title: Barrett's esophagus and adenocarcinoma risk: the experience of the North-Eastern Italian Registry (EBRA).
abstract: OBJECTIVE
  To establish the incidence and risk factors for progression to high-grade intraepithelial neoplasia (HG-IEN) or Barrett's esophageal adenocarcinoma (BAc) in a prospective cohort of patients with esophageal intestinal metaplasia [(BE)].
  
  
  BACKGROUND
  BE is associated with an increased risk of BAc unless cases are detected early by surveillance. No consistent data are available on the prevalence of BE-related cancer, the ideal surveillance schedule, or the risk factors for cancer.
  
  
  METHODS
  In 2003, a regional registry of BE patients was created in north-east Italy, establishing the related diagnostic criteria (endoscopic landmarks, biopsy protocol, histological classification) and timing of follow-up (tailored to histology) and recording patient outcomes. Thirteen centers were involved and audited yearly. The probability of progression to HG-IEN/BAc was calculated using the Kaplan-Meier method; the Cox regression model was used to calculate the risk of progression.
  
  
  RESULTS
  HG-IEN (10 cases) and EAc (7 cases) detected at the index endoscopy or in the first year of follow-up were considered to be cases of preexisting disease and excluded; 841 patients with at least 2 endoscopies {median, 3 [interquartile range (IQR): 2-4); median follow-up = 44.6 [IQR: 24.7-60.5] months; total 3083 patient-years} formed the study group [male/female = 646/195; median age, 60 (IQR: 51-68) years]. Twenty-two patients progressed to HG-IEN or BAc (incidence: 0.72 per 100 patient-years) after a median of 40.2 (26.9-50.4) months. At multivariate analysis, endoscopic abnormalities, that is, ulceration or nodularity (P = 0.0002; relative risk [RR] = 7.6; 95% confidence interval, 2.63-21.9), LG-IEN (P = 0.02, RR = 3.7; 95% confidence interval, 1.22-11.43), and BE length (P = 0.01; RR = 1.16; 95% confidence interval, 1.03-1.30) were associated with BE progression. Among the LG-IEN patients, the incidence of HG-IEN/EAc was 3.17 patient-years, that is, 6 times higher than in BE patients without LG-IEN.
  
  
  CONCLUSIONS
  These results suggest that in the absence of intraepithelial neoplastic changes, BE carries a low risk of progression to HG-IEN/BAc, and strict surveillance (or ablative therapy) is advisable in cases with endoscopic abnormalities, LG-IEN or long BE segments.
authors.affiliation: Department of Pathology, University of Padova, Padua, Italy.
authors.forename: Massimo
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authors.lastname: Rugge
authors.forename: Giovanni
authors.initials: G
authors.lastname: Zaninotto
authors.forename: Paola
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authors.forename: Lisa
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authors.lastname: Zanatta
authors.forename: Francesco
authors.initials: F
authors.lastname: Cavallin
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authors.forename: Ettore
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authors.lastname: Macrì
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authors.forename: Paolo
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authors.lastname: Iuzzolino
authors.forename: Francesco
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authors.lastname: Ferrara
authors.forename: Renato
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authors.forename: Emiliano
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authors.forename: Gaetano
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authors.lastname: Iaderosa
authors.forename: Michele
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authors.forename: Angelo
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authors.forename: Flavio
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authors.forename: Duilio
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authors.lastname: Della Libera
authors.forename: Marco
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authors.lastname: Benini
authors.forename: Laura
authors.initials: L
authors.lastname: Bortesi
authors.forename: Alberto
authors.initials: A
authors.lastname: Meggio
authors.forename: Maria G
authors.initials: MG
authors.lastname: Zorzi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Depretis
authors.forename: Gianni
authors.initials: G
authors.lastname: Miori
authors.forename: Luca
authors.initials: L
authors.lastname: Morelli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cataudella
authors.forename: Emanuele S G
authors.initials: ES
authors.lastname: d'Amore
authors.forename: Emanuele
authors.initials: E
authors.lastname: Dʼamore
authors.forename: Ilaria
authors.initials: I
authors.lastname: Franceschetti
authors.forename: Loredana
authors.initials: L
authors.lastname: Bozzola
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Paternello
authors.forename: Cristina
authors.initials: C
authors.lastname: Antonini
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Mario
authors.forename: Nadia
authors.initials: N
authors.lastname: Dal Bò
authors.forename: Alberto
authors.initials: A
authors.lastname: Furlanetto
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Norberto
authors.forename: Lino
authors.initials: L
authors.lastname: Polese
authors.forename: Silvia
authors.initials: S
authors.lastname: Iommarini
authors.forename: Fabio
authors.initials: F
authors.lastname: Farinati
authors.forename: Giorgio
authors.initials: G
authors.lastname: Battaglia
authors.forename: Giorgio
authors.initials: G
authors.lastname: Diamantis
authors.forename: Stefano
authors.initials: S
authors.lastname: Realdon
authors.forename: Ennio
authors.initials: E
authors.lastname: Guido
authors.forename: Gaetano
authors.initials: G
authors.lastname: Mastropaolo
authors.forename: Daniele
authors.initials: D
authors.lastname: Canova
authors.forename: Antonello
authors.initials: A
authors.lastname: Guerini
authors.forename: Marilisa
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authors.lastname: Franceschi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zirillo
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000453:epidemiology* / Q000473:pathology*; D000368:Aged; D001471:Barrett Esophagus / Q000175:diagnosis / Q000453:epidemiology* / Q000473:pathology*; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000473:pathology*; D004945:Esophagoscopy; D005260:Female; D006801:Humans; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000175:diagnosis / Q000453:epidemiology* / Q000473:pathology*; D016016:Proportional Hazards Models; D012042:Registries; D012307:Risk Factors; D018709:Statistics, Nonparametric