3. Electronic Theses and Dissertations (ETDs) - All submissions
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Item Outcomes of patients with stage IB1 and IB2 Cervical Cancer who have had Wertheim's Hysterectomies with or without adjuvant chemo-radiotherapy as primary treatment at Charlotte Maxeke Johannesburg Academic Hospital(2018) Nascimento-Fonseca, Sandra MarquesBackground Cervical cancer is the 3rd most common female malignancy worldwide. It is classified and managed according to stage as defined by the FIGO Committee on Gynaecology Oncology classification of 2009. Stage specific treatment is tailored according to prognosis and risk of recurrence as determined by tumour type, tumour size, tumour grade, lymph node metastases, lymphovascular space involvement (LVSI), parametrial spread and presence of any other metastatic deposits at presentation. This study only concentrated on patients who presented with Stage IB1 and 1B2 tumours managed by Class III / Meig’s Radical / Wertheim’s hysterectomy and bilateral pelvic lymphadenectomy. Aims Primary Outcome 1. Assess disease free interval and overall survival 2 years post-operatively. Secondary Outcomes 1. Assess adequacy of patient selection 2. Assess risk factors for recurrence 3. Compare recurrence risk of HIV positive patients versus HIV negative patients. 4. Determine surgical and post-surgical complication rate. Materials and Methods This was a retrospective institutional cohort study conducted at the Charlotte Maxeke Johannesburg Academic Hospital. All patients with Stage IB1 or IB2 cervical cancer treated with Wertheim hysterectomies between 2002 and 2012 were included. Surgical records, histology records, further postoperative management records and gynaecological outpatient follow up records were used to collect data for the patients. Histological findings post-operatively determined further management. Surgical margins had to be 10mm clear of tumour with no positive lymph nodes otherwise external beam radiotherapy and brachytherapy or chemo-radiotherapy were recommended in addition to primary surgical management. Results Of the 72 patients initially identified, 69 patients were suitable for study inclusion. The mean age of the study population was 45 years. Study population racial distribution: 68.12% were Black, 26.09% were White, 2.9% were Coloured and 2.9% were Indian. Average parity and gravidity of patients alive at the end of the study was 2.86 and 3.56; while average parity and gravidity of patients deceased at the end of the study was 2.5 and 2.8 respectively. Study population ECOG status: 16% were ECOG 0, 83% were ECOG 1 and 1% were ECOG 2. Overall survival at the end of the study was 86% and patients were disease free postoperatively for an average of 5 years. Thirty three percent of the patients were disease free for more than 5 years. Preoperative clinical staging and postoperative histological staging correlated only in 61% of cases. Correct management by Wertheim’s hysterectomy was rendered to 75% of patients whereas the remainder were incorrectly managed and should have had either a simple hysterectomy with no pelvic lymphadenectomy or radiotherapy only as primary therapy. More advanced stages, tumours ≥ 4cm, adenomatous cell type, > 5mm depth of invasion, >7mm lateral spread, higher number of nodes positive for metastatic disease, surgical margins 10mm, positive lympohovascular space, parametrial and pouch of Douglas (POD) involvement were factors that had a poorer prognosis with regards overall survival, disease-free interval or both. Poorly differentiated tumours were more likely to recur but did not have a poorer prognosis compared with regards to overall survival or disease free interval at 2 or more years compared to well and moderately differentiated tumours. Mortality of HIV reactive patients was 16.7% compared to 12.5% for HIV non-reactive patients. This difference was not statistically significant at the 95% confidence level. HIV status also did not increase risk of recurrence. Lower CD4 counts were shown to have a lower disease-free period and overall survival. Intra-operative surgical complication rate was 6%. Immediate post-operative complication rate was 16%. Of the patients who required DXT or DXT and chemotherapy 33% had side-effects or complications from adjuvant therapy. Patients treated with DXT and chemotherapy had had more side-effects than those treated with DXT only. Conclusion The mean age of the study population was 45 years. This was lower compared to other larger studies possibly due to younger presentation related to HIV disease. HIV positive patients with lower CD4 counts were shown to have poorer prognosis with regards to survival. HIV status was not shown to be a risk factor for recurrence. The overall survival and disease-free period at 5 years was similar to that of other international studies. Only two thirds of the patients were adequately selected for surgery according to the institution’s criteria for a Wertheim’s hysterectomy and therefore it may be necessary to reconsider the pre-operative