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Short segment Barrett’s esophagus—the need for standardization of the definition and of endoscopic criteria
THE AMERICAN JOURNAL OF GASTROENTEROLOGY Copyright © 1998 by Am. Coll. of Gastroenterology Published by Elsevier Science Inc.
Vol. 93, No. 7, 1998 ISSN 0002-9270/98/$19.00 PII S0002-9270(98)00205-6
Clinical reviews Short Segment Barrett’s Esophagus—The Need for Standardization of the Definition and of Endoscopic Criteria Prateek Sharma, M.D., Thomas G. Morales, M.D., and Richard E. Sampliner, M.D. University of Arizona Health Sciences Center and Tucson VA Medical Center Department of Medicine, Section of Gastroenterology, Tucson, Arizona
There has been a recent increase in abstracts and publications reporting intestinal metaplasia in the distal esophagus and cardia. The terms “short segment Barrett’s esophagus,” “intestinal metaplasia of the esophagogastric junction,” and “intestinal metaplasia of the cardia” are being used to describe either similar or different entities. This review article deals with the current data on these issues, the definition of short segment Barrett’s esophagus including the endoscopic and histologic criteria, the rationale for separating short segment Barrett’s esophagus from intestinal metaplasia of the cardia, and a simple classification of intestinal metaplasia. (Am J Gastroenterol 1998;93:1033–1036. © 1998 by Am. Coll. of Gastroenterology)
to dysplasia is well established, and both long and short segments of Barrett’s esophagus can progress to dysplasia and cancer (12–14). PROPOSED DEFINITION Unfortunately, the definition of SSBE varies among investigators, and endoscopic criteria have not been uniformly defined. The length used in the definition has varied from ,3 cm to ,2 cm. In addition, some authors include IM of the esophagogastric junction and IM of the cardia in the definition of SSBE. This review will focus on a working definition of SSBE, endoscopic criteria for its identification, and the rationale for separating SSBE from IM of the cardia. A definition of SSBE needs to include an endoscopic estimation of length, a definition of the endoscopic landmarks to determine that length, a standardized endoscopic technique of measuring the length, and histologic criteria to document the presence of Barrett’s esophagus. Our working definition of SSBE is an abnormal appearing esophageal lining at endoscopy that is ,3 cm in length with IM documented on biopsy. As opposed to SSBE, IM of the cardia lacks distinguishing endoscopic characteristics from normal cardia mucosa in the absence of vital staining. Intestinal metaplasia of the cardia is defined as histologic evidence of IM by biopsy of the proximal stomach within 2 cm of the esophagogastric junction.
INTRODUCTION Barrett’s esophagus is a metaplastic condition that occurs in about 12% of patients with gastroesophageal reflux disease (GERD) (1). The importance of Barrett’s esophagus lies in its potential to develop into adenocarcinoma of the esophagus. The incidence of adenocarcinoma of the esophagus is rapidly increasing (2, 3) and now accounts for up to 50% of esophageal cancers seen in white males in the United States (4). The finding of intestinal metaplasia (IM) on biopsy from any length of columnar epithelium within the tubular esophagus defines Barrett’s esophagus (5). Previous diagnostic criteria for Barrett’s esophagus were based on the length of columnar lining of the esophagus, which usually included segments $3 cm in length (6, 7). However, short segments of IM in the distal esophagus are being reported with increasing frequency (8 –11). Segments of IM ,2–3 cm in length have been referred to as “short segment Barrett’s esophagus” (SSBE). The progression of Barrett’s esophagus
ENDOSCOPIC CRITERIA A length of ,3 cm of Barrett’s epithelium is proposed for the definition of SSBE because $3 cm has been the “traditional” definition of Barrett’s esophagus harkening back to clinical trials in which investigators wanted to ensure that patients had the disease being studied (6, 7). In the clinical setting, endoscopists need to agree upon the endoscopic landmarks and to have a standardized approach to measure the length of SSBE. When endoscopists agree on
Received Sep. 12, 1997; accepted Jan. 6, 1998. 1033
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AJG – Vol. 93, No. 7, 1998 TABLE 1 Clinical Characteristics of Patients With SSBE (Published Manuscripts)
Author (ref #)
SSBE Length
Mean Age
Gender
Ethnicity
8%
65
7
8%
56
17
12.1%
?
100% Male 43% Male ?
95% Caucasian 100% Caucasian 100% Caucasian 100% Caucasian 100% Caucasian
# of Pts
Prevalence
19
Weston et al. (10)
,2 cm
Chalasani et al. (27)
,2.5 cm
Spechler et al. (11)
,3 cm
Johnston et al. (9)
,2.5 cm
4
2.4%
?
?
