Ip Toi Yan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (leaves 81-105). / Abstracts in English and Chinese. / CONTENTS --- p.i-iii / ACKNOWLEDGEMENT --- p.iv / ABSTRACT --- p.v-vi / Chapter Chapter One --- INTRODUCTION --- p.1-2 / Chapter Chapter Two --- LITERATURE REVIEW --- p.3-37 / Chapter 2.1 --- Epidemiology and Etiology of Cervical and Endometrial Cancers --- p.3-4 / Chapter 2.1.1 --- Epidemiology and Etiology of Cervical cancer --- p.4 / Chapter 2.1.1.1 --- Incidence and Mortality --- p.4-6 / Chapter 2.1.1.2 --- Etiology --- p.6-8 / Chapter 2.1.2 --- Epidemiology and Etiology of Endometrial Cancer --- p.9 / Chapter 2.1.2.1 --- Incidence and Mortality --- p.9-11 / Chapter 2.1.2.2 --- Rick Factors --- p.11-14 / Chapter 2.2 --- Pathology of Cervical and Endometrial Cancers --- p.14 / Chapter 2.2.1 --- Pathology of Cervical Cancer --- p.14-15 / Chapter 2.2.1.1 --- Macroscopic Appearance --- p.15 / Chapter 2.2.1.2 --- Histology --- p.15-18 / Chapter 2.2.2 --- Staging of Cervical Cancer --- p.19-21 / Chapter 2.2.3 --- Pathology of Endometrial Cancer --- p.21 / Chapter 2.2.3.1 --- Macroscopic Appearance --- p.22 / Chapter 2.2.3.2 --- Histology --- p.22-24 / Chapter 2.2.4 --- Staging of Endometrial Cancer --- p.24-25 / Chapter 2.2 --- Introduction to Microsatellite Instability (MI) --- p.25 / Chapter 2.3.1 --- DNA structure --- p.25-27 / Chapter 2.3.2 --- Microsatellite --- p.27-28 / Chapter 2.3.3 --- Mismatch Repair (MMR) --- p.28-29 / Chapter 2.3.4 --- Microsatellite Instability (MI) --- p.30-33 / Chapter 2.3.5 --- Microsatellite Instability in various cancers --- p.33-37 / Chapter Chapter Three --- MATERIALS AND METHODS --- p.38-50 / Chapter 3.1 --- Materials --- p.38 / Chapter 3.1.1 --- Patients and Specimens --- p.38-39 / Chapter 3.1.2 --- Chemicals and Reagents --- p.39 / Chapter 3.1.2.1 --- Chemicals --- p.39-40 / Chapter 3.1.2.2 --- Solution --- p.40-41 / Chapter 3.1.2.3 --- Microsatellite Markers --- p.42 / Chapter 3.1.3 --- Major Equipment --- p.43 / Chapter 3.2 --- Methodology --- p.43 / Chapter 3.2.1 --- DNA Extraction --- p.43-45 / Chapter 3.2.2 --- DNA Amplification --- p.45 / Chapter 3.2.2.1 --- End-labeling of Primer --- p.45 / Chapter 3.2.2.2 --- Polymerase Chain Reaction (PCR) --- p.46 / Chapter 3.2.3 --- Electrophoresis of PCR Products and Autoradiography --- p.46-49 / Chapter 3.2.4 --- Determination Of Microsatellite Instability (MI) --- p.49 / Chapter 3.3 --- Statistical Analyses --- p.50 / Chapter Chapter Four --- Result --- p.51-66 / Chapter 4.1 --- Microsatellite Instability in Cervical Cancer --- p.51 / Chapter 4.1.1 --- Prevalence of MI in Cervical Cancer --- p.51 -54 / Chapter 4.1.2 --- MI and Age in Cervical Cancer --- p.55 / Chapter 4.1.3 --- MI and Histological Type in Cervical Cancer --- p.55-56 / Chapter 4.1.4 --- MI and Histologic Grades in Cervical Cancer --- p.56-57 / Chapter 4.1.5 --- MI and Clinical stage in Cervical Cancer --- p.57-58 / Chapter 4.1.6 --- MI and Clinical Status in Cervical Cancer --- p.58-59 / Chapter 4.2 --- Microsatellite Instability in Endometrial Cancer --- p.59 / Chapter 4.2.1 --- Prevalence of MI in Endometrial Cancer --- p.59-62 / Chapter 4.2.2 --- MI and Age Groups in Endometrial Cancer --- p.63 / Chapter 4.2.3 --- MI and Histological Type in Endometrial Cancer --- p.63-64 / Chapter 4.2.4 --- MI and Histologic Grades in Endometrial Cancer --- p.64-65 / Chapter 4.2.5 --- MI and Clinical stage of Endometrial Cancer --- p.65 / Chapter 4.2.6 --- MI and Clinical Status in Endometrial Cancer --- p.66 / Chapter Chapter Five --- Discussion --- p.67-77 / Chapter 5.1 --- MI detection --- p.67-71 / Chapter 5.2 --- MI of Cervical Cancer --- p.71 -74 / Chapter 5.3 --- MI of Endometrial Cancer --- p.74-77 / Chapter Chapter Six --- Conclusions --- p.78-80 / Reference --- p.81-112 / Appendix --- p.113-114

