Objectifs: Examiner les tendances temporelles, les déterminants en lien avec le design des études et la qualité des taux de réponse rapportés dans des études cas-témoins sur le cancer publiées lors des 30 dernières années. Méthodes: Une revue des études cas-témoins sur le cancer a été menée. Les critères d'inclusion étaient la publication (i) dans l’un de 15 grands périodiques ciblés et (ii) lors de quatre périodes de publication (1984-1986, 1995, 2005 et 2013) couvrant trois décennies. 370 études ont été sélectionnées et examinées. La méthodologie en lien avec le recrutement des sujets et la collecte de données, les caractéristiques de la population, les taux de participation et les raisons de la non-participation ont été extraites de ces études. Des statistiques descriptives ont été utilisées pour résumer la qualité des taux de réponse rapportés (en fonction de la quantité d’information disponible), les tendances temporelles et les déterminants des taux de réponse; des modèles de régression linéaire ont été utilisés pour analyser les tendances temporelles et les déterminants des taux de participation. Résultats: Dans l'ensemble, les qualités des taux de réponse rapportés et des raisons de non-participation étaient très faible, particulièrement chez les témoins. La participation a diminué au cours des 30 dernières années, et cette baisse est plus marquée dans les études menées après 2000. Lorsque l'on compare les taux de réponse dans les études récentes a ceux des études menées au cours de 1971 à 1980, il y a une plus grande baisse chez les témoins sélectionnés en population générale ( -17,04%, IC 95%: -23,17%, -10,91%) que chez les cas (-5,99%, IC 95%: -11,50%, -0,48%). Les déterminants statistiquement significatifs du taux de réponse chez les cas étaient: le type de cancer examiné, la localisation géographique de la population de l'étude, et le mode de collecte des données. Le seul déterminant statistiquement significatif du taux de réponse chez les témoins hospitaliers était leur localisation géographique. Le seul déterminant statistiquement significatif du taux de participation chez les témoins sélectionnés en population générale était le type de répondant (sujet uniquement ou accompagné d’une tierce personne). Conclusion: Le taux de participation dans les études cas-témoins sur le cancer semble avoir diminué au cours des 30 dernières années et cette baisse serait plus marquée dans les études récentes. Afin d'évaluer le niveau réel de non-participation et ses déterminants, ainsi que l'impact de la non-participation sur la validité des études, il est nécessaire que les études publiées utilisent une approche normalisée pour calculer leurs taux de participation et qu’elles rapportent ceux-ci de façon transparente. / Objectives: To examine the time trends, study design determinants, and quality of reporting of response rates in published case-control studies of cancer over the past 30 years. Methods: A review was conducted of case-control studies of cancer. Inclusion criteria required publications in 15 major journals, during four publication periods spanning three decades (1984-86, 1995, 2005 and 2013). 370 studies were selected and reviewed. Information on study base ascertainment, data collection methods, population characteristics, response rates, and reasons for non-participation was extracted. Quality of response rate reporting was assessed based on the amount of information reported. Descriptive statistics were used to summarize the quality of the reporting, time trends and the determinants of response rates; linear regression models were used to analyse time trends and determinants of response rates. Results: Overall, the quality of reporting of response rates and reasons for non-participation was very poor, especially for control series. Participation has declined over the past 30 years, and this decline was steeper in studies conducted after 2000. When comparing the response rates in recent studies to that in studies conducted during 1971-1980, there was a greater decline of this rate in population controls (-17.04%, 95% CI: -23.17%, -10.91%) than in cases (-5.99%, 95% CI: -11.50%, -0.48%). Statistically significant determinants of response rates among cases were: cancer type examined, location of the study population, and mode of data collection. The only statistically significant determinant of response rates among medical source controls was location of the study population. The only statistically significant determinant of response rates among population controls was type of respondent (self only or self and proxy) accepted by studies. Conclusion: Response rates in case-control studies of cancer seem to have declined and this decline has accelerated in recent studies. In order to appreciate the true level of non-participation and its determinants, as well as the impact of non-participation on validity of studies, there is a need for more transparent reporting and standardized calculation of response rates in published studies.

