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Introdução: O câncer de pulmão é a causa mais comum de morte por câncer no mundo. Objetivo: Descrever os achados clínicos ecomparar as características do câncer de pulmão em relação ao sexo, à idade e à história tabágica. Métodos: Estudo histórico com revisão de prontuários de 460 pacientes com câncer de pulmão. Resultados: A média de idade foi de 61±10 anos, sendo 359 (78%) homens. A história tabágica foi positiva em 93,7% dos pacientes. Dos 28 pacientes não tabagistas, 23 eram mulheres. Doença pulmonar obstrutiva crônica (DPOC) foi observada em 325 pacientes (70,7%) e pneumonia obstrutiva em 31,5% dos pacientes. Os principais sintomas e sinais respiratórios foram tosse, dispneia, dor torácica e hemoptise em respectivamente, 78,3%, 61,5%, 53,9% e 37,4% dos casos. Os sintomas sistêmicos mais comuns foram emagrecimento em 71,1%, anorexia em 54,1% e febre em 25,4% dos pacientes. Os tipos histológicos mais frequentes foram adenocarcinoma, carcinoma escamoso e carcinoma de células pequenas em respectivamente, 44,4%, 35% e 13,9% dos pacientes. O estádio tumoral foi IA/IB em 10% dos pacientes e IIIB/IV em 65,6% dos casos. Em 16,7% dos casos o tratamento foi cirúrgico. Dor torácica e síndrome da veia cava superior foram mais frequentes nos pacientes com menos de 50 anos. Adenocarcinoma predominou nos pacientes não tabagistas (75% vs 42,1%; p<0,01), e nas mulheres (60,4% vs 39,8%; p<0,005). Não houve diferença significativa em relação ao estádio ou tratamento quando comparados pacientes de acordo com sexo, idade e história tabágica. Conclusões: A prevalência de DPOC entre os pacientes com câncer de pulmão foi elevada. Os sintomas mais comuns foram tosse e emagrecimento e a maioria dos casos era de doença avançada. O tipo histológico mais frequente foi o adenocarcinoma, com prevalência aumentada em mulheres e não tabagistas. Sexo, idade e tabagismo não influenciaram no estadiamento e tratamento. / Introduction: Lung cancer is the most common cause of cancer death worldwide. Aim: To describe clinical findings and to compare the characteristics of lung cancer accordingto gender, age and smoking history. Methods: Retrospective chart reviewof 460 patients with lung cancer. Results: The mean age was 61 ± 10 years; 359 of the patients (78%) were men. The smoking history was positive in 93.7% of the patients. Of the 28 non-smoking patients, 23 were women. Chronic obstructive lung disease (DPOC) was found in 325 patients (70.7%) and obstructive pneumonia in 31.5% of the cases. The most frequent respiratory complains were cough, dyspnea, thoracic pain and hemoptysis in 78.3%, 61.5%, 53.9% and 37.4% of the cases, respectively. The common systemic symptoms were weight loss in 71.1%, anorexia in 54.1% and fever in 25.4%. The most frequent histological types were adenocarcinoma, squamous cell carcinoma and small cell carcinoma in 44.4%, 35% and 13.9%, respectively. The cancer staging was IA/IB in 10% and IIIB/IV in 65.6% of the patients. In 16.7% of the cases the lung cancer was treated by surgery. Thoracic pain and superior vena cava syndrome were more frequent in patients £ 50 years old. The frequency of adenocarcinoma was significantly higher in non-smokers (75% vs 42.1%; p<0.01) and in women (60.4% vs 39.8%; p<0.005). There were no differences in relationship to the cancer staging or treatment when patients were compared according to gender, age and smoking history. Conclusions: The prevalence of COPD was high among patients with lung cancer. The commonest symptoms were cough and weight loss and most of the patients had advanced disease. The most frequent histological type was adenocarcinoma, highly prevailing in non-smoking women. Cancer staging and treatment was not related to gender, age and smoking history.

