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Hand Surgery Department of Clinical Sciences, Malmö Lund University Skäne University Hospital, Malmö, Sweden
Abstract
Hand transplantation is a controversial surgical procedure that can result in useful hand function but requires lifelong medication with immunosuppressive drugs to prevent rejection. Nerve fibres from the recipient’s residual forearm must regenerate into the transplanted hand to reinnervate its intrinsic muscles and sensory receptors. A key issue is restoring sensory functions in the transplanted hand to achieve functional integration. Although more than 70 hand transplants have been performed in more than 50 patients so far, these procedures are only performed in select cases at a few world centres.
Transplantation of kidneys, hearts and livers has improved quality of life for many severely ill people, creating new possibilities for surviving a life-threatening illness. But what about hands? Is it possible to transplant a hand from one individual to another as with a kidney, heart or liver?
The concept of hand transplantation raises several questions. It is easy to assume that such a procedure could be beneficial to people who have lost one or both hands. However, hand transplantation can also create severe problems from the psychological, emotional, ethical, juridical and medical viewpoints. Unlike a heart, kidney or liver transplant to treat a life-threatening illness, many amputees see a hand transplantation as a ‘life-giving’ procedure, restoring their body image and facilitating their occupational and social integration [1]. Therefore, it is extremely important to weigh the benefits against the risks associated with a hand transplant before making the decision to go ahead with the operation [2–9].
Having a transplanted hand that previously belonged to a deceased individual can create substantial psychological problems: The hand is not hidden inside the body like a transplanted kidney or heart, but is freely exposed to the recipient as well as the environment. A transplanted hand bears all the characteristics of the deceased donor with respect to size, colour, hair growth, birthmarks, nevi, possible scars and even fingerprints. This can be hard for the recipient to accept and adjust to mentally, especially since the transplanted hand will lack sensation and sensory feedback for long time. During this period, the new hand may indeed be perceived as a ‘dead man’s hand’ and feel like a foreign object rather than a true part of the recipient’s body.
In the long term, it is possible to achieve fairly good recovery of motor functions as well as some sensory functions in the hand, even if the new hand will never work as well as the recipient’s original hand. If the amputee suffers from severe phantom sensations after the amputation, a transplanted hand can ‘fill the empty space’, helping to ease phantom sensations and phantom pain. Some amputation patients may feel an enormously strong desire to have a ‘normal hand’ when socialising with others, especially with family members. One patient I met said his greatest wish was to be able to lift and embrace his grandchild and hold him close. Other patients consider it most important to be able to shake hands with others and to use their hands in natural gestures.
From a medical viewpoint, the risks and negative consequences of a hand transplant may be quite substantial. As with other types of organ transplants, the body’s immunological system perceives the hand transplant as a foreign object that must be rejected. The consequence is an acute strong immunological reaction when the body tries to reject the new hand [8, 10–12]. A hand consists of several kinds of tissues with strong antigenic properties that rapidly activate the recipient’s immunological system. The skin has especially strong antigenic properties. Over the years, the experiences from transplanting internal organs have been helpful in developing successively better and more effective immunosuppressive drugs. Various types of steroids still have an important role, and cyclosporine, discovered in the 1980s, proved to be an effective immunosuppressant. Tacrolimus, which came in to use about 20 years ago, also proved very effective in inhibiting rejection, and since then several other substances with various modes of action have been developed. The special and complex immunological problems associated with hand transplantation also apply to face transplants, since both are complex tissue allografts (CTAs) characterised by multiple tissues with high antigenic properties. Today the traditional approach to the immunosuppressive regimen is initial treatment with induction agents such as polyclonal (antithymocyte globulins) or monoclonal (alemtuzumab, basiliximab) antibody preparations followed by a maintenance therapy including tacrolimus (FK-506), mycophenolate mofetil (MMF) and prednisone [13, 14]. The immunosuppressive medications must be continued throughout the patient’s lifetime and are associated with several serious risks and side effects, including a severely impaired defence against infections leading to a risk of sepsis, risk for developing diabetes and malignant tumours as well as cardiovascular problems. An amputee wanting to have a hand transplant must be aware of all these risks and ask himself if the benefits of the procedure are really worth all the negative effects [5, 15].
From the surgical point of view, a hand transplant is not very complicated; the procedure can be performed under well-controlled conditions. The potential problems and risks from the transplantation itself and the subsequent medications make it a controversial procedure, and over the years hand transplantation has only been performed with certain restrictions on a limited number of patients and at a limited number of the world’s replantation centres [6].
Hand Transplantation from an International Perspective
The first hand transplantation was performed in 1964 in Ecuador by Dr Robert Gilbert [16, 17]. The hand had to be amputated after 3 weeks due to acute rejection; the surgeons were not sufficiently knowledgeable about the medication required to inhibit rejection. A 30-year period of stagnation followed.
