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PURPOSE: Laryngeal chondrosarcoma is a rare tumor that mostly affects the cricoid cartilage. The aim of this study was to compare outcomes between the various treatments of this pathology as there are no official guidelines for this pathology. METHODS: A retrospective analysis of the pathology database of nine French tertiary care centers was conducted. Outcomes of patients treated by total laryngectomy were compared with those treated by more conservative approaches (endoscopic debulking, median thyrotomy, partial laryngectomy). Two Kaplan-Meier survival analyses were performed: one to assess the overall survival rate and the other to assess laryngeal preservation over time. RESULTS: A total of 43 patients were enrolled: 12 with total laryngectomy as the initial treatment, and 31 who initially underwent laryngeal-preserving treatment. With conservative treatment, laryngeal function was preserved in 96% and 75% of patients at 1 and 5 years, respectively. Conservative treatment did not reduce the overall survival rate. CONCLUSION: These results suggest that laryngeal preservation should be considered as the initial treatment in cases of laryngeal chondrosarcoma.
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Neoplasias Ósseas , Condrossarcoma , Neoplasias Laríngeas , Laringe , Humanos , Estudos Retrospectivos , Condrossarcoma/cirurgia , Laringe/patologia , Neoplasias Laríngeas/cirurgia , Laringectomia/métodos , Neoplasias Ósseas/cirurgia , Resultado do TratamentoRESUMO
PURPOSE: Radiological assessment of osseointegration of mastoid grafts: biological hydroxyapatite (Bio-Oss®) (BHA) versus bioglass S53P4 (Bonalive®) (BG). METHODS: Retrospective (10 ± 4 months post-surgery) monocentric high resolution computed tomography (CT) scan assessment (November 2018 and October 2020) by two independent radiologists (R1, R2), blinded to patient allocation. All patients who had undergone a total mastoid obliteration were eligible. Excluded: complications namely otological acute or chronic infections, unbalanced metabolic disease, long-term cortico-steroid therapy, auto-immune disease, history of allergy to grafting materials and post-surgery CT scan in other centers (n = 8). PRIMARY OUTCOMES: the ratio between two regions of interests (ROI) (graft to otic capsule). SECONDARY OUTCOMES: resorption of mastoid grafts and assessment of clinical tolerance. RESULTS: Included 21 patients (mean age: 29 ± 21 years; 5 females, 16 males). Significantly higher osseointegration for BHA vs. BG (R1 p = 0.043; R2 p = 0.004); almost perfect inter-reader agreement k = 0.922). The ROI ratios for BHA and BG to that of the otic capsule were 0.57 ± 0.11 (R1) and 0.59 ± 0.14 (R2); 0.43 ± 0.11 (R1) and 0.43 ± 0.08 (R2), respectively. Density increased significantly by 399 ± 261 Hounsfield units (HU) (p = 0.008) and decreased by 464 ± 161 HU (p < 0.001) for BHA vs. BG. Resorption rates were 24.1 ± 21.0% and 66.7 ± 15.1% (p = 0.076), respectively. No significant difference in clinical tolerance was observed. CONCLUSION: Post-operative CT scan of mastoid obliteration seems reliable in assessment of biomaterial graft's mid-term feasibility and stability: BHA seems to provide a more optimal osseointegration versus BG with no significant differences in graft resorption and clinical tolerance.
