Uterine cancer is the nation’s most common gynecologic malignancy but is understudied in the geographically and socioeconomically diverse state of Kentucky (KY). This study assessed the frequency, distribution, and survival of uterine corpus malignancies in KY, and specifically the differences between Appalachia (AP) and non-Appalachia (NAP). This study utilizes SEER and Kentucky Cancer Registries to study uterine corpus malignancy between January 1, 2000 and December 31, 2014. The analysis looks at incidence between diagnoses in AP and NAP. Evaluation criteria includes: tumor histology (Type I, Type II, sarcoma, and mixed uterine malignancy), age, race, smoking status, stage at diagnosis, insurance status, and county of residence at diagnosis.

Objective: Delay in diagnosis and treatment of endometrial cancer may be associated with disease progression and impact management and outcomes. Social and cultural barriers influence recognition of symptoms and self-advocacy in seeking and complying with care. Associations between social determinants of health (SDH) and disease presentation, treatment and outcomes has been shown in some healthcare systems. Our objective was to investigate these in Ontario’s universal access system. Methods: Endometrial cancer patients in Ontario diagnosed 2009-2017 were identified, and clinical, social and demographic information extracted from administrative databases. SDH were quantified using previously validated marginalization quintiles (material deprivation, residential instability and ethnic concentration). Associations between SDH, disease stage, treatment and outcome were explored using chi-square, log-rank and logistic regression. Results: 19530 patients were identified. 73% of cancers were confined to the uterus. Stage distribution differed across marginalization quintiles (p<0.001) with advanced disease found more frequently in highly marginalized patients (highest vs lowest quintile): OR=1.28 (95% CI 1.14-1.45) for deprivation, OR=1.2 (95% CI 1.06-1.35) for residential instability and OR=1.3 (95% CI 1.15-1.46) for ethnic concentration (<0.0001)). Highly marginalized patients also had less timely surgery (p<0.0001). Overall survival was shorter in patients in high deprivation and residential instability quintiles (log rank p-value<0.0001) but not in high ethnic concentration quintiles, with HR=1.4 for deprivation (p<0.0001) and HR=1.53 for instability (p<0.0001) for the highest marginalization quintile. Survival differences persisted in more uniform cohorts of early (stage I) disease and endometrioid tumors and on multivariable analysis. Conclusions: Marginalized populations diagnosed with uterine cancer present at more advanced stages, wait longer for surgery and have shorter overall survival. Associations of SDH with uterine cancer presentation and management in Ontario could shed light on the impact of these factors on disease trajectory, drive policies for patient advocacy and redistribution of resources and promote health equity in this population. / Thesis / Master of Public Health (MPH) / Conditions in the social environment in which people are born, live and work are powerful influencers of health and well-being. In fact, these circumstances have also been called Social Determinants of Health (SDH). Cancer outcomes are one of the domains impacted by SDH. In this study, we set out to investigate the association between SDH and uterine cancer outcomes in Ontario, Canada. We guessed that SDH may influence how soon patients with symptoms seek help from their doctors, how quickly their problem is investigated and how well they are able to undergo treatment. We used a tool called the Ontario Marginalization Index to break down Ontario’s uterine cancer patient population into groups according to degree of social, financial and ethnic marginalization. We found that more marginalized patients tended to present to care with more advanced cancers, that they took longer to have surgery for their cancer and that their survival was worse. These findings suggest there is more work to be done to promote health equity in cancer care.

One of the main questions put forth by NASA and the European Space Agency (ESA) is whether or not an organism, especially mankind, can complete an entire life cycle in space. With this in mind, it is essential to study the effect of spaceflight on reproductive tissues. Using simulated microgravity techniques and whole-body radiation we sought to determine if females subjected to a simulated spaceflight environment have increased incidences of uterine cancer. Uterine tissue from mice subjected to simulated spaceflight was analyzed using immunohistochemical staining and western blot analysis. Two pathways commonly activated in cancer were investigated. Additionally, the uterine tissue was evaluated for gross morphological changes using standard histological staining. The findings of this study indicate that none of the treatment parameters used to simulate the spaceflight environment were found to induce uterine cancer.

