To determine the spectrum of ocular surface squamous cell neoplasia (OSSN) in young patients presenting at the St John Eye hospital. The objectives were: (1) documentation of the occurrence of OSSN in young patients at St John Eye hospital (2) to determine the possible role of HIV as a risk factor and the correlation of disease severity with CD4 count.

Objective Several studies have shown that serum copper concentrations are higher in various carcinomas when compared to a healthy population; owing to their role as an inflammatory marker. Zinc acts as a cellular growth protector and it has been demonstrated that its deficiency is involved in several stages of malignant cell transformation. However, the usefulness of the serum zinc and copper determinations in cancer prevention, detection, treatment monitoring and prognosis require further investigation. The aim of this study is to demonstrate the diagnostic and prognostic significance of serum zinc levels (SZL) and serum copper levels (SCL), and the copper/zinc (Cu/Zn) ratio, in non-small cell lung cancer (NSCLC). Materials and Methods Thirty-four patients with NSCLC were prospectively identified, prior to treatment, over a period of one calendar year (February 2003 - January 2004) at the Department of Radiation Oncology, Johannesburg General Hospital (now Charlotte Maxeke Johannesburg Academic Hospital) and the University of the Witwatersrand. SCL and SZL were measured using atomic absorption spectroscopy (AAS) and the Cu/Zn ratio was calculated. Results SCL shows an increase (mean SCL were 0.66mg/L, 0.74mg/L and 0.76mg/L for stage II, III and IV respectively) (P=0.0897); and SZL shows a decrease (0.70mg/L,0.63mg/L and 0.62mg/L for stage II, III and IV respectively) (P=0.199) with advancing stage. The levels of both these trace elements are much lower than the reference range for a normal population. The Cu/Zn ratio increases with stage (0.995, 1.308 and 1.441 for stage II, III and IV respectively). The results were not statistically significant, but a definite trend could be observed. In addition, marked differences were noted between early stages (II) and advanced stages (III and IV) of the disease. Conclusion The lower levels of both trace elements, when compared to a reference range, are an indication of the low levels of immunity and poor general condition of patients with NSCLC (with particular reference to the author‟s institution). A clear trend could be demonstrated of increasing SCLs and decreasing SZLs with progressive stages in NSCLC. The Cu/Zn ratio also reflects similar findings in relation to stages of the disease. The results were not statistically significant, although this can be attributed to a small sample size. While trace element levels and the Cu/Zn ratio cannot be advocated as a tumour marker and prognostic variable for NSCLC at present, they do merit further study, especially in a resource constrained environment, as a simple and inexpensive diagnostic and prognostic test.

A thesis submitted to the Faculty of Medicine, University of the Witwatersrand, for the degree of Doctor of Philosophy in Medicine. / Adenocarcinoma of tbe prostate is the commonest cancer of the western male. Each year more than 120 000 new cases are reported in the United States alone, together with more than 26 000 deaths. Autopsy studies suggest that the majority of prostatic cancer remains clinically undetected, therefore propagating the concept of latent versus aggressive disease. [Abbreviated Abstract. Open document to view full version] / AC2017

Identification of mutations in the mismatch repair genes of hereditary non-polyposis colorectal cancer (HNPCC) families can lead to improved management and screening of affected family members. This study aimed to characterise the mutation profile of MLH1 and MSH2 in a South African colorectal cancer cohort. Twenty patient samples were screened for mutations in MLH1 and MSH2 using Sanger sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA). Three previously reported pathogenic mutations were found using Sanger sequencing, two in MLH1 (c.454-13A>G and c.731_734delGTTA) and one in MSH2 (c.2006-6T>C). Six novel variants were detected using Sanger sequencing, two in MLH1 and four in MSH2. Further investigation of the novel variants strongly suggests that one variant in MLH1 (c.885-1G>A) is pathogenic and two have an unknown contribution towards disease. Molecular diagnostic screening of mutations in MLH1 and MSH2 has the potential to improve surveillance and management of HNPCC in South Africa.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirement for the degree of Masters of Medicine in the branch of Radiation Oncology Johannesburg 2015 / Radiation therapy is a highly effective method of treating oropharyngeal carcinoma, either as a single modality treatment with concurrent chemotherapy or as an adjuvant treatment after surgical resection. There exists an association with human papillomavirus (HPV) and oropharyngeal cancer, dividing oropharyngeal carcinoma into HPV positive oropharyngeal carcinoma and HPV negative oropharyngeal carcinoma. Overall survival has been analysed in these two groups and have been shown to be 80-95% for HPV positive oropharyngeal carcinomas and 57-62% in HPV negative subgroup at 3 years respectively. This retrospective review was intended to analyse patient response to treatment, overall survival, local disease free survival and the difference between HPV positive oropharyngeal carcinoma and HPV negative oropharyngeal carcinoma at Charlotte Maxeke Johannesburg Academic Hospital: Department of Radiation Oncology. Patients and methods A retrospective descriptive study was conducted on patients having received radical radiation therapy, with or without chemotherapy, from January 2009 to December 2012 with a histologically confirmed diagnosis of squamous cell carcinoma involving oropharyngeal sites only. The information obtained from records of forty-eight patients was captured on the prescribed data sheets designed for this study. Results Forty-eight eligible patients were accrued within this retrospective study. The median age of the patient group was 56 years (range 32-78) and comprised of 10 females and 38 males. The performance status was mainly Eastern Cooperative Oncology Group (ECOG) 1 (83%). The radiation therapy dose was within the range 60-70Gy, with majority patients completing 70 Gy (65%). Concurrent chemoradiation was given in 59% of patient group (28 patients). The most common site being the base of tongue (60%), followed by tonsil (36%), soft palate (2%) and posterior pharyngeal wall (2%). Eighty five percent of patients were stage IV oropharyngeal carcinoma. Only 6% of patients were tested for HPV-DNA PCR, and all were HPV positive. A total of 79% patients had a positive smoking history and 50% consumed alcohol regularly. Fifty six percent of patients tested negative for HIV, 14.6% tested positive for HIV and 29.3% had unknown HIV status. At the time of the analyses (March 2014) only 7 (15%) of patients were alive. The 2 year overall survival was 13%, the local disease free survival at 2 years was 59%. None of the prognostic factors were predictive of overall survival using univariate and multivariate analysis. Conclusion Majority of patients present in stage IV lesions with commonest sites of involvement being Base of Tongue. The local disease free survival of 2 years was 59% and the overall survival of 15%. There was no impact of prognostic factors studied on overall survival.

