Primary Motility  Disorders of the  Esophagus
 The Esophageal
 Esophagogastric  Junction

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Volume: Barrett's Esophagus
Chapter: Dysplasia

Without a standardized sampling technique, can the average time required for dysplastic epithelium to develop on Barrett's epithelium be determined and for dysplastic cells to become invasive?

G.N.J. Tytgat (Amsterdam)

The mechanisms that lead to esophageal columnar metaplasia and dysplasia are poorly understood. Although we know that patients with columnar metaplasia usually have rather severe gastroesophageal reflux and often also a component of duodenogastroesophageal (biliary) reflux and have a rather large hiatal hernia (Figure 1) [1] with a common cavity phenomenon, in practice it remains very difficult to predict which patients with reflux disease will develop columnar metaplasia [2].

It is also largely unknown at which time columnar metaplasia develops. Most often patients are discovered as having columnar metaplasia at an age beyond 50 years and it is impossible at that time to appreciate when the columnar metaplasia developed and whether it was progressive.

Which patients are at risk of developing dysplastic changes and the velocity of such developments remains beyond our current understanding. Also the progression of dysplasia from low to high-grade and ultimately to cancer proves to be highly variable from one person to the other. Two studies have looked at that problem more in detail, a European and an American study (Figure 2 [3] and Figure 3 [4]). One can readily see that indeed the velocity of progressive worsening of dysplasia to ultimately early cancer is highly different in the patients shown.

Because it is impossible at present to predict when and how rapidly metaplasia and dysplasia will develop, one has to rely on a standardized sampling protocol. At present most clinicians certainly in the Western world do follow the guidelines designed by the American College of Gastroenterology [5]. In essence the advice is to carry out a surveillance endoscopy with four quadrant biopsies every two cm every three or perhaps every five

Figure 1. Axial length of hiatal hernia. Mean hernia size in patients with Barrett's esophagus was larger than in the other patient groups.

Figure 2. Development and progression of dysplasia in 5 patients with Barrett's esophagus who developed carcinoma. N : negative for dysplasia; L : low grade dysplasia (including indefinite for dysplasia; H: high grade dysplasia; C: carcinoma.

Figure 3. Progression of dysplasia to carcinoma in five patients with Barrett's esophagus.

years when there is no evidence of dysplastic change. If some of the biopsies do reveal lowgrade dysplasia, the advice is to repeat the endoscopy six monthly for the first year, and if there is no further worsening, then to continue surveillance annually. It is somewhat unclear what to do if further biopsies do not reveal dysplastic change. Empirically some would consider the patient at low risk, if there are two further endoscopies without any evidence of dysplasia. In case biopsies do reveal high-grade dysplasia (HGD), the advice is to repeat the biopsies some three months later after intense medical therapy and to have the biopsies checked by another experienced histopathologist. Obviously at that time it is mandatory to also rule out early cancer. Preferably this should be done by endosonography using high frequency ultrasound.

Once HGD is discovered, esophageal resection should be discussed if the patient is a good surgical risk. If esophageal resection is contra-indicated, then ablative therapy should be considered such as mucosal resection of the dysplastic area [6], followed either by additional mucosectomy of the surrounding mucosa or photodynamic therapy or other ablative therapies.

To what extent these guidelines are followed in clinical practice is unknown [7]. Even when followed adequately it is not known whether this methodology allows accurate detection of columnar metaplasia/dysplasia development. Several critical statements have been voiced in the literature, casting doubt on the validity of such screening policy. Yet, despite such inherent weaknesses standardized mucosal sampling remains for the time being the only possible method to detect worsening dysplasia.


1. Cameron AJ. Barrett's esophagus: prevalence and size of hiatal hernia. Am J Gastroenterol 1999;94:2054-205.

2. Weston AP, Badr AS, Hassanein RS. Prospective multivariate analysis of clinical, endoscopic, and histological factors predictive of the development of Barrett's multifocal high-grade dysplasia or adenocarcinoma. Am J Gastroenterol 1999;94:3413-3419.

3. Hameeteman W, Tytgat GNJ, Houthhoff HJ, Van Den Tweel JG. Barrett's oesophagus: development of dysplasia and adenocarcinoma. Gastroenterology 1989;96:249-256.

4. Williamson WA, Ellis FH, Gibb SP, Shahian DM, Aretz HT, Heatley GJ, Watkins E. Barrett's esophagus. Prevalence and incidence of adenocarcinoma. Arch Intern Med 1991;151:2212-2216.

5. Sampliner RE, and The Practice Parameters Committee of the American College of Gastroenterology. Practice guidelines on the diagnosis, surveillance, and therapy of Barrett's esophagus. Am J Gastroenterol 1998;93:1028-1032.

6. Ell C, May A, Gossner L, Pech 0, Günter E, Mayer G, Henrich R, Vieth M, Müller H, Seitz G, Stolte M. Endoscopic mucosal resection of early cancer and high-grade dysplasia in Barrett's esophagus. Gastroenterology 2000;118:670-677.

7. Van Sandick JW, Bartelsman JFWM, Van Lanschot JJB, Tytgat GNJ, Obertop H. Surveillance of Barrett oesophagus: physicians' practices and review of current guidelines. Eur J Gastroenterol Hepatol 2000;12:111-117.

Publication date: August 2003 OESO©2015