Barrett’s Oesophagus is named after a famous British surgeon, Norman Barrett. It describes a condition associated with Reflux Disease in which the normal cells lining the bottom of the oesophagus are replaced by abnormal cells. In turn, these ‘abnormal’ cells are associated with an increased risk of developing oesophageal cancer.
The precise number of people in the general population with Barrett’s isn’t known. However, 20-30% of the adult population have reflux disease (GORD) and of these 5-10% will have Barrett’s. Of all those people referred for an endoscopy by their GP studies suggest that as many as 1 in 5 will be diagnosed with Barrett’s.
Naturally, these are concerning figures and the risk means that it is of paramount importance that those who have suffered with reflux symptoms over a long period of time undergo a gastroscopy to observe any cell damage this may have done.
To explain Barrett’s Oesophagus requires that we get rather technical, hence this being a long and detailed page. It is such an important subject, and of concern to so many people we meet in clinic, that we have decided to provide a very comprehensive guide. We’ve tried to write it in such a way that it is easy to follow but if you have any questions, please call or email us and we will reply to you personally.
When we swallow food and liquid it passes from the throat into the oesophagus. This is essentially a muscular tube which passes through the chest cavity behind the heart and then empties into the stomach where the digestive process starts. The gut is lined by cells a little bit like the wallpaper lines the walls of a room. This is called the “mucosa”. Since different parts of the gut perform different functions these cells vary along its length to reflect these functions. In the oesophagus these cells merely protect the underlying muscle layer and are flat, pale and orientated in layers, very much like those in the skin. This is called stratified epithelium. However, the stomach has many other functions including secreting mucous, acid and enzymes and here the cells are quite different, being more square, red in colour and organised as “columns”. This is called columnar epithelium.
In Barrett’s, the cells at the bottom of the oesophagus change from the stratified type to resemble columnar epithelium. The appearance therefore changes from a pale colour to red “salmon pink” and is sometimes called “columnar-lined oesophagus”.
Barrett’s is also known as “columnar metaplasia”. Metaplasia is a condition in which one adult cell replaces another. In Barrett’s columnar cells replace stratified cells, hence columnar metaplasia.
Strictly speaking Barrett’s is divided into “long segment” and “short segment” disease. If the abnormal cells extend no more than 3cm from the top of the stomach this is defined as short segment and if 3cm or more, long segment. This distinction helps doctors stratify risk as the longer the segment of Barrett’s the more abnormal cells it will contain and the more likely it may progress to cancer. Short segment is about three times as common as long segment Barrett’s.
The “salmon” coloured Barrett’s columnar cells can be seen creeping up the oesophagus and replacing the paler normal oesophageal cells. A slightly different pattern of tiny blood vessels under the surface can be discerned.
Barrett’s is caused by the repeated inflammation of the oesophagus that arises from reflux disease (GORD).
Normally the valve mechanism at the bottom of the oesophagus, known as the lower oesophageal sphincter (LOS), prevents excessive reflux of acid and other stomach contents into the oesophagus. When this valve fails the cells lining the bottom of the oesophagus are exposed to hydrochloric acid, pepsin, bile salts and other substances that are usually kept within the stomach. This can cause inflammation and in response to repeated episodes of inflammation the cells change (undergoing metaplasia) from stratified to columnar epithelium.
Both GORD and Barrett’s can run in families but there is currently no specific genetic test that can predict outcome.
Barrett’s is also associated with obesity, especially in middle aged men, and smoking.
Its worth noting that some patients who develop Barrett’s often do not suffer typical reflux symptoms and so are only diagnosed with Barrett’s when they start to experience symptoms from other conditions including oesophageal cancer.
Its also worth noting that very often symptoms of reflux actually improve as Barrett’s develops. This does not indicate that reflux has resolved or that there is no longer inflammation occurring but probably reflects a change in nervous perception of the symptoms caused by reflux.
Once patients are given the diagnosis of Barrett’s its quite usual that they become very concerned. This is because Barrett’s can be a pre-malignant condition. The most common type of oesophageal cancer in the UK and Europe occurs at the junction of the stomach and oesophagus and is associated with Barrett’s. Known as adenocarcinoma, this type of cancer has been one of the fastest growing malignancies in terms of numbers of people diagnosed for over 30 years. However, it’s important to remember that while Barrett’s is common oesophageal cancer is rare and most people with Barrett’s will not develop cancer.
