Η επιθηλιακή προς μεσεγχυματική μετατροπή είναι ένα φαινόμενο που πιθανότατα εμπλέκεται στην παθογένεια του καρκίνου του λάρυγγα. Η ΕΜΤ εξελισσόμενη μέσα από δαιδαλώδη μονοπάτια μεταγωγής σήματος καταλήγει να προσδώσει στο καρκινικό κύτταρο δομικά και λειτουργικά χαρακτηριστικά που το καθιστούν ικανό να μπορεί να διεισδύει στους ιστούς και να μεθίσταται. Κεντρικό μόριο στα μοριακά μονοπάτια που διαμεσολαβούν την ΕΜΤ στον καρκίνο του λάρυγγα είναι μια κινάση, η ILK, που δέχεται σήματα από τις ιντεγκρίνες και τους υποδοχείς αυξητικών παραγόντων. Στους επιθηλιακούς καρκίνους αναφέρεται η εμπλοκή της σε λειτουργίες όπως ρύθμιση του κυτταρικού κύκλου, αποφυγή της απόπτωσης, νεοαγγειογένεση, απώλεια των δομών συνοχής του κυττάρου, έκφραση μεταλλοπρωτεασών και αναδιαμόρφωση του κυτταροσκελετού. Στο λαρυγγικό καρκίνο όμως κρίσιμα φαινόμενα για τον μεταστατικό-επιθετικό χαρακτήρα των κυττάρων, όπως, η εξαφάνιση των E-cadherin, η μετακίνηση των β-catenin στον πυρήνα και η συσχέτιση μεταξύ τους, που διαπιστώθηκαν, δεν βρέθηκε να συνδέονται με την υπερέκφραση της ILK καθιστώντας προφανώς άλλους μηχανισμούς υπεύθυνους για την επιτέλεση αυτών των λειτουργιών. Ιδιαίτερα ενδιαφέρουσα όμως ήταν και η εντόπιση της ILK στον πυρήνα των κυττάρων του καρκίνου του λάρυγγα δίνοντας μια νέα προοπτική στην έρευνα για τον ρόλο της ILK στον καρκίνο. Στο μονοπάτι μεταγωγής σήματος της ILK στο λαρυγγικό καρκίνο βρέθηκε πως συμμετέχει και η ενεργοποιημένη Akt με την οποία επίσης σχετίζονται πολλές κρίσιμες λειτουργίες για το καρκινικό κύτταρο. Ωστόσο η p-Akt στο λαρυγγικό καρκίνο φαίνεται πως έχει κάποιο ρόλο αντίθετο με την λειτουργία του καρκινικού κυττάρου καθώς χαρακτηρίζει όγκους καλύτερης διαφοροποίησης. Ο λαρυγγικός καρκίνος τέλος διαπιστώθηκε πως χαρακτηρίζεται από την έκφραση υποδοχέων ανδρογόνων και οιστρογόνων καθιστώντας πολύ πιθανό το ρόλο αυτών των μορίων στην παθογένεια της νόσου. Ενδιαφέρουσα για την πιθανότητα εμπλοκής των υποδοχέων στερεοειδών ορμονών του φύλου στην ΕΜΤ ίσως να είναι η συσχέτιση των υποδοχέων ανδρογόνων και οιστρογόνων με την ILK και p-Akt αντίστοιχα. Οι υποδοχείς οιστρογόνων μάλιστα χαρακτηρίζοντας όγκους λάρυγγα αρχικών σταδίων ίσως θα μπορούσε να αποδειχτεί μόριο με προγνωστική αξία αλλά και θεραπευτικός στόχος. Τέλος η μελέτη της έκφρασης της ILK, της p-Akt και των υποδοχέων στεροειδών ορμονών του φύλου δεν ανέδειξε μια διαφορετική έκφραση μεταξύ υπεργλωττιδικών και γλωττιδικών καρκίνων του λάρυγγος ώστε να υποστηρίξει την ύπαρξη ενός μοριακού υποβάθρου στην παρατήρηση της ανόμοιας κλινικής συμπεριφοράς μεταξύ όγκων από τις δύο αυτές ανατομικά διακριτές περιοχές. / Epithelial to mesenchymal transition (EMT) is a process possibly implicated in the pathogenesis of laryngeal cancer. EMT is a type of epithelial cell plasticity which is characterized by long lasting phenotypic and molecular modifications of the epithelial cell as a result of a transforming procedure leading to a cell of mesenchymal type. This molecular procedure seems to be pivotal for the metastasis of epithelial cancers and its attribution to the epithelial cells is the gain of structural and functional traits which enable them to invade the tissues and metastaze. In the current study ILK expression, which is a central molecule in the signal transduction pathways of EMT, seems to be implicated in human laryngeal carcinoma. Furthermore, localization of ILK in the nucleus possibly suggests novel nuclear functions of ILK. In addition, enhanced ILK expression in laryngeal carcinoma correlates with activation of Akt. Moreover, while activated Act seems to characterize well differentiated tumors, loss of E-cadherin and activation of β-catenin were correlated with high grade carcinomas. Finally, in laryngeal cancer, mechanisms other than ILK overexpression seem to account for downregulation of E-cadherin and activation of β-catenin. Additionaly this study concluded that estrogen and androgen receptors are expressed in laryngeal carcinomas, indicating their possible role in the pathogenesis of this disease. It is interesting that the receptors of gender-related steroid hormones could have a possible relation to epithelial to mesenchymal transition phenomenon since a correlation between androgen and estrogen receptors with ILK and p-Akt respectively, was revealed. Moreover estrogen receptors characterize primary TMN-stage laryngeal carcinomas. This can be very important as it makes a prospect of using ER as a prognostic factor but even more as a novel hormonal therapy for laryngeal carcinomas. Finally the study of molecules like ILK, p-Akt, estrogen and androgen receptors did not reveal any differentiantal expression between glotic and supraglotic laryngeal carcinomas in order to support the existence of a molecular background, at least as far as those molecules are concerned, to the distinct clinical outcome of those different anatomically-derived laryngeal carcinomas. Metastasis is a rapid development in the ominous course of cancer. The effort to interpret the molecular basis of this phenomenon is not a subject of simple academic interest since the exploit of the molecular mechanisms so as to gain the control of metastasis could be the ‘‘bet’’ for a futuristic ‘‘molecular surgery’’.

