Current Guideline Definitions of Barrett’s Esophagus May Fall Short in Detecting Esophageal Cancers

Barrett’s esophagus is characterized by the gradual change of the normally flat epithelial cells lining the esophagus to columnar cells resembling those in the intestinal tract. It is the only known precursor of esophageal cancer, including esophageal adenocarcinoma (EAC) and esophagogastric junction adenocarcinoma (EGJAC). Early detection of esophageal cancer is imperative, as it brings 5-year survival rates up to 50% versus the 5% rate seen with late-stage diagnosis.

The definition of Barrett’s esophagus can vary based on different clinical guidelines. For example, the American Gastrointestinal Association, American College of Gastroenterology and European Society for Gastrointestinal Endoscopy require the presence of columnar epithelium with intestinal metaplasia to make a Barrett’s esophagus diagnosis. Furthermore, the British Society of Gastroenterology, the European Society for Gastrointestinal Endoscopy and the American College of Gastroenterology require a length of at least 1 centimeter of intestinal metaplasia to confirm a diagnosis, while other guidelines do not restrict the length of columnar tissue to make a Barrett’s esophagus diagnosis.

Based on these differences, researchers from the University of Michigan Medical School and the LTC Charles S. Kettles Veterans Affairs Medical Center in Ann Arbor, Michigan, conducted a retrospective analysis to investigate the esophageal cancer detection rates of esophageal endoscopies using differing Barrett’s esophagus definitions.

The study, led by Michelle Russin, M.D., included data from 244 veterans diagnosed with EAC or EGJAC from January 1, 2017, to December 31, 2021, within the Veterans Health Administration Central Cancer Registry, who had an endoscopy at least 1 year before the cancer diagnosis. The results from the analysis were published earlier this month in Clinical Gastroenterology and Hepatology.

The researchers manually reviewed endoscopy reports and available images and used Siewert classification to create two cohorts. In the Siewert classification system, tumors are categorized by the distance of the tumor epicenter from the esophagogastric junction (EGJ). Malignancies, such as EAC, with a distance of more than 1 centimeter from the EGJ were classified as Siewert 1. Those with less than 1 centimeter proximity to the EGJ, such as EGJAC, were defined as Siewert 2.

A total of 136 patients with EAC (Siewert 1) and 108 with EGJAC (Siewert 2) were included in the analysis. The results showed that intestinal metaplasia was present in 97% of patients in the Siewert 1 group and 98% of those in the Siewert 2 cohort. However, the detection rate fell significantly when using guideline definitions of Barrett’s esophagus that require at least 1 centimeter in length of intestinal metaplasia. Under this criterion, the rate was only 66% for the Siewert 1 group and 40% for the Siewert 2 group.

When excluding segments with less than 1 centimeter of intestinal metaplasia from Barrett’s esophagus diagnoses, the investigators estimate that approximately 20% of esophageal cancer cases may be missed. They wrote, “…our results suggest that the detection rate of [endoscopy] for [Barrett’s esophagus] is compromised if definitions exclude lengths [less than] 1 cm, particularly for subsequent [Siewert 2] cancer.”

“Our results support the importance of [intestinal metaplasia] as a precursor for the development of EAC and likely for EGJAC,” the investigators added.

The authors acknowledge study limitations, such as a veteran-only study sample, which may differ in certain characteristics from a non-veteran population. On the other hand, having a nationally representative sample from multiple health facilities was a strength of the study.