Cervical cancer is reported to be the first among the five leading cancers affecting women in South Africa and the leading cancer among Black females. There is a high incidence and mortality rate among underserved and under-screened women presenting with cervical cancer as they are often unable to access screening facilities. Very little has been done to establish the factors in private health care provision that influence the implementation of cervical screening programmes. The study investigates factors influencing cervical cancer screening programme implementation among private medical practitioners in Soshanguve to establish whether private practitioners assume their roles in cervical screening. The intention is to provide guidelines for a screening programme that could be implemented in private health facilities. The study is qualitative, explorative, descriptive and contextual, using interviews and observation as the main data-collection methods. Lack of awareness and interest, failure to inform patients about cervical screening, age and gender of medical practitioners were among the factors identified. The study concluded that awareness programmes about cervical screening and materials containing information on cervical cancer and predisposing factors should be designed. The utilization of cheaper laboratory service providers could increase participation by making the test affordable and accessible to cash patients. The establishment of a private Pap clinic within medical practices or even as an independent entity is also recommended. / Health Studies / M.A. (Public Health)

SOCIAL WORK / MA(SS) (SOCIAL WORK)

Text in English / Cervical cancer remains the leading cause of cancer mortality among women worldwide, a burden in the developing countries and commonly detected through symptoms at later invasive stages. The study aimed at establishing knowledge and awareness of the importance of cervical cancer screening in the Makhuduthamaga Sub-district by exploring the perceptions of women and professional nurses and through the review of the National Cervical Cancer Screening Policy (2013). Recommendations to address the gap in knowledge and to inform the National Cervical Cancer Screening Policy were developed based on the study findings. A mixed-method approach was used in this study through a sequential explanatory design, which is quantitatively driven was used. Quantitative data were obtained by using a researcher developed checklist. The checklist was developed from variables stated in the National Cervical Cancer Screening Policy and was used to review its implementation. Qualitative data was obtained through in-depth interviews with individual women and focus group discussions with professional nurses. The study was conducted in ten randomly selected clinics of Makhuduthamaga Sub-district. Purposive sampling was done to obtain qualitative data. An average score of 9.7 was obtained for all ten clinics that participated in the study with regard to the evaluation of the implementation of the National Cervical Cancer Screening Policy. Only 6 (60%) clinics implemented the policy whereas 4 (40%) clinics did not implement the policy. Women and professional nurses perceived cervical cancer screening as important. Lack of knowledge among women regarding cervical cancer screening contributed to the majority of women not screening for cervical cancer. Lack of resources, the 10 year interval of normal cervical cancer screening, the use of disposable vaginal speculums and brushes, lack of standardized cervical cancer screening training, centralization of cytology laboratories came out as factors that negatively influence the uptake of cervical cancer screening. Cervical cancer screening awareness campaigns, availability of resources and standardized in-service trainings on cervical cancer screening were recommended to enhance the cervical cancer screening uptake. Key concepts: / Health Studies / D. Litt. et Phil. (Health Studies)

<div> Advancements in cancer treatments have increased rapidly in recent years, but cures remain elusive. Surgical tumor resection is a central treatment for many solid malignancies. Residual tumor at surgical margins leads to tumor recurrence. Novel tools for assessing residual tumor at surgical margins could improve surgical outcomes by helping to maximize the extent of resection. Ambient ionization-mass spectrometry (MS) methods generate and analyze ions from minimally prepared samples in near-real-time (e.g. seconds to minutes). These methods leverage the high sensitivity and specificity of mass spectrometry for analyzing gas phase ions and generating those ions quickly and with minimal sample preparation. Recent work has shown that differential profiles of ions, corresponding to phospholipids and small metabolites, are detected from cancerous and their respective normal tissue with ambient ionization-MS methods. When properly implemented, ambient ionization-MS could be used to assess for tumor at surgical margins and provide a molecular diagnosis during surgery. </div><div><br></div><div>The research herein reports efforts in developing rapid intraoperative ambient ionization-MS methods for the molecular assessment of cancerous tissues. Touch spray (TS) ionization and desorption electrospray ionization (DESI) were utilized to analyze kidney cancer and brain cancer.</div><div><br></div><div> As a demonstration of the applicability of TS-MS to provide diagnostic information from fresh surgical tissues, TS-MS was used to rapidly analyze renal cell carcinoma and healthy renal tissue biopsies obtained from human subjects undergoing nephrectomy surgery. Differential phospholipid profiles were identified using principal component analysis (PCA), and the significant ions were characterized using multiple stages of mass spectrometry and high resolution/exact mass MS. The same TS-MS analyzed renal tissues were subsequently analyzed with DESI-MS imaging to corroborate the TS-MS results, and the significant DESI-MS ions were also characterized with MS.</div><div><br></div><div>Significant efforts were made in developing and evaluating a standalone intraoperative DESI-MS system for analyzing brain tissue biopsies during brain tumor surgery. The intraoperative DESI-MS system consists of a linear trap quadrupole mass spectrometer placed on a custom-machined cart that contains all hardware for operating the mass spectrometer. This instrument was operated in the neurosurgical suites at Indiana University School of Medicine to rapidly analyze brain tissue biopsies obtained from glioma resection surgeries. A DESI-MS library of normal brain tissue and glioma was used to statistically classify the brain tissue biopsies collected in the operating room. Multivariate statistical methodologies were employed to predict the disease state and tumor cell percentage of the samples. A DESI-MS assay for detecting 2-hydroxyglutarate (2HG), the oncometabolic product of the isocitrate dehydrogenase (IDH) mutation (a key glioma prognostic marker), was developed and applied to determine the IDH mutation status during the surgical resection. The strengths, weaknesses, and areas of future work in this field are discussed. </div><div><br></div>