Neuropeptides are present in nerve fibers of the upper and lower airways. Local release of these substances may be of importance for the pathophysiology of airway disorders and may play a role in responses to different stimuli. However, little is known about the distribution of neuropeptides in the larynx. The superior laryngeal nerve is one of the vagal branches supplying the larynx. The aim of the present study was to investigate the fiber composition of this nerve and to analyse the distribution of different neuropeptides and mast cells in the larynx. The internal and the external branches of the superior laryngeal nerve had a similar number and size of the nerve fibers. Numerous unmyelinated fibers were evenly distributed in the branches. A large majority of the fibers were sensory myelinated and unmyelinated fibers; only a few of the myelinated fibers of the external branch ( 2-10 %) were motor. About a quarter of the unmyelinated fibers of the internal and the external branches had their cell bodies in the brainstem, and single myelinated and unmyelinated fibers emanated from the superior cervical ganglion. In every superior laryngeal nerve examined one to three spherical paraganglia were observed. These paraganglia contained cells which were similar to the type I and type II cells found in the carotid body and the paraganglia of the recurrent laryngeal nerve. Thin-walled sinusoidal blood vessels which were sometimes fenestrated were also present The laryngeal mucosa was supplied with nerve fibers exhibiting substance P- and calcitonin gene-related peptide-like immunoreactivity with regional differences in the distribution. The laryngeal side of the epiglottis and the ventral recess were richly supplied, and the vocal cords showed no evidence of immunoreactive nerve fibers. The distribution of connective tissue mast cells and mucosal mast cells/globular leucocytes was similar to that of nerve fibers displaying substance P- and calcitonin gene-related peptide-like immunoreactivity. These cells were found in close approximation to nerve fibers. Acetylcholinesterase-positive ganglionic cells in the larynx showed vasoactive intestinal polypeptide-, neuropeptide Y-and enkephalin-like immunoreactivity. Neuropeptide Y-like immunoreactivity was co-localized with tyrosine-hydroxylase/dopamine beta-hydroxylase-like immunoreactivity in nerve fibers in some blood vessel walls. Enkephalin-like immunoreactivity was rarely found in this location and co-localization with tyrosine- hydroxylase-like immunoreactivity was not detected. In glands and some blood vessel walls neuropeptide Y- and enkephalin-like immunoreactivity were localized in nerve fibers showing a positive acetylcholinesterase reaction and vasoactive intestinal polypeptide-like immunoreactivity. Thus, this indicates that neuropeptide Y is present in both the sympathetic and parasympathetic nervous systems, while enkephalin and vasoactive intestinal polypeptide are confined to the parasympathetic nervous system in the rat larynx. The present study shows that the superior laryngeal nerve is mainly sensory, and the study also provides a morphological basis for neuropeptide effects in laryngeal physiology/pathophysiology. / <p>S. 1-27: sammanfattning, s. 29-97: 6 uppsatser</p> / digitalisering@umu

Orientador: Norma Sueli Pinheiro Módolo / Resumo: Justificativa e Objetivos: a diferença na incidência de eventos adversos perioperatórios (EAPs) entre tubo traqueal (TT), máscara laríngea (ML) e máscara facial (MF) ainda é questão controversa no tocante à anestesia em crianças com infecção de vias aéreas superiores (IVAS). O objetivo desta revisão sistemática foi comparar o risco de EAPs entre os dispositivos de via aérea após anestesia em pacientes pediátricos com IVAS. Métodos: foi conduzida revisão sistemática de acordo com as recomendações da Colaboração Cochrane e declaração PRISMA. A estratégia de busca foi realizada nas principais bases de dados eletrônicas (PubMed, EMBASE, Cochrane CENTRAL, Lilacs, Scielo, Scopus e Web of Science) e a última pesquisa foi realizada em 30 de junho de 2015. Não houve restrições quanto a idioma, data, revista ou publicação. Foram incluídos somente estudos avaliando EAPs em pacientes com IVAS submetidos à anestesia e cujas vias aéreas tenham sido manejadas com MF, ML ou TT. Dados de cada ensaio clínico randomizado (ECR) foram combinados utilizando o modelo de efeito randômico para cálculo do risco relativo (RR). Resultados: dos 680 estudos identificados, 5 eram ECRs e foram incluídos na análise final. Não houve diferença estatisticamente significante entre os diferentes dispositivos estudados com relação a broncoespasmo (RR 0,47, IC 95% 0,04-6,25, p=0,57), laringoespasmo (RR 0,84, IC 95% 0,56-1,27, p=0,41), dessaturação arterial de oxigênio (RR 0,66, IC 95% 0,38-1,16, p=0,15), apneia (RR... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Background: rate of perioperative adverse events (PAEs) among tracheal tube (TT), laryngeal mask airway (LMA), and facemask (FM) remains a controversial issue during anesthesia in children with an upper respiratory tract infection (URTI). The aim of the present study was to compare the risk of PAEs among the different airway devices after anesthesia in pediatric patients with an URTI. Methods: a systematic review according to the Cochrane Handbook and PRISMA guidelines was conducted. The search was performed in the main electronic databases (PubMed, EMBASE, Cochrane CENTRAL, Lilacs, Scielo, Scopus and Web of Science) and the last one was carried out in June 30, 2015. There were no language, year of publication, or publication status restriction. Only randomized clinical trial evaluating anesthesia in children with URTI and who were submitted to either of the airway devices were included. Data from each trial was combined using the random effects models to calculate the pooled relative risk (RR) and 95% confidence intervals. Results: from 680 studies identified, 5 randomized clinical trials were included in the final analysis. There were no statistical difference with regard to bronchospasm (RR 0.47, CI 95% 0.04-6.25, p=0.57), laryngospasm (RR 0.84, CI 95% 0.56-1.27, p=0.41), arterial oxygen desaturation (RR 0.66, CI 95% 0.38-1.16, p=0.15), apnea or breath holding (RR 0.91, CI 95% 0.49-1.67, p=0.75), sore throat (RR 0.87, CI 95% 0.39-1.96, p=0.74), and hospital readmission (RR... (Complete abstract click electronic access below) / Doutor

