Bilateral Hand Transplantation Research Articles

Inpatient Rehabilitation Challenges in a Quadrimembral Amputee After Bilateral Hand Transplantation

Bilateral forearm and hand transplantation poses unique challenges especially in the setting of bilateral lower limb amputations. A 57-yr-old man with bilateral transradial amputations and bilateral transtibial amputations after remote streptococcal sepsis was admitted for inpatient rehabilitation because of severe debilitation after forearm/hand transplantations. He required 6 wks of bed rest to allow the healing of the allografts but developed profound deconditioning. Because of weight-bearing precautions and other complications such as femoral neurapraxia, he required the use of body weight-support apparatus to ambulate with lower limb prostheses, keeping weight off the allografts. He progressed to walking 600 ft using a platform-wheeled walker at a modified independent level, to climbing four stairs with minimal assistance, and to being able to toss a small football using his right hand, indicating improved flexor function in this hand. Tacrolimus levels were maintained without clinical evidence of acute rejection. Through an individualized therapy regimen, careful monitoring of the allografts and dedicated support staff, rehabilitation training of a previous quadrimembral amputee after bilateral hand transplantations can be successful.

Skin Area Quantification in Preparation for Concomitant Upper Extremity and Face Transplantation: A Cadaver Study and Literature Review

Numerous experiments in composite tissue allotransplantation (CTA) have identified skin as the most antigenic, with recent experimentation from our laboratory finding a direct correlation between large antigenic skin loads and chimerism. Therefore, in preparation for clinical application of concomitant upper extremity (UExt) and face transplantation, we aimed to identify the exact skin quantities accompanying various upper UExt and concomitant scenarios using a cadaver study. Five fresh cadavers were obtained and dissections were performed to simulate five different UExt transplant levels. Exact skin quantities (cm²) and total body surface area (TBSA) percentages were calculated using digital image analysis for both unilateral and bilateral hand transplant levels. UExt measurements were then cross-analyzed with our laboratory's facial/scalp alloflap data for similar evaluation of various concomitant CTA scenarios. Skin quantities for unilateral hand transplants ranged from 335 (± 58) to 787 (± 82) cm², and from 670 (± 117) to 1575 (± 163) cm² for bilateral. Concomitant CTA quantities (from "unilateral wrist-level with face" to "bilateral elbow-level with face/scalp") extended from 1010 (± 81) to 2766 (± 202) cm², totaling a range of 5.6% to 15.4% TBSA. The findings presented here, for the first time, define exact skin quantities and TBSA percentages accompanying unilateral, bilateral, and concomitant hand/face transplant scenarios. Unilateral UExt transplants contain between 335 and 787 cm² and bilateral between 670 and 1575 cm². Concomitant face/scalp and UExt transplants contain between 1000 and 2800 cm², equating 5% to 15% TBSA. Furthermore, there exists a tremendous void in research and some inconsistencies between animal investigation and clinical experience related to large skin-bearing CTAs. These concerns warrant further investigation by all teams pursuing concomitant CTA.

The International Registry on Hand and Composite Tissue Transplantation

The International Registry on Hand and Composite Tissue Transplantation was founded in May 2002, and the analysis of all cases with follow-up information up to July 2010 is presented here. From September 1998 to July 2010, 49 hands (17 unilateral and 16 bilateral hand transplantations, including 1 case of bilateral arm transplantation) have been reported, for a total of 33 patients. They were 31 men and 2 women (median age 32 years). Time since hand loss ranged from 2 months to 34 years, and in 46% of cases, the level of amputation was at wrist. Immunosuppressive therapy included tacrolimus, mycophenolate mofetil, sirolimus, and steroids; polyclonal or monoclonal antibodies were used for induction. Topical immunosuppression was also used in several cases. Follow-up ranges from 1 month to 11 years. One patient died on day 65. Three patients transplanted in the Western countries have lost their graft, whereas until September 2009, seven hand grafts were removed for noncompliance to the immunosuppressive therapy in China. Eighty-five percent of recipients experienced at least one episode of acute rejection within the first year, and they were reversible when promptly treated. Side effects included opportunistic infections, metabolic complications, and malignancies. All patients developed protective sensibility, 90% of them developed tactile sensibility, and 82.3% also developed a discriminative sensibility. Motor recovery enabled patients to perform most daily activities. Hand transplantation is a complex procedure, and its success is based on patient's compliance and his or her careful evaluation before and after transplantation.

