Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 5 uppsatser.

A avaliação da presença de destruição óssea provocada por neoplasias malignas de boca e orofaringe é um fator de fundamental importância no estabelecimento da terapêutica adequada para o caso, como também, para a determinação do prognóstico do paciente. O presente estudo teve por objetivo determinar os aspectos clínicos (localização, forma de apresentação e estadiamento) que podem estar associadas com o potencial de infiltração do osso subjacente a lesão, como também determinar a sensibilidade e especificidade do exame físico. A população de estudo consistio de vinte e cinco pacientes (17 homens e 8 mulheres, média de idade de 57,88 anos) portadores de neoplasias malignas de boca e orofaringe atendidos no Ambulatório de Semiologia da Faculdade de Odontologia da Universidade de São Paulo – campus São Paulo, no período de agosto de 2003 a agosto de 2004, os quais foram submetidos ao exame clínico e a tomografia computadorizada (TC). A TC foi considerada o padrão ouro para a avaliação da presença de destruição óssea. Foi observada a presença de infiltração neoplásica para o tecido ósseo adjacente em 68% dos casos (17 pacientes). O exame físico dos pacientes revelou uma sensibilidade de 80% e especificidade de 87,50% na análise de comprometimento do osso, além de uma acurácia de 84%. As lesões que se apresentavam clinicamente como uma úlcera do tipo infiltrativa e lesões do tipo nodulares, não ulceradas, foram as que apresentaram maior potencial de infiltrar-se para o osso, 68,75% e 100% respectivamente. A localização do tumor em determinados sítios, também influenciou diretamente na presença de invasão óssea,principalmente lesões localizadas em região de gengiva, trígono retromolar, palato duro e orofaringe. O estadiamento das lesões revelou relação existente entre o tamanho do tumor e a presença de metástases à distância com a presença de infiltração da neoplasia para o tecido ósseo. Concluindo, observou-se que a identificação de determinados parâmetros clínicos como localização, forma de apresentação clinica, tamanho da lesão e a presença de metástases à distância, associado a um criterioso exame físico regional podem servir como valiosas ferramentas para a análise de envolvimento ósseo por neoplasias malignas de boca e orofaringe. / The assessment of bone destruction by oral and oropharynx malignant neoplasms is a critical factor in the therapeutic planning and to determine the patient prognostic. The aim of this study was to determine the clinical aspects (localization, clinical manifestation and stage) that can be associated with the potential of bone infiltration, and also determine the physical exam sensibility and specificity. The study population consisted of twenty five patients (17 men and 8 women, mean age 57.88 years-old), with malignant neoplasms of the mouth and oropharynx, of the Stomatology Clinic of the College of Dentistry at the Sao Paulo University - campus Sao Paulo, in the period of august 2003 to august 2004, who were submitted to a clinical and computed tomography (CT) examinations. CT was considered the gold standard to evaluate the presence of bone involvement. The presence of bone destruction by the tumor was observed in 68% of the cases (17 patients). The physical examination of the patients revealed 82% of sensibility, 87.50% of specificity, and 84% of accuracy in the assessment of bone invasion by these diseases. The lesions that were clinical considered to be infiltrative ulcer and nodular lesions, non-ulcerated, presented the highest potential to cause bone destruction, 68.75% and 100% respectively. The tumor localization in specific sites also influenced the presence of bone invasion, meanly with the lesions localized in the gingival, retromolar trigone, hard palate and oropharynx. The stage of the lesions revealed a relation between the size and the presence of distant metastasis, with the presence of invasion by the neoplasm. In conclusion, it was determined that the identification of some clinical parameters such localization, clinical presentation, lesion size and the presence of distant metastasis, associated with a perceptive regional physical exam must be use as a value tool is the assessment of bone destruction by oral and oropharynx malignant neoplasms.

