Gold nanoshells (GNS) are a new class of nanoparticles that can be optically tuned to scatter or absorb light from the near-ultraviolet to near-infrared (NIR) region by varying the core (dielectric silica) /shell (gold) ratio. In addition to spectral tunability, GNS are inert and bioconjugatable making them potential labels for in vivo imaging and therapy of tumors. We report the use of GNS as exogenous contrast agents for enhanced visualization of tumors using narrow band imaging (NBI). NBI takes advantage of the strong NIR absorption of GNS to distinguish between blood and nanoshells in the tumor by imaging in narrow wavelength bands in the visible and NIR, respectively. Using tissue-simulating phantoms, we determined the optimum wavelengths to enhance contrast between blood and GNS. We then used the optimum wavelengths for ex-vivo imaging of tumors extracted from human colon cancer xenograft bearing mice injected with GNS. Systemically delivered GNS accumulated passively in tumor xenografts by enhanced permeability and retention (EPR) effect. Ex-Vivo NBI of tumor xenografts demonstrated tumor specific heterogeneous distribution of GNS with a clear distinction from the tumor vasculature. The results of the present study demonstrate the feasibility of using GNS as contrast agents to visualize tumor tissues using NBI technique. / text

A significant challenge in the surgical resection of tumors is accurate identification of tumor margins. Current methods for margin detection are time-intensive and often result in incomplete tumor excision and recurrence of disease. The objective of this project was to develop a near-infrared narrowband imaging (NIR NBI) system to image tumor and its margins in real-time during surgery utilizing the contrast provided by gold nanoparticles (GNPs). NIR NBI images narrow wavelength bands to enhance contrast from plasmonic particles in a widefield, portable and non-contact device that is clinically compatible for real-time tumor margin demarcation. GNPs have recently gained significant traction as nanovectors for combined imaging and photothermal therapy of tumors. Delivered systemically, GNPs preferentially accumulate at the tumor site via the enhanced permeability and retention effect, and when irradiated with NIR light, produce sufficient heat to treat tumor tissue. The NIR NBI system consists of 1) two LED's: green (530 nm) and NIR (780 nm) LED for illuminating the blood vessels and GNP, respectively, 2) a filter wheel for wavelength selection, and 3) a CCD to collect reflected light from the sample. The NIR NBI system acquires and processes images at a rate of at least 6 frames per second. We have developed custom control software with a graphical user interface that handles both image acquisition and processing/display in real-time. We used mice with a subcutaneous tumor xenograft model that received intravenous administration and topical administration of gold nanoshells and gold nanorods. We determined the GNP's distribution and accumulation pattern within tumors using NIR NBI. Ex vivo NIR NBI of tumor xenografts accumulated with GNPs delivered systemically, demonstrated a highly heterogeneous distribution of GNP within the tumor with higher accumulation at the cortex. GNPs were observed in unique patterns surrounding the perivascular region. The GNPs clearly defined the tumor while surrounding normal tissue did not indicate the presence of particles. In addition, we present results from NBI of tumors that received topical delivery of conjugated GNPs. We determined that tumor labeling using topical delivery approach resulted in a more homogenous distribution of GNPs compared to the systemic delivery approach. Finally, we present results from the on-going in vivo tumor margin imaging studies using NIR NBI. Our results demonstrate the feasibility of NIR NBI in demarcating tumor margins during surgical resection and potentially guiding photo-thermal ablation of tumors. / text

