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Genetic mutations affecting chromatin modifiers are widespread in cancers. In malignant peripheral nerve sheath tumors (MPNSTs), Polycomb repressive complex 2 (PRC2), which plays a crucial role in gene silencing, is inactivated through recurrent mutations in core subunits embryonic ectoderm development (EED) and suppressor of zeste 12 homolog (SUZ12), but mutations in PRC2's main catalytic subunit enhancer of zeste homolog 2 (EZH2) have never been found. This is in contrast to myeloid and lymphoid malignancies, which harbor frequent loss-of-function mutations in EZH2. Here, we investigated whether the absence of EZH2 mutations in MPNST is due to a PRC2-independent (i.e., noncanonical) function of the enzyme or to redundancy with EZH1. We show that, in the absence of SUZ12, EZH2 remains bound to EED but loses its interaction with all other core and accessory PRC2 subunits. Through genetic and pharmacological analyses, we unambiguously establish that EZH2 is functionally inert in this context, thereby excluding a PRC2-independent function. Instead, we show that EZH1 and EZH2 are functionally redundant in the slowly proliferating MPNST precursors. We provide evidence that the compensatory function of EZH1 is alleviated upon higher proliferation. This work reveals how context-dependent redundancies can shape tumor-type specific mutation patterns in chromatin regulators.
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Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Neoplasias/metabolismo , Complexo Repressor Polycomb 2/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Cromatina/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Mutação/genética , Proteínas de Neoplasias , Neoplasias/genética , Neurofibroma/genética , Neurofibroma/metabolismo , Complexo Repressor Polycomb 2/genética , Fatores de TranscriçãoRESUMO
The 2007 Banff working classification of skin-containing Tissue Allograft Pathology addressed only acute T cell-mediated rejection in skin. We report the longitudinal long-term histological follow-up of six face transplant recipients, focusing on chronic and mucosal rejection. We identified three patterns suggestive of chronic rejection (lichen planus-like, vitiligo-like and scleroderma-like). Four patients presented lichen planus-like and vitiligo-like chronic rejection at 52 ± 17 months posttransplant with severe concomitant acute T cell-mediated rejection. After lichen planus-like rejection, two patients developed scleroderma-like alterations. Graft vasculopathy with C4d deposits and de novo DSA led to subsequent graft loss in one patient. Chronic active rejection was frequent and similar patterns were noted in mucosae. Concordance between 124 paired skin and mucosal biopsies acute rejection grades was low (κ = 0.2, p = .005) but most grade 0/I mucosal rejections were associated with grade 0/I skin rejections. We defined discordant (grade≥II mucosal rejection and grade 0/I skin rejection) (n = 55 [70%]) and concordant (grade≥II rejection in both biopsies) groups. Mucosal biopsies of the discordant group displayed lower intra-epithelial GranzymeB/FoxP3 ratios suggesting a less aggressive phenotype (p = .08). The grading system for acute rejection in mucosa may require phenotyping. Whether discordant infiltrates reflect a latent allo-immune reaction leading to chronic rejection remains an open question.
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Transplante de Face , Transplante de Rim , Biópsia , Seguimentos , Rejeição de Enxerto/etiologia , Humanos , MucosaRESUMO
INTRODUCTION: No etiologic therapy is available for Duchenne muscular dystrophy (DMD), but mesenchymal stem cells were shown to be effective in preclinical models of DMD. The objective of this study is to investigate the effect of microfragmented fat extracted on a murine model of DMD. METHODS: Fat tissue was extracted from healthy human participants and injected IM into DMD mice. Histological analysis, cytokines, and force measurement were performed up to 4 weeks after injection. RESULTS: Duchenne muscular dystrophy mice injected with microfragmented fat exhibited an improved muscle phenotype (decreased necrosis and fibrosis), a decrease of inflammatory cytokines, and increased strength. DISCUSSION: Administration of microfragmented fat in key muscles may improve muscular phenotype in patients with DMD. Muscle Nerve, 2019.
