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Endoscopic classification of Barrett's esophagus
REVIEW ARTICLE Endoscopic classification of Barrett’s esophagus Moises Guelrud, MD, Elissa E. Ehrlich, MD Boston, Massachusetts
The incidence of esophageal adenocarcinoma has risen steadily over the past 10 years. Patients with Barrett’s esophagus are at increased risk for the development of adenocarcinoma.1,2 Barrett’s esophagus was defined in the past by the macroscopic appearance and length of columnar mucosa in the esophagus. In 1983, Skinner et al.3 restricted the term Barrett’s esophagus to identify only those patients who had columnar epithelium 3 cm or greater in length in the distal esophagus. This criterion was established to prevent overdiagnosis of Barrett’s esophagus. Then, in 1994, Spechler et al.4 published an influential article that stated that goblet cells were present at the gastroesophageal junction in 18% of patients with findings that did not fit the 3 cm of columnar-type epithelium rule. Because goblet cells are a marker of specialized intestinal epithelium, this finding was labeled shortsegment Barrett’s esophagus. The diagnosis of Barrett’s esophagus is established when intestinal metaplasia is found in biopsy specimens obtained from salmon-colored mucosa in the distal esophagus proximal to the junction of the esophagus and stomach. It is this intestinal metaplasia that is associated with the increased risk of adenocarcinoma. The salmon-colored mucosa in the distal esophagus is columnar and consists of a mosaic of fundic mucosa, cardia mucosa, and intestinal metaplasia. Thus, the distribution of intestinal metaplasia within the salmon-colored, columnar mucosa of the esophagus is patchy. The yield of biopsy specimens of columnar-type mucosa in the distal esophagus for the detection of intestinal metaplasia varies from 25% to 50% in short-segment
Current affiliations: Division of Gastroenterology, Tufts University School of Medicine, Tufts New England Medical Center, Boston, Massachusetts. Reprint requests: Moises Guelrud, MD, Tufts University School of Medicine, Director of Advanced Endoscopic Therapy, Division of Gastroenterology, Tufts New England Medical Center, 750 Washington St., Box #233, Boston, MA 02111. Copyright Ó 2004 by the American Society for Gastrointestinal Endoscopy 0016-5107/$30.00 PII: S0016-5107(03)02508-2 58
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Barrett’s esophagus5,6 and up to 80% in longsegment Barrett’s esophagus.7 The development of high-resolution and magnifying endoscopy during the past decade has significantly improved the ability to image the GI mucosal surface and target biopsy specimens. Many studies have demonstrated the diagnostic capabilities and limitations of magnifying endoscopy. For the endoscopist unfamiliar with magnifying endoscopy, the images of the mucosal surface may be difficult to interpret. However, magnifying endoscopy was used to evaluate and differentiate benign from malignant polyps in the colon before its use for examination of the upper-GI tract.8 Conventional endoscopes image only the mucosal surface. Ideally, a method that improves visualization of the mucosa would aid in the detection of Barrett’s esophagus and improve the accuracy of surveillance. Several new and established endoscopic methods are under evaluation (Table 1). Magnification endoscopy with chromoendoscopy is unique in that it provides a more specific evaluation of the fine detail of the mucosal surface, as well as a high yield for targeted biopsy specimens and, consequently, an improvement in diagnostic accuracy. At this time, none of the methods listed in Table 1 has been accepted as superior to standard methods for diagnosis of Barrett’s esophagus or has been consistently demonstrated to improve clinical outcomes of surveillance. However, a role for some of these techniques appears to be emerging.
TERMINOLOGY AND INSTRUMENTS Resolution Resolution is the ability to discriminate mucosal surface details; essentially, the ability to distinctly visualize as separate two objects that are closely approximated. In digital videoimaging, resolution is a function of pixel density. Conventional endoscopes use charged-coupled devices with pixel densities of 100,000 to 200,000. In high-resolution endoscopes, the pixel density can be as high as 850,000. Thus, these instruments improve image quality by increasing resolution; they have the capability to discriminate objects 10 to 71 microns in diameter. By comparison, the human eye can only distinguish items 125 to 167 microns in diameter.9 Magnification endoscopy A magnifying endoscope has the capability to enlarge an image from 31.5 to 3150 optical power though the use of a movable lens, which is controlled by the endoscopist.10 VOLUME 59, NO. 1, 2004
Endoscopic classification of Barrett’s esophagus
Magnifying upper endoscopes Magnifying upper endoscopes have an adjustable focusing system that provides not only a conventional image but also a close-up view. Magnifying upper endoscopes can be used as a standard endoscope during routine examinations when the ‘‘zoom’’ feature is not used. In certain types of magnifying upper endoscopes (e.g., GIF-Q240Z and GIF-Q160Z; Olympus American Corp., Melville, N.Y.), a small lever on the control section of the instrument allows the endoscopist to magnify an image by moving lenses at the tip of the insertion tube. Other types have an electronic magnification function (e.g., EG-410CR and EG-485ZH; Fujinon Inc., Wayne, N.J.). Other prototype instruments have been developed (e.g., EG-3470ZK; Pentax Precision Instrument Corp., Orangeburg, N.Y.). Prior versions of magnifying upper endoscopes lacked high resolution, which limited their use. Newer generation instruments combine high resolution with magnification capability. Chromoendoscopy Chromoendoscopy involves the topical application of chemical dyes (stains) to enhance mucosal visualization during endoscopy. Barrett’s mucosa is frequently translucent when observed with a magnifying endoscope, which allows identification of only the surface capillary structure; the mucosal surface is not easily examined. The sensitivity for detection of a mucosal pattern with magnification alone is only 38%.11 To improve visualization of the mucosal surface, a variety of different enhancement techniques, including application of dyes and acetic acid, have been used in conjunction with magnification. Two types of dyes are used during magnifying endoscopy in patients with Barrett’s esophagus. Contrast stains, which are not absorbed by cells, accentuate tissue topography by concentrating in mucosal depressions, thereby outlining mucosal elevations. Indigo carmine (0.2%) is the prototype contrast dye. Absorptive, or vital, dyes differ in that they are taken up by cells, either by diffusion or active absorption. The vital stains most frequently used in patients with Barrett’s esophagus are Lugol’s iodine solution (0.1%-0.5%), which stains glycogen in normal squamous mucosa, and methylene blue, which is actively absorbed by smallintestinal and colonic epithelium.12,13 Enhanced magnification endoscopy Enhanced magnification endoscopy involves the combined use of magnification and acetic acid, a weak acid (pH 2.5) used for in vivo application. Acetic acid produces reversible, short-term intracelVOLUME 59, NO. 1, 2004
M Guelrud, E Ehrlich
Table 1. Techniques that improve the visualization of the mucosal surface High-resolution endoscopy Chromoendoscopy Magnification endoscopy Magnification endoscopy with chromoendoscopy ) Lugol’s solution ) Methylene blue ) Indigo carmine Enhanced magnification endoscopy ) Acetic acid Narrow band imaging spectroscopy Fluorescence Raman spectroscopy Light-scattering spectroscopy Optical coherent tomography
