Hand Transplant Program Research Articles

Establishing an upper extremity transplantation program: lessons learnt over 12 years.

As one of the early hand transplant programs in the world, we are often asked to educate other programs on the lessons we have learned and on how to set up a successful hand transplantation program. Two decades of global experience with vascularized composite allotransplantation (VCA) of the upper limb have demonstrated improved functional outcomes and quality of life for carefully screened patients. Despite initial reticence about VCA, over 30 patients in the USA have benefited from hand transplantation, with around 80% long-term successes. We have experience with four bilateral upper extremity patients who have undergone bilateral upper extremity allotransplants. This review article highlights our personal experience and lessons with respect to VCA team assembly, logistics, patient selection, perioperative planning, the operative procedure, and postoperative management. Continual learning and critical evaluation are crucial to maintaining a successful upper extremity VCA program. This will ensure that patients who stand to benefit most from this life-enhancing procedure are identified and are others optimized to achieve the best possible outcomes.

Mimicking Clinical Rejection Patterns in a Rat Osteomyocutaneous Flap Model of Vascularized Composite Allotransplantation

IntroductionGraft loss in vascularized composite allotransplantation (VCA) is more often associated with vasculopathy and chronic rejection (CR) than acute cellular rejection (ACR). We present a rat osteomyocutaneous flap model using titrated tacrolimus administration that mimics the graft rejection patterns in our clinical hand transplant program. Comparison of outcomes in these models support a role for ischemia reperfusion injury (IRI) and microvascular changes in CR of skin and large-vessel vasculopathy. The potential of the surgical models for investigating mechanisms of rejection and vasculopathy in VCA and treatment interventions is presented. Materials and MethodsFour rodent groups were evaluated: syngeneic controls (Group 1), allogeneic transient immunosuppression (Group 2), allogeneic suboptimal immunosuppression (Group 3), and allogeneic standard immunosuppression (Group 4). Animals were monitored for ACR, vasculopathy, and CR of the skin. ResultsTransient immunosuppression resulted in severe ACR within 2 wk of tacrolimus discontinuation. Standard immunosuppression resulted in minimal rejection but subclinical microvascular changes, including capillary thrombosis and luminal narrowing in arterioles in the donor skin. Further reduction in tacrolimus dose led to femoral vasculopathy and CR of the skin. Surprisingly, femoral vasculopathy was also observed in the syngeneic control group. ConclusionsTitration of tacrolimus in the allogeneic VCA model resulted in presentations of rejection and vasculopathy similar to those in patients and suggests vasculopathy starts at the microvascular level. This adjustable experimental model will allow the study of variables and interventions, such as external trauma or complement blockade, that may initiate or mitigate vasculopathy and CR in VCA.

Descriptive Study of Patients With Upper Limb Amputation As Possible Candidates for a Hand Transplant in Medellín, Colombia

IntroductionThe amputation of the upper limb, especially of the hand, is a serious trauma with significant functional and psychological impact. Treatment options include adaptation to the stump, use of prostheses, and composite tissue transplantation. Unfortunately, in Colombia, to date, there are no epidemiological data that characterize the sociodemographic and clinical variables of patients with upper limb amputation.ObjectiveTo describe the clinical and epidemiological characteristics of patients with upper limb amputation in two hospital institutions in the city of Medellín during the period 2018-2019 as a basis for developing a hand transplant program in Colombia.MethodsA descriptive cross-sectional study was carried out where a total of 443 medical records were reviewed, of which eight records that met the inclusion criteria were identified. Variables such as age, etiology of amputation, level of amputation, comorbidities, complications, and rehabilitation process were analyzed. The information was collected in the REDCap program, and a descriptive analysis was carried out with the data obtained.ResultsFrom a sample of 443 amputee patients, eight were selected that met the inclusion criteria. There were 7/8 men (87%) aged 43 years. A total of 75% came from rural areas. In 3/8 patients, there was amputation of the dominant limb. The most common mechanisms were shear trauma and crushing in the context of an occupational accident. A total of 50% had a complete extra-hospital amputation, and reimplantation was not attempted in any of the cases. The most frequent levels of amputation were the proximal and distal third of the forearm. The longest follow-up time was 12 months. Only two patients mentioned the possibility of using a prosthesis during rehabilitation.ConclusionsThree young patients were identified, without comorbidities, with amputation of the dominant limb in the context of an occupational accident and without the possibility of rehabilitation with prostheses who benefit from a possible future hand transplant. However, it is necessary to implement a composite tissue transplantation program and public health policies that allow this procedure to be performed in Colombia.

