Antonio Rampazzo

Pathways of sensory recovery after face transplantation.

Background: Severely disfiguring facial injuries have a devastating impact on the patients quality of life. The advent of facial allotransplantation has allowed optimal anatomical reconstruction to be achieved; however, the need for lifelong immunosuppression and unpredictable functional outcomes preclude it from routine acceptance in clinical practice. Evidence from published reports on the first four face transplant recipients indicates improved and accelerated return of sensation to the facial allograft despite suboptimal repair of the sensory nerves. Methods: The authors performed a comparative analysis of the sensory outcomes following face transplantation with the sensory recovery achieved after conventional nerve repair, autologous face and scalp replantation, and vascularized free tissue transfer. Results: Sensory recovery following face transplantation, even when the sensory nerves were not repaired, was comparable to the outcome of microsurgical repair of the peripheral branches of the trigeminal nerve and innervated free flaps. Conclusions: Nearly normal sensory recovery can be expected following facial allotransplantation with or without repair of the sensory nerves. The mechanisms responsible for this surprising outcome include preservation of normal density of the receptors within the facial allograft, regeneration from the recipient bed and allograft margins, transmission of the sensory inputs through afferent fibers contained in the facial nerve, nervi nervorum of the facial nerve, or trigeminofacial communicating rami. Furthermore, immunosuppressive therapy with tacrolimus contributes to the accelerated nerve regeneration. The minimum requirements for quantitative sensory testing and timing of the follow-up assessments are outlined to facilitate comparison of sensory outcomes after face transplantation.

Successes and lessons learned after more than a decade of upper extremity and face transplantation.

Purpose of reviewThis review aims to present the most recent updates on face and upper-extremity allotransplantation. Recent findingsTo date, 27 face and more than 89 upper-extremity allotransplantations have been performed. Both the face and hand transplants restored form, function and patients’ social integration. The complications were comparable with solid organs; however, face transplantation, as well as the combination of face and double hand transplantation, presented with significant morbidity and mortality. Evidence of chronic rejection was confirmed in hand transplants, but it has not been reported yet for facial transplantation. Novel immunosuppressive protocols have allowed a decrease in the number and dosages of traditional immunosuppressants. With increased awareness that following face and hand transplantation, the return of function is more important than anatomical restoration of the missing parts, there has been an important shift in the ethical debate weighing the risks and benefits of face and hand allotransplantation. SummaryEarly results after face and upper extremity transplantation are promising, with 5-year survival rates greater than in solid organ transplants. However, these procedures still need to be closely monitored and the outcome data should be rigorously reported to the central patient registry database to allow continuous surveillance.

The Face as a Sensory Organ

Background: The human face is a highly specialized organ for receiving the sensory information from the environment and for its transmission to the cortex. The advent of facial transplantation has shown that excellent reconstruction of disfiguring defects can be achieved; thus, the expectations are now focused on functional recovery of the transplant. So far, restoration of facial sensation has not received the same attention as the recovery of motor function. Methods: A thorough review of the literature was performed to investigate the current knowledge on the sensory pathways of the human face and their functions to evaluate current methods of sensory assessment and the available data on normal sensation. Results: The presence of Meissner and Ruffini corpuscles, Merkel disks, hair-associated fibers, and intraepidermal free nerve endings was confirmed. Occurrence of extensive cross-communications between trigeminal and facial nerve was substantiated. Two-point discrimination and pressure thresholds represented the most objective measures of facial sensation. Age, sex, and smoker status of the patients were shown to influence normal sensibility values. The most suitable areas for sensory testing based on the tested modality and innervation were inferred. The anatomical course of the nerves and their variations had implications for the harvest of face allografts and repair of the sensory nerves. Conclusions: This review has illustrated the complexity of sensory pathways of the face and their influence on somatic and visceral responses. In view of the discussed data, during facial transplantation, it is important to consider different mechanisms of restoration of facial sensation.

Effectiveness of topical immunosuppressants in prevention and treatment of rejection in face allotransplantation.

Background The use of topical immunosuppressants has been anecdotally reported for the treatment of rejection in vascularized composite allotransplantation. The aim of this study was to evaluate the effectiveness of topical tacrolimus and clobetasol in the prevention and treatment of rejection. Methods Seventy-six hemiface allotransplants, between ACI (RT1a) donors and Lewis (RT1l) recipients, were performed in 11 groups and treated with topical tacrolimus or clobetasol, or in combination with systemic cyclosporine A and anti–&agr;&bgr;–T-cell receptor antibody for 1 week. Topical treatment increased the survival of the allograft in all groups. Results Best outcomes were obtained in the groups treated with systemic therapy and topical tacrolimus. Expression of proinflammatory cytokines interleukin 2, interferon &ggr;, tumor necrosis factor &agr;, and transforming growth factor &bgr; correlated with clinical signs of rejection and the final outcomes. Clobetasol application was associated with a marked depletion of lymphocytic populations, and dermal and epidermal atrophy. Conclusions Both topical tacrolimus and clobetasol were effective in treating episodes of acute rejection, and the best outcomes were achieved when their application was initiated after systemic immunosuppression. Topical tacrolimus proved to be a preferable adjunct agent to the systemic therapy by preventing both the local and systemic complications.

Pediatric vascularized composite allotransplantation.

