Allen Furr

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.

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.

Ethical considerations in human facial tissue allotransplantation.

Background:Human facial tissue allotransplantation is now a clinical reality. Proponents of this new treatment contend that the benefits outweigh the risks, while the critics argue they do not. This debate has been presented in great detail in the bioethics literature but has not been brought to the attention of the plastic surgery community. Methods:The purpose of this paper is to provide a synopsis of the key issues being debated in facial transplantation by presenting to the plastic surgery community a synopsis of an ethical debate published in the 2004 summer issue of the American Journal of Bioethics. Results:Presented is a set of ethical guidelines for facial transplantation in the form of a “target article.” Alongside this are written commentaries from 15 experts in related fields, along with responses to these commentaries. Together, this discussion makes up a landmark exercise in open display and public and professional discussion and evaluation and serves as a comprehensive list of the major ethical issues being debated today in the field of facial tissue allotransplantation. Conclusions:Plastic surgeons play a central role in the care of facially disfigured patients and will therefore lead the introduction of facial tissue allotransplantation into the clinical arena. Consequently, it is important that they be aware of, and indeed that they play a key role in forming, the debate surrounding this new treatment. It is with this in mind that we present this synopsis to the plastic surgery readership.

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.