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A Second Chance at Life

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A Second Chance at Life - Volume 28 Issue 3 - ALEXANDRE G. LELLOUCH, LAURENT A. LANTIERI
Cambridge Quarterly of Healthcare Ethics (2019), 28, 463–467.
© Cambridge University Press 2019.
doi:10.1017/S0963180119000380 463
Commentary
A Second Chance at Life
ALEXANDRE G. LELLOUCH and LAURENT A. LANTIERI
History
Vascularized Composite Allotransplantation (VCA) including Facial Transplantation
(FT) emerged as a unique solution for anatomically restoring faces after disfigure-
ment. It became a clinical reality after the first successful face transplantation in
2005.1 VCA is a rapidly growing new field in plastic surgery; and from November
2005 to the time of this writing in September 2018, 44 transplants have been per-
formed worldwide. It is clear that many more transplantations will be performed
in the future. The main concern in VCA remains the risk of chronic rejection2 and
graft loss3 despite life-long immunosuppression. Scientists are actively working on
new strategies to reduce the burden of immunosuppression and prevent immune
rejection. The most promising approach is the development of tolerance protocols
through the induction of mixed chimerism4. Indeed, it is the sole strategy to have
demonstrated long-term tolerance in solid organ transplantation in humans.5
Currently, the gold standard in reconstructive surgery remains the use of autologous
tissue. This strategy is still very useful to replace limited missing body parts (like
mandible) by tissue transfer (for example, osteomyocutaneous flap). However, the
functional sensory organs (mouth, eyes) cannot be restored adequately by these
conventional surgical techniques.
The goal of face transplantation is not only to restore the patient’s appear-
ance but also, to create a new physiognomy that will allow the facially disfig-
ured person to adapt and reintegrate into life. Before the advent of VCA, the
complexity of the face made surgeons unable to reestablish an “acceptable out-
come,” leaving disfigured patients little chance of social rehabilitation. Nowadays
VCA surgery, while offering new hope, represents an important challenge
(even for the top facility) for the surgical6 and medical7 team. First, there must
be a high level of cooperation between the various specialists including surgeons,
anesthesiologists and nephrologists. Secondly, the management of immune
rejection remains a primary on-going concern due to the untreatable chronic
rejection effect.8
Background
Over the last 20 years, our surgical team has been led by Laurent Lantieri.
Numerous articles have been written on the ethical issues9,10,11 pertaining to FT.
In our hospital, European George Pompidou in Paris, the anatomical study on face
transplantation was performed in 200512. In 2007, we performed our first partial
face transplant case13 (the third in the world); the first successful partial face trans-
plant was performed in 2005 in Amiens, France.14 We determined that in the light
of immunosuppressive regimen improvement, it appeared reasonable to consider
VCA as a clinical option, especially for hand and face transplantation.15
The scientific community continues to debate the ethical dilemmas regarding
FT16. Our team already transplanted a patient after shotgun injury.17 Following the
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Alexandre G. Lellouch and Laurent A. Lantieri
464
success of our first face transplant, we decided to go further with the elabora-
tion of the first full face transplant.18 Our first report evaluating the short-term
quality of life was encouraging.19 Regarding types of disfigurements, the most
frequent situations involve the severely disfiguring facial tumors of neurofi-
bromatosis, shotgun injury, dog bites, and burns; but in our experience, burn
patients are not considered the best candidates for receiving VCA due to the
risk of sensitization after care management.20 Furthermore, there is no benefit
to changing the standardized care management of burn patients (using skin
allograft, blood transfusion) due to the high risk of medical complications.21
In our series of VCA/FT patients with more than five years follow-up, we
demonstrated positive outcomes.22 In addition to improvements in immuno-
suppressive strategies, we described our protocol for management of the facial
nerve (one anastomosis at the trunk). The aim was to simplify and improve
surgical outcomes in FT by avoiding dyskinesia.23 Unfortunately, one of our
FT patients rejected his face leading to a total graft loss within a few months.