assessment of these patients. More advanced stages, tumours ≥ 4cm, adenomatous cell type, poor differentiation, > 5mm depth of invasion, >7mm lateral spread, higher number of nodes positive for metastatic disease, surgical margins ≤ 10mm, positive lympohovascular space, parametrial and pouch of Douglas involvement were factors that had a poorer prognosis with regards to recurrence, overall survival and disease-free interval. However, the rates of recurrence were not statistically significant at a 95% confidence level.Item Knowledge of cervical cancer, Human Papilloma Virus (HPV) and HPV vaccination among primary health care workers in the Mamusa and Naledi sub districs(2017) Ajayi, Adekunle OmoniyiIntroduction: Cervical cancer is a very common female cancer; with up to 524,000 cases being diagnosed annually worldwide.1 Human papilloma virus (HPV) has long been established as the causative factor in the development of cervical cancer.2, 3 HPV vaccination has been found to drastically reduce the development of cervical cancer especially if administered to young people before their sexual debut. This study was to assess the knowledge of primary health care workers in the Mamusa and Naledi sub-districts in the North West Province about cervical cancer, HPV and the HPV vaccine. Methods: This was a descriptive cross-sectional study done with 116 primary health care workers using a self-administered questionnaire that was derived from a duet of questionnaires previously used in Poland and Australia. Adequate knowledge of cervical cancer and HPV vaccination meant getting 70% of the questions asked on the subject correctly while a threshold of 80% was used for adequate knowledge of HPV vaccination. All categories of primary health workers were included in the study asides from pharmacists who were excluded. Descriptive statistics, tests of association and logistic regression analysis was used in the study. The survey was done between September to November 2016 following ethics approval from the University of Witwatersrand. Results: 116 participants were involved in this study. The majority were black female professional nurses with diplomas. The mean age of the participants was 36.6 ± 8.7 years. Only 26% of the respondents had adequate knowledge of cervical cancer. 41% of respondents had adequate knowledge of HPV, while 67% of respondents had adequate knowledge about HPV vaccination. In our study, we found a significant association between knowledge of HPV and the health care worker category (p < 0.001). There was a significant association between knowledge of HPV vaccination and the highest educational level that was attained by the respondents (p= 0.010). Conclusion: Primary health care workers form an integral part in the fight against cervical cancer. Significant gaps still exist in the level of knowledge of health care workers, particularly in relation to cervical cancer and HPV. Improved learning and training opportunities for primary health care workers can help correct the knowledge deficitItem Nanovectors for targeted chemotherapy in cervical cancer(2017) Zardad, Az-ZamakhshariyCervical Intraepithelial Neoplasia (CIN) or Human Papilloma Virus (HPV) is known as the precancerous stages of cervical cancer and may be treated with antineoplastic agents Current treatment includes intravenous administration of Gemcitabine and 5-Fluorouracil however, these drugs have an undesirable side effect profile. This may be overcome by local administration of chemotherapeutic drugs to the site of the cancer. The purpose of this study was to design a drug delivery system that can be locally administered to the site of the cervical cancer and possess thermosonic properties. Designs of three Thermosonic Injectable Organogels (TIO’s) were undertaken using ring opening polymerization (open ring reaction) to formulate three different gels to test the response ability of the gels against thermal and ultrasound exposure. The times taken for these gels to form were recorded at below 15 minutes. All three TIO’s responded differently to thermal and ultrasound stimuli. Physical changes in the gels were noted and further studies were undertaken to confirm their responsiveness towards the dual-stimuli. All three TIO’s showed a dense microstructure containing pores catering for the incorporation of drugs or drug-loaded carriers. Rheological studies showed that there was an increase in viscosity of the gels under increasing heat even though the response differed between TIO formulations. The gels were non-cytotoxic at distinct concentrations ranging between 6.1mg/ml-7.8mg/ml. Solid Lipid Nanospheres (SLN’s) were then designed which encapsulated the mode antineoplastic drug 5-Fluorouracil. The SLN’s were spherical in shape and had an acceptable poly dispersion index (PDI) which was below 0.7 after ultrasonication and filtration of prepared samples. The SLN’s were then incorporated by direct additition and dispersion into the TIO formulations before undertaking the open ring reaction to form Thermosonic Injectable Nano-Organogels (TINO’s). The TINO’s were