Face, Upper Extremity, and Concomitant Transplantation: Potential Concerns and Challenges Ahead

From its origination involving successful rat hind-limb allograft studies using cyclosporine, face and upper extremity composite tissue allotransplantation has since developed into an exciting and promising subset of reconstructive transplant surgery. Current surgical technique involving composite tissue allotransplantation has allowed optimal outcomes in patients with massive facial and/or upper extremity defects; however, with its coexisting immunologic barrier, obligatory lifelong immunosuppression commits each patient to a daily risk of transplant-related complications with many unanswered questions. Since 1998, nearly 50 hand transplantations in 40 patients have been performed around the world at various levels ranging from wrist level to shoulder level. However, the risk-to-benefit ratio remains controversial in bilateral versus unilateral transplantation and has yet to be determined. From recent experience, the two most important determinants of the success of each patient's upper extremity transplant are patient compliance and intense rehabilitation. A total of nine face transplants have been performed since 2005. Multiple aesthetic subunits (i.e., nose, lips, eyelids) with or without underlying craniofacial skeletal defects (i.e., maxilla, mandible) have been successfully restored, thereby providing restoration of vital facial functions (i.e., smiling) in an unprecedented manner. As of today, face transplantation carries an estimated 2-year mortality of 20 percent. Concomitant composite tissue allotransplantation, which involves a variable combination of allograft subtypes, has been performed in two of the nine face transplant patients. These have included simultaneous bilateral hand transplants and tongue with mandible. Future study is warranted to investigate the potential advantages and disadvantages of using this approach versus a staged approach for reconstruction.

Re-emergence of hand-muscle representations in human motor cortex after hand allograft

The human primary motor cortex (M1) undergoes considerable reorganization in response to traumatic upper limb amputation. The representations of the preserved arm muscles expand, invading portions of M1 previously dedicated to the hand, suggesting that former hand neurons are reassigned to the control of remaining proximal upper limb muscles. Hand allograft offers a unique opportunity to study the reversibility of such long-term cortical changes. We used transcranial magnetic stimulation in patient LB, who underwent bilateral hand transplantation 3 years after a traumatic amputation, to longitudinally track both the emergence of intrinsic (from the donor) hand muscles in M1 as well as changes in the representation of stump (upper arm and forearm) muscles. The same muscles were also mapped in patient CD, the first bilateral hand allograft recipient. Newly transplanted intrinsic muscles acquired a cortical representation in LB's M1 at 10 months postgraft for the left hand and at 26 months for the right hand. The appearance of a cortical representation of transplanted hand muscles in M1 coincided with the shrinkage of stump muscle representations for the left but not for the right side. In patient CD, transcranial magnetic stimulation performed at 51 months postgraft revealed a complete set of intrinsic hand-muscle representations for the left but not the right hand. Our findings show that newly transplanted muscles can be recognized and integrated into the patient's motor cortex.

Bilateral Hand Transplantation: Result at 20 Months

On November 2006, a bilateral hand allotransplantation was performed for a 47-year-old female who had suffered radiocarpal amputations 28 years before. Technical aspects of the operation are detailed. Alemtuzumab induction, and triple therapy of tacrolimus, mycophenolate mofetil and prednisone were used to control rejection. The evolution of the result and functioning at 20 months are presented in detail. Two acute rejection episodes occurred and were successfully treated with steroids. In addition the patient developed a factitious visual disorder and a facial basal cell carcinoma. Functionally, at 20 months, the patient had a Hand Registry Functional Score of 69 (good), and a DASH score of 19.