Purpose: This study investigates knowledge about HPV and examines if pediatric dental providers should include HPV education for guardians of patients 10-18 years. Methods: Legal guardians of 10-18 year-old patients of the Virginia Commonwealth University Pediatric Dental Clinic were enrolled in this prospective cohort study. Participants completed a baseline survey, were provided HPV education, completed an initial follow-up survey, and then completed a 6-month follow-up survey. Results: A total of 54 participants completed the baseline and initial follow-up surveys and 17 completed the 6-month follow-up survey. The average number of correct responses was 3.4 of 6 knowledge questions, which significantly improved to 5.4 at follow-up (P<.0001). The greatest increase in the percent responding correctly was regarding HPV and oropharyngeal cancer from 22% baseline to 91% at initial follow-up (P<.0001). Regarding Stage of Change, 14 (23%) of those not initially in the Action group had improved at least 1 stage. At the 6-month follow-up, 3 (43%) guardians reported completing the HPV vaccine series. Conclusions: These results demonstrate limited knowledge about HPV and highlight the pediatric dental provider’s ability to educate. Since the greatest knowledge gap pertained to HPV and oropharyngeal cancer, it is important for pediatric dental providers to increase their role in HPV education. As oral cancers are the purview of dentists, practitioners should be involved with their patients’ consideration of the HPV vaccine.

L'objectif de ces travaux est de connaître et évaluer les caractéristiques épidémiologiques des cancers de la cavité orale et de l'oropharynx. Ces deux localisations partagent des facteurs de risque en commun, et sont de fait souvent regroupées dans les études épidémiologiques. Cependant, la découverte de facteurs de risque spécifiques, telle l'infection par le virus du papillome humain pour les cancers de l'oropharynx, nous conduit à fournir des taux d'incidence spécifiques avec la classification anatomique de ces cancers. En réorganisant les données disponibles dans la base des données du Centre International de Recherche sur le Cancer, nous avons recherché les cas incidents au niveau mondial et recalculé les taux d'incidence dans les registres de 60 pays, pendant la période 1998-2002. La classification TNM n'est pas disponible dans les bases de données du CIRC. Nous avons identifié et contacté les registres du cancer qui ont déclaré son recueil. Cela nous a permis de créer et structurer une base des données innovante et inédite, dont les informations ont été analysées par rapport à la qualité. Finalement nous avons comparé la distribution de stades précoces et avancés dans 8 pays. Les résultats montrent que l'incidence des cancers de la cavité buccale et de l'oropharynx est très hétérogène au niveau mondial par rapport à la sous localisation des tumeurs, à l'âge d'incidence, au ratio homme/femme et au stade clinique.

Die vorliegende retrospektive Studie untersuchte die lokale Rezidiv- und Überlebensrate von Patienten mit Plattenepithelkarzinomen in Abhängigkeit vom Randstatus und Resektionsabstand der Tumorresektion sowie von der postoperativen Therapie. Dabei wurden Daten von 351 Patienten mit Plattenepithelkarzinomen des Oropharynx, Hypopharynx und Larynx ausgewertet, welche zwischen 2005 und 2009 reseziert wurden. Der gesundheitliche Zustand der Patienten wurde anschließend bis Dezember 2011 beobachtet. Im Ergebnis konnte kein Einfluss des Randstatus und des Resektionsabstandes auf die lokale Rezidivrate nachgewiesen werden. Beide Faktoren hatten jedoch einen signifikanten Einfluss auf die Letalitätsrate. Die postoperative Therapie zeigte einen positiven Einfluss auf die lokale Rezidivrate. Sie konnte aber die negativen Prognosefaktoren, die eine Indikation dieser Therapie darstellen, bezüglich der Letalitätsrate nicht ausgleichen. Weiterhin war ein positiver Einfluss der postoperativen Therapie auf das rezidivfreie Überleben (DFS-disease-free survival) sowohl uni- als auch multivariat nachweisbar. Die Gesamtüberlebensrate (OS-overall survival) wurde signifikant positiv durch einen geringeren Randstatus und einen zunehmenden Resektionsabstand (ASR Klassifikation) beeinflusst. Das krankheitsspezifische Überleben (DSS-disease-specific survival) sank bei Auftreten eines lokalen Rezidivs. Aus diesen Ergebnissen kann geschlussfolgert werden, dass eine postoperative Therapie zur Kontrolle lokaler Rezidive von hoher Bedeutung ist. Da lokale Rezidive die Überlebensrate signifikant senken, hat die postoperative Therapie indirekt einen positiven Effekt auf das Überleben. Des Weiteren zeigt sich bei Patienten mit freien Resektionsrändern die höchste Überlebensrate, wobei diese mit zunehmendem Abstand des Karzinoms vom Resektionsrand steigt.