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Colesteatoma da Orelha Média , Processo Mastoide , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Cerâmica , Colesteatoma da Orelha Média/cirurgia , Durapatita , Processo Mastoide/diagnóstico por imagem , Processo Mastoide/cirurgia , Estudos RetrospectivosRESUMO
PURPOSE: Posttreatment follow-up for the recurrence of head and neck squamous cell carcinoma (HNSCC) is a diagnostic challenge. Tissue distortion from radiation and surgery can obscure early detection of recurrence by conventional follow-up approaches such as physical examination or conventional imaging. Fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT is widely validated for the diagnosis of suspected recurrence. Moreover, we have shown in a previous prospective study the high effectiveness of FDG PET/CT in the assessment of subclinical recurrence 12 months after treatment. The aim of this prospective study was to evaluate the effectiveness of an earlier FDG PET/CT, at 6 months after the end of treatment. METHODS: All patients treated for histologically proven HNSCC from April 2009 to May 2012 at the University Hospital of Brest who did not show any findings suggestive of recurrence at 6 months of their usual follow-up underwent an FDG PET/CT examination. FDG PET/CT findings were correlated with histopathology or imaging follow-up. RESULTS: The study included 116 patients. FDG PET/CT examinations were performed within a mean period ± SD of 5.6 ± 1.8 months after treatment. FDG PET/CT examinations exhibited abnormal FDG uptake in 34 patients and found no suspected recurrence in 82 cases. Of these 82 FDG PET/CT considered as negative, only 1 had a recurrence. Among the 34 positive FDG PET/CT, 22 relapsed whereas 12 did not show evidence of recurrence. The sensitivity and specificity of FDG PET/CT in this study for the diagnosis of occult HNSCC recurrence were 96 (22/23) and 87 % (81/93), respectively. The positive predictive value was 65 % (22/34). The negative predictive value was 99 % (81/82). The overall accuracy was 89 % (103/116). Of the 116 patients, FDG PET/CT highlighted 22 (19 %) subclinical recurrences. CONCLUSION: Our study showed the high effectiveness of FDG PET/CT in the assessment of subclinical HNSCC recurrence 6 months after completion of treatment. These results confirmed that FDG PET/CT is more accurate than conventional follow-up physical examination alone in the assessment of recurrence after previous curative treatment for HNSCC, as we previously demonstrated in patients clinically asymptomatic at 12 months.
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Carcinoma de Células Escamosas/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Idoso , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos , Recidiva , Sensibilidade e Especificidade , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
PURPOSE: The objective of this study was to investigate the value of metabolic tumour volume (MTV) assessed with (18)F-FDG PET/CT in predicting event-free survival (EFS) and overall survival (OS) in patients with head and neck squamous cell carcinoma (HNSCC), and particularly to compare it with more conventional parameters such as maximum standardized uptake value (SUVmax). METHODS: Patients referred to our department for (18)F-FDG PET/CT for staging of HNSCC were prospectively included between February 2009 and March 2011. Each patient was scanned using a Philips Gemini PET/CT system at 1 h after injection. The MTV was calculated semiautomatically for the primary site using methods based on SUV with various thresholds: 3-D contour around voxels equal to or greater than 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5 and 7.0 times SUV, or more than 30%, 40% and 50% of SUVmax. ROC analysis was used to test the statistical significance of the differences among the calculated MTVs. EFS and OS were determined using the Kaplan-Meier method and compared with MTV in univariate and multivariate analyses, including the usual prognostic factors: age, sex, primary site, treatment, SCC histologic grade, AJCC stage, TNM classification, tumour SUVmax and SUVpeak. RESULTS: The study included 80 consecutive patients (70 men, 10 women; mean age 62.4 ± 9.0 years). ROC analysis revealed that pretreatment MTV using a threshold of 5.0 times SUV (MTV5.0) was the best parameter to predict recurrence and death after treatment. In univariate analysis, MTV5.0 >4.9 ml was predictive of poor EFS (p < 0.0001) and poor OS (p < 0.0001). In multivariate, MTV5.0 persisted as an independent predictive factor for EFS (p = 0.011) and OS (p = 0.010), while SUVmax became nonsignificant (p = 0.277 for EFS, p = 0.975 for OS). CONCLUSION: Our results suggest that MTV measured by (18)F-FDG PET/CT has independent prognostic value of in patients with HNSCC, stronger than SUVmax.
