Vascularized Composite Allotransplantation of the Hand: A Systematic Review of Eligibility Criteria.

BACKGROUND: Hand transplantation (HT) has emerged as an intervention of last resort for those who endured amputation or irreparable loss of upper extremity function. However, because of the considerable effort required for allograft management and the risks of lifelong immunosuppression, patient eligibility is critical to treatment success. Thus, the objective of this article is to investigate the reported eligibility criteria of HT centers globally. METHODS: A systematic review of the HT literature was conducted according to Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines, using PubMed, Cochrane, Ovid/Medline, and Scopus. Program Web sites and clinicaltrials.gov entries were included where available. RESULTS: A total of 354 articles were reviewed, 101 of which met inclusion criteria. Furthermore, 10 patient-facing Web sites and 11 clinical trials were included. The most reported criteria related to the capacity to manage the allograft posttransplantation, including access to follow-up, insurance coverage, psychological stability, and history of medical compliance. Other factors related to the impact of immunosuppression, such as active pregnancy and patient immune status, were less emphasized. CONCLUSIONS: Because of the novelty of the field, eligibility criteria continue to evolve. While there is consensus on certain eligibility factors, other criteria diverge between programs, and very few factors were considered absolute contraindications. As the popularity of the field continues to grow, we encourage the development of consensus evidence-based eligibility criteria.

Three-Dimensional Computer-Aided Design Modeling and Printing for Accurate Toe-to-Hand Transplantation.

PURPOSE: To introduce toe-to-hand transplantation performed with the assistance of both bone and soft tissue modeling using 3-dimensional printing technology. METHODS: From May 2015 to October 2018, 31 patients (group A, 24 thumbs and 7 fingers) were included. Computed tomography scans were acquired using a spiral computed tomography scanner, and the data were processed with software. Bone, skin, and nail models were created for tailoring the flap taken from the great toe. The impact of foot pathology in terms of pain, disability, and activity restriction was assessed using the Foot Function Index. For comparison, we included 35 patients (group B) who underwent toe-to-hand transplantation without the assistance of 3-dimensional computer-aided modeling. RESULTS: The mean duration of follow-up of groups A and B was 26 months (range, 24-31 months) and 27 months (range, 24-33 months), respectively. The mean Foot Function Index of groups A and B was 5 (range: 0-15) and 17 (range, 0-39), respectively. CONCLUSIONS: Three-dimensional computer-aided modeling and printing provide geometric accuracy in toe-to-hand transplantation. It also may reduce the donor foot morbidity by accurate flap designing and harvesting. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Evaluating Treatment Preferences and Perceptions of a Prosthetic Versus a Transplanted Hand: A Conjoint Analysis-Based Study.

INTRODUCTION: This study used a conjoint analysis-based survey to assess which factors are most influential when considering treatment with a prosthesis or transplant after a unilateral hand amputation. METHODS: Overall, 469 respondents were recruited using Amazon Mechanical Turk and asked to assume that they experienced a hand amputation. To determine preferences for a prosthetic, respondents chose among 11 pairs of alternatives with variations in the following attributes: appearance, function, maintenance, and learning time. Respondents were then presented with descriptions of the risks and outcomes of hand transplantation. The most compelling reasons for and against a transplant were determined and characteristics predictive of support for a transplant were identified. RESULTS: The most important attributes for a prosthesis were "lifelike appearance" and "myolectric function." For hand transplantation, respondents were most concerned about immunosuppression side effects (n = 323, 69%) and the intense nature of surgery (n = 275, 59%), whereas the most positive benefit was the concept of the transplant being "natural" (n = 339, 72%). When faced with the choice of a hand transplant or a prosthetic, approximately 50% of respondents chose a transplantation. Younger age, previous medical experiences, a perceived "familiarity with medical issues," and the regular attendance of religious services were associated with strong support for a hand transplantation (P < 0.01). CONCLUSIONS: When considering a hand prosthesis, respondents are motivated most by appearance and function. Meanwhile, with hand transplantation, the risks of immunosuppression and the intense nature of surgery and recovery are predominant concerns. These findings may help inform patient-physician discussions when considering treatment after unilateral hand amputation.

Two Decades of Hand Transplantation: A Systematic Review of Outcomes.