We published a letter to the editor in the journal Lancet addressing the risk of
face retransplantation.24 Under extremely urgent conditions we pushed forward
in retransplanting the patient.25
Comment
In their paper, McQuinn et al. raise the challenge of human FT post Self-Inflicted
Gunshot Wound (SIGW). The major ethical concern is the potential risk of recur-
rence of such a suicide attempt. According to the manuscript, 25% of the FTs
performed have been in patients identified as survivors of SIGWs, and one
recipient has committed suicide post-transplant.26 This clinical reality has already
been accepted by most VCA surgeons. Interestingly, ballistic trauma patients
have eclipsed burn patients who were initially projected to make up the largest
number of transplants. This confirms the observation that we made in 200427
that ballistic trauma patients can be excellent candidates for FT. Beyond the risk of
suicide, patients’ intellectual ability and their understanding of long-term treatment
is the minimal requisite for suggesting this surgery, and more determinative than
the type of injury itself.
In transplants, as in the rest of modern healthcare, the debate also involves the
cost for society. In our institution, the transplantation of a face led to higher costs
than heart or any other solid organ, and represented twice the costs for a liver
transplantation.28 The question is: how much is society willing to expend resources
to help these people? In the case of face transplant (contrary to solid transplanta-
tion indications), there are no face shortages so far.
A close follow-up post-face transplant is crucial for detecting the first signs of
psychological distress. As reported by the authors, mortality from SIGWs can be
as high as 80%. The survivors have important morbidities and lifelong disabilities.
A global assessment of the possibilities of motor and sensitive function restoration
will help address the risk-benefit ratio in FT. A patient with SIGW suffers signifi-
cant psychological pain that must be treated. The decision to perform a VCA is
multidisciplinary, depending of the psychological state, the surgical feasibility,
and the willingness of the patient. We understand and appreciate the importance
of the role of psychiatrists and psychologists for identifying “low-risk patients.”
These professionals need to make the distinction between known psychosocial
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A Second Chance at Life
465
contraindications (active psychoses, amongst them) and SIGW. Our institution
does not exclude patients with SIGW, viewing VCA as a chance to give the patient
a “second chance” at life.
The patient’s ability to make medical decisions for themselves cannot be
overestimated. A prerequisite for the surgery is fully informed consent to all
aspects of the procedure, which becomes a more complex issue as VCA for chil-
dren is explored,29 along with understanding and committing to the extensive
after-care regimen. This point is particularly important since an inability to
adhere to the post-transplant regimen can lead to adverse outcomes, including
rejection and graft failure. But even with treatment compliance, we cannot rule
out the risk of developing chronic rejection.
The authors stated that the general public in the United States supports
solid organ donation but is hesitant about vascularized composite allotrans-
plantation. But looking back at the first heart transplant, when the world
was amazed by Christian Barnard’s case, support was also not immediate
for taking a heart that had only arrested during surgery with cardioplegia.
This reluctance may be traced to insufficient communication, and lack of
information from the VCA center. Inadequate clarification can lead to confu-
sion and misunderstanding, causing relatives of donors to have misconcep-
tions regarding the procedure, and refusing to donate for VCA. Disfigurement
of their diseased loved one is often a major concern. As surgeons, it is imper-
ative that we restore the donor’s face to its original structure. The general
public remains unaware of this part of the procedure, as does much of the
medical community. This is necessary, to show respect to the donor’s family,
and also the donor.
The ethics of face transplantation go far beyond recipient risk-benefit analysis,
and allocation of resources. It involves all the questions regarding the use of body
parts after death raised in the literature by Mary Shelley’s novel, Frankenstein,
written a century ago. For example, are we an amalgamation of organs? If so, is a
part of personality is transferred when organs are transferred—even more so
when it is related to the face? But a human being is a complex system, and a complex
system is not the addition of simple elements. In VCA, we are not transplanting
personality through a face transplant, but restoring faces to rehabilitate patients
and bring them back to a normal life.
Conclusion
FT goes beyond the restoration of the anatomical subject; it is the retrieval of
the self-esteem. The right to have a face goes beyond improving the quality of
life; it is at the core of human dignity. The atrocities performed on concentration
camp prisoners in World War II, under the guise of “scientific experiments,”
demonstrated the ravages of a loss of dignity. We agree with the conclusion of
the authors regarding the absence of justification for rejecting patients with SIGW.
The allocation of health care resources is very important, but the decision to
provide VCA lies at the health policy decision level; physicians have the profes-
sional duty to provide their patients with the best treatment options available.
VCA is the best treatment option available for SIGW, and needs to be considered
in the therapeutic arsenal for treating it. The report of long-term follow-up will
bring new insight to this topic.