lular cytoplasmic protein denaturation.14 Acetic acid commonly is applied at colposcopy at a 3% dilution to aid detection of small lesions in the uterine cervical mucosa, a mucosa similar to that of the squamocolumnar junction of the esophagus and stomach. Application of 1.5% to 3% acetic acid in the distal esophagus has been shown to enhance the ability to detect small or indistinct remnant islands of columnar epithelium after endoscopic treatment of Barrett’s esophagus. This method is safe, rapid, clean, and inexpensive.15 TECHNIQUE FOR MAGNIFYING ENDOSCOPY The technique for introduction of a magnifying endoscope is the same as that for a standard endoscope. Glucagon can be given intravenously to decrease the contractility of the GI tract and minimize loss of reagents. To apply a dye or acetic acid, a spray catheter (PW-5L; Olympus) is inserted through the accessory channel of the magnifying endoscope. With the catheter tip just visible in the endoscopic field, the dye or diluted acetic acid is sprayed over the mucosal surface from distal to proximal while simultaneously rotating the endoscope to coat the mucosa evenly and in a uniform fashion. To avoid aspiration, the head of the examination table should be elevated, and the least volume of acetic acid necessary should be applied.13,16,17 Chromoendoscopy Before application of methylene blue, the mucus on the mucosal surface must be removed by application of a mucolytic agent to allow the uptake of dye into epithelial cells. Approximately 10 mL of a 10% solution of N-acetylcysteine is sprayed onto the area suspected to be Barrett’s epithelium. After 1 to 2 minutes, approximately 10 to 20 mL of a 0.5% GASTROINTESTINAL ENDOSCOPY
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Table 2. Enhanced magnifying endoscopy classification of Barrett’s mucosa Pattern I - Round II - Reticular III - Villous IV - Ridged
Description Regular circular dots Oval or short tubules Mesh-like villous appearance Cerebroid-like appearance
solution of methylene blue is sprayed with a catheter over the same mucosal surface. It takes approximately 2 minutes for the methylene blue to be absorbed and stain the mucosa. Then, the excess dye is vigorously washed with 120 to 300 mL of tap water by using a 50-mL syringe or a high-pressure water jet system incorporated in some newer magnifying endoscopes. It is important to aspirate excess water and dye from the stomach between the applications of methylene blue and water. After staining with methylene blue, Barrett’s epithelium appears blue, while the esophageal and gastric mucosa remains unstained.13,16,18 When using Lugol’s solution or Indigo carmine, application of the mucolytic agent is unnecessary. The mucus can be effectively removed by flushing tap water over the mucosal area in question. After spraying Lugol’s solution, the normal esophageal mucosa is stained dark brown, while the Barrett’s mucosa will remain unstained. The disadvantage of Lugol’s solution is that it contains iodine and cannot be used in patients with a history of iodine sensitivity.13,16,18-20 Inflammation, such as esophagitis, is a common cause of false-positive staining because the mucosal surface is disrupted and the dye adheres non-specifically. In addition, other types of mucosal trauma, including contact bleeding from manipulation of the spray catheter, can create artifacts that may be confused with mucosal abnormalities. High-grade dysplasia and cancer may appear as nodules and plaques in Barrett’s esophagus; thus, biopsy specimens should be obtained from these focal lesions first.17 Enhanced magnification endoscopy When using acetic acid, the same procedure steps are applied. However, there is no need to remove the surface mucus with a mucolytic agent before covering the mucosa with the acetic acid solution. Usually, 5 to 10 mL of 3% acetic acid are adequate to cover the area suspected to be Barrett’s epithelium. However, in long-segment Barrett’s esophagus, a larger volume may be necessary. Excess acetic acid can be removed by aspiration before observation of the mucosa. Initially, a whitish discoloration of both the esophageal and gastric epithelia is noted. At 2 to 60
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3 minutes after spraying the acetic acid solution, the esophagus remains white, while columnar Barrett’s epithelium and gastric epithelium become reddish. This creates a clearly defined contrast between the normal squamous epithelium of the esophagus and the abnormal columnar epithelium proximal to the gastroesophageal junction, which improves visualization of intestinal metaplasia in Barrett’s esophagus and thus aids the targeting of biopsy specimens. This method also differentiates regenerative squamous epithelium from residual Barrett’s foci epithelium after ablation therapy.15 ENDOSCOPIC CLASSIFICATION Enhanced magnification endoscopy The endoscopic classification of Barrett’s esophagus is based on similarities between the intestinal metaplasia found in the esophagus of patients with Barrett’s esophagus and the intestinal mucosa in the duodenum of patients with celiac sprue as demonstrated with a dissecting microscope.21 This classification system was established for two main purposes: to train endoscopists to detect mucosal changes and to define a reproducible terminology.11 Enhanced magnification endoscopy with acetic acid in the evaluation of the mucosal surface in patients with Barrett’s esophagus was first described by Guelrud et al.11 in 2001. By using enhanced magnification endoscopy in patients with short-segment Barrett’s esophagus without dysplasia, these investigators observed 4 different and characteristic mucosal surface patterns (Table 2): Pattern I, round pits: characterized by an organized and regularly arranged area of circular dots Pattern II, reticular: characterized by circular or oval similarly shaped tubules in regular arrangement Pattern III, villous: characterized by a fine villiform appearance with a regular shape and arrangement without any pits Pattern IV, ridged: characterized by a cerebriform appearance consisting of a thick villous convoluted shape with a regular arrangement The initial study of Guelrud et al.11 included 49 patients undergoing endoscopic surveillance for short-segment Barrett’s esophagus. At the time the study was conducted, a magnification endoscope with standard resolution and a magnification power of 353 was used. A spray catheter was used to apply approximately 10 to 15 mL of 1.5% acetic acid onto the distal esophagus. This technique added an estimated 5 to 8 minutes to the length of a standard VOLUME 59, NO. 1, 2004
Endoscopic classification of Barrett’s esophagus
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Table 3. Classification of Barrett’s esophagus by enhanced-magnification endoscopy First classification 335 d d d d
Pattern Pattern Pattern Pattern
New classification 380
I: round II: reticular III: villous IV: ridged
d d d d d d d
Round pits Tubular pits Thin linear Deep linear Villous Foveolar Cerebroid
Table 4. Yield of biopsy specimens for detection of intestinal metaplasia according to endoscopic pattern (n = 87) Type of epithelium Mucosal pattern Round pits Tubular pits Thin linear Deep linear Villous Foveolar Cerebroid
Fundic
Cardia
87/87 (100%) — — — — — —
— 20/22 (89%) 8/9 (90%) — 11/59 (18.6%) 1/15 (6.5%) 1/21 (4.8%)
Intestinal metaplasia 2/22 1/9 9/9 48/59 14/15 20/21
— (11%) (10%) (100%) (81.4%) (93.5%) (95.2%)
endoscopic examination. The 4 different mucosal surface patterns were observed, and one biopsy specimen was taken from each representative pattern. All patients with Barrett’s esophagus had a villiform mucosal pattern that correlated with the finding of intestinal metaplasia on histopathologic evaluation of the biopsy specimens. The yield of biopsy specimens in the detection of intestinal metaplasia was correlated with the endoscopic pattern. Biopsy specimens from Pattern I mucosa revealed fundic epithelium, and this pattern served as a control for the analysis. Biopsy specimens from Pattern II mucosa revealed cardia mucosa in 90% of cases; intestinal metaplasia was found in two of 18 samples. Analysis showed that Pattern III and Pattern IV mucosa contained intestinal metaplasia in, respectively, 87% and 100% of biopsy specimens. The overall accuracy of enhanced magnification endoscopy for the detection of intestinal metaplasia was 92%; the positive predictive value of Patterns III and IV was 87.5%.11 The classification system was redefined in 2002 based on the study of 87 patients (unpublished data) by using a high-resolution magnifying endoscope (GIF-Q160Z; Olympus) with 380 magnifying power. The original patterns were renamed, and 3 new categories were added: thin linear, deep linear, and foveolar (Table 3). In the new classification, detailed VOLUME 59, NO. 1, 2004
Figure 1. Magnifying endoscopic view (orig. mag. 340), after application of acetic acid, showing small round pits with uniform dot-like appearance (round pit pattern).