Morales et al. (8)
,3 cm
8
7.7%
59
100% Male
GERD Symptoms 53% 100% ? ? 88%
SSBE, short segment Barrett’s esophagus; Pts, patients.
standard criteria and uniformly use the criteria, interobserver agreement in measuring Barrett’s esophagus has been found to have a reliability coefficient of 0.92 (where 1.0 represents perfect agreement) (15). With the patient in the left lateral position, the bite block against the patient’s teeth, and the endoscope placed at the proximal margin of continuous columnar epithelium after moving the tip back and forth, the proximal margin can be measured as the distance from the bite block. The end of the esophagus can be identified by the “endoscopic lower esophageal sphincter” or, in the absence of that, the proximal margin of the hiatal hernia folds (16). The latter reference point should be determined with minimal inflation of the distal esophagus, such that the proximal margin of the gastric folds become apparent. With overinflation, this landmark is obscured by the flattening of folds in the hiatal hernia sac. The length of Barrett’s mucosa is then determined by subtracting the distance of the proximal margin from the distance to the end of the esophagus (15). HISTOLOGICAL CRITERIA Because the yield of IM in Barrett’s esophagus is related to the length of the abnormal appearing epithelium (17), multiple biopsies must be taken of the Barrett’s appearing epithelium. An unresolvable issue is how irregular the squamocolumnar junction has to be in order to warrant biopsy. Previous studies have found that when short segments of columnar epithelium are visualized during endoscopy, IM can be identified histologically in approximately 50% of cases (8, 10). Targeting becomes a difficult technical issue and the endoscopic recognition of IM can be greatly enhanced by either a vital stain such as methylene blue (18) or by magnification endoscopy (19). Histological documentation of SSBE may be difficult. Ideally, an alcian blue stain at pH 2.5 helps identify goblet cells and separates true goblet cells from “pseudogoblet cells” (5). Goblet cells are required to make the diagnosis of IM, which is the premalignant lesion for adenocarcinoma.
SSBE VERSUS GASTRIC CARDIA IM Several investigators have routinely biopsied the region of the esophagogastric junction and reported the prevalence of IM, without differentiating the distal esophagus from the gastric cardia (9, 11). If the above discussed endoscopic criteria are followed, the latter two regions can usually be separated. The term “intestinal metaplasia of the esophagogastric junction” should be avoided. Why is it important to separate SSBE from IM of the cardia? Are these different entities? Indeed, there is an increasing body of evidence suggesting that IM of the cardia has a different etiology than IM of the esophagus. Recent series have found that IM of the cardia is not more common in patients with Barrett’s esophagus than in controls (20, 21). In addition, it is not clear that the cancer risk of these two entities is equivalent. Although the association of SSBE with adenocarcinoma is well established (13, 14, 22), IM of the cardia has yet to be clearly associated with cardia cancer. Inflammation of the gastric cardia, i.e., carditis, may be the precursor lesion for IM of the cardia. There is recent literature to suggest that carditis and IM of the cardia are related to H. pylori infection rather than to GERD (8, 23–25). SSBE, on the other hand, has been found to be a complication of GERD (9, 10). Also, the prevalence of H. pylori infection is no higher in patients with Barrett’s esophagus than in controls (26). There is evidence to suggest that IM of the cardia is equally prevalent in Caucasians and African-Americans, whereas SSBE is most commonly seen in Caucasians (27). This ethnic difference may be a reflection of differences in pathophysiology and/or genetic predisposition. The prevalence of SSBE in published series ranges from 2% to 12% in patients undergoing routine upper endoscopy with biopsy. Tables 1 and 2 summarize currently published series on SSBE in manuscript and abstract form, respectively. It is important to note that only in a few series is it possible to clearly define and separate SSBE from IM of the
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SHORT SEGMENT BARRETT’S ESOPHAGUS
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TABLE 2 Clinical Characteristics of Patients With SSBE (Abstracts)
Author (ref #)
SSBE
Mean Age
Gender
Ethnicity
7%
58
46
33%
63
,2 cm
11
17%
57
70.3% Male 54% Male 27% Male
86% Caucasian 80% Caucasian 45% Hispanic
,0.5–2 cm
32
19.3%
Length
# of Pts.
Prevalence
Hirota et al. (28)
,3 cm
64
Heier et al. (29)
,3 cm
Abo et al. (30) Conio et al. (31)
GERD Symptoms 86% 50% 100% 84%
SSBE, short segment Barrett’s esophagus; Pts, patients.
cardia (8 –11, 27, 28 –31). Other authors have grouped these patients together (32– 40). There is recent data available regarding the prevalence and incidence of dysplasia and adenocarcinoma in patients with SSBE. In our prospective follow-up series of SSBE, the prevalence of dysplasia was 8.5% and the incidence 5.7%/yr in a group of patients followed for a mean of 3 yr (41), comparable to the findings of Weston et al. (42). In the latter study, the incidence of dysplasia in SSBE was significantly less than that in long segment Barrett’s esophagus. None of the patients in this series with SSBE progressed to adenocarcinoma of the esophagus. In contrast, one patient in our series developed adenocarcinoma during surveillance (41). There are currently no prospective studies identifying the incidence of adenocarcinoma in traditional long segment Barrett’s esophagus compared with SSBE. PROPOSED CLASSIFICATION OF IM Norman Barrett, a British surgeon, described a congenitally short esophagus that tethered a tubular segment of the stomach within the chest. Although the “Barrett’s esophagus” that we define in the 1990s is quite different from the initial description by Barrett in 1950, the term “Barrett’s esophagus” is deeply rooted in the medical literature. Intestinal metaplasia is the premalignant lesion for adenocarcinoma of the esophagus and is included in the definition of Barrett’s esophagus. However, since the relative cancer risk between short and long segments of esophageal IM and cardia IM may be different, it is important for clinicians and researchers to discriminate between these entities. We therefore propose a simple classification of IM in the distal esophagus and the gastric cardia (Table 3). Another classification of Barrett’s esophagus has recently been suggested (43). Our classification separates SSBE from long segment Barrett’s esophagus (LSBE), emphasizing a potential difference in cancer risk. It also recognizes the distinction between IM of the esophagus and IM of the cardia. It is important for clinical investigators to have a uniform language to advance our understanding of these common endoscopic and histologic findings. This classification ultimately will help to define the true cancer risk for each of these entities.
