Dissertations / Theses on the topic 'Gynecology Diagnosis'

In the ambulatory assessment of women with abnormal uterine bleeding, the main aim is to reach a diagnosis and thereby allow appropriate treatment. Excluding endometrial pathology, particularly carcinoma and hyperplasia, is of paramount importance. However there is no consensus as to which set of investigations should be used (hysteroscopy, ultrasonography and endometrial sampling). There is a lack of good quality research evidence on the accuracy of the various diagnostic tests in predicting endometrial lesions. This dearth of relevant evidence prompted the research presented in this thesis to address and answer the following research questions: • What is the accuracy of outpatient miniature hysteroscopy / ultrasonography in the identification of premalignant and malignant endometrial lesions? • What is the relative significance of hysteroscopic and ultrasonographic evidence of endometrial atrophy in relation to an insufficient sample on outpatient endometrial biopsy? • What is the risk of premalignant and malignant pathology among endometrial polyps? What is the significance of various risk factors associated with endometrial polyps? • What is the feasibility of multivariable analysis to evaluate combinations of diagnostic tests in the diagnosis of endometrial disease? Findings and Conclusions Positive hhysteroscopy is accurate in ruling in endometrial cancer and hyperplasia (the LR was 51.1 (95% CI 7.9-326.9). Using endometrial thickness >4mm at ultrasound scan, ultrasound is accurate in ruling out endometrial cancer and hyperplasia (the LR was 0.14 (95%CI 0.02-0.64). Insufficient sample on endometrial biopsy was more common among cases with hysteroscopic finding of endometrial atrophy (adjusted OR= 4.79, 95% CI 1.05-21.91, p=0.04) and less common among cases with sonographic endometrial thickness above 5mm (adjusted OR=0.19, 95% CI 0.07-0.53, p=0.001). Therefore insufficient sample may be considered a substitute to absence of pathology provided the hysteroscopic and sonographic endometrial assessment is consistent with endometrial atrophy. Hyperplasia was more frequent in endometrial specimens with polyps than in those without (9.7% vs 4.8%, OR=2.1, 95% CI 0.85-5.2), but the rate of carcinoma in the two groups was not statistically different (4.8% vs 3.2%, OR=1.5, 95% CI 0.46-5.0). Tamoxifen treatment was associated with endometrial polyps (adjusted OR= 8.16, 95% CI 2.01-33.2, p=0.003) but hormone replacement therapy was not (adjusted OR=1.35, 95% CI 0.65 – 2.81, p=0.42). The true clinical value of a test lies in the added information over and above what was already known from the history and examination. It is feasible to develop a stepwise multivariable analytic approach to explore the added value of tests (hysteroscopy or ultrasonography) over and above history when predicting endometrial hyperplasia or cancer. This analytic strategy needs to be applied in larger datasets to draw clinical conclusions.

There have been phenomenal advances in the field of reproductive medicine and success rates following in vitro fertilisation have improved dramatically in recent years. The aim of this project was to improve our understanding of human preimplantation embryo development by identifying potential markers of viability that may aid us in selecting the best embryo for uterine transfer in the clinical embryology laboratory. Investigations into the distribution of cytoskeletal F-actin in human embryos demonstrated that a highly organised actin cortex is important for embryo cleavage and continued development to the blastocyst stage. Whilst they are polarised in the mouse from the oocyte to the blastocyst, the regulatory proteins leptin and STAT3 are co-localised only at the oocyte stage in humans, and are distributed within different cytoplasmic domains in human cleavage stage embryos and blastocysts. Whether polarity in humans is predetermined in the oocyte remains elusive, but none of the evidence generated in this thesis supports this idea. Leptin transiently activates STAT3 via the long form of the leptin receptor, and most significantly in the ICM of human day 6 blastocysts. Morphological features of blastocysts that can be visualised microscopically, such as a double ICM and cytoplasmic projections connecting the ICM to the TE, provide clues to their viability and may help us to choose the most suitable embryo from a cohort when deciding which to transfer. Nuclear volumes may in future contribute to this selection. Using time lapse technology to study cleavage patterns is now a routine occurrence in the clinical embryology laboratory. The results in this thesis show that distinctive patterns of divisions and the site at which blastocysts hatch can provide us with more information than a snap-shot morphological evaluation. Finally, contributing to the development of modelling software and predictive algorithms for the study of human embryos, particularly in time lapse imaging, means that our understanding of this fascinating area of medicine will continue to progress.