Poon Kin-yan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (leaves 119-147). / Abstracts in English and Chinese. / ACKNOWLEDGMENT --- p.i / ABSTRACT --- p.iii / ABBREVIATIONS --- p.viii / TABLE OF CONTENTS --- p.x / Chapter CHAPTER I --- INTRODUCTION --- p.1 / Chapter 1.1 --- Cervical Intraepithelial Neoplasia (CIN) and Cervical Cancer --- p.1 / Chapter 1.1.1 --- Epidemiology --- p.3 / Chapter 1.1.1.1 --- Descriptive Epidemiology --- p.4 / Chapter 1.1.1.2 --- Risk Factors --- p.7 / Chapter 1.1.2 --- Pathology --- p.22 / Chapter 1.1.2.1 --- Macroscopic Appearance --- p.22 / Chapter 1.1.2.2 --- Symptoms and Diagnosis --- p.23 / Chapter 1.1.2.3 --- Staging Classification --- p.25 / Chapter 1.1.2.4 --- Histopathology --- p.29 / Chapter 1.2 --- Microsatellite Instability (MSI) --- p.35 / Chapter 1.2.1 --- Microsatellite --- p.35 / Chapter 1.2.2 --- Mismatch Repair --- p.37 / Chapter 1.2.3 --- Microsatellite Instability (MSI) --- p.38 / Chapter 1.2.4 --- MSI in Various Cancers --- p.42 / Chapter 1.2.5 --- The Role of MSI in Carcinogenesis --- p.49 / Chapter 1.2.6 --- MSI as a Diagnostic / Prognostic Tool --- p.50 / Chapter CHAPTER II --- AIMS OF THE STUDY --- p.53 / Chapter CHAPTER III --- MATERIALS AND METHODS --- p.56 / Chapter 3.1 --- Materials --- p.56 / Chapter 3.1.1 --- Patients and Specimens --- p.56 / Chapter 3.1.2 --- Microsatellite Markers --- p.57 / Chapter 3.2 --- Methods --- p.59 / Chapter 3.2.1 --- Preparation of OCT-embedded Specimen Sections --- p.59 / Chapter 3.2.2 --- Microdissection of Epithelial Cells and Neoplastic Cells from Specimen Sections --- p.60 / Chapter 3.2.3 --- DNA Extraction --- p.60 / Chapter 3.2.3.1 --- Normal Blood --- p.61 / Chapter 3.2.3.2 --- Dissected Cells --- p.62 / Chapter 3.2.4 --- DNA Amplification --- p.64 / Chapter 3.2.4.1 --- End-labeling of Primers --- p.64 / Chapter 3.2.4.2 --- Polymerase Chain Reaction --- p.65 / Chapter 3.2.5 --- Denaturing Polyacrylamide Gel Electrophoresis --- p.66 / Chapter 3.2.6 --- Autoradiography --- p.67 / Chapter 3.2.7 --- Determination of MSI --- p.67 / Chapter 3.2.8 --- HPV Detection --- p.68 / Chapter 3.2.9 --- Statistical Analysis --- p.69 / Chapter CHAPTER IV --- RESULTS --- p.70 / Chapter 4.1 --- Incidence of MSI in Cervix --- p.70 / Chapter 4.1.1 --- Incidence of MSI in Normal Cervix --- p.70 / Chapter 4.1.2 --- Incidence of MSI in CIN --- p.70 / Chapter 4.1.3 --- Incidence of MSI in Cervical Carcinoma --- p.71 / Chapter 4.1.4 --- Correlation of MSI-positive with the Evolution of Cervical Neoplasm --- p.77 / Chapter 4.2 --- Correlation of MSI-positive with Clinicopathological Characteristics in Cervical Carcinoma --- p.77 / Chapter 4.2.1 --- MSI and Age --- p.80 / Chapter 4.2.2 --- MSI and Clinical Stage --- p.80 / Chapter 4.2.3 --- MSI and Histological Grade --- p.80 / Chapter 4.2.4 --- MSI and Clinical Status --- p.81 / Chapter 4.3 --- Comparison between Two Panels of Microsatellite Markers used in MSI Detection --- p.84 / Chapter 4.4 --- Human Papilloma Virus (HPV) Infection in Cervical Neoplasm --- p.89 / Chapter 4.4.1 --- HPV Infection and Typing in CIN and Cervical Carcinoma --- p.89 / Chapter 4.4.2 --- Correlation of MSI-positive with HPV Infection in Cervical Carcinoma --- p.94 / Chapter CHAPTER V --- DISCUSSION --- p.96 / Chapter 5.1 --- MSI Detection --- p.96 / Chapter 5.1.1 --- Techniques in MSI Assays --- p.98 / Chapter 5.1.2 --- Choice of Microsatellite Markers --- p.101 / Chapter 5.1.3 --- Diagnostic Criteria of MSI --- p.105 / Chapter 5.2 --- The Role of MSI in the Carcinogenesis of Cervical Neoplasm --- p.107 / Chapter 5.3 --- The Clinical Significant of MSI in Cervical Carcinoma --- p.111 / Chapter 5.4 --- The Interaction between HPV Infection and MSI in Cervical Carcinoma --- p.113 / Chapter CHAPTER VI --- CONCLUSION --- p.116 / REFERENCES --- p.119