TABLE 3 Proposed Classification of Intestinal Metaplasia Terminology
Length
LSBE SSBE Gastric cardia IM
$3cm ,3cm
Adenocarcinoma Risk
Surveillance Recommended
Yes Yes Unclear
Yes Yes No
IM, intestinal metaplasia; LSBE, long segment Barrett’s esophagus; SSBE, short segment Barrett’s esophagus.
THE FUTURE A simple endoscopic method of detecting IM and dysplasia at the time of endoscopy would prove to be useful in future studies of SSBE. A new and exciting technique, laser-induced fluorescence (LIF) spectroscopy, has the potential to detect dysplasia within Barrett’s epithelium at the time of endoscopy (44). SSBE is more prevalent than LSBE, although its cancer risk may be lower. Larger cohorts of patients with SSBE should be followed for longer time periods to define their exact risk of dysplasia and adenocarcinoma. We also need to better define patients with SSBE who are at a higher risk for the development of adenocarcinoma. A number of biomarkers including p53 mutation, flow cytometry, PCNA, and Ki67 have been studied, but none of these have been superior to dysplasia in predicting malignant outcome. There is an immediate need to identify better biological markers of neoplastic transformation and adenocarcinoma risk in SSBE. CONCLUSIONS Intestinal metaplasia in the distal esophagus and cardia is being reported with increasing frequency. If we are to identify the differential pathophysiology and cancer risks, we need to separate these entities. Patients undergoing upper endoscopy for reflux symptoms and found to have short tongues of columnar appearing mucosa above the gastroesophageal junction should be biopsied. If these biopsies reveal IM, the diagnosis of SSBE is confirmed, thus indicating the need for surveillance. However, we do not advocate routinely biopsying the normal appearing squamoco-
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lumnar junction because of the lack of information on the cancer risk of IM of the cardia. Reprint requests and correspondence: Prateek Sharma, M.D., Tucson VA Medical Center (111G-1), 3601 S 6th Avenue, Tucson, AZ 85723.
REFERENCES 1. Winters C, Spurling TJ, Chobanian SJ, et al. Barrett’s esophagus: A prevalent occult complication of gastroesophageal reflux disease. Gastroenterology 1987;92:118 –24. 2. Pera M, Cameron AJ, Trastek VF, et al. Increasing incidence of adenocarcinoma of the esophagus and esophagogastric junction. Gastroenterology 1993;104:510 –3. 3. Blot WJ, Devesa SS, Kneller RW, et al. Rising incidence of adenocarcinoma of the esophagus and gastric cardia. JAMA 1991;265:1267– 89. 4. Blot WJ, Devesa SS, Fraumeni JF, Jr. Continuing climb in rates of esophageal adenocarcinoma: An update. JAMA 1993;270:1320. 5. Weinstein WM, Ippoliti AF. The diagnosis of Barrett’s esophagus: Goblets, goblets, goblets. Gastrointest Endosc 1996;44:91–5. 6. Skinner DB, Ferguson MK, Soriano A, et al. Selection of operation for esophageal cancer based on staging. Ann Surg 1986;204:391– 400. 7. Spechler SJ, Goyal RK. Barrett’s esophagus. N Engl J Med 1986;315: 362–71. 8. Morales TG, Sampliner RE, Bhattacharyya A. Intestinal metaplasia of the gastric cardia. Am J Gastroenterol 1997;92:414 – 8. 9. Johnston MH, Hammond AS, Laskin W, et al. 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. 10. Weston AP, Krmpotich P, Makdisi WF, et al. Short segment Barrett’s esophagus: Clinical and histological features, associated endoscopic findings and association with gastric intestinal metaplasia. Am J Gastroenterol 1996;91:981– 6. 11. Spechler SJ, Zeroogian JM, Antoniolo DA, et al. Prevalence of metaplasia at the gastroesophageal junction. Lancet 1994;344:1533– 6. 12. Drewitz DJ, Sampliner RE, Garewal HS. The incidence of adenocarcinoma in Barrett’s esophagus: A prospective study of 170 patients followed 4.8 years. Am J Gastroenterol 1997;92:212–5. 13. Schnell TG, Sontag SJ, Chejfec G. Adenocarcinomas arising in tongues or short segments of Barrett’s esophagus. Dig Dis Sci 1992; 37:137– 43. 14. Hameeteman W, Tytgat GNJ, Houthoff HJ, et al. Barrett’s esophagus: Development of dysplasia and adenocarcinoma. Gastroenterology 1989;96:1249 –56. 15. Sampliner RE, Garewal HS, Fennerty MB, et al. Lack of impact of therapy on extent of Barrett’s esophagus in 67 patients. Dig Dis Sci 1990;35:93– 6. 16. McClave SA, Boyce HW, Gottfried MR. Early diagnosis of columnarlined esophagus: A new endoscopic diagnostic criterion. Gastrointest Endosc 1987;33:413– 6. 17. Spechler SJ. Short and ultrashort Barrett’s esophagus—what does it mean? Sem Gastro Dis 1997;8:59 – 67. 18. Canto MI, Setrakian S, Petras RE, et al. Methylene blue selectively stains intestinal metaplasia in Barrett’s esophagus. Gastrointest Endosc 1996;44:1–7. 19. Stevens PD, Lightdale CJ, Green PHR, et al. Combined magnification endoscopy with chromoendoscopy for the evaluation of Barrett’s esophagus. Gastrointest Endosc 1994;40:747–9. 20. Morales TG, Bhattacharyya A, Johnson C, et al. Is Barrett’s esophagus associated with intestinal metaplasia of the gastric cardia? Am J Gastroenterol 1997;92:1818 –22. 21. Weston AP, Krmpotich PT, Cherian R, et al. Prospective evaluation of intestinal metaplasia and dysplasia within the cardia of patients with Barrett’s esophagus. Dig Dis Sci 1997;42:597– 602. 22. Hamilton SR, Smith RRL, Cameron JL. Prevalence and characteristics
AJG – Vol. 93, No. 7, 1998
23. 24.
