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The current benchmark for tongue reconstruction following the excision of locally advanced tumors involves the utilization of free skin or fasciocutaneous flaps, such as anterolateral thigh flap or forearm free flap. They facilitate the volumetric reconstruction of the tongue, leveraging passive mobility from the remaining native tongue tissue. The challenge in tongue reconstruction surgery persists in achieving functional restoration through adequate volume and optimized mobility, using tissue that is both adapted and comparable to native tissue. While the free serratus muscle flap has been described for various indications, its application in tongue reconstructions remains underexploited. Specifically, in cases of locally advanced tumors affecting the mobile tongue, typically within the junctional area and without extension to the floor of the mouth nor to the tip of the tongue, the serratus free flap has shown great results. Reinnervation of the flap is achieved connecting the thoracodorsal nerve to the descending branch of the XII nerve. This technique facilitates functional tongue reconstruction, promoting rapid mucosal epithelialization and reinnervation, which, in turn, preserves muscle volume and sustains adequate trophicity without fibrosis. Regarding these considerations, the pure muscle serratus free flap emerges as a valuable and effective alternative in tongue reconstruction. Notably, there is a dearth of step-by-step operative technique descriptions for this indication in the existing literature. We present a video demonstrating the surgical technique, showcasing procedures as performed at Tenon Hospital (Paris, France).
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OBJECTIVE: Hypoparathyroidism is a known complication of total laryngectomy, although parathyroid preservation and/or reimplantation are not routine. Autofluorescence is a new technique for identifying parathyroid glands intraoperatively. The aim of this study was to evaluate the feasibility of autofluorescence in this context. MATERIALS AND METHODS: A retrospective study of patients undergoing total laryngectomy/pharyngectomy with concomitant thyroidectomy using the Fluobeam® (Fluoptics, Grenoble, France) and frozen section of a parathyroid fragment in case of reimplantation. The rates of identification using autofluorescence, reimplantation, and hypoparathyroidism were evaluated. RESULTS: Eighteen patients (16 males, median age 67) underwent total laryngectomy/pharyngectomy with total thyroidectomy (n = 12) or hemithyroidectomy (n = 6). A median of 2 parathyroid glands were identified per patient. Ninety-two percent were identified by autofluorescence before visualisation. All parathyroids were reimplanted due to devascularization. Temporary hypoparathyroidism occurred in nine patients, and was permanent in one patient. After 34 months of median follow-up (range 1-49), no tumor recurrence was observed in the reimplantation sites. CONCLUSIONS: To our knowledge, this is the largest study to evaluate autofluorescence during total laryngectomy with thyroidectomy. No tumor recurrence occurred in the sites of parathyroid reimplantation.
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Hypoparathyroidism is the most frequent complication in thyroid surgery. The aim of this study was to evaluate the impact of intraoperative parathyroid gland identification, using autofluorescence imaging, on the rate of post-operative (PO) hypoparathyroidism in thyroid cancer surgery. Patients undergoing total thyroidectomy with central neck dissection from 2018 to 2022 were included. A prospective cohort of 77 patients operated on using near-infrared autofluorescence (NIRAF+) with the Fluobeam® (Fluoptics, Grenoble, France) system was compared to a retrospective cohort of 94 patients (NIR-). The main outcomes were the rate of PO hypocalcemia, with three cutoffs: corrected calcium (Cac) < 2.10 mmol/L, <2.00 mmol/L and <1.875 mmol/L, and the rate of permanent hypoparathyroidism, at 12 months. The rate of PO Cac < 2.10 mmol/L was statistically lower in the NIRAF+ group, compared to the control group (36% and 60%, p = 0.003, respectively). No statistically significant difference was observed for the other two thresholds. There was a lower rate of permanent hypoparathyroidism in the NIRAF+ group (5% vs. 14% in the control group), although not statistically significant (p = 0.07). NIRAF is a surgically non-invasive adjunct, and can improve patients' outcomes for thyroid cancer surgery by reducing post-operative temporary hypoparathyroidism. Larger prospective studies are warranted to validate our findings.
