Accuracy of probe-based confocal laser endomicroscopy (pCLE) compared to random biopsies during endoscopic surveillance of Barrett’s esophagus

 

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Abstract

Background For surveillance of Barrett’s esophagus (BE), the current standard of random 4-quadrant biopsies misses 10 – 50 % of esophageal neoplasms, and does not permit real-time decision-making. Probe-based confocal laser endomicroscopy (pCLE) permits real-time in vivo histologic assessment of esophageal mucosa during upper endoscopy. Prospective studies comparing the accuracy of pCLE to 4-quadrant biopsies in routine clinical practice are lacking.

Methods Consecutive patients with BE underwent high definition white light and narrow-band imaging followed by pCLE and targeted biopsy or mucosal resection. Four-quadrant biopsies were obtained during the same session. Baseline variables, real-time pCLE interpretation, and histology results were prospectively recorded. Blinded expert review of pCLE sequences and histology specimens was performed. A sample size of 64 patients was calculated a priori based on 3 % estimated prevalence of high grade dysplasia (HGD) or cancer.

Results In total, 66 patients were included in the study. The prevalence of HGD or cancer was 4.55 %. Both real-time and blinded pCLE correctly identified all cases of cancer. For the primary outcome, real-time pCLE was 98 % specific but only 67 % sensitive for HGD/cancer compared to non-blinded pathologist interpretation. For HGD and cancer, inter-observer agreement was substantial between real-time and blinded endomicroscopists (kappa = 0.6). pCLE identified dysplasia in 75 % of cases where both blinded and unblinded pathology interpretation was low grade dysplasia.

Conclusions pCLE demonstrates high specificity for detecting dysplasia and cancer, but lower sensitivity may limit its utility in routine BE surveillance. pCLE may have a role in confirming LGD in real-time before eradication therapy.