Introduction: Early diagnosis of breast cancer can result in less radical therapy and improved survival. Current screening and diagnostic tools have limitations, as do serum marker antigens due to their low sensitivity. We hypothesised that an immune response is an early event in cancer evolution. Autoantibodies, which are the amplified signals of cancer-derived antigens, can be detected in the peripheral blood of women with early breast cancer. This thesis is a continuation of previous work at the Nottingham Breast Unit aimed at developing new panel of assays for the detection of autoantibodies in breast cancer. The goal of this thesis was to investigate the use of a potentially more reproducible ELISA assay to measure serum autoantibodies to MUC1, p53 and c-myc either singly or in combination within a panel to further clarify a role of AAbs in screening, diagnosis or prognosis of primary breast cancer. Methods: Newly expressed, biotinylated and reconfigured p53 and c-myc antigens and purified MUC1 antigen were used to establish novel in-house ELISA. These were used to measure autoantibodies to the above 3 antigens in the serum of various populations which were collected over a two year period. These populations included an at-risk population (e.g. family history and atypical ductal hyperplasia) and a population of women who had just been diagnosed with primary breast cancer, either non-invasive ductal carcinoma in situ (DCIS) or invasive cancers. Cut-off values were established for each of the autoantibodies based on 2 or 3 standard deviations from the mean of a population of control samples. The control samples were obtained from a population of women who were either deemed ‘normal’ or who had a histological diagnosis of benign breast disease. The assay was validated by assessing effect of sample age as samples were of varying age, reproducibility using Bland Altman coefficient of reproducibility and reliability by establishing the assays ability to distinguish cancer from non-cancer. Results: Eight hundred and ninety eight samples were analysed in the study. One hundred and ten were Control samples. The remaining samples included 381 that were from an at-risk population and 407 that were from a primary breast cancer population. Mean ages of Control, at-risk and primary breast cancer populations were 58.8, 50 and 62.9 years respectively. Data establishing validity of assay confirmed that sample age did not affect signal strength for MUC1 and c-myc autoantibodies. Older samples for the p53 autoantibody had lower signal than recent ones. Reproducibility data was satisfactory and was best in the samples from the group of women with benign breast disease. Using either a 2 or 3 standard deviation cut-off value the assay was also able to distinguish cancer from non-cancer for both MUC1 and p53 autoantibodies. For the c-myc autoantibody, cancer samples showed increased signal compared to non-cancer although this did not reach significance. The at-risk population were routinely followed up in an outpatient clinic dedicated for women at increased risk of breast cancer. An individual positive marker was noted in up to 10% of at-risk patients. The panel of 3 assays showed a raised marker in 18.4%. This was significantly higher than that for the Control population whose panel detection was 9.1% whilst an individual marker was noted in up to 4.5% of samples. Only the c-myc autoantibody had similar prevalence in both Control and at-risk populations. There was no correlation between risk category and autoantibody detection. The specificity for MUC1, p53 and c-myc autoantibody serum tumour markers were 92.4%, 95.2% and 95% respectively. Specificity of the assay can be further increased if two or more markers were needed to be positive before a positive result is deemed for the assay. Thirteen women in the at-risk group developed breast cancer. The panel had a higher sensitivity to detect occult tumours compared to individual markers but at reduced specificity. Two of 13 at-risk patients (15.4%) who developed breast cancer had a raised marker (MUC1 & p53 autoantibodies) within the panel with a mean lead-time of 43.5 months. Further increasing the cut-off value to Mean + 4 standard deviation of Control population increased the specificity of the panel assay to 97.2% without altering the sensitivity to detect occult tumour (15.4%). Primary breast cancer population consisted of patients who were known to have DCIS or invasive breast cancer. The latter group was further subdivided into those who were detected via screening mammogram (screen-detected) and those who presented with a lump (symptomatic). Two of the 3 markers (p53 and c-myc autoantibodies) were significantly raised in the primary breast cancer population compared to the at-risk population as well as the Control group as detailed in earlier paragraph. Individual markers were detected in up to 20.9%, 10.3% and 9.8% for p53, c-myc and MUC1 autoantibodies respectively. The panel detection rate was 35.1%. The tumour markers showed limited use as a prognostic factor. Only the c-myc autoantibody correlated with a poorer survival due to distant metastasis in symptomatic breast cancers. Data for the screen-detected breast cancer cases showed that there were no correlation between any of the 3 serum marker detection and prognosis. Conclusion: Our data demonstrated the three autoantibody assays whether singly or in combination as a panel showed differences not only between cancer and non-cancer but also between Control and at-risk, as well as between at-risk and cancer. The panel showed that one or more assays were positive in 35% of breast cancers with a specificity of 83.6%. The specificity of the assay can be altered to meet clinical needs by either increasing the cut-off value or altering the markers within the panel. Current data in the literature suggests a number of markers that may be added or substituted into the panel to enhance the specificity and sensitivity. However a sensitivity of 15.4% for detection of occult tumour in the at-risk group makes any clinical application for screening in this group less cost effective using the version of the assays described in this thesis. The lead-time in the two patients who did show elevation of an autoantibody suggests that if the sensitivity and specificity can be improved that there is an in-vivo amplification signal, which might allow earlier identification of some breast cancers. Detection of c-myc autoantibodies indicates a poorer prognosis in the symptomatic group. The value of this information needs to be further determined in larger studies and within multivariate analysis. If the current results remain then there may be clinical implication to this early data. Comparison with previous data from the unit revealed that detection of cancer-associated autoantibodies in primary breast cancer and at-risk groups using this methodology appeared to be less sensitive. This may indicate that the current method has been successful in reducing background signal and hence reduce false positive results. It therefore appears that we have established a more reliable and reproducible assay compared to previous study to detect autoantibodies to tumour-associated antigens. However it is noted that this thesis reports single batches of antigens (MUC1, p53 and c-myc) used in the autoantibody assays. Investigation of differences in protein structure and immunogenicity between batches, which might also affect the sensitivity and specificity of these assays, was outside the scope of this thesis but is the subject of ongoing research by other members of the research group.

The Pathways project was undertaken to devise guidelines to facilitate rapid diagnosis of paediatric brain tumours. Methods: A systematic review and meta-analysis of published data on paediatric brain tumour presentation and analysis of the presentation of children newly diagnosed with a brain tumour at four oncology centres was undertaken. The results informed a professional consensus process. Results: 74 papers met the inclusion criteria for the meta-analysis. 56 symptoms and signs at diagnosis were identified. The most frequent symptoms and signs at diagnosis were: headache (33%), nausea and vomiting (32%), abnormalities of gait and coordination (27%), and papilloedema (13%). 139 patients were recruited to a multi-centre cohort study. Symptoms and signs at disease onset and at diagnosis and factors associated with a long and short symptom interval were determined. A shorter symptom interval was associated with nausea and vomiting and motor system abnormalities. A longer symptom interval was associated with head tilt, cranial nerve palsies, endocrine and growth abnormalities and reduced visual acuity. A multi-disciplinary workshop and Delphi consensus voting were used to translate the evidence into a clinical guideline comprising 76 statements advising on the identification and assessment of children who may have a brain tumour.