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Distrofina/genética , Células-Tronco Mesenquimais/citologia , Músculo Esquelético/patologia , Distrofia Muscular de Duchenne/genética , Tecido Adiposo/patologia , Animais , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Força Muscular/fisiologiaRESUMO
BACKGROUND: The national ranking examination (NRE) marks the end of the second cycle (6th university year) of French medical studies and ranks students allowing them to choose their specialty and city of residency. We studied the potential predictive factors of success at the 2015 NRE by students attending a French School of Medicine. METHODS: From March 2016 to March 2017, a retrospective study of factors associated with the 2015 NRE success was conducted and enrolled 242 students who attended their sixth year at the school of medicine of Reims. Demographic and academic data collected by a home-made survey was studied using univariate and then multivariate analysis by generalized linear regression with a threshold of p < 0.05 deemed significant. RESULTS: The factors independently associated with a better ranking at the NRE were the motivation for the preparation of the NRE (gain of 3327 ± 527 places, p < 0.0001); to have participated in the NRE white test organized by la Revue du Praticien in November 2014 (gain of 869 ± 426 places, p < 0.04), to have participated in the NRE white test organized by la conférence Hippocrate in March 2015 (+ 613 places ±297, p < 0.04). The factors independently associated with poor NRE ranking were repeating the first year (loss of 1410 places ±286, p < 0.0001), repeating a year during university course (loss of 1092 places ±385, p < 0.005), attendance of hospital internships in 6th year (loss of 706 places ±298, p < 0.02). CONCLUSIONS: The student motivation and their white tests completion were significantly associated with success at the NRE. Conversely, repeating a university year during their course and attendance of 6th year hospital internships were associated with a lower ranking.
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Avaliação Educacional , Escolaridade , Faculdades de Medicina , Adulto , Feminino , Previsões , França , Humanos , Masculino , Estudos Retrospectivos , Estudantes de Medicina , Adulto JovemRESUMO
BACKGROUND: The volume of the profunda femoris artery perforator (PAP) flap limits its indications to small- and medium-sized breast reconstructions after modified radical mastectomy for cancer. We report a modified PAP flap design, including not only a vertical extension that increases its volume but also the skin surface, which suits larger breasts requiring immediate or delayed breast reconstructions and compare the results with our horizontal skin paddle PAP flap experience. PATIENTS AND METHODS: In our center between November 2014 and November 2016, 51 consecutive patients underwent a PAP flap breast reconstruction following breast cancer. A retrospective analysis on the collected data was performed to compare 34 patients with a bra cup smaller than C who underwent 41 horizontal PAP flap procedures, with those (n = 17) of a bra cup greater than or equal to C who underwent 21 fleur-de-lys PAP flap procedures. Demographic, anthropometric, flap and surgical characteristics, postoperative complication rates, and hospital stay were compared between the two groups. RESULTS: The average flap weight was 480 g (range: 340-735 g) for the fleur-de-lys PAP flap group compared with 222 g (range: 187-325 g) for the horizontal PAP flap procedure (p < 0.001). The mean flap dimensions were 25 × 18 cm for the fleur-de-lys PAP flap group compared with 25 × 7 cm in the horizontal PAP flap group. No flap failure was observed in the fleur-de-lys PAP flap group compared with two flap failures secondary to venous thrombosis in the horizontal PAP flap group (NS). Three patients (14%) experienced delayed healing at the donor site compared with four patients (10%) in the horizontal PAP flap group (NS). CONCLUSION: The fleur-de-lys skin paddle design not only allows an increase of the horizontal PAP flap volume, but also increases the skin surface, with an acceptable donor site morbidity. For medium- or large-sized breasts, the fleur-de-lys PAP flap seems to be ideal when a DIEP flap-based reconstruction is contraindicated.