Les rayonnements ionisants sont un facteur de risque reconnu pour les leucémies chez l'homme pour des fortes doses d'exposition médicale ou accidentelle. En revanche, l'hypothèse de l'existence d'un risque associé aux rayonnements ionisants à des niveaux d’exposition inférieurs, habituellement rencontrés dans l'environnement et de manière continue reste à démontrer. Notre travail propose d’évaluer l’hypothèse de l’existence d’une association entre les expositions environnementales aux radiations ionisantes d’origine naturelle et le risque de leucémie de l’enfant (LA) en utilisant des observations réalisées en France métropolitaine.Les cas de leucémie inclus dans ce travail sont toutes les LA du Registre National des Hémopathies malignes de l’Enfant, qui enregistre l'ensemble des cas de moins de 15 ans diagnostiqués en France métropolitaine, sur la période étudiée.Un premier travail a consisté à étudier la répartition spatiale de l’incidence des leucémies de l’enfant au niveau des 1 916 bassins de vie (BV) définis par l’INSEE. Des méthodes de détection de cluster ont été appliquées sur les 7 675 cas de leucémies de l'enfant diagnostiqués entre 1990 et 2006 afin d’identifier les zones potentiellement associées à un plus fort risque de leucémies aiguës de l’enfant. Cette étude n'a pas mis en évidence d’hétérogénéité spatiale des taux d'incidence des LA de l'enfant au cours de la période 1990-2006 au niveau des BV. Cependant, quelques clusters spatiaux ont été identifiés dans des lieux et périodes spécifiques. Bien que les niveaux de significativité de ces clusters ne soutiennent pas fortement l'existence de facteurs de risque localisés, les clusters peuvent montrer un léger impact de facteurs de risque partagés à l'échelle des BV.Pour tester l’hypothèse de l’existence d’une association entre l’exposition aux radiations ionisantes d’origine naturelle et l’incidence des leucémies de l’enfant, une étude d’incidence basée sur les 9 056 cas de LA de la période 1990-2009 a été réalisée. Cette étude a été complétée par une étude cas-témoins en population fondée sur les 2 763 cas de LA enregistrés sur la période 2002-2007 et un ensemble témoin de 30 000 sujets constituant un échantillon contemporain représentatif de la population pédiatrique française. Dans cette approche, la géolocalisation des adresses des cas et des témoins ainsi que celle des sources d'exposition et leur caractérisation permet de définir les critères de l'intensité d'exposition aux facteurs d'intérêt et de les mettre en relation avec le statut cas vs témoins des sujets.Les données concernant l'exposition à la radioactivité d’origine naturelle ont été produites par l'IRSN (Institut de Radioprotection et de Sûreté Nucléaire). Une cartographie du potentiel d’exhalation du radon émis par le sol et un échantillon national de 10 843 points de mesures localisés dans des habitations ont permis d’estimer l’exposition résidentielle au radon au niveau de la commune et du domicile. L’exposition aux rayonnements gamma telluriques et cosmiques a été estimée par zone d’emploi à partir d’un ensemble de 28 000 mesures issues de la campagne nationale IRSN et de mesures réalisées dans approximativement 1 000 sites couvrant la France entière, dans un but de surveillance de la radioactivité ambiante.Notre étude n’a pas montré d’association entre les leucémies de l’enfant et l’exposition aux radiations ionisantes d’origine naturelle estimée au diagnostic et de façon cumulée pendant l’enfance. Elle avait une bonne puissance pour mettre en évidence les risques attendus d’après les modèles de risque actuels (UNSCEAR) issus des études sur les risques observés à forte dose. Cette question reste néanmoins suffisamment importante et peu explorée pour mériter des études complémentaires dans d’autres pays. / Ionizing radiation due to medical or accidental exposure to high doses is an established risk factor for leukemia in humans. However, the evidence of a risk associated with exposure to ionizing radiation at lower levels usually encountered in the environment remains to be demonstrated. Our work aims to evaluate the hypothesis of the existence of an association between natural background ionizing radiation and the risk of childhood leukemia (CL) using observations made in France.Leukemia cases included in this study are all the CL recorded in the National Registry of Childhood Hematological Malignancies, an exhaustive repository of all cases of patients younger than 15 years old in France over the studied period.First step was the study of the spatial distribution of the incidence of CL at the level of the 1,916 Living Zone (LZ) defined by INSEE. Cluster detection methods have been used on 7,675 cases of CL diagnosed during the period 1990-2006 to identify areas potentially associated with a higher risk of acute childhood leukemia. The study did not show any spatial heterogeneity of incidence of CL during the period at LZ level. However, some spatial clusters were highlighted in specific places and times. Although the levels of significance of these clusters do not strongly support the existence of risk factors, localized clusters can show a slight impact of risk factors shared across LZ, including contextual environmental exposures.To test the hypothesis of the existence of an association between environmental exposure to ionizing radiation of natural origin and incidence of childhood leukemia, an incidence study based on 9,056 cases of CL for the period 1990-2009 was conducted. This study was complemented by a record-based cases-controls study based on the 2,763 cases of CL recorded over the 2002-2007 period and a control set of 30,000 subjects constituting a representative sample of the contemporary French pediatric population. In this approach, localizations of cases and controls and exposure identifications were geocoded and compared to the status cases vs control population.Data of exposure to natural background radiation were produced by the IRSN (Institute for Radiological Protection and Nuclear Safety). Mapping of the “potential radon exhalation emitted by the ground” and a national sampling of 10,843 measurement points located in dwellings were used to estimate residential exposure to radon at a level of granularity of cities and houses. Exposure to terrestrial gamma and cosmic rays was estimated by zone d’emploi based on a set of more than 28,000 environmental measurements in approximately 1,000 sites covering whole France, and by the IRSN national campaign data. Our study did not show any association of childhood leukemia with exposures to natural background radiation estimated nor at diagnosis nor cumulatively during childhood. However it had a good power to highlight the risks expected from current models of risk (UNSCEAR) built from studies on the observed high doses risks. If this work does not support the hypothesis that there is an association between exposure to ionizing radiation from natural sources observed and the incidence of childhood leukemia which may be directly observable at the epidemiologic level, this question remains important enough and not investigated enough to merit further complementary studies in countries where it has not been investigated.