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No. of bitstreams: 1 carvalho_alr_dr_bot.pdf: 1510567 bytes, checksum: 016ef353508cc1d168cdef1d8cf5cea3 (MD5) Previous issue date: 2016-02-24 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Justificativa e Objetivos: a diferença na incidência de eventos adversos perioperatórios (EAPs) entre tubo traqueal (TT), máscara laríngea (ML) e máscara facial (MF) ainda é questão controversa no tocante à anestesia em crianças com infecção de vias aéreas superiores (IVAS). O objetivo desta revisão sistemática foi comparar o risco de EAPs entre os dispositivos de via aérea após anestesia em pacientes pediátricos com IVAS. Métodos: foi conduzida revisão sistemática de acordo com as recomendações da Colaboração Cochrane e declaração PRISMA. A estratégia de busca foi realizada nas principais bases de dados eletrônicas (PubMed, EMBASE, Cochrane CENTRAL, Lilacs, Scielo, Scopus e Web of Science) e a última pesquisa foi realizada em 30 de junho de 2015. Não houve restrições quanto a idioma, data, revista ou publicação. Foram incluídos somente estudos avaliando EAPs em pacientes com IVAS submetidos à anestesia e cujas vias aéreas tenham sido manejadas com MF, ML ou TT. Dados de cada ensaio clínico randomizado (ECR) foram combinados utilizando o modelo de efeito randômico para cálculo do risco relativo (RR). Resultados: dos 680 estudos identificados, 5 eram ECRs e foram incluídos na análise final. Não houve diferença estatisticamente significante entre os diferentes dispositivos estudados com relação a broncoespasmo (RR 0,47, IC 95% 0,04-6,25, p=0,57), laringoespasmo (RR 0,84, IC 95% 0,56-1,27, p=0,41), dessaturação arterial de oxigênio (RR 0,66, IC 95% 0,38-1,16, p=0,15), apneia (RR 0,91, IC 95% 0,49-1,67, p=0,75), dor de garganta (RR 0,87, IC 95% 0,39-1,96, p=0,74) e taxa de readmissão hospitalar (RR 0,76, IC 95% 0,17-3,33, p=0,71). O uso de ML resultou em significante redução da incidência de tosse (RR 0,63, IC 95% 0,45-0,89, p=0,009) comparado aos outros dispositivos de via aérea. Notou-se, também, tendência à redução da incidência de vômito com o uso da ML quando comparado ao TT e MF, embora sem significância estatística (RR 0,57, IC 95% 0,33-1,00, p=0,05). Conclusões: o manejo ideal das vias aéreas em crianças com IVAS permanece incerto. Esta revisão sistemática demonstra que o uso da ML durante anestesia em crianças com IVAS não resultou na diminuição dos mais temidos EAPs. Entretanto, o uso da ML foi mais eficaz em reduzir a incidência de tosse comparado aos outros dispositivos de via aérea. Além disso, houve tendência da ML em reduzir a incidência de vômito. / Background: rate of perioperative adverse events (PAEs) among tracheal tube (TT), laryngeal mask airway (LMA), and facemask (FM) remains a controversial issue during anesthesia in children with an upper respiratory tract infection (URTI). The aim of the present study was to compare the risk of PAEs among the different airway devices after anesthesia in pediatric patients with an URTI. Methods: a systematic review according to the Cochrane Handbook and PRISMA guidelines was conducted. The search was performed in the main electronic databases (PubMed, EMBASE, Cochrane CENTRAL, Lilacs, Scielo, Scopus and Web of Science) and the last one was carried out in June 30, 2015. There were no language, year of publication, or publication status restriction. Only randomized clinical trial evaluating anesthesia in children with URTI and who were submitted to either of the airway devices were included. Data from each trial was combined using the random effects models to calculate the pooled relative risk (RR) and 95% confidence intervals. Results: from 680 studies identified, 5 randomized clinical trials were included in the final analysis. There were no statistical difference with regard to bronchospasm (RR 0.47, CI 95% 0.04-6.25, p=0.57), laryngospasm (RR 0.84, CI 95% 0.56-1.27, p=0.41), arterial oxygen desaturation (RR 0.66, CI 95% 0.38-1.16, p=0.15), apnea or breath holding (RR 0.91, CI 95% 0.49-1.67, p=0.75), sore throat (RR 0.87, CI 95% 0.39-1.96, p=0.74), and hospital readmission (RR 0.76, CI 95% 0.17-3.33, p=0.71). The use of LMA produced a significant reduction of cough (RR 0.63, CI 95% 0.45- 0.89, p=0.009) compared with other airway devices. Also, LMA tended toward a reduction of vomiting compared with other forms of airway management but did not reach statistical significance (RR 0.57, CI 95% 0.33-1.00, p=0.05). Conclusions: the ideal airway management in children with URTI remains obscure. This systematic review demonstrates that the use of LMA during anesthesia for surgery in children with URTI did not result in decrease of the most feared PAEs. However, the use of LMA was better than other airway devices in reducing cough and tended toward a protective effect against vomiting.