There are many confusing terms associated with Barrett’s and its stepwise development to cancer. Barrett’s itself is otherwise known as “columnar metaplasia” because the normal cells lining the bottom of the oesophagus have changed, or undergone metaplasia” from stratified to columnar epithelium. This lining is also known as the mucosa. In response to repeated inflammation these cells can then change further, a process called “dysplasia” which describes the development of abnormal tissue. In fact, dysplasia is further divided according to severity into “low grade” and “high grade”. This signifies a significant increase in risk of the cells progressing to the final step on the path to the development of cancer (carcinoma), “neoplasia”, or new tissue. Again, there are effectively two stages in the development of carcinoma. In the first the cancerous cells are confined to the mucosa. This is called intra-mucosal (or sometimes intra-epithelial) carcinoma. The final step in the development of cancer is when the cells spread through the other layers of the wall of the oesophagus and has therefore become invasive carcinoma.
So, Barrett’s is a pre-malignant condition and it undoubtedly confers an increased risk of developing adenocarcinoma of the oesophagus. The size of this risk remains in dispute but is probably between 30 and 125 times the normal population. Nonetheless, cancer of the oesophagus remains relatively uncommon and so most people diagnosed with Barrett’s will not progress to develop cancer. The size of the risk varies to some extent but overall it is about 0.5% per year and only one in twenty people with Barrett’s will develop cancer. Once dysplasia develops however the risk per year increases significantly. The risk of high grade dysplasia progressing to cancer is at least 10% per year.
How is Barrett’s diagnosed?
Barrett’s itself does not cause any specific symptoms. However, since it is caused by gastro-oesophageal reflux disease (GORD) it is usually diagnosed when patients undergo a gastroscopy (upper gastrointestinal endoscopy) as part of a series of tests into reflux type symptoms. The diagnosis is then made by the operator who will identify the characteristic appearance of dark “salmon red” columnar cells extending into the oesophagus above the stomach.
Having identified the appearances of Barrett’s biopsies will then be taken. These are tiny samples of tissue. Depending on the length of the segment multiple biopsies may be taken and these are then sent to the laboratory for analysis during which a pathologist will examine the tissue under a microscope. They will then be able to describe the typical abnormalities seen with Barrett’s and will also look for evidence of dysplasia or even cancer.
This is a new technique which is still undergoing evaluation. A small capsule is swallowed which then expands into a sponge within about 5 minutes. This is attached to a string which is used by a nurse to withdraw the sponge through the oesophagus. During this process it collects cells lining the surface of the oesophagus. These are then tested for a specific protein (TFF3) which is expressed only by Barrett’s. If positive other tests can potentially be performed to look for genetic markers of dysplasia. RefluxUK is the first private clinic in the UK to offer Cytosponge. You can read more about it here.
Should I have an endoscopy to check if I have Barrett's?
This is called “screening” and there is no evidence that this is justifiable in the general population. However, in patients with reflux symptoms and specific risk factors for the development of oesophageal cancer your specialist may offer an endoscopy.
If I have Barrett’s should I have a regular endoscopy?
Barrett’s is a pre-malignant condition and in a small number of patients will develop into cancer. This is the last stage in a progression through several stages during which the damage to the DNA in the cells at the bottom of the oesophagus gradually becomes more and more severe. Having been diagnosed with Barrett’s there is therefore an argument in favour of performing regular “surveillance” endoscopy with further biopsies to check for progression. There is evidence that this can identify changes at an early stage and improve survival.
However, exactly how often endoscopy should be performed will be dependent on several factors including the length of Barrett’s segment and the findings at previous endoscopy. Usually the interval between endoscopies will be 2-5 years but in some specific cases, for instance when dysplasia is identified, more frequently. You will need to discuss this with the specialist looking after you.
How is Barrett’s treated?
Unless dysplasia or cancer develops current evidence suggests that intervention is not indicated. In other words, the risks of removal of the Barrett’s cells are greater than the likely benefit and should therefore be avoided. However, your specialist will discuss the options for drug treatment and in particular the use of high dose Proton Pump Inhibitors (PPIS) and aspirin.
