Original article
Clinical endoscopy
Incidence of esophageal adenocarcinoma in Barrett's esophagus with low-grade dysplasia: a systematic review and meta-analysis

https://doi.org/10.1016/j.gie.2014.01.009Get rights and content

Background

The natural history of low-grade dysplasia (LGD) in patients with Barrett's esophagus (BE) is unclear.

Objective

We performed a systematic review and meta-analysis of studies that reported the incidence of esophageal adenocarcinoma (EAC) and/or high-grade dysplasia (HGD) among patients with BE with LGD.

Design

Systematic review and meta-analysis of cohort studies.

Patients

Patients with BE-LGD, with mean cohort follow-up ≥2 years.

Main Outcome Measurements

Pooled incidence rates with 95% confidence intervals (CI) of EAC and/or BE-HGD.

Results

We identified 24 studies reporting on 2694 patients with BE-LGD, with 119 cases of EAC. Pooled annual incidence rates of EAC alone and EAC and/or HGD in patients with BE-LGD were 0.54% (95% CI, 0.32-0.76; 24 studies) and 1.73% (95% CI, 0.99-2.47; 17 studies). The results were stable across study setting and location and in high-quality studies. Substantial heterogeneity was observed, which could be explained by stratifying based on LGD/BE ratio as a surrogate for quality of pathology; the pooled annual incidence rates of EAC were 0.76% (95% CI, 0.44-1.09; 14 studies) for LGD/BE ratio <0.15 and 0.32% (95% CI, 0.07-0.58; 10 studies) for LGD/BE ratio >0.15. The annual rate of mortality not related to esophageal disease in patients with BE-LGD was 4.7% (95% CI, 3.2-6.2; 4 studies).

Limitations

Substantial heterogeneity was observed in the overall analysis.

Conclusion

The incidence of EAC among patients with BE-LGD is 0.54% annually. The LGD/BE ratio appears to explain the variation observed in the reported incidence of EAC in different cohorts. Conditions not related to esophageal disease are a major cause of mortality in patients with BE-LGD, although additional studies are warranted.

Section snippets

Search strategy

We conducted a systematic literature search of MEDLINE (1966 to December 31, 2012) and EMBASE (1988 to December 31, 2012) for all relevant articles on the risk of EAC in patients with BE. Key words used in the search included a combination of “Barrett's esophagus,” “Barrett's neoplasia,” “Barrett's epithelium,” or “intestinal metaplasia” and “esophageal cancer,” “esophageal adenocarcinoma,” or “esophageal neoplasia.” The search was restricted to the studies in human participants published in

Results

From a total of 3703 citations identified by using our search strategy, 51 studies reported EAC incidence among patients with BE-LGD. Of these, 17 studies were excluded because they did not meet the study criteria (2 studies had follow-up <2 years;21, 22 2 studies lacked precise details regarding follow-up;23, 24 there were 13 studies with redundant study populations25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37); an additional 10 studies on patients who had undergone anti-reflux surgery

Discussion

Current management strategies for BE-LGD are unclear, and endoscopic eradication therapy is not routinely recommended.1 This is because of relative paucity of data on the natural history of BE-LGD with regard to progression to EAC and/or HGD. Additionally, there are limited data on cause-specific mortality in patients with BE-LGD from which to project cost-effectiveness of surveillance and endoscopic eradication therapy in this cohort of patients. In this systematic review and meta-analysis of

References (71)

  • M. Skacel et al.

    p53 expression in low grade dysplasia in Barrett's esophagus: correlation with interobserver agreement and disease progression

    Am J Gastroenterol

    (2002)
  • P. Sharma et al.

    Dysplasia and cancer in a large multicenter cohort of patients with Barrett's esophagus

    Clin Gastroenterol Hepatol

    (2006)
  • A. Csendes et al.

    Long-term results of classic antireflux surgery in 152 patients with Barrett's esophagus: clinical, radiologic, endoscopic, manometric, and acid reflux test analysis before and late after operation

    Surgery

    (1998)
  • J.B. O'Connor et al.

    The incidence of adenocarcinoma and dysplasia in Barrett's esophagus: report on the Cleveland Clinic Barrett's Esophagus Registry

    Am J Gastroenterol

    (1999)
  • A.E. Abbas et al.