This thesis presents findings from a qualitative study of the emergence and early clinical translation of non-invasive prenatal diagnosis (NIPD) in the UK. Drawing from interviews with a range of experts and users I track the enrolment and translation of this new prenatal testing technology across a variety of clinical and social spaces. I show how encounters with NIPD prompt deep critical examination of the moral, social and political implications - not only of the technology - but of the established clinical practices (routine and specialised prenatal testing) and specific policy contexts (prenatal screening programmes) within which NIPD has begun to sediment. I explore how, as NIPD advances at a rapid pace and emerges within a culturally and politically complex context, the technology both aligns with and disrupts routine practices of prenatal screening and diagnosis. I show how, as the technology divides into two major strands - NIPD and NIPT - at an early stage of development, and before becoming naturalised/normalised within the clinic, scientists, clinicians and policy makers attempt to pin down, define and ‘fix’ the technology, drawing upon and engaging in substantive practices of division, categorisation and classification. I explore ambiguities present within such accounts, highlighting dissenting voices and moments of problematisation, and following this, I show how the ‘troubling’ of boundaries prompts much examination of ethical and social concerns. As a location within which interviewees explored more contentious issues, I show how abortion emerged as central to the discussion of NIPD. I proceed to show how institutionalised, professionalised bioethical debate dominates mainstream discourse, and I explain how a particular construction of the informed, individual choice-maker is mobilised in order to locate moral and political responsibility for testing in the hands of individuals, and to distance political/organisational structures from entanglement with problematic concerns. I explore how clinicians and patients respond to this positioning in multiple ways, both assimilating and questioning the mainstream discourse of ‘informed choice’. In conclusion, I highlight the broader (bio)political aspects of NIPD’s emergence and translation within prenatal screening and diagnosis.

The purpose of this thesis is to study the attitudes, practices and knowledge of Greek women in Perth, Western Australia, regarding cervical cancer screening. This is important because no study has yet examined the cervical screening pattern of this group, despite their low participation rate in screening programs. Qualitative semi-structured interviews among 15 Greek women in Perth were used for data collection. Interviews were conducted both in English and Greek. Eight out of the 15 women interviewed did not participate in frequent screening and many had had only one Pap test in their life. Culture and religion influenced negative attitudes towards cervical screening; these combined with strong emotions of fear towards the disease and lack of knowledge about the purpose of Pap tests, to create powerful barriers to screening. Preoccupation with morality and misconceptions about heredity and the symptomatology of cervical cancer also influenced attitudes towards Pap tests. Further, women's decisions to screen were influenced by the negative behaviour of General Practitioners. A preference was expressed for specialists/gynaecologists and an unwillingness to attend women's health centres.

This thesis deals with the performance of a diagnostic protocol designed to determine the underlying causes of early fetal and perinatal deaths. It is subdivided into three chapters. The first chapter is a review of the literature. It surveys the underlying causes of fetal and perinatal deaths and the informativeness of different tests applied to assess these causes. The second chapter is a manuscrrpt describing the real performance of one of these protocols applied since 1982 in a geographlcally determined area. This area, located in the south east of France, covers annually 23,000 births. This descriptive study carried out on 1019 consecutive stillbirths and perinatal deaths shows the importance of both clinical information and necropsy among the overall tests. This chapter is preceded by an overview of the context and the objectives. In the third chapter, written as a classical chapter of a thesis, a decision tree presents the theoretical performance of each relevant combination of tests for the diagnosis only of fetal causes of death. The theoretical informativeness of each test was coded with the aid of two medical geneticists. Non fetal causes are not considered in this part of the study because the underlying objective of the clinicians who implemented the protocol was only to screen genetic causes of death.
Cette thèse se divise en trois chapitres écrits dans le cadre d'une étude d'évaluation de la performance d'un protocole de diagnostic des causes initiales de mortalité foetale précoce et périnatale. Le premier chapitre est constitué d'une revue de la littérature sur les causes initiales de mortalité et sur l'informativité des examens clinique et paracliniques à la naissance d'un enfant mort-né. Le deuxième chapitre est un manuscrit d'article décrivant la performance réelle d'un protocole de diagnostic mis en place en 1982 dans une zone géographique délimitée du sud est de la France couvrant 23 000 naissances annuelles. Cette étude descriptive porte sur 1019 décès consécutifs. Elle montre l'importance de l'information clinique et de l'autopsie parmi l'ensemble des examens. Elle est précédée d'une présentation du contexte et des objectifs. Le troisième chapitre est rédigé non plus sous la forme d'un article scientifique mais comme un chapitre de thèse classique. Il présente un arbre de décision évaluant la performance théorique de chaque combinaison des différents éléments du protocole. Le codage de l'informativité théorique de chaque élement inclus dans le protocole a été réalisé en collaboration avec deux experts en génétique médicale. Cette performance a été considérée uniquement pour la détermination des causes fœtales de mortalité. En effet, ce protocole mis en place à l'initiative d'une équipe de médecins pédiatres et généticiens, avait seulement pour objectif initiai le dépistage des causes fœtales de décès d'origine génétique et non celles d'origine maternelle ou obstétricale.

Spontaneous preterm birth complicates about 3% of pregnancies before 34 weeks’ gestation and 7 – 12% before 37 weeks’ gestation. It is an important issue to public health worldwide. The aim of this thesis was to identify test(s) which would predict spontaneous preterm birth in early pregnancy when women are asymptomatic and in later pregnancy when they present with symptoms of threatened preterm labour, using systematic reviews and meta-analysis. If women at risk can be identified whether early in pregnancy or when they present with threatened preterm labour, interventions can be deployed to prevent or delay birth and to improve subsequent neonatal mortality/morbidity. Initially 40,243 title and abstract citations were scrutinised, resulting in shortlist of 1,650 full articles in which 319 were included in the systematic reviews, encompassing 22 tests. The quality of studies and accuracy of tests measured with likelihood ratio (LR) was generally poor. There were only a handful of studies for most of the tests. Few tests reached LR+ point estimates >5. In asymptomatic antenatal women these were ultrasonographic cervical funnelling and length measurement, cervico-vaginal prolactin and cervico-vaginal fetal fibronectin screening for predicting spontaneous preterm birth before 34 weeks’ gestation. In this group, tests with LR- point estimates approaching <0.2 were detection of uterine contraction (by mammary stimulating test) and amniotic fluid CRP measurement. In symptomatic women with threatened preterm labour tests with LR+ point estimate >5 were absence of fetal breathing movements, cervical length measurement, amniotic fluid IL6 and IL8, serum CRP and cervico-vaginal hcg for predicting birth within 2-7 days of testing. In this group tests with LR- point estimate <0.2 were measurement of cervico-vaginal hcg, cervical length measurement, absence of fetal breathing movement, amniotic fluid IL6 and IL8, and serum CRP for predicting birth within 2 - 7 days of testing. In conclusion, no exceptional, but many promising tests for predicting spontaneous preterm birth was identified to aid the development of evidence based practice.