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Alexandre G. Lellouch and Laurent A. Lantieri
466
Notes
1. Dubernard J-M, Lengelé B, Morelon E, Testelin S, Badet L, Moure C, et al. Outcomes 18 months
after the first human partial face transplantation. New England Journal of Medicine 2007;
357(24):2451–60.
2. Petruzzo P, Kanitakis J, Testelin S, Pialat J-B, Buron F, Badet L, et al. Clinicopathological findings of
chronic rejection in a face grafted patient. Transplantation 2015;99(12):1–7.
3. Morelon E, Petruzzo P, Kanitakis J, Dakpé S, Thaunat O, Dubois V, et al. Face transplantation:
Partial graft loss of the first case ten years later. American Journal of Transplantation 2017;
17(7):1935–40.
4. Lellouch AG, Ng ZY, Kurtz JM, Cetrulo CL. Mixed chimerism-based regimens in VCA. Current
Transplantation Reports 2016.
5. Kawai T, Sachs DH, Sykes M, Cosimi AB, Immune Tolerance Network. HLA-mismatched renal
transplantation without maintenance immunosuppression. New England Journal of Medicine
2013;368(19):1850–2.
6. Meningaud J-P, Hivelin M, Benjoar M-D, Toure G, Hermeziu O, Lantieri L. The procurement of
allotransplants for ballistic trauma: A preclinical study and a report of two clinical cases. Plastic and
Reconstructive Surgery 2011;127(5):1892–900.
7. Sedaghati-nia A, Gilton A, Liger C, Binhas M, Cook F, Ait-Mammar B, et al. Anaesthesia and
intensive care management of face transplantation. British Journal of Anaesthesia 2013;111(4):
600–6.
8. See note 2, Petruzzo et al. 2015.
9. Petit F, Paraskevas A, Minns AB, Lee WPA, Lantieri LA. Face transplantation: Where do we stand?
Plastic and Reconstructive Surgery 2004;113(5):1429–33.
10. Petit F, Paraskevas A, Garrido I, Lantiéri L. [Could (allo)transplantation be the future of microsur-
gery?] Annales de Chirurgie Plastique et Esthétique 2005;50(1):76–9.
11. Lantieri LA. Face transplantation: The view from Paris, France. Southern Medical Journal 2006;
99(4):421–3.
12. Paraskevas A, Ingallina F, Meningaud J-P, Lantiéri L. [Face allotransplantation: anatomical study,
potential partial and total facial allografts harvesting and clinical application]. Annales de Chirurgie
Plastique et Esthétique 2007;52(5):485–93.
13. Lantieri L, Meningaud J-P, Grimbert P, Bellivier F, Lefaucheur J-P, Ortonne N, et al. Repair of the
lower and middle parts of the face by composite tissue allotransplantation in a patient with
massive plexiform neurofibroma: A 1-year follow-up study. Lancet (London, England) 2008;
372(9639):639–45.
14. See note 1, Dubernard et al. 2007.
15. Lantieri L. [Composite allotransplantation in the upper extremity: From research to clinical reality].
Chirugie de la Main 2009;28(2):67–73.
16. Gordon CR, Siemionow M, Papay F, Pryor L, Gatherwright J, Kodish E, et al. The world’s expe-
rience with facial transplantation: What have we learned thus far? Annals of Plastic Surgery
2009;63(5):572–8.
17. See note 6, Meningaud et al. 2011.
18. Meningaud J-P, Benjoar M-D, Hivelin M, Hermeziu O, Toure G, Lantieri L. Procurement of total
human face graft for allotransplantation: A preclinical study and the first clinical case. Plastic
and Reconstructive Surgery 2010;126(4):1181–90.
19. Lantieri L, Hivelin M, Audard V, Benjoar MD, Meningaud JP, Bellivier F, et al. Feasibility, reproduc-
ibility, risks and benefits of face transplantation: A prospective study of outcomes. American Journal
of Transplantation 2011;11(1):367–78.
20. Duhamel P, Suberbielle C, Grimbert P, Leclerc T, Jacquelinet C, Audry B, et al. Extensively burned
patients still need blood transfusions and skin allografts: Unavoidable HLA sensitization requires
optimization of VCA access. Transplant International 2015;28(10):1229–30.
