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Risks of allogeneic hand transplantation.

A patient undergoing allogeneic hand transplantation needs lifelong immunosuppression with the risk of serious side effects, including life-threatening disease. The question remains: does the eventual improvement in function justify the risk? To answer this question, we try to assess the risks based on a large body of cumulative data derived from more 200,000 kidney transplants using the Collaborative Transplantation Study (CTS). Only selective data which apply to a patient population aged between 15-40 years were used (n = 58,310). Data are compared to the literature references and show superiority with respect to patient numbers, statistics, actuality, and methodology. The CTS data show that the incidence of de novo malignancies is lower than previously reported. The risk of developing any form of cancer is approximately 3%, of developing a skin cancer 1.1%, and of developing a lymphoma 0.58% within 5 years after transplantation. The risk of suffering from a cataract is 11% after 5 years, which is also lower than previously reported. Although the incidence of side effects (particularly malignant disease) is likely to be lower than previously thought, the risk-benefit question must be answered by each hand surgeon for each individual patient.

Adolescent↗

[Bilateral hand transplantation].

In March 2000 we performed a bilateral hand transplantation on a 47-year-old policeman who had lost both hands in a bomb accident. Although he was fitted with myoelectric prostheses, he kept investigating the possibility of hand transplantation. The ethical, surgical, medical, legal and human aspects of this special kind of reconstruction was discussed in a symposium in Vienna, and it was decided to go ahead with it if a suitable candidate presented. The operation was successful, the immunosuppressive regimen well-planned and carried out, the post-operative course without any remarkable events. Under intensive physical therapy, the patient gradually but steadily regained sensory and motor functions in his hands. Now, two years after the operation, the patient is practically independent in the activities of daily living and is able to work at his job.

Activities of Daily Living↗

Psychiatric assessment of candidates for hand transplantation.

An important part of the pretransplant evaluation of candidates for hand transplantation is a psychiatric assessment to formulate psychological benefits and risks of transplantation and determine any appropriate psychosocial interventions to optimize the patient's candidacy for the procedure and prevent psychiatric morbidity. Screening data are presented from 213 individuals who contacted a national referral center for hand surgery regarding hand transplantation, and from the subsequent detailed psychiatric assessments of 9 individuals considering the procedure. Most of the nine patients undergoing intensive psychiatric assessment were assessed as demonstrating an overall favorable profile of psychological benefits and risks. In addition to providing information regarding the psychological experience of patients with amputations and their motivation for hand transplantation, it is hoped this information, as compared with posttransplant outcome data, will help further refine the assessment of candidates for this procedure and possibly other forms of composite tissue allotransplantation.

Adaptation, Psychological↗

Bilateral hand transplantation: bone healing under immunosuppression with tacrolimus, mycophenolate mofetil, and prednisolone.

PURPOSE: Little is known about bone healing after composite tissue transplantation that requires pharmacologic immunosuppression. Bone integration and callus development were assessed in bilateral hand transplantation. METHODS: In this study the course of callus development and callus maturation were assessed by color Doppler sonography and radiography in a double hand transplant and compared with forearm replantation. RESULTS: After hand transplantation, ingrowth of small vessels at the bone junction was observed at week 3, calcified callus became visible at month 4, and bone union was completed at month 11. A similar time course of bone integration was observed after replantation. Plating offered sufficient stability. A recipient periostal flap is thought to have improved blood supply and favored development and induction of callus. CONCLUSIONS: Bone healing after hand transplantation under immunosuppression with tacrolimus, mycophenolate mofetil, and prednisolone is identical to that after forearm replantation.

Amputation, Traumatic↗

Hand transplantation: comparisons and observations of the first four clinical cases.

Twenty, 15, and 8 months after the first four successful human hand transplant procedures were performed in Lyon (France), Louisville (U. S.), and Guangzhou (China), the transplant teams convened in Louisville, Kentucky, to share their experiences at the Second International Symposium on Composite Tissue Allotransplantation. This article presents reconstructive and immunological data from these landmark procedures in tabular format, in an attempt to answer some key questions about early outcomes of clinical hand transplantation. On the basis of these data, the initial outcomes of the first four hand transplants are encouraging and warrant proceeding with additional hand transplantations.

Adult↗

First human double hand transplantation: efficacy of a conventional immunosuppressive protocol.