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Neoplasias da Mama/cirurgia , Mama/anatomia & histologia , Artéria Femoral/transplante , Mamoplastia/métodos , Retalho Perfurante/irrigação sanguínea , Coxa da Perna/cirurgia , Adulto , Idoso , Estética , Feminino , Humanos , Mastectomia , Pessoa de Meia-Idade , Tamanho do Órgão , Satisfação do Paciente/estatística & dados numéricos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE: While anatomical variations of the subscapular vessels are frequently encountered during axillary dissection, little is found in the literature. The aim of this cadaveric study was to define arterial and venous anatomical variations and frequencies of the subscapular vascular pedicle and its terminal/afferent vessels in women. METHODS: We performed 80 dissections of the axillary region on forty female formalin-embalmed cadavers. Each anatomical arrangement was photographed and recorded on a scheme before analysis. RESULTS: We propose a new classification of the subscapular pedicle variations. We observed three types of subscapular arterial variation. The type Ia was the most frequent arrangement (71% of our dissections), the type Ib was observed in 11% and the type II in 18% of cases. We observed four types of subscapular venous variation. The type Ia was observed in 63% of cases, the type Ib in 14%, the type II in 14% and the type III in 10% of cases. CONCLUSIONS: This knowledge of the anatomical variation arrangement and frequencies of the subscapular vascular pedicle will assist the surgeon when dissecting the axillary region for malignant or reconstructive procedures.
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Escápula/irrigação sanguínea , Idoso , Idoso de 80 Anos ou mais , Variação Anatômica , Axila/irrigação sanguínea , Neoplasias da Mama/cirurgia , Cadáver , Feminino , Humanos , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
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.
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Extensively burned patients receive iterative blood transfusions and skin allografts that often lead to HLA sensitization, and potentially impede access to vascularized composite allotransplantation (VCA). In this retrospective, single-center study, anti-HLA sensitization was measured by single-antigen-flow bead analysis in patients with deep, second- and third-degree burns over ≥40% total body surface area (TBSA). Association of HLA sensitization with blood transfusions, skin allografts, and pregnancies was analyzed by bivariate analysis. The eligibility for transplantation was assessed using calculated panel reactive antibodies (cPRA). Twenty-nine patients aged 32 ± 14 years, including 11 women, presented with a mean burned TBSA of 54 ± 11%. Fifteen patients received skin allografts, comprising those who received cryopreserved (n = 3) or glycerol-preserved (n = 7) allografts, or both (n = 5). An average 36 ± 13 packed red blood cell (PRBC) units were transfused per patient. In sera samples collected 38 ± 13 months after the burns, all patients except one presented with anti-HLA antibodies, of which 13 patients (45%) had complement-fixing antibodies. Eighteen patients (62%) were considered highly sensitized (cPRA≥85%). Cryopreserved, but not glycerol-preserved skin allografts, history of pregnancy, and number of PRBC units were associated with HLA sensitization. Extensively burned patients may become highly HLA sensitized during acute care and hence not qualify for VCA. Alternatives to skin allografts might help preserve their later access to VCA.
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Queimaduras/terapia , Antígenos HLA/química , Alotransplante de Tecidos Compostos Vascularizados , Adolescente , Adulto , Aloenxertos , Anticorpos/química , Transfusão de Sangue , Criança , Complemento C1q/química , Estudos Transversais , Criopreservação , Eritrócitos/citologia , Feminino , Glicerol/química , Acessibilidade aos Serviços de Saúde , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Gravidez , Estudos Retrospectivos , Transplante de Pele , Adulto JovemRESUMO
Transoral robotic surgery (TORS) offers new possibilities that have not been experimented in the field of minimally invasive skull base neurosurgery. We propose to evaluate the feasibility of transoral approach to the sella turcica with the da Vinci system on cadavers. We performed four robot-assisted dissections on human fresh cadavers in order to reach the pituitary fossa by the oral cavity. Cavum mucosa dissection was performed by the head and neck surgeon at the console and then the sphenoid was drilled by the neurosurgeon at the bedside, with intraoperative fluoroscopy and a "double surgeon" control. Mucosa closure was attempted with robotic arms. We succeeded in performing a sellar opening in all cadavers with a minimally invasive approach, as the hard palate was never drilled. The video endoscope offered a large view inside the sphenoidal sinus, as observed in transnasal endoscopy, but with 3D visualization. The camera arm could be inserted into the sphenoidal sinus, and instrument arms in the pituitary fossa. Operative time to reach the pituitary fossa was approximately 60 min in all procedures: 20 min of initial setup, 10 min of mucosal dissection, and 30 min of sphenoid surgery. New anatomical landmarks were defined. Advantages and pitfalls of such an unpublished technique were discussed. This is the first cadaveric study reported da Vinci robotic transoral approach to the sella turcica with a minimally invasive procedure. This innovative technique may modify the usual pituitary adenoma removal as the sella is approached infero-superiorly.