mucosal surface descriptions were substituted for mucosal ‘‘patterns.’’ Round pits pattern, formerly Pattern I, is an arrangement characterized by small round pits with a uniform dot-like appearance, signifying fundic columnar epithelium (Fig. 1). Tubular pits pattern, formerly Pattern II, is characterized by ovoid or short tubular pits with a uniform arrangement, signifying cardia mucosal (Fig. 2). Thin linear pattern, a new category, is characterized by thin superficial grooves that may represent cardia mucosa and/or Barrett’s epithelium (Fig. 3). Deep linear pattern, also a new category, is characterized by deep, coarse grooves signifying Barrett’s epithelium (Fig. 4). Villous pattern, formerly Pattern III, is characterized by a uniform mesh-like villous appearance or, more rarely, fingerlike projections, signifying Barrett’s epithelium (Fig. 5). The new category foveolar pattern is characterized by a flat surface interspersed with wide circular pits and the absence of villous structures, signifying Barrett’s epithelium (Fig. 6). Cerebroid pattern, formerly Pattern IV, is characterized by uniform thick, straight tubular or convoluted ridges reminiscent of cerebral gyri, signifying Barrett’s epithelium (Fig. 7). In this ongoing study, the yield observed thus far of biopsy specimens for the detection of intestinal metaplasia correlated by pattern type is shown in Table 4. The usefulness of enhanced magnification endoscopy is supported by the preliminarily published results of a study by Rey and Kuznetsov.22 These investigators studied 37 patients with Barrett’s esophagus by using 3% acetic acid and a new highresolution magnifying endoscope (GIF-160Z, Olympus). Dysplasia was found in biopsy specimens from flat red areas of mucosa. Three types of GASTROINTESTINAL ENDOSCOPY
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Figure 2. Magnifying endoscopic views at 340 (A) and 380 (B), after application of acetic acid, showing ovoid or short tubular pits with a uniform arrangement (tubular pit pattern).
Figure 3. Magnifying endoscopic views at 340 (A) and 380 (B), after application of acetic acid, showing thin superficial grooves (thin linear pattern).
epithelium were identified: fundic, cardia, and intestinal metaplasia. Magnification chromoendoscopy The first attempt at combining magnification and chromoendoscopy with Lugol’s solution and Indigo carmine dye to study Barrett’s esophagus was that of Stevens et al.20 in 1994. They examined 46 patients with symptoms of GERD by using a combination of dye spraying and magnification endoscopy. Barrett’s esophagus was identified in 13 patients, 10 of whom had short-segment Barrett’s esophagus and 3 had long-segment Barrett’s esophagus. All patients with Barrett’s esophagus had a villiform surface pattern 62
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that correlated with the finding of intestinal metaplasia in biopsy specimens. The maximum magnification of the endoscope used for this study was only 335.20 Endo et al.23 proposed another classification of Barrett’s esophagus in 2002. They used a highresolution magnifying endoscope (GIF-Q240Z; Olympus) and methylene blue staining. Based on evaluation of the mucosal pattern for 67 areas of Barrett’s mucosa, these investigators defined 5 distinct patterns (designated types 1 through 5): type 1 is characterized by small round pits; type 2 is described as long straight lines; type 3 has long oval and curved pits; type 4 is a tubular and twisted pattern similar to a branch or gyrus-like structure; VOLUME 59, NO. 1, 2004
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Figure 4. Magnifying endoscopic views at 360 (A) and 380 (B), after application of acetic acid, showing deep, coarse grooves (deep linear pattern).
Figure 5. A, magnifying endoscopic view at 335, after application of acetic acid, showing uniform, mesh-like villous appearance (villous pattern). B, magnifying endoscopic view at 360, after application of acetic acid, showing finger-like projections (villous pattern).
and type 5 is characterized by a villous appearance with flat or finger-like projections. Methylene blue stained 0% of the mucosa identified as types 1 and 2. However, intestinal metaplasia was found in 6% of biopsy specimens from mucosa that exhibited the type 1 pattern. The rate of positive methylene blue staining was 23% for type 3, and 40% of biopsy specimens from this type revealed intestinal metaplasia. Intestinal metaplasia was found in 100% of biopsy specimens from mucosa that exhibited either a type 4 or type 5 pattern. Surprisingly, however, type 4 and type 5 mucosa were stained by methylene blue in only 60% and 50% of cases, respectively. By using high-resolution magnifying endoscopy and spraying Indigo carmine, a nonabsorbed conVOLUME 59, NO. 1, 2004
trast stain, Sharma et al.24 identified 3 mucosal patterns within the columnar mucosa of 80 patients suspected of having Barrett’s esophagus: ridge/ villous, circular, and irregular/distorted. The ridge/ villous pattern was characterized by a regularly arranged villiform pattern with tortuous and thick villi of sausage or cerebriform appearance. The circular pattern had regularly arranged circular or oval areas. In the irregular/distorted pattern, there was marked irregularity and distortion of the cerebriform-villous pattern. Intestinal metaplasia was identified in 57 of 62 (97%) patients with the ridged/ villous pattern and in two of 12 (17%) with the circular pattern. Low-grade dysplasia was found in 18 patients, all of whom had the ridged/villous GASTROINTESTINAL ENDOSCOPY
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Endoscopic classification of Barrett’s esophagus
Figure 6. Magnifying endoscopic views at 380 (A) and 380 (B), after application of acetic acid, showing flat surface interspersed with wide circular pits and absence of villous structures (foveolar pattern).