CoordenaÃÃo de AperfeÃoamento de Pessoal de NÃvel Superior / Objetivou-se realizar a adaptaÃÃo transcultural da Health Belief Model Scale for Cervical Cancer and Pap Smear Test para uso no Brasil e validar o conteÃdo da versÃo brasileira do instrumento traduzido. Trata-se de um estudo metodolÃgico, que para a adaptaÃÃo transcultural, percorreu rigorosamente cinco etapas: traduÃÃo inicial, sÃntese das traduÃÃes, retraduÃÃo, revisÃo por um comità de juÃzes e prÃ-teste. Os participantes dessas etapas foram selecionados obedecendo aos critÃrios estabelecidos pelo referencial metodolÃgico, quais sejam: quatro tradutores, um mediador e seis juÃzes. Na realizaÃÃo do prÃ-teste, ocorrida no Centro de Parto Natural Ligia Barros Costa e Campus do Pici da Universidade Federal do Cearà no mÃs de setembro de 2014, entrevistou-se 40 mulheres, de diferentes nÃveis de escolaridade, utilizando-se a versÃo prÃ-final da escala e um questionÃrio de caracterizaÃÃo sociodemogrÃfica. A validaÃÃo de conteÃdo da versÃo final foi aferida pelo Ãndice de ValidaÃÃo de ConteÃdo, a partir do julgamento de dez juÃzes especialistas, selecionados a partir das experiÃncias de ensino, pesquisa e/ou assistÃncia em SaÃde da Mulher. Os dados referentes Ãs etapas de adaptaÃÃo foram organizados na forma de quadros e analisados descritivamente. Os dados sociodemogrÃficos do prÃ-teste e os resultantes da validaÃÃo de conteÃdo foram analisados no software Statistical Package for the Social Sciences, versÃo 20.0. O estudo foi aprovado no Comità de Ãtica em Pesquisa da Universidade Federal do CearÃ. As duas versÃes produzidas na traduÃÃo inicial, em geral, nÃo apresentaram grandes diferenÃas de traduÃÃo. A segunda etapa foi realizada apÃs avaliaÃÃo das versÃes traduzidas com discussÃo quanto à formulaÃÃo dos itens da versÃo sÃntese, obtendo-se total concordÃncia por parte da pesquisadora e mediador. Na retraduÃÃo da versÃo sÃntese de volta ao idioma inglÃs evidenciou-se que as versÃes resultantes desta etapa nÃo apresentaram grandes divergÃncias em relaÃÃo à versÃo original do instrumento, mostrando-se coerentes, explicitando assim a qualidade da versÃo sÃntese no portuguÃs brasileiro. A partir da avaliaÃÃo das equivalÃncias semÃntica, idiomÃtica, experimental e conceitual pelos juÃzes, onze itens foram modificados apÃs as sugestÃes realizadas, resultando em uma versÃo prÃ-final da escala, aplicada no prÃ-teste. Quatro itens nÃo apresentaram total compreensÃo apÃs avaliaÃÃo das mulheres, sendo modificados segundo as sugestÃes das mesmas. ApÃs todas as modificaÃÃes realizadas na escala, obteve-se a versÃo final do instrumento adaptado ao contexto cultural brasileiro. O Ãndice de ValidaÃÃo de ConteÃdo, calculado a partir das avaliaÃÃes dos juÃzes de conteÃdo, foi de 0,82 e os valores individuais dos itens variaram de 0,80 a 1, sendo considerado adequadamente vÃlido em conteÃdo. Nenhum item foi eliminado, porÃm, quatro foram alocados ao domÃnio motivaÃÃo em saÃde por decisÃo unÃnime dos juÃzes. Pode-se concluir que todo o rigor adotado neste estudo garantiu a obtenÃÃo de um instrumento que se mostrou equivalente à versÃo original, apresentando boa compreensÃo e clareza entre os itens, alÃm de um adequado Ãndice de validaÃÃo de conteÃdo.

