Primary Motility  Disorders of the  Esophagus
 The Esophageal
 Esophagogastric  Junction

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Volume: The Esophagogastric Junction
Chapter: Esophageal columnar metaplasia (Barrett s esophagus)

What dye-spraying technique should be chosen in cylindric mucosa?

H.J. Dittler, W.K.H. Kauer (Munich)

The incidence of adenocarcinoma is increasing faster than any other cancer in the United States or Western Europe [1, 2]. Adenocarcinoma is most common in white males with a male to female ratio of 5:1. The disease becomes more common after the age of 40. In Caucasians the incidence of esophageal adenocarcinoma rose 74% between 1973 and 1982 [3].

Barrett's esophagus (BE) is a condition in which normal squamous epithelium is replaced by metaplastic columnar epithelium [4]. Proper recognition of patients with BE at endoscopy is imperative because of the malignant potential of Barrett's epithelium, which is thought to proceed through a metaplasia-dysplasia-carcinoma sequence [5]. Short segments of Barrett's epithelium have also been demonstrated in association with many gastroesophageal junction adenocarcinomas [6].

Columnar epithelium in the esophagus has a characteristic red color and velvet-like texture that contrasts sharply with the pale, glossy appearance of adjacent squamous epithelium [7]. Although endoscopic examination can usually distinguish columnar from squamous epithelium in the esophagus, the differentiation between specialized columnar epithelium and gastric columnar epithelium can be made only by histological examination of biopsies.

Different staining techniques are available for squamous epithelium in the esophagus or columnar epithelium in the stomach. Vital staining at endoscopy with Lugol's solution has been advocated to better delineate subtle mucosal changes in squamous cells of the esophagus. Normal epithelium with its relatively high glycogen content stains brown, while dysplastic changes or cancer of the squamous epithelium remain unstained [8, 9].

Toluidine blue staining has also been used to better define subtle changes in the mucosal surface of squamous epithelium [10]. An endoscopic dying method with methylene blue solution has been described as accurate and safe for diagnosing cancer and intestinal metaplasia in the stomach [11]. Introduction of methylene blue into the stomach selectively dyed cancer and intestinal metaplasia dark blue, while normal gastric mucosa, the margin and scar of gastric ulcer, erosions, benign polyp and gastritis without intestinal metaplasia remained undyed.

In a recent report by Canto et al. this technique was adopted for detecting intestinal metaplasia and dysplasia in BE. In an ongoing prospective controlled study, she compared the diagnostic yield of endoscopic surveillance using methylene blue directed biopsies with 4-quadrant random biopsies. Methylene blue selectively stains intestinal metaplasia in BE, including cells with dysplasia [12].

In our own ongoing trial we can confirm that the application of methylene blue results in a dark blue coloration of columnar epithelium invaded by cancer or intestinal metaplasia. Normal esophageal mucosa appeared unchanged and from these findings, cancer and intestinal metaplasia were clearly distinguishable from other diseases of the esophageal mucosa. Double staining with Lugol's solution and methylene blue, to make the squamocolumnar junction more pronounced, did not increase the incidence of positive biopsies.

It is essential for the dying method with methylene blue, that the mucosa is not exposed to any mucus. The use of a mucolytic agent before the administration of methylene blue is highly recommended. Although the mechanism of methylene blue dying is not known at present, it seems, that changes of the nature of cells and the mucus or the abnormal secretion of pathological mucus may play a role in the dying process. This certainly needs further investigation.

In conclusion, at the present time single staining with methylene blue seems to be the diagnostic method of choice in detecting cancer or intestinal metaplasia in esophageal columnar epithelium. The mechanism still needs further investigation as well as more clinical data are needed to finally judge its routine use.


1. Blot WJ, Devesa SS, Kneller RW, et al. Rising incidence of adenocarcinoma of the esophagus and gastric cardia. JAMA 1991:265:1287-1289.

2. Boring CC, Squires BA, Tong T. Cancer statistics 1993. Cancer 1993;43:7-26.

3. Reid BJ, Haggitt RC, Rubin CE, et al. Observer variation in the diagnosis of dysplasia in Barrett's esophagus. Hum Pathol 1988;19:166-178.

4. Hamilton SR, Smith RRL, Cameron JL. Prevalence and characteristics of Barrett's esophagus in patients with adenocarcinoma of the esophagus or esophagogastric junction. Hum Pathol 1988;19:942-948.

5. Stein HJ, Siewert JR. Barrett's esophagus: pathogenesis, epidemiology, functional abnormalities, malignant degeneration, and surgical management. Dysphagia 1993;8:276-288.

6. Clark GWB, Smyrk TC, Burdiles P, et al. Is Barrett's metaplasia the source of adenocarcinomas of the cardia? Arch Surg 1994;129:609-614.

7. Spechler SJ, Goyal RK. Barrett's esophagus. N Engl J Med 315:362-371.

8. Misumi A, Harama K, Mura Kami A, et al. Early diagnosis of esophageal cancer. Analysis of 11 cases of esophageal cancer. Ann Surg 1990;210:732.

9. Misumi A, Harama K, Mura Kami A, et al. Role of Lugol dye endoscopy in the diagnosis of early esophageal cancer. Endoscopy 1990;22:12.

10. Contini S, Consigli GF, DiLecce F, et al. Vital staining of oesophagus in patients with head and neck cancer still a worthwhile procedure? Ital J Gastroenterol 1991;21:5.

11. Fennerty MB, Sampliner RE, McGee DL, et al, Intestinal metaplasia of the stomach: identification by a selective mucosal staining technique. Gastrointest Endosc 1992;38:696-698.

12. Canto M, Setrakian S, Chak A, et al. Methylene blue-directed biopsy for improved detection of intestinal metaplasia and dysplasia in Barrett's esophagus: a controlled sequential trial. Gastrointest Endosc 1996;43:332(A165).

Publication date: May 1998 OESO©2015