Paris Workshop on Columnar Metaplasia in the Esophagus and the Esophagogastric Junction
Paris, France, December 11 - 12 2004

I Exploring Esophageal Columnar Metaplasia: a Very Laudable Initiative

Foreword by
Professor Emeritus G. N. J. Tytgat
President of the World Gastroenterology Organisation (Organisation Mondiale de Gastro-Entérologie, OMGE)

Few entities in gastroenterology are obscured by as much confusion and uncertainty regarding definition, diagnosis, grading etc than esophageal columnar metaplasia, or Barrett’s esophagus for short. Yet this nosologic entity is of particular importance as a premalignant lesion, especially now that the incidence of adenocarcinoma continues to rise. It was therefore more than timely and encouraging that René Lambert and Prateek Sharma took the initiative of bringing experts together in Paris from all corners of the world. The brief of this working party was to analyse and discuss points of agreement, of discrepancy and of uncertainty, in an attempt to come to a consensus view on this intriguing disease. The disease is indeed fascinating and challenging, not only because of its oncological significance, but also because columnar metaplasia turns out to be a unique model for studying molecular oncogenesis and also all the novel imaging modalities and facilities for tissue characterization.

Obviously to understand one another, to compare data from basic science and clinical medicine, it is essential that we all speak the same language and use the same definitions and staging modalities. As columnar metaplasia joins the cardia, it is readily conceivable that the endoscopic evaluation is prone to confusion and error. Moreover, much background noise can be created if biopsies are not meticulously targeted to either the genuine cardia or the genuine columnar segment to avoid blurring of the findings. The recognition and analysis in depth of trustworthy and reproducible landmarks (the proximal extent of gastric folds, the distal extent of palisaded vessels) for accurate and precise locating of the esophagogastric junction is obviously of vital importance in this overall diagnostic process, as shown in the detailed report that follows.

The executive office of the World Gastroenterology Organisation (WGO) is very well aware of the key importance of this in-depth analysis. The WGO/OMGE is convinced that the outcome of this working party will ultimately help and teach the practising gastroenterologist. The WGO/OMGE is convinced that Professor Lambert’s creation of such a task force is the appropriate way forward and that the clinical impact will be equal to that seen after his task force on the diagnosis of colonic adenoma and early colonic cancer. It is hoped that the detailed information in this report will benefit our patients suffering from this potentially dangerous entity, and further support research to answer the many unsolved questions: whom and how to survey, how to apply chemoprevention, how to detect the person genuinely at risk, and how to manage low grade and high grade dysplasia or neoplasia and early cancer.

References

• 1 Falk G W. Barrett’s esophagus.  Gastroenterology. 2002;  122 1569-1591
• 2 Shaheen N J. Advances in Barrett’s esophagus and esophageal adenocarcinoma.  Gastroenterology. 2005;  128 1554-1566
• 3 Jankowski J A, Harrison R F, Perry I. et al . Barrett’s metaplasia.  Lancet. 2000;  356 2079-2085
• 4 Sharma P, McQuaid K, Dent J. et al . A critical review of the diagnosis and management of Barrett’s esophagus: the AGA Chicago Workshop.  Gastroenterology. 2004;  127 310-330
• 5 Aoki T. Kawaura Y, Kouzu T, et al. Report of the Research Committee on the Definition of Barrett’s Esophagus (Epithelium) [in Japanese]. In: Sugimachi K, editor. Reports of the research committees of The Japanese Society for Esophageal Diseases.  Chiba: Japanese Society of Esophageal. Diseases ;  2000 20-23
• 6 Axon A, Lambert R, Robaszkiewicz . et al . The Second European Endoscopy Forum (Sintra, Portugal 17 - 18 June 1999): twenty questions on the esophagogastric junction.  Endoscopy. 2000;  32 411-418
• 7 Bombeck C T, Dillard D H, Nyhus L M. Muscular anatomy of the gastroesophageal junction and role of phrenoesophageal ligament: autopsy study of sphincter mechanism.  Ann Surg. 1966;  164 643-654
