Dr. Amitabh Chak, professor of medicine and oncology at Case Western Reserve University’s School of Medicine, explains his involvement in the development of a new device to treat Barrett’s Oesophagus and oesophageal cancer.
Imagine you are diagnosed with a cancer that is known to be fatal within five years. This is a reality for many — oesophageal cancer is one of the fastest growing cancer diagnoses in the United States. Its incidence rate has increased four- to six-fold in the past 30 years.
As a Gastroenterologist, this is what I am up against each day. Most patients don’t discover their oesophageal cancer until symptoms develop, at which point the cancer is advanced.
But what if there was a precursor that was treatable if detected before the cancer formed? There is, it’s a little-known condition called Barrett’s Oesophagus (BO). People with BO typically have gastroesophageal reflux disease (GERD), commonly known as heartburn. Through my work, I came to know these people very well; they were typically Caucasian men, over age 50 and overweight.
Cancer of the oesophagus can only be prevented if we discover Barrett’s Oesophagus first — and most GERD patients who develop Barrett’s are completely unaware they have it. BO can only be diagnosed by performing upper endoscopy, which requires sedation, is invasive and expensive. This is problematic for patients as most do not want to take a day off from work or interrupt their lives, even for an important health procedure. Moreover, the microscopic analysis of endoscopic biopsy samples requires assessment by a highly skilled pathologist — which is, again, expensive and not automatable.
With so many cases of Barrett’s going undiagnosed, we need an alternative to endoscopy - one that is less invasive, affordable and doesn't require sedation.
When I started my endoscopic career in the 1990’s, I was an early adopter of new technologies that helped diagnose and stage cancer: Endoscopic Ultrasound (EUS) and Transnasal Endoscopy. Transnasal endoscopy helped us screen patients without sedation but never caught on nationally.
I was focused on making a difference in this disease and I knew we needed a better way to screen for Barrett's.
Around that same time, my colleague Dr. Sanford Markowitz had developed one of the first stool DNA tests for colon cancer screening. The test revealed that some patients would show methylated vimentin in their stool without any colon polyps or colon cancer. Along with Dr. Joseph Willis, Dr. Markowitz and I asked a simple question - “Could methylated vimentin in patients reflect something abnormal in the stomach or oesophagus, too?”
We began testing Barrett’s and oesophageal cancer cells for these same biomarker changes and discovered that methylated vimentin was a better indicator for BE then it was for colon cancer. We decided if we could somehow brush the lower oesophagus, where abnormal cells originate, to obtain a sample, we could develop a ‘pap smear’ like DNA test for detecting Barrett’s oesophagus.
Together, we set out to design our ‘brush’. We collaborated with design engineers to develop several ideas: a sheathed spiral brush, a sheathed Christmas tree like brush and an encapsulated balloon. The balloon idea was appealing as it could invert and protect the sampled cells, eliminating dilution from the upper oesophagus and mouth. We developed several prototypes with various balloons and textured surfaces. Initially, we tested them on chicken skin to see if the surfaces would pick up enough cells. We then moved to pig explants to determine exactly which texture provided the best yield. A design with V-shaped ridges was selected as it effectively captured cells without causing abrasions. We reduced the size of the balloon capsule to a swallowable vitamin-pill like form factor which was attached to a catheter, making it ideal for administration and retrieval.
The most exciting day was when we saw the functioning prototype with the balloon fully inflated and then inverted back into the capsule as it was designed to do.
We moved on to our first pilot test in humans, and I was my own first guinea pig. The device was easy to swallow and felt comfortable going down. Even though I felt the balloon move across the sphincter and sample the lower oesophagus, it didn’t hurt at all. When removing the capsule, I was surprised to have a bit of discomfort but quickly recalled my medical school physiology, the upper sphincter relaxes when you swallow. A simple swallow as the device is removed from the back of the throat and the capsule comes out easily. The cell collection device is now known as EsoCheck with Collect+Protect Technology; it received FDA 510k clearance and is available from Lucid Diagnostics.
EsoCheck can be administered in a doctor’s office in a short five-minute procedure. Unlike an upper endoscopy, the procedure is minimally invasive and doesn’t require patients to take a day off and is significantly less costly.
Finally, we conducted a pilot study that combined the device with the methylated DNA markers that Dr. Markowitz developed. The test was shown to have greater than 90% sensitivity and specificity at detecting BO, with and without dysplasia, as well as EAC. Today, known as the EsoGuard oesophageal DNA test, this laboratory developed test has the potential to prevent deaths from oesophageal cancer through early detection. EsoGuard has received FDA Breakthrough Device designation in conjunction with EsoCheck.
It has been my greatest honour to be a co-inventor bringing these innovations to life and it turns out that sometimes you have to be willing to swallow your own invention to pioneer a new path forward.