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Oculopharyngeal muscular dystrophy (OPMD) is a rare muscle disease characterized by an onset of weakness in the pharyngeal and eyelid muscles. The disease is caused by the extension of a polyalanine tract in the Poly(A) Binding Protein Nuclear 1 (PABPN1) protein leading to the formation of intranuclear inclusions or aggregates in the muscle of OPMD patients. Despite numerous studies stressing the deleterious role of nuclear inclusions in cellular and animal OPMD models, their exact contribution to human disease is still unclear. In this study, we used a large and unique collection of human muscle biopsy samples to perform an in-depth analysis of PABPN1 aggregates in relation to age, genotype and muscle status with the final aim to improve our understanding of OPMD physiopathology. Here we demonstrate that age and genotype influence PABPN1 aggregates: the percentage of myonuclei containing PABPN1 aggregates increases with age and the chaperone HSP70 co-localize more frequently with PABPN1 aggregates with a larger polyalanine tract. In addition to the previously described PRMT1 and HSP70 co-factors, we identified new components of PABPN1 aggregates including GRP78/BiP, RPL24 and p62. We also observed that myonuclei containing aggregates are larger than myonuclei without. When comparing two muscles from the same patient, a similar amount of aggregates is observed in different muscles, except for the pharyngeal muscle where fewer aggregates are observed. This could be due to the peculiar nature of this muscle which has a low level of PAPBN1 and contains regenerating fibers. To confirm the fate of PABPN1 aggregates in a regenerating muscle, we generated a xenograft model by transplanting human OPMD muscle biopsy samples into the hindlimb of an immunodeficient mouse. Xenografts from subjects with OPMD displayed regeneration of human myofibers and PABPN1 aggregates were rapidly present-although to a lower extent-after muscle fiber regeneration. Our data obtained on human OPMD samples add support to the dual non-exclusive models in OPMD combining toxic PABPN1 intranuclear inclusions together with PABPN1 loss of function which altogether result in this late-onset and muscle selective disease.
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Distrofia Muscular Oculofaríngea , Humanos , Ratones , Animales , Distrofia Muscular Oculofaríngea/genética , Distrofia Muscular Oculofaríngea/patología , Cuerpos de Inclusión Intranucleares/metabolismo , Cuerpos de Inclusión Intranucleares/patología , Xenoinjertos , Modelos Animales de Enfermedad , Chaperonas Moleculares/metabolismo , Proteína I de Unión a Poli(A)/genética , Proteína I de Unión a Poli(A)/metabolismo , Proteína-Arginina N-Metiltransferasas/metabolismo , Proteínas Represoras/metabolismoRESUMEN
OBJECTIVES: The aims of this study were first to calculate the Positive Predictive Value (PPV) of DW-MRI to detect cholesteatoma and then to analyze false positives. METHODS: All temporal bone MRI with DWI sequences performed in our pediatric university hospital between 2005 and 2015 were included retrospectively. 46 patients with a cholesteatoma diagnosis on the MRI report and who underwent surgery were studied. RESULTS: The number of DW-MRI for identification of cholesteatoma has grown in ten years. We calculated an 89% Positive Predictive Value. DW-MRI sensitivities were 100.0% and 70.7% for respectively keratin and squamous epithelium. CONCLUSION: DW-MRI hypersignal is not synonymous of cholesteatoma diagnosis. Indeed, this diagnosis relies on the importance of a proper otoscopic examination, a suggestive medical history, CT scan data and analysis of other MRI sequences, including T1-weighted sequence, to rule out other etiologies of middle ear DW-MRI hypersignal.
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Colesteatoma del Oído Medio , Imagen de Difusión por Resonancia Magnética , Niño , Colesteatoma del Oído Medio/diagnóstico por imagen , Colesteatoma del Oído Medio/cirugía , Humanos , Imagen por Resonancia Magnética , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
The adeno-associated virus (AAV) vector is an efficient tool for gene delivery in skeletal muscle. AAV-based therapies show promising results for treatment of various genetic disorders, including muscular dystrophy. These dystrophies represent a heterogeneous group of diseases affecting muscles and typically characterized by progressive skeletal muscle wasting and weakness and the development of fibrosis. The tropism of each AAV serotype has been extensively studied using systemic delivery routes, but very few studies have compared their transduction efficiency through direct intramuscular injection. Yet, in some muscular dystrophies, where only a few muscles are primarily affected, a local intramuscular injection to target these muscles would be the most appropriate route. A comprehensive comparison between different recombinant AAV (rAAV) serotypes is therefore needed. In this study, we investigated the transduction efficiency of rAAV serotypes 1-10 by local injection in skeletal muscle of control C57BL/6 mice. We used a CMV-nls-LacZ reporter cassette allowing nuclear expression of LacZ to easily localize targeted cells. Detection of ß-galactosidase activity on muscle cryosections demonstrated that rAAV serotypes 1, 7, 8, 9, and 10 were more efficient than the others, with rAAV9 being the most efficient in mice. Furthermore, using a model of human muscle xenograft in immunodeficient mice, we observed that in human muscle, rAAV8 and rAAV9 had similar transduction efficiency. These findings demonstrate for the first time that the human muscle xenograft can be used to evaluate AAV-based therapeutical approaches in a human context.