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Procedimentos Neurocirúrgicos/métodos , Robótica/métodos , Sela Túrcica/cirurgia , Base do Crânio/cirurgia , Idoso , Idoso de 80 Anos ou mais , Cadáver , Estudos de Viabilidade , Feminino , Humanos , Imageamento Tridimensional , Masculino , Palato Mole/anatomia & histologia , Palato Mole/cirurgia , Sela Túrcica/anatomia & histologia , Base do Crânio/anatomia & histologia , Seio Esfenoidal/anatomia & histologia , Seio Esfenoidal/cirurgia , Cirurgia Assistida por ComputadorRESUMO
BACKGROUND: Treatment options for congenital hypoplastic breast anomalies are often open, including radial scoring, parenchymal flaps, and insertion of expanders and implants. Drawbacks of open techniques involve scarring, the use of drains, and inpatient stays. The use of lipofilling to treat breast deformities is increasing, as more research is completed in this area. PATIENTS AND METHODS: We report a retrospective study of 10 patients below the age of 20 following autologous fat transfer between January 1, 2003 and January 1, 2004. (2 Poland syndrome, 3 bilateral tuberous breast, and 5 unilateral micromastia). Age, cup size, the number of sessions, time interval between each session, volumes injected, and complications were recorded. Postoperative mammography, ultrasonography, and MRI were assessed by a specialized radiologist. Patients answered a questionnaire 1 year after the procedure. RESULTS: Mean follow-up was 68 months (60-77 months) and mean age was 17.5 years (15-20 years). Mean number of fat injection sessions was 2 (1-4) and mean volume injected 285 mL per breast (200-500 mL). The time interval between each session was 5 months (3-6 months). Cup size remained unchanged after at least 5 years of follow-up. One case underwent a contralateral breast reduction. The cosmetic results considered satisfactory in almost all the patients after 1 year of follow-up. None of our patients complained of scars or defects at the donor site. All breasts imaging were normal except 1 patient with oil cysts. CONCLUSION: Our preliminary results using lipofilling to treat young patients with breast hypoplasia with lipofilling are very encouraging. The authors believe it is an alternative of choice for the correction of the young woman's breast deformities if the avoidance of scarring is preferred.