The Innsbruck Hand Transplant Program: Update at 8 Years After the First Transplant

We herein provide an update on two bilateral hand and one bilateral forearm transplants with emphasis on immunosuppression (IS), function, morphology, and graft vascular changes at 8 years and 2 years after bilateral hand and 5 years after bilateral forearm transplantation. Between March 2000 and May 2006, three patients underwent bilateral hand or forearm transplantation at our institution. Following induction therapy with antithymocyte globulin (ATG) ( n = 2) or alemtuzumab ( n = 1), tacrolimus, prednisolone ± mycophenolate mofetil (MMF) were given for maintenance IS. Later, tacrolimus ( n = 1) or MMF ( n = 1) was replaced by sirolimus/everolimus for long-term IS. Clinical follow-ups with evaluation of hand function, skin biopsies, X-ray, ultrasound, angiography, computed tomography angiography, electrophysiological studies, and somatosensory evoked potentials were performed at regular intervals. Three, six, and three rejection episodes were successfully treated with bolused steroids, anti-CD25 or anti-CD52 antibodies. Subsequently, skin histology remained normal without any evidence of chronic rejection. Hand function continuously improved during the first 3 years and since then remained stable with minor improvements. Investigation of hand arteries revealed no signs of occlusion or stenosis. Motor and intrinsic hand muscle function continues to improve in all patients. Protective sensation was observed in all patients; however, discriminative sensation was only accomplished after hand but not forearm transplantation. No life-threatening adverse events occurred. Despite immunologic challenging postoperative courses, patients are now free of rejection with moderate levels of IS and good functional results. No signs indicating chronic rejection have been encountered.

Indoleamine 2,3-Dioxygenase and Foxp3 Expression in Skin Rejection of Human Hand Allografts

Human hand transplantation is complicated by skin rejection. To better define the characteristics of infiltrating cells, biopsies from human hand transplants have been investigated for expression of Foxp3 and indoleamine 2,3-dioxygenase (IDO), a key regulatory enzyme to induce T-lymphocyte unresponsiveness. A total of 104 skin biopsies taken from three bilateral hand transplant recipients over 6 years posttransplant were assessed by hematoxylin-eosin histology (graded 1–4b) and immunohistochemistry for IDO and Foxp3 according to a three-grade classification and correlated with the grade of rejection as well as time after transplantation. Overall, rejection ranged between grades 0 and 4a with an average score of 0.94. IDO was expressed in the endothelium independent of rejection. Upon rejection, IDO staining within the cellular infiltrate was significantly increased. Foxp3 in regulatory T cells was mainly found in samples undergoing severe rejection. Expression of IDO and Foxp3 compared well to each other, although the overall expression of Foxp3 was lower when compared to IDO. An increased expression of IDO as well as Foxp3 during rejection late after transplantation was observed. Characteristics of the cellular infiltrate indicate tolerogenic properties of a proportion of the cells and therefore a tendency toward self-limitation of the alloimmune response during skin rejection after hand transplantation.

The International Registry on Hand and Composite Tissue Transplantation

Since May 2002, all groups performing hand transplantations have supplied information to the International Registry on Hand and Composite Tissue Transplantation (IRHCCT). The analysis of all cases with follow-up information up to September 2007 is presented here. From September 1998 to September 2007, 38 hands (18 unilateral and 10 bilateral hand transplantations) and two digits have been reported to IRHCTT, for a total of 30 patients with a follow-up period ranging from 6 months to 9 years. They were 28 males and two females, median age of 34 years. Time since hand loss ranged from 2 months to 34 years and in 50% of cases the level of amputation was at wrist level. Immunosuppressive therapy included tacrolimus, mycophenolate mofetil, rapamycin, and steroids; polyclonal or monoclonal antibodies were used for induction. Topical immunosuppression was also employed in several cases. Patient survival was 100%. Graft survival was 100% at 1 and 2 years. Except for the Chinese patients, current graft survival is 95.6% and cause of graft loss was always no compliance to the treatment. Acute rejection episodes occurred in 85% of the patients within the first year and they were reversible in all compliant patients. Side-effects included opportunistic infections and metabolic complications. All patients developed protective sensibility, 90% of them developed tactile sensibility, and 72% also a discriminative sensibility. Motor recovery enabled patients to perform most daily activities. Hand transplantation is feasible with a high success rate and satisfactory functional outcome.

