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1. Review of survival rates 20-years after conservative surgery for papillary thyroid carcinoma

Author

Abrão Rapoport, Otávio Alberto Curioni, Ali Amar, and Rogério Aparecido Dedivitis

Subjects
Tireoidectomia, Neoplasias da glândula tireoide, Glândula tireoide, Carcinoma papilar, Otorhinolaryngology, RF1-547
Abstract

INTRODUCTION: A less extensive thyroidectomy could be used for patients in the low risk group.OBJECTIVE: To perform a critical follow-up after lobectomy with isthmusectomy for the treatment of papillary thyroid carcinoma in patients with a single nodule limited to the periphery of the lobe.METHODS: Thirty-one patients with thyroid papillary carcinoma operated on till 1993 were selected. They had undergone lobectomy with isthmusectomy. This is a retrospective cohort study in which the oncological outcome (contralateral and regional recurrence) and the reoperation complications (recurrent nerve paralysis/paresis and hypoparathyroidism) were evaluated. Descriptive analysis was employed.RESULTS: In the last decade (2003-2013), 6 (20%) contralateral recurrences were observed in the remaining lobe and in 1 of these cases (3%), contralateral lymph node metastases were noted. A completion thyroidectomy plus lymphadenectomy was performed, without modification of global survival.CONCLUSION: Because of the rate of 20% of contralateral recurrence after a 20-year follow-up, we suggest modification of the surgical paradigm for total thyroidectomy as an initial therapy.

Published
2015
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2. Valor prognóstico da metástase regional no carcinoma epidermoide de língua e soalho bucal

Author

Ali Amar, Abrão Rapoport, Otávio Alberto Curioni, Rogério Aparecido Dedivitis, Claudio Roberto Cernea, and Lenine Garcia Brandão

Subjects
carcinoma de células escamosas, metástase linfática, neoplasias bucais, Otorhinolaryngology, RF1-547
Abstract

A presença da metástase linfonodal é um fator limitante da sobrevida no câncer da boca. OBJETIVO: Avaliar as causas de falha no tratamento dos carcinomas de língua e soalho de boca em função do estadiamento. MÉTODO: Foram analisados 365 casos de carcinoma epidermoide de boca, tratados de 1978 a 2007, sendo 48 T1, 156 T2, 98 T3 e 63 T4, dos quais 193 foram pNo e 172 pN+. RESULTADOS: Entre os casos pN+, foram observados 17/46 recidivas (36,9%) nos casos não irradiados e 46/126 (36,5%) nos casos irradiados. Quanto aos resgates, nos casos pN0, obtivemos 16/51 (31,3%) e, nos pacientes pN+, de 3/77 (3,9%). CONCLUSÃO: O sucesso dos resgates é menor em pacientes com pN+, com maior recidiva local e menor sobrevida.

Published
2013
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3. Avaliação epidemiológica e da resposta terapêutica no câncer da hipofaringe

Author

Ali Amar, Otávio Alberto Curioni, Diógenes Lopes de Paiva, Abrão Rapoport, Rogério Aparecido Dedivitis, Claudio Roberto Cernea, and Lenine Garcia Brandão

Subjects
análise de sobrevida, carcinoma de células escamosas, epidemiologia, estadiamento de neoplasias, neoplasias hipofaríngeas, Otorhinolaryngology, RF1-547
Abstract

Apesar da baixa incidência, avanços diagnóstico e terapêutico, o câncer de hipofaringe ainda possui elevada mortalidade. OBJETIVO: Avaliar retrospectivamente o perfil epidemiológico e a resposta bà cirurgia e rádio/quimioterapia de pacientes portadores de câncer de hipofaringe. MÉTODO: Foram analisados prontuários de 114 pacientes atendidos entre 2002 e 2009 em um hospital terciário com o diagnóstico histopatológico de carcinoma epidermoide. RESULTADOS: A idade média dos pacientes foi 57 anos; 94,7% eram do sexo masculino e 5,3%, do feminino; 98,2% eram tabagistas e 92% etilistas; 72% analfabetos ou com 1º grau incompleto. As queixas principais foram: nódulo cervical (28%), dor e disfagia (22%), odinofagia (12,2%), disfonia (7,8%). O estádio clínico foi: I (1,7%), II (3,5%), III (18,4%), IV (76,3%). O tratamento foi realizado com rádio e quimioterapia exclusivas em 35%, com sobrevida média em 2 anos de 20% e 5 anos de 18%, cirurgia seguida de rádio e quimioterapia em 22,8% com sobrevida em 2 anos de 60,0% e 5 anos 55,0%, quimioterapia exclusiva em 2,6%, e 39,4% sem tratamento. CONCLUSÃO: A maioria dos pacientes já apresentava estádios clínicos avançados e, independentemente da opção terapêutica, apresentam baixa sobrevida, confirmando mau prognóstico desta neoplasia.

Published
2013
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4. A densidade do linfonodo metastático como fator prognóstico no carcinoma espinocelular da língua e soalho bucal The density of metastatic lymph node as prognostic factor in squamous cell carcinoma of the tongue and floor of the mouth

Author

Ali Amar, Abrão Rapoport, Otávio Alberto Curioni, Rogério Aparecido Dedivitis, Cláudio Roberto Cernea, and Lenine Garcia Brandão

Subjects
linfonodos, metástase linfática, neoplasias bucais, neoplasias da língua, prognóstico, lymph nodes, lymphatic metastasis, mouth neoplasms, prognosis, tongue neoplasms, Otorhinolaryngology, RF1-547
Abstract

