Detection of early neoplasia in Barrett’s esophagus using lectin-based near-infrared imaging: an ex vivo study on human tissue
submitted 03. Juli 2017
accepted after revision 10. Oktober 2017
17. Januar 2018 (eFirst)
Background and study aims Endoscopic surveillance for Barrett’s esophagus (BE) is limited by long procedure times and sampling error. Near-infrared (NIR) fluorescence imaging minimizes tissue autofluorescence and optical scattering. We assessed the feasibility of a topically applied NIR dye-labeled lectin for the detection of early neoplasia in BE in an ex vivo setting.
Methods Consecutive patients undergoing endoscopic mucosal resection (EMR) for BE-related early neoplasia were recruited. Freshly collected EMR specimens were sprayed at the bedside with fluorescent lectin and then imaged. Punch biopsies were collected from each EMR under NIR light guidance. We compared the fluorescence intensity from dysplastic and nondysplastic areas within EMRs and from punch biopsies with different histological grades.
Results 29 EMR specimens were included from 17 patients. A significantly lower fluorescence was found for dysplastic regions across whole EMR specimens (P < 0.001). We found a 41 % reduction in the fluorescence of dysplastic compared to nondysplastic punch biopsies (P < 0.001), with a sensitivity and specificity for dysplasia detection of 80 % and 82.9 %, respectively.
Conclusion Lectin-based NIR imaging can differentiate dysplastic from nondysplastic Barrett’s mucosa ex vivo.
* These authors contributed equally to the study.
- 1 Thrift AP, Whiteman DC. The incidence of esophageal adenocarcinoma continues to rise: analysis of period and birth cohort effects on recent trends. Ann Oncol 2012; 23: 3155-3162
- 2 Fitzgerald RC, di Pietro M, Ragunath K. et al. British Society of Gastroenterology guidelines on the diagnosis and management of Barrett’s oesophagus. Gut 2014; 63: 7-42
- 3 El-Serag HB, Naik AD, Duan Z. et al. Surveillance endoscopy is associated with improved outcomes of oesophageal adenocarcinoma detected in patients with Barrett’s oesophagus. Gut 2016; 65: 1252-1260
- 4 Abrams JA, Kapel RC, Lindberg GM. 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
- 5 Boerwinkel DF, Swager A, Curvers WL. et al. The clinical consequences of advanced imaging techniques in Barrett’s esophagus. Gastroenterology 2014; 146: 622-629.e4
- 6 Atreya R, Goetz M. Molecular imaging in gastroenterology. Nat Rev Gastroenterol Hepatol 2013; 10: 704-712
- 7 Bird-Lieberman EL, Neves AA, Lao-Sirieix P. et al. Molecular imaging using fluorescent lectins permits rapid endoscopic identification of dysplasia in Barrett’s esophagus. Nat Med 2012; 18: 315-321
- 8 Liu Z, Miller SJ, Joshi BP. et al. In vivo targeting of colonic dysplasia on fluorescence endoscopy with near-infrared octapeptide. Gut 2013; 62: 395-403
- 9 Tjalma JJ, Garcia-Allende PB, Hartmans E. et al. Molecular fluorescence endoscopy targeting vascular endothelial growth factor A for improved colorectal polyp detection. J Nucl Med 2016; 57: 480-485
- 10 ClinicalTrials.gov. Bethesda (Maryland): National Library of Medicine (US). 200 Feb 29. Identifier CT02129933, VEGF-targeted [Internet]fluorescence near-infrared (NIR) endoscopy in (pre)malignant esophageal lesions (VICE). 24.04.2014 Available from: https://clinicaltrials.gov/ct2/show/NCT02129933
- 11 Sato K, Nagaya T, Choyke PL. et al. Near infrared photoimmunotherapy in the treatment of pleural disseminated NSCLC: preclinical experience. Theranostics 2015; 5: 698-709
- 12 Alam IS, Neves AA, Witney TH. et al. Comparison of the C2A domain of synaptotagmin-I and annexin-V as probes for detecting cell death. Bioconjug Chem 2010; 21: 884-891
- 13 di Pietro M, Boerwinkel DF, Shariff MK. et al. The combination of autofluorescence endoscopy and molecular biomarkers is a novel diagnostic tool for dysplasia in Barrett’s oesophagus. Gut 2015; 64: 49-56
- 14 Dixon MF. Gastrointestinal epithelial neoplasia: Vienna revisited. Gut 2002; 51: 130-131
- 15 Burggraaf J, Kamerling IM, Gordon PB. et al. Detection of colorectal polyps in humans using an intravenously administered fluorescent peptide targeted against c-Met. Nat Med 2015; 21: 955-961
- 16 Foersch S, Kiesslich R, Waldner MJ. et al. Molecular imaging of VEGF in gastrointestinal cancer in vivo using confocal laser endomicroscopy. Gut 2010; 59: 1046-1055
- 17 Kuo JC, Ibrahim AE, Dawson S. et al. Detection of colorectal dysplasia using fluorescently labelled lectins. Sci Rep 2016; 6: 24231
- 18 Waterhouse DJ, Joseph J, Neves AA. et al. Design and validation of a near-infrared fluorescence endoscope for detection of early esophageal malignancy. J Biomed Opt 2016; 21: 84001
- 19 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