NEW YORK (360Dx) – CDx Diagnostics three-dimensional analysis detection and surveillance system has clinical benefits to help preempt esophageal cancer, according to company executives.
The firm's Wide Area Transepithelial Sampling with 3D Tissue Analysis, or WATS3D, enables endoscopists within a few minutes to obtain a wide area, full-thickness transepithelial tissue sample for computer-assisted 3D laboratory analysis.
The system, which has all required US and European marketing approvals, consists of a specially designed sampling brush that enables collecting tissue cells down to a specific depth in the epithelium — the thin tissue forming the outer layer on the body.
A computer system consisting of a neural network algorithm uses the collected cells to create an image of tissue that's read by pathologists deciding whether the cells are cancerous or have a specific grade of dysplasia that means they should be removed.
Data reported at a session during ACG 2018, the annual meeting of the American College of Gastroenterology, in Philadelphia earlier this month, indicate that that samples obtained and analyzed with its three-dimensional detection and surveillance system enables detection of crypt dysplasia, and that the system provides information that forceps biopsy cannot, the presenters said.
The clinical significance of dysplasia involving crypt cells has not been well understood due to limitations in detecting crypt dysplasia by conventional biopsies, the Suffern, New York-based firm said.
The CDx study tested samples from 4,512 patients who had two WATS3D assessments performed six months apart. The researchers said non-dysplastic Barrett's esophagus and low- or high-grade dysplasia can be diagnosed using standard biopsy criteria, but morphologic changes that fall between non-dysplastic Barrett's esophagus and low-grade dysplasia have been traditionally classified as indefinite for dysplasia and often grouped with non-dysplastic Barrett's esophagus.
Clinicians have been unable to distinguish dysplasia involving the crypt cells, located below the epithelial cells, from esophagitis resulting from uncontrolled reflux. The study results are the first to show that WATS3D enables accurate diagnosis of crypt dysplasia as a distinct histology, according to CDx.
Barrett’s esophagus occurs when the normal epithelial lining of the esophagus is replaced by goblet cells that are typically found in the lower gastrointestinal tract. Patients with Barrett's have an increased risk of developing esophageal adenocarcinoma, a cancer that attacks 17,000 people in the US each year, of which more than 15,000 will die, according to the National Cancer Institute.
Patients with Barrett's typically undergo periodic surveillance endoscopy to monitor for pre-cancerous changes to the esophageal lining. Further, clinicians perform more than 5 million upper endoscopies in the US each year on patients with chronic heartburn leading to gastroesophageal reflux disease, or GERD, Mark Rutenberg, CDx Diagnostics founder and CEO, said in an interview.
According to the American Society for Gastrointestinal Endoscopy, up to 15 percent of patients with GERD develop Barrett’s esophagus, and doctors believe most cases of adenocarcinoma of the esophagus begin in Barrett’s tissue.
Doctors performing an upper endoscopy to diagnose Barrett’s esophagus can see that Barrett’s tissue has a different appearance than the normal lining of the esophagus. However, to confirm the diagnosis and look for the precancerous change of dysplasia that cannot be seen by endoscopy, they take biopsies from the esophagus.
Rutenberg said that CDx's WATS3D system addresses inadequacies inherent in current random forceps biopsy testing of the esophagus. Specifically, the technology increases the detection of precancerous cells when an abnormality in the esophagus cannot be detected, he noted, adding that esophageal cancer is preventable when dysplastic cells can be found because they can be destroyed by endoscopic ablation before they become cancerous.
Importantly, in the past decade, companies have begun marketing endoscopic ablation technology that enables clinicians to remove and treat dysplasia. Prior to the development of endoscopic ablation, treatment involved removal of the esophagus, a highly invasive and potentially fatal procedure.
With its computer system, CDx has been able to "fill a gap" left by inaccuracies in diagnosis stemming from having to use random biopsies, and its technology enables broader treatment of patients, Rutenberg said.
"The system addresses two major areas in which we currently have deficiencies — combating sampling error and effectively diagnosing grades of esophageal dysplasia using clear and crisp images," Robert Odze, a professor of pathology at Harvard Medical School and user of the CDx system, said in an interview.
In large multicenter clinical trials, clinicians have found that the system increased the detection of a pre-cancerous condition by more than 400 percent over use of the standard biopsy protocol, he said. It has demonstrated high inter-observer agreement due to the combination of a larger tissue area sampled and use of clear 3D computer imaging, Odze noted.
CDx Diagnostics was founded in 1998 as Oral Scan Laboratories, and it developed an advanced neural network computer and imaging system used to detect pre-cancerous cells in biological specimens. The firm then used the technology to develop a test to detect oral dysplasia and in 2002 began to apply the technology to detecting esophageal dysplasia.
Of $100 million obtained from private investors since its founding, the firm invested $20 million to develop the test for detecting oral dysplasia and $80 million to develop the product for detecting esophageal dysplasia, Rutenberg said.
The firm is also developing its technology to detect pre-cancer dysplasia in areas of the gastrointestinal tract in addition to the mouth and esophagus.
Its near-term goal is to develop a test for detecting bile duct dysplasia, which the firm anticipates could be available in 2019. It is also developing a test that would detect dysplasia in the stomach and inflammatory bowel disease, including Crohn's disease and ulcerative colitis.
Rutenberg noted that leveraging the abundance of tissue samples it has collected, CDx is working with several companies that are developing molecular panels for use in determining the risk for patients with Barrett's esophagus to develop cancer.