A presença de linfonodos metastáticos é aspecto relevante no prognóstico do câncer bucal. OBJETIVO: Avaliar a densidade do linfonodo metastático (pN+) em pacientes com carcinoma espinocelular (CEC) de língua e soalho bucal e sua relação com a sobrevida livre de doença (SLD). MÉTODOS: De 1985 a 2007, 182 pacientes foram avaliados, dos quais 169 eram homens, sendo cinco estádio I, 35 estádio II, 56 estádio III e 85 estádio IV. A densidade do linfonodo foi mensurada por meio de sua mediana e a SLD pelo método de Kaplan-Meier e a diferença de grupo pelo teste log-rank. RESULTADOS:Após média de dissecção de 3,2 linfonodos metastáticos com pacientes, a densidade variou de 0,009 a 0,4, com média 0,09. A SLD a 5 anos foi de 44% e 28% para grupos com densidade linfonodal abaixo e acima da mediana (p = 0,006). O controle loco-regional a 2 anos foi de 71% e 49% para os casos com densidade abaixo e acima da mediana (p = 0,01). Quanto ao estádio pN, o controle loco-regional foi de 70% e 54% para os casos pN1 e pN2, sem significância estatística (0,20%). CONCLUSÃO: A densidade linfonodal pode ser utilizada como indicador prognóstico no CEC de língua e soalho bucal.The presence of metastatic lymph nodes is a relevant prognostic factor in oral cancer. OBJECTIVE: This paper aims to assess metastatic lymph node density (pN+) in patients with tongue and floor-of-mouth squamous cell carcinoma (SCC) and the association of this parameter with disease-free survival (DFS). MATERIALS AND METHODS: A group of 182 patients seen between 1985 and 2007 was included, 169 of which were males. Five were on stage I, 35 on stage II, 56 on stage III, and 85 on stage IV. Median values were considered in lymph node density assessment, and the Kaplan-Meier curve was used to evaluate DFS; survival differences within the group were elicited through the log-rank test. RESULTS: An average 3.2 metastatic lymph nodes were excised from the patients in the group. Density ranged from 0.009 to 0.4, with a mean value of 0.09. Five-year DFS rates were of 44% and 28% for the groups with lymph node densities below and above the median respectively (p = 0.006). Two-year local/regional control was achieved for 71% and 49% for the patients below and above the median density respectively (p = 0.01). In terms of pN staging, local/regional control was achieved in 70% and 54% of pN1 and pN2 patients respectively, albeit without statistical significance (0.20%). CONCLUSION: Lymph node density may be used as a prognostic indicator for tongue and floor-of-mouth SCC.

Published
2012
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5. Significado prognóstico do número de linfonodos no esvaziamento cervical eletivo no câncer de língua e soalho de boca Prognostic significance of the number of lymph nodes in elective neck dissection for tongue and mouth floor cancers

Author

Ali Amar, Helma Maria Chedid, Abrão Rapoport, Claudio Roberto Cernea, Rogério Aparecido Dedivitis, Otávio Alberto Curioni, and Lenine Garcia Brandão

Subjects
carcinoma de células escamosas, esvaziamento cervical, linfonodos, neoplasias bucais, carcinoma, squamous cells, lymph nodes, mouth neoplasms, neck dissection, Otorhinolaryngology, RF1-547
Abstract

A presença de linfonodos metastáticos é aspecto relevante no tratamento do câncer na cabeça e pescoço, resultando em 50% de redução na sobrevida. OBJETIVO: Avaliar o número de linfonodos removidos no esvaziamento cervical e sua relação com o prognóstico. MÉTODOS: Estudo retrospectivo de 143 pacientes portadores de carcinoma epidermoide de língua e soalho bucal, cujo exame histológico evidenciou ausência de metástases linfonodais. Desses, 119 eram masculinos e 24 femininos, com idade média de 54 anos. Quanto ao sítio do tumor primário, 65 eram na língua e 78 no soalho bucal. A distribuição do estádio T foi de quatro T1, 84 T2, 36 T3 e 19 T4. Foram realizados 176 esvaziamentos cervicais, sendo unilateral em 110 casos e bilateral em 33. Desses, 78 radicais e 98 seletivos. Os pacientes foram separados em três grupos, de acordo com os percentis 33 e 66 do número de linfonodos ressecados. RESULTADOS: O número médio de linfonodos ressecados foi de 27, sendo 24 nos esvaziamentos seletivos e 31 nos completos. Não foram observadas diferenças estatisticamente significantes quando relacionado aos estádios T e N. CONCLUSÕES: O maior número de linfonodos dissecados no esvaziamento cervical identifica um grupo de melhor prognóstico nos casos pN0.The presence of metastatic lymph nodes is a relevant aspect in the treatment of head and neck cancer, bringing about a 50% reduction in survival. OBJECTIVE: To assess the number of lymph nodes removed in the neck dissection and their relationship with the prognosis. METHODS: A retrospective study involving 143 patients with tongue and mouth floor epidermoid carcinoma, which histological exam showed no lymph node metastases. Among those, 119 were males and 24 females, with mean age of 54 years. As to the primary tumor site, 65 were in the tongue and 78 in the mouth floor. T stage distribution was of four T1, 84 T2, 36 T3 and 19 T4. We carried out 176 neck dissections, unilateral in 110 cases and bilateral in 33. Of these, 78 were radical and 98 selective. The patients were broken down into three groups, according to the 33 and 66 percentiles of the number of lymph nodes resected. RESULTS: The mean number of resected lymph nodes was 27; 24 in selective dissections and 31 in the complete ones. We did not have statistically significant differences when associated to the T and N stages. CONCLUSIONS: The larger number of lymph nodes dissected in the neck dissection identifies the group of better prognoses among pN0 cases.