INTRODUÇÃO: Os astrocitomas difusamente infiltrativos são os tumores mais freqüentes de Sistema Nervoso Central (SNC) com uma taxa de 5-7 novos casos por 100.000 pessoas ano. São tumores altamente invasivos e estão associados com alterações de alguns genes como EGF (fator de crescimento epidérmico) e o EGFR (receptor do fator de crescimento epidérmico), que podem criar um aumento da atividade mitogênica, acarretando aumento de proliferação e maturação celular, apoptose, angiogênese e metástase. O nível de expressão destes genes pode ser influenciado por alterações genéticas, como a presença de polimorfismos. Uma mudança única de base (SNP) pode alterar a expressão gênica e, sendo assim, estar associada ao aumento do risco de desenvolver astrocitomas. Nesse trabalho, foram analisados 2 SNPs na região não traduzida (c.-191C>A e c.-216G>T) e um SNP no exon 16 (c.2073A>T) do gene EGFR, e um outro SNP na região não traduzida no gene EGF (c.61A>G). Os SNPs foram associados a expressão gênica do EGFR e a sobrevida dos pacientes. MÈTODOS: Foi realizado um estudo caso-controle com 193 casos de astrocitomas difusamente infiltrativos e 200 controles por amplificação por PCR seguido de digestão enzimática. Os produtos digeridos das amostras foram analisados por eletroforese em gel de agarose e poliacrilamida e corados com brometo de etídeo. A expressão gênica foi realizada após extração de RNA do tecido tumoral seguida de transcrição reversa e PCR em tempo real. Testes de qui-quadrado, odds ratio (OR), intervalo de confiança 95% (IC95%), t de Student e curvas de Kaplan-Meier foram realizados para análises estatística. RESULTADOS: A análise das freqüências dos genótipos dos polimorfismos mostrou uma diferença na distribuição entre casos e controles para o polimorfismo c.2073A>T. Pacientes com o genótipo TT apresentou um menor risco para astrocitoma quando comparados com o genótipo AA (OR=0,51, IC95%=0,29-0,99). Nenhuma correlação foi encontrada para os outros polimorfismos analisados. Também não foi encontrada correlação entre os genótipos dos polimorfismos e os níveis de expressão de EGFR e a sobrevida dos pacientes. CONCLUSÃO: Nosso trabalho mostrou haver um possível fator de proteção quando o paciente é portador do genótipo TT, o que pode levar a uma diminuição do risco de desenvolver o tumor. Pacientes com genótipo TT do polimorfismo c.2073A>T do gene EGFR apresentam um menor risco para astrocitomas difusamente infiltrativos do que os com o genótipo AA. / INTRODUCTION: Diffusely infiltrative astrocytomas are the most frequent tumors of the Central Nervous System (CNS) with a rate of 5-7 new cases in 100,000 individuals per year. They are highly invasive, and they are associated to alterations in some genes as EGF (epidermal growth factor) and EGFR (epidermal growth factor receptor), which may increase mitogenic activity, leading to increase of proliferation, cellular maturation, apoptosis, angiogenesis, and metastasis. Genetic alterations, as presence of polymorphisms of single nucleotide change (SNP) could influence their expression level, and thus could be associated to increased risk in developing astrocytomas. In the present study, two SNP of non-coding region (c.-191C>A and c.-216G>T) and one SNP in exon 16 (c.2073A>T) of EGFR, and another SNP of non-coding region of EGF (c.61A>G) were analyzed. The SNPs were associated to EGFR expression level and to survival time. METHOD: a case-control study of 193 of diffusely infiltrative astrocytomas and 200 controls was carried out, with PCR amplification and enzymatic digestion, which products were analyzed in agarose gel or polyacrylamide gel electrophoresis stained by ethidium bromide. EGFR expression level was studied by real time PCR after RNA extraction followed by reverse transcription of tumor tissues compared to epileptic non-neoplastic brain tissues. Stastistical analysis were performed by chi-square, odds ratio (OR), 95% confidence interval (95% CI), Student-t test and Kaplan Meier. RESULTS: The polymorphic genotype frequency was different between case and controls for the polymorphism c.2073A>T. Patients with TT genotype presented lower risk to develop astrocytoma when compared to genotype AA (OR=0.51, CI95%=0.29- 0.99). No other correlation was observed for the remaining studied polymorphisms. There was neither correlation between the polymorphic genotypes and the EGFR expression levels nor with survival time. CONCLUSION: The present study showed a possible protection factor in developing astrocytomas for the patients harboring the genotype TT of c.2073A>T polymorphism of EFGR, thus the patients presenting TT genotype have lower risk to develop diffusely infiltrative astrocytoma than patients presenting the genotype AA.

