Dalibor Vasilic

Composite tissue allotransplantation of the hand and face: a new frontier in transplant and reconstructive surgery

Each year an estimated 7‐million people in the USA need composite tissue reconstruction because of surgical excision of tumors, accidents and congenital malformations. Limb amputees alone comprise over 1.2 million of these. This figure is more than double the number of solid organs needed for transplantation. Composite tissue allotransplantation in the form of hand and facial tissue transplantation are now a clinical reality. The discovery, in the late 1990s, that the same immunotherapy used routinely in kidney transplantation was also effective in preventing skin rejection made this possible. While these new treatments seem like major advancements most of the surgical, immunological and ethical methods used are not new at all and have been around and routinely used in clinical practice for some time. In this review of composite tissue allotransplantation, we: (i) outline the limitations of conventional reconstructive methods for treating severe facial disfigurement, (ii) review the history of composite tissue allotransplantation, (iii) discuss the chronological scientific advances that have made it possible, (iv) focus on the two unique clinical scenarios of hand and face transplantation, and (v) reflect on the critical issues that must be addressed as we move this new frontier toward becoming a treatment in mainstream medicine.

Investigation of risk acceptance in facial transplantation.

Background: The surgical techniques necessary to transplant a human face are well established, and the early success of human hand transplants suggests that the immunological hurdles of transplanting human facial tissues have largely been overcome. Therefore, it is the ethical barriers that pose the greatest challenge to performing facial transplantation. At the center of the ethical debate is the question, “Do the risks posed by the life-long immunosuppression that a recipient would have to take justify the benefits of receiving a face transplant?” In this study, the authors answer this question by assessing the degree of risk individuals would be willing to accept to receive a face transplant. Methods: To quantitatively assess risks versus benefits in facial transplantation, the authors developed the Louisville Instrument for Transplantation, or LIFT, which contains 237 standardized questions. Respondents in three study populations (healthy individuals, n = 150; organ transplant recipients, n = 42; and individuals with facial disfigurement, n = 34) were questioned about the extent to which they would trade off specific numbers of life-years, or sustain other costs, in exchange for receiving seven different transplant procedures. Results: The authors found that the three populations would accept differing degrees of risk for the seven transplant procedures. Organ transplant recipients were the most risk-tolerant group, while facially disfigured individuals were the least risk tolerant. All groups questioned would accept the highest degree of risk to receive a face transplant compared with the six other procedures. Conclusions: This study presents an empirical basis for assessing risk versus benefit in facial transplantation. In doing so, it provides a more solid foundation upon which to introduce this exciting new reconstructive modality into the clinical arena.

Psychosocial implications of disfigurement and the future of human face transplantation.

Summary: Although the first face transplants have been attempted, the social and psychological debates concerning the ethics and desirability of the procedure continue. Critics contend that these issues have not yet been sufficiently addressed. With this in mind, the present article seeks to elaborate on key psychological and social factors that will be central for addressing the ethical and psychosocial challenges necessary to move face transplantation into mainstream medicine. The goals of this article are to (1) discuss the psychosocial sequelae of facial disfiguration and how face transplantation may relieve those problems, and (2) delineate inclusion and exclusion criteria for the selection of research subjects for face transplantation. The article uses concepts from symbolic interaction theory in sociology to articulate a theoretically coherent scheme for comprehending the psychosocial difficulties of facial disfiguration and the advantages offered by facial transplantation. The authors conclude that the psychosocial implications of disfigurement warrant surgical intervention and that research in the area of face transplantation should continue.

Risk assessment of immunosuppressive therapy in facial transplantation.

Background: Immunosuppression-related risks are foremost among ethical concerns regarding facial transplantation. However, previous risk estimates are inaccurate and misleading, because they are based on data from studies using different immunosuppression regimens, health status of the transplant recipients, tissue composition, and antigenicity. This review provides a comprehensive risk assessment for facial transplantation based on comparable data of immunosuppression, recipient health status, and composition and antigenicity of the transplanted tissue. Methods: The risk estimates for face transplantation presented here are based on data reported in clinical kidney (10-year experience) and hand transplantation (5-year experience) studies using tacrolimus/mycophenolate mofetil/corticosteroid therapy. Mitigating factors including ease of rejection diagnosis, rejection reversibility, infection prophylaxis, patient selection, and viral serologic status are taken into account. Results: Estimated risks include acute rejection (10 to 70 percent incidence), acute rejection reversibility (approximating 100 percent with corticosteroid therapy alone), chronic rejection (<10 percent over 5 years), cytomegalovirus disease (1 to 15 percent), diabetes (5 to 15 percent), hypertension (5 to 10 percent), and renal failure (<5 percent). Conclusions: A review of these data indicates that previously reported estimates of immunosuppression-related risks are outdated and therefore should no longer be used. These updated risk estimates should be used by facial transplant teams, institutional review boards, and potential recipients when considering the immunologic risks associated with facial transplantation.