Voice analysis is an important tool in the diagnosis of laryngeal disorders. Among distinct signal processing techniques employed for voice analysis, the spectrogram is commonly used, as it allows for a visualization of the variation of the energy of the signal as a function of the both time and frequency. In this context, this study investigates the use of the global energy of the voice signal, estimated through the spectrogram, as a tool for discrimination between signals obtained from healthy and pathological subjects. This research has also exploited the potential use of the global energy of the voice signal to discriminate distinct laryngeal disorders. In total, 94 subjets were involved in this study, from which 46 were dysphonic and 48 normal. The diagnosis of laryngeal disorders was confirmed by means of a videolaryngoscopic examination. Participants were also subjected to a clinical examination of vocal acoustic through the recording of the sustained vowel. The global energy allowed for the discrimination between normal and disphonic voice. Furthermore, this technique could discriminate the voice signal of patients suffering from left vocal fold paralysis from those suffering from other investigated disorders. The results suggest the global energy of the signal as an auxiliary and alternative tool for the diagnosis between normal and dysphonic voice. / A análise do sinal de voz é uma ferramenta importante no diagnóstico dos distúrbios laríngeos. Dentre as diversas técnicas para o processamento da voz destaca-se o espectrograma por permitir uma visualização da variação da energia do sinal em função do tempo e freqüência. Neste contexto, esta pesquisa investiga a energia global do sinal de voz, estimada a partir do espectrograma, como ferramenta capaz de discriminar esses sinais, obtidos de pacientes com diferentes doenças, daqueles coletados de sujeitos saudáveis. O estudo ainda verifica a possibilidade do uso da energia global na discriminação de distúrbios laríngeos. No total 94 indivíduos participaram desse estudo, sendo 46 disfônicos e 48 eufônicos. Inicialmente os sujeitos foram submetidos a um exame de videolaringoscopia para a determinaçãoção do diagnóstico. Posteriormente eles foram submetidos a um exame clínico de análise acústica vocal por meio da gravação da vogal sustentada. Utilizando a energia global foi possível discriminar as vozes normais das vozes disfônicas. Por meio da energia global foi possível ainda separar as vozes de pacientes portadores de paralisia da prega vocal esquerda de todas as outras doenças laríngeas investigadas. Podemos sugerir a energia global da voz como uma ferramenta auxiliar no diagnóstico diferencial entre vozes normais e disfônicas. / Mestre em Ciências

Ces travaux ont pour objectif, à partir de l’analyse en ciné-IRM du processus de déglutition salivaire chez un sujet sain, d’optimiser le rendement clinique de cette technique pour les dysphagies. Un protocole d’imagerie rapide et une grille d’évaluation (D-GRID) ont été conçus. Leur application a été étudiée chez des patients présentant une tumeur des voies aéro-digestives supérieures, et chez des patients porteurs de Prothèses Intra-Laryngées (PIL). LaD-GRID permet de mesurer et d’évaluer le mécanisme de protection des voies aériennes, de concevoir des programmes de réhabilitation et de suivre l’évolution des dysphagies. L’analyse de la déglutition en ciné-IRM est limitée par l’absence de bolus et la position de decubitus dorsal, mais nos résultats montrent sa fiabilité. La ciné-IRM définit des modèles du déplacement normal ou anormal des structures anatomiques au cours de la déglutition.Les données de l’imagerie dynamique contribuent au développement des PIL. / The aim of this study was to develop the use of fast imaging to assess the swallowing mechanism in healthy volunteers, and to optimize its clinical use in case of oro-pharyngeal dysphagia. A fast imaging protocol during dry swallowing and an evaluation grid (D-GRID) were designed. Healthy subjects, patients with head and neck canceror patients implanted with intra-laryngeal prostheses under went kinetic MRI. True-FISP sequences provide accurate information about morphological aspects of the oro-pharyngo-larynx and displacements of anatomical structures involved in the normal or impaired swallowing mechanism. The analysis of the swallowing process with cine-MRIis restricted because of the lack of bolus and the supine position, but our outcomes are reliable. Patterns of normal orabnormal anatomical structures movements during swallowing are determined by cine-MRI. The development ofIntra-Laryngeal Prostheses represents a therapeutic solution partly based on dynamic MRI data.