Ο καρκίνος του τραχήλου της μήτρας (ΚΤΜ), αποτελεί παγκοσμίως έναν από τους συχνότερα εμφανιζόμενους καρκίνους στο γυναικείο πληθυσμό. Ο ΚΤΜ επιφέρει σημαντική ψυχολογική, κοινωνική και οικονομική επιβάρυνση στους ασθενείς και στα συστήματα υγείας. Η κυριότερη αιτία εμφάνισης της νόσου συσχετίζεται με τη μόλυνση από τον ιό των ανθρώπινων θηλωμάτων – HPV (Human papilloma virus). O HPV συγκαταλέγεται στους πιο συχνά σεξουαλικ ώςμεταδιδόμενους ιούς. Ένα από τα μεγαλυτερα βήματα της δημόσιας υγείας για την προφύλαξη του πληθυσμού έναντι του HPV και κατ’ επέκταση του καρκίνου του τραχήλου της μήτρας, είναι η εισαγωγή του εμβολίου στο Εθνικό Πρόγραμμα Εμβολιασμού. Στα παρακάτω κεφάλαια (θεωρητικό μέρος) γίνεται εκτενής περιγραφή της ιστοπαθολογίας του ΚΤΜ και της βασικής βιολογίας του HPV, καθώς επίσης και του μηχανισμού δράσης του εμβολίου έναντι του ιού. Εν συνεχεία, στο ειδικό μέρος της παρούσας διπλωματικής εργασίας παρατίθενται στοιχεία που αφορούν την ευαισθητοποίηση και την αποδοσχή του πληθυσμού για τον προληπτικό εμβολιασμό έναντι του ιού HPV. / -

Neuroendocrine tumors of the cervix are extremely rare. Women diagnosed with small cell neuroendocrine carcinoma of the cervix have a higher frequency of metastases in the lymph nodes, lymphovascular invasion, recurrence and worse prognosis compared to those with other types of cervical neoplasia. We report the case of a 58-year-old female, with a history of six years of postmenopausal irregular vaginal bleeding, in addition to symptoms related to chronic anemia. Gynecological examination showed a tumor of 4 cm that occupied the upper third of the vagina and protruded through the cervix initially diagnosed as an abortifacient myoma, and sent to histopathology study. 90% of the tumor was small cell neuroendocrine carcinoma grade III, and the remaining 10% was squamous cell carcinoma. The patient underwent into a radical hysterectomy plus bilateral salpingo-oophorectomy, and bilateral pelvic and para-aortic lymphadenectomy. Histopathologic examination of the surgical specimen found endometrium and myometrium compromised by malignancy. Parametrium, annexes and lymph nodes were free of neoplasia. At microscopy, the result was a grade III neuroendocrine carcinoma (small cell carcinoma, infiltrating), with extensive lymphovascular emboli. The immune-histochemical study showed synaptophysin positive in areas with neuroendocrine differentiation. / Los tumores neuroendocrinos de cuello uterino son extremadamente raros. Las mujeres con diagnóstico de carcinoma neuroendocrino de células pequeñas del cuello uterino tienen mayor frecuencia de metástasis en los ganglios linfáticos, invasión linfovascular, recurrencia y peor pronóstico en comparación con aquellos con otros tipos de neoplasias cervicales. Se presenta el caso de una mujer de 58 años, con un tiempo de enfermedad de seis años antes del ingreso, caracterizado por sangrado vaginal irregular posmenopáusica, además de sintomatología relacionada a anemia crónica. En el examen ginecológico, se evidenció tumoración de 4 cm que ocupaba tercio superior de vagina y protruía por el cérvix. Fue diagnosticado como mioma abortivo y enviada a estudio anatomopatológico. El resultado fue carcinoma neuroendocrino de células pequeñas grado III en el 90% y carcinoma epidermoide en el 10%. La paciente fue sometida a histerectomía radical más salpingo-ooferectomía bilateral y linfadenectomía pélvica bilateral y para-aortica. El estudio anatomopatológico de la pieza quirúrgica encontró endometrio y miometrio comprometido por neoplasia maligna. Parametrios, anexos y ganglios linfáticos se encontraron libres de neoplasia. A la microscopía el resultado fue carcinoma neuroendocrino grado III (carcinoma de células pequeñas, infiltrante), con extensa embolia linfovascular. El estudio de inmunohistoquímica arrojó sinaptofisina positivo en las áreas con diferenciación neuroendocrina.