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Carcinoma de Células Escamosas/diagnóstico por imagem , Fluordesoxiglucose F18 , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos TestesRESUMO
Head and neck squamous cell carcinoma (HNSCC) remains a malignancy with high rates of locoregional recurrence and poor prognosis for recurrent cases. Early detection of subclinical lesions is challenging but critical for effective patient management. Imaging surveillance after treatment, particularly 18F-FDG PET/CT, has shown promise in the diagnosis of HNSCC recurrence. The aim was to evaluate the diagnostic performance of 18F-FDG PET/CT according to delay after treatment in detecting subclinical recurrence (SCR) in HNSCC patients. Methods: In this retrospective study, all 18F-FDG PET/CT scans were performed at a single center. All adults with histologically proven HNSCC who were treated with curative intent between January 1, 2006, and December 31, 2021, were included. They had a normal clinical examination before each scan. Patients who underwent an intensive follow-up strategy after treatment had 18F-FDG PET/CT with an intravenous contrast agent at 3-6 mo and annually thereafter for 5 y. The primary endpoint was diagnostic performance (positive and negative predictive values, sensitivity, specificity, and accuracy). Results: In total, 2,566 18F-FDG PET/CT scans were performed among 852 patients, with an average of 3 scans per patient. The overall diagnostic performance measures were as follows: positive predictive value (88%), negative predictive value (98%), sensitivity (98%), specificity (89%), and accuracy (93%). There were no significant differences in diagnostic performance over time. The scans detected 126 cases of SCR (14.8%) and 118 cases of metachronous cancer (13.8%). The incidence of SCR decreased over time, with the highest detection rate in the first 2 y after treatment. Positive predictive value improved over time, reaching 90% for the digital Vision 600 system (third period) compared with 76% for the analog Gemini GXLi system (first period, P < 0.001). Multivariate analysis identified advanced stage, high body mass index, and initial PET/CT upstaging as predictive factors for detection of SCR. Conclusion: Our study demonstrates that 18F-FDG PET/CT has high diagnostic performance in detecting SCR during follow-up after treatment of HNSCC, especially in the first 2 y. Advanced tumor stage, initial PET/CT upstaging, and high body mass index were associated with a higher likelihood of SCR detection. The routine use of 18F-FDG PET/CT during follow-up seems justified for patients with HNSCC.
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Fluordesoxiglucose F18 , Neoplasias de Cabeça e Pescoço , Recidiva Local de Neoplasia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Idoso , Estudos Retrospectivos , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/terapia , Recidiva Local de Neoplasia/diagnóstico por imagem , Adulto , Idoso de 80 Anos ou maisRESUMO
Since recombinant viral vectors have been associated with serious side effects, such as immunogenicity and oncogenicity, synthetic delivery systems represent a realistic alternative for achieving efficacy in gene therapy. A major challenge for non-viral nanocarriers is the optimization of transgene expression in the targeted cells. This goal can be achieved by fine-tuning the chemical carriers and the adding specific motifs to promote cellular penetration. Our study focuses on the development of novel folate-based complexes that contain varying quantities of folate motifs. After controlling for their physical properties, neutral folate-modified lipid formulations were compared in vitro to lipoplexes leading to comparable expression levels. In addition, no cytotoxicity was detected, unlike what was observed in the cationic controls. Mechanistically, the delivery of the transgene appeared to be, in part, due to endocytosis mediated by folate receptor targeting. This mechanism was further validated by the observation that adding free folate into the medium decreased luciferase expression by 50%. In vivo transfection with the folate-modified MM18 lipid, containing the highest amount of FA-PEG(570)-diether co-lipid (w:w; 90:10), at a neutral charge ratio, gave luciferase transgene expression. These studies indicate that modification of lipids with folate residues could enhance non-toxic, cell-specific gene delivery.
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Células Epiteliais/metabolismo , Ácido Fólico/química , Lipossomos/química , Nanopartículas/química , Transfecção/métodos , Animais , Western Blotting , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Receptor 1 de Folato/metabolismo , Ácido Fólico/toxicidade , Células HeLa , Humanos , Lipossomos/toxicidade , Luciferases/genética , Luciferases/metabolismo , Camundongos , Microscopia de Fluorescência , Nanopartículas/toxicidade , Cavidade Nasal/metabolismo , Plasmídeos/química , Plasmídeos/genética , Plasmídeos/metabolismo , Reprodutibilidade dos Testes , Traqueia/metabolismoRESUMO
Cochlear implantation (CI) allows rehabilitation for patients with severe to profound hearing impairment. Although the use of a robotic assistant provides technical assistance to the surgeon, the assessment of the impact of its use on auditory outcomes remains uncertain. We aim to compare the hearing results of patients who underwent bilateral cochlear implantation; one side was performed with manual insertion and the other side with robot-assisted insertion. The electrode array intrascalar positioning and the surgery duration were also studied. This retrospective intra-individual study involved 10 patients who underwent bilateral cochlear implantation. The study included two infants and eight adults. The unique composition of this cohort enabled us to utilize each patient as their own control. Regarding speech disyllabic recognition, pure tone average, ECAP, ratio of array translocation, basilar membrane rupture, and percentage of translocated electrodes, there was no difference between manual and robot-assisted CI groups. This study is the first to compare intra-individual hearing performance after cochlear implantation, either manually or robot-assisted. The number of patients and the time delay between manual and robotic implantation may have led to a lack of power, but there was no apparent difference in hearing performance between manual and robotic implantation.