Figure 7. A, magnifying endoscopic views at 380, after application of acetic acid, showing uniform thick straight tubular ridges. B, magnifying endoscopic views at 380, after application of acetic acid, showing uniform thick convoluted ridges reminiscent of cerebral gyri (cerebroid pattern).
pattern, whereas high-grade dysplasia was detected in 6 patients, all of whom had the irregular/distorted pattern. This study by Sharma et al.,24 published in 2003, was the first in which magnification chemoendoscopy was shown to identify and distinguish between high-grade dysplasia and intestinal metaplasia. The results of a study by Meining and Heldwein,25 which compared two different magnification techniques for the diagnosis of intestinal metaplasia, have been published in abstract form. A total of 41 patients with symptoms of reflux but no known Barrett’s esophagus were included. By using a magnification endoscope, methylene blue was sprayed in 20 patients, and the classification of Endo et al.23 was applied; in the other 21 patients, acetic acid was sprayed on the mucosal surface, and the 64
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pattern classification of Guelrud et al.11 was used. The goal was to compare the accuracy rates of each of these magnifying endoscopy classification systems for the identification of histopathologically confirmed intestinal metaplasia. The pattern classification of Guelrud et al.11 had an accuracy of 62% vs. an accuracy of 55% for that of Endo et al.23 Meining and Heldwein24 concluded that magnification endoscopy improves the detection of intestinal metaplasia at the gastroesophageal junction, but that the accuracy is still low.25 CONCLUSION The distribution of intestinal metaplasia in patients with short- and also with long-segment Barrett’s esophagus is often patchy and irregular. Thus, targeted biopsy specimens are of paramount VOLUME 59, NO. 1, 2004
Endoscopic classification of Barrett’s esophagus
importance for diagnosis. Chromoendoscopy is an effective, readily available method that can enhance endoscopic diagnosis, including the detection of intestinal metaplasia through more accurate targeting of biopsy specimens. When chromoendoscopy is performed with magnifying endoscopy, various mucosal patterns can be recognized that may facilitate the identification of intestinal metaplasia. Application of acetic acid to the mucosal surface is a relatively new method for demonstration of mucosal patterns when combined with magnification endoscopy. The technique of magnification endoscopy is not difficult and adds only 5 to 10 minutes to the length of a standard endoscopic examination. However, the majority of endoscopists have not been trained in the use of magnification endoscopes. The value of magnifying endoscopy with the use of chromoendoscopic dyes or acetic acid in clinical practice currently is under investigation. However, these techniques have significant potential to improve diagnostic accuracy and thereby impact the morbidity and mortality associated with short- and long-segment Barrett’s esophagus at little increase in cost. A number of classification schemes have been proposed to describe the mucosal patterns observed in Barrett’s epithelium by using these techniques. The current proposed classifications are too complex relative to their clinical value. Nevertheless, simplification of these systems will occur over time with increased use of magnifying endoscopy in conjunction with dye or acetic acid spraying. These techniques require further validation in large, multicenter trials so that mucosal patterns can be more clearly defined and standardized. In addition, it will be necessary to assess intra- and interobserver variability in the interpretation of the endoscopic findings and to define the endoscopic criteria for dysplasia and early stage cancer. REFERENCES 1. Blot WJ, Devesa SS, Kneller RW, Fraumeni JF Jr. Rising incidence of adenocarcinoma of the esophagus and gastric cardia. JAMA 1991;265:1287-9. 2. Blot WJ, Devesa SS, Fraumeni JF Jr. Continuing climb in rates of esophageal adenocarcinoma: an update. JAMA 1993; 270:1320. 3. Skinner DB, Walther BC, Riddell RH, Schmidt H, Iascone C, DeMeester TR. Barrett’s esophagus: comparison of benign and malignant cases. Ann Surg 1983;198:554-66. 4. Spechler SJ, Zeroogian JM, Antonioli DA, Wang HH, Goyal RK. Prevalence of metaplasia at the gastro-oesophageal junction. Lancet 1994;344:1533-6.
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5. Johnston MH, Hammond AS, Laskin W, Jones DM. The prevalence and clinical characteristics of short segments of specialized intestinal metaplasia in the distal esophagus on routine endoscopy. Am J Gastroenterol 1996;91:1507-11. 6. Chalasani N, Wo JM, Hunter JG, Waring JP. Significance of intestinal metaplasia in different areas of esophagus including esophagogastric junction. Dig Dis Sci 1997;42:603-7. 7. Eloubeidi MA, Provenzale D. Does this patient have Barrett’s esophagus? The utility of predicting Barrett’s esophagus at the index endoscopy. Am J Gastroenterol 1999;94:937-43. 8. Tada M, Kawai K. Research with the endoscope: new techniques using magnification and chromoscopy. Clin Gastroenterol 1986;15:417-37. 9. Anonymous. Technology status evaluation report. High resolution and high-magnification endoscopy. Gastrointest Endosc 2000;52:854-6. 10. Kiesslich R, Jung M. Magnification endoscopy: does it improve mucosal surface analysis for the diagnosis of gastrointestinal neoplasias? Endoscopy 2002;34:819-22. 11. Guelrud M, Herrera I, Essenfeld H, Castro J. Enhanced magnification endoscopy: a new technique to identify specialized intestinal metaplasia in Barrett’s esophagus. Gastrointest Endosc 2001;53:559-65. 12. Canto MI, Setrakian S, Petras RE, Blades E, Chak A, Sivak MV Jr. Methylene blue selectively stains intestinal metaplasia in Barrett’s esophagus. Gastrointest Endosc 1996;44:1-7. 13. Canto MI. Staining in gastrointestinal endoscopy: the basics. Endoscopy 1999;31:479-86. 14. Cartier R. Practical colposcopy. Basel: Karger; 1978. 15. Guelrud M, Herrera I. Acetic acid improves identification of remnant islands of Barrett’s epithelium after endoscopic therapy. Gastrointest Endosc 1998;47:512-5. 16. Acosta MM, Boyce HW Jr. Chromoendoscopy: where is it useful? J Clin Gastroenterol 1998;27:13-20. 17. Canto MI, Yoshida T, Gossner L. Chromoscopy of intestinal metaplasia in Barrett’s esophagus. Endoscopy 2002;34:330-6. 18. Canto MI. Vital staining and Barrett’s esophagus. Gastrointest Endosc 1999;49:S12-6. 19. Shim CS. Staining in gastrointestinal endoscopy: clinical application and limitations. Endoscopy 1999;31:487-96. 20. Stevens PD, Lightdale CJ, Green PH, Siegel LM, GarciaCarrasquillo RJ, Rotterdam H. Combined magnification endoscopy with chromoendoscopy for the evaluation of Barrett’s esophagus. Gastrointest Endosc 1994;40:747-9. 21. Thompson JJ, Zinsser KR, Enterline HT. Barrett’s metaplasia and adenocarcinoma of the esophagus and gastroesophageal junction. Hum Pathol 1983;14:42-60. 22. Rey JF, Kuznetsov K. Usefulness of chromoscopy with acetic acid and magnification for Barrett esophagus [abstract]. Gastrointest Endosc 2003;57:AB573. 23. Endo T, Awakawa T, Takahashi H, Arimura Y, Itoh F, Yamashita K, et al. Classification of Barrett’s epithelium by magnifying endoscopy. Gastrointest Endosc 2002;55:641-7. 24. 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;52:24-7. 25. Meining A, Heldwein W. Magnification endoscopy for detection of specialized intestinal metaplasia at the esophagogastric junction [abstract]. Gastrointest Endosc 2003;57:AB577.