MCur / Department of Advanced Nursing Science / Historically, cancer is regarded as a disease with very devastating effects on human beings because it leads to many deaths across the world, compared to AIDS, tuberculosis and malaria collectively. Cancer diagnosis has impacted negatively on patients and their immediate families and has caused unbearable consequences. Unlike other chronic diseases, cancer patients undergo different types of treatments which affect their well-being and as a result they tend to have different experiences to those of other chronic diseases sufferers. The study design used was a quantitative cross sectional survey. The purpose was to investigate the impact of cancer diagnosis on cancer patients in Vhembe district. The target population included all patients in the Vhembe District of Limpopo, South Africa who have been diagnosed with cancer in the past six months. Using a probability simple random, a sample of 207 patients diagnosed with cancer, from seven selected hospitals in Vhembe District were selected as respondents and a self -administered questionnaire was used to collect data. Data was analysed using a software package for descriptive statistics (SPSS version 23). Graphs, tables and charts were used to display the results visually and chi-square to compare variables. Ethical principles of privacy, anonymity, informed consent were considered. The findings revealed that cancer diagnosis has negative outcomes as patients experience physical hardship, psychological stress, financial difficulties, as well as interference with family and social life. The study recommended that cancer patients and their families, be supported through the cancer journey. / NRF

<p>My research has focused on the development and translation of ambient ionization mass spectrometry (MS)-based platforms in clinical and surgical settings, specifically in the area of brain cancer diagnostics and surgical decision making. Ambient ionization MS methods, such as those described herein, generate and analyze gas phase ions with high sensitivity and specificity from minimally prepared samples in near-real-time, on the order of seconds to minutes, rendering them well suited to point-of-care applications. We used ambient ionization MS methods, specifically desorption electrospray ionization mass spectrometry (DESI-MS) and extraction nanoelectrospray ionization mass spectrometry (nESI-MS) to molecularly characterize brain cancer biopsies. The characterization was made using diagnostic compounds identified as markers of disease state, tissue composition, tumor type, and genotype in human brain tissue. Methods were developed and validated offline in the laboratory and translated to clinical and surgical settings, thereby generating chemical information on prognostic features intraoperatively and providing valuable information that would be otherwise unavailable. We believe that, with approval, the methodologies described can assist physicians and improve patient outcomes by providing analytical tools and molecular information that can inform surgical decision making and adjuvant treatment strategies, complementing and not interfering with standard of care protocols.</p> <p><br></p> <p>We have successfully demonstrated the use of desorption electrospray ionization mass spectrometry (DESI-MS) for the expedient molecular assessment of human glioma tissue biopsies based on lipid profiles and prognostic metabolites, both at the tumor core and near surgical margins, in two small-scale, clinical studies. Maximal surgical resection of gliomas that avoids non-infiltrated tissue is associated with survival benefit in patients with glioma. The infiltrative nature of gliomas, as well as their morphological and genetic diversity, renders treatment difficult and demands an integrated imaging and diagnostic approach during surgery to guide clinicians in achieving maximal tumor resection. Further, the estimation of tumor cell percentage (TCP), a measure of tumor infiltration at surgical margins, is not routinely assessed intraoperatively. </p> <p>We have previously shown that rapid, offline molecular assessment of tumor infiltration in tissue biopsies is possible and believe that the same assessment performed intraoperatively in biopsied tissue near surgical margins could improve resection and better inform patient management strategies, including postoperative radiotherapy. Using a DESI-MS spectral library of normal brain tissue and glioma biopsies to generate a statistical model to classify brain tissue biopsies intraoperatively, multivariate statistical approaches were used to predict the disease state and tumor cell percentage (TCP) of each biopsy, thereby providing an measure of tumor infiltration at surgical margins via molecular indicators. In addition to assessment of tumor