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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_892_Библиотеки_им_академика_М_И_Перельмана
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Fig. 28.1 Pre- and postoperative pictures of patients who received facial transplantation by Dr.
Eduardo D.Rodriguez and his team (printed with permission and copyrights retained by Eduardo
D.Rodriguez, M.D., D.D.S)
R. R. Colon et al.
Preoperative Considerations
Patient Evaluation andSelection
Patient selection is paramount to success, as the immediate posttransplant rehabilitation and lifelong maintenance require signicant commitment by recipients and
their families. A multidisciplinary team evaluation is performed to evaluate medical, psychosocial, and functional considerations. Important considerations to elucidate are patients’ functional status, associated injuries/decits, medical
history—including chronic conditions and history of malignancy—social support,
and psychiatric conditions.
Initial evaluation includes determining if the patient’s decits could be sufciently addressed with conventional autologous reconstructive methods. If so, these
should be employed and have demonstrated favorable cosmetic and functional outcomes. Those considered suitable candidates should receive vascular imaging and
detailed immunologic evaluation before FT.Lastly, salvage reconstructive options
should be available if the transplant procedure fails or if the allograft necessitates
removal.
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Indications andContraindications
Although no consensus inclusion or exclusion criteria exist, there are some generally aggreged upon indications, and relative contraindications, all of which remain
transplant center specic. FT is typically indicated in patients with functional and
aesthetic decits unamenable to conventional reconstructive techniques. These
include extensive facial soft tissue injury with or without damage to the underlying
craniofacial skeleton.
Relative contraindications focus on medical, psychosocial, and psychiatric
considerations. Medically, patients should be screened for infectious diseases—
particularly human immunodeciency virus (HIV)—hepatitis, active or prior
malignancy, and immunologic or hematologic derangements. Given the lifelong
immunosuppression and medical care required following FT and the assistance
needed in the early postoperative periods, medical noncompliance and lack of
appropriate social support are often considered exclusion criteria for FT.At our
institution, caregiver support is required for FT candidacy. FT should be avoided
in those with active psychiatric disorders, namely, depression and substance use
disorder.
One controversial consideration in FT candidacy is that of blindness. Opponents
of FT in blind patients cite the inability to self-visualize the allograft, thereby prohibiting the identication of signs of potential transplant rejection, including edema
and erythema, and the inability for blind patients to fully comprehend appreciate the
aesthetic outcomes and consequently achieve the psychosocial benet. However,
two transplants have been performed on blind patients, with proponents citing ethical concerns in excluding blind patients from FT.Early psychosocial and transplant
outcomes in these patients appear promising [2–4].
Patient-Specic Planning
The 48 FTs reported in the literature have varied in the extent of tissue transplanted
with varying amounts of soft tissue and bone included, along with specialized structures, such as the tongue. Patient injuries and missing facial structures guide tissue
inclusion. For example, a patient with an intact upper facial third would receive an
allograft limited to the middle and lower facial thirds. Important soft tissue structures that can be included to varying degrees include the nose, ears, eyelids, and oral
mucosa. Bony structures can be included in the allograft to address severely damaged or missing segments of the craniofacial skeleton. Restoration of the craniofacial structure, namely, the vertical and horizontal buttresses, is vital to functional
and aesthetic recovery. Prior FTs have included zygomatic arches, maxillae, mandible, nasal bones, and orbital oors [1, 5]. Of note, a classication system on the
soft tissue and bony defects for FT has been described (Fig.28.2).
