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Nonendoscopic screening tools for early detection of Barrett's esophagus, esophageal adenocarcinoma and dysplasia

Nov. 25, 2025

The need for new screening tools to detect esophageal cancer has led researchers at Mayo Clinic to discover new methods for earlier detection of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC).

BE is a known precursor to EAC, which is lethal when diagnosed after symptom onset. Level 1 evidence shows endoscopic therapy for BE dysplasia can interrupt the progression to EAC. This approach has a reported 80% survival rate compared with 20% when treatment is initiated after symptoms appear.

Early screening remains underutilized, largely because the current diagnostic method — endoscopy — is invasive, expensive and not uniformly accessible. Periodic biopsies are also suggested for patients with BE for surveillance of dysplasia. This has prompted efforts by the research community to develop nonendoscopic, nonphysician-administered screening tools for greater utilization and access.

According to Prasad G. Iyer, M.D., M.S., a gastroenterologist and hepatologist with Mayo Clinic in Arizona, nearly 60% of surveyed patients support these efforts. This finding was published in The American Journal of Gastroenterology.

"The need for less invasive screening tools is well warranted and well supported," says Dr. Iyer. "At Mayo Clinic, we're using novel nonendoscopic, biomarker-enhanced and molecular technology, along with clinical trials and artificial intelligence-powered approaches, to detect disease in its early stages for better patient outcomes."

Mayo Clinic's work on cancer biomarkers and the newly published microRNA study are two examples of innovation and progress toward growing the arsenal of EAC-BE screening tools to achieve the aspirational goal of cancer prevention.

EMERALD: A promising microRNA blood panel test

The 2025 Esophageal MicroRNAs of Barrett, Adenocarcinoma and Dysplasia (EMERALD) study offers a promising blood-based screening alternative to endoscopy for early detection of EAC and BE.

The EMERALD study aimed to develop and test a blood-based assay for detecting EAC and BE, analyzing 792 patient samples from across four countries. It is the largest multicenter biomarker cohort of its kind to date for EAC-BE. The study's core findings were published in Gut in 2025.

Researchers conducted rigorous in silico discovery and selection of microRNAs associated with EAC using publicly available datasets, followed by validation in an independent tissue dataset. Six microRNAs were identified as being overexpressed in patients with EAC compared with the nondiseased control group, as determined using quantitative real-time polymerase chain reaction (qRT-PCR) and trained machine learning algorithms. Dr. Iyer highlights the EMERALD study's potential as a noninvasive screening tool for EAC and Barrett's esophagus in a recent Gut commentary.

The model for EAC was highly discriminative, with an accuracy of more than 95%. Interestingly, EMERALD was also discriminant for BE cases, at 80.6% sensitivity, despite the condition being epithelial.

Additional research is needed to assess the influence of clinically relevant covariates, such as age, sex, body mass index and smoking history, and to replicate the findings in a larger sample set. While the initial results from this study are encouraging, further validation is needed before this test can be commercialized.

Once further tested and validated, this liquid biopsy method could provide a noninvasive way to screen for EAC and BE, thereby enhancing patient access and compliance. It also has the potential for early identification of high-risk patients, ultimately leading to better outcomes and advancing efforts toward disease prevention.

Swallowable esophageal cell collection devices, methylated DNA biomarker-based test

While not as noninvasive as the microRNA blood test, esophageal cell collection using swallowable cell collection devices is another less invasive method to screen for EAC and BE. As a leader in early detection and innovation in cancer care, Mayo Clinic has been testing swallowable cell collection devices with methylated DNA biomarker analysis as a viable alternative to traditional endoscopic screening for the past decade.

Swallowable esophageal cell collection devices are well tolerated by nearly all patients. They are administered by a nurse and take less than 10 minutes from start to finish.

Patients ingest a capsule-shaped device containing a spherical soft foam piece with a string attached. Once in the stomach, the capsule dissolves and the foam sphere inside expands. After a few minutes, a nurse removes the sponge by pulling on the string, collecting cells from the entire length of the esophagus along the way. These cells are then analyzed using biomarker technology. Results from this Mayo Clinic-led study were published in a 2024 issue of Clinical Gastroenterology and Hepatology.

"We've found this approach to be very accurate in detecting Barrett's esophagus and esophageal adenocarcinoma," says Dr. Iyer. "The swallowable device is well tolerated, less invasive and less expensive than the traditional endoscopic procedure, making it more accessible and acceptable to patients."

Dr. Iyer suggests likely widespread use within a year. "Our work with this technology is 10 years in the making, and we are very close to commercial use."

Like the microRNA blood panel, swallowable cell collection with biomarker analysis has the potential for early identification of high-risk patients. With these technologies, research teams at Mayo Clinic continue to move closer to improved outcomes and disease prevention.