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OBJECTIVE: Hypothyroidism is the most common complication of hemithyroidectomy for thyroid nodules. This retrospective cohort study investigated the prognostic factors for hypothyroidism following hemithyroidectomy. METHODS: We included patients who underwent hemithyroidectomy between 2016 and 2017, excluding those with history of preoperative hypothyroidism or malignancy on histopathological examination. The primary endpoint was development of hypothyroidism during follow-up (TSH≥2 above normal). RESULTS: Twenty-six of the 128 included patients (20%) developed postoperative hypothyroidism. The following independent prognostic factors were found: preoperative TSH level>1.5 mIU/L (OR 2.11; P=0.013), and remaining thyroid volume adjusted for body surface area<4.0mL/m2 (OR 1.77; P=0.015). Twenty-one patients (81%) had first TSH values above the upper limit of normal. Postoperatively, first TSH level correlated significantly with the preoperative value (R=0.5779, P<0.001). Levothyroxine was prescribed to 16% of patients, with a mean dose of 0.92µg/kg/day. CONCLUSION: Patients with TSH>1.5 mIU/or remaining thyroid volume adjusted for body surface area<4.0mL/m2 should have intensified clinical and biological follow-up in the first year after surgery.
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Hipotireoidismo , Humanos , Estudos Retrospectivos , Hipotireoidismo/epidemiologia , Hipotireoidismo/etiologia , Tireoidectomia/efeitos adversos , Tiroxina , Fatores de Risco , TireotropinaRESUMO
Importance: Patients with head and neck squamous cell carcinoma (HNSCC) have a significant risk of locoregional recurrence within the first 2 years, with approximately two-thirds of patients experiencing such recurrence. While early recurrence detection may be associated with improved patient outcomes, the association of such detection with survival remains uncertain. Objective: To investigate the association of an intensive posttreatment follow-up strategy using 18F-fludeoxyglucose-positron emission tomography with computed tomography (18FDG-PET/CT) with survival among patients with HNSCC. Design, Setting, and Participants: This case-control study was conducted among patients treated at 1 of 3 locations in Brest, France (University Hospital, Military Hospital, or Pasteur Clinic). The statistical analysis was conducted from January to June 2023. All adults with histologically proven HNSCC who were treated with curative intent between January 1, 2006, and December 31, 2019, and achieved a complete response on imaging at 3 to 6 months were included. They had a minimum of 3 years of follow-up. Exposures: Patients undergoing an intensive posttreatment follow-up strategy had 18FDG-PET/CT (PET/CT group) at months 12, 24, and 36, chosen at the discretion of ear, nose, and throat surgeons. Main Outcomes and Measures: Overall survival (OS) at 3 years. Results: Among 782 patients with HNSCC (642 males [82.1%]; median [IQR] age, 61 [56-68] years), 497 patients had 18FDG-PET/CT during follow-up and 285 patients had conventional follow-up (CFU group). Cox regression analysis showed an association between undergoing 18FDG-PET/CT and lower risk of death (odds ratio, 0.71; 95% CI, 0.57-0.88; P = .002) after adjustment for covariates (age, sex, comorbidities, primary location, stage, surgeon, year of treatment, and treatment). The mean (SD) 3-year OS was significantly better in the PET/CT vs CFU group (72.5% [2.0%] vs 64.3% [2.9%]; P = .002). Analysis based on American Joint Committee on Cancer stage showed significantly better mean (SD) 3-year OS for advanced stages III and IV in the PET/CT group (373 patients) vs CFU group (180 patients; 68.5% [2.4%] vs 55.4% [3.8%]; P < .001), while no significant difference was observed between patients with stage I or II HNSCC. Analysis based on primary tumor site revealed significantly longer mean (SD) 3-year OS for oropharyngeal tumor in the PET/CT group (176 patients) than the CFU group (100 patients; 69.9% [3.5%] vs 60.5% [5.0%]; P = .04). Conclusions and relevance: This case-control study found that use of 18FDG-PET/CT in the standard annual CFU of HNSCC was associated with a 3-year survival benefit, with a larger benefit for patients with advanced initial tumor stage (III-IV) and oropharyngeal disease.