21. Ng ZY, Lellouch AG, Drijkoningen T, Chang IA, Sachs DH, Cetrulo CL. Vascularized composite
Allotransplantation—An emerging concept for burn reconstruction. Journal of Burn Care & Research
2017;38(6):371–8. doi: 10.1097/BCR.0000000000000532.
22. Lantieri L, Grimbert P, Ortonne N, Suberbielle C, Bories D, Gil-Vernet S, et al. Face transplant: Long-
term follow-up and results of a prospective open study. Lancet (London, England) 2016;
388(10052):1398–407.
23. Swanson JW, Yu JW, Taylor JA, Kovach S, Kanchwala S, Lantieri L. The retroauricular approach to
the facial nerve trunk. Journal of Craniofacial Surgery 2017;28(2):347–51.
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A Second Chance at Life
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24. Lantieri L, Grimbert P, Ortonne N, Lemogne C, Wolkenstein P, Hivelin M. Facial transplantation:
Facing the limits, planning the future. Lancet (London, England) 2017;389(10076):1293–4.
25. Breaking news, CNN 19 Apr. Available at https://www.nytimes.com/2018/04/19/world/
europe/jerome-hamon-face-transplant-france.html (last accessed 25 Mar 2019).
26. See note 22, Lantieri et al. 2016.
27. See note 9, Petit et al. 2004.
28. Rüegg EM, Hivelin M, Hemery F, Maciver C, Benjoar MD, Meningaud JP, et al. Face transplanta-
tion program in France: A cost analysis of five patients. Transplantation 2012;93(11):1166–72.
29. Marchac A, Kuschner T, Paris J, Picard A, Vazquez MP, Lantieri L. Ethical issues in pediatric face
transplantation: Should we perform face transplantation in children? Plastic and Reconstructive
Surgery 2016;138(2):449–54.
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... Traumatic injuries (ballistic, high-energy motor vehicle accidents, burns, etc.), congenital diseases, and neoplasia are responsible for severe disfigurements and amputation of functional aesthetic units in patients of all ages. For cases where autologous reconstructive options have been exhausted, vascularized composite allograft (VCA) transplantation offers significant quality of life improvements [1]. Although immense progress has been made in VCA procurement techniques, graft adjustments to the recipient, and post-operative care to achieve optimal results [2,3], a more effective and longer graft preservation method is needed to make VCA transplantation a routine reconstructive procedure. ...
... In the SNMP group, allograft skin were unremarkable and muscle aspect was macroscopically normal with good arterial inflow and venous outflow. Skin biopsies performed after allotransplantation did not show significant rejection episodes, all samples were classified 0 on the Banff scale by the two blinded pathologists besides the SCS group at the euthanasia time point (Banff grade 1 [1,2]). Detailed skin histology is displayed in Supplementary Table S1. ...
Article
Full-text available
The current gold standard for preserving vascularized composite allografts (VCA) is 4°C static cold storage (SCS), albeit muscle vulnerability to ischemia can be described as early as after 2 h of SCS. Alternatively, machine perfusion (MP) is growing in the world of organ preservation. Herein, we investigated the outcomes of oxygenated acellular subnormothermic machine perfusion (SNMP) for 24-h VCA preservation before allotransplantation in a swine model. Six partial hindlimbs were procured on adult pigs and preserved ex vivo for 24 h with either SNMP (n = 3) or SCS (n = 3) before heterotopic allotransplantation. Recipient animals received immunosuppression and were followed up for 14 days. Clinical monitoring was carried out twice daily, and graft biopsies and blood samples were regularly collected. Two blinded pathologists assessed skin and muscle samples. Overall survival was higher in the SNMP group. Early euthanasia of 2 animals in the SCS group was linked to significant graft degeneration. Analyses of the grafts showed massive muscle degeneration in the SCS group and a normal aspect in the SNMP group 2 weeks after allotransplantation. Therefore, this 24-h SNMP protocol using a modified Steen solution generated better clinical and histological outcomes in allotransplantation when compared to time-matched SCS.
... F ace transplantation is limited to severely disfigured patients whose disfigurement cannot be addressed by autologous surgery. 1 To this day, 44 face transplants have been performed worldwide to treat large facial defects due to burns, ballistic injuries, or deforming diseases such as neurofibromatosis. 2 Follow-up reports indicate a true benefit in terms of quality of life for patients who get a second face. 3 We report here an uncommon surgical situation in a face transplant patient-a 57-year-old man who presented with a bifocal mandibular fracture and a nasal bone fracture due to a domestic accident 8 years after his partial face transplantation. Fifteen years after the first face transplant ever performed, it remains crucial to report the outcomes in the mid-and long-term follow-up for each patient. ...
