Primary Motility  Disorders of the  Esophagus
 The Esophageal
 Esophagogastric  Junction

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Volume: Barrett's Esophagus
Chapter: Diagnosis

What is the correlation between the mode of endoscopy (retroflexed versus antegrade) and the diagnosis of Barrett's esophagus?

C.M. Pring, D.M. Beardsmore, G.W.B. Clark (Leeds)

In addressing this issue, three important questions must be answered:

1) How is Barrett's esophagus defined?

2) What extra information is likely to be obtained by retroflexing the endoscope?

3) Will this extra information influence the subsequent management decisions?

Over the course of time the eponymous condition first described by Norman Barrett has changed so much in its definition that it now bears little resemblance to the condition that Barrett first described in his treatise of 1950 [1]. A succession of parameters required to diagnose Barrett's esophagus has evolved over the years. The columnar lined esophagus (CLE) [2], the 3 cm rule [3], specialized columnar epithelium [4] and short segment Barrett's [5] have all been implicated as criteria required to diagnose the condition. The current working definition which probably best describes Barrett's esophagus is "a change from normal esophageal squamous mucosa to columnar mucosa of any length visible on endoscopy and which shows specialized columnar epithelium on histology" [6]. By applying this definition however, specialized columnar epithelium at the gastroesophageal junction (GEJ) itself would not come under the umbrella of Barrett's esophagus.

Anatomically, the GEJ is best defined as lying within the cardia. Hayward described the cardia as the area between the insertion of the phreno-esophageal ligament and the GEJ at the proximal margin of the gastric folds [7]. He also noted that the cardia was normally lined with columnar epithelium which he termed "columnar mucosa junctional epithelium". Paull et al. also described a normal columnar "junctional" epithelium at this point [4]. This mucosa did not demonstrate the characteristic salmon pink pattern which is typical of the columnarized esophagus.

Nonetheless, despite attempts to find a suitable definition for Barrett's esophagus it is clear that the important entity is that of intestinal metaplasia. The malignant potential of what was traditionally termed Barrett's esophagus has been well documented [3]. However confusion over the relevance of columnar epithelium at the cardia has lead to the cardia being neglected. There is though increasing evidence that foci of intestinal metaplasia (IM) at the cardia exist [8] and may have a malignant potential similar to that of traditional Barrett's esophagus [9]. This evidence is complemented by the increasing incidence of adenocarcinoma of the cardia in the Western world [10].

Therefore, rather than correlating the mode of endoscopy with respect to the diagnosis of Barrett's esophagus, the focus of the question should be to correlate the mode of endoscopy with the presence of IM within the esophagus. That is to say, foci of intestinal metaplasia should be sought from the proximal margins of the gastric folds to the level of the squamocolumnar junction.

The next important issue is whether IM at the cardia is a condition which is common and so warrants investigation. Spechler et al. [8] echo the opinion of many in stating that finding intestinal metaplasia at the GEJ is abnormal and that by looking for IM at the cardia they estimate that the prevalence of Barrett's esophagus is 18%. By retroflexing the endoscope this has been shown to increase to 24% [11] and by staining biopsy specimens with alcian blue the prevalence rises even further to 36% [12]

As already mentioned, there is no doubt that IM of the esophagus is a premalignant condition [3]. Any focus of IM is capable of undergoing dysplastic change and ultimately becoming an invasive adenocarcinoma [13]

Columnarization of the esophagus and intestinalisation of the columnar epithelium are a result of the persistent injurious effects of gastric and bile refluxate [14]. The greatest incidence of IM occurs at the most proximal area of columnarization. This is because the pH resulting from the mixing of saliva and gastric acid in the proximal esophagus provides a microenvironment most suitable for the development of IM [15]. However, the columnar epithelium which lines the cardia and was previously described as normal junctional epithelium is itself thought to be a result of reflux disease. Studies in patients under the age of 20 who have no symptoms consistent with reflux disease reveal that there is no such area of junctional epithelium [16]. Bremner's classic experiments on dogs also highlighted the injurious effects of refluxate [17]. Therefore, it is likely that columnarization of the cardia precedes the development of foci of IM within that region, as is observed in the more proximal regions of the esophagus. The importance of IM at the cardia becomes more obvious when one considers that the risk of adenocarcinoma, is proportional to the extent of IM. Therefore, a patient with a long segment of Barrett's metaplasia has a higher risk of developing adenocarcinoma than a patient with a short segment of metaplasia. However within the population as a whole, there is a larger proportion of patients who have IM confined to the cardia than have IM spreading proximally.

