Keywords
face transplantation - tongue transplantation - malignancy - radionecrosis - HIV -
vascularized composite allotransplantation
Vascularized composite allotransplantation (VCA) is progressively being used in reconstructive
surgery. Due to improvements in immunosuppression and clinical management of patients
with solid organ transplantations, VCA has been used in the reconstruction of upper
extremity amputations, with good short- and midterm results, and limited morbidity.[1] Attention has been directed recently to the reconstruction of massive facial defects
with facial transplantation. Although a VCA including the scalp and the ears was reported
in an advanced melanoma patient in 2005 with conceivably poor outcome,[2] the first genuine facial transplantation was performed in France in 2006.[3]
[4] At the time of this writing, 13 cases have been performed in 4 countries, 7 in France,
3 in Spain, 2 in the United States, and 1 in China.[5]
[6]
[7]
[8]
[9]
[10] The etiology of the facial defects was traumatic in most cases, with two cases of
extensive facial neurofibromatosis. The transplanted facial segments have included
mainly the lips, nose, varying segments of maxilla and/or anterior mandible, and other
aesthetic units of the face. Recently a case that included the four eyelids has been
reported.[11] A case of tongue transplantation to treat longue necrosis as a result of surgical
treatment of an advanced malignancy of the floor of the mouth was reported in 2008
with short-patient survival.[12]
The purpose of this article is to report on the technical aspects of a lower face
composite allotransplantation including the tongue, floor of the mouth, and most of
the mandible performed in Spain in August 2009. The facial defect was secondary to
complications of radiotherapy for a squamous cell carcinoma (SCC) of the floor of
the mouth in an HIV-positive patient. To the best of the authors' knowledge, this
is the first case of a facial transplantation including the tongue, and the first
performed in an HIV-positive or postoncologic patient.
Patient and Methods
The Recipient Patient
The recipient patient was an HIV-positive, 42-year-old male on highly active antiretroviral
therapy (HAART) (ritonavir, darunavir, raltegravir, etravirine, and enfuvirtide) with
CD4 counts over 400/mL and negative viral load. The facial defect included the lower
lip, tongue, floor of the mouth, and the body of the mandible, with septic remnants
of mandibular bone bilaterally. The facial defect was secondary to complications of
mandibular radionecrosis after chemoradiotherapy for a SCC of the tongue (T3N0M0)
11 years before. Multiple attempts at surgical reconstruction (including five free
and one pedicled flap performed elsewhere) compounded the defect ([Fig. 1]). The neck was massively scarred and rigid, with virtually absent recipient vessels.
There was a radiation injury to the larynx, with vocal cord palsy in paramedian position,
and a bony ankylosis of the left temporomandibular joint (TMJ).
Figure 1 The composite lower face defect. There was massive scarring and soft tissue collapse,
and septic fistulae.
The patient was fully informed of the limited possibilities of further autologous
reconstructions, and the limited experience in human facial transplantation at that
time. The fact that VCA had never been performed before in HIV-positive patients,
the limited information available about tongue transplantation, the risks of transplantation
after malignancy, and the results of solid organ transplantations in HIV-positive
recipients pertinent to his case were fully explained to the patient. After approval
by an ethical committee, a composite lower facial-mandible-tongue VCA was proposed
to the patient. IRB and National Organization for Organ Transplantation (Organización
Nacional de Trasplantes, ONT) approvals were also obtained.
Preparatory Surgery
An elective surgery was performed (3 months before transplantation and 1 month before
the patient entered the waiting list) to debride the septic bone remnants of the mandible,
and to identify and tag the recipient nerves without time constraints. Hypoglossal,
lingual, inferior alveolar, and lower divisions of the facial nerves were dissected
bilaterally off the thick scar and tagged with colored silicone loops. The infected
remnants of previous attempts at osseous reconstruction were debrided, and the remnants
of the upper denture were removed. The bone defect included the body of the mandible
and the left hemimandible. The left condyle was drilled up to the temporal bone, and
a solid spacer of polymethyl-methacrylate with gentamycin was inserted in the condylar
region to avoid soft-tissue collapse, and allow space for the allogeneic condyle.