Article
Full-text available
Over the past 20 years, vascularized composite allografts (VCAs) have emerged as a realistic option in reconstructive surgery. Long-term follow-up reports indicate that face transplant patients have gained in quality of life and social integration. However, they require close monitoring of their immunosuppressive therapy because they are at high-risk for acute rejection episodes, leading eventually to chronic rejection and allograft loss. Reported acute rejection episodes in VCA recipients occur due to low immunosuppressive therapy (mainly due to lack of patient compliance or decreased doses of immunosuppressants to counter side-effects). Repeated mechanical traumas have recently been shown to trigger acute rejection episodes, especially in hand transplant patients. This article reports our experience of a 10-year follow-up of a 57-year-old face transplant patient and the management of his accidental facial trauma. To our knowledge, our patient is the first to undergo a major trauma on his VCA endangering his graft function and vitality. This report discusses the management of an acute surgical situation in those particular patients, and the challenges that arise to avoid acute rejection of the allograft. Ten years into his face transplant and at 18 months follow-up after his facial trauma, our patient shows great aesthetic and functional outcomes and remains rejection-free; a very encouraging result for all VCA candidates.
... 2 However, despite these improvements, the number of complications (metabolic, infectious, and neoplastic) resulting from long-term immunosuppression 3 presents many ethical issues 4 and remains the source of much controversy. 5,6 Patients who undergo VCA must comply with lifelong maintenance immunosuppression, typically using a standard triple drug regimen (ie, a calcineurin inhibitor, mycophenolate mofetil, and corticosteroids). Strict adherence to therapy helps prevent allograft rejection. ...
Article
Background Since the first successful facial transplantation in 2005, the benefits of this procedure in terms of aesthetics, functionality, and quality of life have been firmly established. However, despite immunosuppressive treatment, long-term survival of the allograft might be compromised by chronic antibody-mediated rejection (CAMR), leading to irreversible necrosis of the tissue. In the absence of therapeutic options, this complication is inevitably life-threatening. Methods We report facial retransplantation in a man, 8 years after his first facial transplantation because of extensive disfigurement from type 1 neurofibromatosis and 6 weeks after complete loss of his allograft due to severe CAMR. We describe the chronology of immune-related problems that culminated in allograft necrosis and the eventual loss of the facial transplant, the desensitisation protocol used for this highly immunosensitised recipient, the surgical technicalities of the procedure, the specific psychological management of this patient, and the results from follow-up at 30 months. Findings Although the patient had a complicated postoperative course with numerous immunological, infectious, cardiorespiratory, and psychological events, he was discharged after a hospital stay of almost 1 year. He has since been able to re-integrate into his community with acceptable restoration of his quality of life. Interpretation This clinical report of the first documented human facial retransplantation is proof-of-concept that the loss of a facial transplant after CAMR can be mitigated successfully by retransplantation combined with an aggressive desensitisation process. Funding Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris.
... 1,2 To date, over 43 facial and 120 upper extremity transplants have been successfully performed worldwide 3,4 with about 20% occurring in burn survivors. 5 However, in contrast to solid organ transplantation (SOT) which are life-saving procedures, VCA is life-enhancing by restoring both a patient's dignity 6 and quality of life through functional and psychosocial rehabilitation. 7 Because of this important distinction, efforts to develop tolerance protocols 8 as well as means for reducing the burden of immunosuppression required by VCA recipients are of paramount importance for further evolution of this field. ...
