Hand transplantation procedures have benefited from the introduction of more specific immunosuppressive agents, with fewer adverse effects and greater efficacy. These immunosuppressants have resulted in a significant improvement in the outcome of solid organ transplantation over the past few decades. Striking successes in the field of kidney, liver, and heart transplantation have encouraged further investigation into the more multifaceted transplants such as composite tissue transplantations.
Composite tissue transplantation of the hand has shown promise in enhancing the quality of life of recipients. One of the most impressive examples of a successful functional outcome is an Austrian man who has been able to return to full-time work as a police officer after bilateral hand transplantation. His new hobbies have included learning to play the piano for the first time and touring around the world on his motorcycle.  Another remarkable example is the case of the first American hand transplant recipient. He is more than 10 years posttransplant and is working as an emergency medical technician (EMT) instructor, with occupational function nearing that of a normal hand.
Between 1998 and the end of 2015, 72 hands and numerous other composite tissue transplantations, including the face, scalp, larynx, femur, and penis, were performed across 13 countries.  The clinical success of hand transplantation and the exceedingly high rate of patient satisfaction have fueled the desire to start hand transplantation programs in many medical centers around the world.
Although the public demand for reconstructive transplantation is increasing, hand transplantation is far more complex and difficult than other forms of organ transplantation. In addition, the medical ethics of hand transplantation have been debated.  Solid organ transplantation for life-threatening disease is now a widely accepted procedure; however, reconstructive transplantation is less widely accepted. Despite the inherent concerns raised by more routine reconstructive transplantation, the results for hand transplantation are considered to be exceptionally favorable from both a physician and patient standpoint. [4, 5]
History Of The Procedure
Historical legend of limb transplantation dates back to 348 AD, when 2 saints, Cosmos and Damian, transplanted a leg obtained from a cadaver to the guard of their temple. No mention of functional success or follow-up exists. The first scientifically documented attempt at hand transplantation took place in Ecuador in 1964. The transplanted hand was rejected because of a lack of proper immunosuppression and was amputated 2 weeks after the initial surgery. 
In 1996, the Louisville Hand Transplant Team was established to evaluate the likelihood of performing successful human hand transplants. Research in small and large animal models followed. In 1997, an international symposium was organized in Louisville, Ky, to evaluate and discuss the relevant scientific and ethical issues of hand transplantation. Clinical trials were subsequently approved.  The first short-term success in human hand transplantation was that of a French patient. The recipient was a right-handed amputee from a saw injury that occurred several years earlier while he was in prison. The patient became noncompliant with the therapeutic immunosuppressive regimen; subsequently, the transplanted limb was removed 29 months later. 
The Louisville team attempted their first hand transplantation in January of 1999. This attempt later became the first official hand transplantation to achieve long-term success and was directed by Dr. Warren C Breidenbach III and surgeons from the Jewish hospital and Kleinert-Kutz associates in Louisville, Ky. The procedure was performed on a 37-year-old man who had lost his left hand in a fireworks accident at the age of 23 years. 
The remarkable success of the Louisville team has led to many single and bilateral hand transplantations all over the world. Dr. Jean-Michel Dubernard performed the world's first double hand transplant in Lyon, France, in January of 2000; in the same year, the first female hand transplant was performed in China. In May 2000, surgeons in Malaysia performed the world's first successful hand and arm transplant in a 1-month-old girl from her deceased identical twin.
In July 2008, the world's first double arm transplant was performed in Munich, Germany. The postoperative course was complicated by three rejection episodes within the first 6 months. After 2 years of extensive physiotherapy, the patient was able to perform full elbow flexion and extension as well as wrist and finger movements and use both hands during daily activities. 
The American and European hand transplantations, with proper preoperative screening and maintenance of immunosuppression, have achieved excellent allograft survival. However, hand transplant rejections have been reported in China as a result of failure to monitor and maintain immunosuppressive therapy appropriately. Overall, patient satisfaction after recovery has been high, and reports of overall functional outcome are far better than those for the preexisting prosthesis. One death was reported following a March 2009 bilateral hand and face transplant in Paris. However, this is thought to have resulted from infection complications related to the face transplant.