• References

• 1 Shaheen NJ, Falk NJ, Iyer PG. et al. ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus. Am J Gastroenterol 2016; 111: 30-50
  CrossrefPubMedGoogle Scholar
• 2 Falk GW, Rice TW, Goldblum JR. et al. Jumbo biopsy forceps protocol still misses unsuspected cancer in Barrett’s esophagus with high-grade dysplasia. Gastrointest Endosc 1999; 49: 170-176 PMID 9925694
  CrossrefPubMedGoogle Scholar
• 3 Kariv R, Plesec TP, Goldblum JR. et al. The Seattle protocol does not more reliably predict the detection of cancer at the time of esophagectomy than a less intensive surveillance protocol. Clin Gastroenterol Hepatol 2009; 7: 653-658 quiz 606
  CrossrefPubMedGoogle Scholar
• 4 Singh S, Manickam P, Amin AV. et al. Incidence of esophageal adenocarcinoma in Barrett’s esophagus with low-grade dysplasia: a systematic review and meta-analysis. Gastrointest Endosc 2014; 79: 897-909 e4; quiz 983 e1, 983 e3
  CrossrefPubMedGoogle Scholar
• 5 Yousef F, Cartwell C, Cantwell MM. et al. The incidence of esophageal cancer and high-grade dysplasia in Barrett’s esophagus: a systematic review and meta-analysis. Am J Epidemiol 2008; 168: 237-249
  CrossrefPubMedGoogle Scholar
• 6 Leggett CL, Gorospe EC. Application of confocal laser endomicroscopy in the diagnosis and management of Barrett’s esophagus. Ann Gastroenterol 2014; 27: 193-199
  PubMedGoogle Scholar
• 7 ASGE TechnologyCommittee. Confocal laser endomicroscopy. Gastrointest Endosc 2014; 80: 928-938
  CrossrefPubMedGoogle Scholar
• 8 ASGS review of Confocal Laser Endomicroscopy. 2016 Available from: https://theasgs.org/position-statements/position-statement-on-confocal-laser-endomicroscopy/
  PubMedGoogle Scholar
• 9 Sharma P, Brill J, Canto M. et al. White Paper AGA: Advanced Imaging in Barrett’s Esophagus. Clin Gastroenterol Hepatol 2015; 13: 2209-2218
  CrossrefPubMedGoogle Scholar
• 10 Bajbouj M, Vieth M, Rosch T. et al. Probe-based confocal laser endomicroscopy compared with standard four-quadrant biopsy for evaluation of neoplasia in Barrett’s esophagus. Endoscopy 2010; 42: 435-440
  Artikel in Thieme ConnectPubMedGoogle Scholar
• 11 Canto MI, Anandasabapathy S, Brugge W. et al. In vivo endomicroscopy improves detection of Barrett’s esophagus-related neoplasia: a multicenter international randomized controlled trial (with video). Gastrointest Endosc 2014; 79: 211-221
  CrossrefPubMedGoogle Scholar
• 12 Sharma P, Meining AR, Coron E. et al. Real-time increased detection of neoplastic tissue in Barrett’s esophagus with probe-based confocal laser endomicroscopy: final results of an international multicenter, prospective, randomized, controlled trial. Gastrointest Endosc 2011; 74: 465-472
  CrossrefPubMedGoogle Scholar
• 13 di Pietro M, Bird-Lieberman EL, Liu X. et al. Autofluorescence-directed confocal endomicroscopy in combination with a three-biomarker panel can inform management decisions in Barrett’s esophagus. Am J Gastroenterol 2015; 110: 1549-1558
  CrossrefPubMedGoogle Scholar
• 14 Sharma P, Savides TJ, Canto MI. et al. The American Society for Gastrointestinal Endoscopy PIVI (Preservation and Incorporation of Valuable Endoscopic Innovations) on Imaging in Barrett’s Esophagus. Gastrointest Endosc 2012; 76: 252-254
  CrossrefPubMedGoogle Scholar
• 15 Kara MA, Ennahachi M, Fockens P. et al. Detection and classification of the mucosal and vascular patterns (mucosal morphology) in Barrett’s esophagus by using narrow band imaging. Gastrointest Endosc 2006; 64: 155-166
  CrossrefPubMedGoogle Scholar
• 16 Wallace M, Lauwers GY, Chen Y. et al. Miami classification for probe-based confocal laser endomicroscopy. Endoscopy 2011; 43: 882-891
  Artikel in Thieme ConnectPubMedGoogle Scholar
• 17 Spechler SJ, Sharma P, Souza RF. et al. American Gastroenterological Association technical review on the management of Barrett’s esophagus. Gastroenterology 2011; 140: e18-52; quiz e13
  PubMedGoogle Scholar
• 18 Gaddam S, Mathur SC, Singh M. et al. Novel probe-based confocal laser endomicroscopy criteria and interobserver agreement for the detection of dysplasia in Barrett’s esophagus. Am J Gastroenterol 2011; 106: 1961-1969
  CrossrefPubMedGoogle Scholar
• 19 Odze RD. Diagnosis and grading of dysplasia in Barrett’s oesophagus. J Clin Pathol 2006; 59: 1029-1038
  CrossrefPubMedGoogle Scholar
• 20 Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics 1977; 33: 159-174
  CrossrefPubMedGoogle Scholar
• 21 Abrams JA, Kapel RC, Lindberg JM. et al. Adherence to biopsy guidelines for Barrett’s esophagus surveillance in the community setting in the United States. Clin Gastroenterol Hepatol 2009; 7: 736-742; quiz 710
  CrossrefPubMedGoogle Scholar
• 22 Wani S, Rubenstein JH, Vieth M. et al. Diagnosis and Management of Low-Grade Dysplasia in Barrett’s Esophagus: Expert Review From the Clinical Practice Updates Committee of the American Gastroenterological Association. Gastroenterology 2016; 151: 822-835
  CrossrefPubMedGoogle Scholar