Clinical evaluation of two bilateral hand allotransplantations at six and three years follow-up

We report a six and three years follow-up clinical evaluation of two bilateral hand allotransplantations from brain-dead multi-organs donors performed in two young adult traumatic hand amputees. Lifelong immunosuppressive treatment included tacrolimus, mycophenolate mofetil and prednisolone. In both patients, early complications were observed but were successfully treated. At follow-up, clinical results allow useful hand function in both patients, by far superior to what can be provided by current myoelectric prostheses. Although the long-term risks-benefits ratio of bilateral hand transplantation is still unknown, these two cases demonstrate that this new treatment is feasible. Further experimental and clinical research is needed to better delineate its role in the future of hand surgery.

Allogreffe de mains : expérience lyonnaise

Hand allograft is a method in the stage of clinical experimentation, which is reserved in France for the treatment of bilateral traumatic amputees. This study reports the Lyon team experience, which is pioneer in this domain. Four patients (3 males and 1 female) underwent seven (one unilateral and three bilateral) hand transplantations from September 1998 to February 2007. The level of amputation was at the wrist or at the mid-forearm. Delay since hand loss ranged from 2.5 to 9 years. The surgical protocol was elaborated and planned case by case. All recipients received the same immunosuppressive treatment. Episodes of acute rejection were observed in the first 3 months after transplantation, which were easily managed after a few days increasing oral prednisone doses and applying topical immunosuppressants. Currently the patients receive the doses of immunosuppressants comparable to those in kidney-grafted patients. We have not registered any severe complication of immunosuppressive treatment up till now (7 years follow-up for the earliest graft). We performed analytical and functional clinical, as well as questionnaire evaluation of patients. The first case (unilateral graft) resulted in graft failure at 2 years due to non-compliance of the patient. The three bilateral graftees demonstrate a favorable evolution despite some immunological (hyperglycemia, serum sickness) and surgical (thrombosis, osteomyelitis, skin loss) complications, which could be managed. The middle and long-term follow-up evaluation revealed good to excellent sensorimotor recovery of 4 hands in both male recipients (4 and 7 years) with satisfactory social adaptation, higher or equal to those expected after post-traumatic replantations at the equivalent level and higher to those obtained with currently available myoelectric prosthesis. The last patient, a young female who has been grafted in February 2007, receives ongoing reeducation course and shows normal progress of functional restoration of both hands. The encouraging results of this clinical experimentation make us currently consider hand allografting as reasonable and useful both for the patients and for evolution of research in composite tissues allotransplantation (CTA). Further long-term careful research and worldwide monitoring of all patients with hand allografts is required to, on the one part, state on the authorization of this surgery, and, on the other part, to better elucidate the mechanisms of successful CTA.

Second Report (1998–2006) of the International Registry of Hand and Composite Tissue Transplantation