Based on the results achieved in single human hand transplantations, we decided to perform the first double hand transplantation with a conventional immunosuppressive protocol in a patient with a high potential for functional recovery. Two years after transplantation the efficacy and the safety of this immunosuppressive protocol are evaluated. The recipient was a 33-yr-old man suffering from a traumatic amputation of both hands in 1996. Five HLA-A, -B, and -DR mismatches were present with the donor; T and B cell cross-match was negative. Immunosuppressive protocol included tacrolimus, prednisone, mycophenolate mofetil and, for induction, antithymocyte globulins and then anti CD25 monoclonal antibody. Reconstitution of lymphocyte populations proceeded normally. Neither anti-HLA antibodies nor chimerism in peripheral blood were detected. Two episodes of acute rejection characterized by maculopapular lesions occurred on days 53 and 82 after transplantation. Skin biopsies revealed a dermal lymphocytic infiltrate. Both episodes were completely and rapidly reversed by topical clobetasol and increased systemic corticosteroid therapy. The only side-effects related to treatment were reversible serum sickness and hyperglycemia. No infectious complications and malignancies occurred. No signs of graft-versus-host disease have been detected. This case of double hand transplantation shows that conventional immunosuppression is effective and safe to ensure survival and functional recovery of the grafted limb.

Adult↗

A position statement in support of hand transplantation.

The scientific basis for human trials of hand transplantation was both experimental and clinical. Prolonged survival of limb transplants was achieved in small and large animals by using novel immunosuppressive drugs. Further, all tissue components of the hand (skin, muscle, tendon, nerve, bone, and joint) were individually transplanted with success in humans. After appropriate institutional review of the ethics, experimental data, treatment protocol, and informed consent, clinical trials were approved. Thirteen hands have been transplanted onto 10 recipients, with resultant low morbidity and no mortality. With the exception of one recipient who requested amputation after the second year, results of hand transplantation have been highly successful. Functional return mirrored that seen after hand replantation. The limbs were progressively integrated into activities of daily living and professional tasks. The hand and patient survival rate exceeds the initial results of any previously transplanted organ. This success strongly supports continuation of these human trials.

Activities of Daily Living↗

Hand transplantation: pertinent data and future outlook.

Transplantation of composite tissue allografts, such as a hand, offers immense potential in reconstructive surgery. Review of current replantation literature suggests the prospect for significant functional return following hand transplant, provided appropriate patient is selected and allograft rejection is prevented. Experimental studies of limb transplantation in rodents have demonstrated the efficacy of combination therapy using multiple immunosuppressants. However, long-term survival of limb allografts could not be achieved in large animal models without significant drug toxicity. Given the potential for organ failure, opportunistic infection, and malignancy resulting from long-term immunosuppression, the risk-benefit ratio for hand transplant must be carefully weighed. Our laboratory has been able to achieve allograft survival with minimum immunosuppression by MHC matching or donor antigen exposure prior to immune maturity in the swine. Future transplantation of composite tissue allografts, therefore, may depend upon such modalities to induce host tolerance without long-term immunosuppression.

Animals↗

Intraosseous wiring in toe-to-hand transplantation.

Although there are many reports on bony fixations in finger replantations, information pertaining to fixation methods in toe-to-hand transplantations is scarce. The results of intraosseous wiring were evaluated in 68 toe-to-hand transplantations in 47 patients. Clinical and radiological evaluation of bony union was conducted an average of 30 months after the procedure. There was no malunion. There was one painless pseudarthrosis, with an overall nonunion rate of 1.5%. Intraosseous wiring is a simple, quick, dependable, and consistent method of fixation in toe-to-hand transplantation.

Adolescent↗

The first Belgian hand transplantation--37 month term results.

The first Belgian hand transplant was a 22 year-old man with a traumatic amputation of his dominant hand at the junction of the middle and distal thirds of the forearm. The donor and recipient had three HLA mismatches. The cross-match was negative. The total ischaemic time was slightly over 6 hours. Immunosuppression included antithymocyte globulins at induction and tacrolimus, mycophenolate mofetil and prednisolone as induction and maintenance therapy. There has been no episode of rejection. The only significant complications, except for transient hyperglycaemia, were psychological. At 37 months post-transplantation, the patient has fully incorporated his transplant into his self-image and is back at work. He has good sensibility (two-point discrimination of 6mm at the thumb and index finger pulps), acceptable wrist and finger motion with functioning intrinsic muscles. According to Chen's criteria, the result is good to excellent.