ABSTRACT: Hand transplantation for upper extremity amputation provides a unique treatment that restores form and function, which may not be achieved by traditional reconstruction and prosthetics. However, despite enhancing quality of life, hand transplantation remains controversial, because of immunological complications, transplant rejection, and medication effects. This systematic literature review sought to collect information on current experiences and outcomes of hand transplants to determine the efficacy and utility of hand transplants. The databases PubMed, Scopus, and Embase were analyzed with combinations of "hand" or "upper extremity" or "arm" and "transplant" or "allograft," with information collected on recipient characteristics, details of transplant, immunological outcomes, functional outcomes, and complications. Functional outcomes, as measured by Disabilities of Arm, Shoulder and Hand score, were compared between patient groups using Wilcoxon signed-rank test or 1-way analysis of variance test and post hoc Tukey test. Within the 108 articles that fulfilled inclusion and exclusion criteria, there were 96 patients with 148 hand transplants. There were 57 patients who experienced acute rejection and 5 patients with chronic rejection. Disabilities of the Arm, Shoulder and Hand scores significantly decreased after hand transplantation and were significantly lower for distal transplants compared with proximal transplants. There were 3 patients with concurrent face transplantation and 2 patients with simultaneous leg transplants. Sixteen patients experienced amputation of the hand transplant, and there were 5 deaths. This study found that hand transplantation provides significant restoration of function and form, especially for proximal transplants. Reduction in complications, such as rejection and amputation, can be achieved by decreasing medication cost and patient education.

5-Year Activity and Participation Outcomes of the First Successful Pediatric Bilateral Hand Transplantation: A Case Report.

AIMS: Describe the 5-year outcomes of the first successful pediatric bilateral hand transplantation. METHODS: The child underwent quadrimembral amputation at age two and received bilateral hand allografts at age eight. Rehabilitation included biomechanical, neurorehabilitation, and occupational approaches in acute and outpatient settings. Therapist observed outcomes, patient-reported measures, and parent-reported measures were repeated over a 5-year period. RESULTS: Observation assessments revealed functional dexterity skills and modified independence to full independence with self-care activities. The parent reported the child had moderate difficulty with upper extremity functioning 25-, 41-, and 48-months post-transplantation, and mild difficulty at 60-months; the child reported no difficulties in this domain at 41 months. Five years post-transplantation the child reported enjoying many age-appropriate activities, and high-quality peer relations were endorsed by both parent and child. CONCLUSION: The child developed hand movements for daily activities and was completing daily activities with improved efficiency. Health-related quality of life outcomes were favorable.

Psychosocial considerations in the assessment of hand transplant candidates: A single-center experience and brief literature review.

Vascularized composite allograft, including hand transplantation (HT), has gained wider usage as a reconstructive treatment over the past 30 years. HT recipients face unique psychosocial challenges compared to their solid organ and/or bone marrow transplant counterparts. Accordingly, the psychosocial evaluation among HT candidates continues to evolve, leaving a lack of consensus as to the critical psychosocial domains and psychometric testing instruments to help evaluate individuals considering HT. The present manuscript describes the psychosocial evaluation process within the Duke HT program, which been contacted by 80 potential candidates since 2014. The Duke HT evaluation process incorporates a comprehensive psychosocial assessment within domains including personality, cognitive function, mood, behavioral adherence, social support, and substance use history, among others. Our experience underscores the potential utility of collecting thorough psychosocial evaluations, supplemented by psychometric test data, to comprehensively assess potential HT candidates.

Complementary Phenomena: Phantom Hand and Phantom Face.

After tissue or limb loss, the development of sensation and perception of the lost or deafferent tissue is defined as a phantom phenomenon. We investigated the presence of phantom phenomena in individuals who underwent a full face transplant as well as those who had a hand transplant. Specifically, we investigated sensory perception of the face on the fingers and sensory perception of the fingers on the face in three full face and four hand transplant patients. In all seven individuals, we used a brush to separately stimulate the right and left sides of the face or the palmar and dorsal faces of the hand. We then asked the individuals if they felt a sensation of touch on any other part of their body and, if so, to describe their perceptions. Changes in the regions of the primary sensory cortex representing the hand and face were defined using fMRI obtained via tactile sensory stimulation of the clinical examination areas. Two of the full face transplant patients reported sensory perceptions such as a prominent sensation of touch on their faces during sensory stimulation of their fingers. Three of the hand transplant patients reported sensory perceptions, which we referred to as finger patches, during sensory stimulation of the face area. In fMRI, overlaps were observed in the cortical hand and face representation areas. We consider the phantom hand and phantom face phenomena we observed to be complementary due to the neighborhood of the representations of the hand and face in the somatosensory cortex.