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Made available in DSpace on 2014-06-11T19:27:54Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-09-17Bitstream added on 2014-06-13T19:56:54Z : No. of bitstreams: 1 gomez_spp_me_arafo.pdf: 720577 bytes, checksum: f32f19712e837651d99f8642d99cbf3c (MD5) / As mudanças nos padrões de respiração nasal afetam profundamente o crescimento craniofacial. Avanços tecnológicos, como a tomografia computadorizada de feixe cônico (TCFC), têm sido utilizados com o propósito de se observar tridimensionalmente, o crânio, a face e o espaço aéreo faríngeo, sendo possível a avaliação das mudanças do espaço aéreo induzidas pelos aparelhos ortopédicos propulsores mandibular. O intuito deste estudo é apresentar um método de avaliação das vias aéreas de fácil reprodutibilidade, e avaliar, mediante a TCFC, os efeitos do aparelho de Herbst bandado no espaço aéreo orofaríngeo (EAOF), nasofaríngeo (EANF) e faríngeo superior (EAFS), em indivíduos com má oclusão classe II divisão 1ª. A amostra foi composta por imagens digitais de 15 indivíduos (idade média inicial de 15,7 anos ± 1.7, após surto de crescimento pubertário) com má oclusão classe II divisão 1ª, tratados com aparelho Herbst bandado (8 meses). Os exames tomográficos foram realizados antes (T1) e após (T2) o tratamento. A fase inicial foi realizada com a orientação do nos planos; axial, coronal e sagital. Foram mensurados: comprimento no software Dolphin 3D ®: comprimento, maior área no corte coronal, maior área no corte sagital, área mínima da secção transversal e volume, de EANF, EAOR e EAFS (orofaringe e nasofaringe). Dois avaliadores previamente calibrados mensuraram duas vezes apenas um tempo das tomografias, para observar a reprodutibilidade (inter-examinador) e replicabilidade (intra-examinador). Sendo confirmada a reprodutibilidade do método, foi avaliado o efeito do aparelho Herbst, analisando os períodos pré (T1) e pós (T2) tratamento ortopédico. A análise estatística dos dados foi realizada em duas etapas. Primeira etapa, a confiabilidade das medidas apresentaram boa replicabilidade (intra-examinador)... / Changes in nasal breathing patterns profoundly affects the craniofacial growth. Technological advances, such as cone beam computed tomography (CBCT), have been used in order to observe three-dimensionally: the skull, face and pharyngeal airway space, with possible assessment of airspace changes induced by orthopedic activators. The purposes of this study are to present a method for assessing airway that is easily reproducted, and evaluate through the CBCT the effects of banded Herbst appliance in the oropharyngeal airspace (EAOF), nasopharyngeal (EANF) and upper pharynx (EAFS) in individuals with malocclusion class II division 1. The sample consisted of digital images of 15 individuals (initial age of 15.7 years ± 1.7, after pubertal growth spurt) with malocclusion class II division 1, treated with banded Herbst appliance (8 months). CBCT scans were performed before (T1) and after (T2) treatment. The initial phase was conducted with the guidance of planes: axial, coronal and sagittal. The following were measured: the largest area in the coronal and sagittal, minimum cross-sectional area and volume of EANF, and EAOR EAFS (oropharynx and nasopharynx) by length in Dolphin 3D® software. Two calibrated evaluator mesured twice time of CBCT to observe the reproducibility (inter-examiner) and repeatability (intra-examiner). Once the reproductability of the method was coinfirmed, the effect of the Herbst applicance was evaluated before (T1) and after (T2) the orthodontic treatment. The statistical analysis was performed in two steps. First step, the reliability of the measurements showed good repeatability (intra-examiner) (ICC ≥ 0.984) and good reproducibility (inter-examiner) (ICC ≥ 0.911) for all measures except the minimum area of cross section of all regions, which showed variability. Second step, once confirmed the reliability of the measuremens, Student t test was appleid, significance... (Complete abstract click electronic access below)