Transplantation Surgery
Face transplantation was performed on August 2009, by a single surgical team, with
sequential dissection on the recipient, procurement of the VCA from the donor, and
insetting-revascularization. The subclavian artery, internal and external jugular
veins on the right side, and the left external jugular vein on the left side were
dissected as recipient vessels. The previously tagged recipient nerves were identified
and the methacrylate condylar spacer was removed. The scarred tissue of the lower
third of the face was removed and the scarred mucosa of the oropharynx was released.
Facial VCA procurement was performed immediately after cardiac cessation, from a fully
HLA-mismatched multiorgan brain-dead donor. The aorta was cross- clamped distal to
the left subclavian take-off to allow the in situ perfusion of both carotid arteries
with cold Celsior preservation solution immediately before heart procurement. The
facial VCA included the skin from the oral commissures to the earlobes, and down to
the upper neck, the mandible from the right angle to the left condyle, the tongue,
the floor of the mouth, the hyoid bone, suprahyoid muscles, and the six major salivary
glands ([Figs. 2] and [3]). The hypoglossal, lingual, inferior alveolar, and lower division of the facial
nerves were dissected up to the skull base. The left mylohyoid nerve was identified
on the inferior alveolar nerve. The right external carotid artery was dissected, the
upper thyroideal, ascending pharyngeal, and posterior auricular arteries were ligated
and divided, and the lingual and facial arteries were included. In the left side,
the internal maxillary artery and its inferior alveolar branch were included, along
with the lingual and facial arteries. The common and internal carotid arteries were
dissected and included in the VCA bilaterally. External jugular, thyrolingual, and
internal jugular veins were also included bilaterally. VCA harvesting took 3.5 hours
(cold ischemia). An end-to-end anastomosis was performed between the distal ends of
both internal carotid arteries at the side table to enhance contralateral arterial
inflow ([Fig. 3]).
Figure 2 The VCA harvested from the donor, including the lower face, tongue, floor of the
mouth, salivary glands, and three-fourths of the mandible.
Figure 3 Schematic drawing of the VCA and vascular connections. CN VII, facial nerve; CN XII,
hypoglossal nerve; V3, third division of the trigeminal nerve.
After minimal transportation time, revascularization of the VCA was performed. End-to-end
anastomosis of the right internal jugular veins and end-to-side anastomosis between
the right subclavian and the right common carotid arteries were performed before the
insetting. Hemostasis of the flap was performed and the left external jugular vein
was anastomosed to the homonymous vessel. The oral and oropharyngeal mucosae were
sutured; the left hypoglossal, lingual, and inferior alveolar nerves were coapted
trying to include the left mylohyoid nerve in an attempt at reinnervation of the suprahyoid
muscles. The left mandibular condyle was fixed with a heavy resorbable suture to the
soft tissues of the temporomandibular fossa, and the left lower facial nerve was coapted.
On the right side, the lingual and hypoglossal nerves were coapted (a short nerve
graft was used for the hypoglossal), the mandible was plated with a single 2-mm plate,
the inferior alveolar nerve was coapted, a short graft was used for lower facial nerve
repair, and the skin was closed.
Results
Clinical Evolution
The immunosuppressive treatment included induction with anti-CD25 basiliximab and
standard triple therapy with tacrolimus, mycophenolate mofetil, and corticosteroids.
Calcineurin inhibitor dosing was modified according to previously described interactions
with antiretroviral drugs.[13] Although the details of acute rejection episodes, clinical course, and functional
results are beyond the scope of the present study, at 16 months posttransplant the
patient is rejection-free, with no evidence of HIV replication or malignancy recurrence,
is swallowing, and starting phonation rehabilitation ([Fig 4]). Mandible excursion is 10 mm probably due to previous injury to the right TMJ.
Two acute rejection episodes occurred on postoperative days 14 and 350 (Banff histological
grade III)[14] and responded to intravenous methylprednisolone 500 mg/24 h for 5 days. At postoperative
month 11 a pseudosarcomatous spindle-cell postsurgical nodule was removed from the
base of the tongue through a sagittal mandible-splitting approach. Although the histological
diagnosis of pseudotumor was firm, tacrolimus was switched to sirolimus. The nodule
has not recurred.
Figure 4 Result at 16 months posttransplantation.
