Narrator: Researchers are looking at a new way of screening for Barrett’s esophagus. You swallow a small capsule like this one [A Nurse shows a Patient a capsule on string]. It contains a sponge called a Cytosponge.

Nurse: So I want you to put the sponge as far back to the back of the throat, nice big gulp of water, and swallow. After five minutes what we do is we gently pull it back, and you might feel like it scratches the back of the throat.

Patient: Okay.

Nurse: Some patients have said that it feels like a brillo pad, but most patients can tolerate it very well. [Nurse gives Patient water and capsule]

Patient: Okay. [Patients swallows capsule]

Narrator: The outer capsule dissolves in about five minutes.

Nurse: Okay?

Patient: Yeah.

Nurse: That’s great. Can I just have a look in your mouth. [Patient opens mouth and Nurse examines] That’s ok, great. I’ve just set the timer for 5 minutes.

[Video skips to 5 minutes later]

Nurse: I want you to just keep your head nice and still for me, and open your mouth, okay. [Nurse gently pulls out the sponge]

Narrator: As the nurse pulls the sponge out, it collects cells from the lining of your oesophagus.

Nurse: I’ll just show you what you’ve just swallowed.

Patient: Sure. [Nurse shows Patient the expanded sponge] Wow.

Narrator: The sponge now goes to the lab to see if the cells show signs of Barrett’s.

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This is a plain English summary of an original research article

Detection of a pre-cancerous throat condition called Barrett’s oesophagus can be improved with the use of an innovative swallowable sponge and laboratory test, a large multicentre trial found.

Heartburn, caused by acid reflux from the stomach up into the gullet (oesophagus), is common among people visiting their GP. It is usually treated with acid suppressants. But acid reflux can lead to Barrett’s oesophagus, which in turn increases the risk of oesophageal cancer.

GPs may send people with heartburn for an endoscopy. It is an awkward procedure but, at present, is the only way to diagnose Barrett’s oesophagus. As a result, most people with Barrett’s are not diagnosed and do not benefit from early treatment when cancer starts to develop.

In the new study, people with heartburn instead swallowed a capsule attached to string. The dissolvable capsule contained a fluffy sponge that GPs then pulled out of the stomach, up through the oesophagus and out of the patient’s mouth to retrieve cell samples. Analysis of these cells under a microscope for a marker called TFF3, developed by the same team, could find tell-tale signs of Barrett’s oesophagus.

The research found that the test – called Cytosponge-TFF3 – could help GPs narrow down which people with heartburn should be sent for an endoscopy.

What’s the issue?

In Barrett’s oesophagus, cells lining the oesophagus have changed as a result of acid reflux. It is not cancer, but it does slightly increase the chance of cancer developing. People diagnosed with Barrett's oesophagus have regular tests to make sure signs of cancer are found early and treatment started promptly. Unfortunately, four in five cases of Barrett’s oesophagus go undiagnosed.

Endoscopy means a tube with a camera on the end being passed down the throat. Samples of cells from areas that do not look normal are taken and examined to make a diagnosis. But endoscopy can be uncomfortable and has some risks associated with sedation.

A common symptom of Barrett’s oesophagus is heartburn. At present, GPs have no easy way of checking such patients for Barrett’s oesophagus, so they send many people who complain of heartburn for an endoscopy. This is expensive, time consuming and unnecessary in 19 out of 20 cases. A tool that would help GPs identify and prioritise those patients who do show signs of Barrett’s oesophagus would be valuable.

What’s new?

The randomised trial was carried out in 109 GP practices across England. It included more than 13,000 patients aged over 50 who had been on heartburn medication for six months or more. Half received usual care, and the rest were given the option of the Cytosponge to help the GP decide if they needed an endoscopy (they could refuse and opt instead for the normal care). The trial compared how many patients from each group were diagnosed with Barrett’s oesophagus within twelve months.

The results showed that:

  • The procedure was acceptable to many. Two in five people who were offered the Cytosponge expressed an interest (39%; 2679 of 6834 people)
  • Two in three of those who expressed an interest in the Cytosponge underwent the procedure (65%; 1750 of 2679)
  • Almost all swallowed the Cytosponge successfully and produced a cell sample for analysis (95%; 1654 of 1750)
  • Just one in 30 of the patients offered the Cytosponge were referred for an endoscopy (3%; 231 of 6834)
  • The Cytosponge improved diagnoses. Ten times as many people offered the Cytosponge were diagnosed with Barrett’s oesophagus, compared with the usual care group
  • Nine of those offered the Cytosponge were diagnosed with signs of early cancer, compared with no early cancer, only advanced disease, in the usual care group
  • There were few side effects of the procedure; the most common was a sore throat.

The findings suggest that the Cytosponge was a useful aid to GPs in deciding which people to send for endoscopy. It increased the numbers diagnosed with Barrett’s oesophagus and with cancer.

Why is this important?

Oesophageal cancer can be treated more easily and successfully if the disease is caught early. At this stage, cancerous cells can be removed by endoscopy. But many patients are not diagnosed until the cancer is advanced, when treatment involves chemotherapy and surgery. So, a reliable screen for the early signs of the disease could save lives and reduce the need for severe and expensive treatments.

