title: Patients With Barrett's Esophagus and Persistent Low-grade Dysplasia Have an Increased Risk for High-grade Dysplasia and Cancer.
abstract: In some patients with Barrett's esophagus (BE) and a confirmed diagnosis of low-grade dysplasia (LGD), the LGD is not detected during follow-up examinations. We would like to avoid the unnecessary risks and costs of ablative treatment for these patients. Therefore, we investigated whether persistent LGD increases risk for high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) and what proportion of patients are no longer found to have dysplasia after an initial diagnosis of LGD.
  
  
  
  In a retrospective study, we collected information on 1579 patients with BE and LGD from 2005 through 2010 by using a nationwide registry of histopathology diagnoses in the Netherlands (PALGA). Confirmed LGD was defined as a diagnosis of LGD that was confirmed by any other pathologist. Persistent LGD was defined as LGD detected at the first and follow-up endoscopy. Data were collected on patients until treatment for HGD, detection of EAC, or the last endoscopy at which a biopsy was collected (through July 2014). We evaluated whether persistent LGD was a risk factor for malignant progression by using univariable and multivariable Cox regression analyses.
  
  
  
  Of individuals with BE and LGD in the database, the diagnosis of LGD was confirmed for 161 patients (10% of total). In these patients, the incidence of HGD and/or EAC was 5.18/100 person-years (95% confidence interval [CI], 4.32-8.10/100 person-years) compared with 1.85/100 person-years (95% CI, 1.52-2.22/100 person-years) in patients for whom LGD was not confirmed at the first endoscopy. The incidence of EAC alone in patients with confirmed LGD was 2.51/100 person-years (95% CI, 1.46-3.99/100 person-years), compared with 1.01/per 100 person-years (95% CI, 0.41-2.10/100 person-years) in patients for whom LGD was not confirmed at the first endoscopy. Of patients in whom LGD was confirmed at the first endoscopic examination, 51% were not found to have dysplasia at the first follow-up endoscopy, and 30% had persistent LGD. In patients with persistent LGD, the incidence of HGD and/or EAC was 7.65/100 person-years (95% CI, 4.45-12.34) and of only EAC was 2.04/100 person-years (95% CI, 0.65-4.92); in patients without persistent LGD, the incidence of HGD and/or EAC was 2.32/100 person-years (95% CI, 1.08-4.40/100 person-years) and of only EAC was 1.45 (95% CI, 0.53-3.21/100 person-years). Persistent LGD was found to be an independent risk factor for the development of HGD and/or EAC, with hazard ratio of 3.5 (95% CI, 1.48-8.28).
  
  
  
  In a large population-based cohort study of patients with BE and LGD, the risk of progression to HGD and/or EAC was higher in patients with confirmed LGD and highest in those with confirmed and persistent LGD.
authors.affiliation: Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: c.kestens@umcutrecht.nl.
authors.forename: Christine
authors.initials: C
authors.lastname: Kestens
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: G Johan A
authors.initials: GJ
authors.lastname: Offerhaus
authors.affiliation: Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Jantine W P M
authors.initials: JW
authors.lastname: van Baal
authors.affiliation: Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Siersema
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology*; D000368:Aged; D001471:Barrett Esophagus / Q000150:complications*; D004938:Esophageal Neoplasms / Q000453:epidemiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D012189:Retrospective Studies; D018570:Risk Assessment; D065310:Squamous Intraepithelial Lesions of the Cervix / Q000150:complications*
keywords: Esophageal Cancer; Esophagus; Marker; Prognostic Factor