O presente trabalho teve como objetivo avaliar o risco de óbito por leucemia, neoplasias do sistema nervoso central e esclerose lateral amiotrófica em adultos em relação à exposição a CM, no Município de São Paulo. Foi realizado um estudo do tipo caso-controle populacional envolvendo 6224 sujeitos. Casos e controles foram extraídos da base de dados do PROAIM, e foram pareados por sexo, faixa etária e distrito administrativo de residência. Foram considerados casos todos os óbitos pelos desfechos específicos, em adultos com 40 anos ou mais, residentes no Município de São Paulo, ocorridos entre 2001 e 2005. Controles foram constituídos por óbitos por todas as outras causas ocorridos no mesmo período. A exposição foi avaliada de acordo com a distância das residências dos sujeitos para a linha de transmissão (LT) mais próxima. Foi encontrado um aumento do risco de óbito por leucemia entre os indivíduos que moravam mais próximo às LT, com OR ajustado de 1,8 (IC 95%: 0,8 - 4,3) e 2,5 (IC 95%: 1,0 - 7,2) entre os sujeitos que moravam a 50 m e entre 50 e 100 m das LT, respectivamente, em relação aos que moravam a mais de 400 m. / This work aimed at evaluating the risk of death by leukemia, brain tumor and amyotrophic lateral sclerosis in adults in relation to magnetic field exposure, in the city of São Paulo. A population-based case-control study was held, and 6224 subjects were enrolled. Cases and controls were selected from the PROAIM database, and were matched by sex, age and district of residence. Cases were all deaths ocurred between 2001 and 2005 by the specific causes, ocurring in adults 40 years and older, living in the city of São Paulo. Controls were selected from all other deaths ocurred at the same period. Exposure to magnetic fields was accessed according to the distance of the dwelling to the closest transmission line (TL). The risk of death by leukemia was elevated within the subjects living closest to the TL, with an adjusted OR of 1,8 (CI 95%: 0,8 - 4,3) and 2,5 (CI 95%: 1,0 - 7,2) for people living within 50 m and within 50 to 100 m away from the TL, respectively, in relation to people living at 400 m or further.

Objetivo: Comparar o comprimento do úmero em fetos portadores de síndrome de Down (T21) com o comprimento do úmero em fetos normais, utilizando instrumentos de referência da população local. Método: Estudo caso-controle retrospectivo que comparou o comprimento do úmero de fetos normais com os fetos com T21, entre 18 semanas e 23 semanas e 6 dias. Os exames dos fetos com T21 foram realizados entre 1994 e 2012. Os controles normais foram avaliados entre 2007 e 2009. Foram analisadas as médias, medianas e desvios-padrão da idade materna, idade gestacional e medida do úmero. Posteriormente, foi feita análise da correlação entre as medidas dos úmeros e a idade gestacional, sendo seus valores expressos em múltiplos da mediana (MoMs). O comprimento do úmero dos fetos com T21 foram confrontados com os fetos normais utilizando o teste t-Student. A medida do úmero foi avaliada considerando-se os níveis de corte abaixo do percentil 10, 5 e 2,5 a fim de obter as respectivas taxas de sensibilidade. Calculou-se, ainda, a razão de verossimilhança (RV). A seguir, foi utilizado um modelo linear geral tendo a idade materna como covariável para controlar na comparação. Comparou-se, também, a medida do comprimento do úmero dos fetos normais da população local com o comprimento do úmero esperado baseado na curva de Jeanty. Os testes foram realizados com nível de significância de 5%. Resultados: Foram incluídos 58 casos com T21 e 1888 controles normais. A sensibilidade do comprimento do úmero para a detecção da T21 utilizando o nível de corte abaixo do percentil 10 foi de 44,8 % com RV de 4,4, abaixo do percentil 5 foi de 34,4 % com RV de 6,9 e abaixo do percentil 2,5 foi de 31,0 % com RV de 12. O valor médio dos úmeros, em MoMs, de fetos com T21 é estatisticamente inferior ao dos fetos normais (p < 0,001), utilizando o teste t-Student. Quando controlada a idade materna na comparação entre os grupos, a diferença permaneceu estatisticamente significativa (p < 0,001). Fez-se uma análise para comparar o comprimento do úmero nos fetos normais da população local com o comprimento do úmero esperado para a curva de Jeanty, e viu-se que os fetos normais locais têm comprimento do úmero estatisticamente significante menor. Conclusões: Existe diferença estatisticamente significante entre o comprimento do úmero de fetos normais e de fetos com T21 na população local (p < 0,001). A sensibilidade para detecção de T21 foi de 44,8%, 34,4% e 31%, para o úmero abaixo do percentil 10, 5 e 2,5, respectivamente. A curva de Jeanty não tem rendimento adequado para uso como controle do crescimento umeral em fetos normais locais, acarretando com seu uso o inevitável aumento da taxa de falsos positivos de úmeros curtos / Objective: This study aimed to compare the humeral length (HL) in fetuses with Down syndrome (T21) with HL in normal fetuses, by using instruments of reference of the local population. Method: A case-control study was conducted comparing HL in normal fetuses with HL in fetuses with T21, aged between 18 weeks and 23 weeks and 6 days. Fetuses with T21 who were examined between 1994 and 2012 were included. The normal controls were evaluated between 2007 and 2009. The averages, medians, and standard deviations were obtained for maternal age, gestational age, and HL. Afterwards, we analyzed the correlation between the HL and the gestational age, with values expressed as multiples of