Bilateral Hand Transplantation Research Articles

18-month outcomes of heterologous bilateral hand transplantation in a child: a case report

Although heterologous vascular composite allotransplantation has become a burgeoning treatment option for adult amputees, there have been no successful cases previously reported in children. Here, we describe the surgical, immunological, and neurorehabilitation details with functional outcomes 18 months after heterologous bilateral hand and forearm transplantation in an 8-year-old child with quadrimembral amputations and a previous kidney transplant. 2 years of extensive preparation by medical and surgical teams preceded the hand-forearm transplantation of this child. The initial immunosuppressive protocol included thymoglobulin, tacrolimus, prednisone, and mycophenolate mofetil. In July, 2015, our vascularised composite allotransplantation team did the first bilateral hand and forearm transplantation in a child, an 8-year-old boy with previous living-related kidney transplantation. The surgery included four teams working simultaneously on the donor and recipient limbs, aided by customised cutting guides that aimed to reduce ischaemia time. Following an extended length of time in hospital, skin biopsies and close monitoring of renal function and drug concentrations occurred weekly for the first 3 months and were slowly tapered to monthly, and then quarterly. Skin biopsies were also done when tissue rejection was suspected. Paediatric-specific rehabilitation techniques were applied to promote patient engagement during rehabilitation. Progress was assessed by monthly sensory and motor function tests during routine clinic visits and with serial functional brain imaging studies, including structural brain MRI, magnetoencephalography and transcranial magnetic stimulation. The surgery lasted 10 h and 40 min. Vascular revision of the ulnar artery was required a few hours postoperatively. There were no further immediate postsurgical complications. Rejection episodes occurred throughout the first year but were reversed. An increase in serum creatinine led to the addition of sirolimus at 3 months after transplantation with concomitant reduction in tacrolimus targets. Sensibility to light touch was present by 6 months after transplantation. Intrinsic hand muscle innervation was present by 7-10 months after transplantation. At 18 months, the child had exceeded his previous adapted abilities. As of 18 months after transplantation surgery he is able to write and feed, toilet, and dress himself more independently and efficiently than he could do before transplantation. He remains on four immunosuppressive medications and functional neuroimaging studies have shown motor and somatosensory cortical reorganisation. Hand transplantation in a child can be surgically, medically, and functionally successful under carefully considered circumstances. Long-term data on the functional trajectory, neurological recovery, psychological sequelae, and the potential late effect of immunosuppression are still needed to support broader implementation of paediatric vascular composite allotransplantation. The Children's Hospital of Philadelphia.

The Effect of Bilateral Hand Transplantation on Perceived Quality of Life in Two Combat Veterans

Abstract Date Presented 3/31/2017 This presentation explores the perceived quality of life in two upper-extremity limb transplant recipients and compares them with a population of bilateral upper-extremity prosthetic users. Primary Author and Speaker: Kaitlyn Jones Additional Authors and Speakers: Carol A. Coté

First two bilateral hand transplantations in India (Part 1): From vision to reality.

Introduction:Vascularized composite tissue allotransplantation is a relatively new concept, which was unavailable in the Indian subcontinent till a bilateral hand transplant was carried out successfully in January 2015.Materials and Methods:The setting up of the transplant programme involved obtaining legal clearances, creating public awareness, harnessing the institutional facilities, drawing up protocols, assembling the surgical team, managing immunological issues, rehabilitation and preparing the ancillary services.Results:Both, the first and second bilateral hand transplants were resounding successes with both the recipients getting back to their original daily routines.Conclusions:The organisation of the hand transplant programme was a large task, which necessitated intensive planning, and cooperation from various teams within and outside the institution. Exemplary team-work was the key to the phenomenal success of these path breaking endeavors in the subcontinent.

First two bilateral hand transplantations in India (Part 4): Immediate post-operative care, immunosuppression protocol and monitoring.