• 8 de Carvalho C A. Studies on the microscopic anatomy of the veins in the esophagogastric transition zone in man.  Rev Hosp Clin Fac Med Sao Paulo. 1966;  21 113-128
• 9 de Carvalho C A. Sur l’angio-architecture veineuse de la zone de transition esophago-gastrique et son interprétation fonctionnelle.  Acta Anat. 1966;  64 126-162
• 10 Makuuchi H. Knack and pitfalls of esophageal surgery [in Japanese]. Tokyo; Bunkodo 2003
• 11 Chandrasoma P T, Der R, Ma Y. et al . Histology of the gastroesophageal junction: an autopsy study.  Am J Surg Pathol. 2000;  24 402-409
• 12 Hoshihara Y, Kogure T, Fukuchi S. et al . Endoscopic observation of longitudinal vessels at the lower esophagus and its clinical significance [in Japanese].  Gastroenterol Endosc. 1986;  28 941-946
• 13 Kilgore S P, Ormsby A H, Gramlich T L. et al . The gastric cardia: fact or fiction?.  Am J Gastroenterol. 2000;  95 921-924
• 14 Sarbia M, Donner A, Gabbert H E. Histopathology of the gastroesophageal junction: a study on 36 operation specimens.  Am J Surg Pathol. 2002;  26 1207-1212
• 15 Takubo K, Arai T, Sawabe M. et al . Structures of the normal esophagus and Barrett’s esophagus.  Esophagus. 2003;  1 37-47
• 16 Takubo K, Vieth M, Honma N. et al . Ciliated surface in the esophagogastric junction zone: a precursor of Barrett’s mucosa or ciliated pseudostratified metaplasia?.  Am J Surg Pathol. 2005;  29 211-217
• 17 Watanabe H, Komukai S, Ochiai A. Histopathological features of Barrett’s esophagus.  Stomach Intestine. 1999;  34 123-132
• 18 Wallner B, Sylvan A, Janunger K G. Endoscopic assessment of the “Z-line” (squamocolumnar junction) appearance: reproducibility of the ZAP classification among endoscopists.  Gastrointest Endosc. 2002;  55 65-69
• 19 Offerhaus G J, Correa P, van Eeden S. et al . Report of an Amsterdam working group on Barrett esophagus.  Virchows Arch. 2003;  443 602-608
• 20 Sharma P, Morales T G, Sampliner R E. Short segment Barrett’s esophagus - the need for standardization of the definition and of endoscopic criteria.  Am J Gastroenterol. 1998;  93 1033-1036
• 21 Jones T F, Sharma P, Daaboul B. et al . Yield of intestinal metaplasia in patients with suspected short-segment Barrett’s esophagus (SSBE) on repeat endoscopy.  Dig Dis Sci. 2002;  47 2108-2111
• 22 Sharma P. Short segment Barrett esophagus and specialized columnar mucosa at the gastroesophageal junction.  Mayo Clin Proc. 2001;  76 331-334
• 23 Spechler S J. The role of gastric carditis in metaplasia and neoplasia at the gastroesophageal junction.  Gastroenterology. 1999;  117 218-228
• 24 Takubo K, Nixon J M, Jass J R. Ducts of esophageal glands proper and Paneth cells in Barrett’s esophagus: frequency in biopsy specimens.  Pathology. 1995;  27 315-317
• 25 Takubo K, Vieth M, Aryal G. et al . Islands of squamous epithelium and their surrounding mucosa in columnar lined esophagus: a pathognomonic feature of Barrett’s esophagus.  Hum Pathol. 2005;  36 269-274
• 26 Takubo K. Pathology of the esophagus. Tokyo; Educa 2000
• 27 Long J D, Orlando R C. Esophageal submucosal glands: structure and function.  Am J Gastroenterol. 1999;  94 2818-2824
• 28 Azuma N, Endo T, Arimura Y. et al . Prevalence of Barrett’s esophagus and expression of mucin antigens detected by a panel of monoclonal antibodies in Barrett’s esophagus and esophageal adenocarcinoma in Japan.  J Gastroenterol. 2000;  35 583-592
• 29 Cameron A J, Zinsmeister A R, Ballard D J. et al . Prevalence of columnar lined Barrett’s esophagus. Comparison of population based clinical and autopsy findings.  Gastroenterology. 1990;  99 918-922
• 30 Chak A, Lee T, Kinnard M F. et al . Familial aggregation of Barrett’s oesophagus, oesophageal adenocarcinoma, and oesophagogastric junctional adenocarcinoma in Caucasian adults.  Gut. 2002;  51 323-328
• 31 Conio M, Cameron A J, Romero Y. et al . Secular trends in the epidemiology and outcome of Barrett’s oesophagus in Olmsted County, Minnesota.  Gut. 2001;  48 304-309
• 32 Connor M J, Weston A P, Mayo M S. et al . The prevalence of Barrett’s esophagus and erosive esophagitis in patients undergoing upper endoscopy for dyspepsia in a VA population.  Dig Dis Sci. 2004;  49 920-924
• 33 Gerson L B, Shetler K, Triadafilopoulos G. Prevalence of Barrett’s esophagus in asymptomatic individuals.  Gastroenterology. 2002;  123 461-467
• 34 Hongo M, Shoji T. Epidemiology of reflux disease and CLE in East Asia.  J Gastroenterol. 2003;  38 Suppl 15 25-30