Published
2012
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6. Esvaziamento cervical no carcinoma epidermoide de laringe: indicação de esvaziamento eletivo contralateral Neck dissection in squamous cell carcinoma of the larynx: indication of elective contralateral neck dissection

Author

Ali Amar, Helma Maria Chedid, Sergio Altino Franzi, and Abrão Rapoport

Subjects
carcinoma de células escamosas, esvaziamento cervical, laringe, carcinoma, squamous cell, larynx, neck dissection, Otorhinolaryngology, RF1-547
Abstract

O planejamento terapêutico dos tumores da laringe inclui a possibilidade de esvaziamento cervical uni ou bilateral. OBJETIVO: Avaliar a prevalência e localização de metástases linfonodais bilaterais ou contralaterais nos tumores de laringe. CASUÍSTICA E MÉTODO: Estudo longitudinal retrospectivo de 272 prontuários de pacientes com carcinoma epidermoide de laringe tratados entre 1996 e 2004, selecionados 104 submetidos à cirurgia com esvaziamento cervical. Avaliada a incidência de metástases bilaterais ou contralaterais, de acordo com a localização e extensão do tumor primário, considerando os subsítios anatômicos e a linha mediana. RESULTADOS: A prevalência de metástases contralaterais nos tumores lateralizados foi de 3,5% nas lesões glóticas e 26% nas lesões supraglóticas. As metástases contralaterais foram infrequentes nos casos N0. Tanto no esvaziamento eletivo como no terapêutico, os níveis linfonodais IIa e III foram os mais acometidos. CONCLUSÃO: Nas lesões glóticas lateralizadas, mesmo nos tumores transglóticos, não há necessidade de esvaziamento contralateral eletivo. Nas lesões da supraglote sem metástases ipsilaterais, a incidência de metástases ocultas não justifica o esvaziamento eletivo contralateral. A linha mediana não é um indicador fidedigno do risco de metástases contralaterais nos tumores da laringe.Unilateral or bilateral neck dissection must be considered in the treatment of laryngeal cancer AIM: To evaluate the prevalence of contralateral metastases in larynx cancer and distribution of these metastases according to lymph node levels in the neck. METHOD: Retrospective longitudinal study of 272 charts from patients with squamous cell cancer of the larynx treated between 1996 and 2004; and we selected 104 surgical cases submitted to neck dissection. We evaluated the incidence of bilateral or contralateral metastases, according to the location and extension of the primary tumor, considering the anatomical sub-sites and the midline. RESULTS: Contralateral metastases in lateral tumors were observed in 3.5% of glottic lesions and in 26% of supraglottic lesions. Contralateral metastases were uncommon in N0 patients. Lymph nodes levels IIa and III were the most commonly involved in the neck. CONCLUSION: In lateral glottic tumors there is no need for elective contralateral neck dissection. In supraglottic lesions without ipsilateral metastases, the incidence of hidden metastasis does not justify elective contralateral dissection. The midline is not a reliable indicator of the risk of contralateral laryngeal tumors.

Published
2012
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7. Spinal accessory nerve neuropathy following neck dissection Neuropatia do nervo acessório espinhal secundária à cirurgia de esvaziamento cervical

Author

Luciana Pereira de Lima, Ali Amar, and Carlos Neutzling Lehn

Subjects
nervos cranianos, eletromiografia, esvaziamento cervical, cranial nerves, electromyography, neck dissection, Otorhinolaryngology, RF1-547
Abstract

Tthe most common complication of neck dissection is shoulder dysfunction due to manipulation of spinal accessory nerve, resulting in trapezius muscle atrophy mainly in procedures involving the posterior neck triangle. AIM: This study used electromyography to evaluate the injury to the spinal accessory nerve following neck dissection. MATERIALS AND METHODS: Prospective case series of 51 patients submitted to 60 neck dissections followed by physical therapy evaluation of shoulder dysfunction. Nerve integrity was evaluated before and after the surgery by means of surface EMG registering the electric activity of the trapezius muscle during voluntary contraction. The patients were grouped according to the type of neck dissection, presence of shoulder pain, impairment during abduction movement and hypotrophy/atrophy of the trapezius muscle. RESULTS: Action potential had median values of 54.3 microV before surgery and 11.6 microV after it (pUma das complicações mais comuns do esvaziamento cervical é a disfunção do ombro devido à manipulação do nervo acessório, que resulta na atrofia do músculo trapézio. OBJETIVO: Avaliar com eletromiografia de superfície (EMGs) a lesão do XI par decorrente do esvaziamento cervical. MATERIAL E MÉTODO: Estudo prospectivo com 51 pacientes (60 esvaziamentos cervicais) tratados de câncer de cabeça e pescoço. A função do nervo acessório foi avaliada no período pré e pós-operatório com registro da atividade elétrica das fibras descendentes do músculo trapézio em contração isométrica voluntária máxima. Os pacientes foram agrupados pelo tipo de esvaziamento e movimento de abdução do braço. RESULTADOS: O potencial de ação apresentou mediana de 54,3 microV no pré-operatório e 11,6 microV no pós-operatório (p

Published
2011
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8. Retardo diagnóstico e terapêutico em pacientes com câncer da laringe em hospital público de referência Diagnostic and therapeutic delay in patients with larynx cancer at a reference public hospital

Author

Ali Amar, Helma Maria Chedid, Sergio Altino Franzi, and Abrão Rapoport

Subjects
carcinoma de células escamosas, neoplasias laríngeas, terapêutica, carcinoma, squamous cell, laryngeal neoplasms, Otorhinolaryngology, RF1-547
Abstract

