Browsing by Subject "Oesophageal cancer"

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    Open Access
    Dysphagia progression-free survival in patients with locally advanced and metastatic oesophageal cancer receiving palliative radiation therapy
    (2020) Bhim, Nazreen; Robertson, Barbara
    Purpose: In patients with advanced oesophageal carcinoma palliation of dysphagia is important to maintaining a reasonable quality of life. The primary aim of this study was to determine the dysphagia progression-free survival (DPFS) in patients with advanced oesophageal carcinoma treated with palliative radiotherapy (RT). Methods: The medical records of all patients with oesophageal carcinoma presenting to Groote Schuur Hospital, Cape Town between January 2015-December 2016 were reviewed and patients who were not candidates for curative treatment and received palliative RT were selected. For these patients, the dysphagia score (DS) was recorded prior to RT, 6 weeks after RT and at each follow-up visit. The DPFS was calculated as the time from completion of RT to worsening in DS by ≥1 point or until death. Other outcomes measured were objective change in DS and survival post RT. Results: The study population comprised 84 patients. Squamous cell cancer was the primary histological subtype (93%). The median duration of DPFS after RT was 73 days, with approximately two-thirds of patients remaining able to swallow at least liquids and soft diet until death. The difference in median duration of DPFS was not statistically significant in stented versus non-stented patients (54 days vs 83 days; p =0.224). The mean change in DS was 0.45 ± 0.89 points following RT and the post RT survival was significantly shorter in patients with stent insertion (81 days vs 123 days; p=0.042). Conclusion: Palliative RT can be used successfully to prolong DPFS in patients with locally advanced and metastatic squamous cell cancer of the oesophagus.
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    Open Access
    NAT1 and NAT2 genetic polymorphisms and environmental exposure as risk factors for oesophageal squamous cell carcinoma: a case-control study
    (2015-03-18) Matejcic, Marco; Vogelsang, Matjaz; Wang, Yabing; Parker, Iqbal M
    Abstract Background Tobacco smoking and red meat consumption are some of the known risk factors associated with the development of oesophageal cancer. N-acetytransferases (NAT1 and NAT2) play a key role in metabolism of carcinogenic arylamines present in tobacco smoke and overcooked red meat. We hypothesized that NAT1 and NAT2 genetic polymorphisms may influence the risk of oesophageal cancer upon exposure to environmental carcinogens. Methods Single nucleotide polymorphisms (SNPs) in the NAT1 and NAT2 genes were investigated by genotyping 732 cases and 768 healthy individuals from two South African populations to deduce the acetylator phenotype (slow, intermediate or rapid) from the combination of the genotyped SNPs. Results The 341 CC genotype (rs1801280) was significantly associated with a reduced risk for oesophageal cancer in the Mixed Ancestry population (OR = 0.31; 95% CI 0.11-0.87). The NAT2 slow/intermediate acetylator status significantly increased the risk among cigarette smokers in the Black population (OR = 2.76; 95% CI 1.69-4.52), as well as among alcohol drinkers in the Mixed Ancestry population (OR = 2.77; 95% CI 1.38-5.58). Similarly, the NAT1 slow/intermediate acetylator status was a risk factor for tobacco smokers in the Black population (OR = 3.41; 95% CI 1.95-5.96) and for alcohol drinkers in the Mixed Ancestry population (OR = 3.41; 95% CI 1.70-6.81). In a case-only analysis, frequent red meat consumption was associated with a significantly increased cancer risk for NAT2 slow/intermediate acetylators in the Mixed Ancestry population (OR = 3.55; 95% CI 1.29-9.82; P = 0.019), whereas daily white meat intake was associated with an increased risk among NAT1 slow/intermediate acetylators in the Black population (OR = 1.82; 95% CI 1.09-3.04; P = 0.023). Conclusions Our findings indicate that N-acetylation polymorphisms may modify the association between environmental risk factors and oesophageal cancer risk and that N-acetyltransferases may play a key role in detoxification of carcinogens. Prevention strategies in lifestyle and dietary habits may reduce the incidence of oesophageal cancer in high-risk populations.
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    The role of inflammation in HPV infection of the Oesophagus
    (BioMed Central Ltd, 2013) Schäfer, Georgia; Kabanda, Siti; van Rooyen, Beverly; Marusic, Martina Bergant; Banks, Lawrence; Parker, M Iqbal
    BACKGROUND: Several human cancers are known to be associated with inflammation and/or viral infections. However, the influence of tumour-related inflammation on viral uptake is largely unknown. In this study we used oesophageal squamous cell carcinoma (OSCC) as a model system since this type of cancer is associated with chronic irritation, inflammation and viral infections. Although still debated, the most important viral infection seems to be with Human Papillomavirus (HPV). The present study focused on a possible correlation between inflammation, OSCC development and the influence of HPV infection. METHODS: A total of 114 OSCC biopsies and corresponding normal tissue were collected at Groote Schuur Hospital and Tygerberg Hospital, Cape Town (South Africa), that were subjected to RNA and DNA isolation. RNA samples were analysed by quantitative Light Cycler RT-PCR for the expression of selected genes involved in inflammation and infection, while conventional PCR was performed on the DNA samples to assess the presence of integrated viral DNA. Further, an in vitro infection assay using HPV pseudovirions was established to study the influence of inflammation on viral infectivity using selected cell lines. RESULTS: HPV DNA was found in about 9% of OSCC patients, comprising predominantly the oncogenic type HPV18. The inflammatory markers IL6 and IL8 as well as the potential HPV receptor ITGA6 were significantly elevated while IL12A was downregulated in the tumour tissues. However, none of these genes were expressed in a virus-dependent manner. When inflammation was mimicked with various inflammatory stimulants such as benzo-alpha-pyrene, lipopolysaccharide and peptidoglycan in oesophageal epithelial cell lines in vitro, HPV18 pseudovirion uptake was enhanced only in the benzo-alpha-pyrene treated cells. Interestingly, HPV pseudovirion infectivity was independent of the presence of the ITGA6 receptor on the surface of the tested cells. CONCLUSION: This study showed that although the carcinogen benzo-alpha-pyrene facilitated HPV pseudovirion uptake into cells in culture, HPV infectivity was independent of inflammation and seems to play only a minor role in oesophageal cancer.