SEARCH

SEARCH BY CITATION

Keywords:

  • Barrett's esophageal adenocarcinoma;
  • Barrett's esophageal adenocarcinoma spreading below squamous epithelium;
  • magnifying endoscopy with narrow-band imaging (ME-NBI)

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Case Report
  5. Discussion
  6. Conflict of Interests
  7. References

It has been described that most cases of Barrett's esophageal adenocarcinoma in Japan are cases of Barrett's esophageal adenocarcinoma on a background of short-segment Barrett's esophagus, frequently occurring rostrad to Barrett's epithelium, adjacent to the squamous epithelium of the right wall of the esophagogastric junction. Barrett's esophageal adenocarcinoma may spread below the squamous epithelium when the tumor is situated adjacent to the squamocolumnar junction, so that it is usually difficult to diagnose its presence and extent by conventional endoscopy alone. We have noted that the spread of Barrett's esophageal adenocarcinoma below the squamous epithelium is recognizable as annular vascular formations (AVF) by magnifying endoscopy with narrow-band imaging (ME-NBI), and have verified it by 3-D stereo-reconstruction using serial sections from a specimen of the same lesion. When horizontalcross-sections of the tissue were viewed from the surface, AVF emerged at a depth of approximately 100 μm from the surface and disappeared at a depth of approximately 300 μm. Therefore, it would be presumed to be difficult to visualize the characteristic structural features by ME-NBI if the carcinomatous glandular ducts were situated deeper than approximately 300 μm underneath a thick layer of squamous epithelium. Thickness of the overlying squamous epithelium may be a limiting factor for whether or not the characteristic structural features can be detected.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Case Report
  5. Discussion
  6. Conflict of Interests
  7. References

THE INCREASING NUMBER of cases of Barrett's esophagus or Barrett's adenocarcinoma over a background of gastroesophageal reflux disease (GERD) has become an issue of concern in Europe and the USA. In particular, among Caucasian males, the incidence of Barrett's adenocarcinoma appears to be exceeding that of squamous cell carcinoma of the esophagus.[1, 2] In Japan, likewise, the number of cases of GERD has tended to increase in recent years,[3] and concern is rising about possible future increase in the incidence of Barrett's adenocarcinoma due to westernization of the dietary habits etc. and decreasing prevalence of Helicobacter pylori infection.

Recently, in Japan, detailed observations of Barrett's superficial carcinoma have been documented, and there are reports purporting to demonstrate the usefulness of magnifying endoscopy with narrow band imaging (ME-NBI) in diagnosing specialized intestinal metaplasia and high-grade dysplasia.[4-8] Reports of cases treated by endoscopic methods following early detection of malignancy have also been sporadically reported in the literature.[9] Barrett's esophageal adenocarcinoma may spread below the squamous epithelium when the tumor is situated adjacent to the squamocolumnar junction (SCJ), so that it is usually difficult to diagnose its presence and extent by conventional endoscopy alone; in such cases, acetic acid spray has been reported to be useful.[10]

In the present report, we describe the case of a patient recently encountered by us in whom a diagnosis of Barrett's esophageal adenocarcinoma spreading below the squamous epithelium was made by ME-NBI. Endoscopic submucosal dissection (ESD) was carried out and the endoscopic findings were verified by 3-D stereo-reconstruction from serial tissue sections of the lesion.

Case Report

  1. Top of page
  2. Abstract
  3. Introduction
  4. Case Report
  5. Discussion
  6. Conflict of Interests
  7. References

THE PATIENT, AN 84-year-old man, with a history of hypertension and hyperlipidemia, had been receiving oral proton pump inhibitor treatment for reflux esophagitis. The patient presented to a neighborhood clinic with a history of heartburn since the end of January 2010, and was diagnosed as having Barrett's esophageal adenocarcinoma by endoscopic examination of the upper gastrointestinal (GI) tract, and was referred to us for treatment. At the initial visit, routine endoscopic examination with indigocarmine spray revealed short-segment Barrett's esophagus (SSBE) at the esophagogastric junction (EGJ) associated with GERD Grade C, along with a red depressed lesion measuring 20 mm in its major axis at the 0 o'clock position in the region of the SSBE. A biopsy specimen taken from that lesion at the previous clinic was diagnosed as well-differentiated adenocarcinoma (Fig. 1). ME-NBI was useful in estimating the lesion extent, as the lesion was recognizable as a brown spot under low-power magnification (Fig. 2).

figure

Figure 1. (a) Short-segment Barrett's esophagus (SSBE) is noted at the esophagogastric junction, associated with gastroesophageal reflux disease Grade C. (b) A red depressed lesion, approximately 20 mm in diameter (arrows), is noted in the anterior wall of the SSBE. (c) Retroflex endoscopic view also shows a lesion (arrows) adjacent to the squamous epithelium. (d) The lesion is more clearly demarcated by indigocarmine spray, and the extent of the lesion is delineated by red arrows.