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 30years. 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.

Hand Transplantation: The Benefits, Risks, Outcomes, and Future.

The field of transplantation came to fruition in 1954 when Joseph Murray, an American plastic surgeon, performed the first kidney transplant in the world.1 Subsequently, most early transplantations in the U.S. were of solid homogeneous organs. Then, in 1964, a hand transplant was performed in Ecuador on a sailor who had lost both arms in an explosion,2 and the possibility of composite tissue allotransplantation (CTA) with heterogeneous tissues then emerged. However, the patient's graft was rejected and was explanted at week 3. The field was stagnant until the 1980s, when the discovery of calcineurin inhibitors improved immunotherapy and made limb transplantation viable. In 1999, a hand was transplanted with long-term success in Louisville, Kentucky,3 reawakening interest in CTA and reconstructive transplantation. By 2009, 53 successful hand transplants had been performed worldwide.4In reconstructive transplantation for catastrophic limb and tissue loss, a one-year graft-survival rate of 96% has been reported5—notable because upper-extremity transplantation is extremely complex. The steps include bone approximation and plating of both the radius and ulna, extensive vessel anastomoses, extensor and flexor tendon repairs, and limb innervation.Hand and arm transplantation optimally restores full motor and sensory function. Investigators6 reported better functional outcomes after tissue transplants than after using prosthetic devices: quantitative testing7 in multiple recipients revealed that CTA methods enabled patients to resume most daily activities, including eating, driving, and writing.6 In one registry,5 all transplant recipients developed protective sensibility against pain, 90% regained tactile sensibility, and 82.3% achieved discriminative (fine) sensibility. However, the greatest benefit was improved quality of life, reported by 75% of recipients.5Despite the benefits of CTA, debate continues on whether the potential for improving a patient's quality of life outweighs the risks: limb transplants are usually elective procedures, yet they necessitate intensive surgery and the same lifelong immunosuppressive therapy as do solid-organ transplants. Risks include opportunistic infection (chiefly cytomegalovirus), metabolic disorders such as diabetes mellitus and Cushing syndrome, and malignancies (skin cancers and lymphoproliferative disease).5,8,9 The graft itself might also fail consequent to infection, acute rejection, intimal hyperplasia, or noncompliance with immunosuppressive medications.5 Acute rejection, which reportedly occurs in 85% of recipients within the first year, typically manifests itself with cutaneous lesions.5,10 Therefore, healthcare providers disagree about when and whether hand transplantation should be offered.11 On the bright side, acute rejection can be reversed with prompt treatment, and we found no reports of graft-versus-host disease or chronic rejection in recipients of hand grafts.Satisfactory survival rates after CTA indicate that the field of reconstructive transplantation will continue to expand. Risk reduction will be crucial, particularly in association with immunotherapy. The Baylor Comprehensive Hand Transplant Program team has developed a protocol for using donor bone marrow and stem cells to modulate the immune system in place of typical immunosuppression during clinical reconstructive transplantation. Success in these efforts may transform the care of patients who experience catastrophic limb loss.We thank Sebastian J. Winocour, MD, FRCSC, and Shayan A. Izaddoost, MD, PhD, Division of Plastic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, for their contributions to the manuscript.

Building a Hand and Upper Extremity Transplantation Program: Lessons Learned From the First 20 Years of Vascularized Composite Allotransplantation.

Background: Upper extremity transplantation is a quality-of-life enhancing treatment for select patients with upper extremity loss. This article reviews the preoperative, intraoperative, and postoperative challenges in the upper extremity transplantation process and the lessons learned from the first 2 decades of hand transplantation. Methods: Key components of the author's hand transplantation protocol including patient selection, donor screening, surgical rehearsal, donor procurement, transplantation, immunosuppression, and patient outcome reporting/follow-up are reported to assist other teams who wish to establish a hand transplantation program. Results: There have been many advancements in the first 20 years of hand transplantation including better patient selection criteria, the recent addition of pediatric patients, improved surgical techniques such as the use of virtual surgical planning, and improved immunosuppression protocols. Improvement has also taken place in the tracking and reporting of hand transplant outcomes, but more work is clearly needed to fully define the benefits of transplantation, especially for pediatric patients. Conclusions: Over the past 20 years, significant progress has been made in upper extremity transplantation although a number of challenges remain including how to best document and share outcome measures, optimize immunosuppression, and diagnose/treat rejection. The authors encourage upper extremity transplant programs to report their experience and protocols to advance hand transplantation as standard of care for properly selected individuals.