A dissertation submitted to the Faculty of Health Sciences, University of the Witwatersrand, in fulfilment of the requirements for the degree of Master of Pharmacy / Cervical Intraepithelial Neoplasia (CIN) or Human Papilloma Virus (HPV) is known as the precancerous stages of cervical cancer and may be treated with antineoplastic agents Current treatment includes intravenous administration of Gemcitabine and 5-Fluorouracil however, these drugs have an undesirable side effect profile. This may be overcome by local administration of chemotherapeutic drugs to the site of the cancer. The purpose of this study was to design a drug delivery system that can be locally administered to the site of the cervical cancer and possess thermosonic properties. Designs of three Thermosonic Injectable Organogels (TIO’s) were undertaken using ring opening polymerization (open ring reaction) to formulate three different gels to test the response ability of the gels against thermal and ultrasound exposure. The times taken for these gels to form were recorded at below 15 minutes. All three TIO’s responded differently to thermal and ultrasound stimuli. Physical changes in the gels were noted and further studies were undertaken to confirm their responsiveness towards the dual-stimuli. All three TIO’s showed a dense microstructure containing pores catering for the incorporation of drugs or drug-loaded carriers. Rheological studies showed that there was an increase in viscosity of the gels under increasing heat even though the response differed between TIO formulations. The gels were non-cytotoxic at distinct concentrations ranging between 6.1mg/ml-7.8mg/ml. Solid Lipid Nanospheres (SLN’s) were then designed which encapsulated the mode antineoplastic drug 5-Fluorouracil. The SLN’s were spherical in shape and had an acceptable poly dispersion index (PDI) which was below 0.7 after ultrasonication and filtration of prepared samples. The SLN’s were then incorporated by direct additition and dispersion into the TIO formulations before undertaking the open ring reaction to form Thermosonic Injectable Nano-Organogels (TINO’s). The TINO’s were analysed for its swelling and erosive properties. Results showed that the TINO’s posesses both swelling and erosive properties. Furthermore, the TINO’s underwent dissolution studies that involved thermal and thermal with ultrasound stimuli to test the drug release rate and the stimuli responsiveness of the TINO. Results of the SLN’s showed a very slow release rate whether exposed to a single (thermal) or both thermal and ultrasound stimuli, indicating that the addition of ultrasound stimuli did not alter the drug release from the SLN’s. However, the incorporation of the SLN’s into the TIO’s prolonged the release rate. Hence increasing the SLN concentration in the TIO’s reduced the response towards ultrasound stimuli. Therefore lower ratios of SLN:TIO provided superior responsiveness compared to higher concentrations of SLN:TIO. TIO 1 and TINO 2 released drug with thermal stimuli and higher drug release occurred with exposure to both thermal and ultrasound stimuli. These TINO’s in conjunction with ultrasound responsiveness may be used as a potential platform for the delivery of antineoplastics in treating cervical cancer. / MT2017

Thesis (Ph. D.)--University of Alabama at Birmingham, 2007. / Title from first page of PDF file (viewed Oct. 13, 2008). Includes bibliographical references.