Events in utero have been linked with diseases throughout life, however there is a lack of consensus regarding the ability of neonatal tests to predict these outcomes. Systematic reviews and meta-analyses were performed, assessing umbilical cord pH and base excess at birth, standards of low birth weight, and the Apgar score, including a total of 218 papers and 26704980 individuals. The prognostic association and predictive accuracy of these tests for adverse outcomes, including neonatal mortality and morbidity, childhood morbidity including cerebral palsy, and adult outcomes, were determined. A decision-analytic model based analysis assessed the cost-effectiveness of varying the umbilical cord pH threshold, and treatment with neonatal hypothermia. This thesis determined that all of the tests examined had a strong association with neonatal mortality, and a significant but smaller association with neonatal morbidity and childhood cerebral palsy. In general, where the association was strong, tests had a high specificity and positive likelihood ratio for adverse outcome, but poor sensitivity and negative likelihood ratio, indicating that negative tests do not reduce the risk. The cost effectiveness analysis showed that the threshold of pH used in current practice to recommend neonatal hypothermia is more effective and less costly than a higher threshold.

Bakgrund: Polycystisk ovarialsyndrom (PCOS) är den vanligaste hormonella rubbningen hos fertila kvinnor, ändå är den okänd för många. Det finns ett flertal symtom där dessa varierar från kvinna till kvinna. Okunskap kring PCOSförekommer både i vården liksom i samhället och diagnosen kan därför vara svåratt upptäcka. Att leva med symtomen från PCOS kan påverka negativt både kroppsligt och psykiskt. Hur kvinnor med diagnosen upplever PCOS behöverlyftas fram och förståelsen för dem behöver ökas både inom vården liksom förkvinnorna med PCOS. Med ökad förståelse kan ett bättre bemötande och vård ges.Syfte: Syftet är att beskriva kvinnors upplevelser av att leva med Polycystiskovarialsyndrom. Metod: Kvalitativ metasyntes med metaetnografisk analysmetod.16 kvalitativa artiklar är inkluderade i resultatet och samtliga artiklar hargenomgått en kvalitetsgranskning. Tre databaser användes vid insamling av data; Cinahl, Medline och PubMed. Resultat: Resultatet lyfter fram att flertalet kvinnorfick diagnos efter en lång tid och där kvinnorna ibland behövde vara påstridiga,medan i andra fall diagnosticerades PCOS som bifynd. Vissa kvinnor kände inte till att deras symtom kunde vara något avvikande och sökte sig därför inte till vården. Information om PCOS från vården mötte inte alltid patienternas behov.Fertilitetsaspekten ansågs vara det som fokuserades mest på från vårdens sida ochatt de psykologiska aspekterna glömdes bort. Symtom som övervikt och hirsutism påverkade det sociala livet negativt och psykisk ohälsa är vanligt förekommande.Slutsats: PCOS behöver uppmärksammas mer och normaliseras. En mer holistiskvård där fokus inte enbart ligger på det medicinska aspekterna, utan även ser till individens behov av stöd och information hade gynnat bemötandet och vårdandet till kvinnor med PCOS.
Background: Polycystic ovary syndrome (PCOS) is the most common hormonal condition amongst fertile women, yet it is still unknown for many. There are several symptoms that may vary from woman to woman. Ignorance of polycystic ovary syndrome occurs in healthcare and in society and can be difficult to detect.Living with the symptoms of PCOS can have a negative effect both physically andmentally. How women with the diagnosis experience PCOS needs to be highlighted and the understanding of them needs to be increased, both inhealthcare and for the women with PCOS. With increased understanding, bettertreatment and care can be provided. Aim: The purpose was to describe women’sexperiences of living with Polycystic ovary syndrome. Method: Qualitative meta synthesis with meta ethnographic analysis method. A total of 16 articles wereincluded and all passed through a quality critique checklist. The articles werecollected from three databases: Cinahl, Medline and PubMed. Findings: It couldtake a long time for a diagnosis to be made and sometimes the women had to be persistent, while others could be diagnoses as an incidental finding. Some womendid not know that their symptoms were not normal and therefore did not seekmedical care. Information about PCOS from the health care did not always meetthe patient’s needs. The fertility aspect was thought to be the main focus from the health care providers and that the phycological aspects were forgotten. Symptoms like overweight and hirsutism affected the social life in a negative way and mental illness was common. Conclusion: Polycystic ovary syndrome needs to be brought more attention to and to be normalized. A more holistic care where not only the main focus is on the medical aspects of PCOS, but instead also sees that the individuals need for support and information can be met.