Hand allotransplantation: operating room set-up and team coordination.

Vascularized composite allotransplantion requires careful planning and precise execution. The Director of the Hand Transplant Program must coordinate many personnel including nurses, anesthesiologists, transplant coordinators, surgeons, support staff, and hospital administrators. The operation is performed only after surgical rehearsal has reinforced the specialized role of each of these team members and the workflow of equipment and personnel has been optimized.

The Innsbruck Hand Transplant Program: An Update More than a Decade after the First Transplant

Introduction: We describe here the outcome after two bilateral hand, one bilateral forearm and one unilateral hand transplantation at 12, 9, 5.5 and 2.5 years after transplantation. Methods: Four patients received a bilateral hand (n=2), a bilateral forearm (n=1) or a unilateral hand transplant between March 2000 and July 2009. Induction therapy with ATG (n=2) or alemtuzumab (n=2) was followed by tacrolimus, prednisolon MMF (n=3) or tacrolimus and MMF (n=1) maintenance IS. Later, sirolimus/everolimus was added under simultaneous withdrawal (n=2) or dose reduction (n=1) of tacrolimus (n=1) or MMF (n=1). Steroids were avoided in one and withdrawn in two patients. Results: Total active range of motion improved continously with a grip strength of 2-10kg. Hand function correlated well with time after transplant and amputation level. Intrinsic hand muscle function recovery and discriminative sensation were observed in all patients. Complications included CMV infection, fungal infection, hypertension, hyperglycemia, transient creatinine increase and headache and a bullous pemphigoid. Three, six, four, and one rejection episode were successfully treated with steroids, anti-CD25, anti-CD52 antibodies and/or intensified maintenance IS. Skin histology at current shows no or mild perivascular lymphocytic infiltrates without signs of progression. Vessels are patent without signs for luminal narrowing or intimal proliferation. Conclusion: The overall functional outcome and patient satisfaction after bilateral hand, bilateral forearm and unilateral hand transplantation are highly encouraging. All patients are now free of rejection with moderate levels of IS.

Potential of a Hand Transplantation Program in Colombia

The protocols and published results on hand transplantation show acceptable results of this technology. None of the registered groups, however has a sufficient number of patients to allow continuity of the process. In Colombia the main problems are violence, drug traffic, and guerrillas. Thanks to the profitability of drug traffic, guerrillas, who initially were created based on ideologic differences, have become terrorist groups whose main source of income is drug traffic. From that interest comes the use of landmines to protect illicit crops. Colombia is the most mined country in the world, followed by Cambodia and Afghanistan, and the only country in Latin America where there are still landmines. The mines, violence, and trauma produce a large number of people with disabilities and amputations. From 1990 to 2006, the number of victims rose from 21 to 1,041 per year. In Colombia, amputations are more frequently due to trauma than to disease. The fact that 88% of the victims are children and people of working age, affects the political and economic development. These alarming numbers generate a challenge for government, which has led to the creation of policies and laws aimed at comprehensive action against mines. This program under the Presidency has among its objectives assistance to victims, including integrated treatment, prostheses, and other procedures, financed entirely by the government. The number, type of victims, and their motivation to be transplanted, along with government programs directed to their attention, are key factors that we think will enable the continuity of our hand transplantation program at the Fundación Santa Fe de Bogotá, giving Colombia the unfortunate privilege of having the largest number of potential patients for transplantation.