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a
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R. R. Colon et al.
b
Fig. 28.2 (a) Soft-tissue defect classication system for facial transplantation. Type 0, oral,
includes upper lip, lower lip, and oral commissures; Type 1, oral-nasal includes nasal softtissue structures with or without type 0; Type 2, oral-nasal-orbital includes infraorbital and
malar regions with or without Type 1; Type 3, full facial includes forehead, supraorbital, and
preauricular and may include all facial soft tissues; (b) skeletal tissue defect classication for
facial transplantation. Type A, Le Fort I-type, includes partial or complete maxilla; Type B, Le
Fort III-type, includes maxilla, inferomedial orbital, and zygomatic bones with or without
nasal, vomer, and ethmoid bones; Type C, monobloc type, includes frontal and supraorbital
bones with or without facial bones in the other types of defects; Subtype M includes partial or
complete mandible (printed with permission and copyrights retained by Eduardo D.Rodriguez,
M.D., D.D.S)
Donor Selection
Donor selection contributes signicantly to aesthetic, functional, and immunologic outcomes. FT donors require additional screening compared to solid organ
donors, beyond immunologic and serologic matching, which includes skin tone,
hair color, and facial structure. The transplant team dictates the extent of immunologic and serologic matching needed, with some centers accepting more mismatch than others. Viral serology matching should also be carefully considered, as
an FT recipient transplanted with Epstein-Barr virus mismatch developed monoclonal B-cell lymphoma [6].
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Immunosuppression Therapy
FT recipients require lifelong immunosuppression, and centers vary in their induction
and maintenance therapy approach. Although induction regimens vary, they often
consist of antithymocyte globulin (ATG) or anti-IL-2 receptor antibody, along with a
combination of tacrolimus, mycophenolate mofetil (MMF), and steroids [7, 8].
Maintenance immunosuppression regimens are less variable, generally consisting of
triple therapy with tacrolimus, mycophenolate mofetil, and a steroid taper [9]. Our
current immunosuppressive regimen includes steroids, ATG, anti-CD20 for induction
immunosuppression, and steroids, tacrolimus, and MMF for maintenance therapy.
The need to prevent rejection must be balanced with the potential complications
of long-term immunosuppression, including kidney damage, metabolic derangements, malignancy, and opportunistic infections [5, 9]. However, this is a delicate
and challenging balance, and much research focuses on safer immunosuppressive
therapies and inducing donor-specic tolerance.
Preparation andPlanning
Facial Transplantation Team
Due to its novelty, FT requires an interdisciplinary group of highly skilled experts.
From preoperative evaluation to long-term follow-up, care of FT patients necessitates physical and occupational therapists, psychiatrists or psychologists, radiologists, nurses, transplant surgeons, and reconstructive surgeons, among others.
Additional groups that facilitate FT success include but are not limited to organ
procurement organizations, local legislative bodies, medical center administration,
and support staff. The collaborative effort between these stakeholders has led to the
development of algorithms for transferring donors to recipient institutions and facilitated simultaneous procurement of solid organs.
Cadaveric Rehearsals
Given the complexities and coordination required for successful FT, cadaveric
rehearsals should be performed, and if possible, with the entire surgical team
together. These rehearsals allow the team to plan for patient-specic operative considerations that would have been identied during recipient evaluation. Additionally,
algorithms and perioperative checklists should be developed to ensure uniformity
and reduce error through this process.
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Imaging
Preoperative imaging of the recipient and donor should be performed through CT
angiography and formal angiography. The benets are twofold: ensuring vessel
patency and identifying anatomic variants that could have potentially catastrophic
outcomes. Ophthalmic artery variants have been described, where the ophthalmic
branches of the external carotid.
Additional Preparation
Importantly, to respect the donor and their families, the donor’s facial integrity
should be restored. This can be achieved through either a 3-D printed or a plaster
mask and allows for any desired end-of-life rituals to be performed.
Surgical Considerations
FT is a challenging procedure because of the unique nature of each patient’s defect
and technical details of the operation. Facial procurement and recipient procedures
are performed simultaneously, and several surgical approaches have been described
in the past 16years. Prior to transplantation, the donor and recipient should both
receive a tracheostomy.