Process of Obtaining Social Consensus and 3-Year Functional Outcomes of the First Hand Allotransplantation in Korea.

BACKGROUND: On February 2, 2017, the surgical team of ten board-certified hand specialists of W Hospital in Korea successfully performed the nation's first hand transplantation at Yeungnam University Medical Center (YUMC). This paper reports on the legal, financial, and cultural hurdles that were overcome to open the way for hand transplantation and its functional outcomes at 36 months after the operation. METHODS: W Hospital formed a memorandum of understanding with Daegu city and YUMC to comply with government regulations regarding hand transplantation. Campaigns were initiated in the media to increase public awareness and understanding. With the city's financial and legal support and the university's medical cooperation, a surgical team performed a left distal forearm hand transplantation from a brain-dead 48-year-old man to a 35-year-old left-handed man. RESULTS: With this successful allotransplantation, the Korean Act on Organ Transplantation has now been amended to include hand transplantation. Korean national health insurance has also begun covering hand transplantation. Functional outcome at 36 months after the operation showed satisfactory progress in both motor and sensory functions. The disabilities of the arm, shoulder, and hand score were 23. The final Hand Transplantation Score was 90 points. Functional brain magnetic resonance imaging shows significant cortical reorganization of the corticospinal tract, and reinnervation of intrinsic muscle is observed. CONCLUSIONS: Hand transplantation at the distal forearm shows very satisfactory outcomes in functional, aesthetical, and psychological aspects. Legal and financial barriers against hand transplantation have long been the most burdensome issues. Despite this momentous success, there have been no other clinical applications of vascularized composite allotransplantation due to the limited acceptance by Korean doctors and people. Further public education campaigns for vascularized composite allotransplantation are needed to increase awareness and acceptance.

Intergender Hand Transplant: A Sex Congruent Hand Transformation.

ABSTRACT: Hand and upper-extremity transplantation restore severely damaged limbs that cannot be repaired with conventional surgical techniques. Over the past 20 years, more than 200 vascularized composite allotransplantations have been performed worldwide, among them 7 were cases of sex unmatched hand transplants. The long term effects of recipient sex hormones and nerve regeneration on the sexually dimorphic physical features of donor upper extremity have not been described previously. We report a case of sex congruent transformation of hand morphology in an intergender hand transplant.

An Individualized Physiotherapy and Rehabilitation Program for Bilateral Hand Transplantations.

METHODS: This article describes a rehabilitation program and the long-term results after its application in 2 double-hand transplantation patients after 9- and 4-year follow-up periods. A personal rehabilitation program was planned to commence as early as possible after postoperative patient stabilization. Splinting, edema, positioning, passive and active joint movements, daily life activity modification and education, and occupational therapy were also emphasized. RESULTS: Positioning, edema, and passive joint movements were started in the acute phase. Strengthening and exercises were continued for 8 weeks and later for functional gains and adaptation to daily living activities. Subjective and overall results were quite satisfactory. The Hand Transplantation Score System, Disabilities of the Arm Shoulder and Hand, Semmes Weinstein Monofilaments, sensory tests, and modified Kapandji index improvements were all within good acceptable ranges. Although rapid recovery and functional development were observed in the first 4 years, these are still continuing at the time of writing. DISCUSSION: The most important determining factors in the success of rehabilitation are to return to daily life and the ability to acquire functional skills. Long-term follow-up of the patients in this study showed that they were able to return to their independent daily lives and that external assistance decreased to a minimum.

Estimation of Health Utility and Quality Adjusted Life Years in Bilateral Hand Transplantation: A Time Trade-off Study.