O carcinoma epidermoide da laringe, apesar dos sintomas precoces, ainda é frequentemente diagnosticado em estádio avançado. Apesar da demora até chegar ao atendimento especializado, o tempo despendido no diagnóstico e a espera para o tratamento definitivo também são importantes para o resultado final. OBJETIVO: Avaliar o intervalo de tempo entre a primeira consulta no especialista e o tratamento nos pacientes com carcinoma epidermoide da laringe. FORMA DE ESTUDO: Coorte histórica longitudinal. MATERIAL E MÉTODO: Estudo de 272 pacientes com carcinoma epidermoide da laringe atendidos consecutivamente entre janeiro de 1996 e dezembro de 2004. Avaliadas as características clínicas e epidemiológicas, assim como sua relação com o tempo despendido entre a consulta inicial e o tratamento. RESULTADO: O intervalo de tempo entre a primeira consulta e o início do tratamento apresentou mediana de 49 dias e média de 57 dias. Não houve diferença em relação ao estadiamento, faixa etária, sexo, naturalidade ou escolaridade. CONCLUSÃO: O tempo entre o atendimento inicial com especialista e o início do tratamento apresentou mediana de 49 dias, similar ao relatado em outros estudos.Laryngeal squamous cell carcinoma is very often diagnosed at advanced stages. The time interval between the specialist consultation and the start of treatment may contribute to better outcomes. AIM: the interval assessment between the first specialist evaluation and the treatment of patients with laryngeal squamous cell carcinoma. STUDY DESIGN: longitudinal historical cohort. MATERIALS AND METHODS: 272 consecutive patients with laryngeal squamous cell carcinoma seen between January, 1996 and December of 2004. Clinical and epidemiological data were evaluated, as well as their association with the time interval between the first specialist visit and the start of treatment. RESULT: the median time between first evaluation and treatment was 49 days. There was no relationship with gender, age, birth place, disease stage or education. CONCLUSION: the treatment median delay was 49 days, similar to what has been reported in other studies.

Published
2010
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9. Avaliação da sobrevida livre de doença em pacientes com carcinoma epidermoide de laringe submetidos à tratamento radioterápico exclusivo ou associado à quimioterapia Assessment of disease-free survival in patients with laryngeal squamous cell carcinoma treated with radiotherapy associated or not with chemotherapy

Author

Helma Maria Chedid, Carlos Neutzling Lehn, Abrão Rapoport, Ali Amar, and Sérgio Altino Franzi

Subjects
carcinoma de células escamosas, neoplasias laríngeas, quimioterapia, radioterapia, taxa de sobrevida, carcinoma, laryngeal neoplasms, disease-free survival, transitional cells, radiotherapy, Otorhinolaryngology, RF1-547
Abstract

No carcinoma epidermoide de laringe em estádios clínicos precoces (I e II), tanto a cirurgia quanto a radioterapia resultam em controle loco-regional significativo. Nos tumores avançados (III e IV), a radioterapia exclusiva tem índices de 32-43% de controle loco-regional. OBJETIVO: É avaliar a sobrevida livre de doença dos pacientes com CEC de laringe submetidos à radioterapia exclusiva e/ou associada à quimioterapia. CASUÍSTICA E MÉTODOS: Estudo retrospectivo de 84 casos de CEC de laringe tratados com radioterapia ou quimioterapia concomitante à radioterapia. Cinquenta e três casos foram tratados com intenção curativa e 31 por irressecabilidade da doença. Quanto ao estádio clínico (EC), 12 eram de EC I, 15 II, 21 III e 5 IV. No segundo grupo, 11 casos eram EC III e 20 IV. RESULTADOS: Idade média foi de 60 anos, sendo 84,5% homens. Cinquenta e oito (69,1%) casos tiveram resposta completa e 26 (30,9%) apresentavam doença persistente ou residual. A sobrevida livre de doença há cinco anos foi de 42,5%, sendo de 62,5% nos pacientes com indicação de preservação de órgãos e 9,75 no grupo de doença irressecável. CONCLUSÃO: A sobrevida livre de doença a cinco anos dos pacientes submetidos à radioterapia por CEC de laringe foi de 62,5%.In early stage (I and II) laryngeal squamous cell carcinoma, both surgery and radiotherapy results in significant local and regional control. In advanced tumors (III and IV), radiotherapy alone has local-regional control rates of 32-43%. AIM: To assess disease-free survival in SCC laryngeal carcinoma patients submitted to radiotherapy alone and/or associated with chemotherapy. MATERIALS AND METHODS: Retrospective study involving 84 cases of laryngeal SCC treated with radiotherapy or chemotherapy together with radiotherapy. Fifty-three cases were treated with intension to cure and 31 because of impossibility to resect the disease. As to clinical stage (CS), 12 were CS I, 15 II, 21 III and 5 IV. In the second group, 11 cases were EC III and 20 IV. RESULTS: Mean age was 60 years, 84.5% were men. Fifty-eight (69.1%) cases had complete response and 26 (30.9%) had persistent or residual disease. Five-year disease-free survival was of 42.5%; 62.5% of the patients with organ preservation indication and 9.75 in the group of irressecable disease. CONCLUSION: disease-free survival of those patients submitted to radiotherapy because of laryngeal SCC was of 62.5%

Published
2010
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10. Indication of elective contralateral neck dissection in squamous cell carcinoma of the hypopharynx Indicação do esvaziamento eletivo contralateral no carcinoma espinocelular da hipofaringe

Author

Ali Amar, Rogério Aparecido Dedivitis, Abrão Rapoport, and André Luiz Quarteiro

Subjects
carcinoma de células escamosas, esvaziamento cervical, hipofaringe, metástase linfática, squamous cell carcinoma, neck dissection, hypopharynx, lymphatic metastasis, Otorhinolaryngology, RF1-547
Abstract