the median (MoMs). The HLs of fetuses with T21 were compared with the HLs in normal fetuses by using Student\'s t-test. The humeri were evaluated considering the cut-off levels below the 10th, 5th, and 2,5th percentiles to obtain the sensitivity. The likelihood ratios (LR) were also calculated. Next, a general linear model was used with maternal age as a covariate to control for comparison of the groups. Comparison was also made between the HL of fetuses in the local population and the expected HL, based on the Jeanty curve. The tests were performed with a significance level of 5%. Results: The study included 58 cases with T21 and 1888 normal controls. The sensitivity of the HL to detect T21 by using a cut-off level below the 10th percentile was 44.8% with a LR of 4.4; below the 5th percentile, the sensitivity was 34.4% with a LR of 6.9; and below the 2.5th percentile, the sensitivity was 31.0% with a LR of 12. The average value of the humerus, in MoMs, of fetuses with T21 is statistically lower than that of normal fetuses (p < 0.001), as measured by using Student\'s t-test. When maternal age was controlled as a covariant in the comparison between groups, the difference remained statistically significant (p < 0.001). An analysis to compare the HL in normal fetuses of the local population with expected HL based on the Jeanty curve concluded that the HL in normal fetuses of the local population is lower than expected. Conclusions: There is a statistically significant difference between the HL of normal fetuses and HL of fetuses with T21 in the local population (p < 0.001). The sensitivity for detection of T21 was 44.8%, 34.4%, and 31% for the humerus below the 10th, 5th and 2.5th percentile, respectively. The Jeanty curve is not adequate to use as growth control for humeri in local normal fetuses, as its use leads to an increase in false positive rates when measuring the proportion of short humeri

Introdução- As Leucemias Linfocíticas Agudas (LLA) constituem-se na mais comum das neoplasias em crianças. Alguns estudos epidemiológicos identificaram riscos aumentados de LLA em crianças expostas a campos magnéticos gerados por linhas de força de alta tensão, porém, essa associação não foi confirmada por outros estudos. Objetivo- Verificar a associação entre exposição a campos magnéticos e a incidência da LLA em crianças residentes na Região Metropolitana de São Paulo, considerando-se a distância das residências das crianças de linhas de transmissão de energia (88, 138, 230, 345 e 440 kV). Métodos- Estudo casocontrole de base populacional. Os casos foram selecionados em cinco hospitais na capital do município de São Paulo, que concentram o atendimento a crianças com LLA. Quatro controles populacionais foram selecionados para cada caso, emparelhados por sexo, idade e cidade de nascimento. Casos e controles foram entrevistados utilizando-se questionário similar para obtenção de informações sobre as variáveis de interesse e potenciais variáveis de confusão. Os domicílios foram avaliados em relação às distâncias de linhas de transmissão de energia mais próxima utilizando-se o Global Positioning System (GPS). Na análise da associação entre campos magnéticos e LLA foi utilizada regressão logística condicional, incluindo o controle de potenciais variáveis de confusão. Foram calculados os odds ratios (OR) e os respectivos intervalos com 95 por cento de confiança (IC95 por cento). Resultados- A associação entre a distância de linhas de transmissão e LLA foi ajustada pela variável escolaridade da pessoa entrevistada, resultando em OR de 2,91 (IC95 por cento 0,92-9,22). Conclusão- Concluiu-se que, crianças residentes a menos de 160 metros de linhas de transmissão de energia na RMSP apresentam risco maior, porém não estatisticamente significativo de desenvolver LLA quando comparadas com as que residem a mais que 160 metros. / Introduction-The Acute Lymphocytic Leukemia (ALL) is the most common cancers in children. Some epidemiological studies have identified increased risk of ALL in children exposed to magnetic fields generated by high voltage power lines, however, this association was not confirmed by other studies. Purpose- Check the association between exposure to magnetic fields and the incidence of ALL in children residing in the Metropolitan Region of São Paulo, considering the distance from childrens home and transmission lines (88, 138, 230, 345 and 440 kV). Methods- A population-based case-control study. The cases were selected in five hospitals in the city of Sao Paulo, which account for the care of children with ALL. Four population controls were selected for each case, matched by sex, age and city of birth. Cases and controls were interviewed using a similar questionnaire to obtain information on the interest variables and potential confounding variables. The homes were evaluated by distances of the nearest transmission lines using the Global Positioning System (GPS). To examine the association between magnetic fields and ALL was used conditional logistic regression, including the control of potential confounding variables. We calculated the odds ratios (OR) and their 95per cent confidence interval (95 per cent CI). Results-The association between the distance of transmission lines and ALL was adjusted by education of the person interviewed, and the OR was 2.91 (95 per cent CI 0.92-9.22). Conclusion- Children living at less than 160 m of power transmission lines in RMSP have higher risk, though not statistically significant, when compared with those living in more than 160 m.

