Low-grade dysplasia in Barrett's esophagus has a high risk of progression

Background and study aims: Surveillance in Barrett's esophagus relies on the detection of dysplasia by histopathology. However, the natural history of this condition, particularly that of low-grade dysplasia (LGD) is poorly understood. This paper describes our experience of LGD over a period of 21 years.

Patients and methods: Between 1984 and January 1995, 357 patients with Barrett's esophagus without dysplasia were recruited for annual surveillance: 34 of these patients developed LGD during this period. This was a retrospective cohort study of this group in terms of survival and cancer outcomes ≥ 8 years after the original diagnosis of LGD, comparing them with the patients who did not develop LGD over the same period, with a histopathological review of the original diagnoses of LGD. The outcomes of 356/357 (99.7 %) of the patients were established in December 2004.

Results: After 8 years, high-grade dysplasia (HGD) or cancer had developed in 9/34 patients with LGD (27 %) and in 16/322 controls (5 %). Cox’s proportional hazards model revealed that the time from the first diagnosis of Barrett's esophagus to the first “event” of either HGD, esophageal cancer, or death did not show a statistically significant difference between the two groups. A further analysis treating death as “loss to follow-up” showed a significantly increased risk for the LGD group to progress to HGD or cancer (hazard ratio 5.9 [95 % confidence interval 2.6 - 13.4], P< 0.001). The histopathology review demonstrated a fair level of agreement between pathologists, with a kappa value of 0.48.

Conclusions: Patients diagnosed with LGD during surveillance of Barrett's esophagus are at a considerably increased risk of progressing to develop esophageal cancer over an 8-year period but most deaths are not cancer-related.

References

• 1 Cameron A J, Ott B J, Payne W S. The incidence of adenocarcinoma in columnar-lined (Barrett's) esophagus.  N Engl J Med. 1985;  313 857-859
• 2 Spechler S J, Robbins A H, Rubins H B. et al . Adenocarcinoma and Barrett's esophagus. An overrated risk?.  Gastroenterology. 1984;  87 927-933
• 3 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
• 4 Jankowski J A, Provenzale D, Moayyedi P. Esophageal adenocarcinoma arising from Barrett's metaplasia has regional variations in the west.  Gastroenterology. 2002;  122 588-590
• 5 Craanen M E, Blok P, Meijer G A. et al . Surveillance in Barrett's oesophagus: a critical reappraisal.  Scand J Gastroenterol Suppl. 2002;  236 4-8
• 6 Sampliner R E. Updated guidelines for the diagnosis, surveillance, and therapy of Barrett's esophagus.  Am J Gastroenterol. 2002;  97 1888-1895
• 7 Watson A, Heading R C, Shepherd N A. (eds). . Guidelines for the diagnosis and management of Barrett's columnar-lined oesophagus.  London: British Society of Gastroenterology. 2005;  54(Suppl 1) 1-42
• 8 Bani-Hani K, Sue-Ling H, Johnston D. et al . Barrett's oesophagus: results from a 13-year surveillance programme.  Eur J Gastroenterol Hepatol. 2000;  12 649-654
• 9 Levine D S, Haggitt R C, Blount P L. et al . An endoscopic biopsy protocol can differentiate high-grade dysplasia from early adenocarcinoma in Barrett's esophagus.  Gastroenterology. 1993;  105 40-50
• 10 Svanholm H, Starklint H, Gundersen H J. et al . Reproducibility of histomorphologic diagnoses with special reference to the kappa statistic.  APMIS. 1989;  97 689-698
• 11 Miros M, Kerlin P, Walker N. Only patients with dysplasia progress to adenocarcinoma in Barrett's oesophagus.  Gut. 1991;  32 1441-1446
• 12 Katz D, Rothstein R, Schned A. et al . The development of dysplasia and adenocarcinoma during endoscopic surveillance of Barrett's esophagus.  Am J Gastroenterol. 1998;  93 536-541
• 13 Reid B J, Blount P L, Rubin C E. et al . Flow-cytometric and histological progression to malignancy in Barrett's esophagus: prospective endoscopic surveillance of a cohort.  Gastroenterology. 1992;  102 (4 Pt 1) 1212-1219
• 14 Montgomery E, Bronner M P, Goldblum J R. et al . Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation.  Hum Pathol. 2001;  32 368-378
• 15 Weston A P, Badr A S, Hassanein R S. Prospective multivariate analysis of clinical, endoscopic, and histological factors predictive of the development of Barrett's multifocal high-grade dysplasia or adenocarcinoma.  Am J Gastroenterol. 1999;  94 3413-3419
• 16 Skacel M, Petras R E, Gramlich T L. et al . The diagnosis of low-grade dysplasia in Barrett's esophagus and its implications for disease progression.  Am J Gastroenterol. 2000;  95 3383-3387
• 17 O’Connor J B, Falk G W, Richter J E. The incidence of adenocarcinoma and dysplasia in Barrett's esophagus: report on the Cleveland Clinic Barrett's Esophagus Registry.  Am J Gastroenterol. 1999;  94 2037-2042
• 18 Ferraris R, Bonelli L, Conio M. et al . Incidence of Barrett's adenocarcinoma in an Italian population: an endoscopic surveillance programme. Gruppo Operativo per lo Studio delle Precancerosi Esofagee (GOSPE).  Eur J Gastroenterol Hepatol. 1997;  9 881-885
• 19 Sharma P, Falk G W, Weston A P. et al . Dysplasia and cancer in a large multicenter cohort of patients with Barrett's esophagus.  Clin Gastroenterol Hepatol. 2006;  4 566-572
• 20 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
• 21 Hameeteman W, Tytgat G N, Houthoff H J. et al . Barrett's esophagus: development of dysplasia and adenocarcinoma.  Gastroenterology. 1989;  96 (5 Pt 1) 1249-1256
• 22 Jankowski J A, Harrison R F, Perry I. et al . Barrett's metaplasia.  Lancet. 2000;  356 2079-2085
• 23 Peters J H, Clark G W, Ireland A P. et al . Outcome of adenocarcinoma arising in Barrett's esophagus in endoscopically surveyed and nonsurveyed patients.  J Thorac Cardiovasc Surg. 1994;  108 813-821
• 24 Streitz Jr J M, Andrews Jr C W, Ellis Jr F H. Endoscopic surveillance of Barrett's oesophagus. Does it help?.  J Thorac Cardiovasc Surg. 1993;  105 383-387
• 25 Van Sandick J W, Van Lanschot J J, Kuiken B W. et al . Impact of endoscopic biopsy surveillance of Barrett's oesophagus on pathological stage and clinical outcome of Barrett's carcinoma.  Gut. 1998;  43 216-222
• 26 Fountoulakis A, Zafirellis K D, Dolan K. et al . Effect of surveillance of Barrett's oesophagus on the clinical outcome of oesophageal cancer.  Br J Surg. 2004;  91 997-1003
• 27 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