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Doenças Mamárias/congênito , Doenças Mamárias/cirurgia , Mamoplastia/métodos , Gordura Subcutânea/transplante , Adolescente , Feminino , Seguimentos , Humanos , Lipectomia , Satisfação do Paciente , Síndrome de Poland/cirurgia , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Neurofibromatosis type 1 (NF1) is a common dominant tumor predisposition syndrome affecting 1 in 3,500 individuals. The hallmarks of NF1 are the development of peripheral nerve sheath tumors either benign (dermal and plexiform neurofibromas) or malignant (MPNSTs). RESULTS: To comprehensively characterize the role of microRNAs in NF1 tumorigenesis, we analyzed 377 miRNAs expression in a large panel of dermal and plexiform neurofibromas, and MPNSTs. The most significantly upregulated miRNA in plexiform neurofibromas was miR-486-3p that targets the major tumor suppressor gene, PTEN. We confirmed PTEN downregulation at mRNA level. In plexiform neurofibromas, we also report aberrant expression of four miRNAs involved in the RAS-MAPK pathway (miR-370, miR-143, miR-181a, and miR-145). In MPNSTs, significant deregulated miRNAs were involved in PTEN repression (miR-301a, miR-19a, and miR-106b), RAS-MAPK pathway regulation (Let-7b, miR-195, and miR-10b), mesenchymal transition (miR-200c, let-7b, miR-135a, miR-135b, and miR-9), HOX genes expression (miR-210, miR-196b, miR-10a, miR-10b, and miR-9), and cell cycle progression (miR-195, let-7b, miR-20a, miR-210, miR-129-3p, miR-449a, and miR-106b). CONCLUSION: We confirmed the implication of PTEN in genesis of plexiform neurofibromas and MPNSTs in NF1. Markedly deregulated miRNAs might have potential diagnostic or prognostic value and could represent novel strategies for effective pharmacological therapies of NF1 tumors.
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Perfilação da Expressão Gênica , MicroRNAs/genética , Neurofibromatose 1/genética , Neurofibromatose 1/patologia , PTEN Fosfo-Hidrolase/metabolismo , Transdução de Sinais/genética , Proteínas Argonautas/genética , Linhagem Celular Tumoral , Análise por Conglomerados , Humanos , Neurofibroma Plexiforme/genética , Neurofibroma Plexiforme/patologia , Proteínas/genética , Proteínas de Ligação a RNA , Ribonuclease III/genética , Homologia de Sequência do Ácido Nucleico , Fatores de TempoRESUMO
BACKGROUND: Venous thrombosis is the main cause of radial forearm flap failure, especially when recipient vessels are compromised by prior radiation therapy or neck dissection. In such conditions, semi-free radial forearm flap (SF-RFF) can be performed to reduce this risk. PATIENTS AND METHOD: We reviewed all SF-RFF procedures performed in our institution for head and neck reconstruction. The flap was harvested as a conventional radial forearm flap but the cephalic vein was dissected along the arm up to the deltopectoral crease and used as the sole drainage vein. RESULT: Seven SF-RFFs were harvested for head and neck reconstructions. The dissection of the cephalic vein lasted less than 25 min in all cases. No flap loss or thrombosis was observed. CONCLUSION: The SF-RFF is a reliable and versatile procedure for facial, oral, or larynx reconstruction. This hybrid version of the radial forearm free flap is particularly appropriate when no suitable recipient veins are available as a result of radiation or prior surgery.
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Retalhos de Tecido Biológico/irrigação sanguínea , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias de Cabeça e Pescoço/cirurgia , Esvaziamento Cervical , Procedimentos de Cirurgia Plástica/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Antebraço/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Background: Venous anatomy of the digits and the hand is poorly reported in the literature compared to arterial anatomy. While knowledge of the venous anatomy is crucial to ensure safe skin incisions, skin flap design, or blood return restoration for digital replantations, data in anatomical and clinical textbooks are rather limited. The purpose of this anatomical study was to describe the venous anatomy of the digits and the hand. Method: Our series reports descriptive results from 10 non-embalmed hand dissections from 5 different corpses. Hands were previously co-injected by arteries followed by veins with a different colored latex before being dissected under optical magnification (x4). Each anatomical specimen was photographed before being analyzed. Results: Each injection revealed both arterial and venous vascular systems. Latex injections were a useful technique to show the dorsal, volar superficial, and deep venous system. There was a constant and reliable topographic vascular anatomy of the superficial venous system of the digits and hand. However, we could not observe a high density of dorsal superficial venous valves as previously reported. Conclusion: The knowledge of the arrangement of the venous system of the digits and the hand should help the surgeon when performing surgical procedures in the hand. The surgeon should take into consideration this venous anatomy when performing skin incisions, skin flaps, or replantation procedures which would preserve the normal venous physiology as much as possible.