BACKGROUND: Hand transplantation and advances in the field of prostheses have opened new frontiers in the restoration of hand function among bilateral hand amputees (BHA). There is only scarce literature evaluating the health utility (HU) and quality adjusted life years (QALY) gained by bilateral hand composite tissue allotransplantation (CTA) or prosthesis over amputation. The study was focused on BHA restored with prosthesis or CTA. METHODS: The HU of three different health states (HS) namely, BHA, using prosthesis or with CTA and net QALYs gained by hand transplantation or prosthesis over amputation were computed by time trade-off (TTO) method among 236 study participants. RESULTS: Among 236 study participants, medical professional (120), general public (89), BHA (23), and bilateral hand transplant recipients (4) were included. The mean HU by TTO method among the study participants (n = 232) as BHA, using prosthesis or CTA was 0.34 (±0.24), 0.50 (±0.26) and 0.69 (±0.26) respectively. Bilateral hand CTA imparted an expected gain of 12.57 (±11.43) mean QALYs over amputation among the study participants. The subgroup analysis displayed higher mean HU in hand CTA recipient HS along with maximum QALY gained by CTA over amputation. CONCLUSIONS: Bilateral hand CTA HS stands above the other 2 HSs, namely BHA and prosthesis, in terms of the health utility. As demonstrated by QALY gain of 12.57, participants' valuation of health utility is notably higher for CTA with acceptance of lifelong immunosuppressant rather than for a state of uncompromised physical health with a bilateral hand amputation.

[Hand Allotransplantation: Care and Challenges].

Hand allotransplantation, a composite tissue allograft, is a time-consuming surgical procedure. This procedure has been shown to significantly improve quality of life in patients with upper extremity loss. The suitability of this procedure must be rigorously evaluated before surgery, and long term antirejection drugs and rehabilitation exercises must be carried out after hand transplantation. Moreover, its success requires close collaboration within the multidisciplinary team. Several related issues are addressed in this article, including the history of hand transplantation surgery, the pros and cons of this procedure, rejection response and immunotherapy, rehabilitation and hand function recovery after hand transplantation, and pre- and post-procedure psychological reactions and evaluations. Response suggestions at the patient and environmental level that reflect the multiple challenges involved in hand transplantation are provided as a reference for clinical decision-makers.

Hand transplantation in the United States: A review of the Organ Procurement and Transplantation Network/United Network for Organ Sharing Database.

Hand transplantation is the most common application of vascularized composite allotransplantation (VCA). Since July 3, 2014, VCAs were added to the definition of organs covered by federal regulation (the Organ Procurement and Transplantation Network (OPTN) Final Rule) and legislation (the National Organ Transplant Act). As such, VCA is subject to requirements including data submission. We performed an analysis of recipients reported to the OPTN to have received hand transplantation between 1999 and 2018. Forty-three patients were identified as having been listed for upper extremity transplantation in the United States. Of these, 22 received transplantation prior to July 3, 2014 and 10 from then to December 31, 2018. Of patients transplanted after 2014, posttransplant functional scores included a decrease in Disabilities of the Arm, Shoulder and Hand questionnaire in 3 of 10 patients, Carroll test scores ranging from 9 to 60 of 99, and monofilament testing with protective sensation achieved in 4 of 6 patients. Complications included rejection in nine recipients with Banff scores from II-IV. One patient experienced graft failure 5 days after transplantation. Of the remaining patients, two were reported as receiving monotherapy and seven receiving dual or triple immunosuppression therapy. The inclusion of VCA in the OPTN Final Rule standardized parameters for safe implementation and data collection.

Long-term outcome after hand and forearm transplantation - a retrospective study.

Between 2000 and 2014, five patients received bilateral hand (n = 3), bilateral forearm (n = 1), and unilateral hand (n = 1) transplants at the Innsbruck Medical University Hospital. We provide a comprehensive report of the long-term results at 20 years. During the 6-20 years follow-up, 43 rejection episodes were recorded in total. Of these, 27.9% were antibody-related with serum donor-specific alloantibodies (DSA) and skin-infiltrating B-cells. The cell phenotype in rejecting skin biopsies changed and C4d-staining increased with time post-transplantation. In the long-term, a change in hand appearance was observed. The functional outcome was highly depending on the level of amputation. The number and severity of rejections did not correlate with hand function, but negatively impacted on the patients´ well-being and quality of life. Patient satisfaction significantly correlated with upper limb function. One hand allograft eventually developed severe allograft vasculopathy and was amputated at 7 years. The patient later died due to progressive gastric cancer. The other four patients are currently rejection-free with moderate levels of immunosuppression. Hand transplantation remains a therapeutic option for carefully selected patients. A stable immunologic situation with optimized and individually adopted immunosuppression favors good compliance and patient satisfaction and may prevent development of DSA.