• 35 Lee J I, Park H, Jung H Y. et al . Prevalence of Barrett’s esophagus in an urban Korean population: a multicenter study.  J Gastroenterol. 2003;  38 23-27
• 36 Locke G R, Talley N J, Fett S L. et al . Prevalence and clinical spectrum of gastroesophageal reflux: a population based study in Olmsted County, Minnesota.  Gastroenterology. 1997;  112 1448-1456
• 37 Rex D K, Cummings O W, Shaw M. et al . Screening for Barrett’s esophagus in colonoscopy patients with and without heartburn.  Gastroenterology. 2003;  125 1670-1677
• 38 Toruner M, Soykan I, Ensari A. et al . Barrett’s esophagus: prevalence and its relationship with dyspeptic symptoms.  J Gastroenterol Hepatol. 2004;  19 535-540
• 39 Cheng K K, Sharp l, McKinney P A. et al . A case/control study of oesophageal adenocarcinoma in women: a preventable disease.  Br J Cancer. 2000;  83 127-132
• 40 Chaves P, Pereira A D, Cruz C. et al . Recurrent columnar-lined esophageal segments-study of the phenotypic characteristics using intestinal markers.  Dis Esophagus. 2002;  15 282-286
• 41 Corey K E, Schmitz S M, Shaheen N J. Does a surgical antireflux procedure decrease the incidence of esophageal adenocarcinoma in Barrett’s esophagus? A meta-analysis.  Am J Gastroenterol. 2003;  98 2390-2394
• 42 Fletcher J, Wirz A, Henry E. et al . Studies of acid exposure immediately above the gastro-oesophageal squamocolumnar junction: evidence of short segment reflux.  Gut. 2004;  53 168-173
• 43 Fletcher J, Wirz A, Young J. et al . Unbuffered highly acidic gastric juice exists at the gastroesophageal junction after a meal.  Gastroenterology. 2001;  121 775-783
• 44 Gammon M D, Schoenberg J B, Ahsan H. et al . Tobacco, alcohol, and socioeconomic status and adenocarcinomas of the esophagus and gastric cardia.  J Natl Cancer Inst. 1997;  89 1277-1284
• 45 Kumagai H, Mukaisho K, Sugihara H. et al . Cell kinetic study on histogenesis of Barrett’s esophagus using rat reflux model.  Scand J Gastroenterol. 2003;  38 687-692
• 46 Lagergren J, Bergstrom R, Nyren O. Association between body mass and adenocarcinoma of the esophagus and gastric cardia.  Ann Intern Med. 1999;  130 883-890
• 47 Lagergren J, Bergstrom R, Adami H O. et al . Association between medications that relax the lower esophageal sphincter and risk for esophageal adenocarcinoma.  Ann Intern Med. 2000;  133 165-175
• 48 Lagergren J, Bergstrom R, Lindgren A. et al . Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma.  N Engl J Med. 1999;  340 825-831
• 49 Peitz U, Vieth M, Pross M. et al . Cardiac-type metaplasia arising in the remnant esophagus after cardia resection.  Gastrointest Endosc. 2004;  59 810-817
• 50 Zhang Z F, Kurtz C, Marshall J R. Cigarette smoking and esophageal and gastric cardia adenocarcinoma.  J Natl Cancer Inst. 1997;  89 1247-1249
• 51 Boch J A, Shields H M, Antonioli D A. et al . Distribution of cytokeratin markers in Barrett’s specialized columnar epithelium.  Gastroenterology. 1997;  112 760-765
• 52 Brittan M, Wright N A. Gastrointestinal stem cells.  J Pathol. 2002;  197 492-509
• 53 Chen Y Y, Wang H H, Antonioli D A. et al . Significance of acid-mucin-positive nongoblet columnar cells in the distal esophagus and gastroesophageal junction.  Hum Pathol. 1999;  30 1488-1495
• 54 Couvelard A, Cauvin J M, Goldfain D. et al . Cytokeratin immunoreactivity of intestinal metaplasia at normal oesophagogastric junction indicates its aetiology.  Gut. 2001;  49 761-766
• 55 El-Zimaity H M, Ramchatesingh J, Saeed M A. et al . Gastric intestinal metaplasia: subtypes and natural history.  J Clin Pathol. 2001;  54 679-683
• 56 El-Zimaity H M, Graham D Y. Cytokeratin subsets for distinguishing Barrett’s esophagus from intestinal metaplasia in the cardia using endoscopic biopsy specimens.  Am J Gastroenterol. 2001;  96 1378-1382
• 57 Glickman J N, Chen Y Y, Wang H H. et al . Phenotypic characteristics of a distinctive multilayered epithelium suggests that it is a precursor in the development of Barrett’s esophagus.  Am J Surg Pathol. 2001;  25 569-578
• 58 Glickman J N, Shahsafaei A, Odze R D. Mucin core peptide expression can help differentiate Barrett’s esophagus from intestinal metaplasia of the stomach.  Am J Surg Pathol. 2003;  27 1357-1365
• 59 Hirota W K, Loughney T M, Lazas D J. et al . Specialized intestinal metaplasia, dysplasia and cancer of the esophagus and esophagogastric junction: prevalence and clinical data.  Gastroenterology. 1999;  116 227-285