INTRODUÇÃO: Alterações genéticas múltiplas são comuns durante a carcinogênese e, nesse panorama, o gene supressor tumoral TP53 é um dos mais associados à transformação maligna. Recentemente, dois genes similares ao TP53, foram identificados, o TP73 e o TP63. O TP63 situa-se no cromossomo 3q e tem papel comprovado no desenvolvimento epidérmico, sendo detectado em vários tecidos humanos. Inúmeros trabalhos relacionaram a expressão da proteína p63 com carcinomas do trato aerodigestivo superior. OBJETIVOS: O presente estudo objetivou avaliar a expressão Imunoistoquímica da proteína p63 e seu valor prognóstico nos carcinomas epidermóides da laringe. CASUÍSTICA E MÉTODOS: Foram estudados retrospectivamente 127 pacientes submetidos a laringectomia total no Instituto Nacional de Câncer, Rio de Janeiro, entre 1998 e 2000. Houve 111 doentes masculinos e 16 femininos, 69 brancos e 58 não-brancos, com idade entre 36 a 93 anos, média de 59 e mediana de 58 anos. Dezenove tumores eram glóticos, 16 supraglóticos e 92 acometiam mais de um local, correspondendo a 15%, 13% e 72% respectivamente. Quanto ao estadiamento clínico, dois casos eram do estádio I (1,6%), 21 do II (16,5%), 82 do III (64,6%) e 22 do IV (17,3%). Noventa e seis pacientes (75,6%) receberam radioterapia complementar. A técnica imunoistoquímica, com anticorpos monoclonais do clone 4A4, foi utilizada para estudar a expressão da p63. O percentual de células imunocoradas positivamente foi estimado conforme os seguintes escores: 0: ausência de imunocoloração; 1: imunocoloração em < 30% das células neoplásicas; 2: imunocoloração em > 30% e < 70% das células neoplásicas; e 3: imunocoloração em > 70% das células neoplásicas. Foram observados 62 casos do escore 3 (+++), 60 do escore 2 (++), 4 do 1 (+) e 1 caso sem expressão (0), correspondendo respectivamente a 48,8%, 47,2%, 3,1% e 0,8% da amostra. Através de análises uni e multivariadas, a imunoexpressão da proteína p63 e os outros fatores de provável impacto prognóstico foram avaliados quanto ao grau de associação aos eventos recidiva e óbito. RESULTADOS: A análise multivariada identificou a imunoexpressão da proteína p63 e o envolvimento da hipofaringe como preditivas para ocorrência de recidiva e óbito pelo carcinoma. A sobrevida global foi de 73,9% em 24 meses e de 59,5% em 60 meses. A sobrevida livre de recorrência foi de 77,2% e 75,1%, e a sobrevida relacionada ao óbito pelo carcinoma foi de 79% e 67% em 24 e 60 meses respectivamente. CONCLUSÕES: Apenas a recidiva associou-se estatisticamente à expressão da proteína p63. A p63 se mostrou altamente expressa nos carcinomas epidermóides de laringe e, apesar dos poucos casos com expressão reduzida, a hipoexpressão da p63 foi preditiva de um pior prognóstico nesses doentes. / INTRODUCTION: Multiple genetic changes are common during carcinogenesis and, in this scene, the gene TP53 is one of the most associated with malignant transformation. Recently, two related genes to the TP53, were identified, the TP73 and TP63. The TP63 stands on the chromosome 3q and has a proven role in the epidermal development, being detected in several human tissues. Many work linked the expression of p63 protein with carcinomas of the upper aero-digestive tract. OBJECTIVE: The objective of this study was to evaluate the immunohistochemical expression of p63 protein and its prognostic value in squamous cell carcinomas of the larynx. CASUISTRY AND METHODS: The p63 expression has been examined in 127 patients who were submitted to total laryngectomy, with or without adjuvant radiotherapy, in the Brazilian National Cancer Institute, between 1998 and 2000. There were 111 male patients and 16 female, 69 white and 58 non-white, aged between 36 to 93 years, average 59 and median of 58 years. Nineteen tumors were glottic, 16 supraglottic and 92 affected more than one place, corresponding to 15%, 13% and 72% respectively. As to the clinical staging, two cases were stage I (1.6%), 21 of the II (16.5%), 82 of the III (64.6%) and 22 of the IV (17.3%). Ninety-six patients (75.6%) received complementary radiotherapy. The immunohistochemical technique with the use of monoclonal antibodies of clone 4A4, has been used to study the expression of p63. The percentage of positive cells was estimated as the following scores: 0: no immunostaining; 1: immunostaining in <30% of neoplastics cells; 2: immunostaining in >30% and <70% of neoplastics cells; And 3: immunostaining in >70% of neoplastics cells. Sixty two cases were observed in score three, 60 in score two 4 in score one (+) and 1 case without expression (0), corresponding respectively to 48.8%, 47.2%, 3.1% and 0.8% of the sample. Through uni and multivariate analysis, the immunoexpression of p63 protein and the other factors likely to impact prognosis were evaluated on the degree of association to recurrence and death. RESULTS: The multivariate analysis identified the immunoexpression of protein p63 and the involvement of the hypopharynx as statistically significant for the risk of recurrence and death by cancer. The overall survival was 73.9% in 24 months and 59.5% at 60 months. CONCLUSIONS: The disease-free survival was 77.2% and 75.1%, and the disease-specific survival was 79% and 67% at 24 and 60 months respectively. The p63 protein was highly expressed in squamous cell laryngeal carcinomas. In spite of few cases with reduced expression, p63 protein underexpression was statistically associated to the recurrence and may have a negative impact upon prognosis.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Microvascularization of human superior membranous vocal folds tends to be parallel to the long axis. This pattern of microvascularization changes with disease. The objective this study was to describe microvascular changes in the human vocal folds with polypoid alterations as differential diagnosis with other laryngeal diseases. A retrospective study was conducted to describe alterations in the microvasculature of the vocal folds of eleven patients having polyps, who underwent laryngeal microsurgery and subsequent rigid and contact laryngoscopy. To study the microvascular changes, D Ávila (2002) classification was used. The vocal folds were divided in three regions: superior membranous, superior cartilaginous, and subglottic. The twelve types of microvessels described by D Ávila were identified in the study and 74 altered microvessels were found; dilated parallel and branching micro vessels predominated. Our findings highlight that microvascularization of the vocal folds changes with polyp formation; and the presence of branching microvessels in the surface of vocal cord lesions suggests a diagnosis of polyp formation. / A microvascularização da face superior membranosa da prega vocal humana tende a ser paralela ao seu longo eixo. Este padrão de vascularização modifica-se na presença de patologias. O objetivo deste trabalho foi descrever as alterações microvasculares que ocorrem na prega vocal humana acometida por pólipo. Através de estudo retrospectivo foram descritas as alterações microvasculares que ocorreram nas pregas vocais de 11 pacientes de ambos os gêneros, portadores de pólipos, atendidos nas Clínicas de Dr. Jeferson D Ávila e Dr. Edilson Cunha e submetidos à microcirurgia da laringe e às endoscopias rígida e de contato da laringe. Para descrever as alterações microvasculares foi utilizada a classificação de D Ávila (2002) e as pregas vocais foram dividas em 3 faces: face superior membranosa, face superior cartilaginosa e face subglótica. Os 12 tipos de microvasos descritos por D Avila foram identificados neste estudo, tendo sido encontrados 74 microvasos alterados, havendo predominância dos microvasos paralelo ectásico e ramificado em rede. Nossos achados ressaltam que a microvascularização da prega vocal está alterada na presença de pólipo e que a presença de microvaso do tipo ramificado em rede na superfície de uma lesão única ou múltipla de prega vocal sugere fortemente a presença de pólipo de prega vocal.