Orientador: René Aloísio da Costa Vieira / Banca: Jair Cortez Montovani / Banca: José Magrin / Resumo: O câncer de boca e orofaringe apresentam incidência elevada em nosso meio, sendo o diagnóstico realizado em estádio avançado, onde a sobrevida é limitada. Neste sentido, faz-se importante avaliar e aprimorar métodos que visem ao diagnóstico precoce destas lesões. O uso do lugol ou do azul de toluidina tem limitações, e o exame clínico de rotina não é realizado rotineiramente na prática clínica, mesmo em populações de alto risco. A pesquisa neoplasia primária em pacientes de risco constitui um bom modelo na avaliação de novas metodologias de diagnóstico precoce do câncer de boca e orofaringe, sendo que a taxa de segunda neoplasia primária varia de 1 a 40%. Recentemente, o aparecimento de endoscópios com o recurso do Narrow-band imaging (NBI) tem demonstrado uma elevação na acurácia do diagnóstico de lesões neoplásicas, porém o número de trabalhos é limitado, havendo pouca experiência em nosso meio. Estudo prospectivo de pacientes portadores de carcinoma espinocelular de boca, orofaringe e esôfago, sem tratamento prévio, atendidos no Hospital de Câncer de Barretos no período de janeiro a agosto de 2010. Procurou-se avaliar a pesquisa de lesões préneoplásicas e segunda tumor primário (STP) na boca e orofaringe, utilizando-se o exame físico, associado a endoscopia com luz branca e a endoscopia com o recurso do NBI. As lesões visualizadas foram biopsiadas e as imagens digitalizadas. Utilizou-se a classificação patológica de WHO. Procurou-se avaliar a sensibilidade, especificidade, acurácia valores preditivos positivos e negativos e teste kappa da técnica do NBI em relação à técnica tradicional avaliando em as lesões pré-neoplásicas e neoplásicas. Foram avaliados 144 pacientes, sendo a maioria homens (86,8%), portadores de CEC de boca (44,4%), fumantes (80,6%) e etilistas (58,3%), com tumores em estádio STP em cabeça e pescoço... (resumo completo, clicar acesso eletrônico abaixo) / Abstract: Oral and oralpharyngeal cancer have high incidence in our country, being diagnosed at advanced stages, where survival is limited. In this sense is important to evaluate and improve methods aimed at early diagnosis, such as lugol's solution and toluidine, but both have limitations, and clinical evaluation, not always used in clinical practice, even in high risks population.The research of second primary tumor in high risks pacients is a good way to evaluate new methods of earlier diagnosis of oral and oralpharyngeal cancers. It's important to remember that the rate of second primary tumor varies between 1 to 40%. Recently, advent of endoscopes with the NBI feature (narrow band imaging) in endoscopy has demonstrated an increase in accuracy in cancer diagnosis, but the number of publications are still limited, with little experience in our midst. Cross-sectional, prospective, study of patients with oral carcinoma, pharynx and esophagus, untreated, in Cancer Hospital of Barretos, between january and august in 2010. Second primary tumor (SPT) in oral and oropharynx was searching using the association between clinical evaluation with white light endoscopy and NBI endoscopy. When lesions were presented it was biopsied and images digitalized. WHO pathologic classification was performed. The results of the both methods were compared regarding sensitivity, specificity, accuracy, positive predictive value and negative predictive value and kappa test. We evaluated 144 patients, being the majority men (86.8%) with OSCC (oral squamous cell carcinomas) (44.4%), smokers (80.6%) and alcoholics (58.3%), clinical stage neoplasia III and IV (77.0%). We identified nine neoplastic lesions and 16 dysplasia lesions. Head and neck SPT rate was 6,3%, but the rate of premalignant lesions and malignant in oral cavity and oropharynx was 17.4% and 30.0% when the primary site was oral cavity, 25.0% for esophagus... (Complete abstract click electronic access below) / Mestre