• 60 Lambert R, Hainaut P, Parkin D M. Premalignant lesions of the esophagogastric mucosa.  Semin Oncol. 2004;  31 489-512
• 61 Latchford A, Eksteen B, Jankowski J. The continuing tale of cytokeratins in Barrett’s mucosa: as you like it.  Gut. 2001;  49 746-747
• 62 Mohammed I A, Streutker C J, Riddell R H. Utilization of cytokeratins 7 and 20 does not differentiate between Barrett’s esophagus and gastric cardiac intestinal metaplasia.  Mod Pathol. 2002;  15 611-616
• 63 Ormsby A H, Goldblum J R, Rice T W. et al . Cytokeratin subsets can reliably distinguish Barrett’s esophagus from intestinal metaplasia of the stomach.  Hum Pathol. 1999;  30 288-294
• 64 Salo J A, Kivilaakso E O, Kiviluoto T A. et al . Cytokeratin profile suggests metaplastic epithelial transformation in Barrett’s oesophagus.  Ann Med. 1996;  28 305-309
• 65 Takubo K, Honma N, Arai T. Multilayered epithelium in Barrett’s esophagus.  Am J Surg Pathol. 2001;  25 1460-1461
• 66 Trudgill N J, Suvarna S K, Kapur K C. et al . Intestinal metaplasia at the squamocolumnar junction in patients attending for diagnostic gastroscopy.  Gut. 1997;  41 585-589
• 67 Wallner B, Sylvan A, Stenling R. et al . The Z-line appearance and prevalence of intestinal metaplasia among patients without symptoms or endoscopical signs indicating gastroesophageal reflux.  Surg Endosc. 2001;  15 886-889
• 68 Wallner B, Sylvan A, Janunger K G. et al . Immunohistochemical markers for Barrett’s esophagus and associations to esophageal Z-line appearance.  Scand J Gastroenterol. 2001;  36 910-915
• 69 Auvinen M I, Sihvo E I, Ruohtula T. et al . Incipient angiogenesis in Barrett’s epithelium and lymphangiogenesis in Barrett’s adenocarcinoma.  J Clin Oncol. 2002;  20 2971-2979
• 70 Buskens C J, Sivula A, van Rees B P. et al . Comparison of cyclooxygenase 2 expression in adenocarcinomas of the gastric cardia and distal oesophagus.  Gut. 2003;  52 1678-1683
• 71 Eksteen J A, Scott P A, Perry I. et al . Inflammation promotes Barrett’s metaplasia and cancer: a unique role for TNFalpha.  Eur J Cancer Prev. 2001;  10 163-166
• 72 Fennerty M B, Triadafilopoulos G. Barrett’s-related esophageal adenocarcinoma: is chemoprevention a potential option?.  Am J Gastroenterol. 2001;  96 2302-2305
• 73 Jenkins G J, Doak S H, Griffiths A P. et al . Early p53 mutations in nondysplastic Barrett’s tissue detected by the restriction site mutation (RSM) methodology.  Br J Cancer. 2003;  88 1271-1276
• 74 Kumagai Y, Toi M, Inoue H. Dynamism of tumour vasculature in the early phase of cancer progression: outcomes from oesophageal cancer research.  Lancet Oncol. 2002;  3 604-610
• 75 Moriya A, Grant J, Mowat C. et al . In vitro studies indicate that acid catalysed generation of N-nitrosocompounds from dietary nitrate will be maximal at the gastro-oesophageal junction and cardia.  Scand J Gastroenterol. 2002;  37 253-261
• 76 Sonnenberg A, Fennerty M B. Medical decision analysis of chemoprevention against esophageal adenocarcinoma.  Gastroenterology. 2003;  124 1758-1766
• 77 Wilson K T, Fu S, Ramanujam K S. et al . Increased expression of inducible nitric oxide synthase and cyclooxygenase-2 in Barrett’s esophagus and associated adenocarcinomas.  Cancer Res. 1998;  58 2929-2934
• 78 Wilson K T. Angiogenic markers, neovascularization and malignant deformation of Barrett’s esophagus.  Dis Esophagus. 2002;  15 16-21
• 79 Pohl H, Welch H G. The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence.  J Natl Cancer Inst. 2005;  97 142-146
• 80 Botterweck A AM, Shouten L J, Volovics A. et al . Trends in incidence of adenocarcinoma of the oesophagus and gastric cardia in ten European countries.  Internat J Epidemiol. 2000;  29 645-654
• 81 Brown L M, Devesa S S. Epidemiologic trends in esophageal and gastric cancer in the United States.  Surg Oncol Clin N Am. 2002;  11 235-256
• 82 Bytzer P, Christensen P B, Damkier P. et al . Adenocarcinoma of the esophagus and Barrett’s esophagus: a population-based study.  Am J Gastroenterol. 1999;  94 86-91
• 83 Parkin D M, Whelan S L, Ferlay J. et al .Cancer incidence in five continents. IARC publ. no. 155. Lyon; IARC press 2002. [Distributed by Oxford University Press]
• 84 SEER. Incidence Public US Database 1973 - 1995. National Cancer Institute. Bethesda, Maryland, USA; National Institutes of Health 1998