by Wai Ching Wa, Gina. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1990. / Bibliography: leaves 303-314. / Chapter 1. --- INTRODUCTION --- p.1 / Chapter 2. --- LITERATURE REVIEW ON CERVIX UTERI / Chapter 2.1 --- HISTOLOGY OF CERVIX UTERI --- p.4 / Chapter 2.2 --- CYTOLOGY OF CERVIX UTERI --- p.5 / Chapter 2.3 --- CERVICAL EPITHELIAL LESIONS / Chapter 2.3.1 --- Squamous Metaplasia --- p.7 / Chapter 2.3.2 --- Cervical Intraepithelial Neoplasia --- p.9 / Chapter 2.3.3 --- Viral Infections --- p.17 / Chapter 2.4 --- DIAGNOSTIC APPROACH TO CERVICAL LESIONS --- p.20 / Chapter 2.5 --- DIAGNOSTIC VARIABILITY OF CERVICAL LESIONS --- p.21 / Chapter 2.6 --- IMPORTANCE OF CERVICAL CARCINOMA IN HONG KONG --- p.21 / Chapter 3. --- LITERATURE REVIEW ON NASOPHARYNX / Chapter 3.1 --- HISTOLOGY OF NASOPHARYNX --- p.22 / Chapter 3.2 --- CYTOLOGY OF NASOPHARYNX --- p.24 / Chapter 3.3 --- NASOPHARYNGEAL EPITHELIAL LESIONS / Chapter 3.3.1 --- 'Squamous Metaplasia' --- p.25 / Chapter 3.3.2 --- Nasopharyngeal Intraepithelial Neoplasia --- p.26 / Chapter 3.3.3 --- Viral Infections --- p.27 / Chapter 3.4 --- DIAGNOSTIC APPROACH TO NASOPHARYNGEAL LESIONS --- p.28 / Chapter 3.5 --- IMPORTANCE OF NASOPHARYNGEAL CARCINOMA IN HONG KONG --- p.29 / Chapter 4. --- LITERATURE REVIEW ON MORPHOMETRY / Chapter 4.1 --- QUANTITATIVE ASSESSMENT OF CELL FEATURES --- p.30 / Chapter 4.2 --- TERMINOLOGY --- p.31 / Chapter 4.3 --- APPROACHES TO SAMPLING --- p.32 / Chapter 4.4 --- SOURCES OF VARIATION --- p.32 / Chapter 4.5 --- METHODOLOGY FOR MORPHOMETRY --- p.33 / Chapter 4.6 --- FEATURES FOR MORPHOMETRY IN INTRAEPITHELIAL NEOPLASIA --- p.35 / Chapter 4.7 --- PREVIOUS MORPHOMETRIC STUDIES ON INTRAEPITHELIAL NEOPLASIA --- p.36 / Chapter 5. --- MATERIALS AND METHODS / Chapter 5.1 --- MATERIALS / Chapter 5.1.1 --- Cervix Uteri --- p.41 / Chapter 5.1.2 --- Nasopharynx --- p.41 / Chapter 5.2 --- METHODS / Chapter 5.2.1 --- Equipment --- p.42 / Chapter 5.2.2 --- Pilot Study for Reproducibility --- p.43 / Chapter 5.2.3 --- Estimation of Minimum Sample Size --- p.43 / Chapter 5.2.4 --- Morphometric Procedures --- p.44 / Chapter 5.2.5 --- Statistical Analysis --- p.48 / Chapter 5.2.6 --- Comparison of Visual Diagnosis of Cervical smears and biopsies --- p.49 / Chapter 5.2.7 --- Survey of Subjective Assessment Criteria for Cervical Biopsies and Smears --- p.50 / Chapter 6. --- RESULTS / Chapter 6.1 --- PILOT STUDY / Chapter 6.1.1 --- Intraobserver Reproducibility --- p.52 / Chapter 6.1.2 --- Minimum Sample Size --- p.52 / Chapter 6.2 --- CERVIX / Chapter 6.2.1 --- Maturation Sequence of Cervical Epithelium --- p.53 / Chapter 6.2.2 --- Differences of Morphometric Means between various groups of Cervical Biopsies --- p.56 / Chapter 6.2.3 --- Discriminant Analysis of Cervical Biopsies --- p.58 / Chapter 6.2.4 --- Differences of Morphometric Means between various groups of Cervical Smears --- p.60 / Chapter 6.2.5 --- Discriminant Analysis of Cervical Smears --- p.61 / Chapter 6.2.6 --- Comparison of Cervical Smears and Biopsies --- p.62 / Chapter 6.2.7 --- Subjective Assessment Criteria for Cervical Biopsies and Smears --- p.63 / Chapter 6.3 --- NASOPHARYNX / Chapter 6.3.1 --- Maturation Sequence of Nasopharyngeal Epithelium --- p.65 / Chapter 6.3.2 --- Differences of Morphometric Means between various groups of Nasopharyngeal Biopsies --- p.68 / Chapter 6.3.3 --- Discriminant Analysis of Nasopharyngeal Biopsies --- p.70 / Chapter 6.4 --- COMPARISON OF CERVIX UTERI AND NASOPHARYNX --- p.71 / Chapter 7. --- DISCUSSION / Chapter 7.1 --- CERVIX UTERI / Chapter 7.1.1 --- Maturation Sequence --- p.73 / Chapter 7.1.2 --- Discrimination of different groups in Biopsies --- p.76 / Chapter 7.1.3 --- Discrimination of different groups in Smears --- p.77 / Chapter 7.1.4 --- Comparison of Smears and Biopsies --- p.78 / Chapter 7.1.5 --- Subjective Assessment Criteria --- p.80 / Chapter 7.1.6 --- Future directions --- p.81 / Chapter 7.2 --- NASOPHARYNX / Chapter 7.2.1 --- Maturation Sequence --- p.81 / Chapter 7.2.2 --- Discrimination of different groups --- p.84 / Chapter 7.2.3 --- Nasopharyngeal Cytology --- p.84 / Chapter 7.2.4 --- Future directions --- p.85 / Chapter 7.3. --- COMPARISON OF CERVIX UTERI AND NASOPHARYNX / Chapter 