New diagnostic tools
Diagnosis of Barrett's Oesophagus currently requires an endoscopist pushing an endoscope down your throat and taking biopsies from suspect areas to be examined by a histopathologist in the lab. All rather time consuming and expensive (at £600 a time for the NHS).
So doctors are often reticent about referring patients reporting heartburn which is common and usually curable with an antacid or acid suppressant medicine. This may mean patients with pre-cancerous Barrett's may be missed.
CytospongeTM may be the answer. The capsule can be swallowed like a tablet whilst keeping hold of the string. The capsule dissolves, the sponge expands and it is pulled back out by the string.
Development of the Cytosponge has been carried out by the Cambridge based team led by Dr Rebecca Fitzgerald and funded by Cancer Research UK and the Medical Research Council.
Millions of cells are harvested this way from anywhere between the stomach and the mouth. It is not feasible to start examining them all under a microscope as with a normal biopsy and various methods may be used to examine them.
The cells are removed by soaking the sponge in a histological fixative and centrifuging the resultant mass. Biomarkers have been identified that indicate a particular possibility of Barrett's Oesophagus and for Oesophageal cancers.
If these biomarkers are detected, the patient will require a normal endoscopy for further appraisal.
The advantages of Cytosponge are it is considerably cheaper than an endoscopy (about £25 a time), takes less time, requires less skill (a nurse at a GP practice could administer it) and it could be used as an initial screening for any patient who reports persistent heartburn so more cases of Barrett's may be discovered before it's too late.
At the time of writing, Cytosponge is undergoing final trials and hopefully will be released for general use soon. (Expected 2020.)
A you tube video may be viewed by clicking on the link.
Similar to Cytosponge, Esophacap, developed at Johns Hopkins University in US, also uses a sponge cell collection system. A study published in 2019 concluded, “EsophaCap ... is a promising, well-tolerated, low-cost esophageal sampling strategy for BE diagnosis.” [t-iii]
Non-endoscopic balloon device being developed by Cleveland Medical Center USA, harvests DNA . “To enable non-endoscopic targeted sampling of the distal esophagus, we designed and built an encapsulated, inflatable, surface-textured balloon. The device is swallowed in a pill-sized capsule attached to a thin silicone catheter. After delivery to the stomach, the balloon is inflated by injecting air through the catheter and then gently withdrawn 3 to 6 cm back through the esophagus to sample the luminal epithelial surface. The balloon is then deflated and inverted back into the capsule, thus protecting the acquired biosample from further dilution or contamination in the proximal esophagus and the oropharynx. After retrieval of the capsule through the mouth, DNA is extracted from the balloon surface for molecular analysis.” [t-iv]
Presently undergoing trials, this looks at changes in the way genes are expressed when cells start to turn from normal towards cancer. Cells release small amounts of their DNA and RNA into the blood which is then transferred into the saliva. DNA contains not only the genes which determine the blueprint of the body. It also has switches which can turn these genes on. This is called epigenetics. RNA is the molecule that is produced when particular genes are activated. It is then translated into proteins which do the work in the cells. The new spit test aims to assess how DNA and RNA levels change from normal people to those in cancer and to use these changes to detect cancer risk.
A paper published in 2018 highlighted, “The oral microbiome in BE patients was markedly altered and distinguished BE with relatively high accuracy. The oral microbiome represents a potential screening marker for BE” [t-v]
Analysing our breath was originally thought may prove a feasible way of detecting lung cancer.
As scientists started exploring further, however, they discovered the “Volatile Organic Compounds” detectable in breath via spectrometry could reveal far more information and detect other cancers, especially gastro-oesophageal and the potentially pre-cancerous condition, Barrett’s Oesophagus.
To take the test, patients breathe into a device similar to a breathalyser. The test looks for chemical compounds in the exhaled breath that are unique to patients with oesophageal cancer.
(Image courtesy of Owlstone Therapeutics)
A study published in 2018 [t-vi] showed “the potential of breath analysis in noninvasive diagnosis of Oesophago-Gastric Cancers in the clinical setting”, and another the same year [t-vii] concluded “The oral microbiome in BE [Barrett’s Esophagus] patients was markedly altered and distinguished BE with relatively high accuracy. The oral microbiome represents a potential screening marker for BE, and validation studies in larger and distinct populations are warranted.”
Trials are being run concurrently with the SPIT test, mentioned above, with the hope these will become available triage tools for doctors to identify those to be added to regular surveillance endoscopic screening programmes, in 2024.
The Breath and SPIT tests work in different ways.
“A breath test measures chemicals that are found in the breath. These chemicals are found in very tiny quantities and may be coming directly from the abnormal areas of the stomach. The new spit test does something different. It is looking at changes in the way genes are expressed when cells start to turn from normal towards cancer.”
This entry has been added since the last print edition of the encyclopaedia.
From CDx Diagnostics, this consists of a brush used via endoscope to sample cells from an area of the oesophagus rather than pinpoints with traditional biospies.
The harvested cells are then scanned using Artificial Intelligence, in a similar way to those harvested by cytosponge.