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Neoplasias de Cabeça e Pescoço , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Masculino , Adulto , Humanos , Pessoa de Meia-Idade , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18 , Seguimentos , Estudos de Casos e Controles , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/terapia , Recidiva Local de Neoplasia , Tomografia por Emissão de PósitronsRESUMO
INTRODUCTION: Presbycusis is the physiological decrease in hearing due to advancing age and begins well before the sixth decade. These recommendations recall the principles of early diagnosis of presbycusis and the means of optimal rehabilitation as soon as the first symptoms appear. MATERIAL AND METHODS: The recommendations are based on a systematic analysis of the literature carried out by a multidisciplinary group of ENT physicians, audiologists, geriatricians and hearing specialists from all over France. They are classified as grade A, B, C or professional agreement according to a decreasing level of scientific evidence. RESULTS: The diagnosis of presbycusis is more difficult at the beginning of its evolution but a certain number of tools are available for its early diagnosis and its face-to-face or remote management. CONCLUSION: In the case of a clinical profile suggestive of presbycusis in a young subject, especially if there are several family cases, it is recommended to propose a genetic investigation. Free-field speech audiometry in noise is recommended to measure intelligibility in a realistic environment. Questionnaires in addition to audiometric tests would allow the best assessment of the patient's disability. Hearing rehabilitation with a hearing aid or cochlear implant may slow or prevent cognitive decline. Combined auditory and cognitive rehabilitation should be offered regardless of the time since the hearing was fitting. It is recommended to integrate programs accessible via smartphones, tablets or the Internet, that include different training domains to complement face-to-face sessions.
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INTRODUCTION: Presbycusis is the physiological decrease in hearing due to advancing age and begins well before the sixth decade. These recommendations recall the principles of early diagnosis of presbycusis and the means of optimal rehabilitation as soon as the first symptoms appear. MATERIAL AND METHODS: The recommendations are based on a systematic analysis of the literature carried out by a multidisciplinary group of doctors and audioprosthetists from all over France. They are graded A, B, C or expert opinion according to decreasing level of scientific evidence. RESULTS: The diagnosis of presbycusis is more difficult at the beginning of its evolution but a certain number of tools are available for its early diagnosis and its management in face-to-face or even distance learning. CONCLUSION: In case of a clinical profile suggestive of presbycusis in a young subject, especially if there are several family cases, it is recommended to propose a genetic investigation. It is recommended to perform free-field speech audiometry in noise to measure intelligibility in an environment as close as possible to reality. Questionnaires can be used in addition to audiometry to best assess the patient's disability. It is recommended that hearing rehabilitation with a hearing aid or cochlear implant may slow or prevent cognitive decline. Combined auditory and cognitive rehabilitation should be offered regardless of the time elapsed since the fitting. It is recommended to integrate programs accessible via smartphones, tablets or the Internet, integrating different training domains in addition to face-to-face sessions.
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Audiologia , Geriatria , Otolaringologia , Presbiacusia , Humanos , Idoso , Presbiacusia/terapia , Presbiacusia/reabilitação , CogniçãoRESUMO
Rhabdomyosarcoma of the larynx has been very rarely described in pediatric population. There are 3 histological subtypes: embryonal, pleomorphic, and alveolar. With regard to the English literature, we present the first case of alveolar rhabdomyosarcoma of the larynx ever described in a child. This tumor has been diagnosed on an endoscopic biopsy. Thus, a unilateral arytenoidectomy has been performed. This tumor has a poor prognosis. Lymph node metastases were successfully treated by chemotherapy and radiotherapy. Surgery has shifted from radical to conservative combined with adjuvant treatments.