Since May 2002 all groups performing hand transplantations have supplied detailed information to the International Registry on Hand and Composite Tissue Transplantation. This report provides a review of all hand transplants performed to date. From September 1998 to February 2006 eighteen male patients underwent 24 hand/forearm/digit transplantations (eleven unilateral and four bilateral hand transplantations, two bilateral forearm transplantations, one thumb transplantation). The level of amputation was mostly at the distal forearm or wrist. Patient average age was 32. Time since hand loss ranged from 2 months to 22 years. Immunosuppressive therapy included tacrolimus, mycophenolate mofetil, rapamycin and steroids; polyclonal or monoclonal antibodies were used for induction. Topical immunosuppression was administered in some patients. Follow-up period ranged from 34 to 85 months. Patient survival was 100%. Graft survival was 100% at 1 and 2 years. Two cases of graft failure at a later date occurred and were caused by severe inflammation and progressive rejection in a non-compliant patient. In addition, 6 hands were lost due to a rejection process as the Chinese recipients did not take their immunosuppressive treatment. These failures were communicated in January 2006. Acute rejection episodes occurred in 12 patients within the first year. Rejection was completely reversible in all compliant patients. Side-effects included opportunistic infections and metabolic complications. No life-threatening complications or malignancies were reported. As it would have been very difficult to analyse transplantation functional results in a standardized way, the Registry has performed a functional score system. All patients had achieved protective sensation and in 17 of them also discriminative sensation. Extrinsic and intrinsic muscle recovery enabled patients to perform most daily activities and 90% of the recipients returned to work, and improved manual skills allowed them not only to resume their previous jobs but also, in some cases, to find more suitable employment. Fifteen recipients reported an improvement of their quality of life and we evaluated as a very important point as patient satisfaction and well-being are mandatory goals of hand transplantation.

Bilateral Hand Transplantation: Six Years After the First Case

In this study we present our experience concerning bilateral hand transplantation. Two cases were performed: the first in January 2000 and the second in April 2003. Both recipients received the same immunosuppressive treatment, which was similar to those used in solid organ transplantation, including tacrolimus, prednisone and mycophenolate mofetil while antithymocyte globulins were added for induction. Both recipients presented two episodes of acute rejection (maculopapular lesions) in the first 3 months after transplantation; however, these were easily reversed after a few days increasing oral steroid doses and using topical immunosuppressants. The first recipient presented hyperglycemia and serum sickness while the second recipient suffered a thrombosis of the right ulnar artery and an osteomyelitis of left ulna. All the complications were successfully treated. Functional Magnetic Resonance Imaging (fMRI) showed that cortical hand representation progressively shifted from the lateral to the medial region in the motor cortex. After 6 and 2 years respectively, they showed a relevant sensorimotor recovery particularly of sensibility and activity of intrinsic muscles. They were able to perform the majority of daily activities and to lead a normal social life. The first recipient has been working since 2003. They are both satisfied with their grafted hands.

Status 5 Years after Bilateral Hand Transplantation

Graft survival and function early after hand transplantation is good. It remains unknown, however, whether long-term survival is limited by chronic rejection. We here describe the clinical course and the status 5 years after bilateral hand transplantation with emphasis on immunosuppression (IS), function, morphology and graft vascular changes. Clinical observation, evaluation of hand function, skin biopsies, X-ray, ultrasound, angiography, CT angiography, electrophysiologic studies including compound motor and sensory action potentials (CMAP, CSAP) and somatosensory evoked potentials were performed and results recorded at regular intervals. Following reduction of IS one mild (grade II) rejection episode occurred at 4 years. Subsequently, skin histology remained normal and without signs of chronic rejection. Hand function continuously improved during the first 3 years and remained stable with minor improvement thereafter. CMAP and CSAP progressively increased during the observation period. Latencies of the cortical responses were prolonged but amplitudes were within normal range. Investigation of hand vessels revealed no signs of occlusion but showed revascularization of a primarily occluded right radialis artery. Motor and sensory function improved profoundly between years 1 and 5 after hand transplantation. No signs whatsoever of chronic rejection have been observed.

Cortical motor activation patterns following hand transplantation and replantation

We studied cortical activation patterns by functional MRI in a patient who received bilateral hand transplantation after amputation 6 years ago and in a patient who had received unilateral hand replantation within 2 hours after amputation. In the early postoperative period, the patient who had had the hand transplantation revealed strong activation of a higher motor area, only weak activation of the primary sensorimotor motor cortex and no activation of the primary somatosensory cortex. At 1-year follow-up, a small increase in primary sensorimotor motor cortex activation was observed. Activation of the primary somatosensory cortex was only seen at the 2 year follow-up. By contrast, after hand replantation, the activation pattern was similar to that of the uninjured hand within 6 weeks. This included activation of the primary sensorimotor motor cortex, higher motor areas and primary somatosensory cortex. Transplantation after long-standing amputation results in cortical reorganization occurring over a 2-year period. In contrast, hand replantation within a few hours preserves a normal activation pattern.

