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Until recently, cancer of the oesophagus was a very uncommon tumour in Australia and other western populations. However during the past three decades, there have been very large increases in the incidence of this disease. Indeed, rates of oesophageal cancer have risen faster than any other cancer in the United Statesand similar dramatic increases in incidence have been observed in Europe and Australia. With increasing population prevalence of the causes of cancer of the oesophagus in western soc ....Until recently, cancer of the oesophagus was a very uncommon tumour in Australia and other western populations. However during the past three decades, there have been very large increases in the incidence of this disease. Indeed, rates of oesophageal cancer have risen faster than any other cancer in the United Statesand similar dramatic increases in incidence have been observed in Europe and Australia. With increasing population prevalence of the causes of cancer of the oesophagus in western societies (namely acid reflux, obesity and poor diet), there are strong grounds for predicting that incidence will continue to rise, and that oesophageal cancer will constitute an increasingly large burden on society. Unfortunately, treatment options are limited, survival is often short, and there is no way of identifying which tumours will respond to therapy. This proposal will collect treatment and health outcomes data for a population-based cohort of patients with oesophageal cancer. The goal is to identify prognostic and predictive markers to aid patients and clinicians when making treatment decisions, as now exist for breast cancer. Such markers may also serve as novel targets for therapy. The proposed study builds upon the platform of the Australian Cancer Study [ACS], one of the world's largest studies of oesophageal cancer. This represents a unique opportunity to investigate a pressing clinical problem by building upon a study of acknowledged international importance.Read moreRead less
Barrett's Oesophagus And Reflux Oesophagitis : Efficacy Of Medical Vs Surgical Management
Funder
National Health and Medical Research Council
Funding Amount
$510,750.00
Summary
Gastro-oesophageal reflux disease is very common. In some people it leads to oesophageal cancer, which is increasing in incidence more rapidly than any other cancer in the developed world. Significant resources are required for its diagnosis, surveillance and treatment. There are two main forms of treatment, acid suppressing drugs which may be required for the rest of the person's life, or surgery. The goal of treatment is the control of the symptoms such as heartburn, and the prevention of canc ....Gastro-oesophageal reflux disease is very common. In some people it leads to oesophageal cancer, which is increasing in incidence more rapidly than any other cancer in the developed world. Significant resources are required for its diagnosis, surveillance and treatment. There are two main forms of treatment, acid suppressing drugs which may be required for the rest of the person's life, or surgery. The goal of treatment is the control of the symptoms such as heartburn, and the prevention of cancer. It is relatively easy to determine if the symptoms are controlled, and both medical and surgical treatments do this. It is not as easy to measure if a treatment will reduce the risk of cancer, because it takes so long to develop. We will compare a group of patients with reflux disease treated with drugs with a group treated by surgery. In each group we will take oesophageal tissue before treatment and compare it with similar tissue taken after treatment. We will look for reductions in abnormal cells and genes that are in diseased tissue and are important in the development of cancer. This study will help us understand the mechanisms by which reflux causes damage to the oesophagus and how it ultimately leads to cancer. We will learn if medical or surgical treatment is better in healing the underlying damage in the oesophagus, and which treatment is more likely to prevent cancer developing. It may result in more effective management of reflux in our community and help reduce the number of cases of oesophageal cancer.Read moreRead less
Barrett's oesophagus (BO) is a condition that arises in some patients with chronic reflux (heartburn) and increases the risk of developing cancer of the oesophagus. However, the exact mechanisms involved in its development are unknown. This project aims to investigate how a protein called sonic hedgehog might be involved using novel cell culturing techniques that allow us to model the growth of oesophageal tissue in the laboratory. This could lead to development of new therapies for treating BO.