25.
26.
27.
28.
29. 30. 31. 32. 33. 34.
35. 36. 37. 38. 39.
40. 41. 42.
43. 44.
of Barrett’s esophagus in patients with adenocarcinoma of the esophagus or esophagogastric junction. Hum Pathol 1988;19:942– 8. Goldblum JR, Vicari J, Falk GW, et al. Carditis and intestinal metaplasia: It’s all H. pylori. Gastroenterology 1997;112:A129. Hirota WK, Loughney TM, Lazas DJ, et al. Is Helicobacter pylori associated with specialized intestinal metaplasia of the esophagus or stomach? A prospective study of 889 patients. Gastroenterology 1997; 112:A149. Spechler SJ, Wang HH, Chey YY, et al. GERD versus H. pylori infections as potential causes of inflammation in the gastric cardia. Gastroenterology 1997;112:A297. Blaser MJ, Perez-Perez GI, Lindenbaum J, et al. Association of infection due to Helicobacter pylori with specific upper gastrointestinal pathology. Rev Infect Dis 1991;13:S704 – 8. Chalasani N, Wo JM, Hunter JG, et al. Significance of intestinal metaplasia in different areas of esophagus including esophagogastric junction. Dig Dis Sci 1997;42:603–7. Hirota WK, Loughney TM, Lazas DJ, et al. The prevalence and demographics of specialized intestinal metaplasia at the esophagogastric junction in a cohort of 889 prospectively studied patients. Gastroenterology 1997;112:A149. Heier SK, Seif F, Webber S, et al. Short segment Barrett’s esophagus: Clinical and histologic findings. Gastroenterology 1996;110:A132. Abo SR, Stevens PD, Abedi M, et al. Prevalence of short segment Barrett’s epithelium in patients with gastroesophageal reflux disease. Gastroenterology 1995:A43. Conio M, Aste H, Bonelli L. “Short” Barrett’s esophagus: A condition not to be underestimated. Gastrointest Endosc 1994;40:111. Bak YT, Park IB, Kim JH, et al. Validity of specialized columnar epithelium as a diagnostic criterion of short segment Barrett’s esophagus. Gastroenterology 1996;110:A55. Nandukar S, Ng T, Adams S, et al. Short segment Barrett’s esophagus: Prevalence, diagnosis and associations. Gastroenterology 1996;110: A207. Dias Pereira A, Suspira A, Chaves P, et al. Short segments of Barrett’s epithelium and intestinal metaplasia in normal appearing gastroesophageal junctions. Are they the same or different conditions? Gastroenterology 1996;110:A95. Clark GWB, Ireland AP, Peters JH, et al. Short segment Barrett’s esophagus: A prevalent complication of gastroesophageal reflux disease with malignant potential. Gastroenterology 1996;110:A1379. Ballinger PJ, Hogan WJ, Bohorfoush AG, et al. Short segment Barrett’s epithelium: Prevalence and accuracy of endoscopic detection. Gastrointest Endosc 1993;39:A93. Cameron AJ, Kamath PS, Carpenter HA. Prevalence of Barrett’s esophagus and intestinal metaplasia at the esophagogastric junction. Gastroenterology 1997;112:A82. Sherman F, Baig Z, Choudhry U, et al. The prevalence of specialized columnar epithelium in patients with symptoms and/or signs of gastroesophageal reflux disease. Gastrointest Endosc 1997;45:A232. Cooper BT, Cox MA, Gearty JC, et al. Prevalence of specialized columnar epithelium at the cardia of patients with gastroesophageal reflux disease without obvious Barrett’s esophagus: Comparison with normal controls. Gastroenterology 1997;112:A93. Trakal E, Butti AL, Ortiz GA, et al. Precancerous and non-precancerous Barrett’s esophagus. Gastroenterology 1997;112:A760. Sharma P, Morales TG, Bhattacharyya A, et al. Dysplasia in short segment Barrett’s esophagus: A prospective three year follow up. Am J Gastroenterol 1997;92:2012– 6. Weston AP, Krmpotich PT, Cherian R, et al. Prospective long term endoscopic and histological follow up of short segment Barrett’s esophagus: Comparison with traditional long segment Barrett’s esophagus. Am J Gastroenterol 1997;92:407–13. Spechler SJ, Goyal RK. The columnar-lined esophagus, intestinal metaplasia, and Norman Barrett. Gastroenterology 1996;110:614 –21. Pahjehpour M, Overholt BF, Vo-Dinh T, et al. Endoscopic fluorescence detection of high grade dysplasia in Barrett’s esophagus. Gastroenterology 1996;111:93–101.