Introdução: O câncer de pulmão é a causa mais comum de morte por câncer no mundo. Objetivo: Descrever os achados clínicos ecomparar as características do câncer de pulmão em relação ao sexo, à idade e à história tabágica. Métodos: Estudo histórico com revisão de prontuários de 460 pacientes com câncer de pulmão. Resultados: A média de idade foi de 61±10 anos, sendo 359 (78%) homens. A história tabágica foi positiva em 93,7% dos pacientes. Dos 28 pacientes não tabagistas, 23 eram mulheres. Doença pulmonar obstrutiva crônica (DPOC) foi observada em 325 pacientes (70,7%) e pneumonia obstrutiva em 31,5% dos pacientes. Os principais sintomas e sinais respiratórios foram tosse, dispneia, dor torácica e hemoptise em respectivamente, 78,3%, 61,5%, 53,9% e 37,4% dos casos. Os sintomas sistêmicos mais comuns foram emagrecimento em 71,1%, anorexia em 54,1% e febre em 25,4% dos pacientes. Os tipos histológicos mais frequentes foram adenocarcinoma, carcinoma escamoso e carcinoma de células pequenas em respectivamente, 44,4%, 35% e 13,9% dos pacientes. O estádio tumoral foi IA/IB em 10% dos pacientes e IIIB/IV em 65,6% dos casos. Em 16,7% dos casos o tratamento foi cirúrgico. Dor torácica e síndrome da veia cava superior foram mais frequentes nos pacientes com menos de 50 anos. Adenocarcinoma predominou nos pacientes não tabagistas (75% vs 42,1%; p<0,01), e nas mulheres (60,4% vs 39,8%; p<0,005). Não houve diferença significativa em relação ao estádio ou tratamento quando comparados pacientes de acordo com sexo, idade e história tabágica. Conclusões: A prevalência de DPOC entre os pacientes com câncer de pulmão foi elevada. Os sintomas mais comuns foram tosse e emagrecimento e a maioria dos casos era de doença avançada. O tipo histológico mais frequente foi o adenocarcinoma, com prevalência aumentada em mulheres e não tabagistas. Sexo, idade e tabagismo não influenciaram no estadiamento e tratamento. / Introduction: Lung cancer is the most common cause of cancer death worldwide. Aim: To describe clinical findings and to compare the characteristics of lung cancer accordingto gender, age and smoking history. Methods: Retrospective chart reviewof 460 patients with lung cancer. Results: The mean age was 61 ± 10 years; 359 of the patients (78%) were men. The smoking history was positive in 93.7% of the patients. Of the 28 non-smoking patients, 23 were women. Chronic obstructive lung disease (DPOC) was found in 325 patients (70.7%) and obstructive pneumonia in 31.5% of the cases. The most frequent respiratory complains were cough, dyspnea, thoracic pain and hemoptysis in 78.3%, 61.5%, 53.9% and 37.4% of the cases, respectively. The common systemic symptoms were weight loss in 71.1%, anorexia in 54.1% and fever in 25.4%. The most frequent histological types were adenocarcinoma, squamous cell carcinoma and small cell carcinoma in 44.4%, 35% and 13.9%, respectively. The cancer staging was IA/IB in 10% and IIIB/IV in 65.6% of the patients. In 16.7% of the cases the lung cancer was treated by surgery. Thoracic pain and superior vena cava syndrome were more frequent in patients £ 50 years old. The frequency of adenocarcinoma was significantly higher in non-smokers (75% vs 42.1%; p<0.01) and in women (60.4% vs 39.8%; p<0.005). There were no differences in relationship to the cancer staging or treatment when patients were compared according to gender, age and smoking history. Conclusions: The prevalence of COPD was high among patients with lung cancer. The commonest symptoms were cough and weight loss and most of the patients had advanced disease. The most frequent histological type was adenocarcinoma, highly prevailing in non-smoking women. Cancer staging and treatment was not related to gender, age and smoking history.