• 85 Vizcaino A P, Moreno V, Lambert R. et al . Time trends incidence of both major histologic types of esophageal carcinomas in selected countries 1973 - 1995.  Int J Cancer. 2002;  99 860-888
• 86 Ye W, Chow W H, Lagergren J. et al . Risk of adenocarcinomas of the esophagus and gastric cardia in patients with gastroesophageal reflux diseases and after antireflux surgery.  Gastroenterology. 2001;  121 1286-1293
• 87 Zheng T, Mayne S T, Holford T R. et al . Time trend and age-period-cohort effects on incidence of esophageal cancer in Connecticut 1935 - 89.  Cancer Causes Control. 1992;  3 481-492
• 88 Cameron A J, Souto E O, Smyrk T C. Small adenocarcinomas of the esophagogastric junction: association with intestinal metaplasia and dysplasia.  Am J Gastroenterol. 2002;  97 1375-1380
• 89 El-Serag H B, Mason A C, Petersen N. et al . Epidemiological differences between adenocarcinoma of the oesophagus and adenocarcinoma of the gastric cardia in the USA.  Gut. 2002;  50 368-372
• 90 Ekstrom A M, Signorello M B, Hansson L E. et al . Evaluating gastric cancer misclassification: a potential explanation for the rise in cardia cancer incidence.  J Natl Cancer Inst. 1999;  91 786-790
• 91 Ichikura T, Ogawa T, Kawabata T. et al . Is adenocarcinoma of the gastric cardia a distinct entity independent of subcardial carcinoma?.  World J Surg. 2003;  27 334-338
• 92 Nakamura T, Ide H, Eguchi R. et al . Adenocarcinoma of the esophagogastric junction: a summary of responses to a questionnaire on adenocarcinoma of the esophagus and the esophagogastric junction in Japan.  Dis Esophagus. 2002;  15 219-225
• 93 Okabayashi T, Gotoda T, Kondo H. Early carcinoma of the gastric cardia in Japan: is it different from that in the West?.  Cancer. 2000;  89 2555-2559
• 94 Ormsby A H, Goldblum J R, Rice T W. et al . The utility of cytokeratin subsets in distinguishing Barrett’s-related oesophageal adenocarcinoma from gastric adenocarcinoma.  Histopathology. 2001;  38 307-311
• 95 Sharma P, Weston A P, Morales T. et al . Relative risk of dysplasia for patients with intestinal metaplasia in the distal oesophagus and in the gastric cardia.  Gut. 2000;  46 9-13
• 96 Stein H J, Feith M, Siewert J R. Cancer of the esophagogastric junction.  Surg Oncol. 2000;  9 35-41
• 97 Taniere P, Borghi-Scoazec G, Saurin J C. et al . Cytokeratin expression in adenocarcinomas of the esophagogastric junction: a comparative study of adenocarcinomas of the distal esophagus and of the proximal stomach.  Am J Surg Pathol. 2002;  26 1213-1221
• 98 Taniere P, Martel-Planche G, Maurici D. et al . Molecular and clinical differences between adenocarcinomas of the esophagus and of the gastric cardia.  Am J Pathol. 2001;  158 33-40
• 99 Watanabe H, Tanabe T, Yagi K. et al . Comparison of carcinoma of the esophagogastric junction with Barrett’s esophageal cancer from the aspect of structural development [in Japanese].  Stomach Intestine. 2001;  36 634-650
• 100 Anderson L A, Murray L J, Murphy S J. et al . Mortality in Barrett’s oesophagus: results from a population based study.  Gut. 2003;  52 1081-1084
• 101 Drewitz D J, Sampliner R E, Garewal H S. The incidence of adenocarcinoma in Barrett’s esophagus: a prospective study of 170 patients followed 4.8 years.  Am J Gastroenterol. 1997;  92 212-215
• 102 Eckardt V F, Kanzler G, Bernhard G. Life expectancy and cancer risk in patients with Barrett’s esophagus: a prospective controlled investigation.  Am J Med. 2001;  111 33-37
• 103 Rudolph R E, Vaughan T L, Storer B E. et al . Effect of segment length on risk for neoplastic progression in patients with Barrett esophagus.  Ann Intern Med. 2000;  132 612-620
• 104 Shaheen N J, Crosby M A, Bozymski E M. et al . Is there publication bias in the reporting of cancer risk in Barrett’s esophagus?.  Gastroenterology. 2000;  119 333-338
• 105 van der Burgh A, Dees J, Hop W CJ. et al . Oesophageal cancer is an uncommon cause of death in patients with Barrett’s esophagus.  Gut. 1996;  39 5-8
• 106 Guelrud M, Herrera I, Essenfeld H. et al . Intestinal metaplasia of the gastric cardia: a prospective study with enhanced magnification endoscopy.  Am J Gastroenterol. 2002;  97 584-589
• 107 Guelrud M, Herrera I, Essenfeld H. et al . Enhanced magnification endoscopy: a new technique to identify specialized intestinal metaplasia in Barrett’s esophagus.  Gastrointest Endosc. 2001;  53 559-565