analysed for its swelling and erosive properties. Results showed that the TINO’s posesses both swelling and erosive properties. Furthermore, the TINO’s underwent dissolution studies that involved thermal and thermal with ultrasound stimuli to test the drug release rate and the stimuli responsiveness of the TINO. Results of the SLN’s showed a very slow release rate whether exposed to a single (thermal) or both thermal and ultrasound stimuli, indicating that the addition of ultrasound stimuli did not alter the drug release from the SLN’s. However, the incorporation of the SLN’s into the TIO’s prolonged the release rate. Hence increasing the SLN concentration in the TIO’s reduced the response towards ultrasound stimuli. Therefore lower ratios of SLN:TIO provided superior responsiveness compared to higher concentrations of SLN:TIO. TIO 1 and TINO 2 released drug with thermal stimuli and higher drug release occurred with exposure to both thermal and ultrasound stimuli. These TINO’s in conjunction with ultrasound responsiveness may be used as a potential platform for the delivery of antineoplastics in treating cervical cancer.Item Trends and determinants of the incidence and mortality of cervical cancer in South Africa (1994-2012)(2017) Olorunfemi, GbengaCervical cancer (CC) is the leading cause of female cancer morbidity and mortality in South Africa, despite the introduction of preventive programs. However, there is a paucity of information on current CC rates and trends in South Africa. This study aimed to evaluate the national trends and determinants of CC over a 19 year period (1994-2012). We conducted temporal analyses of age-standardised incidence rates (ASIR) from 1994 to 2009 and age-standardised mortality rates (ASMR) from 2004 to 2012 using data from the National Cancer Registry and Statistics South Africa, respectively. We also evaluated a novel surrogate measure (complement of MR: IR ratio) to calculate five-year relative survival rates of CC (2004-2009). Temporal analyses were stratified by the province of residence, histological type, population- and age-groups, while linear regression models were fitted to determine the average annual percent change (AAPC) of the time trends. Spatial distribution was conducted by utilising the GIS coordinates of SA to map the provincial ASMR. Unconditional logistic regression analyses were carried out for three casecontrol studies using data from the hospital-based Johannesburg Cancer Case-Control Study (JCCCS) (1995-2010), to evaluate the effect of HIV infection; tobacco smoking and alcohol abuse and sexual and reproductive behaviours on the risk CC in Black South Africans. The cases were participants with CC while controls were other female cancer participants that had no known association with CC and its risk factors. There were 75,099 incident cases and 25,101 mortalities from CC in the periods studied with women below 50 years accounting for 43.1% of the cases and 35.7% deaths. The ASIR was 22.1/100,000 in 1994 and 23.3/100,000 in 2009 and there was an average annual decrease in incidence of 0.9% (AAPC=-0.9%, P-value<0.001). The ASMR decreased slightly from 13.9/100,000 in 2004 to 13.1/100,000 in 2012 (AAPC = -0.6%, P-value < 0.001). Based on current trends, the ASIR and ASMR were predicted to increase to 26.3/100,000 and 14.6/100,000 in 2030, respectively. From 2004 to 2012, five provinces had increased mortality rates (AAPC: 1.2 – 8.3, P-value<0.001) while four provinces had decreased mortality rates (AAPC: -16.6 - -1.0, P-value<0.001). In 2012, the ASMR in Black population group was 5.7-fold higher than in the White population group. The highest mortality was recorded in Mpumalanga Province (19.8/100,000) and the least in the Eastern Cape Province (8.9/100,000). From 2000 to 2009, the ASIR of adenocarcinoma of the cervix was relatively low (2.00 to 2.6 per 100,000 women) and stable, while the incidence of squamous cell carcinoma was high (17.0 to19.0 per 100,000 women) and the rate increased by 1.4% annually. The relative survival rates were higher in White and Indians/Asian women (60-80%) than in Blacks and Coloureds (40- 50%). The results of the JCCCS studies showed that the association between CC and HIV infection increased from two-fold (adjusted odds ratio, (adjOR) =1.98; 95% CI: 1.34-2.92) during the pre-anti-retroviral therapy (ART) era (1995-2003) to three-fold (adjOR=2.94 95%CI: 2.26- 3.83) in the ART era (2004-2010). Current tobacco smoking (adjOR=2.1, 95%CI: 1.10-4.01) and snuff use (adjOR=1.3, CI: 1.08-1.61) increased the likelihood of CC among Black women in South Africa. The risk of CC increased with prolonged use of hormonal contraceptives (P-value for trend = 0.003) and high parity (>6) (adjOR=4.5, 95%CI: 2.85- 7.25). The incidence and mortality of CC are probably underestimated due to underreporting of cancer in the country. South Africa had minimal changes in overall CC rates between 1994 and 2012, despite the initiation of a population-based CC screening program in 2000 and the nationwide roll out of ART in 2004. There was a marked disparity in