The Leeds hand transplant programme: Review of the laboratory management of the first six cases.

The UK hand transplantation programme is hosted by the Department of Plastic and Reconstructive Surgery at Leeds Teaching Hospitals under the leadership of Professor Simon Kay. Since programme launch in 2013, ten procedures in six individuals have been performed involving unilateral or bilateral transplants. The multi-disciplinary team that delivers the programme includes the transplant immunology service. The laboratory experience in programme support is reported here.

The histocompatibility and immunogenetics of hand transplantation.

This short review will be concerned with the literature that has developed connected with the immunogenetic and tissue compatibility aspects of hand transplantation and will also draw on connected work in the more general area of vascularized composite allotransplantation (VCA) which includes face, abdominal wall uterus and larynx.

Attitudes of Hand Surgeons and Hand Reconstruction Patients Toward Hand Allotransplantation in Taiwan.

BACKGROUND: Recent advances in immunosuppressive protocols have increasingly made hand allotransplantation a realistic reconstructive option with more than 100 cases performed worldwide. While attitudes toward allotransplantation have been assessed for North American surgeons and patients alike, similar assessments have previously remained unconducted in Asia in general and Taiwan in specific. This study examines the perceptions of both Taiwanese hand surgeons and hand reconstruction patients. METHODS: An email-based survey was sent to all active members of the Taiwanese Society for Surgery of the Hand. Surgeon training backgrounds and practice profiles were gathered as well as current beliefs on indications, risks, ethicality, priority of psychosocial issues, and obstacles to implementation. Patients receiving rehabilitation at Chang Gung Memorial Hospital Linkou after severe upper extremity injuries were invited to complete a patient survey. Demographics, injury characteristics, understanding of allotransplantation and immunosuppression, willingness to donate, and willingness to receive transplantation were assessed. RESULTS: Forty-four hand surgeons responded (24.3% response rate). The majority (61.4%) considered hand allotransplantation to be a high-risk operation, although 40% supported the development of hand allotransplantation under current techniques and immunosuppression. Bilateral hands loss was the most commonly accepted indication for transplant (90.9%), whereas dominant hand loss was less frequently accepted (43.2%). Treatment compliance and functional outcomes were the most frequent psychosocial issues of concern regarding patient counseling. Patient respondents were mostly in the fifth decade of life (29.5%) with at least a high school education (75.0%). Most were aware of the feasibility of hand transplantation (68.2%). Patients were more likely than surgeons to consider nondominant hand, multiple-digit, and thumb-only amputations as indications for transplantation. Functional outcomes and financial considerations were the most frequent patient concerns. CONCLUSIONS: This study indicates there is support for hand allotransplantation as a solution for limb loss in both hand surgeons and hand patients in Taiwan. This study adds to the lack of knowledge regarding surgeon and patient attitudes toward allotransplantation in Asia, although further work is required to assess the willingness of broader Taiwanese medical to refer candidates and for the general population to donate.

Measuring Functional Outcomes After Bilateral Vascularized Composite Hand Allotransplantation: A Report of 3 Cases.

