Cambridge ‘pill-on-a-thread’ test could be less invasive alternative to endoscopies for Barrett’s oesophagus monitoring

The ‘pill-on-a-thread’ test invented in Cambridge could be used as a far less invasive alternative to endoscopies for half of all patients with Barrett’s oesophagus, a known precursor to oesophageal cancer, a study has shown.

It can help stratify patients diagnosed with the condition, meaning many of them could avoid having a camera passed down into the stomach numerous times during monitoring.

First author Dr W Keith Tan, honorary registrar in gastroenterology and hepatology at Addenbrooke’s Hospital, said: “Our ability to identify patients at low versus high risk using the capsule sponge – which may be as accurate as the current gold standard, endoscopy – is a great step forward.

“The capsule sponge can be administered easily and quickly by nurses with only limited training required and will not need to take up precious endoscopy resources, which may be better for patients and more cost-effective for the NHS.”

Fewer than one in five patients survive oesophageal cancer for five or more years following diagnosis - a figure that has barely changed over the past three decades. Yet the numbers diagnosed have increased four-fold since the 1970s.

Barrett’s oesophagus is a known risk factor for the disease and is characterised by changes in the shape and structure of cells in the lining of the oesophagus.

These cells initially change to resemble those in the lining of the intestines, but over time can change to a pre-cancerous state known as dysplasia.

Patients with low-grade dysplasia have about a one in 10 chance of developing oesophageal cancer, but the risk doubles to one in five for those with high-grade dysplasia.

However, dysplasia can be treated without surgery, and the treatment significantly reduces the risk of cancer developing.

Barrett’s oesophagus is typically diagnosed after a patient reports symptoms such as persistent heartburn. An endoscopy - in which a camera is passed down into the stomach - is the traditional method of diagnosis, but there are long waiting times for initial endoscopy investigations on the NHS.

Patients who are diagnosed with Barrett’s oesophagus are then monitored to look for dysplasia or early cancer through regular endoscopies and may undergo 10 or more over their lifetime.

If the cancer is caught early, it increases the chances of successful treatment and means the treatment can be performed down the endoscope as a day-case, without chemotherapy or an operation.

Prof Rebecca Fitzgerald, director of the Early Cancer Institute at the University of Cambridge and honorary consultant gastroenterologist at Addenbrooke’s Hospital, who specialises in Barrett’s oesophagus, said: “It’s extremely important to monitor patients so that we can catch the dysplasia and prevent it developing to cancer – and if someone is unfortunate enough to develop cancer, we can catch it early and treat it.

“But the chances of Barrett’s progressing to cancer are low, and endoscopies are not very pleasant procedures. Added to that, endoscopies are not always a reliable way of spotting early cancers and can depend on the skill of the person doing the endoscopy and the equipment being used. What we need is an alternative surveillance method that’s less invasive, easier to administer and more reliable.”

As the Cambridge Independent has reported, Prof Fitzgerald and colleagues have developed the capsule sponge test as an alternative to the endoscope.

It involves patients swallowing a pill connected to a thread. The pill dissolves in the stomach to release a sponge, which lightly scrapes off some of the cells in the oesophagus as it is drawn back up.

The samples from the capsule test are stained with a chemical and examined under a microscope to detect two key markers that suggest the cells are pre-cancerous. These are abnormalities in the protein p53 that helps to prevent tumours developing and cells that appear abnormal or irregular when examined under a microscope, known as atypia.

To date, most of the research on the capsule sponge has focused on diagnosing Barrett’s oesophagus but now Prof Fitzgerald and her team have studied monitoring the condition more effectively using the technique.

The study, published in The Lancet on Monday (23 June) by researchers at the University of Cambridge, Addenbrooke’s Hospital and Queen Mary University of London, recruited 910 patients from 13 UK hospitals whose Barrett’s oesophagus was being monitored

The patients underwent both the capsule sponge test and an endoscopy. About 15 per cent were classed as high risk, meaning that they had abnormal p53 and/or atypia and, of these, 38 per cent of these patients were found to be at a pre-cancerous stage.

Those with both markers were at the highest risk, with 85 per cent at a pre-cancerous stage.

Patients with neither of the two markers, but whose Barrett’s oesophagus was over a certain length and who met other risk factors related to age and sex, were classed as moderate risk.

Over half (54 per cent) were classed as low risk because they had neither of the two markers and did not meet other risk factors. Endoscopy showed that just two of these 495 patients – 0.4 per cent - had a high-grade dysplasia that needed follow-up and neither had cancer.

Prof Peter Sasieni from the Cancer Research UK Cancer Prevention Trials Unit, Queen Mary University of London, said: “Our findings suggest that the capsule sponge could help stratify patients with Barrett’s oesophagus by risk and that half of them will fall into the low-risk group. Given that the risk of these individuals progressing to dysplasia and then to oesophageal cancer is so low, it should be safe to replace their usual endoscopy with the capsule sponge.”

Prof Fitzgerald, a fellow at Trinity College, added: “We are very excited by these results, which could lead to a test that is much more accessible and less operator dependent to improve standards for monitoring for patients with Barrett’s across the NHS and beyond.”

Duncan Cook, 57, a plumbing and heating engineer from Cambridge who participated in the research, welcomed the results.

For almost 20 years, he has had regular endoscopies to monitor his Barrett’s oesophagus.

“I have a busy job and being able to have the sponge instead of an endoscopy would be much easier and save a lot of time,” he said.

“The first time I had the sponge, I was a bit nervous. It’s quite a big pill to swallow, but it’s much better than going for endoscopies. The sponge test is faster, you don’t need sedation for it, and you don’t need to find someone to come with you to drive you home after. I was able to have the test done and go right back to work after.”