‘Pill on a string’ can detect cancer of the gullet

cancer of gulletResearchers have developed a ‘pill on a string’ that could help doctors detect esophageal cancer – cancer of the gullet – at an early stage.

Researchers said that ‘cytosponge’ sits within a pill which, when swallowed, dissolves to show a sponge that scrapes off cells when withdrawn up the gullet. It allows doctors to collect cells from all along the gullet, whereas standard biopsies take individual point samples.

Esophageal cancer is often preceded by Barrett’s esophagus, a condition in which cells within the lining of the esophagus begin to change shape and can grow abnormally.

Between one and five people in every 100 with Barrett’s esophagus go on to develop esophageal cancer in their life-time, which can be difficult to treat.

At present, Barrett’s esophagus and esophageal cancer are diagnosed using biopsies, which look for signs of dysplasia, the proliferation of abnormal cancer cells.

Now, researchers from the University of Cambridge have shown that variations in mutations across the esophagus mean that biopsies may miss cells with important mutations.

A sample was more likely to pick up key mutations if taken using the Cytosponge, developed by Rebecca Fitzgerald at the Medical Research Council Cancer Research Unit at the University of Cambridge.

“The trouble with Barrett’s esophagus is that it looks bland and might span over 10cm,” said Fitzgerald.

“We created a map of mutations in a patient with the condition and found that within this stretch, there is a great deal of variation amongst cells,” she said.

“Some might carry an important mutation, but many will not. If you’re taking a biopsy, this relies on your hitting the right spot. Using the Cytosponge appears to remove some of this game of chance,” she said.

Fitzgerald and colleagues carried out whole genome sequencing to analyse paired Barrett’s esophagus and esophageal cancer samples taken at one point in time from 23 patients, as well as 73 samples taken over a three-year period from one patient with Barrett’s esophagus.

The researchers found patterns of mutations in the genome that provided a ‘fingerprint’ of the causes of the cancer. The team found fingerprints which they believe are due to the damage caused to the esophagus by stomach acid splashing onto its walls; the same fingerprints could be seen in both Barrett’s esophagus and esophageal cancer, suggesting that these changes occur very early on the process.

Even in areas of Barrett’s esophagus without cancer, the researchers found a large number of mutations in their tissue – on average 12,000 per person (compared to an average of 18,000 mutations within the cancer).

Many of these are likely to have been ‘bystanders’, genetic mutations that occurred along the way but that were not actually implicated in cancer.

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