Estudo com objetivo de avaliar e comparar o desempenho teórico e prático de estudantes de enfermagem submetidos a estratégias de ensino-aprendizagem, aula expositivo-dialogada e atividade prática em laboratório de habilidades ou aula simulada, no manejo da via aérea em emergências por meio da máscara laríngea (ML). Estudo com delineamento experimental, abordagem quantitativa, de intervenção tipo Ensaio Clínico Randomizado Controlado. A população consistiu dos estudantes do oitavo período, bacharelado, da Escola de Enfermagem de Ribeirão Preto e a amostra de 17 estudantes, randomizados para grupo controle (GC) e grupo intervenção (GI). O GC foi submetido à aula expositivo-dialogada seguida de atividade prática em laboratório de habilidades com manequim de baixa fidelidade e o GI à aula simulada em laboratório utilizando o mesmo manequim. Elaboraram-se os instrumentos de avaliação escrita, cenário de simulação e avaliação clínica objetiva e estruturada no cenário de simulação (checklist), validados em aparência e conteúdo por comitê de juízes. A estratégia de coleta de dados foi Workshop intitulado \"Manejo da via aérea em emergências: uso da ML\". Foram avaliados teste escrito e OSCE (Exame Clínico Objetivo Estruturado) - avaliação clínica estruturada em Laboratório de Simulação, este último empregando como ferramenta o manequim de média-fidelidade. A atividade foi filmada e analisada por três avaliadores. Analisaram-se os desfechos: desempenho teórico no teste escrito e prático no OSCE, tempo de execução do OSCE, tempo para obtenção da primeira ventilação eficaz, número de tentativas para inserção da ML até obtenção de ventilação efetiva. Resultados: 16 estudantes eram do sexo feminino e um do sexo masculino, a idade média 24,4±4,2 anos. No pré-teste a nota média do GC de 6,6±1,0 e do GI de 6,5±0,5 e a mediana para ambos 6,5. No pós-teste a nota média do GC foi 8,4±0,8 (mediana 8,5), do GI de 8,6±1,1 (mediana 8,6). Comparando-se as médias obtidas no pré-teste por ambos os grupos, não há diferença estatisticamente significante (p=07427). Tal fato também pôde ser constatado no pós-teste (p=0,7117). Comparando as notas pré e pós-teste do GC evidenciou diferença estatisticamente significante (p=0,0025) o que também ocorreu para o GI (p=0,0002). A média no OSCE do GC foi 7,8±0,52 e GI 8,4±0,89; comparou-se tais notas verificando-se que não há diferença estatisticamente significante (p=0,0822). A média obtida pelo GC no pós-teste foi maior que a média obtida no OSCE e, para o GI, são equivalentes. O tempo médio de execução do OSCE pelo GC foi 479,8±183,3s (mediana 468,5s) e no GI 520,3±157s (mediana 506s), não havendo diferença estatisticamente significante (p=0,6311) e também para obtenção da primeira ventilação eficaz (p=0,9835). A média do nº tentativas para inserção da ML pelo GC 1,63±0,74 e GI 1,56±0,63. Embora os resultados não apontem diferença estatisticamente significante entre as médias dos grupos no pós-teste, para o GI os escores foram superiores. No presente estudo, apesar de diferentes estratégias de ensino abordarem o manejo da via aérea em emergências com a ML, os resultados demonstram que as mesmas foram eficazes e os objetivos de aprendizagem foram alcançados, pois houve incremento nas notas obtidas no pós-teste e no OSCE em ambos os grupos. / Study aimed to evaluate and compare the theoretical and practical performance of nursing students subjected to teaching and learning strategies, exhibition-dialogued class, and practical activity in skill lab or simulated class in airway management in emergencies through laryngeal mask (LM). This is a study of experimental design, quantitative approach, intervention type, Controlled Randomized Trials. The population consisted of students in the eighth semester from the Bachelor\'s Degree of the University of São Paulo at Ribeirão Preto College of Nursing and the sample consisted of 17 students, randomly assigned to the control group (CG) and the intervention group (IG). The CG was subjected to exhibition-dialogued class followed by practical activity in skill lab with low-fidelity mannequin and the IG to simulated class in the lab using the same mannequin. Written evaluation instruments, simulation scenario and objective structured clinical evaluation in simulation scenario (checklist) were developed and validated in appearance and content by a committee of judges. The strategy for data collection was the workshop entitled \"Airway management in emergencies: use of LM\". They were evaluates through written test and the OSCE (Objective Structured Clinical Examination) - structured clinical evaluation in Simulation Laboratory, the latter employing the medium-fidelity mannequin as tool. The activity was filmed and analyzed by three evaluators. The outcomes were analyzed: theoretical performance in written and practical test in the OSCE, the OSCE runtime, time to obtain the first effective ventilation, number of attempts to insert the LM to obtain effective ventilation. Results: 16 students were female and one male, mean age 24.4±4.2 years. In the pre-test the score average of CG was 6.6±1.0 and of IG was 6.5±0.5 and the median for both was 6.5. At post-test, the