Extracorporeal Perfusion in Vascularized Composite Allotransplantation: Current Concepts and Future Prospects.

Severe injuries of the face and limbs remain a major challenge in today's reconstructive surgery. Vascularized composite allotransplantation (VCA) has emerged as a promising approach to restore these defects. Yet, there are major obstacles preventing VCA from broad clinical application. Two key restrictions are (1) the graft's limited possible ischemia time, keeping the potential donor radius extremely small, and (2) the graft's immunogenicity, making extensive lifelong monitoring and immunosuppressive treatment mandatory. Machine perfusion systems have demonstrated clinical success addressing these issues in solid organ transplantation by extending possible ischemia times and decreasing immunogenicity. Despite many recent promising preclinical trials, machine perfusion has not yet been utilized in clinical VCA. This review presents latest perfusion strategies in clinical solid organ transplantation and experimental VCA in light of the specific requirements by the vascularized composite allograft's unique tissue composition. It discusses optimal settings for temperature, oxygenation, and flow types, as well as perfusion solutions and the most promising additives. Moreover, it highlights the implications for the utility of VCA as therapeutic measure in plastic surgery, if machine perfusion can be successfully introduced in a clinical setting.

From Auto- to Allotransplantation: Immunomodulatory Protocol for Hand and Arm Transplantation.

AIM: To achieve a favorable risk-benefit balance for hand transplantation, an immunomodulatory protocol was developed in the laboratory and translated to clinical application. METHODS: Following donor bone marrow infusion into transplant recipients, hand and arm allografts have been maintained on low-dose tacrolimus monotherapy. RESULTS: Good-to-excellent functional recovery has been achieved in patients compliant with medication and therapy, thus restoring autonomous and productive lives. CONCLUSION: The risk-benefit balance can be tilted in favor of the hand transplant recipients by using an immunomodulatory protocol with minimum immunosuppression.

Outcomes after hand and upper extremity transplantation.

Hand and upper extremity transplantation (HUET) has emerged as the most frequently performed reconstructive procedure in the burgeoning field of vascularized composite allotransplantation (VCA). VCA refers to a form of transplant with multiple tissue types that represents a viable treatment option for devastating injuries where conventional reconstruction would be unable to restore form and function. As hand transplantation becomes increasingly more common, discussions on advantages and disadvantages of the procedure seem to intensify. Despite encouraging functional outcomes, current immunosuppressive regimens with their deleterious side-effect profile remain a major concern for a life-changing but not life-saving type of transplant. In addition, a growing number of recipients with progressively longer follow-up prompt the need to investigate potential long-term sequelae, such as chronic rejection. This review will discuss the current state of HUET, summarizing outcome data on graft survival, motor and sensory function, as well as immunosuppressive treatment. The implications of these findings for VCA in terms of achievements and challenges ahead will then be discussed.

Hand Transplantation: Evolution of a Personal Outlook.

The field of vascularized composite allotransplantation-combining advances in reconstructive surgery, transplantation, and immunology-offers great promise for patients with heretofore unsolvable problems. In the last 30 years, hand transplantation has progressed through the phases of being a research subject, a controversial clinical procedure, a more widely accepted and expanding field, and now a promising endeavor undergoing refined indications. Although many lessons have been learned, few procedures in the author's experience have been as life-transformative in restoring the body image, motor and sensory functions, activities of daily living, and personal autonomy as successful hand transplantation.

The miracle of face transplantation after 10 years.

INTRODUCTION: At the 10th year anniversary of the first face transplantation, there are currently 36 patients worldwide, who are the recipients of faces coming from human donors. AREAS OF AGREEMENT: Despite the initial debates and ethical concerns, face transplantation became a clinical reality with satisfactory functional outcomes. AREAS OF CONTROVERSY: The areas of controversy still include the impact of lifelong immunosuppression on otherwise healthy patients as well as the selection process of face transplant candidates. GROWING POINTS: Other concerns include financial support for this new generation of transplants as well as social reintegration and patients return to work after face transplantation. AREAS TIMELY FOR DEVELOPING RESEARCH: Based on over 20 years of research experience in the field of vascularized composite allotransplantation, and clinical experience as a leading surgeon of the US first face transplantation, this review will summarize the well-known facts as well as unexpected outcomes and challenges of face transplantation.

Guiding Strategies for the Future of Vascularized Composite Allotransplantation: A Systematic Review of Organ Donation Campaigns.

BACKGROUND: Since the 1990s, the field of vascularized composite allotransplantation has gained momentum, offering unprecedented solutions for patients with defects not amenable to autologous reconstruction. As with solid organ donation, the vascularized composite allotransplant donor pool remains limited. This systematic review identifies past successes and failures in organ donation campaigns to guide future strategies for expanding vascularized composite allotransplant donation. METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Three databases (PubMed/MEDLINE, PsycINFO, and Embase) were searched through July 31, 2019. The study compiled solid organ and vascularized composite allotransplant campaigns that aimed to increase donor registration. Articles depicting the current state of vascularized composite allotransplant donation were also assessed. RESULTS: Of an initial 3318 articles identified, 40 were included. Six articles described direct mail or print interventions, 10 depicted Web-based interventions, 13 dealt with interpersonal interventions, and seven used multimodal interventions. Four articles described the current state of vascularized composite allotransplant donation. A qualitative synthesis was conducted. The authors found that social media campaigns can have a robust but fleeting effect on registration trends and that interpersonal interventions are effective at increasing registration rates. In addition, the opportunity for participants to immediately register as organ donors, by means of either return mail, in-person, or online, is vital to campaign success. CONCLUSIONS: Public organ donation campaigns have had success in increasing organ donor registration rates, particularly through the use of social media and interpersonal interventions that allow for immediate registration. Synthesizing this information, we propose a multimodal campaign to expand the vascularized composite allotransplant donor pool.