Introduction:Being able to counter immune-mediated rejection has for decades been the single largest obstacle for the progress of vascular composite allotransplantation (VCA). The human immune system performs the key role of differentiating the 'self ' from the 'non-self '. This, although is quintessential to eliminate or resist infections, also resists the acceptance of an allograft which it promptly recognises as 'non-self'.Materials and Methods:Pre-operative evaluation of the recipient evaluation included immunological assessment in the form of panel reactive antibodies (PRA), human leucocyte antigen (HLA) typing, donor-specific antibody detection assays (DSA) and complement-dependent cytotoxicity assays (CDC). Induction immunosuppression was by thymoglobulin and the maintenance by the standard triple-drug therapy.Results:Both the recipients were managed by the standard triple drug therapy and have had only minor episodes of rejections thus far which have been managed appropriately.Discussion:Induction immunosuppression was by thymoglobulin and the maintenance by the standard triple-drug therapy. Various groups have tried various other formulations and regimes as well.Conclusion:A comprehensive plan has to be drawn up for immunological screening, selection and the post-operative immunosuppressant usage. The ultimate goal of these immunosuppression modalities is to achieve a state of donor-specific tolerance.

First two bilateral hand transplantations in India (Part 2): Technical details.

Introduction:This article deals with two patients who underwent bilateral hand transplantation following amputation of both upper limbs at the distal third of the foream.Materials and Methods:The first patient had a history of loss of hands in a train accident , with possiblity of a run over element during the injury. The second patient lost his both hands in a mine blast. The preoperative work up included detailed clinical and psychological evaluation. The donor retrieval was similar in both the cases and the donors were housed in our own instittution. The donor preparation, recipient preparation and the transplant procedure was similar except for the need of primary tendon transfers in the left hand of the first patient.Results:The first patient needed a free flap transfer to cover compromised skin flap on the left hand on the second day. The second hand transplant was uneventful. Both the recipients are now back to their normal daily routines.Conclusions:Hand transplantation is a potentially life altering procedure, but to optimise the results, it is imperative that there is a meticulous planning and diligent execution with utmost importance to the detail coupled with a synchronised team effort.

First two bilateral hand transplantations in India (Part 3): Rehabilitation and immediate outcome.

Introduction:This report covers the strategies adopted for rehabilitation for the first and second dual hand transplants performed in India.Materials and Methods:The team, under a trained physiatrist, including physiotherapy and occupational therapy personnel, was involved in the management of both these patients. The management protocol was developed considering previous reports as well as our management strategies in the rehabilitation of the replanted hands. The involvement of the team with the patients started in the 1st week itself and continued on a daily basis for the entire year.Results:Outcome analysis was performed at 6 months and 1 year using the disability of shoulder and hand evaluation and hand transplant scoring system. Functional magnetic resonance imaging was done at the end of 1 year to assess the cortical integration of the transplanted hand.Conclusion:Despite more than 110 hands being transplanted worldwide, hand transplant remains an experimental procedure. It is still not considered the “standard of care” for hand amputees. Outcome analyses performed worldwide do indicate that the procedure can provide a substantial improvement in the quality of life for the hand amputee, especially the bilateral amputees.

Ex Situ Perfusion of Human Limb Allografts for 24 Hours.

Vascularized composite allografts, particularly hand and forearm, have limited ischemic tolerance after procurement. In bilateral hand transplantations, this demands a 2 team approach and expedited transfer of the allograft, limiting the recovery to a small geographic area. Ex situ perfusion may be an alternative allograft preservation method to extend allograft survival time. This is a short report of 5 human limbs maintained for 24 hours with ex situ perfusion. Upper limbs were procured from brain-dead organ donors. Following recovery, the brachial artery was cannulated and flushed with 10 000 U of heparin. The limb was then attached to a custom-made, near-normothermic (30-33°C) ex situ perfusion system composed of a pump, reservoir, and oxygenator. Perfusate was plasma-based with a hemoglobin concentration of 4 to 6 g/dL. Average warm ischemia time was 76 minutes. Perfusion was maintained at an average systolic pressure of 93 ± 2 mm Hg, flow 310 ± 20 mL/min, and vascular resistance 153 ± 16 mm Hg/L per minute. Average oxygen consumption was 1.1 ± 0.2 mL/kg per minute. Neuromuscular electrical stimulation continually displayed contraction until the end of perfusion, and histology showed no myocyte injury. Human limb allografts appeared viable after 24 hours of near-normothermic ex situ perfusion. Although these results are early and need validation with transplantation, this technology has promise for extending allograft storage times.

