim, MD, PhD

Laurie Barclay, MD

July 07, 2003

July 7, 2003 — Editor's Note: A French-Italian team performed the first hand transplant in September 1998, but the hand had to be removed after 23 months because the patient was not compliant with immunosuppressive therapy. Now this team has successfully performed the first double hand transplant with an excellent functional result, according to a case report published in the July issue of the Annals of Surgery .

The recipient was a 33-year-old man with bilateral amputation after a blast injury. Before transplantation, a psychiatric team determined his ability to understand the potential risks, the absolute necessity for immunosuppressive therapy, and his motivation to cope with intensive rehabilitation.

After procurement of the upper extremities from a multiorgan cadaveric donor, the surgical team prepared graft and recipient stumps, then attached the hands using bone fixation, arterial and venous anastomoses, nerve sutures, joining of tendons and muscles, and skin closure. Immunosuppressive treatment included tacrolimus, prednisone, and mycophenolate mofetil, with antithymocyte globulins and then CD25 monoclonal antibody for induction.

There were no surgical complications. Two episodes of acute skin rejection with maculopapular lesions resolved completely in 10 days on increased steroids.

A comprehensive rehabilitation program consisted of physiotherapy starting 12 hours after surgery twice daily for the first year, with controlled-motion passive exercises for the first two weeks, followed by active exercises to improve forearm pronation, wrist and finger extension, and pinch strength. At two months, the addition of electrostimulation and occupational therapy improved development of extrinsic and intrinsic muscles and sensory function.

By six months, the patient had sensitivity to pain and thermal stimuli on the dorsal and palmar aspect of both hands, on all fingertips except the left thumb, and on the anterior side of both forearms. By nine months, intrinsic muscles began to function, with continued recovery by 12 months. Electromyography and somatosensory evoked potentials confirmed partial reinnervation.

By one year, the patient could perform the same daily activities that were possible with myoelectric prostheses used before transplantation, and he could also perform additional activities including holding a pen, a glass, or a pair of scissors; shaving; and other personal hygiene tasks.

By 15 months, sensorimotor recovery tests revealed good functional return, except for limited active range of motion of the wrists, and quality of life had improved. Mean pinch grip was 300 g bilaterally; grip strength was 150 g; and he could perform several dissociated movements involving the fingers and thumbs.

Functional magnetic resonance imaging (fMRI) at 2, 4, 6, and 12 months showed cortical reorganization, with a progressive shift of cortical hand representation from the lateral to the medial region in the motor cortex.

Ongoing psychological support and evaluation revealed that during the first three months, the patient was worried about the eventual outcome and troubled by seeing the transplanted hands. However, by three months, he considered "the" hands to be "his own" hands. He continued to be compliant with the immunosuppressive regimen and with rehabilitation program, and his self-report showed satisfaction.

Although the surgical team felt that these results were at least as good as those achieved with replanted upper extremities, they await longer follow-up to demonstrate the final functional restoration. In the 15 months since the manuscript was submitted, the patient has had continued improvements and no complications.

To find out more about this landmark procedure and its feasibility on a broader scale, Medscape's Laurie Barclay interviewed coauthor Nadey S. Hakim, MD, PhD, surgical director of the Transplantation Unit in St. Mary's Hospital in London, U.K.

Medscape: How successful was this double hand transplant in terms of functional outcome and quality of life?

Dr. Hakim: Denis Chatelier, who is the first ever person in the world to receive a double hand transplant, is doing very well since his transplant in January 2001. He is leading a normal life, back to his usual job in a factory, which involves using his hands. His function is back to over 65% of normal, which is a very reasonable result.

Medscape: Does he still require ongoing therapy?

Dr. Hakim: He has physical therapy at his local hospital, one hour daily.

Medscape: What are the combined costs to double transplantation, including surgery, immunosuppressive treatment, and extensive rehabilitation? Who pays these costs, and what is the justification for the expense if functional recovery is limited?

Dr. Hakim: The cost of the transplant including surgery, immunosuppression, and extensive rehabilitation is more than other transplants such as kidney or liver, because indeed it involves the extensive rehabilitation. The cost is paid by the government in France and therefore there is no cost incurred by the patient himself. There is, of course, justification for the expenses because by transplanting the patient we are hoping that he would achieve an even better function within time, and patients transplanted in the future might get even better by refining the technique and improving on the immunosuppression.

Medscape: How likely are recipients to remain compliant with immunosuppressive treatment and with the intensive rehabilitation needed for optimal results?

Dr. Hakim: Regarding compliance, only one patient so far has been noncompliant and unfortunately has lost his limb, and that was the first ever transplant, performed in France in 1998. This led us to be more careful in the selection of our patients.

Medscape: Are more double transplants planned? How likely is it that this procedure will be widely used and accepted?

Dr. Hakim: There have already been two others, the most recent two months ago with an excellent result. More hand transplants are planned, mainly in Europe and the United States. I do not believe that the procedure will be very widely used and possibly not accepted by everyone but, regardless of that, over 22 hand transplants have been performed in the world and more will happen.

Medscape: What criteria will be used for future recipients?

Dr. Hakim: It has become more acceptable to do a double hand transplant than a single hand transplant from the ethical point of view. We learned our lesson from the first hand transplant that it's very important for the recipient to be a good patient, one who will take his meds regularly. So compliance is a major criterion, which we determine through psychological assessment. From a medical and technical viewpoint, we have also found that the more distal the amputation, the better the result. A patient with stumps just above the wrist has a much better chance for success than one with stumps closer to the elbow.

Medscape: How difficult is it to find suitable donors? In case of limited availability, how will optimal use and distribution of available limbs be facilitated?

Dr. Hakim: It is not very easy to find donors. It is more difficult to have a donor family give consent to donate the limbs, as these are visible structures. However, it has been possible so far to achieve some success with organ donation.

Medscape: Do you envision the need for transplantation committees to determine who should receive hand transplants, or is this more likely to be an individual decision based on patient criteria and donor availability?

Dr. Hakim: It will most likely be an individual hospital decision, but each hospital will have a large committee addressing this, including a psychologist, psychiatrist, physical therapist, and other medical and surgical specialists all involved in the selection.

Medscape: What is the significance of the cortical reorganization seen on fMRI?

Dr. Hakim: The significance of the cortical reorganization seen on MRI is very important because this is the most important element showing that the limbs transplanted have had their neurological connection reinstated and that the brain has been reorganized in a way to recognize the movements into those new limbs.

Medscape: Are there any ethical considerations to double hand transplantation?

Dr. Hakim: It is more acceptable to perform a double hand transplant in view of the risks taken and the immunosuppression necessary. A patient with only one lost limb can live a reasonable life; however, someone with no limbs whatsoever is considered [disabled] enough to go through that major surgery.

Ann Surg. 2003;238:128-136

Reviewed by Gary D. Vogin, MD