The International Registry on Hand and Composite Tissue Transplantation

Since May 2002 all groups performing hand transplantations have supplied detailed information to the International Registry on Hand and Composite Tissue Transplantation. This inaugural report provides a review of all hand transplants performed to date. Between September 1998 and September 2004, 18 male patients underwent 24 hand/forearm/digit transplantations (11 monolateral and 4 bilateral hand transplantations, 2 bilateral forearm transplantations, and 1 thumb transplantation). The level of amputation was mostly at the distal forearm or wrist. The average age of the patient was 32 years. Time since hand loss ranged from 2 months to 22 years. Immunosuppressive therapy included tacrolimus, mycophenolate mofetil, rapamycin, and steroids; polyclonal or monoclonal antibodies were used for induction. Topical immunosuppression was administered in some patients. Follow-up period ranged from 17 to 70 months. Patient survival was 100%. Graft survival was 100% at 1 and 2 years. Two cases of graft failure at a later date were caused by severe inflammation and progressive rejection in a noncompliant patient. Acute rejection episodes occurred in 12 patients within the first year. Rejection was reversible in all compliant patients. Side effects included opportunistic infections and metabolic complications. No life-threatening complications or malignancies were reported. All patients had achieved protective sensation, and 17 patients also achieved discriminative sensation. Extrinsic and intrinsic muscle recovery enabled patients to perform most daily activities. Despite the enormous antigen load associated with composite tissue allograft, hand transplantation became a clinical reality with immunosuppression comparable to transplantation of solid organs.

LONG-TERM RESULTS OF TWO CASES OF BILATERAL HAND TRANSPLANTATION: LYON EXPERIENCE

O130 Aims: To report our experience about bilateral hand allotransplantation. Methods: The first bilateral hand transplantation was performed in January 2000 and the second case on April 30, 2003. The first recipient was a 33-year old man with bilateral amputation at midforearm level from four years and the second recipient was a 22-year old man with amputation at proximal forearm level on the right side and at wrist level on the left side from two years. The immunosuppressive protocol included tacrolimus, mycophenolate mofetil, prednisone and, for induction, antithymocyte globulins. An intensive rehabilitation program started 12 hours after surgery and included physiotherapy, electrostimulation and occupational therapy. Results: An arterial thrombosis, which was quickly reversed, occurred at day 1 post-transplantation in the second recipient. Side-effects included transient hyperglycemia during the first month post-transplantation in the first recipient and an ostheomyelitis at day 152 in the second patient with complete resolution after 6 months of antibiotics. During the follow-up period no malignancies occurred and no signs of graft-versus-host disease were shown in either patient. Only two episodes of acute skin rejection (asymptomatic maculopapular lesions) occurred on days 52 and 82 and on days 55 and 86 in the first and in the second recipient respectively. In all cases the episodes resolved by increasing oral steroid dose within 10-15 days. Nerve regeneration has been demonstrated by histological studies, electromyography and sensitive tests as well as cortical reorganization by functional magnetic resonance imaging in both patients. In the first bilateral hand transplantation there is a normal sensitivity to pain and thermal stimuli and a good sensitivity to dynamic and static pressure with some errors in discrimination of the localisation. Intrinsic musculature recovery started at 9 months and at present he can dissociate each single finger movement. His grip and pinch strength is 3 Kg and 1.5 Kg respectively. The patient is able to perform the same daily activities that were possible with the myoelectric prostheses before the transplantation. In addition, several activities such as holding a pen or a glass or a pair of scissors, shaving, taking care of his personal hygiene that were impossible before are at present easily performed by the patient. In the second bilateral hand transplantation there is a normal sensitivity to pain and thermal stimuli, a discrete tactile sensation and a discriminative sensation ranging between 8 and 15 mm. Intrinsic musculature recovery started at 6 months on the left side and at 9 months on the right side. His grip strength is 8 kg on the right and 10 Kg on the left side while his pinch strength is more than 1 kg on both sides. He is already able to take care of his personal hygiene and to hold several objects, such as a glass. Conclusions: Although these results are very encouraging, other cases are required.