Foi desenvolvido um questionário para utilização, na prática, do Modelo de Crenças de Saúde (MCS) usando informações tanto populares como médicas sobre a prevenção do câncer cérvico-uterino. As crençaas foram identificadas pelos quatro componentes principais do MCS (percepção da suscetibilidade e da gravidade da doença e de beneficios e de barreiras à ação preventiva), e foram calculadas medidas individuais para cada componente do MCS, a conduta preventiva anterior e os conhecimentos do exame de Papanicolaou e de câncer cérvico-uterino. O instrumento foi elaborado em cinco etapas e a análise estatística incluiu a descrição de cada questio, associações entre conduta e cada componente do MCS e entre conduta e conhecimento da doença e do exame de Papanicolaou. O estudo foi realizado com entrevistas de 300 mulheres numa cidade do interior do Brasil. Os resultados indicaram que os componentes do MCS estavam ligados fracamente à conduta preventiva, mas o componente suscetibilidade evidenciou menor variação e maior relação com a conduta. Apesar do MCS não se apresentar como um forte preditor de conduta, foi confirmado seu uso para explicar a conduta. Os resultados estatísticos são apresentados de forma descritiva. Algumas crenças e conflitos entre crenças puderam ser facilmente identificados e discutidos. Foram propostas sugestões para programas de educação relativos à prevenção do câncer cérvico-uterino e para uso do MCS na avaliação de mudanças de conduta preventiva da população nos programas educacionais. / A questionnaire was developed wich allows the translation of the Health Belief Hodel to practice, using both, popular and medical informations in cervical cancer prevention. Belief identification have been limited to the four major dimensions of the HBH (perceptions of susceptibility, seriousness, barriers and benefits), and individual measures were calculated for each HBH dimensions, the retrospective preventive behavior and knowledge of cervical smear and cervical cancer. Instrument refinement occurred in five stages and the descriptive statistical anal~sis included each question description, and relationship between each HBM dimension and preventive behavior, and between kncwledge and behavior. The study was performed by interviews with 300 women in a inside, country city in Brazil. The results are indicating that the HBM components were weakly related with the preventive behavior, but susceptibility showed lower variation and were more closer to behavior. In spite that the HBM was not a strcnger predictor of preventive behavior, its capacity to explain behaviors was confirmed. Descriptive statistics was used to present results. Some beliefs and belief conflicts were easily identified and discussed. Sugestions were offered for programing health education in cervical cancer prevention and for use the HBM descriptive data to evaluate education impact in preventive behavior changes in a population.

Foi desenvolvido um questionário para utilização, na prática, do Modelo de Crenças de Saúde (MCS) usando informações tanto populares como médicas sobre a prevenção do câncer cérvico-uterino. As crençaas foram identificadas pelos quatro componentes principais do MCS (percepção da suscetibilidade e da gravidade da doença e de beneficios e de barreiras à ação preventiva), e foram calculadas medidas individuais para cada componente do MCS, a conduta preventiva anterior e os conhecimentos do exame de Papanicolaou e de câncer cérvico-uterino. O instrumento foi elaborado em cinco etapas e a análise estatística incluiu a descrição de cada questio, associações entre conduta e cada componente do MCS e entre conduta e conhecimento da doença e do exame de Papanicolaou. O estudo foi realizado com entrevistas de 300 mulheres numa cidade do interior do Brasil. Os resultados indicaram que os componentes do MCS estavam ligados fracamente à conduta preventiva, mas o componente suscetibilidade evidenciou menor variação e maior relação com a conduta. Apesar do MCS não se apresentar como um forte preditor de conduta, foi confirmado seu uso para explicar a conduta. Os resultados estatísticos são apresentados de forma descritiva. Algumas crenças e conflitos entre crenças puderam ser facilmente identificados e discutidos. Foram propostas sugestões para programas de educação relativos à prevenção do câncer cérvico-uterino e para uso do MCS na avaliação de mudanças de conduta preventiva da população nos programas educacionais. / A questionnaire was developed wich allows the translation of the Health Belief Hodel to practice, using both, popular and medical informations in cervical cancer prevention. Belief identification have been limited to the four major dimensions of the HBH (perceptions of susceptibility, seriousness, barriers and benefits), and individual measures were calculated for each HBH dimensions, the retrospective preventive behavior and knowledge of cervical smear and cervical cancer. Instrument refinement occurred in five stages and the descriptive statistical anal~sis included each question description, and relationship between each HBM dimension and preventive behavior, and between kncwledge and behavior. The study was performed by interviews with 300 women in a inside, country city in Brazil. The results are indicating that the HBM components were weakly related with the preventive behavior, but susceptibility showed lower variation and were more closer to behavior. In spite that the HBM was not a strcnger predictor of preventive behavior, its capacity to explain behaviors was confirmed. Descriptive statistics was used to present results. Some beliefs and belief conflicts were easily identified and discussed. Sugestions were offered for programing health education in cervical cancer prevention and for use the HBM descriptive data to evaluate education impact in preventive behavior changes in a population.