• 108 Guelrud M, Ehrlich E E. Endoscopic classification of Barrett’s esophagus.  Gastrointest Endosc. 2004;  59 58-65
• 109 Hamamoto Y, Endo T, Nosho K. et al . Usefulness of narrow-band imaging endoscopy for diagnosis of Barrett’s esophagus.  J Gastroenterol. 2004;  39 14-20
• 110 Hurlstone D P. Barrett’s esophagus: a role for high-resolution magnification chromoendoscopy?.  J Gastroenterol Hepatol. 2002;  17 633-635
• 111 Inoue H, Kumagai Y, Yoshida T. et al . High magnification endoscopic diagnosis of the superficial esophageal cancer.  Dig Endosc. 2000;  12 (Suppl) S32-S35
• 112 Kiesslich R, Hahn M, Herrmann G. et al . Screening for specialized columnar epithelium with methylene blue: chromoendoscopy in patients with Barrett’s esophagus and a normal control group.  Gastrointest Endosc. 2001;  53 47-52
• 113 Kumagai Y, Inoue H, Nagai K. et al . Magnifying endoscopy, stereoscopic microscopy, and the microvascular architecture of superficial esophageal carcinoma.  Endoscopy. 2002;  34 369-375
• 114 Lambert R, Rey J F, Sankaranarayanan R. Magnification and chromoscopy with the acetic acid test.  Endoscopy. 2003;  35 437-445
• 115 Meining A, Ott R, Becker I. et al . The Munich Barrett follow up study: suspicion of Barrett’s oesophagus based on either endoscopy or histology only - what is the clinical significance?.  Gut. 2004;  53 1402-1407
• 116 Meining A, Rosch T, Kiesslich R. et al . Inter- and intra-observer variability of magnification chromoendoscopy for detecting specialized intestinal metaplasia at the gastroesophageal junction.  Endoscopy. 2004;  36 160-164
• 117 Mokhashi M S, Wildi S M, Glenn T F. et al . A prospective, blinded study of diagnostic esophagoscopy with a superthin, stand-alone, battery-powered esophagoscope.  Am J Gastroenterol. 2003;  98 2383-2389
• 118 Ragunath K, Krasner N, Raman V S. et al . A randomized, prospective cross-over trial comparing methylene blue-directed biopsy and conventional random biopsy for detecting intestinal metaplasia and dysplasia in Barrett’s esophagus.  Endoscopy. 2003;  35 998-1003
• 119 Saeian K, Staff D M, Vasilopoulios S. et al . Unsedated transnasal endoscopy accurately detects Barrett’s metaplasia and dysplasia.  Gastrointest Endosc. 2002;  56 472-478
• 120 Sharma P, Weston A P, Topalovski M. et al . Magnification chromoendoscopy for the detection of intestinal metaplasia and dysplasia in Barrett’s oesophagus.  Gut. 2003;  52 24-27
• 121 Shibuya K, Hoshino H, Chiyo M. et al . High magnification bronchovideoscopy combined with narrow band imaging could detect capillary loops of angiogenic squamous dysplasia in heavy smokers at high risk for lung cancer.  Thorax. 2003;  58 989-995
• 122 Sorbi D, Gostout C J, Henry J. et al . Unsedated small-caliber esophagogastroduodenoscopy (EGD) versus conventional EGD: a comparative study.  Gastroenterology. 1999;  117 1301-1307
• 123 Toyoda H, Rubio C, Befrits R. et al . Detection of intestinal metaplasia in distal esophagus and esophagogastric junction by enhanced-magnification endoscopy.  Gastrointest Endosc. 2004;  59 15-21
• 124 Yao K, Oishi T. Microgastroscopic findings of mucosal microvascular architecture as visualized by magnifying endoscopy.  Dig Endosc. 2001;  13 (Suppl) S27-S33
• 125 Yasuda K. Clinical use of high resolution and high magnification endoscopy for upper gastrointestinal lesions.  Dig Endosc. 2001;  13 (Suppl) S36-S39
• 126 Yoshida T, Inoue H, Usui S. et al . Narrow-band imaging system with magnifying endoscopy for superficial esophageal lesions.  Gastrointest Endosc. 2004;  59 288-295
• 127 Canto M I, Setrakian S, Willis J E. et al . Methylene blue staining of dysplastic and nondysplastic Barrett’s esophagus: an in vivo and ex vivo study.  Endoscopy. 2001;  33 391-400
• 128 Endo T, Awakawa T, Takahashi H. et al . Classification of Barrett’s epithelium by magnifying endoscopy.  Gastrointest Endosc. 2002;  55 641-647
• 129 Gono K, Obi T, Yamaguchi M. et al . Appearance of enhanced tissue features in narrow-band endoscopic imaging.  J Biomed Optics. 2004;  9 568-577
• 130 Muto M, Katada C, Sano Y. et al . Narrow band imaging: a new diagnostic approach to visualize angiogenesis in superficial neoplasia.  Clin Gastroenerol Hepatol. 2005;  3 S16-S20
• 131 Connor M J, Sharma P. Chromoendoscopy and magnification endoscopy for diagnosing esophageal cancer and dysplasia.  Thorac Surg Clin. 2004;  14 87-94