Preeclampsia (PE) is the leading cause of poor maternal and perinatal outcomes in both developed and developing countries. Even though the condition is treatable in the developed world, mothers from developing countries still suffer dramatic events due to limited resources. There is the need to identify readily available measures in addition to existing biomarkers that can predict PE. Thus, this thesis evaluated suboptimal health status (SHS) and prospective levels of oxidative stress (OS) biomarkers and angiogenic growth mediators (AGMs) with placental anatomy and pathology in normotensive and preeclamptic births in a Ghanaian Population. This longitudinal nested case-control study was based on the Ghanaian Suboptimal Health Status Cohort Study (GHOACS) that recruited 593 normotensive pregnant women (NTN-PW) at baseline (10-20 weeks gestation) from the Komfo Anokye Teaching Hospital between June 2017 and May 2019. Suboptimal health status, a subjective health measure was evaluated using the Suboptimal Health Status Questionnaire-25 (SHSQ-25) at baseline, and participants were subsequently classified into suboptimal health status (SHS) and optimal health status (OHS). Baseline participants were followed at 21-31 weeks, 32-42 weeks of pregnancy and 48 hours-2 weeks postpartum. Of the 593, 488 pregnant mothers aged 18-45 years completed the study and 105 were lost to follow-up. Data on sociodemographic, clinical, obstetric and anthropometric characteristics were collected from participants in addition to urine and venous blood samples. The panel of objective biomarkers of AGMs (placental growth factor [PIGF], vascular endothelial growth factor-A [VEGF-A], soluble endoglin [sEng] and soluble VEGF receptor-1 also known as soluble fms-like tyrosine kinase [sFlt-1]) in addition to OS biomarkers (8-epiprostaglandinF2 alpha [8-epi-PGF2α], 8-hydroxy-2-deoxyguanosine [8-OHdG] and total antioxidant capacity [TAC]) were evaluated across the 4-time sampling periods (10-20, 21-31, 32-42 weeks, and 48 hours-2 weeks postpartum) using ELISA. Placenta tissues were collected after delivery and examined for macroscopical, histopathological and immunohistochemical analyses. Data were analysed using SPSS, GraphPad Prism, XLSTAT and R Core. There were significant associations between SHS and imbalances in AGMs and OS (Study I: cross-sectional). The incidence of PE was high among SHS pregnant women (30.7%) compared to OHS pregnant women (8.8%), and SHS was an independent risk indicator for PE (Study II: longitudinal nested case-control). Compared to using the biomarkers alone, combining biomarkers of AGMs and OS, particularly 8- OHdG/PlGF ratio measured at 21-31 weeks (mid-pregnancy) yielded the best area under the curve, sensitivity, specificity, positive and negative predicted values for predicting the likelihood of SHS and OHS pregnant women developing PE (Study III: longitudinal nested case-control). Placental abnormalities and imbalance in the expression of AGMs and OS were associated more with SHS pregnant mothers who developed PE, particularly early-onset PE than late-onset PE (Study IV: case-control). In contrast to normotensive pregnancy, longitudinal profiling of AGMs and OS showed different patterns across the 4-time sampling periods with significant imbalance among SHS more than OHS mothers who later developed PE. Unlike, the single biomarkers, combined AGMs and OS ratios measured at mid-pregnancy yielded more significant hazard ratios in association with PE development (Study V: longitudinal cohort). Thus, combined evaluation of SHS, biomarkers of AGMs and OS together with placental examination increased the understanding of the aetiology, diagnosis and prognosis of PE, and created a window of opportunity for developing potentially predictive, preventive and personalised medicine in both high-and low-resource maternal and child health settings.