Bilateral hand transplantation: Supporting the patient's choice

Bilateral hand transplantation, as a fairly new reconstructive option for amputees, raises major ethical questions. This article, which is based on the reflections arising from the rich experience of Lyon's team in this field, addresses the topic of supporting the patient in his choice for or against this procedure. How should autonomy be understood in this particular setting? The developing field of composite tissue allotransplantation needs to establish a common thinking on this subject. The article emphasises that, even if it is their right to decide, patients have to be carefully supported to help them make the most consolidated choice possible in this challenging procedure. We deal with the question of the choice between the uncertainty in this innovative procedure and a life-threatening treatment to alleviate a handicap. We outline that the entire process of hand allograft is a unique opportunity for the patients to strengthen and exercise their autonomy in interaction with the medical team.

Technology and vascularized composite allotransplantation (VCA)-lessons learned from the first bilateral pediatric hand transplant.

The reconstructive principle of replacing "like with like" is best met with vascularized composite allotransplantation in which the components of an existing defect are "matched" to the greatest extent possible in a single stage restoration. Hand transplantation is a labor-intensive and time-intensive process and can be conceptualized into distinct phases that include (1) patient selection and preoperative preparation, (2) technical execution of the procedure, and (3) postoperative rehabilitation and follow-up. The advent of technological innovations, such as 3D printing technology, novel implant technology, as well as innovative imaging technology, such as functional magnetic resonance imaging have the potential of favorably affecting all phases of this process, thus contributing to improved outcomes. The use of these technologies in the world's first case of bilateral hand transplantation in a pediatric patient is discussed.

Use of Video Clips to Assess the Outcomes of Bilateral Hand Transplantation.

Given the initial success of hand transplantation, there has been increased interest in determining functional independence and activities of daily living after hand transplantation. However, the metrics and methodologies used to study these outcomes have not yet been standardized. The goal of this article was to assess the role of video clips in assessing the outcomes of bilateral hand transplantation. We have performed 3 bilateral hand transplantations at our institution. Video clips were taken at standardized time points on our index bilateral hand transplantation patient, and the patient sent multiple home-video clips demonstrating new aspects of function when these improvements have occurred. The index patient demonstrated functional independence and activity of daily living performance without assistance in video clips ranging from 9 months to 2.5 years posttransplantation. He completed the 9-hole peg test with his left hand at 9 months follow-up and with both the hands by 1.5 years. His own video clips demonstrated his ability to perform spontaneous tasks including lawn mowing, driving and swimming. In our experience, the video tools aid in assessing outcomes of hand transplantation and may be incorporated along with multiple objective scoring tests. They can also be used to generate additional standardized tests for functional assessment and may allow retrospective grading as new scoring systems are developed.

Psychosocial Outcomes after Bilateral Hand Transplantation.

Background:Since the first successful hand transplantation in 1998, there have been multiple reports about surgical technique, transplant survival, and immunosuppression. However, very limited published data exist on psychosocial outcomes following hand transplantation.Methods:We report psychosocial outcomes in a patient with bilateral hand transplants at the midforearm level with serial follow-ups over 3.5 years. Different metrics used to study psychosocial outcomes included the following: SF-12, CES-D, Dyadic Adjustment Scale, Rosenberg SE, and EQ-5D.Result:Preoperatively, our patient did not have any evidence of depression (CES-D = 3), had a nonstressful relationship with his spouse (Dyadic Adjustment Scale = 100), and self-esteem was in the normal range (Rosenberg SE = 21). These metrics and his additional scales (SF-12 MCS, EQ-5D, and EQ-VAS) did not change appreciably and were within the normal range for the entire duration of 3.5-year follow-up at all different time points.Conclusion:With the increasing popularity of hand transplantation and the increasing awareness of the importance of psychosocial parameters in overall success, appropriate, comprehensive, and standardized measurements are important. These should be an integral part of patients’ screening and follow-up.