7.3.1 --- Morphometric data --- p.85 / Chapter 7.3.2 --- Discriminant Analysis --- p.87 / Chapter 8. --- CONCLUSIONS --- p.89 / Chapter APPENDIX A --- Survey of subjective assessment criteria for cervical biopsies and smears / Tables A1-A7 --- p.92 / Chapter APPENDIX B --- Results of pilot study / Tables B1-B6 --- p.100 / Chapter APPENDIX C --- Morphometric data and results of statistical tests for cervical biopsies / Fig. C1-C61 --- p.104 / Tables C1-C19 --- p.166 / Chapter APPENDIX D --- Morphometric data and results of statistical tests for cervical smears / Fig. D1-D2 6 --- p.179 / Tables D1-D3 --- p.206 / Chapter APPENDIX E --- Comparison of cervical smears and biopsies / Tables E1-E3 --- p.208 / Chapter APPENDIX F --- Morphometric data and results of statistical tests for nasopharyngeal biopsies / Fig. F1-F61 --- p.211 / Tables F1-F12 --- p.273 / Chapter APPENDIX G --- Comparison of nasopharyngeal and cervical biopsies / Tables G1-G15 --- p.282 / Chapter APPENDIX H --- Pictures of materials and equipment / Fig. H1-H21 --- p.291 / REFERENCES --- p.303

Orientador: Luis Otavio Zanatta Sarian / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-11-07T13:22:12Z (GMT). No. of bitstreams: 1 Oliveira_AntonioCarlosZulianide_D.pdf: 2312185 bytes, checksum: 6a45c1be8238c13c3a584fdc2ef426e4 (MD5) Previous issue date: 2013 / Resumo: Introdução: Ensaios clínicos das últimas duas décadas do século XX demonstraram a superioridade da radioterapia associada à quimioterapia na abordagem do carcinoma espinocelular do colo do útero (CEC). Contudo, tais estudos abordaram todos os estádios clínicos e para o subgrupo de mulheres com CEC estádio IIIB e os benefícios da quimioterapia não foram totalmente comprovados. Objetivos: Esta tese divide-se em dois estudos: 1) uma comparação histórica de sobrevida livre de doença (SLD), sobrevida total (ST) e toxicidade de tratamento em mulheres com CEC IIIB submetidas à braquiterapia de baixa taxa de dose (BBTD) versus braquiterapia de alta taxa de dose exclusiva (BATD) versus braquiterapia de alta taxa de dose associada à quimioterapia (BATD-QT) e 2) um ensaio clínico aleatorizado comparando esses mesmos parâmetros em mulheres submetidas à BATD versus BATD-QT. Métodos: Na comparação histórica de tratamentos, foram levantados os dados de evolução de pacientes admitidas entre 1985 e 2005 no CAISM-UNICAMP e seguidas até 2007, totalizando 230 pacientes com CEC IIIB que receberam BBTD (42 pacientes), BATD (155 pacientes) ou BATD-QT (33 pacientes). As SLD e ST das mulheres nos três grupos foram comparadas usando curvas de sobrevida tipo Kaplan-Meyer e testes de log-rank. Já o ensaio clínico aleatorizado foi realizado entre setembro de 2003 e julho de 2010. Foram incluídas no estudo 147 mulheres com CEC IIIB. Após aceitarem participar e assinarem o termo de consentimento, as mulheres foram randomizadas para BATD ou BATD-QT através de planilha de aleatorização criada pelo programa SAS e trazida ao conhecimento de pacientes e médicos através de envelopes opacos. Todas as mulheres receberam teleterapia com dose de 45Gy para a região pélvica em 25 frações, 14,4Gy de reforço no(s) paramétrio(s) comprometido(s) e BATD em quatro frações semanais de 7Gy, prescritos no ponto A. O grupo BATD-QT recebeu cisplatina concomitante semanal (40mg/m2) durante a teleterapia pélvica. O follow-up durou até janeiro de 2013, (72 pacientes do grupo com cisplatina e 75 no grupo-controle), com o seguimento médio de 54,9 meses (intervalo interquartil = 55,4 meses). Comparações de SLD e ST foram realizadas usando curvas de Kaplan-Meyer, testes de log-rank e modelos multivariados de Riscos Proporcionais de Cox, os quais englobaram características clínicas das mulheres como variáveis de controle. Resultados: Na comparação histórica, a SLD média para o grupo BATD foi de 60%, para BBTD 45% e para BATD-QT foi de 65% (p = 0,02). Já a ST foi de 65% para o grupo BATD, 49% para BBTD e a ST em dois anos para o grupo BATD-QT foi de 86% (p = 0,02). A toxicidade retal de grau II foi de 7% para o grupo que recebeu BBTD, de 4% para BATD e 7% para o grupo BATD-QT, que teve um caso de toxicidade retal grau IV. No ensaio clínico aleatorizado, mulheres alocadas no grupo BATD-QT tiveram SLD