• 132 Brand S, Wang T D, Schomacker K T. et al . Detection of high-grade dysplasia in Barrett’s esophagus by spectroscopy measurement of 5-aminolevulinic acid-induced protoporphyrin IX fluorescence.  Gastrointest Endosc. 2002;  56 479-487
• 133 Endlicher E, Knuechel R, Hauser T. et al . Endoscopic fluorescence detection of low and high grade dysplasia in Barrett’s oesophagus using systemic or local 5-aminolaevulinic acid sensitisation.  Gut. 2001;  48 314-319
• 134 Georgakoudi I, Jacobson B C, van Dam J. et al . Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett’s esophagus.  Gastroenterology. 2001;  120 1620-1629
• 135 Kara M A, Peters F P, ten Kate F JW. et al . Endoscopic video autofluorescence imaging may improve the detection of early neoplasia in patients with Barrett’s esophagus.  Gastrointest Endosc. 2005;  61 679-685
• 136 Wallace M B, Perelman L T, Backman V. et al . Endoscopic detection of dysplasia in patients with Barrett’s esophagus using light-scattering spectroscopy.  Gastroenterology. 2000;  119 677-682
• 137 Buskens C J, Westerterp M, Lagarde S M. Prediction of appropriateness of local endoscopic treatment for high-grade dysplasia and early adenocarcinoma by EUS and histopathologic features.  Gastrointest Endosc. 2004;  60 703-710
• 138 Murata Y, Napoleon B, Odegaard S. High-frequency endoscopic ultrasonography in the evaluation of superficial esophageal cancer.  Endoscopy. 2003;  35 429-435
• 139 Owens M M, Kimmey M B. The role of endoscopic ultrasound in the diagnosis and management of Barrett’s esophagus.  Gastrointest Endosc Clin N Am. 2003;  13 325-334
• 140 Scotiniotis I A, Kochman M L, Lewis J D. et al . Accuracy of EUS in the evaluation of Barrett’s esophagus and high-grade dysplasia or intramucosal carcinoma.  Gastrointest Endosc. 2001;  54 689-696
• 141 Brand S, Poneros J M, Bouma B E. et al . Optical coherence tomography in the gastrointestinal tract.  Endoscopy. 2000;  32 796-803
• 142 Cilesiz I, Fockens P, Kerindongo R. et al . Comparative optical coherence tomography imaging of human esophagus: how accurate is localization of the muscularis mucosae?.  Gastrointest Endosc. 2002;  56 852-857
• 143 The Paris endoscopic classification of superficial neoplastic lesions . Esophagus, stomach, and colon.  Gastrointest Endosc. 2003;  58 (Suppl 6) S3-S43
• 144 Alikhan M, Rex D, Khan A. et al . The variable pathologic interpretation of columnar-lined esophagus by general pathologists in community practice.  Gastrointest Endosc. 1999;  50 23-26
• 145 Dixon M F. Gastrointestinal epithelial neoplasia: Vienna revisited.  Gut. 2002;  51 130-131
• 146 Haggitt R C. Barrett’s esophagus, dysplasia, and adenocarcinoma.  Hum Pathol. 1994;  25 982-993
• 147 Japanese Society for Esophageal Diseases .Guidelines for the clinical and pathologic studies on carcinoma of the esophagus. 9th edn. Tokyo; Kanehara 1999
• 148 Jankowski J A, Wright N A, Meltzer S J. et al . Molecular evolution of the metaplasia - dysplasia - adenocarcinoma sequence in the esophagus.  Am J Pathol. 1999;  54 965-973
• 149 Levine D S, Blount P L, Rudolph R E. et al . Safety of a systematic endoscopic biopsy protocol in patients with Barrett’s esophagus.  Am J Gastroenterol. 2000;  95 1152-1157
• 150 Morales C P, Souza R F, Spechler S J. Hallmarks of cancer progression in Barrett’s oesophagus.  Lancet. 2002;  360 1587-1589
• 151 Ozawa S, Ando N, Kitagawa Y. et al . Molecular alterations in Barrett’s esophagus and adenocarcinoma [in Japanese].  Nippon Geka Gakkai Zasshi. 1999;  100 235-239
• 152 Reid B J, Blount P L, Rabinovitch P S. Biomarkers in Barrett’s esophagus.  Gastrointest Endosc Clin N Am. 2003;  13 369-397
• 153 Reid B J, Levine D S, Longton G. et al . Predictors of progression to cancer in Barrett’s esophagus: baseline histology and flow cytometry identify low- and high-risk patient subsets.  Am J Gastroenterol. 2000;  95 1669-1676
• 154 Reid B J, Prevo L J, Galipeau P C. et al . Predictors of progression in Barrett’s esophagus II: baseline 17p (p53) loss of heterozygosity identifies a patient subset at increased risk for neoplastic progression.  Am J Gastroenterol. 2001;  96 2839-2848
• 155 Reid B J, Blount P L, Feng Z. et al . Optimizing endoscopic biopsy detection of early cancers in Barrett’s high-grade dysplasia.  Am J Gastroenterol. 2000;  95 3089-3096