Lymph node metastases (LNM) are common in hypophariyngeal carcinomas; the neck dissection is an important therapeutic approach. AIM: to analyze the incidence and distribution of LNM and failures in treating the contralateral neck. METHODS: a retrospective study of 174 patients with hypopharyngeal cancer treated from 1978 to 2003. The distribution of LNM and regional recurrences were evaluated. RESULTS: 44% of the cases were false negatives and 4.9% were false positives. Among the 48 patients who underwent bilateral ND, 29 had bilateral metastases and one had contralateral metastasis. Contralateral neck recurrences occurred in 12 cases that underwent unilateral ND. Among the nine patients with contralateral neck recurrence alone, eight were surgically salvaged. The risk of contralateral metastases was related to clinical staging (p=0.003) and involvement of the medial wall of the pyriform sinus (p=0.03), but not to radiotherapy (p=0.28). CONCLUSION: Contralateral metastases were more frequent when the medial wall of the pyriform sinus was affected, in the presence of ipsilateral palpable metastases and clinical stage IV.As metástases linfonodais são frequentes nos carcinomas da hipofaringe e o esvaziamento cervical é parte importante do tratamento. OBJETIVO: Avaliar a incidência e distribuição das metástases linfonodais e as falhas no tratamento do pescoço contralateral. MÉTODOS: Estudo retrospectivo de 174 pacientes com carcinoma epidermoide de hipofaringe tratados entre 1978 e 2003. Foi avaliada a distribuição das metástases linfonodais e as recidivas regionais. RESULTADOS: Foram diagnosticados 44% de casos falso-negativos e 4,9% falso-positivos. Dos 48 pacientes submetidos ao esvaziamento bilateral, 29 apresentaram metástases bilaterais e um apresentou metástase contralateral apenas. As recidivas cervicais contralaterais ocorreram em 12 casos submetidos ao esvaziamento unilateral. Dos 9 pacientes com recidiva cervical contralateral isolada, 8 pacientes foram resgatados cirurgicamente. O risco de metástases contralaterais relacionou-se com o estadiamento clínico (p=0,003) e com o comprometimento da parede medial do recesso piriforme (p=0,03), mas não com a realização de radioterapia (p=0,28). CONCLUSÕES: As metástases contralaterais nos carcinomas da hipofaringe foram mais frequentes quando a parede medial do recesso piriforme estava comprometida, na presença de metástases palpáveis ipsilaterais e estádio clínico IV.

Published
2009
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11. Prognostic factors in the treatment of squamous cell carcinoma of the larynx: partial surgery x radical surgery

Author

Maria da Graça Caminha Vidal, Onivaldo Cervantes, Marcio Abrah ão, Flávio Carneiro Hojaij, and Ali Amar

Subjects
Otorhinolaryngology, RF1-547
Abstract

Summary: The present study aimed at assessing the other sites as the carcinoma spreads, as well as therapeutic results, in larynx preservation and patient survival. Study type: It is a Longitudinal Historical Cohort Study, a retrospective clinical study. Materials and Methods: A hundred and sixty (160) patients treated at 'Escola Paulista de Medicina' ('Paulista' Medical School) - São Paulo Hospital, from January 1988 to December 2004 were examined as for the spreading of their larynx carcinoma. Those patients whose evaluations were at least two years old after treatment were the only ones accepted. The parametric tests used were: Test X2, Fisher's test, and Kaplan-Meier's curve. Results: The posterior commissure and the infraglottis were significant in terms of the laryngectomy: glottal tumors AC: (p=0.03) AP: (p=0.0001); AC: (p=0.0007) AP: (p

Published
2007
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12. Lack of association between classical HLA genes and asymptomatic SARS-CoV-2 infection