Discussion
Autologous reconstruction of massive facial defects, especially those involving the
perioral and periocular regions yields modest results at best. Facial transplantation
has emerged as a novel treatment for these unfortunate patients. With 13 cases performed
by 8 different teams at the time of this writing, facial transplantation should still
be considered an experimental procedure. Issues such as long-term results, immunological
singularities of the face, and the role of bone marrow in facial transplantation are
largely unanswered questions. From a medical standpoint, neither the oncological precedents
nor the HIV status of the patient contraindicated per se the transplantation.[15] Solid organ transplantation has been successfully reported in HIV-positive patients
with negative viral load and CD4 counts over 200 cells/mL. A disease-free interval
of 5 years after malignancy is commonly considered safe before solid organ transplantation.
Although VCA has not been reported before in either category of oncologic and HIV-positive
patients, it is the opinion of the authors that in severe cases the risk-benefit ratio
is favorable in these medically complex recipients.
Pseudosarcomatous spindle-cell nodule is a benign reparative pseudotumor described
mainly in the bladder and less frequently in the pharynx, after surgical insults.
Pathological diagnosis is challenging as it can be easily mistaken for a high-grade
malignancy. Complete surgical resection is adequate curative treatment.[16]
In contradistinction to hand transplantation, facial defects and facial transplants
are remarkably heterogeneous from an anatomical point of view. Surgical considerations
are thus especially pertinent to facial transplantation. Some details of this case
deserve comment. Facial VCA procurement from the donor after cardiac cessation and
exsanguination makes dissection more expeditious, and avoids the significant bleeding
associated and any potential interference with the procurement of other vital organs.
On the other hand, it prolongs ischemia time, it needs special training to identify
empty vessels, and effective hemostasis is more difficult to achieve. The in situ
perfusion with cold preservation solution before VCA dissection probably makes this
increase in ischemia time less relevant.[17] Although it has been demonstrated that increased ischemia time is detrimental to
muscle function[18] and increases acute rejection episodes,[16] the global benefits of dry harvesting the face may outweigh the drawbacks. To compensate
for this extra ischemia time and to allow for effective hemostasis, the revascularization
was performed before the insetting. The bleeding was not profuse, but progressive
swelling of the flap made insetting of the right side very difficult, and dictated
the use of nerve grafts for the right facial and hypoglossal nerves. Probably the
insetting should have been done before revascularization, at the price of 2 more hours
of ischemia time.
Anatomically, this case had some unique features. The incorporation of the tongue
and the left hemimandible dictated the inclusion of bilateral lingual arteries, lingual
and hypoglossal nerves, and the left internal maxillary artery and its inferior alveolar
branch ([Fig. 2]). Musculoperiosteal blood supply can nourish segments of the mandible, but the endosteal
system from the inferior alveolar artery is necessary for hemimandibular or larger
segments.[19] The massive scarring of the neck posed significant difficulties to this case. The
absence of recipient vessels in both sides of the neck dictated the use of the right
subclavian artery as the sole recipient artery. Although the rich vascular network
of the face allows contralateral flow across the midline with unilateral vascular
supply,[7]
[20]
[21] the end-to-end anastomosis of the internal carotid arteries is a simple and rapid
surgical maneuver to increase this crossed circulation. Recipient nerve dissection
and tagging was considered paramount for sensorimotor recovery and function of the
VCA, and it was performed as an elective preparatory surgery to allow unrestricted
operating time. This maneuver proved to be very helpful.
The inclusion of the maxillary bones and upper denture in the VCA, to obtain dental
occlusion, was ruled out early during the planning of the case, on anatomical grounds.
Because the upper dental arch was removed during the preparatory surgery, plans were
made to fit an upper prosthetic denture according to that of the donor. Tongue swelling,
the limited movement of the right TMJ, and the reduction of the mandible performed
at the time of pseudotumor resection have delayed prosthodontic care. Likewise, the
inclusion of the larynx in the composite VCA was initially considered because of the
radiation injury and the vocal cord palsy, but the likelihood of satisfactory nerve
regeneration after coaptation of the scarred superior laryngeal and recurrent nerves
was considered poor and the idea abandoned.
In conclusion, a successful lower face composite VCA including the tongue and mandible
was performed and the surgical details reported herein. To the best of the authors'
knowledge this is the first case reported of this type of facial transplantations.