Adult↗

Basic principles on toe-to-hand transplantation.

Within the last three decades, toe-to-hand transplantation has become a well-established method for function and appearance reconstruction after trauma and in congenital hand anomalies. An otherwise healthy and cooperative patient is the ideal candidate for toe transplantation after trauma. In such patient, even primary toe transplantation is possible, if the stump is clean and viable. If secondary reconstruction after completed wound healing is considered, emphasis should be laid on tissue sacrifice during the acute management of non-replantable amputations at the hand. Specific considerations regarding selection of toe(s) to be transplanted, technique of toe harvest and inset, sequence of transplantations if more than one digit is to be reconstructed such as in the metacarpal hand, and postoperative regimen are important to achieve satisfying functional and aesthetic results on both recipient and donor sites. A trimmed great toe is ideal for thumb reconstruction if the amputaiton is located at or distal to the middle metacarpal shaft. However, in more proximal amputations a second toe may be more suitable as it allows transmetatarsal harvest without increasing donor site morbidity. Distal finger reconstruction with partial toe or second toe warp around flap gives most gratifing result to those patients who are critically concerned about their body images and also those who need distal fingers for jobs or recreation activities. Combined second and third toe or third and fourth toe transplantations are particular useful in metacarpal hand reconstruction to provide tripod pinch. The role of toe-to-hand transplantation in the new millenium assuming progress in tissue engineering, gene transfer, and the development of new immunosuppressive drugs is discussed.

Amputation, Traumatic↗

Different reference frames can lead to different hand transplantation decisions by patients and physicians.

Different frames of reference can affect one's assessment of the value of hand transplantation. This can result in different yet rational decisions by different groups of individuals, especially patients and physicians. In addition, factors other than frames of reference can affect one's evaluation of hand transplantation, which can result in different decisions.

Attitude of Health Personnel↗

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.

Adult↗

Sensory recovery and Meissner corpuscle number after toe-to-hand transplantation.

This study investigated the possible relationship between sensory recovery and receptor number after toe-to-hand transplantation. Moving two-point discrimination was measured after a course of sensory re-education. Meissner corpuscle number was then quantified by light microscopic examination of multiple sections of glabrous skin obtained at pulp reduction and from site-matched normal toe and fingertip skin. Meissner corpuscle number per millimeter was 0.94 in normal toe skin (n = 4), and 0.37 after toe-to-hand transplantation (n = 34). A significant correlation existed between moving two-point discrimination and Meissner corpuscle number (r = -0.62; p < 0.001). No significant relationship was found between moving two-point discrimination and patient age or interval from injury to reconstruction. The results suggest that despite sensory re-education, there may be a level of receptor reinnervation below which good sensory recovery may not be obtained.

Adolescent↗

Double hand transplantation: functional outcome after 18 months.

In March 2000, we performed a double hand transplantation on a patient who had suffered traumatic hand amputations 6 years previously. The transplantations were both successful and, 18 months later, the patient has regained some complex hand functions and remarkably good tactile gnosis.

Amputation, Traumatic↗

Arterial stiffening influence of sympathetic nerve activity: evidence from hand transplantation in humans.

Studies in animals and humans suggest that sympathetic activity exerts a stiffening influence on large and middle-sized artery walls. We sought to obtain further evidence on this issue by measuring radial artery distensibility in an allotransplanted and thus denervated hand using the contralateral artery as control. In 2 men, blood pressure was measured by a semiautomatic device (Dinamap). Diastolic diameter, systo-diastolic diameter excursion (ultrasound Wall Track system), and distensibility (Reneman formula) of both radial arteries were measured at a level corresponding to 4 cm below the suture of the transplanted hand 40 days after surgery and every 4 weeks for the next 6 months. After surgery, systo-diastolic diameter excursion and distensibility were much greater in the transplanted radial artery than in the contralateral vessel, reaching values similar to the contralateral ones after 4 months, when signs of reinnervation of the transplanted hands had appeared. Radial deinnervation was accompanied by an increased arterial distensibility, which provides further evidence of the sympathetic stiffening effect on arterial wall in humans.

Adult↗