Article
Transplantation of vascularized composite allografts (VCAs) provides a means of restoring complex anatomical and functional units following burns and other disfigurement otherwise not amenable to conventional autologous reconstructive surgery. While short- to intermediate-term VCA survival is largely dependent on patient compliance with medication, the myriad of side effects resulting from lifelong systemic immunosuppression continue to pose a significant challenge. Topical immunosuppression is therefore a logical and attractive alternative for VCA. Current formulations are limited though, by poor skin penetration but this may be mitigated by conjugation of immunosuppressive drugs to TyroSpheres for enhanced delivery. Therefore, we investigated the topical application of FK506-TyroSpheres (in the form of a gel dressing) in a clinically-relevant non-human primate (NHP) VCA model to determine if allograft survival could be prolonged at reduced levels of maintenance systemic immunosuppression. 6 MHC-mismatched cynomolgus macaques (Macaca fascicularis) served as reciprocal donors and recipients of radial forearm fasciocutaneous flaps. Standard Bacitracin ointment and FK506-TyroSpheres were applied every other day to the VCAs of animals in Groups 1 (controls, n=2) and 2 (experimental, n=4) respectively before gradual taper of systemic FK506. Clinical features of VCA rejection still developed when systemic FK506 fell below 10 ng/mL despite application of FK506-TyroSpheres and prolonged VCA survival was not achieved. However, unwanted systemic FK506 absorption was avoided with TyroSphere technology. Further refinement to optimize local drug delivery profiles to achieve and maintain therapeutic delivery of FK506 with TyroSpheres is underway, leveraging significant experience in controlled drug delivery to mitigate acute rejection of VCAs.
... Although the question of the legitimacy of performing a VCA in the context of a suicide attempt is highly controversial, we fully agree with the authors that a suicide attempt in itself is not a contraindication for VCA. 3 Furthermore, previous facial reconstruction surgeries performed on the patient, which we consider essential data in this context, have not been described. Autologous reconstruction surgery must be attempted as a first-line treatment, especially for small defect such as the nose and for which many surgical options exist. ...
Article
Introduction Twenty three years after the first successful upper extremity transplantation, the role of vascularized composite allotransplantation (VCA) in the world of transplantation remains controversial. Face and upper extremity reconstruction via transplantation have become successful options for highly selected patients with severe tissue and functional deficit when conventional reconstructive options are no longer available. Despite clear benefit in these situations, VCA has a significant potential for complications that are more frequent when compared to visceral organ transplantation. This study intended to perform an updated systematic review on such complications. Materials and methods MEDLINE database via PubMed, Embase and Cochrane Library were searched. Face and upper extremity VCA performed between 1998 and 2021 were included in the study. Relevant media and press conferences reports were also included. Complications related to face and upper extremity VCA were recorded and reviewed including their clinical characteristics and complications. Results One hundred fifteen patients underwent facial (43%) or upper extremity (57%) transplantation. Overall, the surgical complication rate was 23%. Acute and chronic rejection was identified in 89% and 11% of patients, respectively. Fifty eight percent of patients experienced opportunistic infection. Impaired glucose metabolism was the most common immunosuppression-related complication other than infection. Nineteen percent of patients ultimately experienced partial or complete allograft loss. Conclusions Complications related to VCA are a significant source of morbidity and potential mortality. Incidence of such complications is higher than previously reported and should be strongly emphasized in patient consent process. Strict patient selection criteria, complex preoperative evaluation, consideration of alternatives, and thorough disclosure to patients should be routinely performed prior to VCA indication.
Article
Full-text available
Amputations and devastating injuries throughout the body can now be reconstructed by transplanting vascularized composite allografts (VCAs) of the extremities, face, penis, scalp, skull, abdominal wall, and even the uterus. While functional and quality of life outcomes have been highly promising, the requirement for, and complications from long-term immunosuppression have predictably been reported in VCA recipients as with solid organ transplantation. Immunologic tolerance represents an alternative strategy to prevent rejection of VCAs without the need for immunosuppression. Clinically, long-term tolerance of allografts without maintenance immunosuppression has been achieved in kidney transplantation patients through the induction of mixed chimerism, whereby both donor and recipient-derived lymphohematopoietic elements co-exist within the recipient. This paper serves to review the currently available evidence from both clinical and experimental studies on mixed chimerism based regimens in VCA.
Article
Full-text available
Background: In 2005, face transplantation ceased to be fiction and became a scientific reality. Today, 10 teams from six different countries have performed 32 face transplantations. Immunosuppressive treatments are similar to other solid organ transplants, and patients have experienced a significant functional improvement. The authors are logically considering expanding face transplantation to children; however, children are not simply small adults. Methods: The authors searched for pediatric patients in need of restoration of fundamental functions of the face, such as orbicularis oris or oculi muscle closure by, first, selecting cases from a pediatric plastic surgery reference center and, second, analyzing the feasibility of face transplantation in those patients. The authors then identified the specific problems that they would encounter during a pediatric face transplant. The authors identified three potential candidates for pediatric face transplantation. Results: Children's youth imposes additional ethical and psychological considerations, such as the balance of risk to benefit when it is quality of life, not life itself, that is at stake; the process of informed consent; the selection process; and the protection of privacy against media exposure. The question becomes not whether children should be included as candidates for face transplantation but whether any ethical barriers should preclude children as candidates for a full face transplant. Conclusion: After careful consideration of the physical, psychological, and ethical aspects of such a procedure, the authors found no such barrier that would either disqualify such vulnerable subjects as profoundly disfigured children or conflict with their best interests.