Download figure to PowerPoint

figure

Figure 2. (a,b) The lesion is recognizable as a brown spot by magnifying endoscopy with narrow band imaging under low magnification. Extent of the lesion is delineated by red arrows.

Download figure to PowerPoint

ME-NBI (red square frame in Fig. 3a) revealed circinate blood vessels in structural patterns varying widely in size (Fig. 3b). Histopathologically, this region was composed of sparsely arranged cells showing the features of well-differentiated adenocarcinoma (Fig. 3c). ME-NBI finding (yellow square frame in Fig. 3a), in contrast, showed reticular vascular patterns, with densely and regularly arranged cells showing features of differentiated adenocarcinoma (Fig. 4). Endoscopic ultrasonographic (EUS) examination done on a later day demonstrated hypoechoic areas varying considerably in size within the second and third layers, whereas the third layer appeared smooth; hence, there were no findings indicative of any obvious submucosal invasion (Fig. 5). The lesion, therefore, was diagnosed as 0 IIc, intramucosal carcinoma (20 mm in diameter) on a background of SSBE, and ESD was carried out. After marking with an argon plasma coagulator, ESD was carried out and completed without any complications, such as bleeding or perforation. Histopathologically, the lesion was a well-differentiated adenocarcinoma measuring 17 × 11 mm in size, classified as intramucosal cancer, with no venous invasion, but showing lymphatic invasion within the lamina propria mucosae. The hypoechoic areas in the third layer noted on EUS were found to be dilated esophageal glands. Histological mapping of the specimen revealed differentiated carcinoma spreading extensively below the squamous epithelium (Fig. 6). When reviewed, ME-NBI findings of the same region showed sporadic annular vascular formations (AVF) under normal squamous epithelium (Fig. 7). We prepared 80 3-μm serial sections from a specimen of the region showing AVF, then carried out immunostaining of the superficial blood vessels for CD31 (brown staining = positive), captured the stained tissue data on a personal computer (Fig. 8a), and carried out 3-D stereo-reconstruction of frontal views of the region using a software program (Ratoc System Engineering Co., Tokyo, Japan). When superimposed serial tissue sections were cut vertically from the surface down towards the muscularis mucosae, AVF emerged at a depth of approximately 100 μm from the surface and disappeared at a depth of approximately 300 μm (Fig. 8b–d). It follows that when a horizontal cross-sectional view of the stereo-reconstructed image was observed from the surface, blood vessels appeared to be surrounding carcinomatous ducts, which were considered as the structures visualized as the AVF by ME-NBI.

figure

Figure 3. (a) Endoscopic narrow-band image. (b) Magnifying endoscopy with narrow band imaging finding of the region in the red square frame in part (a). Note the structural patterns varying widely in size and encasing circinate blood vessels. (c) Histopathological image of the lesion shown in part (b) showing sparsely arranged cells with features suggestive of differentiated adenocarcinoma.

Download figure to PowerPoint

figure

Figure 4. (a) Magnifying endoscopy with narrow band imaging finding of the region in the yellow square frame in Figure 3(a). Note the elliptical vascular pattern. (b) Histopathological image of the legion shown in part (a) showing densely and regularly arranged cells with features suggestive of differentiated adenocarcinoma.

Download figure to PowerPoint

figure

Figure 5. Hypoechoic areas are noted within the second and third layers. The third layer appears smooth and shows no finding indicative of any obvious submucosal invasion.

Download figure to PowerPoint

figure

Figure 6. (a) Histological mapping of a fixed, resected tissue specimen. Red line, intramucosal cancer; green circle, esophageal gland. Well-differentiated adenocarcinoma, 17 × 11 mm, DMM, ly (+) (in LPM), /v (−), HM/VM (−). (b) Histopathological image of section 11 in part (a). Carcinoma extensively spreading below the squamous epithelium, with an underlying dilated esophageal gland.

Download figure to PowerPoint

figure

Figure 7. (a) Annular vascular formations (AVF; arrows) are noted below the normal squamous epithelium. (b) High-magnification of AVF noted in part (a).

Download figure to PowerPoint

figure

Figure 8. (a) Superficial blood vessels stained brown are noted in this CD31-immunostained section. (b–d) Eighty serial sections of the specimen shown in part (a) were prepared, tissue data were captured on a personal computer, and 3-D stereo-reconstruction was carried out of the frontal views. Red represents blood vessels and white represents ductal carcinoma. Blood vessels appear to be surrounding the ductal carcinoma.