Plastic Surgeon's Risk Acceptance in Facial Transplantation

Background: A great deal of ethical debate has accompanied the introduction of facial tissue allotransplantation into the clinical arena. Critics contend that the risks of lifelong immunosuppression do not justify the benefits of this new non–life-saving reconstructive procedure, whereas proponents argue that they do. Absent from this debate are the opinions of individuals with real-life experiences with the risks and benefits associated with this new treatment. Methods: In this study, the authors question facially disfigured individuals (n = 33) and the reconstructive surgeons who treat them (n = 45), organ transplant recipients (n = 42) and the professionals who manage their immunosuppression medication (n = 37), and healthy volunteer controls (n = 148) to determine the amount of risk they are willing to accept to receive facial tissue allotransplantation. A survey with psychometrically reliable and validated questions was administered to the above five groups, and appropriate statistical analysis was used to analyze and compare the data within and between groups. Results: Of the five groups studied, reconstructive surgeons would accept the least amount of risk for a facial tissue allotransplant, followed by transplant specialists, then kidney transplant recipients, then facially disfigured individuals, and finally healthy control volunteers, who would accept the most amount of risk. Conclusions: The authors’ data indicate that reconstructive surgeons are the least tolerant of risks compared with the other groups studied concerning facial tissue allotransplantation. This is particularly important because they are the primary caregivers to facially disfigured patients and, as such, will be the ones to lead the effort to move this new reconstructive treatment into the clinical arena.

Risk acceptance in laryngeal transplantation.

Purpose: Advancements in the fields of head and neck surgery and immunology have paved the way for new quality of life‐improving procedures such as larynx transplantation. To quantitatively assess the risks versus benefits in larynx transplantation, we used a questionnaire‐based survey (Louisville Instrument For Transplantation [LIFT]) to measure the degree of risk individuals are willing to accept to receive different types of transplantation procedures.

Facial transplantation: an anatomic and surgical analysis of the periorbital functional unit.

Background: Complete loss of eyelid pair is associated with chronic discomfort, corneal ulceration, and visual impairment. Contemporary reconstructive techniques rarely provide functionally acceptable results. Composite tissue allotransplantation may provide a viable alternative. This study reports on neurovascular anatomy and technical details of harvesting an isolated periorbital unit and discusses its functional potential. Methods: Twenty-four hemifaces (12 fresh cadavers) were dissected to study surgically relevant neurovascular structures and to develop an efficient harvest method. Angiographic analysis was performed in seven hemifaces following harvest. Results: The superficial temporal and facial vessels demonstrated consistent location and diameters. Anatomic variability was characterized by the absence of the frontal branch of the superficial temporal artery or facial-to-angular artery continuation, but never of both vessels in the same hemiface. Angiographic analysis demonstrated filling of the eyelid arcades, provided the anastomoses between the internal and external carotid branches were preserved. The facial nerve exhibited consistent planar arrangement and diameters in the intraparotid and proximal extraparotid regions, but less so in the distal nerve course. The inferior zygomatic and buccal branches frequently coinnervated the orbicularis oculi and lower facial muscles with an unpredictable intermuscular course. Based on the foregoing, an effective surgical harvest of the periorbital composite was developed. Conclusions: Surgical harvest of a functional periorbital allotransplant is technically feasible. Revascularization of the isolated periorbital unit is influenced by variations in regional anatomy and cannot be guaranteed by a single vascular pedicle. The orbicularis oculi muscle and its innervation can be preserved, and recovery, albeit without the certainty of reflexive blinking, is expected.

New Approaches to Antibody Therapy

The past years have seen the emergence of a new field in plastic surgery: composite tissue allotransplantation (CTA). While it has been used differently depending on context, CTA generally applies to the allotransplantation of vascularized tissues for the purpose of tissue reconstruction. While CTA has been performed for a few decades now (vascularized tendon and bone allotransplants were performed in select experimental settings as early as the 1980s and 1990s), the holy grail of CTA – the transplantation of vascularized tissues that contain a skin component – was achieved only recently (September 23, 1998) with the first human hand transplantation in Lyon (France). The allotransplantation of a hand, 54 years after the first kidney transplantation, was considered a landmark accomplishment. While the reconstructive aspects of the procedure were – and are – relatively straightforward, the skin is highly susceptible to immune rejection, and no immunosuppressive regimen prior to 1998 had been efficacious at preventing the rejection of a transplanted hand. Hand transplantation, and recently face transplantation, became possible with the advent of new immunosuppressive regimens, an era inaugurated by the introduction of cyclosporine in 1978. Ultimately, the combination regimen of tacrolimus (also called FK506), mycophenolate mofetil (MMF), and steroids fostered the first successful hand transplantation. In recent years, other immunosuppressive agents acting via different mechanisms have been introduced. While these agents are changing the way CTA recipients are induced or desensitized immediately following transplantation, it is important to point out that the maintenance immunosuppressive regimen following CTA is still roughly the same as it was at the time of the first procedures, when it was first established by Ustuner et al. To understand antibody therapies in CTA, it is important to consider our historical understanding of immune rejection and the difference between immunosuppression and immunomodulation as two different approaches toward preventing it.