average score of CG was 8.4±0.8 (median 8.5), of IG was 8.6±1.1 (median 8.6). Comparing the averages obtained in the pre-test for both groups, there was no statistically significant difference (p=0.7427). This fact could also be observed in the post-test (p=0.7117). Comparing notes of pre and post-test of CG there was a statistically significant difference (p=0.0025) which also occurred for IG (p=0.0002). The mean of the OSCE for CG was 7.8±0.52 and for IG was 8,4±0,89; compared to such notes and it was verified that there is no statistically significant difference (p=0.0822). The average obtained by CG in the post-test was higher than the average obtained IG in the OSCE, and for IG they were equivalent. The average execution time of the OSCE for CG was 479.8 ± 183.3s (median 468.5s) and for IG 520.3±157s (506s median), with no statistically significant difference (p=0.6311) and also for obtaining the first effective ventilation (p=0.9835). The average of attempts to insert the LM by CG was 1.63±0.74 and by IG was 1.56±0.63 GI. Although the results do not indicate a statistically significant difference between the averages of the groups in the post-test, the scores were higher for IG. In this study, although different teaching strategies addressing airway management in emergencies through LM were used, the results show that they were effective and the learning objectives have been achieved, because there was an increase in the scores obtained in the post-test and in the OSCE in both groups.

A diminuição da sobrevida registrada para pacientes com câncer de laringe nas últimas décadas pode estar relacionada a mudanças nos padrões de tratamento. Na literatura recente, há uma polëmica sobre o tratamento de tumores laríngeos em estádio clínico T3 devido ao emprego disseminado de estratégias de preservação de orgãos (Hoffman, 2006). Embora os critérios de inclusão para o grupo de preservação de órgãos tendam a selecionar tumores de \"baixo volume\", a escolha de uma determinada estratégia depende também da formação profissional do médico, da experiência e da infraestrutura do hospital e dos desejos dos pacientes. Essa consideração pressupõe uma distribuição homogênea dos pacientes entre os grupos de tratamento. No entanto, deve-se destacar o papel prognóstico das variáveis relacionadas ao tumor, ao paciente e à opção terapêutica na prática clínica. Objetivo: Avaliar as características clínicas, patológicas e a expressão de biomarcadores ativados pela via do EGFR em uma série de casos em relação à evolução e ao prognóstico. Metodologia: No presente estudo, 145 pacientes consecutivos com diagnóstico de carcinomas avançados de laringe cT3N0-3M0 foram analisados retrospectivamente. Foram incluídos casos de carcinoma epidermoide de supraglote, glote, subglote e transglotte, tratados em uma única instituição por quatro diferentes estratégias de tratamento (cirurgia exclusiva; cirurgia mais terapia adjuvante; radioterapia exclusiva, e radioquimioterapia). Os dados foram obtidos a partir do Registro de Câncer do Hospital A.C. Camargo, São Paulo (1990-2007). Uma série de variáveis clínicas e patológicas foi avaliada pelo métodos de Kaplan-Meier e de regressão de Cox. Opções de tratamento também foram avaliadas como fator prognóstico. Associações entre características clínico-patológicas do tumor e sobrevida, sobrevida livre de doença e risco de morte, foram investigadas. Resultados: Três variáveis clínicas, as variáveis terapêuticas e cinco variáveis patológicas, foram estatisticamente significativas na estimativa de sobrevida específica em 5 anos (CS-5a). A sobrevida foi influenciada negativamente pela invasão do tumor primário do espaço pré-epiglótico (45,5%, P = 0,003), pescoço clínico (cN) positivo (37,6%, P = 0,031), invasão da área retrocricóide (0,0%, P = 0,009) , invasão linfática (44,1%, P = 0,015), extravasamento capsular (43,1%, P = 0,003), pescoço patológico (pN) positivo (42,9%, P = 0,001), linfonodos positivos nos níveis cervicais IV-VI (33,3%, P = 0,008), margens cirúrgicas positivas (22,2%, P = 0,001). O tratamento teve impacto na sobrevida (CS-5a): a taxa foi de 51,6%, quando houve tratamento adjuvante (devido a achado patológico positivo na peça operatória), diminuiu até 41,5% no grupo de radioterapia exclusiva (P = 0,039). Cirurgia exclusiva e radioquimioterapia influenciaram a sobrevida de maneira semelhante (74,0% ; 77,5%). Considerando variáveis clínicas e terapêuticas, resultaram ser fatores prognósticos independentes: invasão do espaço paraglótico (RR multivariado 1,92; IC 1,02-3,61), pescoço clínico (cN) positivo (RR multivariado 2,24; IC 1,11-4,50), invasão do espaço pré-epiglótico (RR multivariado 2,65; IC 1,46-4,81) e tratamento radioterapico exclusivo (RR multivariado 2,88; IC 1,31-6,30); incluindo as variáveis patológicas, resultaram ser fatores prognósticos independentes achados patológicos de extravasamento capsular (RR multivariado 3,09; IC 1,56-6,12) e margens cirúrgicas comprometidas (RR multivariado 3,45; IC 1,11-10,75). A investigação de expressão imunoistoquímica de dez biomarcadores das vias de transdução de sinal ativadas pelo receptor tirosina quinase Erb B (EGFR, Erb B2, Erb B3, Erb