THE INTERNATIONAL REGISTRY ON HAND AND COMPOSITE TISSUE ALLOGRAFT

O132 Aims: Since May 2002 all groups performing hand transplantations have supplied detailed information to the International Registry on Hand and Composite Tissue Transplantation. This inaugural report provides a comprehensive review of all hand transplants performed to date. Methods: From September 1998 to March 2004 nineteen male patients underwent 25 hand/forearm/digit transplantations (12 monolateral and 4 bilateral hand transplantations, 2 bilateral forearm transplantations, 1 thumb transplantation). Recipients were all males aged between 19 and 52 (average 32 years). Time since amputation ranged from two months to 22 years (mean 5.4 yrs). Immunosuppressive therapy included tacrolimus, mycophenolate mofetil, rapamycin and steroids; polyclonal or monoclonal antibodies were used for induction. Topical immunosuppression was administered in some patients. Results: Acute rejection episodes occurred in 75 % of the patients. In most cases treatment of the first rejection episode included high-dose intravenous steroids; in cases where no steroids were administered intravenously, oral steroid treatment was increased. Tacrolimus, corticosteroid or flumix ointment (alone or in combination between them) was applied in all cases of rejection. Treatment of a second, third or fourth rejection episode varied considerably, but it was completely reversible in all compliant patients. In one case, following the patient’s non-compliance with immunosuppressive therapy, cutaneous lichenoid-like lesions occurred. Side-effects included opportunistic infections, such as CMV infections, and metabolic complications, such as transient hyperglycemia, and increase in creatinine values. No life-threatening complications or malignancies were reported. All transplants were technically successful, and only minor surgical complications were observed. There was one case of early perioperative arterial thrombosis which was quickly reversed. Patient as well as graft survival was 100 % at 2 years. Two cases of graft failure at a later date were caused by severe inflammation and progressive rejection in a non-compliant patient Nerve regeneration was particularly good in all patients, showing a satisfactory degree of protective sensation recovery (i.e. the ability to detect pain, thermal stimuli and gross tactile sensation). A certain degree of discriminative sensation was also reported, although this was not to the same degree at all parts of the graft. At two years post-transplantation 12 hands showed different degrees of discriminative sensation recovery. Motor recovery began with extrinsic muscle function, allowing the patients to perform grasp and pinch activities. Function of intrinsic muscles was only observed at a later stage, starting at 12 months post-transplantation in the majority of patients. Patients showed the ability to perform the majority of daily activities. Conclusions: Despite the enormous antigen load associated with CTA, hand transplantation became a clinical reality with immunosuppression comparable to transplantation of solid organs.

Advances in composite tissue allograft transplantation as related to the hand and upper extremity

The clinical transplantation of composite tissue allografts (CTA) such as human hand or larynx is stimulating discussions among surgeons at national and international forums on the indications, ethical aspects, toxic effects of immunosuppression, and functional results of the first reported cases of unilateral and bilateral hand transplantation. This Clinical Perspective article presents the latest advances in clinical and experimental research related to the field of CTAs. The article presents the historic aspects of CTA, a broad view of the current state of composite tissue transplantation, the mechanism of allograft rejection, current experimental and clinical protocols, and, finally, the future prospects of the standard use of CTAs. It is clear that there is a substantial demand for routine use of CTAs but the treatment protocols need to be optimized and the functional outcomes need to be improved.

Cortical reorganization in motor cortex after graft of both hands

Cortical organization shifts after sensory deprivation, but the reversibility of this reorganization has not been studied. Here, using functional magnetic resonance imaging (fMRI), we investigated the dynamics of cortical reorganization in a patient's motor cortex before and after bilateral hand transplantation. We found that amputation-induced cortical reorganization was reversed following hand transplantation.