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The incidence of esophageal adenocarcinoma has risen steadily over the past 10 years. Patients with Barrett’s esophagus are at increased risk for the development of adenocarcinoma.1,2 Barrett’s esophagus was defined in the past by the macroscopic appearance and length of columnar mucosa in the esophagus. In 1983, Skinner et al.3 restricted the term Barrett’s esophagus to identify only those patients who had columnar epithelium 3 cm or greater in length in the distal esophagus. This criterion was established to prevent overdiagnosis of Barrett’s esophagus. Then, in 1994, Spechler et al.4 published an influential article that stated that goblet cells were present at the gastroesophageal junction in 18% of patients with findings that did not fit the 3 cm of columnar-type epithelium rule. Because goblet cells are a marker of specialized intestinal epithelium, this finding was labeled shortsegment Barrett’s esophagus. The diagnosis of Barrett’s esophagus is established when intestinal metaplasia is found in biopsy specimens obtained from salmon-colored mucosa in the distal esophagus proximal to the junction of the esophagus and stomach. It is this intestinal metaplasia that is associated with the increased risk of adenocarcinoma. The salmon-colored mucosa in the distal esophagus is columnar and consists of a mosaic of fundic mucosa, cardia mucosa, and intestinal metaplasia. Thus, the distribution of intestinal metaplasia within the salmon-colored, columnar mucosa of the esophagus is patchy. The yield of biopsy specimens of columnar-type mucosa in the distal esophagus for the detection of intestinal metaplasia varies from 25% to 50% in short-segment
Current affiliations: Division of Gastroenterology, Tufts University School of Medicine, Tufts New England Medical Center, Boston, Massachusetts. Reprint requests: Moises Guelrud, MD, Tufts University School of Medicine, Director of Advanced Endoscopic Therapy, Division of Gastroenterology, Tufts New England Medical Center, 750 Washington St., Box #233, Boston, MA 02111. Copyright Ó 2004 by the American Society for Gastrointestinal Endoscopy 0016-5107/$30.00 PII: S0016-5107(03)02508-2 58
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Barrett’s esophagus5,6 and up to 80% in longsegment Barrett’s esophagus.7 The development of high-resolution and magnifying endoscopy during the past decade has significantly improved the ability to image the GI mucosal surface and target biopsy specimens. Many studies have demonstrated the diagnostic capabilities and limitations of magnifying endoscopy. For the endoscopist unfamiliar with magnifying endoscopy, the images of the mucosal surface may be difficult to interpret. However, magnifying endoscopy was used to evaluate and differentiate benign from malignant polyps in the colon before its use for examination of the upper-GI tract.8 Conventional endoscopes image only the mucosal surface. Ideally, a method that improves visualization of the mucosa would aid in the detection of Barrett’s esophagus and improve the accuracy of surveillance. Several new and established endoscopic methods are under evaluation (Table 1). Magnification endoscopy with chromoendoscopy is unique in that it provides a more specific evaluation of the fine detail of the mucosal surface, as well as a high yield for targeted biopsy specimens and, consequently, an improvement in diagnostic accuracy. At this time, none of the methods listed in Table 1 has been accepted as superior to standard methods for diagnosis of Barrett’s esophagus or has been consistently demonstrated to improve clinical outcomes of surveillance. However, a role for some of these techniques appears to be emerging.
TERMINOLOGY AND INSTRUMENTS Resolution Resolution is the ability to discriminate mucosal surface details; essentially, the ability to distinctly visualize as separate two objects that are closely approximated. In digital videoimaging, resolution is a function of pixel density. Conventional endoscopes use charged-coupled devices with pixel densities of 100,000 to 200,000. In high-resolution endoscopes, the pixel density can be as high as 850,000. Thus, these instruments improve image quality by increasing resolution; they have the capability to discriminate objects 10 to 71 microns in diameter. By comparison, the human eye can only distinguish items 125 to 167 microns in diameter.9 Magnification endoscopy A magnifying endoscope has the capability to enlarge an image from 31.5 to 3150 optical power though the use of a movable lens, which is controlled by the endoscopist.10 VOLUME 59, NO. 1, 2004
Endoscopic classification of Barrett’s esophagus
Magnifying upper endoscopes Magnifying upper endoscopes have an adjustable focusing system that provides not only a conventional image but also a close-up view. Magnifying upper endoscopes can be used as a standard endoscope during routine examinations when the ‘‘zoom’’ feature is not used. In certain types of magnifying upper endoscopes (e.g., GIF-Q240Z and GIF-Q160Z; Olympus American Corp., Melville, N.Y.), a small lever on the control section of the instrument allows the endoscopist to magnify an image by moving lenses at the tip of the insertion tube. Other types have an electronic magnification function (e.g., EG-410CR and EG-485ZH; Fujinon Inc., Wayne, N.J.). Other prototype instruments have been developed (e.g., EG-3470ZK; Pentax Precision Instrument Corp., Orangeburg, N.Y.). Prior versions of magnifying upper endoscopes lacked high resolution, which limited their use. Newer generation instruments combine high resolution with magnification capability. Chromoendoscopy Chromoendoscopy involves the topical application of chemical dyes (stains) to enhance mucosal visualization during endoscopy. Barrett’s mucosa is frequently translucent when observed with a magnifying endoscope, which allows identification of only the surface capillary structure; the mucosal surface is not easily examined. The sensitivity for detection of a mucosal pattern with magnification alone is only 38%.11 To improve visualization of the mucosal surface, a variety of different enhancement techniques, including application of dyes and acetic acid, have been used in conjunction with magnification. Two types of dyes are used during magnifying endoscopy in patients with Barrett’s esophagus. Contrast stains, which are not absorbed by cells, accentuate tissue topography by concentrating in mucosal depressions, thereby outlining mucosal elevations. Indigo carmine (0.2%) is the prototype contrast dye. Absorptive, or vital, dyes differ in that they are taken up by cells, either by diffusion or active absorption. The vital stains most frequently used in patients with Barrett’s esophagus are Lugol’s iodine solution (0.1%-0.5%), which stains glycogen in normal squamous mucosa, and methylene blue, which is actively absorbed by smallintestinal and colonic epithelium.12,13 Enhanced magnification endoscopy Enhanced magnification endoscopy involves the combined use of magnification and acetic acid, a weak acid (pH 2.5) used for in vivo application. Acetic acid produces reversible, short-term intracelVOLUME 59, NO. 1, 2004
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Table 1. Techniques that improve the visualization of the mucosal surface High-resolution endoscopy Chromoendoscopy Magnification endoscopy Magnification endoscopy with chromoendoscopy ) Lugol’s solution ) Methylene blue ) Indigo carmine Enhanced magnification endoscopy ) Acetic acid Narrow band imaging spectroscopy Fluorescence Raman spectroscopy Light-scattering spectroscopy Optical coherent tomography