Avec plus de 600 000 nouveaux cas par an, les cancers des voies aéro-digestives supérieures (VADS) se classent au sixième rang mondial. Ces cancers, traditionnellement causés par la consommation chronique de tabac et d’alcool, connaissent depuis une trentaine d’années de profonds changements épidémiologiques. Alors que l’incidence des cancers développés dans la cavité orale, le larynx et l’hypopharynx tend à se stabiliser voire à régresser en raison de la diminution du tabagisme, ceux développés dans l’oropharynx sont en nette augmentation. Cette augmentation est attribuée aux papillomavirus oncogènes et notamment au génotype 16 (HPV16). Les cancers de l’oropharynx (COP) HPV-induits représentent une pathologie distincte des autres cancers des VADS tant au niveau épidémiologique, clinique, histologique que biologique. Ils affectent des sujets plus jeunes, sont extrêmement lymphophiles et leur pronostic est significativement meilleur. L’émergence de ces cancers impose dès aujourd’hui de réfléchir à des stratégies diagnostiques, thérapeutiques et de surveillance spécifiques. Néanmoins, ces objectifs ne pourront être pleinement atteints qu’à condition de mieux comprendre leur histoire naturelle ainsi que leurs mécanismes oncogéniques propres. L’objectif de ce travail est de contribuer à une meilleure compréhension des mécanismes biologiques distinguant les COP HPV-induits de leurs homologues HPV-négatifs sur la base de l’analyse de leur profil d’expression génomique. A partir d’une cohorte de 38 COP, sélectionnés sur des critères stricts, nous avons identifié un set d’ARNm et de miRNA dont l’expression est exclusivement corrélée au statut HPV. L’analyse fonctionnelle de ces sets confirme que les bases biologiques des COP varient en fonction de leur statut HPV et confortent au niveau moléculaire des données cliniques et pathologiques déjà connues ou fortement suspectées (différenciation tumorale, infiltration lymphocytaire…). Cette étude souligne également le rôle potentiel de plusieurs voies de signalisation dont les dérégulations contribueraient au développement de ces tumeurs. L’exploration plus approfondie de ces voies pourrait à terme permettre de mieux comprendre ces tumeurs et avoir d’éventuelles retombées thérapeutiques. / Head and neck squamous cell carcinomas (HNSCCs) represent the sixth most common form of cancer with an annual incidence of approximately 600,000 new cases worldwide. Tobacco and alcohol abuse are the traditional risk factors. Whilst the incidence of oral cavity, larynx and hypopharynx cancers is stabilizing or falling, because of a drop in tobacco consumption, those arising in the oropharynx are on the increase. This epidemiologic change has been attributed to high-risk human papillomavirus and particularly to type 16 (HPV16), which is now recognized as a causative agent in a growing subset of oropharyngeal squamous cell carcinomas (OPSCCs).HPV-induced OPSCCs represent a distinct subgroup, separate from other HNSCCs, with unique epidemiologic, clinical, pathological and molecular characteristics. They affect young patients, are highly lymphophilic and have markedly improved survival outcomes compared to those with HPV-negative HNSCC. The emergence of these cancers demands special attention, as in the coming years diagnosis, treatment and follow up in HNSCC may vary according to HPV status. However, these objectives will not be fully achieved without a better understanding of their natural history and specific oncogenic mechanisms. The goal of this work is to contribute to a better understanding of the biological basis that differentiates HPV-induced OPSCCs from their HPV-negative counterparts. To this end, we have investigated global changes in gene expression in a cohort of 38 strictly selected OPSCCs. We have identified a set of mRNA and miRNA that discriminated between OPSCCs solely according to HPV16 status. The functional analysis of these 2 sets confirms that the biological basis of OPSCCs varies according to their HPV status and consolidates at the molecular level known or suspected clinical and pathological data (e.g tumoral differentiation, lymphoid infiltrations…). This study highlights the potential role of several pathways that, once deregulated, could contribute to the development of HPV-induced OPSCC. Further investigation is required for a more comprehensive understanding of the biological properties of HPV related OPSCCs. These properties may be exploited to develop novel therapeutic agents.