At the end of 2009, 50 hands had been transplanted on 36 patients (single and double)  . In November 2007, the Louisville team performed the first hand transplant done successfully with a groundbreaking steroid-free protocol using Campath (alemtuzumab), a monoclonal antibody, administered in a single dose preoperatively without steroid maintenance therapy afterward. This was done in a 54-year-old male who lost his hand 30 years prior in a machine press accident. [10, 11]
By the end of 2008, 8 annual international Composite Tissue Allotransplantation (CTA) symposiums had been held to discuss the latest research, clinical findings, updates on outcomes of the past recipients, and future considerations. The first American conference was held in Philadelphia in July 2008, and the American Society for Reconstructive Transplant Surgery was founded in the same year. Despite various nonscientific criticisms from both the medical and nonmedical communities, each year, more surgeons attempt various CTA transplants, such as the face, larynx, and abdomen, and most report an excellent degree of success.
Amputation of the hand and upper extremity can be caused by systemic diseases, such as cardiovascular disease or diabetes mellitus, bone or soft tissue malignancies, congenital birth defects, and trauma. Upper extremity limb loss has a significant psychosocial impact on the individual, in terms of both aesthetic and functional aspects. The disability related to the amputation includes missed work and loss of ability to resume regular work duties.
Contrary to claims made by opponents of hand transplantation, prostheses cannot fully duplicate the intricate actions of a native hand as well as a transplanted hand can.  The appearance of a normal hand also has a positive psychological impact upon the recipient. All the transplanted hands to date have developed protective sensation, and close to 90% have achieved some form of discriminative sensation. Even advanced myoelectric prostheses lack the advantage of providing sensation. [4, 12]
A 2015 study reported the international experience with 107 known transplanted hand/upper extremities in 72 patients. The patient survival rate for unilateral or bilateral hand transplantation in isolation was 98.5%, with an overall graft survival rate of 83.1%. 
Patients with amputations of one or both hands above the wrist and below the elbow are potential candidates for single or bilateral hand transplantation. Candidacy of above-elbow amputees has been debated; however, in July of 2008, the first bilateral above-elbow transplantation was succssfully performed in Munich, Germany.
Recipients must be in good health and aged 18-65 years. Hand transplantation should not be attempted in children. The decision to undergo such an extensive and complex procedure in an attempt to improve one's quality of life while maintaining a complete understanding and acceptance of the negative impact that immunosuppressive therapy may have on overall health can only be made by a capable and competent adult.
The possible complications of the procedure and the expected functional outcome of the transplanted hand need to be clearly discussed with the amputee. The decision to proceed is made solely by the recipient with the unbiased guidance of a chosen patient advocate. The surgeon is responsible for providing the appropriate information with regard to all available treatment options as well as their risks and benefits. Younger patients and those with an amputation below the elbow have more reliable outcomes and functional recovery than older patients with multiple comorbidities. Because of the superiority of a transplanted limb over prosthesis with regard to appearance, functionality, and, especially, sensation, patients who report satisfaction and functional ability with a prosthetic hand are still potential candidates for hand transplantation.
The image below illustrates the transverse cross-section of the mid forearm and the structures involved in the attachment of the donor hand to the recipient.
During the surgery, the ulnar and radial bones of the recipient and donor are attached with rigid plate-and-screw fixation. The bony structure and the size of the hand of the donor should be assessed preoperatively and should be similar to that of the recipient. The tendons in the forearm of both recipient and the donor need to be attached to their corresponding tendons or muscles and marked with labels intraoperatively, as shown in the image below.
In several previous cases, atrophy of the recipient tendon required the entire wad of flexor or extensor tendons of the donor to be attached to the residual tendon in the recipient. Despite concerns of loss of postoperative fine tendon function, this type of tendon attachment had to be used in the Louisville 2006 hand transplantation, and the postoperative outcome was better than expected. Such atrophy may make the recipient's anatomy confusing and more difficult to assess intraoperatively.
Finally, the radial and ulnar artery and vein and multiple peripheral veins on the dorsal and ventral side need to be identified in the mid forearm of both the recipient and the donor. The radial, ulnar, and median nerves also need to be identified.
The hand donor exclusion criteria should be surveyed meticulously by the regional organ procurement organization (OPO) involved. These criteria include the following:
Current intravenous drug use
Tattoo within past 6 months
Any systemic or limb-related neuropathies
The donor must be aged 18-65 years and matched for gender, skin tone, race, age, viral status, blood type, and size (must be within 15% of recipient size). Also, the donor should not require excessive vasopressors to maintain blood pressure prior to harvest. Currently, transplant is contraindicated in children younger than 18 years and persons older than 65 years. A possible exception to this is transplantation of a limb to a child from an identical twin who is not going to survive. One such case has been reported with success. Since immunosuppression is not required in such rare cases, this factor is removed from the ethical considerations.
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