Gene Expression And DNA Methylation In Barrett's Oesophagus And Oesophageal Adenocarcinoma
Funder
National Health and Medical Research Council
Funding Amount
$383,655.00
Summary
The oesophagus (gullet) is the tube through which food and drinks pass from the mouth to the stomach. In Barrett's oesophagus, the normal lining of the lower oesophagus is replaced by an abnormal type of lining called intestinal metaplasia as a result of severe gastroesophageal reflux. Gastroesophageal reflux is one of the most common of all diseases, affecting up to a quarter of all adults, and Barrett's oesophagus itself occurs in 0.5 - 1% of the adult population. In a minority of patients wit ....The oesophagus (gullet) is the tube through which food and drinks pass from the mouth to the stomach. In Barrett's oesophagus, the normal lining of the lower oesophagus is replaced by an abnormal type of lining called intestinal metaplasia as a result of severe gastroesophageal reflux. Gastroesophageal reflux is one of the most common of all diseases, affecting up to a quarter of all adults, and Barrett's oesophagus itself occurs in 0.5 - 1% of the adult population. In a minority of patients with Barrett's oesophagus, further abnormalities in the cells lining the lower oesophagus occur, leading to dysplasia and adenocarcinoma (glandular cell type cancer). This project will provide the first comprehensive map of two of the most important genetic mechanisms (gene expression and DNA methylation) by which Barrett's oesophagus evolves into Barrett's dysplasia and adenocarcinoma. The specimens studied in this project differ from previous studies in that they are taken from the same patients at different times, as these patients' Barrett's oesophagus either remains stable or progresses to worse disease. Essentially all the known human genes will be studied and the relevance of genes identified as important will be confirmed using highly accurate methods. With this information, it may be possible to develop genetic tests that can predict which patients are at risk of developing worse disease including cancer. In other parts of this project, genes which influence the likelihood of survival for patients with oesophageal adenocarcinoma will be identified, a simple test to more accurately identify patients with cancer spread to lymph nodes may be developed, and a blood test to detect oesophageal adenocarcinoma will be tested.Read moreRead less
Ablative Therapies For Barrett's Oesophagus - Evaluation Of New Clinical And Experimental Therapies
Funder
National Health and Medical Research Council
Funding Amount
$302,310.00
Summary
Barrett's oesophagus arises when repeated episodes of gastro-oesophageal reflux lead to the oesophageal lining undergoing change to a lining more like that of the intestine. This new lining predisposes to cancer, a problem which is rapidly becoming more common. Recent research has focused on techniques which could reverse this process. Destruction (ablation) of Barrett s oesophagus can be followed by regeneration with a normal looking lining. A range of techniques have been used for this. Howeve ....Barrett's oesophagus arises when repeated episodes of gastro-oesophageal reflux lead to the oesophageal lining undergoing change to a lining more like that of the intestine. This new lining predisposes to cancer, a problem which is rapidly becoming more common. Recent research has focused on techniques which could reverse this process. Destruction (ablation) of Barrett s oesophagus can be followed by regeneration with a normal looking lining. A range of techniques have been used for this. However, the behavior of the regenerated lining is unknown, and there still remains potential for cancer. We are currently evaluating endoscopic ablation using Argon Plasma Coagulation within clinical trials. There is also scope for the development of better approaches to ablation. We hypothesize that an suitable liquid has the potential to more evenly and more easily ablate the lining. Delivery of a liquid substance to lower oesophagus can be achieved through a tube which confines liquid to the lower oesophagus. However, to make this approach acceptable it is necessary to determine the best treatment agent, and to test the delivery system. We will first do this using animal models, before future application in patients. A further key issue is whether the cells which repopulate the oesophagus are genetically normal or abnormal. After ablation it is likely that the cells which repopulate the lining are sourced from the same cells which were the source of the abnormal lining, and these cells could inherit genetic alterations. This could increase the risk of cancer. Hence, we plan to assess certain genes in biopsies taken from tissue before and after ablation to determine genetic normality. In Australia endoscopic ablative techniques are currently being introduced into clinical practice without evaluation. Hence the question of whether ablation actually reduces the risk of cancer and how to best perform ablation should be addressed before clinical application becomes widespread.Read moreRead less
A Trial Of Position Control Therapy For Treatment Of Infantile Gastro-oesophageal Reflux
Funder
National Health and Medical Research Council
Funding Amount
$533,290.00
Summary
Reflux of stomach contents into the gullet and mouth is a very common condition which interrupts feeding and sleep routine in infants. If reflux is not treated, more severe problems may manifest and patients may require anti-reflux surgery. Left-side positioning after feeding is the only non-drug approach proven to reduce the frequency of reflux in infants. This project will determine, by clinical trial, the role for left side positioning for reducing reflux related symptoms in infants.