Fundação de Apoio a Pesquisa e à Inovação Tecnológica do Estado de Sergipe - FAPITEC/SE / Staphylococcus aureus has been considered a major public health problem worldwide due mainly to the ability to develop resistance to antibiotics. The prevalence of methicillin resistant strains of S. aureus (MRSA) in both hospital and community settings has been increasing, with cases of infections and deaths reported in healthy children and adults. Bacteriocins have been identified as promising alternatives for the control of this pathogen. However, besides the therapeutic use of these peptides still not approved, some studies indicate the possibility of selection of resistant strains. Therefore, prior to the therapeutic use of bacteriocins, studies must be carried out to understand the effect that bacteriocin may have on the selection of resistant strains to avoid the current problem with lineages resistant to traditional antibiotics. In view of the above, the objective of this study was to verify the antimicrobial activity of nisin against strains of MRSA and MSSA isolated from the oropharynx of health professionals and verify the selection of strains resistant to bacteriocin. For the genotypic characterization of the MRSA and MSSA strains, the nucA, LuckPV, mecA and mecC genes were tested. The MSSA lines were positive for amplification of the nucA gene only, confirming the identification of genus and species of these strains. For MRSA strains, the only gene that was not detected was mecC, confirming the methicillin resistance phenotype and that these strains are of human origin and of community environments. The results obtained by the agar diffusion test demonstrated that 80% of the MSSA strains (n = 30) were inhibited by nisin and only one MRSA line (n = 6) showed no sensitivity to bacteriocin. The MIC of MSSA strains ranged from 97.7 to 1250 IU / mL and from MRSA strains of 937.50 to 5000 IU / mL. The DBM for MSSA strains varied from 97.7 IU / mL to values greater than 50,000 IU / mL, and for MRSA, this variation was between 5000 IU / mL at values greater than 10,000 IU / mL depending on the lineage. For most lineages DBM was higher than MIC, showing that the effect of bacteriocin depends on bacteriocin concentration: low concentrations exert bacteriostatic effect and high concentrations bactericidal effect. The addition of increasing concentrations of the bacteriocin to the BHI medium generally resulted in the increase in the lag phase and decrease in the specific growth rate and maximal DO reached by the MSSA and MRSA cultures. MSSA and MRSA strains were transferred for approximately 30 generations in the presence of bacteriocin and a decrease in sensitivity was observed with a consequent increase in nisin MIC for all strains tested. The bacteriocin resistance phenotype has been shown to be a stable trait for these strains and may be associated with a genetic factor. It has also been observed that the use of nisin may trigger cross-resistance to some antibiotics. The results obtained demonstrated that nisin is efficient in controlling the growth of MSSA and MRSA. However, the fact that these lines demonstrate resistance to bacteriocin after transfer in the presence of the same indicates the need to develop strategies to avoid in the future the current problem of resistance to antibiotics. The best way to use bacteriocins therapeutically is to suggest that it is in combination with traditional antibiotics. / Staphylococcus aureus têm sido considerado um dos maiores problemas de saúde pública a nível mundial devido, principalmente, a habilidade de desenvolver resistência a antibióticos. A prevalência de linhagens de S. aureus resistentes a meticilina (MRSA) tanto em ambiente hospitalar quanto em ambientes comunitários têm aumentado, sendo descritos casos de infecções e relatos de mortes em crianças e adultos saudáveis. Bacteriocinas tem sido apontadas como alternativas promissoras para o controle deste patógeno. Entretanto, além do uso terapêutico destes peptídeos ainda não ser aprovado, alguns estudos indicam a possibilidade de seleção de linhagens resistentes. Portanto, antes do uso terapêutico de bacteriocinas, estudos precisam ser realizados para o entendimento do efeito que a bacteriocina possa ter na seleção de linhagens resistentes para evitar o problema da atualidade com linhagens resistentes aos antibióticos tradicionais. Diante do exposto, o objetivo deste trabalho foi verificar a atividade