Introdução: O câncer de pulmão é a causa mais comum de morte por câncer no mundo. Objetivo: Descrever os achados clínicos ecomparar as características do câncer de pulmão em relação ao sexo, à idade e à história tabágica. Métodos: Estudo histórico com revisão de prontuários de 460 pacientes com câncer de pulmão. Resultados: A média de idade foi de 61±10 anos, sendo 359 (78%) homens. A história tabágica foi positiva em 93,7% dos pacientes. Dos 28 pacientes não tabagistas, 23 eram mulheres. Doença pulmonar obstrutiva crônica (DPOC) foi observada em 325 pacientes (70,7%) e pneumonia obstrutiva em 31,5% dos pacientes. Os principais sintomas e sinais respiratórios foram tosse, dispneia, dor torácica e hemoptise em respectivamente, 78,3%, 61,5%, 53,9% e 37,4% dos casos. Os sintomas sistêmicos mais comuns foram emagrecimento em 71,1%, anorexia em 54,1% e febre em 25,4% dos pacientes. Os tipos histológicos mais frequentes foram adenocarcinoma, carcinoma escamoso e carcinoma de células pequenas em respectivamente, 44,4%, 35% e 13,9% dos pacientes. O estádio tumoral foi IA/IB em 10% dos pacientes e IIIB/IV em 65,6% dos casos. Em 16,7% dos casos o tratamento foi cirúrgico. Dor torácica e síndrome da veia cava superior foram mais frequentes nos pacientes com menos de 50 anos. Adenocarcinoma predominou nos pacientes não tabagistas (75% vs 42,1%; p<0,01), e nas mulheres (60,4% vs 39,8%; p<0,005). Não houve diferença significativa em relação ao estádio ou tratamento quando comparados pacientes de acordo com sexo, idade e história tabágica. Conclusões: A prevalência de DPOC entre os pacientes com câncer de pulmão foi elevada. Os sintomas mais comuns foram tosse e emagrecimento e a maioria dos casos era de doença avançada. O tipo histológico mais frequente foi o adenocarcinoma, com prevalência aumentada em mulheres e não tabagistas. Sexo, idade e tabagismo não influenciaram no estadiamento e tratamento. / Introduction: Lung cancer is the most common cause of cancer death worldwide. Aim: To describe clinical findings and to compare the characteristics of lung cancer accordingto gender, age and smoking history. Methods: Retrospective chart reviewof 460 patients with lung cancer. Results: The mean age was 61 ± 10 years; 359 of the patients (78%) were men. The smoking history was positive in 93.7% of the patients. Of the 28 non-smoking patients, 23 were women. Chronic obstructive lung disease (DPOC) was found in 325 patients (70.7%) and obstructive pneumonia in 31.5% of the cases. The most frequent respiratory complains were cough, dyspnea, thoracic pain and hemoptysis in 78.3%, 61.5%, 53.9% and 37.4% of the cases, respectively. The common systemic symptoms were weight loss in 71.1%, anorexia in 54.1% and fever in 25.4%. The most frequent histological types were adenocarcinoma, squamous cell carcinoma and small cell carcinoma in 44.4%, 35% and 13.9%, respectively. The cancer staging was IA/IB in 10% and IIIB/IV in 65.6% of the patients. In 16.7% of the cases the lung cancer was treated by surgery. Thoracic pain and superior vena cava syndrome were more frequent in patients £ 50 years old. The frequency of adenocarcinoma was significantly higher in non-smokers (75% vs 42.1%; p<0.01) and in women (60.4% vs 39.8%; p<0.005). There were no differences in relationship to the cancer staging or treatment when patients were compared according to gender, age and smoking history. Conclusions: The prevalence of COPD was high among patients with lung cancer. The commonest symptoms were cough and weight loss and most of the patients had advanced disease. The most frequent histological type was adenocarcinoma, highly prevailing in non-smoking women. Cancer staging and treatment was not related to gender, age and smoking history.

In this work several algorithms for diaphragm detection in 2D views of cone-beam computed tomography (CBCT) raw data are developed. These algorithms are tested on 21 Siemens megavoltage CBCT scans of lungs and the result is compared against the diaphragm apex identified by human experts. Among these algorithms dynamic Hough transform is sufficiently quick and accurate for motion determination prior to radiation therapy. The diaphragm was successfully detected in all 21 data sets, even for views with poor image quality and confounding objects. Each CBCT scan analysis (200 frames) took about 38 seconds on a 2.66 GHz Intel quad-core 2 CPU. The average cranio-caudal position error was 1.707 ± 1.117 mm. Other directions were not assessed due to uncertainties in expert identification.