Vol. 93, No. 7, 1998 ISSN 0002-9270/98/$19.00 PII S0002-9270(98)00205-6
Clinical reviews Short Segment Barrett’s Esophagus—The Need for Standardization of the Definition and of Endoscopic Criteria Prateek Sharma, M.D., Thomas G. Morales, M.D., and Richard E. Sampliner, M.D. University of Arizona Health Sciences Center and Tucson VA Medical Center Department of Medicine, Section of Gastroenterology, Tucson, Arizona
There has been a recent increase in abstracts and publications reporting intestinal metaplasia in the distal esophagus and cardia. The terms “short segment Barrett’s esophagus,” “intestinal metaplasia of the esophagogastric junction,” and “intestinal metaplasia of the cardia” are being used to describe either similar or different entities. This review article deals with the current data on these issues, the definition of short segment Barrett’s esophagus including the endoscopic and histologic criteria, the rationale for separating short segment Barrett’s esophagus from intestinal metaplasia of the cardia, and a simple classification of intestinal metaplasia. (Am J Gastroenterol 1998;93:1033–1036. © 1998 by Am. Coll. of Gastroenterology)
to dysplasia is well established, and both long and short segments of Barrett’s esophagus can progress to dysplasia and cancer (12–14). PROPOSED DEFINITION Unfortunately, the definition of SSBE varies among investigators, and endoscopic criteria have not been uniformly defined. The length used in the definition has varied from ,3 cm to ,2 cm. In addition, some authors include IM of the esophagogastric junction and IM of the cardia in the definition of SSBE. This review will focus on a working definition of SSBE, endoscopic criteria for its identification, and the rationale for separating SSBE from IM of the cardia. A definition of SSBE needs to include an endoscopic estimation of length, a definition of the endoscopic landmarks to determine that length, a standardized endoscopic technique of measuring the length, and histologic criteria to document the presence of Barrett’s esophagus. Our working definition of SSBE is an abnormal appearing esophageal lining at endoscopy that is ,3 cm in length with IM documented on biopsy. As opposed to SSBE, IM of the cardia lacks distinguishing endoscopic characteristics from normal cardia mucosa in the absence of vital staining. Intestinal metaplasia of the cardia is defined as histologic evidence of IM by biopsy of the proximal stomach within 2 cm of the esophagogastric junction.
INTRODUCTION Barrett’s esophagus is a metaplastic condition that occurs in about 12% of patients with gastroesophageal reflux disease (GERD) (1). The importance of Barrett’s esophagus lies in its potential to develop into adenocarcinoma of the esophagus. The incidence of adenocarcinoma of the esophagus is rapidly increasing (2, 3) and now accounts for up to 50% of esophageal cancers seen in white males in the United States (4). The finding of intestinal metaplasia (IM) on biopsy from any length of columnar epithelium within the tubular esophagus defines Barrett’s esophagus (5). Previous diagnostic criteria for Barrett’s esophagus were based on the length of columnar lining of the esophagus, which usually included segments $3 cm in length (6, 7). However, short segments of IM in the distal esophagus are being reported with increasing frequency (8 –11). Segments of IM ,2–3 cm in length have been referred to as “short segment Barrett’s esophagus” (SSBE). The progression of Barrett’s esophagus
ENDOSCOPIC CRITERIA A length of ,3 cm of Barrett’s epithelium is proposed for the definition of SSBE because $3 cm has been the “traditional” definition of Barrett’s esophagus harkening back to clinical trials in which investigators wanted to ensure that patients had the disease being studied (6, 7). In the clinical setting, endoscopists need to agree upon the endoscopic landmarks and to have a standardized approach to measure the length of SSBE. When endoscopists agree on
Received Sep. 12, 1997; accepted Jan. 6, 1998. 1033
1034
SHARMA et al.
AJG – Vol. 93, No. 7, 1998 TABLE 1 Clinical Characteristics of Patients With SSBE (Published Manuscripts)
Author (ref #)
SSBE Length
Mean Age
Gender
Ethnicity
8%
65
7
8%
56
17
12.1%
?
100% Male 43% Male ?
95% Caucasian 100% Caucasian 100% Caucasian 100% Caucasian 100% Caucasian
# of Pts
Prevalence
19
Weston et al. (10)
,2 cm
Chalasani et al. (27)
,2.5 cm
Spechler et al. (11)
,3 cm
Johnston et al. (9)
,2.5 cm
4
2.4%
?
?
Morales et al. (8)
,3 cm
8
7.7%
59
100% Male
GERD Symptoms 53% 100% ? ? 88%
SSBE, short segment Barrett’s esophagus; Pts, patients.