Upper Extremity Ultra-High Field MR Imaging of Bilateral Hand Transplant Patient

Upper Extremity Ultra-High Field MR Imaging of Bilateral Hand Transplant Patient

Vascularised composite allotransplants: Transplant of upper extremities and face.

Transplantation of solid organs and bone marrow has become a highly acceptable and often the only available clinical solution in many situations. It has been practiced across the globe for quite a long time since the first kidney transplant in 1954. Transplantation of tissues other than these, which was termed composite tissue allotransplantation and currently as vascularised composite allotransplantation (VCA) is gaining acceptance as a solution for complex reconstructive problems. This involves the transfer of multiple types of tissue such as bone, muscle, nerve, skin and blood vessels. The advantage of these over the conventional reconstructive methods is its ability to give aesthetically and functionally superior equal composite substitute to the missing or deformed part. The composite tissues transplanted commonly include the upper extremities, face and abdominal wall. Among these, hand transplants were the first to be done and have been carried out more than any other VCA. This article reviews the current scenario of VCA especially of the hand and face, in the light of experience of the two bilateral hand transplants done recently in India.

Hand and upper extremity transplantation: an update of outcomes in the worldwide experience.

Hand/upper extremity transplantation is the most common form of vascularized composite allotransplantation performed to date. An Update of worldwide outcomes is reported. The authors summarize the international experience with 107 known transplanted hand/upper extremities in 72 patients. Data from published medical literature, national and international meetings, lay press reports, and personal communications were utilized to provide the most up-to-date summary. Although 24 losses (including four mortalities) are known, three of the four reported mortalities and eight of 24 limb losses were caused by multiple type vascularized composite allotransplantations (combined upper and lower limb or upper limb and face). Seven more losses were attributable to 15 patients in the early experience in China. In the United States and Western Europe, only three other non-acute graft losses have been reported, resulting in a patient survival rate for unilateral or bilateral hand transplantation in isolation of 98.5 percent and an overall graft survival rate of 83.1 percent. Published functional outcomes continue to demonstrate improvement in function and quality of life. The international experience supports the idea that, for properly selected individuals, hand and upper extremity transplantation should be considered an important treatment option.

Outcomes After Bilateral Hand Allotransplantation

The clinic era of composite tissue allotransplantation was inaugurated by hand allotransplantation in 1998, giving rise to many controversies and scepticism because of the lifelong immunosuppression, the unclear risk-benefit ratio, and the uncertain long-term functional results of the procedure. The aim of this study was to evaluate the outcomes and the risk/benefit balance in bilateral hand allotransplantation. The study included 5 cases of bilateral hand allotransplantation performed in a single center, with a follow-up ranging from 3 to 13 years. The recipients (4 men, 1 woman) were young. The level of amputation was distal in all cases except for 2 patients amputated at the midforearm level. All the recipients initially received the same immunosuppressive treatment that included tacrolimus, mycophenolate mofetil, prednisone, and, for induction, antithymocyte globulins. Patient and graft survival was 100%. All recipients showed adequate sensorimotor recovery (protective and tactile sensitivity and partial recovery of intrinsic muscles), they were able to perform the majority of activities of daily living, and had a normal social life. Most complications occurred in the first posttransplant year and were successfully managed. All recipients experienced at least 1 episode of acute rejection, which was easily reversed by increasing oral steroid dose or by intravenous steroids, except for patient 3, who presented 6 episodes of acute rejection, the latest 2 treated with Campath-1H. Although bilateral hand transplantation may be a satisfactory treatment option for amputees, a careful selection of candidates and a rigorous evaluation of recipients after transplantation are imperative.