Introduction: Ameloblastomas are locally aggressive with a high recurrence rate, warranting continuity jaw resection. The preservation of the inferior alveolar nerve during ablative surgery in the treatment of ameloblastoma is contentious. Studies have suggested salvaging the nerve by pulling it out of the tumour prior to resection. There are presently no studies that have explored the surgical merit of nerve preservation in the treatment of ameloblastomas. Aim: To determine the histological association of mandibular solid and multicystic ameloblastoma to the inferior alveolar nerve, in situ and in separately removed segments of the nerve in order to determine the feasibility of preserving the nerve during ablative surgery for mandibular ameloblastomas. Materials and Methods: 13 resected hemimandibulectomy specimens were histologically examined with respect to the course and association of the inferior alveolar canal/nerve and the ameloblastoma. In group 1 (8 patients) this association was examined with the nerve within the mandibular segment following resection whilst in group 2 (5 patients) the nerve was explanted from the resected tumour and examined separately. In group 1 the closest histologic distance between tumour cells and the inferior alveolar canal was measured. Results: Perineural and intraneural ameloblastoma involvement of the inferior alveolar nerve was confirmed in 62.5% and 40% of cases in groups 1 and 2 respectively. Tumour cells were noted abutting directly onto the nerve in Group 1. Tumour cells were removed together with the pulled out nerve in Group 2. There was no correlation between the histological variants of ameloblastoma and the presence of tumour either in situ or within the pulled-out nerve bundle. Conclusion: Both peri- and intraneural involvement of the inferior alveolar nerve was histologically confirmed in solid and multicystic hemimandibular specimens both in situ within the tumour as well as in separately removed segments of the nerve. Preservation of the inferior alveolar nerve during ablative surgery for mandibular ameloblastomas cannot be advocated.

Epithelial cancers such as colorectal cancers are highly predominant in the Southern African population, and are attributable to a number of factors, including genomic instability due to histone modifications and aberrant DNA methylation of gene promoters, as well as the inactivation of tumour-suppressor genes or the activation of oncogene pathways. The Wnt/β-catenin pathway plays a vital role in the regulation of intestinal epithelial cells, and is aberrantly activated in colon neoplasms. Krüppel-like factor 4 (KLF4) is a tumour suppressor gene that is hypermethylated at its promoter region and therefore down-regulated in colon cancer cells. This zinc finger transcription factor is crucial in colon cancer cells, where its induction has been proposed to regulate tumourigenesis. Over recent years, epigenetic modulators such as histone deacetylase (HDAC) inhibitors and DNA methyltransferase (DNMT) inhibitors have been investigated with regards to their potential anticancer activities. The following study assessed the in vitro effects of the HDAC inhibitor Valproic acid and DNMT inhibitor Zebularine on the expression of KLF4 in early (SW480) and late stage (DLD-1) colon cancer, and breast (MCF-7) cancer cells. At the onset, bioinformatics tools were utilised to predict and assess the methylation status and to examine methylation patterns within the KLF4 and CTNNB1 (β-catenin) genes. In association with this, methylated DNA within early and late stage colon cancer cells was quantified. Here, the 5’ untranslated region of KLF4 was highly methylated, while CTNNB1 displayed a low frequency of methylation. Following drug treatments, with Valproic acid and Zebularine respectively, gene expression profiles showed that high dosages increased the expression of KLF4 relative to low doses in early stage cancer cells; however the greatest induction of KLF4 was observed in late stage cancer cells in response to a high dose combination treatment with Valproic acid and Zebularine. CTNNB1 was antagonistically regulated relative to KLF4, wherein its expression was down-regulated post-treatment. Breast cancer cells surprisingly exhibited opposing results, with both KLF4 and CTNNB1 being up-regulated following high dose treatments, and the low dose treatments displaying the greatest anti-tumourigenic activities. Confocal microscopy results illustrated that KLF4 was localised in the nucleus and nuclear periphery, where it could associate directly with β-catenin. Thus in response to epigenetic therapy, KLF4 was differentially expressed in early and late stage colon cancer cells as a tumour suppressor. The down-regulation of β-catenin in colon cancer cells resulted in the suppression of the Wnt signalling pathway, thereby exerting anti-tumourigenic and anti-proliferative properties on the cells. Therefore, this study concludes that Valproic acid and Zebularine may serve as potential anti-cancer agents in the pursuit of an epigeneic therapy for colorectal cancer.

by Lesley Walton. / Thesis (M.Ph.)--Chinese University of Hong Kong, 1988. / Bibliography: leaves 105-131.

Thesis (General Surgery)) -- University of Limpopo, 2012.

Thesis (Ph. D.)--University of Washington, 2002. / Vita. Includes bibliographical references (leaves 165-186).