When should I repeat an upper endoscopy (EGD) for Barrett's esophagus with reactive epithelial atypia (indefinite for dysplasia)?

Repeat EGD for Barrett's Esophagus with Reactive Epithelial Atypia (Indefinite for Dysplasia)

Repeat EGD in 8-12 weeks after intensifying acid suppression to twice-daily PPI therapy. 1

Immediate Management Steps

Optimize Acid Suppression First

• Do not perform surveillance biopsies in the presence of active inflammation (erosive esophagitis, Los Angeles grade C or D), as inflammation causes reactive changes that mimic dysplasia and lead to overdiagnosis. 1
• Intensify acid suppression to twice-daily PPI therapy (taken 30-60 minutes before meals) for 8-12 weeks before repeating endoscopy. 1, 2
• This waiting period allows inflammation to resolve and helps distinguish true dysplasia from reactive atypia. 1

Confirm Diagnosis with Expert Pathology Review

• All indefinite for dysplasia diagnoses should be confirmed by an expert GI pathologist before proceeding with repeat endoscopy, given significant interobserver variability in this category. 1
• Reactive atypia has a 27% rate of AMACR immunoreactivity (a dysplasia marker), highlighting the diagnostic challenge in distinguishing it from true dysplasia. 3

Repeat Endoscopy Protocol (at 8-12 Weeks)

Technical Requirements

• Use high-definition white-light endoscopy as the standard of care, which is more sensitive than standard-definition for detecting BE-related neoplasia. 1
• The endoscopist should have expertise in managing Barrett's neoplasia, ideally with experience in endoscopic resection, as they best recognize subtle mucosal abnormalities. 1

Biopsy Protocol

• Follow the Seattle protocol: four-quadrant biopsies every 1-2 cm throughout the Barrett's segment. 1
• Target any visible lesions first (nodularity, ulceration, plaques, areas of depression, strictures, mucosal discoloration—no matter how subtle). 1
• Document the extent using the Prague classification (circumferential and maximal extent). 1

Critical Rationale for This Timing

High Risk of Missed Dysplasia

• A systematic review found a 25.3% missed adenocarcinoma rate (diagnosed within 1 year) in patients with nondysplastic BE and low-grade dysplasia, emphasizing the need for careful repeat examination. 1
• Prevalent dysplasia is common (9.3%) in patients initially diagnosed with indefinite for dysplasia, including high-grade dysplasia and adenocarcinoma. 4

Persistent Indefinite for Dysplasia Carries Higher Risk

• If indefinite for dysplasia persists on repeat endoscopy (occurs in 30% of cases), the progression rate to low-grade dysplasia is 7.86 per 100 patient-years versus 4.78 for non-persistent cases. 4
• Persistent indefinite for dysplasia confers a 3-fold increased risk (OR 3.23) of progression to low-grade dysplasia. 4

Subsequent Management Based on Repeat Findings

If Downgraded to Nondysplastic Barrett's

• Manage as nondysplastic Barrett's esophagus with surveillance every 3-5 years. 1, 5

If Indefinite for Dysplasia Persists

• Continue close surveillance every 6 months given the 3-fold increased progression risk. 4
• Consider this a higher-risk category requiring more intensive monitoring than standard nondysplastic Barrett's. 4

If Upgraded to Low-Grade Dysplasia

• Perform surveillance every 6 months for two examinations, then annually unless it reverts to nondysplastic Barrett's. 1
• Refer to an expert center for discussion of endoscopic eradication therapy versus continued surveillance. 1

If High-Grade Dysplasia or Adenocarcinoma Found

• Immediate referral for endoscopic resection and ablation therapy at an expert center. 1

Common Pitfalls to Avoid

• Do not repeat endoscopy before optimizing acid suppression—this leads to persistent inflammation and continued diagnostic uncertainty. 1
• Do not accept indefinite for dysplasia without expert pathology review—interobserver variability is highest in this category, and up to 40% of high-grade dysplasia cases have adenocarcinoma at resection. 6
• Do not perform surveillance at standard nondysplastic intervals if indefinite for dysplasia persists—these patients require closer monitoring. 4
• Do not skip the Seattle protocol—sampling error is a major cause of missed dysplasia. 1