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Neoplasias Laríngeas , Laringe , Rabdomiossarcoma Alveolar , Rabdomiossarcoma , Criança , Humanos , Neoplasias Laríngeas/patologia , Laringectomia , Laringe/patologia , Rabdomiossarcoma/patologia , Rabdomiossarcoma Alveolar/diagnóstico , Rabdomiossarcoma Alveolar/patologia , Rabdomiossarcoma Alveolar/terapiaRESUMO
Adenoid cystic carcinoma is a slowly growing malignant tumor with high local recurrence, perineural and vascular invasion. This tumor might arise from the glands of upper respiratory tract and oral cavity (eg, salivary or serous or mucous). Here we report the case of a 65-year-old woman who was referred to our unit for left retro-auricular radiating pain with trigger points and frontal headache since 6 months. There was no involvement of cranial nerves. Imaging screening using MRI, Positron emission tomography with 2-[fluorine-18] fluoro-2-deoxy-D-glucose, Gallium-68 DOTA-Phe1-Tyr3-Octreotide (68Ga DOTATOC) Positron emission tomography-CT suggested a suspicion of schwannoma or paraganglioma of the jugular foramen. However, the CT-guided biopsy revealed presence of adenoid cystic carcinoma. These warrants performing mandatory histological analysis combined with imaging screening suspicion of schwannoma or paraganglioma.
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The aims of this multicenter study were to identify clinical and preoperative PET/CT parameters predicting overall survival (OS) and distant metastasis-free survival (DMFS) in a cohort of head and neck squamous cell carcinoma patients treated with surgery, to generate a prognostic model of OS and DMFS, and to validate this prognostic model with an independent cohort. Methods: A total of 382 consecutive patients with head and neck squamous cell carcinoma, divided into training (n = 318) and validation (n = 64) cohorts, were retrospectively included. The following PET/CT parameters were analyzed: clinical parameters, SUVmax, SUVmean, metabolic tumor volume (MTV), total lesion glycolysis, and distance parameters for the primary tumor and lymph nodes defined by 2 segmentation methods (relative SUVmax threshold and absolute SUV threshold). Cox analyses were performed for OS and DMFS in the training cohort. The concordance index (c-index) was used to identify highly prognostic parameters. These prognostic parameters were externally tested in the validation cohort. Results: In multivariable analysis, the significant parameters for OS were T stage and nodal MTV, with a c-index of 0.64 (P < 0.001). For DMFS, the significant parameters were T stage, nodal MTV, and maximal tumor-node distance, with a c-index of 0.76 (P < 0.001). These combinations of parameters were externally validated, with c-indices of 0.63 (P < 0.001) and 0.71 (P < 0.001) for OS and DMFS, respectively. Conclusion: The nodal MTV associated with the maximal tumor-node distance was significantly correlated with the risk of DMFS. Moreover, this parameter, in addition to clinical parameters, was associated with a higher risk of death. These prognostic factors may be used to tailor individualized treatment.
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Fluordesoxiglucose F18 , Neoplasias de Cabeça e Pescoço , Fluordesoxiglucose F18/metabolismo , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Prognóstico , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Carga TumoralRESUMO
BACKGROUND: External ear canal exostoses are usually bilateral and broad-based, secondary to external ear canal chronic cold exposure, especially water. OBJECTIVES: The objectives were to analyze the influence of the surgeon's experience on the 3-year recurrence and on the complication. We also studied the influence of prolonged exposure to cold water on the incidence of recurrence. MATERIAL AND METHODS: This monocentric retrospective study included 98 ears operated for canalplasty between 2009 and 2016 by nine different operators including one senior, a junior, and seven beginner surgeons. Senior, Junior, and Beginner groups were compared. RESULTS: 3-year recurrence rate was higher in the Beginner and Junior groups than in the Senior group (69% and 38% vs 18%, P = .001). Although there was a difference between the Beginner (69%) and Junior (38%) groups, it was not significant (P = .407). Among the recurrences, 48% had continued exposure to cold water while only 7% of the ears without recidivism were still exposed (P < .001, OR = 1.25 [4.4; 36.1]). The complication rates were similar between groups, concerning pain (8% vs 30% vs 12%), per procedure perforation (17% vs 10% vs 16%), scarring disorders (25% vs 20% vs 13%), and osteitis (8% vs 0% vs 1%). Hearing was unaffected. CONCLUSIONS: This is the first study evaluating the risk of recurrence of external ear canal exostoses after canalplasty based on the surgeon's experience. This risk of recurrence seems to decrease with the surgeon's experience. There was no difference in complication rates.