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Dependovirus/genética , Técnicas de Transferencia de Gen , Vectores Genéticos/genética , Músculo Esquelético/metabolismo , Transducción Genética , Animales , Dependovirus/clasificación , Femenino , Expresión Génica , Genes Reporteros , Terapia Genética/métodos , Vectores Genéticos/administración & dosificación , Humanos , Inyecciones Intramusculares , Masculino , Ratones , Ratones Noqueados , Ratones Transgénicos , Serogrupo , TransgenesRESUMEN
OBJECTIVES: The benefits of a rehabilitation programme before lung surgical resection for cancer remain to be defined. The purpose of this observational study was to assess the efficacy of preoperative rehabilitation and postoperative rehabilitation on short- and long-term outcomes in patients who were at high operative risk. METHODS: Between January 2010 and December 2012, 20 consecutive non-operable patients (16 men and 4 women, mean age 66 years) with clinical N0 lung cancer were included. Eligibility criteria were lung function below guideline thresholds and/or associated severe comorbidities. The protocol included a cardiorespiratory perioperative rehabilitation programme. These patients were followed up at 5 years. RESULTS: The average increase in forced expiratory volume (FEV)1 and of VO2max preoperatively was 12% and 3.5 ml/kg/min, respectively. All patients underwent a pulmonary surgical resection procedure. The morbidity and mortality rates were 20% and 5%, respectively. Nineteen patients returned home upon the completion of postoperative rehabilitation. After 5-year follow-up, the Kaplan-Meier 5-year survival rate was 52%. CONCLUSIONS: Perioperative pulmonary rehabilitation seems to allow surgical management of lung cancer by lung resection in first-line, non-eligible patients. The long-term survival of operated high-risk patients is encouraging despite the high complication rate.
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Neoplasias Pulmonares/cirugía , Pulmón/fisiopatología , Neumonectomía/métodos , Adulto , Anciano , Femenino , Estudios de Seguimiento , Volumen Espiratorio Forzado , Francia/epidemiología , Humanos , Pulmón/cirugía , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/rehabilitación , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Pruebas de Función Respiratoria , Tasa de Supervivencia/tendencias , Factores de TiempoRESUMEN
BACKGROUND: The interval between surgery and adjuvant chemotherapy (AC) is a predictive factor of survival in high-risk colon cancer (CC). This study aimed to evaluate the impact of intraoperative sentinel lymph node (SLN) analysis using the one-step nucleic acid amplification (OSNA) technique on the time interval between surgery and AC. METHODS: We performed a prospective study analyzing 56 consecutive patients who had surgery for CC between July 2012 and October 2014, including 20 patients needing AC. SLN status was determined intraoperatively in 17 patients in the OSNA group; when positive, a portacath (PAC) was placed during the procedure for upcoming AC. In the remaining patients, we proceeded without SLN status determination and the PAC was installed after definitive histopathological analysis of the specimen if needed. RESULTS: There was no difference between the groups regarding cancer staging, duration of hospitalization (7.5days in the OSNA group and 10days in the control group, p=0.43) and major complications (20% vs 30% respectively, p=0.55). The time interval between surgery and adjuvant chemotherapy was significantly shorter in the OSNA group at 35 (±8) days vs 67 (±36) days (p=0.021). CONCLUSION: SLN status determination by the OSNA technique is safe, feasible and could significantly reduce time between surgery and adjuvant chemotherapy in a pilot study.