Trabalho prospectivo estudando a matriz extracelular da parede vesical em pacientes com extrofia vesical comparados ao grupo controle, pela microscopia óptica comum e luz polarizada com morfometria, quantificando-se as fibras colágenas e reticulínicas. Estudou-se 17 pacientes de ambos os sexos, biopsiando-se toda a parede vesical e empregando colorações HE, PS e Reticulina. Diferenças estatisticamente significantes foram notadas na análise quantitativa de fibras colágenas e reticulínicas o número de fibras colágenas foi significativamente maior e o número de fibras reticulínicas foi menor no grupo de pacientes com extrofia vesical quando comparado ao grupo controle. / A prospective study was done to evaluate the detrusor muscle\'s extracellular matrix in classical bladder exstrophy in comparison to a control group, by use of light microscopy and polarization method with morphometry, to quantify collagen and reticular fibers. Seventeen patients from both sexes were analysed and samples were obtained from the bladder and stained with Haematoxylin-eosin, Picrosirius red and the silver impregnation method. There were significant differences when comparing the quantity of collagen and reticular fibers. The collagen fibers were more abundant in the exstrophy bladders compared to controls, while the reticular fibers were present in smaller amounts.

INTRODUÇÃO: O desenvolvimento das habilidades auditivas sofre influência dos estímulos sonoros aos quais as crianças são expostas. Filhos ouvintes de pais surdos (CODAs - Children of Deaf Adults) geralmente não recebem os estímulos de fala da mesma forma que crianças filhas de ouvintes. Tendo em vista que as informações sonoras são importantes para o processo maturacional do sistema auditivo, torna-se pertinente a análise das habilidades auditivas de CODAs que foram pouco expostas à linguagem oral na primeira infância. OBJETIVO: Comparar o processamento auditivo de crianças filhas de surdos, que foram pouco expostas à língua oral no início de suas vidas, com o de crianças filhas de ouvintes. MÉTODO: Participaram deste estudo 60 crianças, na faixa etária entre 5 e 10 anos de idade, com avaliação audiológica básica (audiometria, logoaudiometria e imitanciometria) dentro dos limites de normalidade, destras, sem histórico de doenças sistêmicas e/ou neurológicas que pudessem afetar o sistema nervoso central e sem aprendizado prévio de música ou de segunda língua oral. Foram formados dois grupos semelhantes quanto a idade e sexo, sendo o Grupo Estudo (GE) composto por 30 crianças filhas de surdos sinalizadores, e o Grupo Controle (GC), por 30 crianças filhas de ouvintes. Os testes selecionados foram: Pediatric Speech Intelligibility em português, Dicótico de Dígitos, Padrão de Frequência, Gaps-In-Noise e também testes de Memória para Sons Instrumentais e Verbais. RESULTADOS: Houve diferença estatisticamente significante de desempenho entre os dois grupos, em todos os testes aplicados, com pior desempenho para o GE. Na análise de desempenho dos grupos por faixa etária, foi possível observar que a média de desempenho do GE ficou abaixo da apresentada pelo GC em todos os testes e em todas as idades avaliadas, sendo a diferença de desempenho entre os grupos maior em faixas etárias menores (5 e 6 anos). CONCLUSÕES: Pode-se concluir que a pouca exposição a estímulos linguísticos orais no início da infância, associada a fatores específicos da vivência de grande parte dos CODAs estudados, contribuiu para o baixo desempenho do GE nos testes. Assim, esses resultados indicam que estímulos sonoros ambientais, sobretudo os de linguagem oral, exercem importante influência no desenvolvimento das habilidades auditivas. Este estudo chama a atenção para a importância do acompanhamento auditivo de filhos ouvintes de pais surdos, assim como para a necessidade de exposição destas crianças aos sons linguísticos orais desde o início de suas vidas / INTRODUCTION: The development of auditory skills is influenced by the sound stimuli to which children are exposed. Hearing children of deaf adults (CODAs) do not usually receive speaking stimuli in the same way as those of hearing adults. Given that sound information is important to the maturation process of the auditory system, it is pertinent to analyze the auditory skills of hearing children of deaf signer adults that were little exposed to oral language in their infancy. OBJECTIVE: To compare the auditory processing of CODAs that were little exposed to oral language in their early infancy with that of children of hearing adults. METHOD: A total of 60 children aged 5-10 years participated in the present study. All participants received normal ratings in their basic audiometric evaluation (audiometry, speech audiometry and imitanciometry). They were right-handed, without a history of systemic and/or neurological diseases that might affect the central nervous system, and without previous musical or second spoken language training. Two groups similar in age and sex were established: the Study Group (SG) comprised 30 children of deaf signer adults and the Control Group (CG) comprised 30 children of hearing adults. The tests selected were Pediatric Speech Intelligibility, Dichotic Digits, Pitch Pattern, Gaps-In-Noise, and Memory for Instrumental Sounds and Verbal Sounds. RESULTS: The SG performed significantly worse than the CG for all tests. Moreover, an analysis of the performance of the groups per age range revealed that for all age ranges assessed, the SG performance average was below that of the CG average; the performance difference between the groups was greater in younger children (5- and 6-year olds). CONCLUSIONS: It can be concluded that the low exposure to oral linguistic stimuli during infancy, associated with specific aspects of the experience of a large proportion of the CODAs studied, contributed to the low performance of the SG in the tests. These results indicate that ambient sound stimuli, especially those related to oral language, strongly influence auditory skills. This study highlights to the importance of the auditory follow-up of hearing CODAs, as well as to the need for exposing these children to oral linguistic sounds from a very early age

