This is a UK-wide registry of all patients being treated with HALO radiofrequency ablation (RFA) for dysplasia (pre-cancerous changes) and early cancer in Barrett’s oesophagus. HALO RFA is a safe and effective minimally-invasive therapy for patients with HGD in Barrett’s oesophagus. It can be delivered through an endoscope, removing the need for surgery or general anaesthetic. It has recently been recommended by NICE. UCL Hospitals runs this registry for the whole country, and over 200 patients have already been recruited nationwide. We will shortly be publishing the results of this study, although interim results are very favourable, showing a high success rate.
2) Pro-BOOST – prospective randomised controlled trial of Barrett’s Oesophagus surveillance using high definition white light endoscopy, with and without enhanced Optical imaging and Spectroscopy to Target high risk lesions.
This study tests ground-breaking endoscopic imaging technology coupled with our very own optical biopsies to help accurately diagnose lesions in patients with Barrett’s oesophagus. The aim is to reduce the number of routine biopsies we take during surveillance endoscopy. It will also pave the way for targeting endoscopic therapy, based on the combined power of endoscopic high definition technology and optical measurements.
This is a nationwide randomised controlled trial, which means that all participants will be randomly allocated into one of two groups. It aims to recruit over 3000 patients in the UK. The study will examine the important question of how best to monitor Barrett’s patients using endoscopic surveillance.
Most patients currently undergo surveillance endoscopy every two years. For the majority no abnormality is ever found, but the endoscopy may cause the patient discomfort. Therefore, it may be better to do endoscopies only when patients feel that they need one, such as if they develop new symptoms. This study aims to address the uncertainty by dividing patients into 2 groups. One group will continue to have two-yearly surveillance, and the other will undergo endoscopy at the patient’s request only. All patients will be followed up for 10 years, which is necessary before we can decide if any one practice is favourable. UCL Hospitals has recruited more patients to this important trial than almost any other hospital in the UK.
4) BEST2 - Evaluation of a Non-Endoscopic Immunocytological Device (Cytopill) for Barrett’s Oesophagus Screening via a Case-Control Study.
Our colleagues in Cambridge have developed a screening test for Barrett's oesophagus. This involves participants swallowing a capsule on a string just before they have an endoscopy. Inside the capsule is a little sponge which pops out when the capsule reaches the stomach. The sponge is then removed through the mouth. It is covered with cells from the lining of the oesophagus, which can then be tested. The procedure is simple and painless. Eventually, we hope to use this to screen the entire British population for risk of developing oesophageal (gullet) cancer. For now, we are developing this device so that it will be able to accurately categorise cancer risk for individual patients. To do this we will use different molecular tests applied to cells collected by the sponge device. The study is a ‘case-control’ study design in which the cases will be patients with known Barrett’s oesophagus, and controls will be individuals with reflux or indigestion (dyspepsia) symptoms referred for endoscopy. Four centres with expertise in Barrett’s oesophagus will recruit patients. These include UCL Hospitals, Cambridge, Nottingham and Newcastle.
5) Metabonomics – assessing exhaled breath to detect dysplasia in Barrett’s oesophagus. Study in collaboration with Imperial College London.
The air that we exhale (breathe out) is different to the air we breathe in. Exhaled air has lots of waste products, including carbon dioxide and many other gases. We already know that when people develop diseases, the nature of these gases changes subtly. We are exploring whether we can detect the minute differences in exhaled gases from patients with Barrett’s oesophagus, dysplasia (pre-cancerous changes) and oesophageal cancer. This study currently has no funding, however, and we do not know how long we will be able to continue running it. Despite this, our initial results from the first 50 patients are remarkably encouraging, and we believe it may hold a key to future population screening.
6) BEGS - The Barrett’s Oesophagus Gene Study. Study in collaboration with Cambridge University.
There is increasing evidence that there may be an underlying genetic predisposition to Barrett’s oesophagus. Genetic studies are usually difficult to conduct because they depend on identifying a large number of affected individuals. This UK-wide study provides a unique opportunity to identify genes which make people more likely to develop Barrett’s oesophagus. If the research is successful, we may be able to detect people at risk with a simple blood test.