significativamente melhor (RR = 0,52, 95% CI 0,28-0,98, p = 0,04), porém não houve diferença em relação a ST (RR = 0,67, 95% CI 0,37-1,183, p = 0,16). Mulheres com Karnofsky <90 tiveram uma SLD significativamente pior (RR = 2,52, 95% CI 1,23-4,78, p = 0,01). O mesmo ocorreu para as mulheres com invasão parametrial bilateral até a parede óssea (RR = 2,93, 95% CI 1,21-7,13, p = 0,02), e a hemoglobina média durante o tratamento <10mg/dL (RR = 2,22, 95% CI 1,01-4,93, p = 0,04). A ST também foi menor em mulheres com Karnofsky <90 (RR = 2,75, 95% CI 1,29-5,87, p <0,01), e hemoglobina média durante o tratamento <10mg/dL (RR = 2,82, 95% CI 1,27-6,29, p = 0,01). Conclusões: Na revisão da série histórica, as pacientes que receberam braquiterapia de alta taxa de dose tiveram melhores SLD e ST, e as taxas de toxicidade não foram diferentes entre os três grupos. O ensaio clínico, que é o único estudo controlado randomizado comparando a BATD-QT e BATD para CEC IIIB, sugere que há um pequeno, mas significativo, benefício na SLD com a adição de cisplatina à BATD, com uma toxicidade aceitável / Abstract: Introduction: Clinical trials of the last two decades of the twentieth century demonstrated the superiority of radiotherapy combined with chemotherapy in the management of squamous cell carcinoma of the cervix (SCC). However, such studies have addressed all clinical stages and for the subgroup of women with stage IIIB SCC the benefits of chemotherapy have not been fully proven. Objectives: This thesis is divided into two studies: 1) a historical comparison of disease-free survival (DFS), overall survival (OS) and toxicity of treatment in women with SCC IIIB undergoing low-dose rate brachytherapy (LDR) brachytherapy versus high dose rate exclusive (HDR) brachytherapy versus high dose rate associated with chemotherapy (CHT) and 2) a randomized clinical trial comparing these parameters in women undergoing HDR versus CHT. Methods: In the historical comparison of treatments, data on the outcomes of patients admitted between 1985 and 2005 in CAISM-Unicamp and followed until 2007 were collected, totaling 230 patients with SCC stage IIIB who received either LDR (42 patients), HDR (155 patients) or CHT (33 patients). The DFS and OS of women in the three groups were compared using Kaplan-Meyer survival curves and the "log-rank" test. The randomized clinical trial was conducted between September 2003 and July 2010. A total of 147 with SCC stage IIIB were included. After accepting to participate and signing the consent form, women were randomized to HDR or CHT through a randomization spreadsheet created by SAS program and concealment allocation of patients through opaque envelopes. Patients of either the CHT or HDR groups received external-beam radiation (45 Gy) to the entire pelvic region in 25 fractions over a 5-week period. Compromised parametria were treated with 14.4 Gy boost. High-dose rate brachytherapy consisted of four weekly fractions of 7 Gy prescribed to point A. Patients in the CHT group also received concomitant weekly cisplatin (40mg/m2) during the pelvic external beam radiotherapy. The follow-up lasted until January 2013 (72 patients in the cisplatin group and 75 in the control group), with a mean follow-up of 54.9 months (interquartile range = 55.4 months). Comparisons of DFS and OS were performed using Kaplan-Meyer log-rank tests and multivariate models of Cox proportional hazards model, which encompassed the clinical characteristics of women as control variables. Results: In the historical comparison, the DFS for the group HDR was 60% , 45% for LDR and 65% for CHT (p = 0.02). The OS was 65% for the HDR group, 49% for LDR and 86% for CHT (p = 0.02). The Grade II rectal toxicity was 7% for LDR, 4% in HDR patients and 7% in CHT group, which had a case of rectal toxicity grade IV. In the randomized clinical trial, women in the CHT group had significantly better DFS (RR = 0.52, 95% CI from 0.28 to 0.98, p = 0.04), but there was no difference in OS (RR = 0.67, 95% CI 0.37 to 1.183, p = 0.16). Women with Karnofsky <90 had a significantly worse DFS (RR = 2.52, 95% CI 1.23 to 4.78, p = 0.01). The same was true for women with bilateral parametrial invasion to the bone wall (RR = 2.93, 95% CI 