INTRODUÇÃO: A hidrolaparoscopia transvaginal (HLT) é uma técnica de exploração das estruturas tubo-ovarianas em pacientes inférteis sem alteração pélvica determinada. O procedimento consiste no acesso via vaginal da cavidade pélvica com trocarte e introdução de óptica que é acoplada ao sistema de videodocumentação. O exame é realizado em ambulatório com anestesia local. A visibilização é conseguida graças a hidroflotação das estruturas pélvicas provocada pela instilação de soro fisiológico ou solução de lactatoringer. Trata-se de uma das técnicas vídeo-endoscópicas ginecológica mais recentes descrita na literatura, ainda em fase de estudos. Este método permite o diagnóstico de afecções da pelve posterior como, endometriose, cistos ovarianos, aderências, hidrossalpinge, miomas e estudo da tuba distal em pacientes laqueadas. O estudo desenvolvido tem por objetivo avaliar a técnica operatória em si, assim como os achados através deste método e a segurança e eficácia de um novo um novo instrumental, mais particularmente uma agulha de Veress modificada, desenvolvida especificamente para este procedimento. Este instrumental difere de outros utilizados e descritos na literatura por apresentar um dispositivo de segurança em sua base que tem por finalidade fixar a parte interna da ponta da agulha, oferecendo maior segurança ao adentrar-se às cegas na cavidade pélvica através do fórnice vaginal posterior. CASUÍSTICA E MÉTODOS: Para realização do estudo selecionou-se 38 pacientes laqueadas que apresentavam desejo de gravidez. Foram excluídas pacientes que apresentassem outra afecção pélvica e aquelas cujos parceiros apresentavam espermograma alterado com indicação de fertilização in vitro. O procedimento foi realizado com a paciente em posição ginecológica. Após a anti-sepsia da vulva e vagina procedeu-se à infiltração de 2 ml de lidocaína com vasoconstritor em porção mediana do fórnice vaginal posterior aproximadamente 1,5 cm abaixo da inserção da parede vaginal na cérvice uterina. Depois disto puncionava-se através do local previamente anestesiado com a agulha, objeto deste estudo, já envolta por uma cânula similar a um trocarte, até transpassar-se a parede vaginal e obter-se acesso à cavidade pélvica. Introduzia-se 100 ml de soro fisiológico ou solução de lactato-ringer com lidocaína 2% sem vasoconstritor diluída em uma proporção de 1/100. Após remover a agulha introduzia-se através da cânula uma óptica de 2,9 mm com ângulo de 30º acoplada a um sistema de vídeodocumentação; confirmava-se o acesso ao interior da cavidade e prosseguia-se a instilação de líquido e inspeção da mesma. RESULTADOS: 1) Obteve-se acesso à cavidade pélvica em 36 (94,7%) das pacientes. 2) A quantidade de líquido utilizada variou de 300 a 1500 ml. 3) O escore médio de dor foi de 2,3 na escala visual analógica de dor. O escore médio nas pacientes nas quais se utilizou quantidades 600ml foi de 2,7 e 1,7 respectivamente. 4) Os achados mais comuns durante o procedimento foram de aderências pélvicas velamentosas, além de hidrossalpinge e salpingectomia distal em alguns casos. 5) Não houve qualquer complicação nos 38 casos estudados. CONCLUSÕES: 1) O novo instrumental de hidrolaparoscopia transvaginal (agulhas de Veress modificada) é eficaz em acessar a cavidade pélvica, é seguro e de fácil manuseio. 2) A hidrolaparoscopia transvaginal é um método realizável em âmbito ambulatorial, reprodutível, bem tolerado, de baixo custo e com boa capacidade diagnóstica
INTRODUCTION: Transvaginal hydrolaparoscopy (THL) is a technique for pelvic exploration in patients without pelvic pathology. The procedure consists of accessing the pelvic cavity with a trocar and introduction of an optic coupled to a videodocumentation system. The exam is performed in outpatient under local anesthesia. Visualization is achieved through hydroflotation of the pelvis\'s structures, following instillation of saline or Ringer\'s lactate solution. It is one of the most recently described gynecological videoendoscopic techniques in the literature and still in trial phase. This method enables the diagnosis of alterations in the posterior pelvis, such as endometriosis; ovarian cysts; adhesions; hydrosalpinx; myomas; and evaluation of the distal tube in patient with tubal ligation. The objective of the study was to evaluate the technique itself, as well as the findings using this method and the efficiency of the new instrument, in particular the modified Veress needle that has been developed specifically for this procedure. This instrument differs from others described in the literature because it has a safety device in its base designed to fix the inner part of needle\'s tip, thereby offering greater safety during blind insertion into the pelvic cavity through the posterior fornix. MATERIAL AND METHODS: A total of 38 patients with tubal ligation were selected that had expressed the desire to become pregnant. Patients with other pelvic alteration and whose partner presented abnormal semen analisys with indication for in vitro fertilization were excluded. The procedure was performed in gynecologic position. After antisepsis of the vulva and vagina, 2 ml of lidocaine with adrenaline was perfomed of posterior fornix at midline, approximately 1.5 cm below the insertion of the vaginal wall in the uterine cervix. After this, the Veress needle previously covered with a cannula that is similar a trocar, was inserted through the anesthetized area until it reached the pelvic cavity. A hundred milliliter of saline or Ringer\'s lactate solution with 2% lidocaine, without adrenaline and diluted to 1:100 was introduced. After removal of the Veress needle, a rigid 2,9 mm endoscope with a 30º optical angle coupled to a videodocumentation system was inserted trough the cannula to confirm the access into pelvic cavity. The liquid has continued instilled and the inspection was undertaken. RESULTS: 1) the pelvic cavity was accessed in 36 (94.7%) patients; 2) the distention media volume used was 300 to 1500 ml; 3) the mean score for pain using the visual analog pain scale was 2.3. This score for the patients that received 600 ml was 2.7 and 1.7, respectively; 4) the most common findings during the procedure were filamentous pelvic adhesions, besides hydrosalpinx and distal salpingectomy in some cases 5) there were no complications in any of the 38 cases studied. CONCLUSIONS: 1)The new transvaginal hydrolaparoscopy instrument (modified Veress needle) is effective to access the pelvic cavity, safe and easy handle; 2) transvaginal hydrolaparoscopy is feasibility in outpatient basis and is reproducible, well tolerated, inexpensive and offers a good diagnostic capacity

Introdução: Aproximadamente 2% a 26% das mulheres submetidas à esterilização demonstram arrependimento em algum momento de sua vida. A reversão cirúrgica pode ser realizada por laparotomia, minilaparotomia ou laparoscopia. Para tanto, é necessário avaliarem-se as condições tubárias para prognosticar o procedimento cirúrgico. Para a avaliação anatômica da tuba procede-se à histerossalpingografia para a análise da porção proximal à cicatriz cirúrgica da laqueadura, e a laparoscopia para a porção distal. Neste estudo prospectivo transversal, avaliou-se a porção distal das tubas pela hidrolaparoscopia transvaginal (HLT) como alternativa à laparoscopia diagnóstica. Métodos: No período de agosto de 2001 a abril de 2004, 38 pacientes sem outra afecção pélvica, com idade inferior a 40 anos, índice de massa corpórea menor que 35 kg/m2, e cujos parceiros não apresentavam espermograma alterado com indicação de fertilização in vitro, foram submetidas à HLT, em ambulatório e sob anestesia local. A reversão cirúrgica foi efetuada em 30 pacientes por minilaparotomia, que foi considerada \"padrão-ouro\" para determinar a acurácia dos achados da HLT. Resultados: 1) Obteve-se acesso à cavidade pélvica em 36 (94,7%) pacientes; em duas (5,3%) houve falha de acesso. 2) Das 30 pacientes que se mantiveram no estudo, em duas (6,7%) não se obteve acesso à cavidade pélvi-ca, e das 28 (93,3%) pacientes avaliadas em um total de 56 tubas, o prognóstico foi correto em 25 (89,3%) e insatisfatório em três (10,7%). A falha prognóstica decorreu de hidrossalpinge e laqueadura em dois pontos em cada uma das tubas em uma paciente e de hidrossalpinge em outras duas pacientes. 3) Não houve qualquer complicação nos 38 casos estudados. Conclusões: A HTL é método que per-mite a visualização das fímbrias e do coto distal das tubas de pacientes laqueadas. Constitui método com alto índice de acerto na análise da possibilidade de recanalização cirúrgica pós-laqueadura, mas a presença de hidrossalpinge prejudica a avaliação do prognóstico da reversibilidade.
Background: The rate of post sterilization regret in women is about 2% to 26% de-pending on the moment of life they are living. Surgical reversibility can be carried out with the use of laparotomy, minilaparotomy or laparoscopy. However, tubal condi-tions must be assessed for the surgical prognosis. Hysterosalpingography is useful for assessing the proximal surgical scar of the ligated tube, and laparoscopy is used for evaluating the distal portion. Distal portion of ligated tubes were evaluated by transvaginal hydrolaparoscopy (THL) as an alternative to laparoscopy in this investi-gation. Method: Between August 2001 and April 2004, 38 female candidates for sterilization reversal without any other pelvic disease, aged up to 40 years old, pre-senting body mass index <35 kg/m2, whose partners did not present abnormal es-permogram, and without indication for in vitro fertilization were submitted to outpa-tient THL under local anesthesia. Surgical reversal was accomplished in 30 patients with minilaparotomy, considered the golden-pattern for analyzing the accuracy of THL findings. Results: 1) Pelvic cavity was achieved in 36 (94.7%) patients, and the access failed in the other two (5.3%). 2) Out of the 30 patients who were kept in the study, failure in achieving the pelvic cavity occurred in two (6.7%) of them. In the remaining 28 (93.3%) women or 56 tubes, THL diagnosis was correct in 25 (89.3%) and unsatisfactory in the other three (10.7%). Prognosis failure was result of hy-drosalpinge, and one of these three patients presented two points ligated in both tubes as well. 3) There were no THL complications in all cases. Conclusion: THL is a technique useful for allowing visualization of fimbriae and distal stump of ligated tubes, and for accurately previewing the possibility of surgical reversal, although the presence of hydrosalpinge can interfere in the THL prognosis for tubal reversibility.