• 156 Robert M E. Defining dysplasia in Barrett esophagus.  J Clin Gastroenterol. 2003;  36 (Suppl) S19-S25
• 157 Rudolph R E, Vaughan T L, Kristal A R. et al . Serum selenium levels in relation to markers of neoplastic progression among persons with Barrett’s esophagus.  J Natl Cancer Inst. 2003;  95 750-757
• 158 van der Woude C J, Jansen P L, Tiebosch A T. et al . Expression of apoptosis-related proteins in Barrett’s metaplasia - dysplasia - carcinoma sequence: a switch to a more resistant phenotype.  Hum Pathol. 2002;  33 686-692
• 159 Inadomi J M, Sampliner R, Lagergren J. et al . Screening and surveillance for Barrett esophagus in high-risk groups: a cost/utility analysis.  Ann Intern Med. 2003;  138 176-186
• 160 Shaheen N J, Provenzale D, Sandler R S. Upper endoscopy as a screening and surveillance tool in esophageal adenocarcinoma: a review of the evidence.  Am J Gastroenterol. 2002;  97 1319-1327
• 161 Spechler S J, Barr H. Review article: screening and surveillance of Barrett’s oesophagus: what is a cost-effective framework?.  Aliment Pharmacol Ther. 2004;  19 (Suppl 1) 49-53
• 162 Corley D A, Levin T R, Habel L A. et al . Surveillance and survival in Barrett’s adenocarcinomas: a population-based study.  Gastroenterology. 2002;  122 633-640
• 163 Fennerty M B. Endoscopic diagnosis and surveillance of Barrett’s esophagus.  Gastrointest Endosc Clin N Am. 2003;  13 257-267
• 164 Fountoulakis A, Zafirellis K D, Dolan K. Effect of surveillance of Barrett’s oesophagus on the clinical outcome of oesophageal cancer.  Br J Surg. 2004;  91 997-1003
• 165 Gudlaugsdottir S, Blankenstein M V, Dees J. et al . A majority of patients with Barrett oesophagus are unlikely to benefit from endoscopic cancer surveillance.  Eur J Gastroenterol Hepatol. 2001;  13 639-645
• 166 Jones T F, Sharma P, Daaboul B. et al . Yield of intestinal metaplasia in patients with suspected short-segment Barrett’s esophagus (SSBE) on repeat endoscopy.  Dig Dis Sci. 2002;  47 2108-2111
• 167 Sampliner R E. Practice Parameters Committee of the American College of Gastroenterology. Updated guidelines for the diagnosis, surveillance, and therapy of Barrett’s esophagus.  Am J Gastroenterol. 2002;  97 1888-1895
• 168 Sonnenberg A, Soni A, Sampliner R E. Medical decision analysis of endoscopic surveillance of Barrett’s oesophagus to prevent oesophageal adenocarcinoma.  Aliment Pharmacol Ther. 2002;  16 41-50

7 Participants: Hugh Barr M. D., Cranfield Postgraduate Medical School, Gloucester GL1 3NN, UK; Jacques J Bergman M. D., Academic Medical Centre, 1105 AZ Amsterdam, The Netherlands; Marcia I Canto M. D., Johns Hopkins Hospital, Baltimore, Maryland 21 205, USA; Takao Endo M. D., Sapporo Medical University, Sapporo 060 - 8543, Japan; Rikiya Fujita M. D., Cancer Institute Hospital, Tokyo 170 - 8455, Japan; Pierre Hainaut Ph. D., International Agency for Research on Cancer, Lyon 69 372, France; Robert H Hawes M. D., Medical University of South Carolina, Charleston, South Carolina 29 425 2220, US; Yoshio Hoshihara M. D., Toranomon, Minato-ku, Tokyo 105 - 8470 Japan; Haruhiro Inoue MD, Showa Northern Yokohama Hospital, Yokohama 224 - 8504 Japan; Edgar Jaramillo M. D., Karolinska Hospital, Stockholm, Sweden; Michael Jung M. D., St Hildergardis Krankenhaus, 55 131 Mainz, Germany; Teruo Kouzu M. D., Chiba University School of Medicine, Chiba 260 - 8677, Japan; René Lambert MD, International Agency for Research on Cancer, Lyon 69 372, France; Charles J Lightdale M. D., Columbia Presbyterian Medical Center, New York 10 032, USA; Hiroyasu Makuuchi M. D., School of Medicine, Tokai University, Kanagawa 259 - 1193 Japan; Hirohumi Niwa M. D., St. Marianna University School of Medicine, Kawasaki 216 - 8511, Japan; Jean François Rey M. D., Institut Arnault Tzanck, St Laurent du Var 06 700, France; Robert Riddell M. D., Department of Pathology, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada; Richard E Sampliner M. D., University of Arizona Health Science Center, Tucson, Arizona 85 724 0001, USA; Prateek Sharma M. D., VA Medical Center Kansas City, Missouri 64 128, USA; Stuart J Spechler M. D. , VA Medical Center, Dallas, Texas 75 216, USA; Kaiyo Takubo M. D., Tokyo Metropolitan Geriatric Hospital, Tokyo,173 - 0015, Japan; Hisao Tajiri M. D., The Jukei University School of Medicine, Tokyo 1 058 461, Japan; Hidenobu Watanabe M. D., Niigata University School of Medicine, Niigata 951 - 8510, Japan