Author

Astrid Marchal, Elizabeth T. Cirulli, Iva Neveux, Evangelos Bellos, Ryan S. Thwaites, Kelly M. Schiabor Barrett, Yu Zhang, Ivana Nemes-Bokun, Mariya Kalinova, Andrew Catchpole, Stuart G. Tangye, András N. Spaan, Justin B. Lack, Jade Ghosn, Charles Burdet, Guy Gorochov, Florence Tubach, Pierre Hausfater, Clifton L. Dalgard, Shen-Ying Zhang, Qian Zhang, Christopher Chiu, Jacques Fellay, Joseph J. Grzymski, Vanessa Sancho-Shimizu, Laurent Abel, Jean-Laurent Casanova, Aurélie Cobat, Alexandre Bolze, Alessandro Aiuti, Saleh Al-Muhsen, Fahd Al-Mulla, Ali Amara, Mark S. Anderson, Evangelos Andreakos, Andrés A. Arias, Lisa M. Arkin, Hagit Baris Feldman, Paul Bastard, Alexandre Belot, Catherine M. Biggs, Dusan Bogunovic, Anastasiia Bondarenko, Alessandro Borghesi, Ahmed A. Bousfiha, Petter Brodin, Yenan Bryceson, Manish J. Butte, Giorgio Casari, John Christodoulou, Roger Colobran, Antonio Condino-Neto, Stefan N. Constantinescu, Megan A. Cooper, Murkesh Desai, Beth A. Drolet, Xavier Duval, Jamila El Baghdadi, Philippine Eloy, Sara Espinosa-Padilla, Carlos Flores, José Luis Franco, Antoine Froidure, Peter K. Gregersen, Bodo Grimbacher, Filomeen Haerynck, David Hagin, Rabih Halwani, Lennart Hammarström, James R. Heath, Elena W.Y. Hsieh, Eystein Husebye, Kohsuke Imai, Yuval Itan, Emmanuelle Jouanguy, Elżbieta Kaja, Timokratis Karamitros, Kai Kisand, Cheng-Lung Ku, Yu-Lung Lau, Yun Ling, Carrie L. Lucas, Tom Maniatis, Davood Mansouri, László Maródi, France Mentré, Isabelle Meyts, Joshua D. Milner, Kristina Mironska, Trine H. Mogensen, Tomohiro Morio, Lisa F.P. Ng, Luigi D. Notarangelo, Antonio Novelli, Giuseppe Novelli, Cliona O'Farrelly, Satoshi Okada, Keisuke Okamoto, Tayfun Ozcelik, Qiang Pan-Hammarström, Jean W. Pape, Rebeca Perez de Diego, Jordi Perez-Tur, David S. Perlin, Graziano Pesole, Anna M. Planas, Carolina Prando, Aurora Pujol, Anne Puel, Lluis Quintana-Murci, Sathishkumar Ramaswamy, Laurent Renia, Igor Resnick, Carlos Rodríguez-Gallego, Anna Sediva, Mikko R.J. Seppänen, Mohammad Shahrooei, Anna Shcherbina, Ondrej Slaby, Andrew L. Snow, Pere Soler-Palacín, Vassili Soumelis, Ivan Tancevski, Ahmad Abou Tayoun, Şehime Gülsün Temel, Christian Thorball, Pierre Tiberghien, Sophie Trouillet-Assant, Stuart E. Turvey, K. M. Furkan Uddin, Mohammed J. Uddin, Diederik van de Beek, Donald C. Vinh, Horst von Bernuth, Joost Wauters, Mayana Zatz, Pawel Zawadzki, Serge Bureau, Yannick Vacher, Anne Gysembergh-Houal, Lauren Demerville, Abla Benleulmi-Chaachoua, Sebastien Abad, Radhiya Abassi, Abdelrafie Abdellaoui, Abdelkrim Abdelmalek, Hendy Abdoul, Helene Abergel, Fariza Abeud, Sophie Abgrall, Noemie Abisror, Marylise Adechian, Nordine Aderdour, Hakeem Farid Admane, Frederic Adnet, Sara Afritt, Helene Agostini, Claire Aguilar, Sophie Agut, Tommaso Francesco Aiello, Marc Ait Kaci, Hafid Ait Oufella, Gokula Ajeenthiravasan, Virginie Alauzy, Fanny Alby-Laurent, Lucie Allard, Marie-Alexandra Alyanakian, Blanca Amador Borrero, Sabrina Amam, Lucile Amrouche, Marc Andronikof, Dany Anglicheau, Nadia Anguel, Djillali Annane, Mohammed Aounzou, Caroline Aparicio, Gladys Aratus, Jean-Benoit Arlet, Jeremy Arzoine, Elisabeth Aslangul, Mona Assefi, Adeline Aubry, Laetitia Audiffred, Etienne Audureau, Christelle Nathalie Auger, Jean-Charles Auregan, Celine Awotar, Sonia Ayllon Milla, Delphine Azan, Laurene Azemar, Billal Azzouguen, Marwa Bachir Elrufaai, Aïda Badsi, Prissile Bakouboula, Coline Balcerowiak, Fanta Balde, Elodie Baldivia, Eliane-Flore Bangamingo, Amandine Baptiste, Fanny Baran-Marszak, Caroline Barau, Nathalie Barget, Flore Baronnet, Romain Barthelemy, Jean-Luc Baudel, Camille Baudry, Elodie Baudry, Laurent Beaugerie, Adel Belamri, Nicolas Belaube, Rhida Belilita, Pierre Bellassen, Rawan Belmokhtar, Isabel Beltran, Ruben Benainous, Mourad Benallaoua, Robert Benamouzig, Amélie Benbara, Jaouad Benhida, Anis Benkhelouf, Jihene Benlagha, Chahinez Benmostafa, Skander Benothmane, Miassa Bentifraouine, Laurence Berard, Quentin Bernier, Enora Berti, Astrid Bertier, Laure Berton, Simon Bessis, Alexandra Beurton, Celine Bianco, Clara Bianquis, Frank Bidar, Philippe Blanche, Clarisse Blayau, Alexandre Bleibtreu, Emmanuelle Blin, Coralie Bloch-Queyrat, Marie-Christophe Boissier, Diane Bollens, Marion Bolzoni, Rudy pierre Bompard, Nicolas Bonnet, Justine Bonnouvrier, Shirmonecrystal Botha, Wissam Boucenna, Fatiha Bouchama, Olivier Bouchaud, Hanane Bouchghoul, Taoueslylia Boudjebla, Noel Boudjema, Catherine Bouffard, Adrien Bougle, Meriem Bouguerra, Leila Bouras, Agnes Bourcier, Anne Bourgarit Durand, Anne Bourrier, Fabrice Bouscarat, Diane Bouvry, Nesrine Bouziri, Ons Bouzrara, Sarah Bribier, Delphine Brugier, Melanie Brunel, Eida Bui, Anne Buisson, Iryna Bukreyeva, Côme Bureau, Jacques Cadranel, Johann Cailhol, Ruxandra Calin, Clara Campos Vega, Pauline Canavaggio, Marta Cancella, Delphine Cantin, Albert Cao, Lionel Carbillon, Nicolas Carlier, Clementine Cassard, Guylaine Castor, Marion Cauchy, Olivier Cha, Benjamin Chaigne, Salima Challal, Karine Champion, Patrick Chariot, Julie Chas, Simon Chauveau, Anthony Chauvin, Clement Chauvin, Nathalie Chavarot, Kamélia Chebbout, Mustapha Cherai, Ilaria Cherubini, Amelie Chevalier, Thibault Chiarabini, Thierry Chinet, Richard Chocron, Pascaline Choinier, Juliette Chommeloux, Christophe Choquet, Laure 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Rodero, Carlos Rodrigo, Luis Antonio Rodriguez, Carlos Rodriguez-Gallego, Agustí Rodriguez-Palmero, Carolina Soledad Romero, Anya Rothenbuhler, Damien Roux, Nikoletta Rovina, Flore Rozenberg, Yvon Ruch, Montse Ruiz, Maria Yolanda Ruiz del Prado, Juan Carlos Ruiz-Rodriguez, Joan Sabater-Riera, Kai Saks, Maria Salagianni, Oliver Sanchez, Adrián Sánchez-Montalvá, Silvia Sánchez-Ramón, Laire Schidlowski, Agatha Schluter, Julien Schmidt, Matthieu Schmidt, Catharina Schuetz, Cyril E. Schweitzer, Francesco Scolari, Luis Seijo, Analia Gisela Seminario, Piseth Seng, Sevtap Senoglu, Mikko Seppänen, Alex Serra Llovich, Virginie Siguret, Eleni Siouti, David M. Smadja, Nikaia Smith, Ali Sobh, Xavier Solanich, Jordi Solé-Violán, Catherine Soler, Betül Sözeri, Giulia Maria Stella, Yuriy Stepanovskiy, Annabelle Stoclin, Fabio Taccone, Jean-Luc Taupin, Simon J. Tavernier, Loreto Vidaur Tello, Benjamin Terrier, Guillaume Thiery, Karolina Thorn, Caroline Thumerelle, Imran Tipu, Martin Tolstrup, Gabriele Tomasoni, Julie Toubiana, Josep Trenado Alvarez, Vasiliki Triantafyllia, Jesús Troya, Owen T.Y. Tsang, Liina Tserel, Eugene Y.K. Tso, Alessandra Tucci, Şadiye Kübra Tüter Öz, Matilde Valeria Ursini, Takanori Utsumi, Pierre Vabres, Juan Valencia-Ramos, Ana Maria Van Den Rym, Isabelle Vandernoot, Valentina Velez-Santamaria, Silvia Patricia Zuniga Veliz, Mateus C. Vidigal, Sébastien Viel, Cédric Villain, Marie E. Vilaire-Meunier, Judit Villar-García, Audrey Vincent, Dimitri Van der Linden, Alla Volokha, Fanny Vuotto, Els Wauters, Alan K.L. Wu, Tak-Chiu Wu, Aysun Yahşi, Osman Yesilbas, Mehmet Yildiz, Barnaby E. Young, Ufuk Yükselmiş, Marco Zecca, Valentina Zuccaro, Jens Van Praet, Bart N. Lambrecht, Eva Van Braeckel, Cédric Bosteels, Levi Hoste, Eric Hoste, Fré Bauters, Jozefien De Clercq, Catherine Heijmans, Hans Slabbynck, Leslie Naesens, Benoit Florkin, Mary-Anne Young, Amanda Willis, Paloma Lapuente-Suanzes, Ana de Andrés-Martín, Matilda Berkell, Valerio Carelli, Alessia Fiorentino, Surbhi Malhotra, Alessandro Mattiaccio, Tommaso Pippucci, Marco Seri, Evelina Tacconelli, Michiel van Agtmael, Anne Geke Algera, Brent Appelman, Frank van Baarle, Diane Bax, Martijn Beudel, Harm Jan Bogaard, Marije Bomers, Peter Bonta, Lieuwe Bos, Michela Botta, Justin de Brabander, Godelieve de Bree, Sanne de Bruin, David T.P. Buis, Marianna Bugiani, Esther Bulle, Osoul Chouchane, Alex Cloherty, Mirjam Dijkstra, Dave A. Dongelmans, Romein W.G. Dujardin, Paul Elbers, Lucas Fleuren, Suzanne Geerlings, Theo Geijtenbeek, Armand Girbes, Bram Goorhuis, Martin P. Grobusch, Florianne Hafkamp, Laura Hagens, Jorg Hamann, Vanessa Harris, Robert Hemke, Sabine M. Hermans, Leo Heunks, Markus Hollmann, Janneke Horn, Joppe W. Hovius, Menno D. de Jong, Rutger Koning, Endry H.T. Lim, Niels van Mourik, Jeaninne Nellen, Esther J. Nossent, Frederique Paulus, Edgar Peters, Dan A.I. Pina-Fuentes, Tom van der Poll, Bennedikt Preckel, Jan M. Prins, Jorinde Raasveld, Tom Reijnders, Maurits C.F. J. de Rotte, Michiel Schinkel, Marcus J. Schultz, Femke A.P. Schrauwen, Alex Schuurmans, Jaap Schuurmans, Kim Sigaloff, Marleen A. Slim, Patrick Smeele, Marry Smit, Cornelis S. Stijnis, Willemke Stilma, Charlotte Teunissen, Patrick Thoral, Anissa M. Tsonas, Pieter R. Tuinman, Marc van der Valk, Denise P. Veelo, Carolien Volleman, Heder de Vries, Lonneke A. Vught, Michèle van Vugt, Dorien Wouters, A.H. Zwinderman, Matthijs C. Brouwer, W. Joost Wiersinga, Alexander P.J. Vlaar, Miranda F. Tompkins, Camille Alba, Daniel N. Hupalo, John Rosenberger, Gauthaman Sukumar, Matthew D. Wilkerson, Xijun Zhang, Justin Lack, Andrew J. Oler, Kerry Dobbs, Ottavia M. Delmonte, Jeffrey J. Danielson, Andrea Biondi, Laura Rachele Bettini, Mariella D’Angiò, Ilaria Beretta, Luisa Imberti, Alessandra Sottini, Virginia Quaresima, Eugenia Quiros-Roldan, Camillo Rossi, Riccardo Castagnoli, Daniela Montagna, Amelia Licari, and Gian Luigi Marseglia