Dissertation submitted in full compliance with the requirements for the Master's degree in Technology: Radiography, Durban Institute of Technology, Durban, 2004.
The object of this study was to use Transvaginal ultrasound to evaluate the thickness of the endometrium to exclude endometrial abnormality in Black South African women with postmenopausal uterine bleeding. Transvaginal ultrasound is an excellent diagnostic method for assessing endometrial pathology. The study was carried out at the Gynaecological Ultrasound Department, King Edward VIII Hospital. The study included 76 Black women with postmenopausal uterine bleeding. The thickness of the endometrium was measured by Transvaginal ultrasound. The measurement included both endometrial layers (double-layer technique). The Transvaginal ultrasound measurement was compared with the histopathological diagnosis of the biopsy specimens. At the end of the investigation, findings obtained were 3.9% non-representative, 44.8% endometrial adenocarcinomas, 14.5% benign polyp, 3.9% chronic Endometritis, 17.1% benign endometrium, 5.3% endometrial hyperplasia, 9.2% atrophic endometrium, 3.9% myometrial invasion and 1.3% Malignant Mixed Mullerian Tumour. In this study, the thickness of the endometrial echo varied from 5mm to 35mm, with a mean of 18,2mm. When the thickness of the endometrial echo was compared with the histopathological results, the mean value for non-representative was 7.83mm, much lower than the thickness of an active endometrium (13.25mm). In cases with atrophic endometrium, the thickness ranged from 6mm to 30mm with a mean of 15.86mm. The mean value obtained for cases with endometrial adenocarcinoma was 20.32mm (range 11 to 35mm). The sensitivity, specificity and accuracy of Transvaginal ultrasound for detecting endometrial malignancy were 100% if the cutoff limit of 4mm was used In conclusion, this study using Transvaginal ultrasound demonstrated that a thickness limit greater than 8mm was considered in detecting malignancy. No malignant endometrium was thinner than 5mm. Therefore in women with postmenopausal uterine bleeding and an endometrium less than 4mm, it may be justified not to perform further investigations. Transvaginal ultrasound is a simple, well-tolerated safe and reliable method for identifying endometrial thickness in postmenopausal Black South African women.
M

碩士
國立交通大學
材料科學與工程學系奈米科技碩博士班
101
Gynecologic cancer is a clinically typical female cancer, usually has a poor prognosis. It is deadly because it lacks any clear early detection or screening test. Therefore, early detection of cancer provides the best opportunity for successful management. The diagnosis and prognosis of cancer is evaluated by cancer spreading, tissue staining and with the clinical database experience. The universally accepted prognostic factors for patients are stage, grade and volume of residual disease. But this method are still considered preliminary, large uncertainty still exists in the existing diagnostic methods, there is still much room for improvement. In this study, we established a novel platform that can be used to assess basic parameters of cell response for the rapid diagnosis of gynecologic cancer clinical stages, and enhance the assessment of prognosis. We collected the different stages of clinical ovarian cancer and endometrioid adenocarcinoma (EMCA) specimens which isolated from tumor tissues or ascites. Cancer cells were cultured on different sizes of nanodot arrays. CA125 staining was used to confirm the MUC16 expression of ovarian cancer cells. We observed the cell viability, adhesion, cytoskeletal organization, and cell area by scanning electron microscopy (SEM) and immunostaining to establish a database for cancer cell behavior. These SEM and immunostaining images result shows that there were different cell responses with different nanodot arrays in each clinical stage. After statistics, serous type of ovarian cancer could diagnose stages used cell viability methods on 50-nm nanodot array and could diagnose grades used cell area and focal adhesions methods on 100-nm and 300-nm nanodot arrays. Clear cell type of ovarian cancer could diagnose stages used cell viability method on 50-nm and 100-nm nanodot arrays and could diagnose grades used cell area and focal adhesions methods on 10-nm and 100-nm nanodot arrays. Above all ovarian cancer could diagnose stages and grades used cell area method on 10-nm and 300-nm nanodot arrays. EMCA could diagnose stages used actin filment method on 300-nm nanodot array and could diagnose grades used cell area, focal adhesions and actin filment methods on 300-nm, 100-nm and 50-nm nanodot arrays. In the prognosis results, we found above 70 % primary cancer cells revealed positive viability expression on poor prognosis patients compared to good prognosis patients. In cell attachment, both vinculin and actin revealed negative expression on poor prognosis patients compared to good prognosis patients. Therefore, we can evaluate clinical stages and prognosis of gynecologic cancer patients by using different nanodot arrays with various cell detections. We expected that the nanodot arrays can be used not only as the clinical stage of a rapid diagnostic platform, but also provide method for assessment of the clinical prognosis of gynecologic cancer patients in vitro.