Download figure to PowerPoint

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Case Report
  5. Discussion
  6. Conflict of Interests
  7. References

IT HAS BEEN described that most cases of Barrett's esophageal adenocarcinoma in Japan, unlike those reported from Europe and the USA, are cases of Barrett's esophageal adenocarcinoma on a background of SSBE, frequently occurring rostrad to Barrett's epithelium, adjacent to the squamous epithelium of the right wall of the EGJ.[11] Barrett's esophageal adenocarcinoma characteristically spreads below the squamous epithelium and, furthermore, adenocarcinomas, which destroy normal squamous epithelium, can expose the surface.[12] Oyama et al. have stated that routine endoscopic findings of tumor spreading below the squamous epithelium include the following: the tumor is as thick as a submucosal tumor, abnormal blood vessels can be seen through the overlying squamous epithelium, and there are pores etc. in the squamous epithelium.[13] Yamagata et al. reported the usefulness of acetic acid spray, and that the findings thereof consisted of pale whitening changes such as pores, small white plaques and sulciform structures.[10]

We have noted that the spread of Barrett's esophageal adenocarcinoma below the squamous epithelium is recognizable as AVF by ME-NBI, and have verified it by 3-D stereo-reconstruction using serial sections from a specimen of the same lesion. When horizontal cross-sections of the tissue were viewed from the surface, AVF emerged at a depth of approximately 100 μm from the surface and disappeared at a depth of approximately 300 μm. Therefore, it would be presumed to be difficult to visualize the characteristic structural features by ME-NBI if the carcinomatous glandular ducts were situated deeper than approximately 300 μm underneath a thick layer of squamous epithelium. Thickness of the overlying squamous epithelium may be a limiting factor for whether or not the characteristic structural features can be detected. The ability of identifying the said structural features, therefore, is to carry out the ME-NBI observation under maximum magnification, with the overlying squamous epithelium kept thinned by pressing it with the tip hood of the endoscope.

Conflict of Interests

  1. Top of page
  2. Abstract
  3. Introduction
  4. Case Report
  5. Discussion
  6. Conflict of Interests
  7. References

AUTHORS DECLARE NO conflict of interests for this article.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Case Report
  5. Discussion
  6. Conflict of Interests
  7. References
  • 1
    Cameron AJ. Epidemiology of Barrett's esophagus and adenocarcinoma. Dis. Esophagus 2002; 15: 106108.
  • 2
    Devesa SS, Blot WJ, Fraumeni JF Jr. Changing patterns in the incidence of esophageal and gastric carcinoma in the United States. Cancer 1998; 83: 20492053.
  • 3
    Hongo M, Shoji T. Epidemiology of reflux disease and CLE in East Asia. J. Gastroenterol. 2003; 38 (Suppl 15): 2530.
  • 4
    Goda K, Tajiri H, Ikegami M, Urashima M, Nakayoshi T, Kaise M. Usefulness of magnifying endoscopy with narrow band imaging for the detection of specialized intestinal metaplasia in columnar-lined esophagus and Barrett's adenocarcinoma. Gastrointest. Endosc. 2007; 65: 3646.
  • 5
    Kara MA, Ennahachi M, Fockens P, ten Kate FJ, Bergman JJ. Detection and classification of the mucosal and vascular patterns (mucosal morphology) in Barrett's esophagus by using narrow band imaging. Gastrointest. Endosc. 2006; 64: 155166.
  • 6
    Sharma P, Bansal A, Mathur S et al. The utility of a novel narrow band imaging endoscopy system in patients with Barrett's esophagus. Gastrointest. Endosc. 2006; 64: 167175.
  • 7
    Sharma P, Weston AP, Topalovski M, Cherian R, Bhattacharyya A, Sampliner RE. Magnification chromoendoscopy for the detection of intestinal metaplasia and dysplasia in Barrett's oesophagus. Gut 2003; 52: 2427.
  • 8
    Singh R, Anagnostopoulos GK, Yao K et al. Narrow-band imaging with magnification in Barrett's esophagus: Validation of a simplified grading system of mucosal morphology patterns against histology. Endoscopy 2008; 40: 457463.
  • 9
    Ikeda K, Isomoto H, Oda H et al. Endoscopic submucosal dissection of a minute intramucosal adenocarcinoma in Barrett's esophagus. Dig. Endosc. 2009; 21: 3436.
  • 10
    Yamagata T, Hirasawa D, Fujita N et al. Efficacy of acetic acid-spraying method in diagnosing extension of Barrett's cancer under the squamous epithelium. Dig. Endosc. 2012; 24: 309314.
  • 11
    Tomoyuki K, Yasuhiko A, Katsunori I et al. Diagnosis of Barrett's cancer by the normal endoscopy observation. Stom. Intest. (Tokyo) 2011; 12: 18001814. (In Japanese with English abstract).
  • 12
    Tadakazu S, Ryoji K, Hatsu T. Pathological feature of esophagogastric adenocarcinoma. Stom. Intest. (Tokyo) 2009; 7: 10831094. (In Japanese with English abstract).
  • 13
    Oyama T, Tomori A, Takahashi A et al. Diagnosis of lateral extension of Barrett's high grade dysplagia using magnified endoscopy. Stom. Intest. (Tokyo) 2011; 12: 18361842. (In Japanese with English abstract).