Anaesthetic management of bilateral hand transplantation.

Sir, Vascularised composite tissue allotransplantation is now considered a feasible reconstructive option for patients with upper extremity loss. We are reporting the anaesthetic management of the first hand transplantation in India, world's first in a non-white. A 31 year-old male patient who lost both his hands in a train accident was put on the waiting list of the transplant programme 2 years back. Donor became available when the family of a 24 year-old healthy male patient, diagnosed to be brain dead, came forward with the willingness to donate both his hands. Pre-operatively, the recipient received tacrolimus, mycophenolate mofetil and valganciclovir orally. Under local anaesthesia, right sub-clavian central line, right dorsalis pedis arterial line and two 16 G peripheral lines in the feet were introduced. Thymoglobulin 1 mg/kg, methylprednisolone 500 mg and piperacillin/tazobactam 4.5 g were given intravenously. The hand harvesting was performed under tourniquet and the limbs were perfused with cold HDK solution through the brachial vessels before amputation. Other organs were harvested only after the hand harvesting was done. The recipient received a standard anaesthesia protocol: induction with propofol, pancuronium for muscle relaxation, morphine as analgesic, maintenance with oxygen and nitrous oxide (1:2) with isoflurane (1%), and mechanical ventilation. Supra-clavicular brachial plexus catheters were placed bilaterally with the aid of an ultrasound probe and 10 ml bupivacaine 0.25% was given on each side. Intra-operatively, the patient received methylprednisolone 500 mg and bolus of intravenous fluid with 1 meq/kg sodium bicarbonate prior to reperfusion. The surgery took 17 h; in the last 4 h he went into severe hypotension requiring colloids (1.5 L) and 7 units of packed red blood cells (PRBC). Vasoconstrictors were avoided for fear of vasospasm at the anastomotic sites. The patient had received 12.5 L of Ringer lactate intra-operatively. At the end of the surgical procedure, bilateral supraclavicular block was repeated with 10 ml of 0.5% bupivacaine. The patient was ventilated for 3 h until he became normothermic. The patient [Figure 1] had an uneventful post-operative period and was shifted out of the transplant Intensive Care Unit after 2 weeks. Figure 1 Post-operative picture of the patient The Pittsburgh Upper Extremity Transplant Anesthesiology Protocol offers important guidelines and recommendations for management of upper extremity transplant recipients focusing on fluid management, intraoperative monitoring and regional anaesthesia strategies.[1] In addition, problems associated with massive blood loss, hypothermia and reperfusion injury should be taken care of. The ideal time of limb procurement is prior to solid organ harvest, i.e., before the aorta is cross-clamped, given the concern for ischaemia time.[2] Use of tourniquet minimises blood loss in the heart-beating donor and reduces the risk of destabilisation due to blood loss.[3] The standard immunosuppression involves induction therapy with antibodies combined with multi-drug maintenance therapy. Since these surgeries involve massive blood loss,[4] with an inherent risk of dilutional coagulopathy and rhabdomyolysis,[5] multiple large intravenous access is essential, so is arrangement of at least 10 units of PRBC and adequate products. The goals of haemodynamic management include avoidance of hypotension, reduction of vasopressor use and improving oxygenation to the graft.[1] During microsurgeries with multiple vessel anastomoses, improved oxygenation to graft is usually accomplished by haemodilution and controlled hypertension by means of volume expansion. Hence, aim is to have a well-filled patient with a good urine output. As viscous blood tends to clot around the anastomotic sites, haemoglobin of >10 g/dL is not recommended. In addition, regional anaesthesia provides vasodilatation which improves perfusion of the graft. Intra-operatively we supplemented general anaesthesia with brachial plexus block using 0.25% bupivacaine, mainly to obtain vasodilatation. However, post-operatively 0.5% bupivacaine was used aiming intense block that provided maximum vasodilatation with analgesia and motor block. Declaration of Patient Consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

International Registry On Hand and Composite Tissue Transplantation.