Hand Transplantation–Polish Program

Background Hand transplantations (HTs) are performed in specialized centers proceeding within a board-accepted transplantation program. In Poland such requirements are met by the Subdepartment or Replantation of Limbs of St. Jadwiga Hospital in Trzebnica. The goal of this study was to present the experience of the Center after 3 years of activity. Material and Methods On creating the “waiting list of would-be hand recipients,” we adhered to the inclusion criteria commonly used by other centers. Among 52 potential candidates seen over a 4-year period, the selection process and inclusion criteria yielded 13 patients who were preliminary candidates for an HT. They proceeded to a formal hospital admission to obtain a detailed evaluation including invasive diagnostic tests. The group consisted of 12 men of age 21–42 years with single dominant hand amputations and 1 woman of 23 years with amputations of both hands. Within this group we performed 3 HTs in 3 men of 32, 42, and 30 years old: 2006 and in 2007 at mid-forearm level and in 2008 at the distal forearm level. The times elapsed from amputation to HT were 14, 6, and 7 years, respectively. Results The first patient achieved total motion of fingers equal to 63% of that of his unaffected hand. Evaluation using the SF-36 protocol gave a result of 50; by DASH, 95; by CFSS (according to Lanzetta and Petruzzo), 84 (excellent). He had only 1 mild rejection episode. Our second HT failed. The third patient has a good hand function, namely, 80% of the finger motion of the unaffected hand and sensitivity reaching his finger tips. No rejection episodes were observed. Conclusion On the basis of these results, we plan to proceed with the hand transplantation program.

Requirements for the Development of a Hand Transplantation Program

Since 1998, 42 hand transplants in 30 patients have been performed in countries such as France, United States, China, Austria, Malaysia, Italy, Belgium, Poland, Spain, and Germany. Now, with recent improvements in immunosuppression, the clinical applicability may expand and the ethical obstacles may soon be overcome, allowing multiple US institutions to perform hand allotransplantation. The main purpose of this article is to facilitate access to pertinent details in regards to hand transplantation, such as donor/recipient selection criteria, immunosuppressive therapies, and associated complications. It is a comprehensive literature review compiled from published reports from multiple hand transplant programs throughout the world. Due to its inherent complexity, hand transplantation should only be attempted at institutions within the US capable of orchestrating a specialized multidisciplinary team, and each institution's protocol should be extremely detailed and individualized.

Ethical Considerations in the Early Composite Tissue Allograft Experience: A Review of the Louisville Ethics Program

This paper reviews the formulation and evolution of the ethical component in one of the earliest clinical composite tissue allograft (CTA) programs, the hand transplantation program in Louisville, Kentucky, USA. The purpose was to derive lessons and define principles to give guidance for future programs and introduction of new CTA. We reviewed the initial ethical considerations, including input from respected ethical scholars, guidelines for innovative procedures transparency in public and professional scrutiny, and compliance with human studies regulations (IRB approval). We found the initial focus on ethics, scholarly input, guidelines for innovative procedures, and human studies protection regulations to be valid. Moreover, we noted the effect of autonomy in subjective, quality-of-life benefits on equipoise and effective risk–benefit analysis in effective informed consent. We found that psychiatric screening and support to be exceptionally valuable in protecting autonomy, suitability for participation, assessing personality organization, and determining compliance ability. We conclude that the program ethical principles were validated. For future CTA programs and procedures, we recommend an ethical emphasis with adherence to high standards and transpire to independence to scrutiny and oversight. We recommend protection of autonomy judgments in equipoise judgment and informed consent. We recommend skilled psychiatric screening and support. We endorse scholarship, scientific accuracy, and data sharing.

Functional results of the Italian hand transplantation program

Functional results of the Italian hand transplantation program

Ethical considerations in composite tissue allotransplantation.

Ethical issues posed by the hand transplant program conducted by hand and plastic surgeons at Jewish and University Hospitals, Louisville, Kentucky, are examined in this essay. Because a composite tissue allotransplantation (CTA) is an experimental procedure, it raises issues as to the protection of human subjects. The background for the emergence of medical ethics as a discipline is indicated and the processes employed by the CTA team in order to address ethical concerns are discussed. Questions are posed as to the justifications for certain procedures and those pertaining to the goals of medicine, informed consent, and patient quality of life. Other issues include benefits versus risks, patient autonomy and medical paternalism or non-maleficence. The Louisville team seems to have dealt conscientiously with all ethical questions that have been posed and has treated the hand recipient with competence and continuity of care. No reasons based in ethical concerns have surfaced that would in any way discredit the program.