lular cytoplasmic protein denaturation.14 Acetic acid commonly is applied at colposcopy at a 3% dilution to aid detection of small lesions in the uterine cervical mucosa, a mucosa similar to that of the squamocolumnar junction of the esophagus and stomach. Application of 1.5% to 3% acetic acid in the distal esophagus has been shown to enhance the ability to detect small or indistinct remnant islands of columnar epithelium after endoscopic treatment of Barrett’s esophagus. This method is safe, rapid, clean, and inexpensive.15 TECHNIQUE FOR MAGNIFYING ENDOSCOPY The technique for introduction of a magnifying endoscope is the same as that for a standard endoscope. Glucagon can be given intravenously to decrease the contractility of the GI tract and minimize loss of reagents. To apply a dye or acetic acid, a spray catheter (PW-5L; Olympus) is inserted through the accessory channel of the magnifying endoscope. With the catheter tip just visible in the endoscopic field, the dye or diluted acetic acid is sprayed over the mucosal surface from distal to proximal while simultaneously rotating the endoscope to coat the mucosa evenly and in a uniform fashion. To avoid aspiration, the head of the examination table should be elevated, and the least volume of acetic acid necessary should be applied.13,16,17 Chromoendoscopy Before application of methylene blue, the mucus on the mucosal surface must be removed by application of a mucolytic agent to allow the uptake of dye into epithelial cells. Approximately 10 mL of a 10% solution of N-acetylcysteine is sprayed onto the area suspected to be Barrett’s epithelium. After 1 to 2 minutes, approximately 10 to 20 mL of a 0.5% GASTROINTESTINAL ENDOSCOPY
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Table 2. Enhanced magnifying endoscopy classification of Barrett’s mucosa Pattern I - Round II - Reticular III - Villous IV - Ridged
Description Regular circular dots Oval or short tubules Mesh-like villous appearance Cerebroid-like appearance
solution of methylene blue is sprayed with a catheter over the same mucosal surface. It takes approximately 2 minutes for the methylene blue to be absorbed and stain the mucosa. Then, the excess dye is vigorously washed with 120 to 300 mL of tap water by using a 50-mL syringe or a high-pressure water jet system incorporated in some newer magnifying endoscopes. It is important to aspirate excess water and dye from the stomach between the applications of methylene blue and water. After staining with methylene blue, Barrett’s epithelium appears blue, while the esophageal and gastric mucosa remains unstained.13,16,18 When using Lugol’s solution or Indigo carmine, application of the mucolytic agent is unnecessary. The mucus can be effectively removed by flushing tap water over the mucosal area in question. After spraying Lugol’s solution, the normal esophageal mucosa is stained dark brown, while the Barrett’s mucosa will remain unstained. The disadvantage of Lugol’s solution is that it contains iodine and cannot be used in patients with a history of iodine sensitivity.13,16,18-20 Inflammation, such as esophagitis, is a common cause of false-positive staining because the mucosal surface is disrupted and the dye adheres non-specifically. In addition, other types of mucosal trauma, including contact bleeding from manipulation of the spray catheter, can create artifacts that may be confused with mucosal abnormalities. High-grade dysplasia and cancer may appear as nodules and plaques in Barrett’s esophagus; thus, biopsy specimens should be obtained from these focal lesions first.17 Enhanced magnification endoscopy When using acetic acid, the same procedure steps are applied. However, there is no need to remove the surface mucus with a mucolytic agent before covering the mucosa with the acetic acid solution. Usually, 5 to 10 mL of 3% acetic acid are adequate to cover the area suspected to be Barrett’s epithelium. However, in long-segment Barrett’s esophagus, a larger volume may be necessary. Excess acetic acid can be removed by aspiration before observation of the mucosa. Initially, a whitish discoloration of both the esophageal and gastric epithelia is noted. At 2 to 60
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3 minutes after spraying the acetic acid solution, the esophagus remains white, while columnar Barrett’s epithelium and gastric epithelium become reddish. This creates a clearly defined contrast between the normal squamous epithelium of the esophagus and the abnormal columnar epithelium proximal to the gastroesophageal junction, which improves visualization of intestinal metaplasia in Barrett’s esophagus and thus aids the targeting of biopsy specimens. This method also differentiates regenerative squamous epithelium from residual Barrett’s foci epithelium after ablation therapy.15 ENDOSCOPIC CLASSIFICATION Enhanced magnification endoscopy The endoscopic classification of Barrett’s esophagus is based on similarities between the intestinal metaplasia found in the esophagus of patients with Barrett’s esophagus and the intestinal mucosa in the duodenum of patients with celiac sprue as demonstrated with a dissecting microscope.21 This classification system was established for two main purposes: to train endoscopists to detect mucosal changes and to define a reproducible terminology.11 Enhanced magnification endoscopy with acetic acid in the evaluation of the mucosal surface in patients with Barrett’s esophagus was first described by Guelrud et al.11 in 2001. By using enhanced magnification endoscopy in patients with short-segment Barrett’s esophagus without dysplasia, these investigators observed 4 different and characteristic mucosal surface patterns (Table 2): Pattern I, round pits: characterized by an organized and regularly arranged area of circular dots Pattern II, reticular: characterized by circular or oval similarly shaped tubules in regular arrangement Pattern III, villous: characterized by a fine villiform appearance with a regular shape and arrangement without any pits Pattern IV, ridged: characterized by a cerebriform appearance consisting of a thick villous convoluted shape with a regular arrangement The initial study of Guelrud et al.11 included 49 patients undergoing endoscopic surveillance for short-segment Barrett’s esophagus. At the time the study was conducted, a magnification endoscope with standard resolution and a magnification power of 353 was used. A spray catheter was used to apply approximately 10 to 15 mL of 1.5% acetic acid onto the distal esophagus. This technique added an estimated 5 to 8 minutes to the length of a standard VOLUME 59, NO. 1, 2004
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Table 3. Classification of Barrett’s esophagus by enhanced-magnification endoscopy First classification 335 d d d d
Pattern Pattern Pattern Pattern
New classification 380
I: round II: reticular III: villous IV: ridged
d d d d d d d
Round pits Tubular pits Thin linear Deep linear Villous Foveolar Cerebroid
Table 4. Yield of biopsy specimens for detection of intestinal metaplasia according to endoscopic pattern (n = 87) Type of epithelium Mucosal pattern Round pits Tubular pits Thin linear Deep linear Villous Foveolar Cerebroid
Fundic
Cardia
87/87 (100%) — — — — — —
— 20/22 (89%) 8/9 (90%) — 11/59 (18.6%) 1/15 (6.5%) 1/21 (4.8%)
Intestinal metaplasia 2/22 1/9 9/9 48/59 14/15 20/21
— (11%) (10%) (100%) (81.4%) (93.5%) (95.2%)
endoscopic examination. The 4 different mucosal surface patterns were observed, and one biopsy specimen was taken from each representative pattern. All patients with Barrett’s esophagus had a villiform mucosal pattern that correlated with the finding of intestinal metaplasia on histopathologic evaluation of the biopsy specimens. The yield of biopsy specimens in the detection of intestinal metaplasia was correlated with the endoscopic pattern. Biopsy specimens from Pattern I mucosa revealed fundic epithelium, and this pattern served as a control for the analysis. Biopsy specimens from Pattern II mucosa revealed cardia mucosa in 90% of cases; intestinal metaplasia was found in two of 18 samples. Analysis showed that Pattern III and Pattern IV mucosa contained intestinal metaplasia in, respectively, 87% and 100% of biopsy specimens. The overall accuracy of enhanced magnification endoscopy for the detection of intestinal metaplasia was 92%; the positive predictive value of Patterns III and IV was 87.5%.11 The classification system was redefined in 2002 based on the study of 87 patients (unpublished data) by using a high-resolution magnifying endoscope (GIF-Q160Z; Olympus) with 380 magnifying power. The original patterns were renamed, and 3 new categories were added: thin linear, deep linear, and foveolar (Table 3). In the new classification, detailed VOLUME 59, NO. 1, 2004
Figure 1. Magnifying endoscopic view (orig. mag. 340), after application of acetic acid, showing small round pits with uniform dot-like appearance (round pit pattern).