PURPOSE: Currently, numerous assessment tools are available to measure functional outcomes after bilateral hand transplantation. The purpose of this article is to present our experience utilizing quantitative assessment tools for functional evaluation and to describe our results after bilateral hand transplantation. METHODS: A single surgeon's experience with bilateral hand transplantation from 2011 to 2016 was retrospectively reviewed. Three bilateral hand transplantations were performed in 2 adults and 1 child. A minimum 2-year follow-up evaluation was available. For the adult patients, postoperative outcome measures included patient-reported pain and disability scores, return of sensation, muscle strength, range of motion, and return to work/activities of daily living, the Hand Transplant Scoring System (HTSS), the Sollerman hand function test, and complications. For our pediatric patient, postoperative outcome measures included the Functional Independence Measure for children (WeeFIM) scale, a functional independence measure for children, the 9-Hole Peg Test, the Box and Block test, and complications. RESULTS: Our 2 adult patients were age 28 and our pediatric patient was age 8 at transplantation. Follow-up ranged from 2 to 7 years. The functional assessments were performed over a period from 11 to 48 months after transplantation. Both adult patients achieved functional independence and the HTSS, Short Form-36 Health Score (SF-36), DASH, and Sollerman tests demonstrated sequential improvement compared with pretransplantation scores assessed with the use of prostheses. Our pediatric patient demonstrated improvement in his Box and Block test score for each hand at sequential visits after transplantation. His 9-Hole Peg Test demonstrated improvement, and his WeeFIM assessment at 20 months indicated a greater level of independence. CONCLUSIONS: Patient-reported outcomes and the Sollerman test when used in addition to the HTSS appear to reflect functional improvement in adult patients after bilateral hand transplantation. Although children pose a unique challenge with functional assessment, we found the WeeFIM assessment, 9-Hole Peg Test, and the Box and Block test helpful in evaluating functional outcomes in our pediatric patient. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic V.

Topical tacrolimus and steroids modulate T cells in acute rejection of hand allotransplantation: Two case reports.

Acute rejection is not uncommon after vascularized composite allotransplantation. We reported the effects of adjunctive topical immunosuppressant with topical tacrolimus (Protopic®) and steroid cream (Clobetasol®) in the management of acute rejection in two hand transplantation patients. Case 1 is a 45-year-old male with distal forearm deficit 4 years ago and Case 2 is a 30-year-old male with a proximal forearm deficiency 2 years ago, respectively. Both of them suffered from occupational accident and received hand allotransplantation. Induction was performed with antithymocyte globulins and methylprednisolone. Maintenance therapy consisted of tacrolimus (FK506), mycophenolate mofetil, and prednisone. Both cases experienced acute rejection, which we treated with topical tacrolimus and Clobetasol for 2 weeks, combined with systemic immunosuppressant maintenance therapy without adding pulse-steroid therapy. Clinically, both cases recovered after adjunctive treatments. The skin biopsies showed significantly decreased perivascular lymphocyte infiltration after topical treatment. Immunohistochemical staining showed that CD3+ T-cells and CD20+ B-cells were suppressed in the recovery phase. FoxP3-positive regulatory T cells were increased after treatment. Topical tacrolimus and Clobetasol as an adjunctive treatment with maintenance systemic immunosuppressives may be useful to control acute rejection, which correlated with modulation of lymphocyte activation, especially T cells. The treatment needs further investigation with gaining more comparable data.

Grasping with a new hand: Improved performance and normalized grasp-selective brain responses despite persistent functional changes in primary motor cortex and low-level sensory and motor impairments.

Hand loss can now be reversed through surgical transplantation years or decades after amputation. Remarkably, these patients come to use their new hand to skilfully grasp and manipulate objects. The brain mechanisms that make this possible are unknown. Here we test the hypothesis that the anterior intraparietal cortex (aIPC) - a multimodal region implicated in hand preshaping and error correction during grasping - plays a key role in this compensatory grasp control. Motion capture and fMRI are used to characterize hand kinematics and brain responses during visually guided grasping with a transplanted hand at 26 and 41 months post-transplant in patient DR, a former hand amputee of 13 years. Compared with matched controls, DR shows increasingly normal grasp kinematics paralleled by increasingly robust grasp-selective fMRI responses within the very same brain areas that show grasp-selectivity in controls, including the aIPC, premotor and cerebellar cortices. Paradoxically, over this same time DR exhibits significant limitations in basic sensory and motor functions, and persistent amputation-related functional reorganization of primary motor cortex. Movements of the non-transplanted hand positively activate the ipsilateral primary motor hand area - a functional marker of persistent interhemispheric amputation-related reorganization. Our data demonstrate for the first time that even after more than a decade of living as an amputee the normative functional brain organization governing the control of grasping can be restored. We propose that the aIPC and interconnected premotor and cerebellar cortices enable grasp normalization by compensating for the functional impact of reorganizational changes in primary sensorimotor cortex and targeting errors in regenerating peripheral nerves.