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BACKGROUND: Serosanguinous drainage after breast reconstruction by deep inferior epigastric perforator flap (DIEP) can limit patient's discharge. We introduced fibrin sealant in immediate breast reconstruction by DIEP flap to reduce drainage after mastectomy with axillary dissection. MATERIALS AND METHODS: We performed an open study on 30 consecutive female aged from 28 to 63 years old. All underwent immediate breast reconstructions by DIEP flaps after mastectomy and axillary dissection for cancer. Patients were divided in group 1 (N = 15) without fibrin sealant and group 2 (N = 15) where the flap, thoracic, and axillary areas were sprayed with 5 mL of liquid fibrin sealant before drains insertion. There was no difference in the patient's BMI, height, weight or age between both the groups. Blake suction drains were placed under the flap and in the axillary area. RESULTS: No adverse effects were reported, after a 20-month median follow-up. Drainage volumes or durations were not correlated to the patient's BMI, nor the height, weight or age. Thoracic drainage duration was longer than abdominal drainage in both the groups. Average drained volumes from the thoracic area were lower (427 vs. 552 mL; P = 0.015) and thoracic drains were removed earlier (5.47 vs. 6.33 days P = 0.022), in group 2 than in group 1. The length of stay was also reduced after the use of fibrin sealant (5.53 vs. 6.33 days; P = 0.032). CONCLUSION: This study introduce the interest of fibrin sealant to significantly decrease the postoperative drainage volume and duration in the thoracic area after immediate breast reconstruction by DIEP flap.
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Adesivo Tecidual de Fibrina/uso terapêutico , Mamoplastia , Adesivos Teciduais/uso terapêutico , Adulto , Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/cirurgia , Feminino , Humanos , Tempo de Internação , Excisão de Linfonodo , Mastectomia Radical Modificada , Pessoa de Meia-Idade , Período Pós-Operatório , Retalhos Cirúrgicos , Adulto JovemRESUMO
The objective of this review article is to summarize the published details and media citations for all seven face transplants performed to date to point out deficiencies in those reports so as to provide the basis for examining where the field of face transplantation stands, and to act as a stimulus to enhance the quality of future reports and functional outcomes. Overall long-term function of facial alloflaps has been reported satisfactorily in all seven cases. Sensory recovery ranges between 3 and 6 months, and acceptable motor recovery ranges between 9 and 12 months. The risks and benefits of facial composite tissue allotransplantation, which involves mandatory lifelong immunosuppression analogous to kidney transplants, should be deliberated by each institution's multidisciplinary face transplant team. Face transplantation has been shown thus far to be a viable option in some patients suffering severe facial deficits which are not amenable to modern-day reconstructive technique.
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Traumatismos Faciais/cirurgia , Transplante de Face , Adulto , Queimaduras por Corrente Elétrica/cirurgia , Transplante de Face/efeitos adversos , Feminino , Rejeição de Enxerto/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Neurofibromatose 1/cirurgia , Complicações Pós-Operatórias/epidemiologia , Recuperação de Função Fisiológica , Estudos Retrospectivos , Resultado do Tratamento , Ferimentos por Arma de Fogo/cirurgiaRESUMO
Since 2005, at least 38 face transplantations have been performed worldwide. Available recommendations on psychological management are based on isolated cases or small case series, either not focused on mental health or with a short follow-up. We propose herein a clinical commentary on psychological and psychiatric outcomes from the follow-up of a prospective single-center cohort of six patients over a period of 3.5 to 9â¯years. Seven patients received a face transplant between January 2007 and April 2011: two patients with neurofibromatosis, four with self-inflicted ballistic trauma, one with self-immolation. One patient died at 63â¯days of cerebral sequelae from cardiac arrest in the setting of bacterial infection. The six other patients were routinely evaluated with unstructured psychological interviews up to May 2016 and with the Short Form 36-item health survey and the Mini-International Neuropsychiatric Interview at one year and at the end of the follow-up. Clinically meaningful observations were the following: a history of mental disorders before disfigurement was associated with poor physical and mental outcomes, including poor adherence and one suicide; untreated depression was associated with poor adherence; acceptance of the new face occurred rapidly and without significant distress in all of the patients; fear of transplant rejection was present to some degree in all of the patients and did not substantially differ from other transplantation settings; media exposure may be disturbing but may also have had positive psychological effects on some of the patients. Mental health issues related to chronic rejection and re-transplantation remain to be explored.