The procedure starts with careful neck dissection elevating a subplatysmal ap,
followed by circumferential exposure of the key anatomical structures such as the
veins (internal jugular and facial veins), arteries (common carotid artery, external
and internal carotid arteries, facial artery, occipital artery, and lingual artery), and
the nerves (facial nerves and hypoglossal nerves). Next, periorbital structures are
dissected carefully to avoid ocular complications such as ectropion, lid retraction,
and loss of blink reex. Finally, excision of the parotid and submandibular glands is
performed to prevent sialoceles.
Osteotomies on both donor and recipient are guided by CAD/CAM cutting
guides to maximize cephalometric and occlusal relationships between the recipient
and donor skeletons [10]. Two patients of our FT cohort received tooth-bearing
maxillomandibular transplants to address ballistic composite midface injuries [10].
Both cases included bilateral mandibular sagittal split osteotomies and Le Fort III
osteotomies to incorporate the mandibular and maxillary teeth while reestablishing
facial structure and projection. Skeletal inset and xation were executed before the
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vascular anastomoses to prevent kinking of the vascular pedicles. Computer-aided
intraoperative surgical navigation was employed to project a virtual surgical plan on
the recipient’s skeletal defect, increasing the accuracy of allograft inset [10]
(Figs. 28.3 and 28.4). Bony alignment and appropriate skeletal xation are conrmed using intraoperative CT.
Adequate vascular perfusion is vital for successful transplantation, so we advocate for a bilateral arterial supply using the external carotid arteries and corresponding veins. Vascular anastomoses are executed using an operating microscope
to increase precision. Indocyanine green uorescence angiography is used to conrm allograft perfusion prior to disconnecting the allograft from the donor’s major
vessels and following vascular anastomoses in the recipient [11] (Fig.28.5). To
prevent synkinesis, the allograft facial nerve branches are anastomosed distally, in
proximity to the target muscles. Sensory nerve coaptation is executed when
possible.
Fig. 28.3 Computer-aided design and manufacturing of patient-specic skeletal cutting guides.
The allograft included skeletal subunits to augment facial projection while preserving retaining
ligaments and muscular insertion sites. Donor (left) and recipient (right) planned osteotomies and
custom cutting guides (printed with permission and copyrights retained by Eduardo D.Rodriguez,
M.D., D.D.S)
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Fig. 28.4 Real-time intraoperative surgical navigation can be leveraged to conrm accurate skeletal inset and compare the skeletal segments planned (green) with actual (gray) position (printed
with permission and copyrights retained by Eduardo D.Rodriguez, M.D., D.D.S)
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Fig. 28.5 Indocyanine green uorescence angiography to verify appropriate allotransplant arterial
perfusion and venous outow (printed with permission and copyrights retained by Eduardo
D.Rodriguez, M.D., D.D.S)
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Postoperative Considerations
Outcomes
48 FT have been performed to date. Few reports on long-term outcomes are available, but the available data demonstrates the procedure’s favorable functional, aesthetic, and psychosocial outcomes. Motor and sensory recovery occurs primarily in
the rst year post-surgery [12]. Motor function is generally apparent around postoperative month (POM) 6 to 8 but may be present earlier [13]. Patients report satisfactory recovery of speech, lip competence, facial expression, and swallowing. Sensory
recovery generally begins around POM 3, even in patients where sensory nerve
coaptation was not conducted. At POM 8, patients report two-point discrimination
and recovery of light touch, pain, and thermal sensation [13].
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Rejection
Allograft acute and chronic immunologic rejection is an expected complication following FT. Most patients have experienced at least one acute rejection episode,
which presents clinically as erythema and swelling of the facial allograft. On the
other hand, chronic rejection presents as premature aging, leukoderma, and mucosal
dryness secondary to tissue brosis [14]. To date, no FT patients have experienced
hyperacute rejection or graft-versus-host disease.
Routine skin biopsies are the current gold standard for rejection surveillance.