CC rates by population group, age and province. HIV-infected women and those who use tobacco are more likely to develop CC, therefore targeted programs should be introduced to inform women about risk factors for CC. Maternal and child health initiatives should also involve CC control activities since a considerable number of women of the reproductive age (15 – 49 years) were affected.Item Reasons why women present with late stages of cervical cancer at Chris Hani Baragwanath academic hospital(2016-11-04) Mbodi, LangananiBackground and objectives Current estimates of the number of new cases of cervical cancer in South Africa suggest that there are about 5743 new cases and 3027 deaths from the disease per year. It is still unclear or poorly defined why women present late. The purpose of this study was to determine the stages of cervical cancer that women present with at Chris Hani Baragwanath Academic Hospital and to identify factors associated with late presentation. Methods This was a prospective study conducted at all the gynecology units of the O& G department at CHBAH in Soweto, Gauteng Province over 12 months period between January and December 2013. Results A total of 111 women were recruited into the study. Only 104 women were included in the study. Two (2) women withdrew due to personal reasons. Three (3) women were excluded as their fully histology report could not be retrieved. Two (2) women could not continue with the interview due to pain and discomfort. x The mean age of women was 50.2 years (SD±12.30) with an IQR of 40.50-49.50. The mean ages for stage 1 were 42.22 (SD±10.34), 51.00 (SD±12.54) for stage 2, 51.60 (SD±12.34) for stage 3 and 47.10 (SD±13.35) for stage 4 [p-value of 0.16]. The majority of women (67.31%) in our study are from a poor socio-economic environment with a combined family earning of less than three thousands rand. Abnormal vaginal bleeding was the commonest reason for consultation (48.54%). 43 women (41.75%) first discussed the problems with their family members for input and advice before consulting any healthcare facility. Almost 48% of women still do not know about Pap smear. Conclusion Women with late stages of cervical cancer are more likely to be older than 50 years, come from a low socio-economic background and more likely to have not completed high school. There is an increase in incidences of adeno-carcinoma presenting with stages 3 and 4 of the disease. Vaginal bleeding remain the commonest symptom and probably a red flag for cervical cancer in post-menopausal women. However, many women delay seeking healthcare in our public health facility even after identifying the signs and symptoms suggestive of cervical cancer. We speculate discussing with family members and seeking opinion could be the result for delayed consultation. There is a need to continued education on cervical cancer warning signs and screening programs.Item The in vitro effects of HAART on the expression of muci and NFkB1 in a cervical cancer cell line, HCS-2(2015-04-13) Thabethe, Kutlwano RekgopetsweCervical cancer is the third most commonly diagnosed cancer globally and it has also been identified as one of three AIDS defining malignancies. Highly active antiretroviral therapy (HAART) is a combination of three or more antiretroviral drugs which are classified as nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs). HAART has been shown to play a significant role in reducing the incidence of some AIDS defining malignancies, although its effect on cervical cancer is still unclear. It is hypothesized that HAART might reduce cancer risk by interacting with different signalling molecules and pathways that are involved in cancer in order to induce cell death and thus inhibit cell proliferation. The broader aim of this study was to understand the relationship between cervical cancer and HAART. This was achieved by studying the expression of key signalling molecules in cancer; MUC1 and NFkB (P65) and morphological features using scanning electron microscopy following 24 hour treatment of a cervical cancer cell line, HCS-2 with drugs which are commonly used as part of HAART; Emtricitabine (FTC), Tenofovir disoproxil fumarate (TDF), Efavirenz (EFV), Atripla combination (ATP) and Kaletra combination (LPV/r) at their clinical plasma concentrations. Quantitative real time polymerase chain reaction (qPCR) was used in order to study the gene expression of MUC1 and P65 and the data was analysed using the 2-ΔΔCT method to calculate fold change. The statistical analysis was conducted using JMP 11 software. MUC1 and P65 gene expression was reduced following drug treatment. Protein expression was studied by means of Immunofluorescence and MUC1 and P65 protein expression was reduced following drug treatment. Scanning electron microscopy revealed characteristic features of apoptotic cell death such as loss of cell contacts, reduced density and size of microvilli, increase in surface blebbing and budding and degradation of apoptotic bodies following treatment with all the drugs. In conclusion, the drugs used in this study