Is Skin the Most Allogenic Tissue in Vascularized Composite Allotransplantation and a Valid Monitor of the Deeper Tissues?

Since the 1960s, skin has been considered to be the most allogenic tissue in humans. This tenet has remained unquestioned in the reconstructive transplant arena, which has led to skin serving as the sole monitor for early rejection in vascularized composite allotransplantation. In this article, the authors question the validity of this belief. The authors' hypothesis is that skin is not always an accurate monitor of rejection in the deep tissues, thus questioning the positive and negative predictive value of the punch biopsy for suspected vascularized composite allotransplantation rejection. A search was carried out identifying vascularized composite allotransplantation publications where the allogenicity of transplanted skin was evaluated. Eighteen publications claimed skin was found to be the most allogenic tissue in humans, justifying its use as a superior monitor for rejection. Eight publications demonstrated skin to be a poor monitor of rejection deeper to the skin. Two vascularized composite allotransplantation animal studies reported skin rejecting simultaneously with the deeper tissues. Finally, three publications discussed a skin and kidney allograft, transplanted simultaneously, indicating skin allogenicity was equivalent to the that of the kidney allograft. Much of the literature in human vascularized composite allotransplantation claims skin to be an excellent monitor of the deep tissues. The conclusion from this study is that skin does not always function as a good monitor for what could be rejecting in the deep tissues. The authors believe continued research is necessary to focus on expanding novel monitoring techniques and technologies to accurately diagnose vascularized composite allotransplantation rejection without tissue destruction.

Emerging Ethical Challenges Raised by the Evolution of Vascularized Composite Allotransplantation.

BACKGROUND: Despite early skepticism, the field of vascularized composite allotransplantation (VCA) has demonstrated feasibility. The ethics of VCA have moved past doubts about the morality of attempting such transplants to how to conduct them ethically. METHODS: Leaders of each program performing and/or evaluating VCA in the United States were invited to participate in a working group to assess the state and future of VCA ethics and policy. Four meetings were held over the course of 1 year to describe key challenges and potential solutions. RESULTS: Working group participants concluded that VCA holds great promise as treatment for patients with particular injuries or deficits, but the field faces unique challenges to adoption as standard of care, which can only be overcome by data sharing and standardization of evaluation and outcome metrics. CONCLUSIONS: Adequate attention must be given to concerns including managing the uniquely intense physician-patient relationship, ethical patient selection, ensuring patients have adequate representation, informing and earning the trust of the public for donation, standardizing metrics for success, and fostering an environment of data sharing. These steps are critical to transitioning VCA from research to standard of care and to its insurance coverage inclusion.

OPTN Vascularized Composite Allograft Waiting List: Current Status and Trends in the United States.

BACKGROUND: Vascularized composite allograft (VCA) transplantation is a developing area in the field of transplantation. METHODS: This study used Organ Procurement and Transplantation Network (OPTN) VCA waiting list and transplant data from July 3, 2014 through February 28, 2018, to characterize the OPTN VCA waiting list in terms of composition, removal patterns, waiting time, resulting transplants, and trends over time. RESULTS: Between implementation of the OPTN VCA waiting list on July 3, 2014 and February 28, 2018, 54 candidates-53.7% were male, 79.6% were white, and 70.4% aged 18 to 44 years-were added to the OPTN VCA waiting list. Of these, 22 received deceased donor VCA transplants (6 bilateral upper limb, 4 unilateral upper limb, 5 craniofacial, 1 scalp, 1 abdominal wall, 1 penile, and 4 uterine), and 6 received living donor uterine transplants. Registrations increased in 2016 after uterine and penile transplants were introduced in the United States, resulting in a large shift in the composition of the VCA waiting list. Waiting times for VCA candidates vary greatly, with some VCA candidates receiving deceased donor transplants quickly and others waiting more than 3 years before transplantation. CONCLUSIONS: The field of VCA transplantation and the composition of the OPTN VCA waiting list are evolving rapidly. Additional research is needed to understand these changes and investigate whether differences in need or differences in access have resulted in the variation seen on the VCA waiting list.

The advent of the restorative plastic surgeon.

Plastic surgery is presently typified by the existence of discrete clinical identities, namely that of the cosmetic plastic surgeon and the reconstructive plastic surgeon. The emergence of vascularized composite allotransplantation has been accompanied by the development of a third distinct clinical identity, that of the restorative plastic surgeon. The authors describe the core competencies that characterize this new identity, and discuss the implications of the advent of this new professional paradigm.