1.21 to 7.13, p = 0.02), and mean hemoglobin during treatment <10mg/dL (RR = 2.22, 95% CI 1.01 to 4.93, p = 0.04). The OS was also lower in women with Karnofsky <90 (RR = 2.75, 95% CI 1.29 to 5.87, p <0.01), and mean hemoglobin during treatment <10mg/dL (RR = 2, 82, 95% CI 1.27 to 6.29, p = 0.01). Conclusions: Patients who received HDR had better DFS and OS, and toxicity rates were not different among the three groups. The randomized trial, which is the only randomized controlled study comparing HDR and CHT for CEC IIIB, suggests that there is a small but significant DFS benefit with the addition of cisplatin to HDR, with acceptable toxicity / Doutorado / Oncologia Ginecológica e Mamária / Doutor em Ciências da Saúde

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / A ideia de seguimento, na perspectiva de acompanhar de mulheres com diagnÃstico de CÃncer de Colo Uterino (CCU), identificar como estÃo sendo encaminhadas e tratadas no Sistema Ãnico de SaÃde (SUS), possibilita conhecer variÃveis, eventos e condiÃÃes que proporcionam uma avaliaÃÃo dessa Ãrea do cuidado e do sistema. à elevado o nÃmero de casos de CCU, que apesar de prevenÃveis e controlÃveis com os conhecimentos e as tecnologias existentes, apresenta taxas de morbidade e de mortalidade elevadas, sendo os aspectos associados ao acesso e à qualidade do seguimento fatores estreitamente relacionados a esse desfecho. Diante do exposto, o trabalho objetivou avaliar o seguimento de mulheres com CCU na perspectiva dos sistemas de informaÃÃo de saÃde e de mulheres que nÃo obtiveram registros de seguimento nestes sistemas. Trata-se de pesquisa documental, avaliativa e de campo, realizada em quatro etapas: listagem nominal de mulheres com diagnÃstico de CCU, residentes em Fortaleza-CE, registradas em 2008 no SISCOLO de Fortaleza; busca nominal de mulheres com diagnÃstico de CCU nas APAC-Onco, AIH e DeclaraÃÃo de Ãbito (DO); busca nominal de mulheres com diagnÃstico de CCU no prontuÃrio eletrÃnico das pacientes; e realizaÃÃo das entrevistas com mulheres nÃo identificadas na 2 e 3 etapas. As entrevistas foram realizadas por meio de visita domiciliÃria, de setembro a dezembro de 2010. Os resultados evidenciaram 80 casos de mulheres com diagnÃstico de CCU, residentes em Fortaleza-CE, em 2008. Destas, 2,6% encontravam-se abaixo de 25 anos, 61,2% na faixa de 25 a 59 anos e 36,2% apresentaram idade acima de 60 anos. O carcinoma epidermÃide invasivo acometeu 81,2% das mulheres, enquanto que o adenocarcinoma apresentou-se em 18,2% dos casos. A anÃlise nos sistemas de informaÃÃo SIA/SUS, SIH/SUS e SIM identificou procedimentos que caracterizaram seguimento de mulheres com diagnÃstico de CCU, em 50% das mulheres diagnosticadas. Da outra metade, 16,2% obtiveram seguimento identificado no prontuÃrio eletrÃnico; 33,7% nÃo apresentaram informaÃÃes de seguimento em nenhuma das fontes citadas, tendo estas sido selecionadas para entrevista. No entanto, destas, apenas 20% foram entrevistas, pois as demais nÃo ofereciam informaÃÃes suficientes para o acesso à pesquisadora. As entrevistas revelaram baixas condiÃÃes socioeconÃmicas destas mulheres. Os resultados de Papanicolaou foram entregues com cerca de um mÃs e na data agendada. Na identificaÃÃo de aspectos relacionados ao encaminhamento da paciente com CCU para outros nÃveis de referÃncia, 87,5% recebeu encaminhamento para algum tipo de instituiÃÃo com nÃvel de complexidade mais alto; quanto ao estado atual de seguimento, das mulheres entrevistadas, apesar da maioria ter realizado procedimentos que caracterizaram seguimento, ainda foi evidente a necessidade da educaÃÃo permanente para a qualificaÃÃo profissional, a fim de evitar iniquidades no atendimento à mulher acometida pelo CCU. Houve evidÃncia de subregistro no SIH. Confirmou-se a tese de que as informaÃÃes de seguimento das mulheres com CCU, em Fortaleza-CE, nÃo refletem a real magnitude de seguimento das mulheres que obtiveram diagnÃstico de CCU, uma vez que se constatou o acesso destas à realizaÃÃo dos procedimentos necessÃrios para o seguimento adequado.

Thesis (Ph. D.)--University of Washington, 2002. / Vita. Includes bibliographical references (leaves 130-145).

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.