Objectifs : Évaluer l’incidence de la macrosomie fœtale en fonction des différentes définitions (poids de naissance >4000g, >4500g, ≥90ième percentile de Kramer) en vigueur et comparer la prévalence de la morbidité maternelle et périnatale associée à la macrosomie entre les populations Cris et les populations du Québec. Des courbes postnatales spécifiques aux Cris de l’Est de la Baie-James seront proposées. Devis : Comparaison de deux cohortes prospectives Cris et Québec. La cohorte des populations Cris de l’Est de la Baie-James, comporte 2546 femmes recrutées de 2000-2010, au cours de l’étude sur la macrosomie fœtale chez les Cris de l’Est de la Baie James. La cohorte du Québec est composée de 97475 femmes et provient de l’essai clinique randomisé multicentrique QUARISMA, 2008-2010, cette étude promulguant la réduction du taux d’accouchement par  césarienne. Méthodes : Les risques de macrosomie fœtale et de la morbidité maternelle et périnatale sont évalués par des modèles de régression logistique d’équations d'estimation généralisées (EEG) ajustés et comparés selon l’ethnicité, Cris et Québec. GEE. Le groupe de référence étant les femmes du Québec. Les courbes de croissance spécifiques aux Cris sont construites par régression quantile. Résultats : Plus du tiers, soit 36,76%, des Cris et 9,329% des nouveau-nés du Québec, ont un poids de naissance >4000g. Les résultats attestent montrent que 10,92% des Cris de l’Est de la Baie-James ont un poids de naissance de plus de 4500g, ce taux est de 1,23% au Québec. La définition de la macrosomie fœtale, par un poids néonatal ≥90ième percentile de Kramer, identifie 40,02% des bébés Cris, pour 8,83% des nourrissons du  Québec, comme macrosomes. Les Cris sont plus à risque de macrosomie fœtale, comparativement à la population générale du Québec, ces associations sont statistiquement significatives : RC=5,22; 95% IC (4,66-6,05,98), pour un poids de naissance >4000g, RC=8,10; 95% IC (6,22-10,77), pour un poids de naissance >4500g et RC=6,22; 95% IC (5,77-6,72), pour un poids de naissance ≥90ième percentile de Kramer. Le risque de la morbidité périnatale majeure, de la macrosomie fœtale, est généralement moins important pour les Cris que pour la population générale du Québec : 0,76; 95% IC 0,62-0,94. La macrosomie fœtale devrait être décrite par un poids de naissance≥95ième percentile de Kramer, pour les Cris, mais préférablement au 90ième percentile des courbes postnatales spécifiques aux Cris de l’Est de la Baie-James. Les poids de naissance diagnostique spécifiques aux Cris de l’Est de la Baie-James, au 90ième percentile de la 40ième semaine d’aménorrhée, sont de 4 417g pour les filles et 4 488g pour les garçons. Conclusions : Les courbes de Kramer diagnostiquent systématiquement plus de macrosomes chez les Cris que dans la population du Québec. Par contre, le risque de morbidité périnatale majeure est inférieur pour ces communautés autochtones, aux différents seuils décrivant la macrosomie fœtale, ce qui suggère l’utilisation de courbes spécifiques aux Cris et permettrait de diminuer les interventions obstétricales non nécessaires chez les gros bébés Cris, donc non-macrosomes.
Objective: Assess the impact of fetal macrosomia based on definitions (birth weight> 4000 g,> 4500g, ≥90ième percentile Kramer) currently used in Quebec and compare the prevalence of maternal and perinatal morbidity associated with macrosomia between the Cree populations of Eastern James Bay and the general population of Quebec. Specific postnatal curves for the Cree will be constructed. Design: Comparison of two prospective cohort Cree and Quebec. Cohort of Cree populations of eastern James Bay, has recruited 2546 women from 2000 to 2010, during the study of fetal macrosomia in the Cree of eastern James Bay. Quebec cohort consisted of 97,475 women and comes from the multicenter randomized clinical trial QUARISMA 2008-2010, this study promulgates the reduction of caesarean delivery rate. Methods: The risk of fetal macrosomia, maternal and perinatal morbidity, by ethnicity, Cree and Quebec, are evaluated by generalized estimating equations models (GEE). GEE models were adjusted to control for potentially confounding factors. The reference group is Quebec women. The specific growth curves of the Cree are built by quantile regression. Results: More than a third, 36.8%, of Cree populations of Eastern James Bay and 9.3% of newborns in Quebec have a birth weight> 4000g. For a birth weight> 4500g, the results show that 10.9% of the Cree, have a birth weight of more than 4500g, the rate is 1.2% in Quebec. The definition of fetal macrosomia by neonatal birth weight≥90th percentile of Kramer identifies 40.02% Cree’s for 8.8% of infants of Quebec as macrosomic. The Cree population are more at risk of fetal macrosomia, compared to the general population of Quebec, these associations were statistically significant: OR = 5.2; 95% CI (4.6 to 6.0) for birth weight> 4000g, OR = 8.1; 95% CI (6.2 to 10.7) for birth weight> 4500g and OR = 6.2; 95% CI (5.7 to 6.7) for birth weight percentile ≥90th Kramer. The risk of major perinatal morbidity associated with fetal macrosomia, is generally less important for the Cree than for the general population of Quebec: 0.76; 95% CI 0.62-0.94. Fetal macrosomia should be described by birth weight ≥95th percentile of Kramer, for the Cree, but preferably at the 90th percentile of the specific postnatal curves of Cree populations of Eastern James Bay. The specific Cree birth weight thresholds for diagnosing fetal macrosomia, at the 90th percentile of the 40th week of gestation, are 4 417g for the girls and 4 488g for the boys. Conclusion: Kramer’s curves diagnose systematically too much macrosomic Cree babies compare to the general population of Quebec. Futhermore, the risk of major maternal and perinatal morbidity is lower for these indigenous communities, at the different definitions of fetal macrosomia, suggesting the use of specific curves for the Cree, to reduce obstetrics interventions not required in large, but non macrosomic, Cree babies.