standard criteria and uniformly use the criteria, interobserver agreement in measuring Barrett’s esophagus has been found to have a reliability coefficient of 0.92 (where 1.0 represents perfect agreement) (15). With the patient in the left lateral position, the bite block against the patient’s teeth, and the endoscope placed at the proximal margin of continuous columnar epithelium after moving the tip back and forth, the proximal margin can be measured as the distance from the bite block. The end of the esophagus can be identified by the “endoscopic lower esophageal sphincter” or, in the absence of that, the proximal margin of the hiatal hernia folds (16). The latter reference point should be determined with minimal inflation of the distal esophagus, such that the proximal margin of the gastric folds become apparent. With overinflation, this landmark is obscured by the flattening of folds in the hiatal hernia sac. The length of Barrett’s mucosa is then determined by subtracting the distance of the proximal margin from the distance to the end of the esophagus (15). HISTOLOGICAL CRITERIA Because the yield of IM in Barrett’s esophagus is related to the length of the abnormal appearing epithelium (17), multiple biopsies must be taken of the Barrett’s appearing epithelium. An unresolvable issue is how irregular the squamocolumnar junction has to be in order to warrant biopsy. Previous studies have found that when short segments of columnar epithelium are visualized during endoscopy, IM can be identified histologically in approximately 50% of cases (8, 10). Targeting becomes a difficult technical issue and the endoscopic recognition of IM can be greatly enhanced by either a vital stain such as methylene blue (18) or by magnification endoscopy (19). Histological documentation of SSBE may be difficult. Ideally, an alcian blue stain at pH 2.5 helps identify goblet cells and separates true goblet cells from “pseudogoblet cells” (5). Goblet cells are required to make the diagnosis of IM, which is the premalignant lesion for adenocarcinoma.
SSBE VERSUS GASTRIC CARDIA IM Several investigators have routinely biopsied the region of the esophagogastric junction and reported the prevalence of IM, without differentiating the distal esophagus from the gastric cardia (9, 11). If the above discussed endoscopic criteria are followed, the latter two regions can usually be separated. The term “intestinal metaplasia of the esophagogastric junction” should be avoided. Why is it important to separate SSBE from IM of the cardia? Are these different entities? Indeed, there is an increasing body of evidence suggesting that IM of the cardia has a different etiology than IM of the esophagus. Recent series have found that IM of the cardia is not more common in patients with Barrett’s esophagus than in controls (20, 21). In addition, it is not clear that the cancer risk of these two entities is equivalent. Although the association of SSBE with adenocarcinoma is well established (13, 14, 22), IM of the cardia has yet to be clearly associated with cardia cancer. Inflammation of the gastric cardia, i.e., carditis, may be the precursor lesion for IM of the cardia. There is recent literature to suggest that carditis and IM of the cardia are related to H. pylori infection rather than to GERD (8, 23–25). SSBE, on the other hand, has been found to be a complication of GERD (9, 10). Also, the prevalence of H. pylori infection is no higher in patients with Barrett’s esophagus than in controls (26). There is evidence to suggest that IM of the cardia is equally prevalent in Caucasians and African-Americans, whereas SSBE is most commonly seen in Caucasians (27). This ethnic difference may be a reflection of differences in pathophysiology and/or genetic predisposition. The prevalence of SSBE in published series ranges from 2% to 12% in patients undergoing routine upper endoscopy with biopsy. Tables 1 and 2 summarize currently published series on SSBE in manuscript and abstract form, respectively. It is important to note that only in a few series is it possible to clearly define and separate SSBE from IM of the
AJG – July 1998
SHORT SEGMENT BARRETT’S ESOPHAGUS
1035
TABLE 2 Clinical Characteristics of Patients With SSBE (Abstracts)
Author (ref #)
SSBE
Mean Age
Gender
Ethnicity
7%
58
46
33%
63
,2 cm
11
17%
57
70.3% Male 54% Male 27% Male
86% Caucasian 80% Caucasian 45% Hispanic
,0.5–2 cm
32
19.3%
Length
# of Pts.
Prevalence
Hirota et al. (28)
,3 cm
64
Heier et al. (29)
,3 cm
Abo et al. (30) Conio et al. (31)
GERD Symptoms 86% 50% 100% 84%
SSBE, short segment Barrett’s esophagus; Pts, patients.
cardia (8 –11, 27, 28 –31). Other authors have grouped these patients together (32– 40). There is recent data available regarding the prevalence and incidence of dysplasia and adenocarcinoma in patients with SSBE. In our prospective follow-up series of SSBE, the prevalence of dysplasia was 8.5% and the incidence 5.7%/yr in a group of patients followed for a mean of 3 yr (41), comparable to the findings of Weston et al. (42). In the latter study, the incidence of dysplasia in SSBE was significantly less than that in long segment Barrett’s esophagus. None of the patients in this series with SSBE progressed to adenocarcinoma of the esophagus. In contrast, one patient in our series developed adenocarcinoma during surveillance (41). There are currently no prospective studies identifying the incidence of adenocarcinoma in traditional long segment Barrett’s esophagus compared with SSBE. PROPOSED CLASSIFICATION OF IM Norman Barrett, a British surgeon, described a congenitally short esophagus that tethered a tubular segment of the stomach within the chest. Although the “Barrett’s esophagus” that we define in the 1990s is quite different from the initial description by Barrett in 1950, the term “Barrett’s esophagus” is deeply rooted in the medical literature. Intestinal metaplasia is the premalignant lesion for adenocarcinoma of the esophagus and is included in the definition of Barrett’s esophagus. However, since the relative cancer risk between short and long segments of esophageal IM and cardia IM may be different, it is important for clinicians and researchers to discriminate between these entities. We therefore propose a simple classification of IM in the distal esophagus and the gastric cardia (Table 3). Another classification of Barrett’s esophagus has recently been suggested (43). Our classification separates SSBE from long segment Barrett’s esophagus (LSBE), emphasizing a potential difference in cancer risk. It also recognizes the distinction between IM of the esophagus and IM of the cardia. It is important for clinical investigators to have a uniform language to advance our understanding of these common endoscopic and histologic findings. This classification ultimately will help to define the true cancer risk for each of these entities.