mucosal surface descriptions were substituted for mucosal ‘‘patterns.’’ Round pits pattern, formerly Pattern I, is an arrangement characterized by small round pits with a uniform dot-like appearance, signifying fundic columnar epithelium (Fig. 1). Tubular pits pattern, formerly Pattern II, is characterized by ovoid or short tubular pits with a uniform arrangement, signifying cardia mucosal (Fig. 2). Thin linear pattern, a new category, is characterized by thin superficial grooves that may represent cardia mucosa and/or Barrett’s epithelium (Fig. 3). Deep linear pattern, also a new category, is characterized by deep, coarse grooves signifying Barrett’s epithelium (Fig. 4). Villous pattern, formerly Pattern III, is characterized by a uniform mesh-like villous appearance or, more rarely, fingerlike projections, signifying Barrett’s epithelium (Fig. 5). The new category foveolar pattern is characterized by a flat surface interspersed with wide circular pits and the absence of villous structures, signifying Barrett’s epithelium (Fig. 6). Cerebroid pattern, formerly Pattern IV, is characterized by uniform thick, straight tubular or convoluted ridges reminiscent of cerebral gyri, signifying Barrett’s epithelium (Fig. 7). In this ongoing study, the yield observed thus far of biopsy specimens for the detection of intestinal metaplasia correlated by pattern type is shown in Table 4. The usefulness of enhanced magnification endoscopy is supported by the preliminarily published results of a study by Rey and Kuznetsov.22 These investigators studied 37 patients with Barrett’s esophagus by using 3% acetic acid and a new highresolution magnifying endoscope (GIF-160Z, Olympus). Dysplasia was found in biopsy specimens from flat red areas of mucosa. Three types of GASTROINTESTINAL ENDOSCOPY
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Figure 2. Magnifying endoscopic views at 340 (A) and 380 (B), after application of acetic acid, showing ovoid or short tubular pits with a uniform arrangement (tubular pit pattern).
Figure 3. Magnifying endoscopic views at 340 (A) and 380 (B), after application of acetic acid, showing thin superficial grooves (thin linear pattern).
epithelium were identified: fundic, cardia, and intestinal metaplasia. Magnification chromoendoscopy The first attempt at combining magnification and chromoendoscopy with Lugol’s solution and Indigo carmine dye to study Barrett’s esophagus was that of Stevens et al.20 in 1994. They examined 46 patients with symptoms of GERD by using a combination of dye spraying and magnification endoscopy. Barrett’s esophagus was identified in 13 patients, 10 of whom had short-segment Barrett’s esophagus and 3 had long-segment Barrett’s esophagus. All patients with Barrett’s esophagus had a villiform surface pattern 62
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that correlated with the finding of intestinal metaplasia in biopsy specimens. The maximum magnification of the endoscope used for this study was only 335.20 Endo et al.23 proposed another classification of Barrett’s esophagus in 2002. They used a highresolution magnifying endoscope (GIF-Q240Z; Olympus) and methylene blue staining. Based on evaluation of the mucosal pattern for 67 areas of Barrett’s mucosa, these investigators defined 5 distinct patterns (designated types 1 through 5): type 1 is characterized by small round pits; type 2 is described as long straight lines; type 3 has long oval and curved pits; type 4 is a tubular and twisted pattern similar to a branch or gyrus-like structure; VOLUME 59, NO. 1, 2004
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Figure 4. Magnifying endoscopic views at 360 (A) and 380 (B), after application of acetic acid, showing deep, coarse grooves (deep linear pattern).
Figure 5. A, magnifying endoscopic view at 335, after application of acetic acid, showing uniform, mesh-like villous appearance (villous pattern). B, magnifying endoscopic view at 360, after application of acetic acid, showing finger-like projections (villous pattern).
and type 5 is characterized by a villous appearance with flat or finger-like projections. Methylene blue stained 0% of the mucosa identified as types 1 and 2. However, intestinal metaplasia was found in 6% of biopsy specimens from mucosa that exhibited the type 1 pattern. The rate of positive methylene blue staining was 23% for type 3, and 40% of biopsy specimens from this type revealed intestinal metaplasia. Intestinal metaplasia was found in 100% of biopsy specimens from mucosa that exhibited either a type 4 or type 5 pattern. Surprisingly, however, type 4 and type 5 mucosa were stained by methylene blue in only 60% and 50% of cases, respectively. By using high-resolution magnifying endoscopy and spraying Indigo carmine, a nonabsorbed conVOLUME 59, NO. 1, 2004
trast stain, Sharma et al.24 identified 3 mucosal patterns within the columnar mucosa of 80 patients suspected of having Barrett’s esophagus: ridge/ villous, circular, and irregular/distorted. The ridge/ villous pattern was characterized by a regularly arranged villiform pattern with tortuous and thick villi of sausage or cerebriform appearance. The circular pattern had regularly arranged circular or oval areas. In the irregular/distorted pattern, there was marked irregularity and distortion of the cerebriform-villous pattern. Intestinal metaplasia was identified in 57 of 62 (97%) patients with the ridged/ villous pattern and in two of 12 (17%) with the circular pattern. Low-grade dysplasia was found in 18 patients, all of whom had the ridged/villous GASTROINTESTINAL ENDOSCOPY
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Figure 6. Magnifying endoscopic views at 380 (A) and 380 (B), after application of acetic acid, showing flat surface interspersed with wide circular pits and absence of villous structures (foveolar pattern).
