title: Identification of volumetric laser endomicroscopy features predictive for early neoplasia in Barrett's esophagus using high-quality histological correlation.
abstract: OBJECTIVE
  Volumetric laser endomicroscopy (VLE) provides a circumferential scan that enables visualization of the subsurface layers of the esophageal wall at 7 μm resolution. The aims of this study were to identify VLE features of Barrett's esophagus (BE) neoplasia and to develop a VLE prediction score.
  
  
  METHODS
  A database of VLE images from endoscopic resection specimens, precisely correlated with histology, from patients with BE with and without neoplasia was used. Features potentially predictive for early BE neoplasia were identified by unblinded evaluation of 25 VLE-histology images. In a learning phase, 20 VLE images with or without BE neoplasia were scored by 2 VLE experts, blinded to histology. A prediction score was created by using multivariable logistic regression analyses and validated by scoring 40 VLE images (50% neoplastic) by using area under receiver operating characteristic (ROC) curve (AUC) analysis.
  
  
  RESULTS
  Three VLE features independently predictive for BE neoplasia were identified: (1) lack of layering; (2) higher surface than subsurface signal; (3) presence of irregular, dilated glands/ducts. A VLE neoplasia prediction score was developed with the following: (1) 6 points; (2) 6 or 8 points for equal or higher surface signal; and (3) 5 points. The ROC curve of this prediction score showed an AUC of 0.81 (95% confidence interval, 0.71-0.90). A cut-off value of ≥8 was associated with sensitivity and specificity of 83% and 71%, respectively.
  
  
  CONCLUSIONS
  When high-quality ex vivo VLE-histology correlation was used, the VLE features of layering, surface signal, and irregular glands/ducts were independently and significantly associated with BE neoplasia. A VLE prediction score for BE neoplasia was developed and validated, with promising accuracy. (Clinical trial registration number: NCT01862666.).
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Anne-Fré
authors.initials: AF
authors.lastname: Swager
authors.affiliation: Department of Pathology and Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Guillermo J
authors.initials: GJ
authors.lastname: Tearney
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Cadman L
authors.initials: CL
authors.lastname: Leggett
authors.affiliation: Department of Medical Oncology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Martijn G H
authors.initials: MGH
authors.lastname: van Oijen
authors.affiliation: Department of Pathology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Sybren L
authors.initials: SL
authors.lastname: Meijer
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Bas L
authors.initials: BL
authors.lastname: Weusten
authors.affiliation: Department of Gastroenterology and Hepatology, Catharina Hospital, Eindhoven, the Netherlands.
authors.forename: Wouter L
authors.initials: WL
authors.lastname: Curvers
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Jacques J G H M
authors.initials: JJGHM
authors.lastname: Bergman
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000368:Aged; D019540:Area Under Curve; D001471:Barrett Esophagus / Q000473:pathology*; D055088:Early Detection of Cancer; D004938:Esophageal Neoplasms / Q000473:pathology*; D004945:Esophagoscopy; D005260:Female; D006801:Humans; D000069416:Intravital Microscopy; D016015:Logistic Models; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D015999:Multivariate Analysis; D012372:ROC Curve; D015203:Reproducibility of Results; D041623:Tomography, Optical Coherence