    Barrett's esophagus: the role of laparoscopic fundoplication

    Ann Thorac Surg

    (2004)
  • J.M. O'Riordan et al.

    Long-term clinical and pathologic response of Barrett's esophagus after antireflux surgery

    Am J Surg

    (2004)
  • D.E. Low et al.

    Histological and anatomic changes in Barrett's esophagus after antireflux surgery

    Am J Gastroenterol

    (1999)
  • K.M. Desai et al.

    Efficacy of laparoscopic antireflux surgery in patients with Barrett's esophagus

    Am J Surg

    (2003)
  • M. Conio et al.

    Long-term endoscopic surveillance of patients with Barrett's esophagus. Incidence of dysplasia and adenocarcinoma: a prospective study

    Am J Gastroenterol

    (2003)
  • B.J. Reid 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)
  • T. Wong et al.

    Barrett's surveillance identifies patients with early esophageal adenocarcinoma

    Am J Med

    (2010)
  • E. Montgomery et al.

    Dysplasia as a predictive marker for invasive carcinoma in Barrett esophagus: a follow-up study based on 138 cases from a diagnostic variability study

    Human Path

    (2001)
  • W. Hameeteman et al.

    Barrett's esophagus: development of dysplasia and adenocarcinoma

    Gastroenterology

    (1989)
  • S.J. Spechler et al.

    Adenocarcinoma and Barrett's esophagus. An overrated risk?

    Gastroenterology

    (1984)
  • S. Singh et al.

    Statins are associated with reduced risk of esophageal cancer, particularly in patients with Barrett's esophagus: a systematic review and meta-analysis

    Clin Gastroenterol Hepatol

    (2013)
  • F. Kastelein et al.

    Proton pump inhibitors reduce the risk of neoplastic progression in patients with Barrett's esophagus

    Clin Gastroenterol Hepatol

    (2013)
  • C. Hur et al.

    The cost effectiveness of radiofrequency ablation for Barrett's esophagus

    Gastroenterology

    (2012)
  • T.K. Desai et al.

    The incidence of esophageal adenocarcinoma in non-dysplastic Barrett's esophagus: a meta-analysis

    Gut

    (2012)
  • C.H. Lim et al.

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

    Endoscopy

    (2007)
  • S. Wani et al.

    Esophageal adenocarcinoma in Barrett's esophagus after endoscopic ablative therapy: a meta-analysis and systematic review

    Am J Gastroenterol

    (2009)
  • S. Bhat et al.

    Risk of malignant progression in Barrett's esophagus patients: results from a large population-based study

    J Natl Cancer Inst

    (2011)
  • F. Hvid-Jensen et al.

    Incidence of adenocarcinoma among patients with Barrett's esophagus

    N Engl J Med

    (2011)
  • S. Wani

    Management of low-grade dysplasia in Barrett's esophagus

    Curr Opin Gastroenterol

    (2012)
  • K.W. Jung et al.

    Epidemiology and natural history of intestinal metaplasia of the gastresophageal junction and Barrett's esophagus: a population-based study

    Am J Gastroenterol

    (2011)
  • A. Stang

    Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses

    Eur J Epidemiol

    (2010)
  • Cited by (176)

    • Low-grade dysplasia in Barrett's esophagus: A problematic diagnosis

      2023, Gastroenterologia y Hepatologia
      Citation Excerpt :

      In patients with NDBE, LGD and HGD, the risk of neoplastic progression is around 0.2–0.5%, 0.7% and 7% per year respectively.22,23 A meta-analysis based on 47 studies showed that the incidence of EAC in BE was 6.1 per 1000 person-years24; in patients with HGD the incidence is estimated in 6 per 100 patient-years25 and 0.54% per year for LGD.26 The incidence of EAC in patients with BE increases progressively with age specially in patients over 70 years of age.27,28

    • Today's Toolbox for Barrett's Endotherapy

      2023, Techniques and Innovations in Gastrointestinal Endoscopy
    View all citing articles on Scopus

    DISCLOSURE: All authors disclosed no financial relationships relevant to this publication.

    See CME section; p. 983.

    Drs Singh and Manickam contributed equally to the article.

    View full text