Composite tissue allotransplantations can be indicated when autologous transfers fail to restore human appearance. We report the reproducibility, difficulties, serious adverse events and outcomes of our patients. Five patients were included in a registered clinical research protocol after thorough screenings assessed by an independent expert committee systematically discussing the alternative options. One patient suffered from plexiform neurofibromas, two from third degree burns and two from gunshot injuries.They were included on a national waiting list with a dedicated face procurement procedure. Transplants were harvested from heart beating brain-dead donors before other tissues and organs. Induction immunosuppressive therapy included antithymocyte globulins, steroids, mycophenolate mophetil and tacrolimus. Maintenance therapy included the last three ones associated with extracorporeal-photopheresis. Four patients were transplanted with 7-to 38-month followup. One could not due to multiple panel reactive antibodies after 18 months on waiting list. Acute cellular rejections were controlled by conventional treatment. Opportunistic infections affected all patients and lead one patient to die two month after the transplantation. Voluntary facial activity appeared from 3 to 5 month. Face transplantation has been reproducible under conventional immunosuppression. Major improvements in facial aesthetic and function allowed patients to recover social relations and improved their quality of life.

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A composite tissue allotransplantation of the total face along with the scalp and the auricles is technically feasible. The authors' flap provided reliable vascularization and was obtained in a standardized fashion in less than 11 hours. The graft contained all of the perioral muscles, branches of the facial nerve, eyelid structures, and major salivary glands.

Therapeutic, V.

Data on clinical, mycologic characteristics, and outcome of posttraumatic mucormycosis are scarce and often limited to case reports. From the French nationwide “RetroZygo” study, we compared posttraumatic mucormycosis cases with other forms of mucormycosis. We also reviewed reports of posttraumatic mucormycosis in the English-language literature from 1993 to 2013. We included all proven or probable cases for which underlying condition, route of infection, surgical and antifungal treatments, and outcome were detailed. From our cohort, posttraumatic mucormycosis (n = 16) differed significantly from other forms (n = 85) by rarity of underlying disease (31.2% vs 81%, p < 0.0001), frequency of cutaneous localization (87% vs 7%, p < 0.0001), short time before diagnosis (4.5 vs 21 d, p = 0.0002), species involved (Apophysomyces elegans complex and Saksenaea vasiformis), surgical requirement (93.7% vs 47%, p = 0.0006) and better survival (87.5% vs 47.6% at day 90, p = 0.03). We studied 122 cases of posttraumatic mucormycosis through our literature review. Most frequently reported traumas were traffic (37%), domestic accidents (15.1%), or natural disasters (13.4%). Mucormycosis occurred after extensive soft-tissue damage in 47.5% cases, with symptoms occurring a median of 9.5 days after trauma with necrosis being reported in 76.2% cases. Dissemination was found in 9% of patients, and bacterial coinfection in 41%. Nineteen percent of cases occurred in the Middle East or in India where Apophysomyces elegans complex was the predominant species recovered. Awareness of mucormycosis as a cause of posttrauma soft-tissue infection is warranted, especially in cases of soil-contaminated wounds. Survival is higher than in other forms of mucormycosis, but morbidity remains high.

Many more patients would benefit from vascularized composite allotransplantation if less toxic and safer immunosuppressive protocols will become available. Tolerance induction protocols with donor cells co-transplantation are one of the promising pathways to reduce maintenance immunosupressive regimens. We investigated the role of donor bone marrow cells (BMC), mesenchymal stromal cells (MSC) and in vivo created chimeric cells (CC) used as supportive therapies in a fully MHC-mismatched rat face transplantation model. Twenty-four fully MHC-mismatched hemiface transplantations were performed between ACI (RT1 a ) donors and Lewis (RT1 l

: Therapeutic, II.(Figure is included in full-text article.).

Purpose: The hallmark of neurofibromatosis type 1 (NF1) is the onset of dermal or plexiform neurofibromas, mainly composed of Schwann cells. Plexiform neurofibromas can transform into malignant peripheral nerve sheath tumors (MPNST) that are resistant to therapies.Experimental Design: The aim of this study was to identify an additional pathway in the NF1 tumorigenesis. We focused our work on Wnt signaling that is highly implicated in cancer, mainly in regulating the proliferation of cancer stem cells. We quantified mRNAs of 89 Wnt pathway genes in 57 NF1-associated tumors including dermal and plexiform neurofibromas and MPNSTs. Expression of two major stem cell marker genes and five major epithelial-mesenchymal transition marker genes was also assessed. The expression of significantly deregulated Wnt genes was then studied in normal human Schwann cells, fibroblasts, endothelial cells, and mast cells and in seven MPNST cell lines.Results: The expression of nine Wnt genes was significantly deregulated in plexiform neurofibromas in comparison with dermal neurofibromas. Twenty Wnt genes showed altered expression in MPNST biopsies and cell lines. Immunohistochemical studies confirmed the Wnt pathway activation in NF1-associated MPNSTs. We then confirmed that the knockdown of NF1 in Schwann cells but not in epithelial cells provoked the activation of Wnt pathway by functional transfection assays. Furthermore, we showed that the protein expression of active b-catenin was increased in NF1-silenced cell lines. Wnt pathway activation was strongly associated to both cancer stem cell reservoir and Schwann-mesenchymal transition.Conclusion: We highlighted the implication of Wnt pathway in NF1-associated tumorigenesis. Clin Cancer Res; 20(2); 358-71. Ó2013 AACR.