Made available in DSpace on 2014-07-29T15:27:26Z (GMT). No. of bitstreams: 1 Dissertacao_Linamar.pdf: 1949828 bytes, checksum: 59aa4c0da0250e8c1a8fb3c195d72988 (MD5) Previous issue date: 2009-04-17 / The treatment of uterine cancer, a slow-growing form of the disease, is particularly effective in regard to precursor lesions. In order to understand this illness from the perspective of health sociology, this study focused on women afflicted with uterine cancer. Semi-structured interviews were employed in an attempt to perceive these women s representations. The interviews revealed the coexistence of positive and negative aspects in experiences with cancer and confirmed the stigma borne by both the illness and the treatment. Results showed that public health policies and available health services need to complement individual prevention measures in attributing priority to information about the illness and the treatment, thus covering all dimensions of people s lives. This conclusion highlights the need for a humanized health system that guarantees access to quality health services and exposes the interface between sociology and health, which is essential for the promotion of humanization within the sociocultural context of the health-illness process. / O tratamento do câncer do colo do útero, uma doença com desenvolvimento lento, é eficaz, principalmente nas lesões precursoras. Para compreender essa doença, na perspectiva da sociologia aplicada à saúde, realizou-se um estudo com mulheres que vivenciaram a experiência do câncer uterino, mediante entrevista semiestruturada, visando apreender as representações criadas por elas. As entrevistas revelaram a coexistência tanto de aspectos positivos quanto negativos na experiência com a doença e confirmaram o estigma que a doença e o tratamento carregam. Os resultados demonstram que as ações de políticas públicas em saúde, dos serviços de saúde disponíveis, precisam ser complementares às ações individuais de prevenção, no sentido de priorizar a informação e o esclarecimento sobre a doença e o tratamento, contemplando as demais dimensões da vida dos sujeitos. Isso aponta para a necessidade de um sistema de saúde humanizado, que apresente garantias de acesso a bens e serviços de saúde de qualidade, evidenciando a interface entre a sociologia e a saúde, que é imprescindível para o alcance das propostas de humanização no contexto sociocultural do processo saúde-doença.