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第12916号 / 論医博第2091号 / 新制||医||1009(附属図書館) / 32126 / 京都大学大学院医学研究科医学専攻 / (主査)教授 増永 慎一郎, 教授 伊達 洋至, 教授 鈴木 実 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20997号 / 医博第4343号 / 新制||医||1027(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 鈴木 実, 教授 平井 豊博, 教授 伊達 洋至 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Le FcRn ou récepteur néonatal du Fc des IgG est un récepteur " clé " qui prolonge la demi-vie des IgG et de l’albumine et assure leur biodistribution. Récemment, son rôle s'est étendu à la réponse immunitaire humorale et anti-tumorale. Par ailleurs, certains travaux indiquent que le niveau d’expression du FcRn dans les différents tissus pourrait être à l’origine d’une modulation de ses fonctions. Dans ce contexte, nous avons démontré que l’expression du FcRn était diminuée dans le tissu cancéreux par rapport au tissu sain, chez des patients atteints du cancer du poumon et que cet effet était corrélé à leur pronostic. Afin de comprendre les répercussions de cette diminution sur la tumorigenèse, nous avons mis en place le modèle murin de métastases pulmonaires B16F10, chez les souris FcRn-/-. L'absence de FcRn influence la réponse anti-tumorale, en altérant le nombre de cellules dendritiques et des TCD8+. Pour la première fois, nous avons montré que l'absence du FcRn influençait le développement/maturation et fonctions des cellules NK, fragilisant ainsi encore plus l'immunosurveillance antitumorale. Ces résultats mettent en avant un nouveau rôle du FcRn dans la biologie des cellules NK. Les mécanismes à l’origine de cet effet restent à élucider. / FcRn or neonatal receptor for the Fc portion of IgG is a "key" receptor since it extends the half-life of IgGs and albumin and ensures their biodistribution. Recently, its role has been extended to the humoral and anti-tumor immune. Moreover, some studies indicate that the expression level of FcRn in the different tissues may modulate its functions. In this context, we showed that the expression of FcRn was decreased in lung cancer tissue compared to healthy tissue, in patients with NSLC. This decreased expression is correlated with the prognosis of the patients. In order to understand the impact of the reduced FcRn expression on tumorigenesis, we implemented a murine model of lung metastases, implanting B16F10 cells in FcRn deficient mice. The absence of FcRn influences the anti-tumor response, by altering the number of dendritic cells and TCD8+ cells. We showed for the first time that the lack of FcRn altered the development / maturation and the functional activity of NK cells, thus weakening even more anti-tumor immunosurveillance. These new results on NK highlight a new role of FcRn in the biology of NK cells. The mechanisms underlying this effect need to be elucidated.

L’un des aspects les plus critiques dans les planifications dosimétriques des traitements par radiothérapie est la délinéation des limites de la tumeur. Cette délinéation se fait généralement sur les images anatomiques de tomodensitométrie (TDM). Mais récemment, il est recommandé de faire cette délinéation pour les cancers broncho-pulmonaires non à petites cellules (CBNPC) sur les images fonctionnelles de Tomographie par Émission de Positon (TEP) pour prendre en compte les caractéristiques biologiques de la cible. Jusqu’à ce jour, aucune technique de segmentation ne s’est révélée satisfaisante pour les images TEP en application clinique. Une solution pour ce problème est proposée dans cette étude. Méthodes : Les optimisations de notre méthode ont consisté principalement à faire l’ajustement des seuils directement à partir des corps des patients au lieu de le faire à partir du fantôme. Résultats : Pour les lésions de grands axes supérieurs à 20 mm, notre technique de segmentation a montré une bonne estimation des mesures histologiques (la moyenne de différence de diamètre entre données mesurées et déterminées avec notre technique = +1,5 ± 8,4 %) et une estimation acceptable des mesures TDM. Pour les lésions de grands axes inférieurs ou égaux à 20 mm, cette méthode a montré un écart avec les mesures dérivées des données histologiques ou bien des données TDM. Conclusion : Cette nouvelle méthode d’ajustement montre une bonne précision pour la délimitation des lésions de grands axes compris entre 2 et 4,5 cm. Néanmoins, elle n’évalue pas correctement les lésions les plus petites, cela peut être dû à l’effet du volume partiel / Tumor delineation is a critical aspect in radiotherapy planning treatment and is usually performed on the anatomical images of a computed tomography (CT) scan. Recently, for non-small cell lung cancer, it has been recommended to use functional Positron Emission Tomography (PET) images to take into account the target biological characteristics. However, today, there is no satisfactory segmentation technique for PET images in clinical applications. In the present study, a solution of this problem is proposed. Methods: The optimizations of tumor delineation consisted primarily on the thresholds adjustment directly from patients, rather than phantoms. The development and the validation of this adjustment were done by comparing segmented lesions on PET images with two different gold standards: measurements performed on CT images of the selected lesions and histological measurements of surgically removed tumors. Results: For lesions greater than 20 mm, our segmentation technique showed very good estimation of histological measurements (mean difference diameter between measured and calculated data equal to +1.5 ± 8.4 %) and an acceptable estimation of CT measurements. For lesions smaller or equal to 20 mm, the method showed a large gap with the measurements derived from histological or CT data. Conclusion: This novel segmentation technique shows very high accuracy for the lesions of large axes between 2 and 4.5 cm. Nevertheless, it does not correctly evaluate smaller lesions probably because of the partial volume effect