Tissue samples are histologically assessed using the Banff classication, which
grades inammatory cell inltration and epithelial involvement [15]. Noninvasive
monitoring methods and blood biomarkers have attracted interest from the VCA
centers; however, their use remains experimental [1]. Once a diagnosis of allograft
rejection is established, treatment should be initiated as soon as possible. Treatment
usually consists of IV pulse dose corticosteroids, adjustment of maintenance immunosuppressants, and plasmapheresis if needed [13].
Other Complications
Close postoperative follow-up is crucial to detect immunologic and operative complications. Postoperative CT and angiography are performed early in the postoperative course to evaluate the technical success and detect complications.
Palatal and oor of the mouth wound dehiscence, necrosis, and stula formation
have been documented in approximately half of the FT patients to date [10]. They
generally manifest at the recipient–donor suture lines and could happen even in the
presence of an adequate palatal blood supply. Sialocele is another common complication, which may occur even if major salivary glands are excluded from the
allograft and can be treated with drainage and botulinum toxin injections [10, 16].
Regular assessment of dental and periodontal health is crucial to avoid dental caries,
tooth loss, periodontal disease, and infections.
Skeletal stability is affected by the dynamic forces on the bone-to-bone interface during functional recovery. One of our patients presented with mandibular
nonunion on postoperative day (POD) 108, possibly due to a brous contracture
at the proximal mandibular segment. This complication was managed with open
reduction and internal xation with a titanium plate [10]. Postoperative malocclusion is a frequent complication among maxillomandibular containing FTs,
even in patients who presented a Class I occlusion immediately after surgery
[10]. The absence of motor tone and proprioceptive feedback during recovery of
speech and mastication in the rst 6 to 9 months posttransplantation is likely
associated with progressive development of malocclusion [17]. Close patient
follow-up is crucial to avoid and manage postoperative malocclusion. A revisional Le Fort advancement can also be employed. However, we advocate for a
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preemptive application of orthodontic elastics immediately following transplantation to avoid the need for malocclusion revision surgery.
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Revision Surgeries
Revision surgery plays an important role in the management of FT patients. Most
FT recipients undergo follow-up procedures, which can be aimed at addressing
facial soft tissue, craniofacial skeleton, dentition, oronasal cavity, salivary glands,
and periorbital tissue [18]. The average time to rst revision surgery is 149±179days,
and patients receive on average 4.8 revision procedures. The combined experience
of VCA centers has demonstrated the safety of revision surgeries performed at
diverse time points. Our center’s experience demonstrates that revision surgery to
address malocclusion and loss of the donor-recipient intraoral interface integrity
can be performed without compromising the allograft [18]. A facial re- transplantation
was recently performed in a patient to address chronic allograft rejection, demonstrating the feasibility of this approach as a salvage option [19].
Future Directions
Since the rst successful transplant in 2005, signicant advances have been made in
the eld, allowing for the rst successful combined VCA transplantation. A combined face and bilateral hand transplantation was performed on a severe burn victim
by our institution in 2020. As of the time of publication, the patient is progressing
well clinically and psychosocially.
The FT donor pool is an important limitation to the procedure. Current legislation for VCA donation requires additional consent beyond solid organ donation protocols. Efforts should be made to amend the policy to include VCA.The expansion
of online resources regarding the procedure is crucial to increase public awareness
and approval. It is our hope that policy changes and increasing awareness will lead
to increased donor supply, thereby increasing the opportunity for those in need.
Further, a larger donor pool will improve immune matching, leading to better overall outcomes. Cross-sex donation is a potential avenue for increasing the available
donor pool.
As lifelong immunosuppression to avoid rejection is associated with signicant
complications, VCA centers continue to explore multiple venues for donor-specic
tolerance induction [20, 21]. Lastly, topical/local immunosuppression and stem cell
therapies have shown promise in preclinical studies and can potentially contribute
to safer immunosuppressive regimens [22].
Acknowledgments The authors would like to acknowledge the donor patients and families for
selessly donating the gift of life and the recipient patients and families.
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