infiltration, we have developed DESI-MS assays for detecting the oncometabolite 2-Hydroxyglutarate (2HG) to detect isocitrate dehydrogenase (IDH) mutations in gliomas intraoperatively. Knowledge of IDH genotypes at the time of surgical resection could improve patient outcomes, as more aggressive tumor resection of IDH-mutated gliomas is associated with increased survival. While assessments of IDH genotype are typically not available until days after surgery, we have demonstrated the ability to provide this information is less than five minutes. An intraoperative DESI-MS system has successfully been used in a proof-of-concept clinical study and intraoperative performance validation of this platform is ongoing. The findings of these two studies as well as strengths, weaknesses, and areas of improvement for upcoming future iterations of the research are discussed.</p> <p><br></p> <p>Point-of-care applications necessitate the adaptation of MS methodologies to smaller devices. Miniature mass spectrometers (Mini MS) boast small footprints, simple operation, and low power consumption, noise levels, and cost, making them attractive candidates for point-of-care use. In a small-scale clinical study, we demonstrated the first application of a Mini MS for determination of IDH mutation status in gliomas intraoperatively. This study paves a path forward for the application of Mini MS in the OR. With its small footprint and low power consumption and noise level, this application of miniature mass spectrometers represents a simple and cost-effective platform for an important intraoperative measurement. </p> <p><br></p> <p>While MS-based methods of tissue analysis can detect molecular features of interest and rapidly produce large quantities of data, their inherent speed is rarely utilized because they are traditionally coupled with time-consuming separation techniques (e.g., chromatography). Ambient ionization MS, specifically DESI-MS, is well suited for high-throughput applications due to its lack of sample preparation and purification techniques. In an attempt to rapidly characterize microarrays of tissue biopsies, we developed a high-throughput DESI-MS (HT-DESI-MS) method for the rapid characterization of disease state, human brain tumor type, glioma classification, and detection of IDH mutations in tissue microarrays (TMA) of banked and fresh human brain tissue biopsies. We anticipate that HT-DESI-MS analysis of TMAs could become a standard tool for the generation of spectral libraries for sample classification, the identification of biomarkers through large-scale studies, the correlation of molecular features with anatomical features when coupled to digital pathology, and the assessment of drug efficacy. </p>

This thesis addresses the three principal questions concerning the development of CT urography for investigating haematuria and each question is the subject of a separate chapter. The questions are: What is the reasoning behind using CT urography? What is the optimum diagnostic strategy using CT urography? What are the problems with using CT urography and how may solutions be provided? Haematuria can signify serious disease such as urinary tract stones, renal cell cancer, upper tract urothelial cancer (UTUC) and bladder cancer (BCa). CT urography is defined as contrast enhanced CT examination of kidneys, ureters and bladder. The technique used here includes unenhanced, nephrographic and excretory-phases for optimized diagnosis of stones, renal masses and urothelial cancer respectively. The reasoning behind using excretory-phase CT urography for investigating haematuria is based on results showing its high diagnostic accuracy for UTUC and BCa. Patients with haematuria are classified as low risk or high risk for UTUC and BCa, by a risk score, determined by the presence/absence of risk factors: age > 50 years, visible or nonvisible haematuria, history of smoking and occupational exposure. The optimum diagnostic strategy for patients at high risk for urothelial cancer, uses CT urography as a replacement test for ultrasonography and intravenous urography and as a triage test for flexible and rigid cystoscopy, resulting in earlier diagnosis and potentially improving prognosis. For patients at low risk, ultrasonography, unenhanced and nephrographic-phase CT urography are proposed as initial imaging tests. Problems with using CT urography include false positive results for UTUC, which are eliminated by retrograde ureteropyelography-guided biopsy, an innovative technique, for histopathological confirmation of diagnosis. Recommendations for the NHS and possible future developments are discussed. CT urography, including excretory-phase imaging, is recommended as the initial diagnostic imaging test before cystoscopy for patients with haematuria at high risk for urothelial cancer.