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Transplante de Face/psicologia , Adulto , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
The management of large congenital melanocytic nevi (lCMN) is based exclusively on iterative surgical procedures in the absence of validated medical therapy. The aim of our study was to develop an intra-lesional medical treatment for lCMN. Seventeen patients harboring NRAS-mutated lCMN were included. Nevocytes obtained from lCMN displayed an overactivation of mitogen-activated protein kinase and phosphoinositide 3-kinase (Akt) pathways. Mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK) and Akt inhibitors reduced the nevosphere diameter in sphere-forming assays, as well as cell viability and proliferation in in vitro assays. Standardized lCMN explants were then cultured ex vivo with the same inhibitors, which induced a decrease in MelanA+ and Sox10+ cells in both epidermis and dermis. Finally, intradermal injections of these inhibitors were administered within standardized lCMN xenografts in Rag2-/- mice. They induced a dramatic decrease in nevocytes in treated xenografts, which persisted 30 days after the end of treatment. Using original nevus explant and xenograft preclinical models, we demonstrated that intradermal MEK/Akt inhibition might serve as neoadjuvant therapy for the treatment of NRAS-mutated congenital melanocytic nevi to avoid iterative surgeries.
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Antineoplásicos/administração & dosagem , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Nevo Pigmentado/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Neoplasias Cutâneas/tratamento farmacológico , Animais , Proliferação de Células/efeitos dos fármacos , Criança , Pré-Escolar , Feminino , GTP Fosfo-Hidrolases/genética , Humanos , Lactente , Injeções Intradérmicas , Injeções Intralesionais , Antígeno MART-1/metabolismo , Masculino , Melanócitos/efeitos dos fármacos , Melanócitos/patologia , Proteínas de Membrana/genética , Camundongos , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Nevo Pigmentado/congênito , Nevo Pigmentado/genética , Nevo Pigmentado/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fatores de Transcrição SOXE/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Pele/citologia , Pele/patologia , Neoplasias Cutâneas/congênito , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The deep inferior epigastric perforator (DIEP) flap is a workhorse of breast reconstruction. Risks of herniation derive from violation of the rectus abdominis muscle anterior rectus sheath and might be reduced by minimally invasive laparoscopic dissection ("MILD") of the deep inferior epigastric vessels. The authors performed a feasibility study on five anatomical subjects and performed a secondary right breast reconstruction on a 67-year-old woman. A 30-degree laparoscope was used with laparoscopy ports inset to preserve the flap. Blunt preperitoneal dissection followed by carbon dioxide insufflation allowed the deep inferior epigastric pedicle to be dissected and clip-sectioned. The anterior rectus sheath was opened around the perforating vessels, and the flap was anastomosed on the internal mammary vessels. The length of incision in the anterior rectus sheath was compared between laparoscopic and conventional approaches. The mean incision length in the anterior rectus sheath was 3 cm versus 12 cm in the classic approach. Average duration of laparoscopic flap harvest was 50 minutes, including a mean of 30 minutes for deep inferior epigastric dissection. Adhesions led to a 1-cm peritoneal laceration in our first anatomical subject. There were no preoperative or postoperative complications in the clinical case. The clinical procedure duration was 8 hours 15 minutes, with the anterior rectus sheath incision reduced from the conventional 12 cm to 5 cm. Flap ischemia lasted 50 minutes. The patient was discharged on postoperative day 5. This anatomical study and first successful laparoscope-assisted DIEP flap harvest prove that reduced trauma to the anterior rectus sheath is feasible and promising.