Made available in DSpace on 2014-06-11T19:23:07Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-03-16Bitstream added on 2014-06-13T18:50:21Z : No. of bitstreams: 1 boldrinijunior_d_me_botfm.pdf: 512291 bytes, checksum: 8823a68fb6704d2438a0ce58e025b019 (MD5) / Fundação Pio Xii - Barretos / O câncer de boca e orofaringe apresentam incidência elevada em nosso meio, sendo o diagnóstico realizado em estádio avançado, onde a sobrevida é limitada. Neste sentido, faz-se importante avaliar e aprimorar métodos que visem ao diagnóstico precoce destas lesões. O uso do lugol ou do azul de toluidina tem limitações, e o exame clínico de rotina não é realizado rotineiramente na prática clínica, mesmo em populações de alto risco. A pesquisa neoplasia primária em pacientes de risco constitui um bom modelo na avaliação de novas metodologias de diagnóstico precoce do câncer de boca e orofaringe, sendo que a taxa de segunda neoplasia primária varia de 1 a 40%. Recentemente, o aparecimento de endoscópios com o recurso do Narrow-band imaging (NBI) tem demonstrado uma elevação na acurácia do diagnóstico de lesões neoplásicas, porém o número de trabalhos é limitado, havendo pouca experiência em nosso meio. Estudo prospectivo de pacientes portadores de carcinoma espinocelular de boca, orofaringe e esôfago, sem tratamento prévio, atendidos no Hospital de Câncer de Barretos no período de janeiro a agosto de 2010. Procurou-se avaliar a pesquisa de lesões préneoplásicas e segunda tumor primário (STP) na boca e orofaringe, utilizando-se o exame físico, associado a endoscopia com luz branca e a endoscopia com o recurso do NBI. As lesões visualizadas foram biopsiadas e as imagens digitalizadas. Utilizou-se a classificação patológica de WHO. Procurou-se avaliar a sensibilidade, especificidade, acurácia valores preditivos positivos e negativos e teste kappa da técnica do NBI em relação à técnica tradicional avaliando em as lesões pré-neoplásicas e neoplásicas. Foram avaliados 144 pacientes, sendo a maioria homens (86,8%), portadores de CEC de boca (44,4%), fumantes (80,6%) e etilistas (58,3%), com tumores em estádio STP em cabeça e pescoço... / Oral and oralpharyngeal cancer have high incidence in our country, being diagnosed at advanced stages, where survival is limited. In this sense is important to evaluate and improve methods aimed at early diagnosis, such as lugol´s solution and toluidine, but both have limitations, and clinical evaluation, not always used in clinical practice, even in high risks population.The research of second primary tumor in high risks pacients is a good way to evaluate new methods of earlier diagnosis of oral and oralpharyngeal cancers. It’s important to remember that the rate of second primary tumor varies between 1 to 40%. Recently, advent of endoscopes with the NBI feature (narrow band imaging) in endoscopy has demonstrated an increase in accuracy in cancer diagnosis, but the number of publications are still limited, with little experience in our midst. Cross-sectional, prospective, study of patients with oral carcinoma, pharynx and esophagus, untreated, in Cancer Hospital of Barretos, between january and august in 2010. Second primary tumor (SPT) in oral and oropharynx was searching using the association between clinical evaluation with white light endoscopy and NBI endoscopy. When lesions were presented it was biopsied and images digitalized. WHO pathologic classification was performed. The results of the both methods were compared regarding sensitivity, specificity, accuracy, positive predictive value and negative predictive value and kappa test. We evaluated 144 patients, being the majority men (86.8%) with OSCC (oral squamous cell carcinomas) (44.4%), smokers (80.6%) and alcoholics (58.3%), clinical stage neoplasia III and IV (77.0%). We identified nine neoplastic lesions and 16 dysplasia lesions. Head and neck SPT rate was 6,3%, but the rate of premalignant lesions and malignant in oral cavity and oropharynx was 17.4% and 30.0% when the primary site was oral cavity, 25.0% for esophagus... (Complete abstract click electronic access below)

Optical imaging methods incorporating observation of the mucosal surface of organs with narrowband filtered light are diagnostic tools with a significant development in recent years and have become an integral and inseparable part of the diagnostic process of benign and malignant pathologies of the mucosal surface of various anatomical systems of the human body. Malignant and premalignant lesions of the upper aero-digestive tract (UADT) are no exception. The present work demonstrates the benefits of evaluation of changes in microvascular architecture by narrowband imaging. Its major advantage is a more accurate diagnosis of premalignant and malignant mucosal pathologies in the head and neck region based on the identification of significant changes in superficial vascularity. There is a very strong correlation of these vascular changes with the final histopathological analysis. The present data have shown that videoendoscopic examination with narrowband imaging significantly improves the distinction between benign and malignant mucosal lesions even in the UADT pathologies with a similar tendency to neoangiogenesis (squamous cell papilloma vs. squamous cell carcinoma). It also refines the determination of surface extension of tumoral changes and helps to localize and accurately diagnose tumors of...

Diagnosis of laryngeal and hypopharyngeal cancer is often in advanced stages of cancer, resulting in elimination of the possibility of treatment with the least mutilating effect for the patient. The huge progamination. ress in diagnostic process of mucosal tumors of the head and neck has been started with the development of new optical endoscopic imaging methods that are able to visualize initiating discrete mucosal changes with pathological vascularization easier and more accurately. The aim of this dissertation is to evaluate the benefit of Narrow Band Imaging (NBI), especially in the differentation of benign, precancerous and malignant changes in three groups of patients, it means in preoperative diagnostics in outpatient department (group I), during the endoscopic surgery (group II) and also in follow-up of patients after curative radiotherapy (group III). The vascular changes within the observed lesion or in close contact with the laryngeal/hypopharyngeal lesion were classified according to two classifications (Ni and Arens) and subsequently correlated with the histopathological results. The dissertation confirmed that NBI plays a key role in early detection of precancerous and malignant changes, in discrimination between benign and malignant vascular patterns with statistical significance. We...