TABLE 3 Proposed Classification of Intestinal Metaplasia Terminology
Length
LSBE SSBE Gastric cardia IM
$3cm ,3cm
Adenocarcinoma Risk
Surveillance Recommended
Yes Yes Unclear
Yes Yes No
IM, intestinal metaplasia; LSBE, long segment Barrett’s esophagus; SSBE, short segment Barrett’s esophagus.
THE FUTURE A simple endoscopic method of detecting IM and dysplasia at the time of endoscopy would prove to be useful in future studies of SSBE. A new and exciting technique, laser-induced fluorescence (LIF) spectroscopy, has the potential to detect dysplasia within Barrett’s epithelium at the time of endoscopy (44). SSBE is more prevalent than LSBE, although its cancer risk may be lower. Larger cohorts of patients with SSBE should be followed for longer time periods to define their exact risk of dysplasia and adenocarcinoma. We also need to better define patients with SSBE who are at a higher risk for the development of adenocarcinoma. A number of biomarkers including p53 mutation, flow cytometry, PCNA, and Ki67 have been studied, but none of these have been superior to dysplasia in predicting malignant outcome. There is an immediate need to identify better biological markers of neoplastic transformation and adenocarcinoma risk in SSBE. CONCLUSIONS Intestinal metaplasia in the distal esophagus and cardia is being reported with increasing frequency. If we are to identify the differential pathophysiology and cancer risks, we need to separate these entities. Patients undergoing upper endoscopy for reflux symptoms and found to have short tongues of columnar appearing mucosa above the gastroesophageal junction should be biopsied. If these biopsies reveal IM, the diagnosis of SSBE is confirmed, thus indicating the need for surveillance. However, we do not advocate routinely biopsying the normal appearing squamoco-
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lumnar junction because of the lack of information on the cancer risk of IM of the cardia. Reprint requests and correspondence: Prateek Sharma, M.D., Tucson VA Medical Center (111G-1), 3601 S 6th Avenue, Tucson, AZ 85723.
REFERENCES 1. Winters C, Spurling TJ, Chobanian SJ, et al. Barrett’s esophagus: A prevalent occult complication of gastroesophageal reflux disease. Gastroenterology 1987;92:118 –24. 2. Pera M, Cameron AJ, Trastek VF, et al. Increasing incidence of adenocarcinoma of the esophagus and esophagogastric junction. Gastroenterology 1993;104:510 –3. 3. Blot WJ, Devesa SS, Kneller RW, et al. Rising incidence of adenocarcinoma of the esophagus and gastric cardia. JAMA 1991;265:1267– 89. 4. Blot WJ, Devesa SS, Fraumeni JF, Jr. Continuing climb in rates of esophageal adenocarcinoma: An update. JAMA 1993;270:1320. 5. Weinstein WM, Ippoliti AF. The diagnosis of Barrett’s esophagus: Goblets, goblets, goblets. Gastrointest Endosc 1996;44:91–5. 6. Skinner DB, Ferguson MK, Soriano A, et al. Selection of operation for esophageal cancer based on staging. Ann Surg 1986;204:391– 400. 7. Spechler SJ, Goyal RK. Barrett’s esophagus. N Engl J Med 1986;315: 362–71. 8. Morales TG, Sampliner RE, Bhattacharyya A. Intestinal metaplasia of the gastric cardia. Am J Gastroenterol 1997;92:414 – 8. 9. Johnston MH, Hammond AS, Laskin W, et al. 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. 10. Weston AP, Krmpotich P, Makdisi WF, et al. Short segment Barrett’s esophagus: Clinical and histological features, associated endoscopic findings and association with gastric intestinal metaplasia. Am J Gastroenterol 1996;91:981– 6. 11. Spechler SJ, Zeroogian JM, Antoniolo DA, et al. Prevalence of metaplasia at the gastroesophageal junction. Lancet 1994;344:1533– 6. 12. Drewitz DJ, Sampliner RE, Garewal HS. The incidence of adenocarcinoma in Barrett’s esophagus: A prospective study of 170 patients followed 4.8 years. Am J Gastroenterol 1997;92:212–5. 13. Schnell TG, Sontag SJ, Chejfec G. Adenocarcinomas arising in tongues or short segments of Barrett’s esophagus. Dig Dis Sci 1992; 37:137– 43. 14. Hameeteman W, Tytgat GNJ, Houthoff HJ, et al. Barrett’s esophagus: Development of dysplasia and adenocarcinoma. Gastroenterology 1989;96:1249 –56. 15. Sampliner RE, Garewal HS, Fennerty MB, et al. Lack of impact of therapy on extent of Barrett’s esophagus in 67 patients. Dig Dis Sci 1990;35:93– 6. 16. McClave SA, Boyce HW, Gottfried MR. Early diagnosis of columnarlined esophagus: A new endoscopic diagnostic criterion. Gastrointest Endosc 1987;33:413– 6. 17. Spechler SJ. Short and ultrashort Barrett’s esophagus—what does it mean? Sem Gastro Dis 1997;8:59 – 67. 18. Canto MI, Setrakian S, Petras RE, et al. Methylene blue selectively stains intestinal metaplasia in Barrett’s esophagus. Gastrointest Endosc 1996;44:1–7. 19. Stevens PD, Lightdale CJ, Green PHR, et al. Combined magnification endoscopy with chromoendoscopy for the evaluation of Barrett’s esophagus. Gastrointest Endosc 1994;40:747–9. 20. Morales TG, Bhattacharyya A, Johnson C, et al. Is Barrett’s esophagus associated with intestinal metaplasia of the gastric cardia? Am J Gastroenterol 1997;92:1818 –22. 21. Weston AP, Krmpotich PT, Cherian R, et al. Prospective evaluation of intestinal metaplasia and dysplasia within the cardia of patients with Barrett’s esophagus. Dig Dis Sci 1997;42:597– 602. 22. Hamilton SR, Smith RRL, Cameron JL. Prevalence and characteristics
AJG – Vol. 93, No. 7, 1998
23. 24.