Subjects
HLA, association, asymptomatic infection, COVID-19, population stratification, Genetics, QH426-470
Abstract

Summary: Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B∗15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B∗15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the United States (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B∗15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections studied, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified.

Published
2024
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13. Secondary flows in statistically unstable turbulent boundary layers with spanwise heterogeneous roughness

Author

Ali Amarloo, Pourya Forooghi, and Mahdi Abkar

Subjects
Secondary flows, Roughness heterogeneity, Unstable/convective boundary layer, Large-eddy simulation, Engineering (General). Civil engineering (General), TA1-2040
Abstract

Large-scale secondary motions are known to occur in turbulent flows over surfaces with spanwise roughness heterogeneity. Numerical studies often use adjacent high- and low-roughness longitudinal strips to investigate these secondary rolls in boundary layers without any thermal stratification. In the present study, the effect of unstable thermal stratification on secondary rolls in a very high-Reynolds-number turbulent flow with spanwise-heterogeneous roughness is investigated by means of large-eddy simulation. The strength of the unstable stratification is systematically changed from L/h=−20 to L/h=−1, where L and h are Monin-Obukhov length and boundary-layer height, respectively. This range covers the transition from neutral stratification to unstable stratification. The results show that the positive buoyancy associated with the unstable thermal stratification acts against the roughness-induced secondary rolls. In the case of unstable stratification, secondary rolls are completely canceled out by buoyancy and replaced by new stronger convection-induced rolls rotating in opposite directions.