Article
Vascularized composite allotransplantation (VCA) has demonstrated utility in the reconstruction of extensive soft-tissue defects following severe burns. However, pre-VCA events such as multiple transfusions, previous transplantation and pregnancies, the use of skin allografts, and mechanical support devices may result in sensitization and ultimately exclude a burn patient, who may benefit most through VCA, from a hand or face transplant. The authors sought to identify the immunologic challenges involved. All reported VCA cases up to July 2016 were reviewed. Relevant data analyzed include patient demographics, burn etiology, type and extent of VCA performed, pretransplant panel reactive antibody (PRA) status, extent of human leukocyte antigen (HLA) mismatch between donor and recipient, and immunologic outcomes. Of the 142 known cases of VCA to date, 30 (mean age = 36 years) were performed for burn reconstruction (mean interval to surgery = 8.3 years). Thermal and electrical burns were most common and performed in 20 and 30% of all reported upper extremity and craniofacial VCA cases, respectively, despite highly variable pretransplant PRA (0-98%). HLA-matching statuses between donors and recipients varied from 2/6 to 6/6. No obvious relationship could be observed between the incidence and severity of acute rejection with the patient's PRA and HLA-matching statuses, although more extensive treatment was required to reverse rejection episodes in sensitized patients (PRA > 0%). Further development and refinement of clinically relevant immunomodulatory protocols is required to achieve immunosuppression minimization and/or successful transplantation tolerance to enable long-term survival of both the VCA itself and the patient.
Article
Ten years after the first face transplantation we report the partial loss of this graft. After two episodes of acute rejection (AR) occurred and completely reversed in the first post-transplantation year, ninety months post-transplantation the patient developed de novo class II-donor specific antibodies, without clinical signs of AR. Some months later she developed several skin rejection episodes treated with steroid pulses. Despite rapid clinical improvement, some months later the sentinel skin graft underwent necrosis. Microscopic examination showed intimal thickening, thrombosis of the pedicle vessel and C4d deposits on the endothelium of some dermal vessels of the facial graft. Flow magnetic resonance imaging of the facial graft showed a decrease of the distal right facial artery flow. Three steroid pulses of 500 mg each, followed by Intravenous Immunoglobulins (2g/kg), 5 sessions of plasmapheresis and Bortezomib 1.3 mg/m(2) , were administered. Despite rescue therapy with Eculizumab, necrosis of the lips and the perioral area occurred, which led to surgical removal of the lower lip, labial commissures and part of the right cheek in May 2015. In January 2016 the patient underwent conventional facial reconstruction because during the re-transplantation evaluation a small-cell lung carcinoma was discovered causing the patient's death in April 2016. This article is protected by copyright. All rights reserved.
Article
Background: Exposure of the common trunk of the facial nerve has traditionally been approached based on principles of parotidectomy, which is associated with high rates of facial nerve palsy and landmarks that may be unreliable. On the basis of experience gained with vascularized composite allotransplantation of the face, the authors propose a retroauricular approach that may be more time-effective and safe. Methods: In the proposed retroauricular facial nerve approach, an incision is made posterior to the ear in the retroauricular sulcus, and dissection proceeds anteriorly to the mastoid fascia to the base of the conchal bowl. The anteroinferior edge of the external auditory canal is followed as a reference structure to locate the facial nerve trunk (FNT), coursing between the stylomastoid foramen (posteromedially) and entering the parotid gland (anteriorly). Twelve unilateral FNT dissections were performed in 6 fresh human cadaver heads. Six dissections were performed for illustration and proof of concept using full facial transplant, conventional, and limited retroauricular exposures; 6 additional dissections were performed by trainees to assess reliability and replicability of technique. Results: The FNT was successfully identified in all 12 dissections. Trainees tended toward being more time efficient in exploring the anatomy when using the limited retroauricular technique than with the conventional approach, 7.8 ± 0.78 minutes versus 13.0 ± 3.3 minutes (P = 0.089). No intraoperative injury to any critical structure was noted with either technique. Conclusion: A retroauricular approach to the FNT based on liberating anterior tissues from the auditory canal provides expedient and aesthetic exposure of the FNT.
