Primary Motility  Disorders of the  Esophagus
 The Esophageal
 Esophagogastric  Junction

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Volume: Barrett's Esophagus
Chapter: Dysplasia

What are the elements of an endoscopic biopsy protocol that would minimize sampling errors?

A.P. Weston (Kansas City)

The ability of endoscopic biopsies to detect early cancers and/or high-grade dysplasia (HGD) in Barrett's esophagus is dependent upon a number of factors: the endoscopists, the video image quality and type of endoscope used, the type of biopsy forcep used, and the biopsy protocol performed.

Examination of Barrett's mucosa and intense scrutiny for any surface irregularities that could be indicative of HGD and or cancer is very dependent upon the patience, skill and keenness of the endoscopists and equipment used (fiber optic versus video endoscope, type of video image processing system and its display). Newer generation endoscopes with improved image processing and display capabilities that markedly enhance the color image and resolution will undoubtedly lead to increased detection of advanced dysplasia/early cancers.

A number of studies have prospectively evaluated biopsy tissue samples in terms of volume of tissue obtained and its depth. Bernstein et al. [1] showed that large capacity biopsy forceps obtained significantly larger sized (volume, p = 0.02) specimens compared to standard biopsy forceps and that needle versions of biopsy forceps obtain deeper biopsy specimens than non-needle versions. Hence, when dealing with surveillance of Barrett's esophagus mucosa for dysplasia/cancer, sampling error can be reduced by using a biopsy forceps that obtains a specimen that has a greater surface area/volume of tissue per biopsy.

Three studies have compared endoscopic biopsy histology to surgical pathology after esophagectomy in patients with Barrett's HGD. Cameron and Carpenter [2] obtained four-quadrant biopsies at 2 cm intervals using standard biopsy forceps of 19 Barrett's HGD patients with normal mucosal appearance. Two (10.5%) unsuspected T1smN0M0 adenocarcinomas were found on esophagectomy in these 19 HGD cases. Falk et al. [3] compared endoscopic diagnosis of HGD with surgical pathologic diagnosis in Barrett's patients. In this study, four-quadrant biopsies were taken of Barrett's esophagus at 2 cm intervals with either standard and jumbo biopsy forceps with results shown in Table I.

Overall, cancer was missed in a third of cases of HGD patients when using an endoscopic biopsy protocol of four-quadrant every 2 cm, irrespective of biopsy forceps type (33% for jumbo and 38% for standard).

Table I. Endoscopic biopsy versus surgical pathology diagnosis in patients with Barrett's high-grade dysplasia: effect of biopsy forceps.

Most recently, Reid et al. [4] have publisheddefinitive results that clearly establish the need to perform biopsies at 1 cm intervals to optimize thedetection of early cancers in Barrett's esophagus patients with HGD. The Seattle HGD endoscopic biopsy protocol entails:

1) use of a therapeutic scope in order to use large particle/jumbo biopsy forceps;
2) initial careful scrutiny of entire Barrett's mucosa for any irregularities (tiny nodules, patches of friability/erythema, erosions, ulcers, strictures, or regions where esophageal wall appears fixed and or poorly distensible). These areas are separately target biopsies with jumbo biopsy forceps;
3) 4 quadrant jumbo biopsies at 1 cm intervals throughout length of Barrett's esophagus (and inclusive of any neosquamous reepithelialized tissue growth and cardia). Using this protocol, the extent, stage, and endoscopic appearance of 45 cancers that were detected within 123 HGD Barrett's esophagus patients was examined comparing 1 cm 4 quadrant method to a modeled, 2 cm 4 quadrant method. In 82% (37 of 45), the cancer was detected in biopsies from a single 1 cm level of the esophagus, and in 31 patients (69%) cancer was detected in a single endoscopic biopsy specimen. Three patients had multifocal cancers and 5 had cancer detected within two adjacent 1 cm levels. Target biopsies of endoscopically visible lesions yielded a diagnosis of cancer in 15/45 (33%) of patients. These authors then examined how many cancers would have been detected using a four-quadrant 2 cm protocol in those patients without visible lesions - only 13 or 26 cancers would have been diagnosis (50% miss rate using four-quadrant, 2 cm protocol). Hence, a standard of care has been established for HGD. Full implementation of the Seattle protocol (4 quadrant jumbo biopsies every 2 cm during surveillance of uncomplicated Barrett's esophagus followed by 4 quadrant biopsies at 1cm intervals once HGD has been identified) should be embraced, preached and utilized in daily practice until definitive objective, prospective data establishes an alternative gold standard.


1. Bernstein DE, Barkin JS, Reiner DK, Lubin J, Phillips RS, Grauer L. Standard biopsy forceps versus large-capacity forceps with and without needle. Gastrointest Endosc 1995;41:573-576.

2. Cameron AJ, Carpenter HA. Barrett's esophagus, high-grade dysplasia, and early adenocarcinoma. A pathological study. Am J Gastroenterol 1997;92:586-591.

3. Falk GW, Rice TW, Goldblum JR, et al. Jumbo biopsy forceps protocol still misses unsuspected cancer for Barrett's esophagus with high-grade dysplasia. Gastrointest Endosc 1999;49:170-176.

4. Reid BJ, Blount PL, Feng Z, Levine DS. Optimizing endoscopic biopsy detection of early cancers in Barrett's high-grade dysplasia. Am J Gastroenterol 2000;95:3089-3095.

Publication date: August 2003 OESO©2015