The new study shows that the Cytosponge could serve as a screening tool for early cancer. Ten times as many cases of Barrett’s oesophagus were found in the patients offered the procedure. The results imply that nine in ten cases in the usual-care group were missed – perhaps storing up trouble for later years.

The results show that, in principle, GPs could use the Cytosponge to quickly screen patients with heartburn and identify those most in need of an endoscopy and possible further treatment.

However, widespread use of the Cytosponge is likely to increase the number of patients sent for endoscopy. That increases the chances of over-diagnosing Barrett’s oesophagus (identifying changes to cells that would not progress to cancer) and causing unnecessary concern among some people .

What’s next?

Restrictions on the use of endoscopy during the COVID-19 pandemic mean the Cytosponge is already available in hospitals in Scotland. The research team argue it would have most benefit if offered as a screening tool in primary care settings such as GP surgeries. For that to happen, they need to analyse the costs and economic benefits, and to explore the reasons why, in the study, more than half declined the procedure. They are looking at different ways to describe and explain it.

The team is training a computer to spot the unusual cells that indicate a case of Barrett’s oesophagus. Machine learning would reduce the burden on individual oncologists and allow the process to be scaled up and automated.

The researchers are also working to enhance the technique and use laboratory tests in addition to TFF3 to identify the patients with Barrett’s who are most at risk for cancer. They are also exploring whether nurses in other community settings, such as pharmacies or mobile vans, could carry out the procedure.

You may be interested to read

The full paper: Fitzgerald R, and others. Cytosponge-trefoil factor 3 versus usual care to identify Barrett's oesophagus in a primary care setting: a multicentre, pragmatic, randomised controlled trial. Lancet 2020;396:333-344

Comment on the findings: Hanada Y and Wang KK. Screening for Barrett's oesophagus: is now the time? Lancet 2020;396:292-293

A video by the researchers describing the Cytosponge procedure

An economic evaluation of the use of the Cytosponge for Barrett oesophagus: Swart N, and others. Economic evaluation of Cytosponge®-trefoil factor 3 for Barrett esophagus: A cost-utility analysis of randomised controlled trial data. EClinical Medicine 2021;37:100969 


Funding: The study was funded by Cancer Research UK, the NIHR, the NHS, Medtronic, and the UK’s Medical Research Council.

Conflicts of Interest: Two authors are named on relevant patents. Several hold shares and have received fees from associated companies.

Disclaimer: NIHR Alerts are not a substitute for professional medical advice. They provide information about research which is funded or supported by the NIHR. Please note that views expressed in NIHR Alerts are those of the author(s) and reviewer(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.

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Study author

We were delighted and surprised by the scale of the benefit. We expected to find more cases but to find ten times as many was unexpected. This is a really simple test that can be done in ten minutes in a GP surgery.

Some patients we diagnosed had signs of early cancer and so they could go and get treatment. It’s really fulfilling to be able to say that I met some of these patients who were truly grateful and that just makes it all worthwhile.

Rebecca Fitzgerald, Professor of Cancer Prevention, University of Cambridge

Lived experience

Having had a number of endoscopies myself, I am aware of the considerable discomfort and associated anxiety that goes with this procedure. Part of the answer lies in the medication used to sedate and the skill of the person performing the endoscopy, but if there a way to reduce unnecessary endoscopies for patients who can be diagnosed or have their concerns placated by other examination or history taking, then this would be a major benefit to patients.

It is an important step to find that the new technique may tighten diagnosis, so that patients and clinicians are more confident that the right patients are sent for endoscopy. It should lead to better treatment for individual patients.

Because of COVID and other factors, endoscopies are not being done as much as previously. It is important to recognise that in any implementation strategy.

Jennifer Bostock, Public contributor, Folkestone, Kent


From my primary care perspective, managing long-term dyspepsia represents a complex area of decision-making about a very common symptom. This trial, albeit with small numbers, suggests the tantalising possibility of an approach that could facilitate earlier diagnosis of potentially treatable gastro-oesophageal cancer.

My practice team discussed the paper. We were reassured by the detailed safety and acceptability data, but we wanted to know more about experience with the sponge outside of the trial: training and monitoring requirements, and the risks with less experienced users. We wondered how long the procedure would take, and the resource implications of moving an investigation that is typically the responsibility of specialist care into primary care. Might there be a role for embedding this within community specialist clinics?

If this were to come into mainstream practice, how would clinicians react to a negative test in the presence of on-going symptoms? Endoscopy would still be warranted for further assessment, including because it can find other conditions that guide future management, such as hiatus hernias or non-cancerous ulcers.

In our experience endoscopy is usually acceptable, but there are certainly patients for whom fear of endoscopy or hospital care is a barrier to care. This test could be an option for them and perhaps especially in the COVID-19 era, where access to secondary care may be more complex and patients may be more fearful. I will be watching out for evolving evidence in real world practice.

Sharon Dixon, GP, Oxford


This paper could reduce the burden of endoscopy services in diagnosing Barret’s esophagus. Upper gastrointestinal endoscopy generates aerosol and the paper suggests a viable alternative in this era of the COVID-19 pandemic.

Ademola Adeyeye, Consultant Surgical Oncologist and Senior Lecturer in Surgery, Afe Babalola University (ABUAD), Nigeria & previous Visiting Honorary Fellow to the University Hospitals of Leicester NHS Trust

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