The study will also investigate the presence of heartburn and Barrett’s oesophagus in relatives of Barrett’s oesophagus patients in the UK. In addition, this study will examine how genes and environment interact to affect patient outcomes. If you sign up, we may also ask to contact your relatives to invite them to take part as well. We are delighted that we have already enrolled over 150 patients to this study.
Many patients who develop Barrett’s oesophagus do not go on to develop oesophageal cancer. What is special about those who do? Can we detect who is at high risk? Just like the BEGS study, the SOCS study is looking at the genetic make up of patients with these diseases. The aim is to enroll thousands of cancer patients from around the UK. This study is also coordinated from Cambridge, and we are proud to be actively recruiting patients at UCL Hospitals to participate in the study.
8) Barrett's oesophagus in obese, normal weight-obese and normal weight patients
One of the factors which sometimes causes patients to develop Barrett’s oesophagus is obesity. This study is trying to understand the nature of the relationship between weight and Barrett’s oesophagus, and is being carried out exclusively at UCL Hospitals. We are weighing and measuring people who come for endoscopy, and measuring various hormones which predispose to obesity. We hope to see whether patients with Barrett’s oesophagus have different levels of these hormones compared to patients who do not have the condition.
This is a new approach to detecting the future risk of cancer in Barrett’s oesophagus. We are collaborating with colleagues in Oslo, Norway to analyse tissue from patients with Barrett’s to identify certain unique features that may be indicative of future cancer risk. These experiments involve a technique referred to as nuclear textural analysis, which describes the chromatin/DNA distribution pattern of nuclei. This technique has potential as a novel measure of chromosomal instability, an important variable in Barrett’s patients.
2) Understanding the Physical Parameters Measured by Elastic Scattering Spectroscopy (ESS)
When white light is used to illuminate tissue, the reflected light carries with it information about the microscopic structure of the tissue. This procedure is called ESS. This information may be used to assess the likelihood of cancer developing or, in fact, whether cancer has already developed. Unfortunately, it is difficult to decode information from the reflected light due to the complex structure of tissue and the way that light interacts with it. We are, however, developing detailed models of the physical process by which light is reflected by tissue, which will improve our ability to analyse the data obtained from the reflections.
3) Mid Infra-red spectroscopy of Barrett’s Biopsies
This is an exciting and new area of research. We have started early experiments using the unique characteristics of mid infra-red spectroscopy and using Barrett’s oesophagus tissue to analyse unique characteristics that would help differentiate them from normal tissue. We hope to show that we can accurately detect not only Barrett’s oesophagus tissue but high grade dysplasia, using the specific mid infra-red spectral signatures of each tissue type.
4) Novel Biomarkers of Future Cancer Risk in Barrett’s Oesophagus
It has already been shown that when cells start to display abnormal histological characteristics and dysplasia, there is a direct correlation with the amount of DNA content within them. This abnormal DNA content, called aneuploidy, can identify those at risk of progression to cancer. We have state-of-the-art equipment that can easily detect this change, and we have been using it for years to establish which patients are most at risk, and tailoring their surveillance and therapy accordingly. We are using this established tool to study new biomarkers which will help us strengthen the test by which we can identify those at risk.
5) Cell cycle markers to predict future cancer risk in patients with Barrett’s Oesophagus
The development of dysplasia, neoplasia and malignancy in patients such as those with Barrett’s oesophagus is thought to be associated with defects in the genes that control the cell cycle, and ultimately proliferation and death. There are specific identified molecules that regulate the cell’s progression through the cell cycle, and abnormalities in these have been shown to be associated with dysplasia and cancer in Barrett’s oesophagus. We have undertaken experiments identifying a selection of these cell cycle markers, and are currently in the process of conducting a larger series of experiments with colleagues at Leica Microsystems to confirm that there is a potential association. This could provide a new and easy to use tool for not only detecting areas of dysplasia, but also contributing to existing biomarkers to help strengthen the way in which we can predict cancer risk in patients.