Le cancer du poumon chez la femme était une maladie rare au début du XXème siècle. Son incidence a fortement augmenté durant ces vingt dernières années dans les pays développés et particulièrement en France du fait de l’augmentation de la consommation de cigarettes dans la population féminine. L’étude des risques de cancer du poumon liés à la consommation de cigarettes des femmes a soulevé la question d’une éventuelle plus grande susceptibilité des femmes vis-à-vis du tabac dans la survenue du cancer du poumon par rapport aux hommes. Les résultats des études épidémiologiques sur le sujet sont divergents et l’hypothèse selon laquelle les hormones joueraient un rôle dans cette plus grande susceptibilité des femmes a été proposée pour expliquer ces différences. Objectifs : Les objectifs de cette thèse sont de donner des estimations récentes du risque de cancer du poumon chez la femme associé à la consommation de cigarettes en France, de comparer le risque de cancer du poumon chez les femmes et chez les hommes et d’étudier le rôle des hormones dans le risque de cancer du poumon.Matériel et méthodes : L’étude de la consommation de cigarettes chez les femmes et la comparaison des risques de cancer du poumon associé à cette consommation a été réalisée à partir des données de l’étude ICARE. Les cas de cancer du poumon ont été identifiés dans 10 départements incluant un registre général de cancer. Au total, 2276 cas de cancer du poumon chez les hommes et 2780 témoins ont été inclus ainsi que 650 cas de cancers du poumon féminins et 775 témoins. Les témoins étaient issus de la population générale, avec une distribution âge et sexe conforme à celle des cas et une répartition par statut socioéconomique conforme à celle des départements dont sont issus les cas. L’analyse du rôle des hormones et des facteurs reproductifs sur le risque du cancer du poumon a été menée par une analyse poolée, réunissant 9 études internationales. Cette étude a été réalisée dans le cadre du consortium ILCCO. Au total, 4547 cas et 4176 témoins ont été inclus dans l’analyse.Résultats : Notre étude a montré que le risque de cancer du poumon associé à la consommation de cigarettes est 8 fois plus élevé chez les femmes fumeuses par rapport aux non fumeuses en France. La quantité moyenne fumée, la durée totale de consommation et le délai depuis l’arrêt sont les 3 principales caractéristiques de consommation qui modulent le risque de cancer du poumon. La fraction de risque attribuable à la consommation de cigarettes est estimée à 55% [47 %-63 %]. La comparaison du risque de cancer du poumon entre les hommes et les femmes est très influencée par la présence des non fumeurs. . Bien que nous n’ayons pas trouvé de différence de risque de cancer du poumon entre les hommes et les femmes fumeurs lorsque l’on considère tous les types histologiques réunis, nous avons constaté que les femmes relativement aux hommes étaient plus à risque de cancer à petites cellules et de cancer épidermoïde, qui sont les types histologiques les plus liés à la consommation de cigarettes. Concernant l’étude sur le rôle des hormones dans la survenue de cancer du poumon, nos résultats montrent que plus l’âge à la ménopause est tardif et plus la durée des cycles menstruels est longue, moins le risque de cancer du poumon est important. Nous avons également montré que l’ovariectomie était associée positivement avec le risque de cancer du poumon. Conclusion : Nos résultats semblent indiquer que les femmes fumeuses sont peut-être plus à risque de développer un carcinome à petites cellules ou un cancer épidermoïde par rapport aux hommes fumeurs. L’étude sur les facteurs hormonaux a montré une association négative avec l’exposition prolongée aux hormones, qui n’est pas très cohérente avec un risque de cancer du poumon associé au tabac plus important chez les femmes que chez les hommes. / The incidence of female lung cancer in developed countries has been increasing since 1950 and particularly in France where the cigarettes consumption has also increased. Since 1980, a growing number of epidemiological surveys have pinpointed the risk of female lung cancer related to smoking. Consecutively, a debate on gender differences in lung cancer risk has appeared, but still in progress nowadays. The reproductive factors could explain these differences. In order to have recent and reliable data on the association between cigarettes smoking and the risk of lung cancer in women and to compare the lung cancer risk associated with smoking exposure between genders, we analyzed the data of a French population-based case-control study, ICARE. The role of the reproductive factors in lung