In the Journals

Many esophageal cancers missed after negative endoscopy in patients with Barrett's esophagus

A large proportion of esophageal adenocarcinomas were diagnosed within 1 year after a negative index endoscopy in adults diagnosed with nondysplastic Barrett’s esophagus, or Barrett’s esophagus with low-grade dysplasia, according to results from a recent study.

“Based on a systematic review and meta-analysis of 24 cohort studies in adults with BE … followed for at least 3 years after negative index endoscopy …, we observed a high magnitude of missed [esophageal adenocarcinomas] … diagnosed within 1 year of negative index endoscopy,” Siddharth Singh, MBBS, from the Mayo Clinic in Rochester, Minn., and colleagues wrote. “Additional resources should be allocated to detect missed [esophageal adenocarcinomas].” 

Siddharth Singh, MBBS

Siddharth Singh

The research team examined 24 cohort studies found in MEDLINE, Embase and Web of Science from initiation of each study to May 31, 2015. The studies included data on adults with Barrett’s esophagus (BE), which included either baseline nondysplastic BE or BE with low-grade dysplasia. Data on incident or missed EACs after negative index endoscopy were available over at least a 3-year follow-up period.

The main outcome was the proportion of missed EACs (defined as being diagnosed within 1 year after negative index endoscopy) and incident EACs (diagnosed more than 1 year after initial endoscopy in which BE was diagnosed). 

The researchers identified 820 total EACs found at follow-up, of which 25.3% were missed within 1 year of endoscopy. The other 74.7% were classified as incident EACs; however, the researchers wrote that there was substantial heterogeneity among the studies. In 15 studies where only the patients with nondysplastic BE were included, 23.9% of EACs were missed.

“These data persist over a wide variety of study types and chronological time periods of BE cohort studies,” the researchers wrote. “Additional studies need to be performed to determine if enhanced endoscopic detection using advanced imaging techniques, longer inspection time, an increased number of biopsies, and more assiduous application of the early repeat endoscopy (ie, within 1 year of diagnosis) would enable BE surveillance to reach its real potential in decreasing the burden of EAC; cost-effectiveness analyses of such an approach are warranted to understand the implications of these findings.” – by Suzanne Reist 

Disclosures: Singh reports no relevant financial disclosures. Please see the full study for a list of all other authors’ relevant financial disclosures.

A large proportion of esophageal adenocarcinomas were diagnosed within 1 year after a negative index endoscopy in adults diagnosed with nondysplastic Barrett’s esophagus, or Barrett’s esophagus with low-grade dysplasia, according to results from a recent study.

“Based on a systematic review and meta-analysis of 24 cohort studies in adults with BE … followed for at least 3 years after negative index endoscopy …, we observed a high magnitude of missed [esophageal adenocarcinomas] … diagnosed within 1 year of negative index endoscopy,” Siddharth Singh, MBBS, from the Mayo Clinic in Rochester, Minn., and colleagues wrote. “Additional resources should be allocated to detect missed [esophageal adenocarcinomas].” 

Siddharth Singh, MBBS

Siddharth Singh

The research team examined 24 cohort studies found in MEDLINE, Embase and Web of Science from initiation of each study to May 31, 2015. The studies included data on adults with Barrett’s esophagus (BE), which included either baseline nondysplastic BE or BE with low-grade dysplasia. Data on incident or missed EACs after negative index endoscopy were available over at least a 3-year follow-up period.

The main outcome was the proportion of missed EACs (defined as being diagnosed within 1 year after negative index endoscopy) and incident EACs (diagnosed more than 1 year after initial endoscopy in which BE was diagnosed). 

The researchers identified 820 total EACs found at follow-up, of which 25.3% were missed within 1 year of endoscopy. The other 74.7% were classified as incident EACs; however, the researchers wrote that there was substantial heterogeneity among the studies. In 15 studies where only the patients with nondysplastic BE were included, 23.9% of EACs were missed.

“These data persist over a wide variety of study types and chronological time periods of BE cohort studies,” the researchers wrote. “Additional studies need to be performed to determine if enhanced endoscopic detection using advanced imaging techniques, longer inspection time, an increased number of biopsies, and more assiduous application of the early repeat endoscopy (ie, within 1 year of diagnosis) would enable BE surveillance to reach its real potential in decreasing the burden of EAC; cost-effectiveness analyses of such an approach are warranted to understand the implications of these findings.” – by Suzanne Reist 

Disclosures: Singh reports no relevant financial disclosures. Please see the full study for a list of all other authors’ relevant financial disclosures.

    Perspective
    Nirav Thosani

    Nirav Thosani

    In this study, Visrodia and colleagues conducted a meta-analysis of 24 cohort studies with at least 3-year follow-up and reported 25% missed rate for esophageal adenocarcinomas (EAC) within 1 year of index endoscopy that diagnosed either nondysplastic Barrett’s esophagus (BE) or BE with low grade dysplasia in adults. This is an alarming high rate of missed EAC and deserves attention. These results highlight the need for stricter adherence to diagnostic protocol guidelines, further focus on advanced imaging, and a more proactive stance in treatment of gastroesophageal reflux disease (GERD). Highly prevalent, GERD occurs in 30% of Americans, and is the precursor to BE and EAC.

    Systemic four-quadrant biopsy is more effective than non-systemic biopsy at detecting BE. Although effective, multiple biopsies are cumbersome and often cost prohibitive. Dysplasia and EAC can be multifocal within the length of BE and may not be endoscopically distinguishable from nondysplastic BE resulting in a high rate of sampling errors. A recent meta-analysis showed promising results with advanced endoscopic imaging techniques and these need to be incorporated in clinical practice.

    While proton pump inhibitor (PPI) regimens are effective, they may cause patients to ignore reflux until it is too late. These medications improve acid exposure, but not other types of reflux, like bile, that can also cause damage to the esophagus and has been shown to be a factor in EAC. The key is to understand the patient’s underlying condition, and provide a continuum of care for managing GERD in order to prevent it from progressing to BE.

    Patients now have other options that can improve the underlying condition — which may be a weak lower esophageal sphincter (LES) muscle with or without a small (≤ 2 cm) hiatal hernia. Non-surgical options include Stretta therapy that uses low levels of radiofrequency energy to improve the size and structure of the weak LES muscle which results in reduced frequency of transient sphincter relaxations (tLESRs) and reflux events. Stretta has been extensively studied and has shown a durable effect lasting from 4–10 years. Other options include minimally invasive versions of endoscopic fundoplication for patients with weak LES and a small hiatal hernia. For patients with significantly altered anatomy such as a large hiatal hernia, laparoscopic antireflux surgery remains the option. An individualized patient centered approach to GERD and BE at specialized treatment centers is highly needed.

    • Nirav Thosani, MD, MHA
    • Ertan Digestive Disease Center of Excellence Memorial Hermann Hospital Texas Medical Center, Houston Assistant Professor of Gastroenterology, Hepatology, and Nutrition McGovern Medical School, UTHealth

    Disclosures: Thosani reports no relevant financial disclosures.