As documented above, therefore, the effects of gastroesophageal reflux disease (GERD) (which is thought to affect 40% of the adult population) increase the risk of developing IM. Whether the presence of H. pylori also contributes to this process at the cardia remains a topic of hot debate [18]. However, a clearer understanding of the anatomy and physiology at the cardia and an increased awareness of its pathology have highlighted the clinicians' interest in this area. It could be argued though that any patient who is being endoscoped for GERD should be thoroughly assessed for foci of IM at the cardia.

Delineating the cardia can be difficult, even in the hands of the most skilled endoscopists. Examining the cardia is achieved most effectively by retroflexing the endoscope. It is recommended that the standard to be employed in any endoscopy unit should be one of circumferential antegrade and retrograde biopsies from the proximal margins of the gastric folds (i.e. the GEJ) up to the squamocolumnar junction. This will ensure the best chance of uncovering foci of IM within the esophagus.

The importance of being able to diagnose IM at the cardia becomes even more apparent when one considers treatment. It is recognized that patients found to have IM benefit from being enrolled in a surveillance programme [19]. It has also been suggested that antireflux surgery leads to a regression of IM at the cardia and protection in progression to adenocarcinoma [20]. Given the worrying increase in the incidence of adenocarcinoma of the cardia, many would argue that patients presenting with reflux disease should not be denied the opportunity to halt their potential march from GERD to IM at the cardia and adenocarcinoma.

Therefore a comprehensive investigation of patients presenting with GERD should include an extensive search for foci of IM within the esophagus. Circumferential antegrade and retrograde endoscopy and biopsy is probably the only way to achieve this and hence reduce the number of patients who fall victim to the metaplasia, dysplasia, carcinoma sequence which complicates Barrett's esophagus.


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10. Blot WJ, Devesa SS, Kneller RW, Fraumeni JF. The rising incidence of adenocarcinoma of the oesophagus and gastric cardia. JAMA 1991;265:1287-1289.

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12. Nandurkar S, Talley NJ, Martin CJ, Ng THK, Adams S. Short segment Barrett's oesophagus: prevalence, diagnosis and associations. Gut 1997;40:710-715.

13. Reid BJ, Weinstein WM. Barrett's oesophagus and adenocarcinoma. Ann Rev Med 1987;38:477-492.

14. Kauer WK, Peters JH, DeMeester TR, Ireland AP, Bremner CG, Hagen JA . Mixed reflux of gastric and duodenal juices is more harmful to the oesophagus than gatric juice alone. The need for surgical therapy re-emphasised. Ann Surg 1995;222:525-533.

15. Fitzgerald RC, Omary MB, Triadafilopoulos G. Dynamic effects of acid on Barrett's oesophagus. An ex vivo proliferation and differentiation model. J Clin Invest 1996;98:2120-2128.

16. Chandrasoma P. Pathophysiology of Barrett's oesophagus. Semin Thorac Cardiovasc Surg 1997;9:270-278.

17. Bremner CG, Lynch VP, Ellis FH. Barrett's oesophagus: congenital or acquired? An experimental study of oesophageal mucosal regeneration in the dog. Surgery 1970;68:209-216.

18. Bowrey DJ, Clark GWB Williams GT. Patterns of gastritis in patients with gastro-oesophageal reflux disease. Gut 1999;45:798-803.

19. Peters JH, Clark GWB, Ireland AP, Chandrasoma P, Smyrk TC, DeMeester TR. Outcome of adenocarcinoma arising in Barrett's oesophagus in endoscopically surveyed and nonsurveyed patients. J Thor Cardiovasc Surg 1994;108(5):813821.

20. DeMeester SR, Campos GM, DeMeester TR. The impact of an antireflux procedure on intestinal metaplasia of the cardia. Ann Surg 1998;228:547-556.

Publication date: August 2003 OESO©2015