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Hearing loss is the most common sensory defect, due in most cases to a genetic origin. Variants in the GJB2 gene are responsible for up to 30% of non-syndromic hearing loss. Today, several deafness genotypes remain incomplete, confronting us with a diagnostic deadlock. In this study, whole-genome sequencing (WGS) was performed on 10 DFNB1 patients with incomplete genotypes. New variations on GJB2 were identified for four patients. Functional assays were realized to explore the function of one of them in the GJB2 promoter and confirm its impact on GJB2 expression. Thus, in this study WGS resolved patient genotypes, thus unlocking diagnosis. WGS afforded progress and bridged some gaps in our research.
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Conexina 26/genética , Surdez/genética , Predisposição Genética para Doença , Perda Auditiva/genética , Surdez/epidemiologia , Surdez/patologia , Feminino , Genoma Humano/genética , Genótipo , Perda Auditiva/epidemiologia , Perda Auditiva/patologia , Humanos , Masculino , Mutação/genética , Linhagem , Regiões Promotoras Genéticas/genética , Sequenciamento Completo do GenomaRESUMO
OBJECTIVE: To report outcome and predictive factors in patients with N3 (> 6 cm) non-metastatic locally advanced head and neck squamous cell carcinoma (LAHNSCC) treated with a conservative approach or with initial surgery. METHODS: 104 patients were included: 69 treated with radiotherapy (RT) ± chemotherapy (CT) and 35 with nodal surgery with or without primary tumour resection, which was completed in 30 patients by adjuvant RT ± CT. Positron-emission tomography-computed tomography (PET-CT) guided surveillance after RT ± CT was standard. RESULTS: Two-year overall survival (OS) and locoregional control (LRC) were 39.4% and 37.5%, respectively. In univariate analysis, body mass index (BMI), performance status (PS), p16 status and haemoglobin value influenced OS and disease-free survival (DFS). In multivariate analysis, p16 positive status and BMI ≥ 25 remained independent prognostic factors for better OS (p = 0.023) and DFS (p = 0.002). Only under/normal weight remained an independent and adverse significant prognostic factor in multivariate analysis for regional control (RC). Patients treated with primary RT ± CT had slightly better 2-year OS (43.5% versus 33.3%, p = 0.31). CONCLUSIONS: Patients with N3 LAHNSCC have poor prognosis, but long term LRC is achievable, especially in overweight patients and those with a good PS.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapiaRESUMO
As a model to dissect the effects of CpG-oligonucleotides (CpG) on rituximab (RTX)-mediated therapeutic killing of autoimmune or malignant B lymphocytes, nude mice were grafted with Daudi human B cells. These mice were then injected with RTX alone or together with CpG. The human B cell aggregate was measured, and the reactive infiltrate analyzed after selective depletion of murine circulating cells. Macrophages (MØ) were identified in infiltrates, but not polymorphonuclear neutrophils (PMN), as confirmed by the failure of quantitative polymerase chain reaction to detect transcripts for PMN-specific myeloperoxidase in graft extracts. Evidence that MØ predominate over PMN in the anti-B cell RTX-induced immune mechanisms, include the presence of MØ-derived cytokines, and the lack of consequences of depletion of NK cells or B lymphocytes on the CpG-mediated effects on RTX. Interestingly however, removal of circulating PMN reduced the number of MØ attracted by the Daudi B cells. Our interpretation that CpG-induced complement activation is required for PMN to influence MØ was first based on overproduction of C5a in treated mice. This excess was due to the binding of the inhibitor of the alternative pathway of complement to CpG, as demonstrated by the elution of factor H from CpG-affinity-chromatography columns. Thus MØ are recruited to the tissue in the presence of C5a, and exploited locally by RTX.