The IRHCTT includes hand and face allotransplantations. Methods: Since September 1998 66 upper extremity transplantations (22 unilateral and 22 bilateral transplants) have been reported, for a total of 44 patients. They were 35 males and 9 females, median age 32.5 years. In the majority of cases the level of amputation was distal, but there were also 6 arm transplantations. Since November 2005 20 cases of partial or complete face transplantations have been reported, 15 males and 5 females, median age 46 years. In the majority of cases the deficit included cheek, nose, chin, lips and perioral area. The patients presented impairment or impossibility of swallowing, eating, drinking and speaking. In hand and face transplantation the imunosuppressive therapy included tacrolimus, mycophenolate mofetil, sirolimus and steroids; polyclonal or monoclonal antibodies were used for induction. Follow-up ranges from 8 months to 15 years for upper extremity transplantation and from 6 months to 8 years for face transplantation. Results: One simultaneous face and bilateral hand transplantation died on day 65, one bilateral arm transplantation for congestive heart failure on day 1 and one bilateral hand transplantation for sepsis on day 101. Another case of face transplantation died for pharyngo-laryngeal neoplasia three years after transplantation. Six patients transplanted have lost their grafted hands during the follow-up. 75% percent of hand recipients and 50% of face recipients experienced at least one episode of acute rejection within the first post-transplant year that was reversible when promptly treated. The first cases of chronic rejection were reported and the cause was often the patients’ non-compliance. Complications included, as in solid organ transplantation, opportunistic infections, metabolic complications and malignancies. Hand-grafted patients developed protective sensibility, 90% of them tactile sensibility and 80% also a partial discriminative sensibility Motor recovery enabled patients to perform most daily activities. Face-grafted patients improved their aesthetic aspect and they were able to perform some activities such as eating, drinking and speaking, living a normal social life. Conclusions: Hand and face transplantations are successful procedures, however careful evaluation of patients before and after transplantation and their compliance are indispensable.

Rehabilitation After Bilateral Hand Transplantation in the Quadrimembral Patient

The hand transplantation is a unique entity in the fields of medicine and rehabilitation. Hand therapy and rehabilitation programs are consistently reported as essential to a successful functional outcome for the hand transplant patient. In September 2011, our medical center performed their first bilateral hand and forearm transplant on a 28-year-old female 4 years after losing her lower extremities and upper extremities due to multiorgan system failure and pressure-induced extremity ischemia. She participated in 4 months of hand therapy, occupational therapy, and physical therapy at our institution, and then returned to her hometown to continue with an intensive therapy program. At 16 months after transplantation, she had sensory return to diminished protective level and motor return to all transplanted muscles except for intrinsics. Our hand therapy team established a treatment program based on literature, collaboration with other transplant centers, and clinical experience. Now, 2 years after our first hand transplant case, we assess our plan and program, offer suggestions for developing a treatment program and encourage therapist to collaborate with their own transplant team and others around the United States and the world.

Editorial introductions

Editorial introductions

Secondary Surgery for Functional Improvement After Hand Transplantation

Unilateral and bilateral hand transplantations have been performed worldwide with good midterm functional results. The role of secondary surgery to improve function in the patients with hand transplant has not been uniformly agreed upon. A series of 10 secondary procedures were performed in 5 surgeries on 3 patients with bilateral upper extremity transplantation. There was 1 incidence of acute rejection after 1 procedure. The functional improvement was evaluated subjectively by the patients as substantial. Secondary procedures can upgrade function after hand transplantation and provide unique opportunities for deep-tissue biopsies. The proinflammatory stimulus of the surgery can theoretically precipitate an acute rejection. The pharmacologic interference of some immunosuppressive drugs with wound healing should also be considered.