BackgroundVascularized composite allotransplantation (VCA) has experienced a growing acceptance, which has led to a debate centered on extending the indications of the procedure to include pediatric patients. The aim of this article was to discuss such indications based on the evidence in pediatric solid organ transplantation, reconstructive surgery in children, and VCA in adult patients. MethodsPapers published on the outcomes of pediatric solid organ transplantation, growth after replantation of extremities, vascularized autologous tissue transfer, craniofacial surgery, orthognathic procedures, facial fractures, and outcomes after repair of peripheral nerves in children were reviewed. ResultsAlthough the outcomes of solid organ transplantation in children have improved, the transplanted organs continue to have a limited lifespan. Long-term immunosuppressive therapy exposes the patients to an increased lifetime risk of infections, diabetes, hypertension, dyslipidemia, cardiovascular disease, and malignancy. Growth impairment and learning disabilities are other relevant drawbacks, which affect the pediatric recipients. Nonadherence to medication is a common cause of graft dysfunction and loss among the adolescent transplant recipients. Rejection episodes, hospitalizations, and medication adverse effects contribute negatively to the quality of life of the patients. Although normal growth after limb transplantation could be expected, pediatric facial transplant recipients may present with arrest of growth of transplanted midfacial skeleton. ConclusionsConsidering the non–life-threatening nature of the conditions that lead to eligibility for VCA, it is suggested that it is premature to extend the indications of VCA to include pediatric patients under the currently available immunosuppressive protocols.

Microsurgical Anatomy of the Terminal Hypoglossal Nerve Relevant for Neurostimulation in Obstructive Sleep Apnea.

Neurostimulation of the hypoglossal nerve has shown promising results in the treatment of obstructive sleep apnea. This anatomic study describes the detailed topography of the hypoglossal nerves motor points as a premise for super‐selective neurostimulation in order to optimize results and minimize the risk of complications related to main nerve trunk manipulation.

Establishing the Feasibility of Face Transplantation in Granulomatosis With Polyangiitis.

Granulomatosis with polyangiitis (GPA; formerly Wegeners granulomatosis) is a rare vasculitis that commonly starts in the craniofacial region. We report a case that was masked by prior facial trauma and associated with pyoderma gangrenosum (PG). Disease progression and aggressive debridements led to severe facial tissue loss. The decision to perform a face transplant was controversial because of the risk of disease relapse on the facial allograft. We reviewed renal transplant outcomes in GPA for possible relevance. A PubMed search retrieved 29 studies. Patient and graft survival, relapse, morbidity, mortality, rejection and immunosuppression were assessed. Ten‐year patient survival and graft survival were 84.4% and 72.6%, respectively. GPA relapse occurred in 31.5%, and upper airway/ocular relapse occurred in 17.8% (resolved in 76.9%). Mortality was 12.3%. Acute and chronic rejection rates were 14.9% and 6.8%, respectively. Traditional posttransplant immunosuppression was effective. Our review suggests that GPA renal transplant outcomes are comparable to general renal transplant cohorts. Furthermore, transplanted GPA patients exhibit lower disease relapse secondary to lifelong immunosuppression. This supported our decision to perform a face transplant in this patient, which has been successful up to the present time (1‐year posttransplantation). Untreated GPA and PG are potential causes of worse surgical outcomes in the craniofacial region.

Surgical Management of Mandibular Intraosseous Schwannomas.

Abstract Intraosseous schwannomas of the mandible are rare tumors that usually arise from peripheral nerve sheaths of the main trunk or branches of the inferior alveolar nerve (IAN). A systematic review of the English literature through PubMed was conducted from 1945 to 2016. Forty-nine patients of mandibular intraosseous schwannomas were identified. The most common location of the tumor was the posterior mandible (61.2%). There were 28 patients in whom the tumor involved the IAN (57.1%). The most commonly performed procedures included enucleation through a mucoperiosteal flap and a bone window (73%), curettage (10%), segmental mandibulectomy (10%), and sagittal split ramus osteotomy (6%). The recurrence rate was 6%: all 3 recurrent patients occurred in the posterior area. The authors report a 72-year-old female with a schwannoma of the IAN which was removed through a sagittal split of the mandible, although there was a bony defect of the external cortex after biopsy of the lesion. The nerve was reconstructed with a sural nerve graft. Due to the slow growing nature and encapsulation of schwannomas, surgical resection seems the best treatment with optimal functional outcomes and low recurrence rate even with a minimally invasive approach. Sagittal split ramus osteotomy and segmental mandibulectomy are reserved to large or posterior lesions to aid with radical resection or improve exposure and reconstruction.

Addressing Religious and Cultural Differences in Views on Face Transplantation

Up to present more than 80 cases of composite tissue allotransplants (CTA) have been reported across the world. The geographical distribution of the reported cases is prominently in favor of Europe and North America. It is therefore questionable if the religious and cultural views could have a role in determining the diffusion of face transplantation practice in different countries. While Christianity and Islam encourage organ donation, Buddhism, Shinto, and conservative branches of Judaism have had a tormented process of acceptance of brain death concept and cadaveric organ donation. No religion is formally against transplantation from deceased donors. Specific religious bans against face transplantation do not exist; however, a wide gap is present between the religious stances and the popular beliefs. Education on indications, organ procurement procedures, and treatment of the donor is needed to clarify erroneous beliefs and address the fears, helping the diffusion of the practice.

Radiation Wounds and Their Management: Reconstructive Options

The following chapter focuses on the wounds and unstable scars caused by radiation injury and their reconstructive management. The radiation wounds are challenging to treat and oftentimes would require radical debridement of the involved soft tissues and the bone, if necessary. Mainstay of reconstruction relies on bringing healthy, well-vascularized soft tissue from areas outside the zone of radiation injury. In addition, previously irradiated tissues are at risk for wound healing complications. Prophylactic flaps could be performed to reduce the risk, should a need to operate on irradiated tissues without any evidence of wound arise. Reconstructive options include regional flaps or free tissue transfers which are demonstrated with typical case examples in this chapter.