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Anticorpos Monoclonais/administração & dosagem , Citotoxicidade Celular Dependente de Anticorpos/efeitos dos fármacos , Modelos Animais de Doenças , Linfoma de Células B/imunologia , Linfoma de Células B/terapia , Macrófagos/metabolismo , Oligodesoxirribonucleotídeos/administração & dosagem , Animais , Anticorpos Monoclonais Murinos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Complemento C5a/genética , Complemento C5a/metabolismo , Fator H do Complemento/metabolismo , Via Alternativa do Complemento/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Depleção Linfocítica , Linfoma de Células B/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/patologia , Camundongos , Camundongos Endogâmicos , Camundongos Nus , Camundongos SCID , Transplante de Neoplasias , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Neutrófilos/metabolismo , Neutrófilos/patologia , RituximabRESUMO
CD6 is one of a pair of related genes encoding CD5-associated receptors on all T cells and a subset of B cells. The current availability of "T1h", a humanized anti-CD6 monoclonal antibody for B cell-mediated autoimmune disorders revives analysis of the B-cell subset expression of CD6, particularly in primary Sjögren's syndrome (SS). Refined phenotype of B-lymphocytes peripheral blood (PB), bone marrow and tonsils revealed that the overlap between the expression of CD6 is less close to that of CD5 than currently acknowledged. In contrast to CD5, CD6 is absent on transitional B cells, while present on mature and memory B cells. Interestingly, the PB proportion of CD6(+) B cells is decreased in patients with primary SS, as opposed to those with rheumatoid arthritis. The reduction in primary SS does not result from the shedding of CD6 from the membrane of B cells, but from the lowering of memory B lymphocytes. It may result from the ability of CD6 to make transmigration of CD27(+) memory B cells into the salivary glands (SGs) easier. Consistent with this view is our finding that CD166 (one of the ligands for CD6) is highly expressed on epithelial cells of patients' SGs. This study is relevant in that the humanized T1h anti-CD6 becomes an alternative to anti-CD20 for treatment of primary SS.
Assuntos
Antígenos CD/biossíntese , Antígenos de Diferenciação de Linfócitos T/biossíntese , Subpopulações de Linfócitos B/metabolismo , Linfócitos B/metabolismo , Movimento Celular , Síndrome de Sjogren/imunologia , Anticorpos Monoclonais/metabolismo , Antígenos CD/sangue , Antígenos CD/genética , Antígenos de Diferenciação de Linfócitos T/sangue , Antígenos de Diferenciação de Linfócitos T/genética , Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/patologia , Linfócitos B/imunologia , Linfócitos B/patologia , Medula Óssea/patologia , Antígenos CD5/imunologia , Contagem de Células , Diferenciação Celular , Linhagem da Célula , Células Epiteliais/imunologia , Humanos , Memória Imunológica , Tonsila Palatina/patologiaRESUMO
INTRODUCTION: Rhabdomyosarcoma (RMS) arises from mesenchymal cells committed to skeletal muscle. It is the most frequent soft-tissue sarcoma in children and makes up 5% of all pediatric malignant tumors. In this population, there are two main histological forms, which are the embryonal or the alveolar RMS. The retro auricular location is extremely rare. We present 2 cases of children with left retro-auricular RMS occurring at a very early stage of post natal development. CASE REPORTS: Two children were included in the RMS 2005 Protocol. The first child, aged 5-days, was managed by surgical resection in two steps after a previous incomplete resection which was followed by 8 chemotherapy cycle. The second, aged 3-days, was managed by surgical resection of the tumor bed, completed by 8 chemotherapy cycle. On regular follow up for over 6 years after the diagnosis, both patients are free of recurrence. DISCUSSION: RMS is a fast-growing malignant and aggressive tumor originating from skeletal muscle. It occurs in the first decade of life and is associated with genetic conditions. With an unusual clinical presentation and anatomical location, both benign and malignant tumors can be suspected. Diagnosis can be performed with CT-scan or MRI and confirmed by biopsy. The treatment is based on chemotherapy followed by radiotherapy or surgical resection. In our two patients, the treatment program achieved complete disease control, with good prognosis especially because of anatomical location as well as early diagnosis.