The second hand transplantation was performed on 25 September 1998 at the Edouard Herriot Hospital in Lyon, France, by a team led by surgeons Jean-Michel Dubernard, Earl Owen from Sydney and Nadey Hakim from London [18]. A hand from a recent motorcycle accident victim was transplanted onto 48-year-old New Zealander Clint Hallem, who was brought to Lyon for the procedure. The operation took 14 h and was hailed as a breakthrough in the world press. Unfortunately, it ended in disappointment as it became necessary to amputate the hand after 3 years. The patient, Clint Hallem, appeared on TV and blamed himself. He also told the New York Times how he had not been able to continue taking the heavy medication and how, on his own initiative, he had stopped the immunosuppressive medications necessary to inhibit rejection. Hallem also made clear that he had not been able to accept the new body part and he felt ‘mentally isolated’ from the hand. This was a severe disappointment, and it was now realised that selecting suitable patients is essential for a successful hand transplant.
On 25 January 1999, just a few months after the hand transplantation in Lyon, the first American hand transplantation was performed in Louisville, Kentucky, by a team led by Warren Breidenback [2]. The patient, Matthew Scott, had lost a hand in a fireworks accident several years earlier. The surgery went well and Scott is today the longest surviving successful hand transplant recipient in the world.
The first double-hand transplantation was performed in January 2000 in Lyon when the 33-year-old Denis Chatelier received two new hands from a deceased man. Chatelier had lost his hands when a homemade rocket exploded. Soon thereafter, on 17 March of the same year, a double-hand transplant was performed at University Hospital Innsbruck by Raimund Margreiter and colleagues [4, 19]. After about 6 months this patient began to recover sensation in the hands, and after 1 year he could shave himself, hold a pencil and use a pair of scissors [7]. In the ensuing years, several successful single- and double-hand transplantations were performed in several centres in the USA, Europe, South America and Asia [14]. The first complete double arm transplantation was performed in August 2008 by Christoph Hoehnke and Edgar Biemer on farmer Karl Merck, who had lost both arms in a 2002 combine accident [20]. The surgery was performed in Munich in the hospital that Merck himself had approached after watching a TV programme about hand transplants and after trying to make several homemade arm prostheses. The surgery was successful and without complications.
A few months after the surgery, Merck could move his new fingers and hands since the tendons and muscles in the hand transplants were attached to corresponding muscles in the recipient’s remaining arm stumps. After intense physiotherapy, he rapidly gained the ability to open doors and operate a light switch.
Although most hand transplants are performed to replace hands that are lost due to traumatic amputation, the indications may vary. In October 2010, Dr Marco Lanzetta at the Italian Institute of Hand Surgery in Monza (Milan in Italy) performed a bilateral hand transplant on a 52-year-old female who suffered quadrimembral amputation as a result of sepsis. Britain’s first hand transplant was carried out on 27 December 2011 by a team led by Dr Simon Kay at Leeds General Infirmary. Mark Cahill, a 51-year-old former publican, had been left with a nonfunctioning right hand as a result of gout and a subsequent infection. In a newspaper interview in the Telegraph on 4 January 2013, Cahill claimed that he had already gained some movement in his fingers following the operation. He expressed delight at his ‘brand-new hand’, hoping that it would enable him to once again cut his own food, dress himself and play properly with his grandson.
All hand transplants that are performed worldwide are registered and closely monitored in the International Registry on Hand and Composite Tissue Transplantation (www.handregistry.com) [6, 20]. To date more than 70 hand transplants have been performed on more than 50 patients in various parts of the world (www.handregistry.com, accessed 10 April 2013). This means that more than 20 patients have received two new hands at the same time.
Since the first transplant on Clint Hallem in 1998, emphasis has been placed on the risk of acute rejection episodes. Often there are episodes of beginning rejection that need immediate medical treatment. A hand consists of several types of tissues with varying antigenicity, and the tendency for rejection can vary. The early stages of a rejection reaction are first obvious in the skin, so it is advantageous that the hand is fully visible and not hidden in the body as in other types of organ transplantations [21].
Transplanted hands can have fairly good function, at least as good as if the patient’s own hand had been replanted after an amputation [8, 18, 22–25]. Muscles and tendons in the transplanted hand are attached to the recipient’s corresponding muscles and tendons. Consequently, the recipient may be able to move the fingers in the transplanted hand after only a few days. Recovery of sensation in the transplanted hand is a much more complicated issue but necessary to achieve functional integration of the new hand. The recipient’s nerve trunks, measuring 2–3 mm in diameter, are adapted to the corresponding nerve trunks in the transplanted hand. Regenerating nerve fibres from the recipient’s nerve trunks then have to advance and grow down the endoneural tubes, i.e. the Schwann cell tubes in the nerve trunks of the transplanted hand, to reinnervate its peripheral sensory receptors – a time-consuming process requiring months and years before there is any recovery of useful sensibility in the transplanted hand.
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