Article
Background: More than 30 face transplantations have been done worldwide since 2005 but no documented long-term follow-up has been reported in the literature. We aimed to answer remaining question about the long-term risks and benefits of face transplant. Methods: In this single-centre, prospective, open study, we assessed 20 patients presenting with facial defects. Ten patients were selected, and, after three were secondarily excluded, seven were transplanted: two with neurofibromatosis 1, one with a burn, and four with self-inflicted facial gunshot injuries. We report the long-term outcomes of six face allotransplant recipients at an average of 6 years (range 3·4-9 years) after the transplantation. All admissions to hospital except for planned revisions and immunosuppressive follow-up therapy were reported as adverse events (safety endpoint). Predefined immunological, metabolic, surgical, and social integration endpoints were collected prospectively. Patients underwent quantitative health-related quality of life assessments through Short Form 36 health questionnaires. This study was registered with ClinicalTrials.gov, number NCT00527280. Findings: Two of seven patients died: one at 65 days due to transplant destruction with concomitant pseudomonas infection and the second at 3·4 years after transplantation by suicide. The six patients alive at long-term follow-up presented with functional transplants. Safety endpoints were related to infection in the first month, acute rejection from 1 day to 7 years after transplantation, or side-effects of immunosuppressive therapy. Recurrent rejection episodes justified maintenance therapy with high-dose steroids at high levels in all patients at last follow-up, yet none of the patients developed diabetes. Three patients were found to have hypertension with one requiring therapy. All patients had a noticeable reduction in glomerular filtration rate. All recipients and their families accepted their transplant. Improvements in social integration and quality of life were highly variable among the patients and depended on baseline levels and psychiatric comorbidities. Interpretation: These long-term results show the crucial effect of patients' social support and pre-existing psychiatric conditions on the risk-benefit ratio of facial transplantation. Careful preoperative patient selection and long-term postoperative follow-up programmes under strict institutional review board controls should be used for any future grafts of this type. Funding: Protocole Hospitalier de Recherche Clinique (PHRC) National.
Article
We thank Gaucher and Jarraya [1] for their comments on our study [2]. This first SAFB analysis of the strength and breadth of HLA sensitization (supporting information [2]) in extensively burned patients was initiated after facing reduced access to VCA transplants for burned candidates. We described its impact on future VCA access and addressed the sensitizating factors and their alternatives. A recent report confirmed this risks of humoral rejection of VCA on sensitized patients [3]. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Article
Skin chronic rejection (CR) in vascularized composite allotransplantation has not been included in the Banff classification yet. We report a face-transplant patient who developed cutaneous clinicopathologic changes suggestive of CR. The recipient was a 27-year-old man with severe disfigurement of the lower face due to a pyrotechnic explosion. He received a facial allograft, including mandible, cheeks, lips, and chin, in November 2009. Immunosuppression included antithymocyte globulins and bone-marrow infusion then steroids, tacrolimus, and mycophenolate mofetil. During the first posttransplant year the acute rejection episodes were characterized by reversible oedema and erythema of the graft. Subsequently, the patient developed primary asymptomatic Epstein-Barr virus (EBV) infection, followed by EBV+ B-cell lymphoma and hepatic EBV-associated posttransplant smooth muscle tumors; therefore, the immunosuppressive treatment was greatly reduced. Since the second posttransplant year, the allografted facial skin became progressively sclerotic and presented pigmented macules on a background of hypopigmentation and teleangiectasias, resulting in a poikilodermatous aspect. Skin biopsies showed epidermal atrophy, basal cell vacuolization, and diffuse dermal sclerosis in the absence of significant dermal cell infiltration. The dermal capillaries showed thickened walls and narrowed lumina, whereas the large vessels did not show significant alterations. Neither donor-specific antibodies nor vascular Cd4 deposits were detected. A dysfunction of the graft functions occurred. It was evidenced by a decrease in mouth opening and modification of some phonemes although lip closure was still possible allowing food intake. This is the first report suggestive of CR in a face allotransplantation after immunosuppression minimization.