The overall objective of the research presented in this dissertation was to assess exposure to endocrine disrupting chemicals (EDCs), polychlorinated biphenyls (PCBs), phthalates, and bisphenol A (BPA) in the general population and evaluate their associations with adverse reproductive health effects, including cancers, in women. Given the proven contribution of unopposed estrogens to the risk for endometrial neoplasia or breast cancer, renewed health concerns have aroused about estrogen mimicking EDCs found in food, personal care products or as environmental contaminants. Our meta-analysis showed that exposure to estrogen mimicking PCBs increased summary risk of breast cancer and endometriosis. We further evaluated the relationship between endometriosis and breast cancer, and EDCs using a bioinformatics method. Our bioinformatics approach was able to identify genes with the potential to be involved in interaction with PCB, phthalates and BPA that may be important to the development of breast cancer and endometriosis. Therefore, we hypothesized that exposure to EDCs such as PCBs, phthalates, and BPA, results in adverse reproductive health effects in women. Using subject data and biomarkers available from the Center for Disease Controls National Health and Nutrition Examination Survey database we conducted a cross-sectional study of EDCs in relation to self-reported history of endometriosis, uterine leiomyomas, breast cancer, cervical cancer, ovarian cancer, and uterine cancer. Significantly higher body burdens of PCBs were found in women diagnosed with breast cancer, ovarian cancer, and uterine cancer compared to women without cancer. PCB 138 was significantly associated with breast cancer, cervical cancer, and uterine cancer, while PCBs 74 and 118 were significantly associated with ovarian cancer. The sum of dioxin-like PCBs were significantly associated with ovarian cancer (OR of 2.02, 95% CI: 1.06-3.85) and the sum of non-dioxin-like PCBs were significantly associated with uterine cancer (OR of 1.12, 95%CI: 1.03-1.23). Significantly higher body burdens of PCBs were also found in women diagnosed with endometriosis and uterine leiomyomas. Documenting the exposure to EDCs among the general U.S. population, and identifying agents associated with reproductive toxicity have the potential to fill research gaps and facilitate our understanding of the complex role environmental chemicals play in producing toxicity in reproductive organs.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Uterine cancers are considered to be one of the most important malignant diseases of the female genital tract, preceded only by breast cancer. The tumor cells may produce oxidative disturbances as well as damage to the antioxidant system. Cancer may also induce alterations in blood coagulation, ranging anywhere from slight platelet activation to thrombus formation, which impair the quality of life of these patients. This study aimed to evaluate the influence of uterine cervix cancer and its treatments, such as conization and radiotherapy (RTX), on the possible development of thrombogenic processes, on the oxidative profile and on coagulation disorders. Variations in the oxidative profile were analyzed through the determination of parameters such as TBARS and protein carbonyl content and antioxidant defenses were determined from the activity of catalase and reduced glutathione (GSH). Thromboembolic disorders were evaluated by the activity of enzymes such as NTPDase, E-NPP and 5 -nucleotidase, since all of these are present in the platelet membrane, as well as the activity of ADA which has an important role in the degradation of adenosine, which in turn is known for possessing tumor promoting functions. The evaluation of oxidative and antioxidant parameters revealed that TBARS levels, protein carbonyl, GSH and the activity of catalase were enhanced in the non treated group when compared to the other groups. The increased levels of oxidants may reflect their enhanced production by tumor cells, since it is known that antioxidant levels are enhanced at the beginning of the neoplasic transformation in an attempt to neutralize the enhanced free radical production. As for the enzymes involved in the thrombogenic process, the results revealed a significant inhibition of NTPDase in groups treated for a long time ago by CNZ or RTX, when compared to the more recently treated groups and the control. The reduced ATP hydrolysis could be acting to prevent ADP formation, since this nucleotide is the main agent that promotes platelet aggregation. The reduced AMP hydrolysis in all the treated groups, may be a result of the reduced production of adenosine due to the effectiveness of the treatments. In the conization and RTX treated groups, E-NPP activity, both in serum and platelets, was reduced when compared to the control and non treated groups, which could be a reflection of reduced nucleotide degradation, due to the absence of tumor cells and, in turn, lower production of adenosine, which is a tumor promoting agent and is also the substrate for ADA. The probable absence of tumor cells due to the effectiveness of the treatments and the reduced adenosine concentration may be responsible for the reduced ADA activity found in the same groups. The inhibition of enzymes such as E-NPP, 5 -nucleotidase and ADA in