B4, RAS, MEK, ERK, mTOR, PTEN, p53) mostrou associação entre expressão imunoistoquímica positiva de ErbB3 e ErbB4 e expressão de biomarcadores da via MAPKs e AKT-PI3K (MEK e mTOR). A positividade desses biomarcadores, ou seja, a desregulação da rede ErbB foi associada à invasão linfática, ponto de partida do acometimento linfonodal que resultou ser fator prognóstico independente entre as variáveis clínicas e patológicas (extravamento capsular). Conclusões: Entre as variáveis clínicas e terapêuticas, resultaram ser fatores prognósticos independentes: invasão do espaço paraglótico, pescoço clínico (cN) positivo, invasão do espaço pré-epiglótico e tratamento radioterápico exclusivo. Quando foram incluídas as variáveis patológicas, resultaram ser fatores prognósticos independentes achados patológicos de extravasamento capsular e margens cirúrgicas comprometidas. A positividade dos biomarcadores estudados (desregulação da rede ErbB), foi associada a invasão linfática. / The decreased survival recorded for patients with laryngeal cancer in the last decades may be related to changes in patterns of management; in literature a recent debate has been dedicated to the management of clinical stage T3 due to the disseminated use of organ preservation strategies (Hoffman, 2006). Although inclusion criteria for organ preservation group tends to select \"low volume\" tumors, in clinical practice the choice of a determined strategy depends also to medical and hospital experience and infrastructure and on patients\' wishes. This consideration may suppose an homogenous distribution of the patients among the treatment groups, however in clinical practice several clinico-pathological and therapeutic prognostic factors are considered for therapeutic decision. Objectives: Evaluate clinical and pathological characteristics and expression of biomarkers activated by the EGFR cascade in a case series and analise the association with outcomes and prognosis. Materials and method: In the present study 145 consecutive patients with diagnosis of laryngeal advanced carcinomas, cT3N0-3M0, were retrospectively analyzed, including cancer of the supraglottis, glottis, subglottis and trans-glottis, treated in a single institution by four different treatment strategies (exclusive surgery, surgery and adjuvant therapy, radiotherapy alone, and radiochemotherapy). Data was obtained from the Cancer Registry, Hospital AC Camargo, São Paulo (1990-2007). A set of clinical and pathological variables were assessed by Kaplan-Meier and Cox regression methods. Treatment option was also assessed as prognostic factor. Associations between clinical-pathological features of the tumor and survival, disease free-survival and risk of death, were investigated. Results: Three clinical variables, the therapeutic variable and five pathological variables, were statistically significant in estimating cancer specific survival at 5 years (CS-5y). Survival was negatively influenced by primary tumour spreading as filling of pre-epiglottic space (45.5%, P = 0.003), clinical neck (cN) positive (37.6%, P = 0.031), invasion of retrocricoid area (0.0%, P = 0.009), lymphatic invasion (44.1%, P = 0.015), extra-capsular nodal spread (43.1%, P = 0.003), pathological neck (pN) positive (42.9%, P = 0.001), positive IV-VI levels cervical nodes (33.3%, P = 0.008), positive surgical margins (22.2%, P = 0.001); treatment impacted on CS-5y, it decreases at 51.6% if adjuvant treatment (positive pathological finding on operative specimen), up to 41.5% in exclusive radiotherapy group (P = 0.039); exclusive surgery and radio-chemotherapy influenced survival similarly (74.0%; 77.5%). Among clinical e therapeutic variables, invasion of paraglottic space (HR adjusted 1.92; IC 1.02-3.61), positive clinical neck (cN) (HR adjusted 2,24; IC 1,11-4,50), invasion of pre-epiglottic space (HR adjusted 2,65; IC 1,46-4,81) and exclusive radiotheraphy (RR adjusted 2,88; IC 1,31-6,30) resulted to be independent prognostic factors; including pathological variables, extracapsular node invasion (HR adjusted 3,09; IC 1,56-6,12) and positive resection margins (HR adjusted 3,45; IC 1,11-10,75) were independent prognostic factors. Exploration of immunohistochemical expression of ten biomarkers of the signal transduction pathways activated by tyrosine kinases receptor Erb B (EGFR, Erb B2, Erb B3, Erb B4, RAS, MEK, ERK, mTOR, pTEN, p53) showed association between positive immunohistochemical expression of ErbB3 and ErbB4 and biomarkers of MAPKs and AKT-PI3K pathways (MEK and mTOR); the dysregulation of the Erb B network was associated with lymphatic invasion, starting point for lymph-nodes involvement that resulted to be clinical independent prognostic factors. Conclusion: Among clinical and therapeutic variables, the identified independent prognostic factors were: invasion of paraglotic space, clinically positive neck, invasion of pre-epiglotic space and radiotherapy alone. When pathologic variables were included, extracapsular spread and positive surgical margins were identified as independent prognostic factors. Positive results of the studied biomarkers (dysregulation of Erb B network) was associated with lymphatic invasion.