Published
2022
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14. TIM-1 Ubiquitination Mediates Dengue Virus Entry

Author

Ophélie Dejarnac, Mohamed Lamine Hafirassou, Maxime Chazal, Margaux Versapuech, Julien Gaillard, Manuel Perera-Lecoin, Claudia Umana-Diaz, Lucie Bonnet-Madin, Xavier Carnec, Jean-Yves Tinevez, Constance Delaugerre, Olivier Schwartz, Philippe Roingeard, Nolwenn Jouvenet, Clarisse Berlioz-Torrent, Laurent Meertens, and Ali Amara

Subjects
Biology (General), QH301-705.5
Abstract

Summary: Dengue virus (DENV) is a major human pathogen causing millions of infections yearly. Despite intensive investigations, a DENV receptor that directly participates in virus internalization has not yet been characterized. Here, we report that the phosphatidylserine receptor TIM-1 is an authentic DENV entry receptor that plays an active role in virus endocytosis. Genetic ablation of TIM-1 strongly impaired DENV infection. Total internal reflection fluorescence microscopy analyses of live infected cells show that TIM-1 is mostly confined in clathrin-coated pits and is co-internalized with DENV during viral entry. TIM-1 is ubiquitinated at two lysine residues of its cytoplasmic domain, and this modification is required for DENV endocytosis. Furthermore, STAM-1, a component of the ESCRT-0 complex involved in intracellular trafficking of ubiquitinated cargos, interacts with TIM-1 and is required for DENV infection. Overall, our results show that TIM-1 is the first bona fide receptor identified for DENV. : Dejarnac et al. find that the phosphatidylserine receptor TIM-1 is a bona fide DENV receptor that mediates virus uptake through the clathrin-mediated pathway. TIM-1 is ubiquitinated at two lysines in its cytoplasmic tail and interacts with STAM-1 for efficient DENV infection.

Published
2018
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15. A Global Interactome Map of the Dengue Virus NS1 Identifies Virus Restriction and Dependency Host Factors

Author

Mohamed Lamine Hafirassou, Laurent Meertens, Claudia Umaña-Diaz, Athena Labeau, Ophelie Dejarnac, Lucie Bonnet-Madin, Beate M. Kümmerer, Constance Delaugerre, Philippe Roingeard, Pierre-Olivier Vidalain, and Ali Amara

Subjects
Biology (General), QH301-705.5
Abstract

Dengue virus (DENV) infections cause the most prevalent mosquito-borne viral disease worldwide, for which no therapies are available. DENV encodes seven non-structural (NS) proteins that co-assemble and recruit poorly characterized host factors to form the DENV replication complex essential for viral infection. Here, we provide a global proteomic analysis of the human host factors that interact with the DENV NS1 protein. Combined with a functional RNAi screen, this study reveals a comprehensive network of host cellular processes involved in DENV infection and identifies DENV host restriction and dependency factors. We highlight an important role of RACK1 and the chaperonin TRiC (CCT) and oligosaccharyltransferase (OST) complexes during DENV replication. We further show that the OST complex mediates NS1 and NS4B glycosylation, and pharmacological inhibition of its N-glycosylation function strongly impairs DENV infection. In conclusion, our study provides a global interactome of the DENV NS1 and identifies host factors targetable for antiviral therapies.

Published
2017
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16. Axl Mediates ZIKA Virus Entry in Human Glial Cells and Modulates Innate Immune Responses

Author

Laurent Meertens, Athena Labeau, Ophelie Dejarnac, Sara Cipriani, Laura Sinigaglia, Lucie Bonnet-Madin, Tifenn Le Charpentier, Mohamed Lamine Hafirassou, Alessia Zamborlini, Van-Mai Cao-Lormeau, Muriel Coulpier, Dorothée Missé, Nolwenn Jouvenet, Ray Tabibiazar, Pierre Gressens, Olivier Schwartz, and Ali Amara

Subjects
Biology (General), QH301-705.5
Abstract

Summary: ZIKA virus (ZIKV) is an emerging pathogen responsible for neurological disorders and congenital microcephaly. However, the molecular basis for ZIKV neurotropism remains poorly understood. Here, we show that Axl is expressed in human microglia and astrocytes in the developing brain and that it mediates ZIKV infection of glial cells. Axl-mediated ZIKV entry requires the Axl ligand Gas6, which bridges ZIKV particles to glial cells. Following binding, ZIKV is internalized through clathrin-mediated endocytosis and traffics to Rab5+ endosomes to establish productive infection. During entry, the ZIKV/Gas6 complex activates Axl kinase activity, which downmodulates interferon signaling and facilitates infection. ZIKV infection of human glial cells is inhibited by MYD1, an engineered Axl decoy receptor, and by the Axl kinase inhibitor R428. Our results highlight the dual role of Axl during ZIKV infection of glial cells: promoting viral entry and modulating innate immune responses. Therefore, inhibiting Axl function may represent a potential target for future antiviral therapies. : ZIKA virus (ZIKV) is responsible for congenital microcephaly. Meertens et al. show that the Axl receptor is expressed in microglia and astrocytes in the human developing brain. They also highlight the dual role of Axl during infection, which promotes viral entry and dampens innate immune responses in glial cells.

Published
2017
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