25.
26.
27.
28.
29. 30. 31. 32. 33. 34.
35. 36. 37. 38. 39.
40. 41. 42.
43. 44.
of Barrett’s esophagus in patients with adenocarcinoma of the esophagus or esophagogastric junction. Hum Pathol 1988;19:942– 8. Goldblum JR, Vicari J, Falk GW, et al. Carditis and intestinal metaplasia: It’s all H. pylori. Gastroenterology 1997;112:A129. Hirota WK, Loughney TM, Lazas DJ, et al. Is Helicobacter pylori associated with specialized intestinal metaplasia of the esophagus or stomach? A prospective study of 889 patients. Gastroenterology 1997; 112:A149. Spechler SJ, Wang HH, Chey YY, et al. GERD versus H. pylori infections as potential causes of inflammation in the gastric cardia. Gastroenterology 1997;112:A297. Blaser MJ, Perez-Perez GI, Lindenbaum J, et al. Association of infection due to Helicobacter pylori with specific upper gastrointestinal pathology. Rev Infect Dis 1991;13:S704 – 8. Chalasani N, Wo JM, Hunter JG, et al. Significance of intestinal metaplasia in different areas of esophagus including esophagogastric junction. Dig Dis Sci 1997;42:603–7. Hirota WK, Loughney TM, Lazas DJ, et al. The prevalence and demographics of specialized intestinal metaplasia at the esophagogastric junction in a cohort of 889 prospectively studied patients. Gastroenterology 1997;112:A149. Heier SK, Seif F, Webber S, et al. Short segment Barrett’s esophagus: Clinical and histologic findings. Gastroenterology 1996;110:A132. Abo SR, Stevens PD, Abedi M, et al. Prevalence of short segment Barrett’s epithelium in patients with gastroesophageal reflux disease. Gastroenterology 1995:A43. Conio M, Aste H, Bonelli L. “Short” Barrett’s esophagus: A condition not to be underestimated. Gastrointest Endosc 1994;40:111. Bak YT, Park IB, Kim JH, et al. Validity of specialized columnar epithelium as a diagnostic criterion of short segment Barrett’s esophagus. Gastroenterology 1996;110:A55. Nandukar S, Ng T, Adams S, et al. Short segment Barrett’s esophagus: Prevalence, diagnosis and associations. Gastroenterology 1996;110: A207. Dias Pereira A, Suspira A, Chaves P, et al. Short segments of Barrett’s epithelium and intestinal metaplasia in normal appearing gastroesophageal junctions. Are they the same or different conditions? Gastroenterology 1996;110:A95. Clark GWB, Ireland AP, Peters JH, et al. Short segment Barrett’s esophagus: A prevalent complication of gastroesophageal reflux disease with malignant potential. Gastroenterology 1996;110:A1379. Ballinger PJ, Hogan WJ, Bohorfoush AG, et al. Short segment Barrett’s epithelium: Prevalence and accuracy of endoscopic detection. Gastrointest Endosc 1993;39:A93. Cameron AJ, Kamath PS, Carpenter HA. Prevalence of Barrett’s esophagus and intestinal metaplasia at the esophagogastric junction. Gastroenterology 1997;112:A82. Sherman F, Baig Z, Choudhry U, et al. The prevalence of specialized columnar epithelium in patients with symptoms and/or signs of gastroesophageal reflux disease. Gastrointest Endosc 1997;45:A232. Cooper BT, Cox MA, Gearty JC, et al. Prevalence of specialized columnar epithelium at the cardia of patients with gastroesophageal reflux disease without obvious Barrett’s esophagus: Comparison with normal controls. Gastroenterology 1997;112:A93. Trakal E, Butti AL, Ortiz GA, et al. Precancerous and non-precancerous Barrett’s esophagus. Gastroenterology 1997;112:A760. Sharma P, Morales TG, Bhattacharyya A, et al. Dysplasia in short segment Barrett’s esophagus: A prospective three year follow up. Am J Gastroenterol 1997;92:2012– 6. Weston AP, Krmpotich PT, Cherian R, et al. Prospective long term endoscopic and histological follow up of short segment Barrett’s esophagus: Comparison with traditional long segment Barrett’s esophagus. Am J Gastroenterol 1997;92:407–13. Spechler SJ, Goyal RK. The columnar-lined esophagus, intestinal metaplasia, and Norman Barrett. Gastroenterology 1996;110:614 –21. Pahjehpour M, Overholt BF, Vo-Dinh T, et al. Endoscopic fluorescence detection of high grade dysplasia in Barrett’s esophagus. Gastroenterology 1996;111:93–101.