cancer was analyzed pooling, 9 international epidemiological studies included in ILCCO consortium.The ICARE study included 2276 male and 650 female cases and 2780 male and 775 female controls. Lifetime smoking exposure was represented by the comprehensive smoking index (CSI) which combines total duration of smoking, the mean intensity and the time since cessation. The pooled analysis of the reproductive factors included a total of 4547 cases and 4176 controls were included.Among the ever smokers, the relative risk of lung cancer was similar among men and women after adjustments for age, département, education, BMI, occupational exposure and chronic bronchitis. However, we found that women have a 2-fold greater risk than men of developing either small cell carcinomas or squamous cell carcinomas. Alternatively, the association was similar between men and women for the adenocarcinomas. As regard the reproductive factors, we found that longer is the age at menopause, lower is the lung cancer risk. Moreover, longer is the duration of cycle, lower is the lung cancer risk. The ovariectomy is also associated with an increasing risk of lung cancer.Our findings suggest that women might be more susceptible than men to develop small cell carcinoma or squamous cell carcinoma in response to the carcinogenic effect of cigarettes smoking. The analysis on the reproductive factors showed an inverse association between hormonal exposure and lung cancer indicating a likely complex relationship between the two factors.

Le cancer de la cavité orale représente un problème important de santé publique en France où les taux d’incidence sont parmi les plus élevés au monde. Bien qu’une détection précoce soit possible, ces tumeurs sont souvent diagnostiquées à un stade avancé et sont ainsi responsables de plus de 1500 décès par an. L’objectif général est de clarifier le rôle et l’impact des différents facteurs de risque dans la survenue des cancers de la cavité orale en France, notamment d’examiner de façon détaillée le rôle du tabac et de l’alcool par localisation anatomique précise, et d’étudier les associations avec d’autres facteurs de risque potentiels (indice de masse corporelle, antécédents médicaux, antécédents familiaux de cancer, consommations de café et de thé). Ce travail s’appuie sur les données d’une large étude cas-témoins en population générale, l’étude ICARE. Il porte sur un sous-ensemble de ces sujets (772 cas de cancer de la cavité orale et 3555 témoins). Les résultats montrent que le tabac augmente le risque de cancer de la cavité orale même pour des quantités et/ou durées faibles, alors que l’augmentation de risque liée à l’alcool n’est observée que pour de fortes consommations. L’effet conjoint du tabac et de l’alcool est plus que multiplicatif. Les associations avec les consommations d’alcool et de tabac varient selon la sous localisation : les associations les plus fortes sont observées pour le plancher buccal, les plus faibles pour les gencives. L’étude des autres facteurs de risque a mis en évidence : une association inverse entre risque de cancer de la cavité orale et indice de masse corporelle, avec un risque plus faible chez les personnes en surpoids ou obèses ; un risque augmenté lorsqu’un parent du 1er degré a été atteint d’un cancer des voies aéro-digestives supérieures ; un risque élevé chez les personnes présentant des antécédents de candidose buccale ; un risque diminué chez les consommateurs de thé ou de café. A partir de ces premiers résultats, il est envisagé de construire un score prédictif de cancer de la cavité orale permettant d’identifier les sujets à risque élevé sur lesquels cibler préférentiellement les actions de dépistage. / Cancer of the oral cavity is a major public health problem in France. Incidence rates are among the highest in the world. Although early detection is possible and effective, these tumors are often diagnosed at an advanced stage and are thus responsible for over 1,500 deaths per year. The objective of this work was to clarify the role and impact of several risk factors in the development of cancers of the oral cavity in France, particularly to examine the role of tobacco smoking and alcohol drinking by subsite, and to explore associations with other potential risk factors (body mass index, medical history, family history of cancer, tea and coffee consumption). We analyzed detailed data from 772 cases of cancer of the oral cavity and 3555 controls included in a large population-based case-control study, the ICARE study. Tobacco smoking increased the risk of oral cavity cancer even for low quantities and/or durations, while alcohol drinking increased this risk only in heavy drinkers. The combined effect of tobacco and alcohol was greater than multiplicative. Associations with alcohol and tobacco consumption varied depending on subsite: the strongest associations were observed for the floor of the mouth, the lowest for the gums. The analysis of other risk factors showed: an inverse association between oral cancer risk and body mass index with a lowered risk among overweight or obese; an increased risk associated with an history of head and neck cancer in 1st degree relatives; an elevated risk in people with a history of oral candidiasis and a decreased risk among consumers of tea or coffee. From these first results, it is planned to develop an oral cancer risk score to identify high-risk individuals for screening.