all the treated groups may suggest the role of these enzymes in sequentially controlling the concentrations of nucleotides in the extracellular environment. NTPDase appears to be more sensitive to changes caused by the passing of time after the end of the treatments. We may say that the surgery itself causes greater alterations in enzymes such as E-NPP, 5 -nucleotidase and ADA from platelets, because in the groups recently treated by CNZ these activities were enhanced as compared with the group recently treated by RTX, possibly as a result of platelet alteration, which would be responsible for the enzymatic alterations observed. NTPDase is more involved in the control of platelet aggregation and the enzymes 5`-nucleotidase, E-NPP and ADA are more involved in controlling adenosine concentrations. / Os carcinomas uterinos despontam como uma das doenças malignas mais importantes do trato genital feminino, precedido apenas pelo câncer de mama. As células tumorais podem originar distúrbios oxidativos, bem como prejuízo das defesas antioxidantes desses pacientes. O câncer também pode induzir alterações na coagulação sangüínea que vão desde uma pequena ativação plaquetária até a formação de trombos na circulação, os quais prejudicam a qualidade de vida desses pacientes. Este trabalho teve como objetivo avaliar a influência do carcinoma cervical uterino e de tratamentos como a conização (CNZ) e a radioterapia (RTX) sobre o possível desenvolvimento de processos trombogênicos, sobre o perfil oxidativo e sobre os distúrbios da coagulação. As variações no perfil oxidativo foram analisadas pela determinação de parâmetros como o conteúdo de TBARS e de proteína carbonil, e as defesas antioxidantes através da atividade da enzima catalase e dos níveis de glutationa reduzida (GSH). As desordens tromboembólicas foram analisadas pela determinação da atividade de enzimas como a NTPDase, a E-NPP e a 5 -nucleotidase, enzimas presentes na membrana plaquetária, bem como através da atividade da enzima ADA a qual tem a importante função na degradação da adenosina, que reconhecidamente desempenha funções promotoras de tumor. A avaliação dos parâmetros oxidativos e antioxidantes revelou que os níveis de TBARS, de proteína carbonil, de GSH e a atividade da enzima catalase estavam aumentados no grupo de pacientes não tratados em relação aos demais grupos. O aumentado nível de oxidantes pode ser reflexo de um aumento na sua produção pela célula tumoral. Os antioxidantes podem estar aumentados possivelmente por estar no início da transformação neoplásica tumoral na tentativa de compensar o aumento da produção de espécies reativas. Com relação às enzimas envolvidas nos processos tromboembólicos, os resultados revelaram que ocorreu uma inibição significativa da enzima NTPDase nos grupos tratados há mais tempo tanto por CNZ quanto por RTX, em relação aos grupos tratados recentemente e em relação ao grupo controle. A reduzida hidrólise do ATP poderia estar atuando como forma de prevenção contra a formação do ADP, visto que este nucleotídeo é o principal agente promotor da agregação plaquetária. No caso da enzima 5 -nucleotidase observamos uma reduzida hidrólise do AMP, em todos os grupos tratados, que pode ser o resultado da reduzida produção de adenosina pela efetividade dos tratamentos. Em todos os grupos tratados por CNZ e RTX a atividade da E-NPP, tanto em soro quanto em plaquetas, estava reduzida em relação ao grupo controle e ao grupo com neoplasia não-tratada, podendo ser o reflexo da reduzida degradação de nucleotídeos, pela ausência das células tumorais, formando menos adenosina, a qual é um agente promotor de tumor e também o substrato para a ADA. A ausência de células tumorais pela efetividade dos tratamentos e a reduzida concentração de adenosina, pode ser responsável pela reduzida atividade da ADA nos mesmos grupos. A inibição da atividade das enzimas E-NPP, 5 -nucleotidase e da ADA nos grupos tratados, pode sugerir o papel dessas enzimas no controle seqüencial das concentrações de nucleotídeos no meio extracelular. A enzima NTPDase parece ser um pouco mais sensível às mudanças provocadas pelo tempo transcorrido após o término dos tratamentos. Pode-se inferir também, que a cirurgia causa maiores alterações nas enzimas E-NPP, 5 -nucleotidase e ADA de plaquetas, pelo fato de que nos grupos tratados recentemente por CNZ estas atividades encontram-se aumentadas em relação grupo tratado recentemente por RTX. Sugere-se, com esses resultados, que há uma possível alteração nas plaquetas, causada pelo processo cirúrgico, o qual seria o responsável pelas modificações enzimáticas observadas e que os tratamentos foram efetivos em combater as células tumorais uma vez que, de uma maneira geral há uma inibição das atividades das enzimas em questão, e também devido ao fato de que os testes de coagulação, possíveis indicadores de trombose associada ao câncer, não demonstraram-se alterados. Corroborando estes achados os exames citopatológicos apresentaram alterações celulares compatíveis com a normalidade. A enzima NTPDase demonstra-se estar envolvida no controle da agregação plaquetária e as enzimas 5`-nucleotidase, E-NPP e ADA parecem estar mais envolvidas no controle dos níveis de adenosina. Palavras-chave: Câncer de útero, radioterapia, conização, estresse oxidativo, plaquetas, trombose, NTPDase, E-NPP, ADA.