4-14-4 Rule: More Biopsies Needed For Eosinophilic Esophagitis

Briefly noted: AL Krarup et al. Endoscopy. 2021 Jan;53(1):15-24. doi: 10.1055/a-1206-0852. Implementation of a biopsy protocol to improve detection of esophageal eosinophilia: a Danish registry-based study

In 2011, leaders of regional endoscopy units in Northern Denmark reached a consensus on a protocol to take eight biopsy samples in dysphagia patients (four biopsies from 4 cm and 14 cm above the esophagogastric junction-“4-14-4 rule”) regardless of the macroscopic appearance.

Key finding:  The number of patients with esophageal eosinophilia detected per year increased 50-fold after the protocol was implemented in 2011 (median of 1 [interquartile range 0-3] vs. 52 [47-56]; P < 0.001), and the number of biopsy samples per patient doubled (median 4 [4-5] vs. 8 [6-9]; P < 0.04). In total, there were 309 with esophageal eosinophilia identified from 2007-2017.

My take: This study provides more data that more biopsies help identify more cases of eosinophilic esophagitis.

Related blog posts:

  • Best Approach for Identifying Eosinophilic Esophagitis Prior studies have shown higher yield when taking 5 or 6 biopsies rather than fewer biopsies; thus, the location of biopsies may not be as important as the number of specimens. Also, prior studies have shown that having another pathologist review the slides can increase the yield by ~20%; this indicates that careful review of specimens by itself is helpful.  Perhaps, more specimen containers will increase the time that a pathologist reviews the biopsies.
  • Looking Twice for Eosinophilic Esophagitis

Best Approach for Identifying Eosinophilic Esophagitis

A recent study (K Radicic, RF Stokes. Clin Gastroenterol Hepatol 2019; 1408-9) indicated that taking biopsies from three esophageal areas (proximal, mid, and distal)  improved the likelihood of identifying eosinophilic esophagitis (EoE).

Key findings:

  • In their study, among 96 patients with EoE, 55.2% were positive (>15 eos/hpf) in only 1 of the 3 levels.
  • 17 patients (17.7%) were positive in the mid-esophagus alone, and 6 patients (6.3%) were positive in the proximal esophagus alone.

The authors state that a 2-level biopsy protocol missed the diagnosis of EoE in roughly 1 of 5 patients.

My take: This study is provocative. However, the reasons why 3 levels improved their yield could be related to other factors rather than location.

  1. Prior studies have shown higher yield when taking 5 or 6 biopsies rather than fewer biopsies; thus, the location of biopsies may not be as important as the number of specimens
  2. Prior studies have shown that having another pathologist review the slides can increase the yield by ~20%; this indicates that careful review of specimens by itself is helpful.  Perhaps, more specimen containers will increase the time that a pathologist reviews the biopsies.

My view is that if adequate numbers of biopsies are taken from several locations, a single jar for all the specimens should suffice (& reduce costs) –though a formal study could be beneficial to confirm this.

Related blog posts:

From NASPGHAN 2014 EoE Slide Set