antimicrobiana da nisina contra cepas de MRSA e MSSA isoladas da orofaringe de profissionais da área de saúde e verificar a seleção de linhagens resistentes à bacteriocina. Para a caracterização genotípica das linhagens MRSA e MSSA, foram testados os genes nucA, LuckPV, mecA e mecC. As linhagens MSSA foram positivas para amplificação apenas do gene nucA, confirmando a identificação de gênero e espécie destas linhagens. Para as linhagens MRSA, o único gene que não foi detectado foi o meC, confirmando o fenótipo de resistência a meticilina e que estas linhagens são de origem humana e de ambientes comunitários. Os resultados obtidos pelo teste de difusão em ágar demonstraram que 80% das linhagens MSSA (n=30) foram inibidas pela nisina e apenas uma linhagem MRSA (n=6) não apresentou sensibilidade à bacteriocina. A CIM das linhagens de MSSA variou de 97,7 a 1250UI/mL e das linhagens MRSA de 937,50 a 5000 UI/mL. A DBM para as linhagens de MSSA variou de 97,7 UI/mL a valores superiores a 50000 UI/mL, e para MRSA esta variação ficou entre 5000 UI/mL a valores maiores que 10000 UI/mL dependendo da linhagem. Para a maioria das linhagens a DBM foi maior que a CIM, mostrando que o efeito da bacteriocina depende da concentração da mesma: baixas concentrações exercem efeito bacteriostático e altas concentrações efeito bactericida. A adição de concentrações crescentes da bacteriocina ao meio BHI resultaram, de maneira geral, no aumento da fase lag e diminuição da velocidade específica de crescimento e DO máxima atingida pelas culturas MSSA e MRSA. Linhagens de MSSA e MRSA foram transferidas por aproximadamente 30 gerações na presença da bacteriocina e foi observada diminuição na sensibilidade com consequente aumento da CIM da nisina para todas as linhagens testadas. O fenótipo de resistência à bacteriocina demonstrou ser uma característica estável para estas linhagens, podendo estar associado a um fator genético. Foi observado também que a utilização da nisina pode desencadear resistência cruzada a alguns antibióticos. Os resultados obtidos demonstraram que a nisina é eficiente em controlar o crescimento de MSSA e MRSA. Entretanto, o fato destas linhagens demonstrarem resistência a bacteriocina após transferência na presença da mesma indica a necessidade de desenvolver estratégias para evitar no futuro o problema atual de resistência a antibióticos. A melhor maneira de usar bacteriocinas terapeuticamente sugere-se que seja em combinação com antibióticos tradicionais. / São Cristóvão, SE

Introduction: Lymphoepithelial carcinoma (LEC) in the oropharynx is rare. Current understanding of the disease is derived mainly from case reports and small case series, prompting further elucidation of its epidemiology and prognostic factors that affect outcome. The aim of this retrospective cohort study was to examine demographic characteristics, clinicopathologic features, and prognostic factors in patients with oropharyngeal LEC. Methods: The U.S. National Cancer Institute’s SEER registry was queried to obtain data on patients with primary oropharyngeal LEC from 1975 to 2016. Variables examined include age at diagnosis, sex, race, year of diagnosis, primary site of tumor origin, tumor size, extent, nodal status, overall stage, tumor grade, surgical treatment, and county socioeconomic status (SES). Kaplan-Meier univariable and Cox regression model multivariable analyses were conducted to identify independent predictors of survival. Results: In total, 199 cases of primary LEC in the oropharynx were found. Overall survival rates at 2-, 5-, and 10-years were 81.0%, 74.0%, and 56.0%, respectively. Disease-specific survival rates at 2-, 5-, and 10-years were 85.0%, 80.0%, and 77.0%, respectively. Multivariable analysis identified older age at diagnosis, Black race, and tonsil primary site to be independent predictors of worse survival. Contrarily, a more recent year of diagnosis, surgical resection, and higher county SES were identified to be associated with an improved prognosis. Conclusion: Oropharyngeal LEC is a rare malignancy that is diagnosed mostly in White males in the fifth decade of life. Patient age, race, year of diagnosis, primary site of tumor origin, surgical treatment, and county SES were found to significantly affect survival. Although oropharyngeal LEC is associated with a relatively favorable prognosis, detecting disease early and including surgical resection in treatment may aid in further improving survival.