Once dysplasia or cancer develops further treatment becomes necessary. The precise type of treatment will depend upon the nature of the abnormalities. and there are several options now available
Photodynamic therapy (PDT): Abnormal cells in the Barrett’s segment are destroyed by light directed by laser. It has largely been replaced by radiofrequency ablation.
Endoscopic radiofrequency ablation (RFA): A small coil is guided towards the abnormal section of oesophagus. This emits heat which destroys abnormal cells which are subsequently replaced by normal cells.
Argon plasma coagulation: A jet of argon gas is directed at abnormal cells. An electric current is transmitted by the gas which then burns the cells.
Endoscopic mucosal resection (EMR): Barrett’s cells, in the absence of invasive cancer, are confined to the layer of cells which lines the oesophagus (the mucosa). This can be lifted of the underlying muscle layers, a little bit wallpaper off the walls of a room before being removed. The procedure is performed endoscopically using special instruments which enable resection of the abnormal tissue. Even early cancers can be removed using this technique, avoiding major surgery.
Should I take PPis?
Barrett’s is caused by Gastro Oesophageal Reflux Disease (GORD). Reflux causes chronic inflammation at the bottom of the oesophagus and the major contributor to this is acid from the stomach. This is why antacid drugs are the mainstay of treatment for the symptoms caused by reflux. The most powerful antacid are PPIs (Proton Pump Inhibitors) such as Omeprazole and Nexium.
PPIs have now also been shown to confer a survival benefit in patients with Barrett’s. A big scientific study called the AspECT trial published in 2018 demonstrated that patients who took high doses of PPIs enjoyed a survival benefit over those who did not. There was a further benefit enjoyed if aspirin was added. However, PPIs are associated with other conditions and in particular with Small Intestinal Bacterial Overgrowth (SIBO) in which there is an abnormal colonisation of the gut by bacteria. Consequently, having been diagnosed with Barrett’s we would advise that you should discuss the benefits and risks treatment with your specialist.
Should I have an operation?
Barrett’s is a pre-cursor to the most common type of oesophageal cancer in the UK. Adenocarcinoma, which develops at the bottom of the oesophagus at the junction with the stomach is almost always associated with Barrett’s. The “metaplasia” that defines Barrett’s occurs as a consequence of reflux and probably as a healing response to the inflammation that occurs when the oesophagus is bathed in acid, bile, pepsin and other components of gastric juice. Gastric acid can cause DNA damage in Barrett’s cells, cause proliferation of Barrett’s and also cause secretion of cytokines, the chemical messengers associated with inflammation. There is clear evidence from clinical trials that PPIs improve survival in patients with Barrett’s. There is also evidence that it’s not just acid that causes a problem- bile salts also seem to cause release of cytokines and may even be more chemically active in low acid environments, for instance when patients are taking PPI’s. So, if reflux causes Barrett’s and Barrett’s is associated with cancer surely an operation that stops reflux will also prevent cancer developing? It’s quite possible that this is the case.
In fact a study published in 2019 suggested that Barrett’s regressed following LINX® implantation and there is other “observational” evidence that successful anti-reflux surgery reduces the development of both dysplasia (the precursor of cancer and cancer itself). However, while hypothetically the theory is very appealing, we don’t actually have definite proof from a prospective scientific study that this is the case. Why not?
Firstly, most people with Barrett’s don’t develop cancer. The risk is about 0.5% per year and so it would require following many thousands of people over many years to see a difference between those who had surgery and those who didn’t. Secondly, it’s also known that PPIs confer an improved survival in Barrett’s and any study would have to compare two groups of patients in which one took PPIs and the other had surgery. So, it would be very hard to construct a scientific study comparing outcomes in a disease that takes many years to develop. It’s unlikely that such a study will ever be performed. So, the answer to the question is that as things stand there is no evidence that having an anti-reflux operation will stop the development of cancer any more than PPIs.
However, the bigger question is what should people who have persistent symptoms do despite PPIs if they also have Barrett’s, who can’t or don’t want to take PPIs? This question applies to many people as 20-30% who take PPIs to control reflux still suffer regular symptoms and an increasing number of patients do not want to take these powerful drugs indefinitely. The answer again is unknown, but it seems sensible to consider that surgery may well confer the additional benefit of reducing the risk of developing cancer in addition to abolishing reflux symptoms.
For these reasons some people will consider that the potential for prevention of the development of cancer may well be another reason to consider surgery.