Figure 7. A, magnifying endoscopic views at 380, after application of acetic acid, showing uniform thick straight tubular ridges. B, magnifying endoscopic views at 380, after application of acetic acid, showing uniform thick convoluted ridges reminiscent of cerebral gyri (cerebroid pattern).
pattern, whereas high-grade dysplasia was detected in 6 patients, all of whom had the irregular/distorted pattern. This study by Sharma et al.,24 published in 2003, was the first in which magnification chemoendoscopy was shown to identify and distinguish between high-grade dysplasia and intestinal metaplasia. The results of a study by Meining and Heldwein,25 which compared two different magnification techniques for the diagnosis of intestinal metaplasia, have been published in abstract form. A total of 41 patients with symptoms of reflux but no known Barrett’s esophagus were included. By using a magnification endoscope, methylene blue was sprayed in 20 patients, and the classification of Endo et al.23 was applied; in the other 21 patients, acetic acid was sprayed on the mucosal surface, and the 64
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pattern classification of Guelrud et al.11 was used. The goal was to compare the accuracy rates of each of these magnifying endoscopy classification systems for the identification of histopathologically confirmed intestinal metaplasia. The pattern classification of Guelrud et al.11 had an accuracy of 62% vs. an accuracy of 55% for that of Endo et al.23 Meining and Heldwein24 concluded that magnification endoscopy improves the detection of intestinal metaplasia at the gastroesophageal junction, but that the accuracy is still low.25 CONCLUSION The distribution of intestinal metaplasia in patients with short- and also with long-segment Barrett’s esophagus is often patchy and irregular. Thus, targeted biopsy specimens are of paramount VOLUME 59, NO. 1, 2004
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importance for diagnosis. Chromoendoscopy is an effective, readily available method that can enhance endoscopic diagnosis, including the detection of intestinal metaplasia through more accurate targeting of biopsy specimens. When chromoendoscopy is performed with magnifying endoscopy, various mucosal patterns can be recognized that may facilitate the identification of intestinal metaplasia. Application of acetic acid to the mucosal surface is a relatively new method for demonstration of mucosal patterns when combined with magnification endoscopy. The technique of magnification endoscopy is not difficult and adds only 5 to 10 minutes to the length of a standard endoscopic examination. However, the majority of endoscopists have not been trained in the use of magnification endoscopes. The value of magnifying endoscopy with the use of chromoendoscopic dyes or acetic acid in clinical practice currently is under investigation. However, these techniques have significant potential to improve diagnostic accuracy and thereby impact the morbidity and mortality associated with short- and long-segment Barrett’s esophagus at little increase in cost. A number of classification schemes have been proposed to describe the mucosal patterns observed in Barrett’s epithelium by using these techniques. The current proposed classifications are too complex relative to their clinical value. Nevertheless, simplification of these systems will occur over time with increased use of magnifying endoscopy in conjunction with dye or acetic acid spraying. These techniques require further validation in large, multicenter trials so that mucosal patterns can be more clearly defined and standardized. In addition, it will be necessary to assess intra- and interobserver variability in the interpretation of the endoscopic findings and to define the endoscopic criteria for dysplasia and early stage cancer. REFERENCES 1. Blot WJ, Devesa SS, Kneller RW, Fraumeni JF Jr. Rising incidence of adenocarcinoma of the esophagus and gastric cardia. JAMA 1991;265:1287-9. 2. Blot WJ, Devesa SS, Fraumeni JF Jr. Continuing climb in rates of esophageal adenocarcinoma: an update. JAMA 1993; 270:1320. 3. Skinner DB, Walther BC, Riddell RH, Schmidt H, Iascone C, DeMeester TR. Barrett’s esophagus: comparison of benign and malignant cases. Ann Surg 1983;198:554-66. 4. Spechler SJ, Zeroogian JM, Antonioli DA, Wang HH, Goyal RK. Prevalence of metaplasia at the gastro-oesophageal junction. Lancet 1994;344:1533-6.
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5. Johnston MH, Hammond AS, Laskin W, Jones DM. The prevalence and clinical characteristics of short segments of specialized intestinal metaplasia in the distal esophagus on routine endoscopy. Am J Gastroenterol 1996;91:1507-11. 6. Chalasani N, Wo JM, Hunter JG, Waring JP. Significance of intestinal metaplasia in different areas of esophagus including esophagogastric junction. Dig Dis Sci 1997;42:603-7. 7. Eloubeidi MA, Provenzale D. Does this patient have Barrett’s esophagus? The utility of predicting Barrett’s esophagus at the index endoscopy. Am J Gastroenterol 1999;94:937-43. 8. Tada M, Kawai K. Research with the endoscope: new techniques using magnification and chromoscopy. Clin Gastroenterol 1986;15:417-37. 9. Anonymous. Technology status evaluation report. High resolution and high-magnification endoscopy. Gastrointest Endosc 2000;52:854-6. 10. Kiesslich R, Jung M. Magnification endoscopy: does it improve mucosal surface analysis for the diagnosis of gastrointestinal neoplasias? Endoscopy 2002;34:819-22. 11. Guelrud M, Herrera I, Essenfeld H, Castro J. Enhanced magnification endoscopy: a new technique to identify specialized intestinal metaplasia in Barrett’s esophagus. Gastrointest Endosc 2001;53:559-65. 12. Canto MI, Setrakian S, Petras RE, Blades E, Chak A, Sivak MV Jr. Methylene blue selectively stains intestinal metaplasia in Barrett’s esophagus. Gastrointest Endosc 1996;44:1-7. 13. Canto MI. Staining in gastrointestinal endoscopy: the basics. Endoscopy 1999;31:479-86. 14. Cartier R. Practical colposcopy. Basel: Karger; 1978. 15. Guelrud M, Herrera I. Acetic acid improves identification of remnant islands of Barrett’s epithelium after endoscopic therapy. Gastrointest Endosc 1998;47:512-5. 16. Acosta MM, Boyce HW Jr. Chromoendoscopy: where is it useful? J Clin Gastroenterol 1998;27:13-20. 17. Canto MI, Yoshida T, Gossner L. Chromoscopy of intestinal metaplasia in Barrett’s esophagus. Endoscopy 2002;34:330-6. 18. Canto MI. Vital staining and Barrett’s esophagus. Gastrointest Endosc 1999;49:S12-6. 19. Shim CS. Staining in gastrointestinal endoscopy: clinical application and limitations. Endoscopy 1999;31:487-96. 20. Stevens PD, Lightdale CJ, Green PH, Siegel LM, GarciaCarrasquillo RJ, Rotterdam H. Combined magnification endoscopy with chromoendoscopy for the evaluation of Barrett’s esophagus. Gastrointest Endosc 1994;40:747-9. 21. Thompson JJ, Zinsser KR, Enterline HT. Barrett’s metaplasia and adenocarcinoma of the esophagus and gastroesophageal junction. Hum Pathol 1983;14:42-60. 22. Rey JF, Kuznetsov K. Usefulness of chromoscopy with acetic acid and magnification for Barrett esophagus [abstract]. Gastrointest Endosc 2003;57:AB573. 23. Endo T, Awakawa T, Takahashi H, Arimura Y, Itoh F, Yamashita K, et al. Classification of Barrett’s epithelium by magnifying endoscopy. Gastrointest Endosc 2002;55:641-7. 24. 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;52:24-7. 25. Meining A, Heldwein W. Magnification endoscopy for detection of specialized intestinal metaplasia at the esophagogastric junction [abstract]. Gastrointest Endosc 2003;57:AB577.
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