Targeted detection of Barrett’s neoplasia: A case report
Barrett’s esophagus (BE) is a precursor condition for esophageal adenocarcinoma (EAC). This case report describes the in vivo use of a fluorescently-labeled peptide heterodimer specific for epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor (HER2) to identify residual neoplasia in a 52-year-old female patient with BE. This targeted contrast agent was topically administered after an incomplete endoscopic mucosal resection of high-grade dysplasia with carcinoma in situ. A flexible fiber-coupled multi-modal scanning fiber endoscope was used to capture near-infrared fluorescence images. This instrument was passed through the working channel of a standard upper endoscope for use as an accessory. Increased fluorescence intensity was observed from nodular mucosa as a real-time “red flag” to identify the presence of neoplasia. Pathologic tests were conducted on the resected tissues, confirming the presence of stage T1a EAC. The expression EGFR and HER2 was confirmed by immunohistochemistry ex vivo. These findings support integrated imaging as a potential strategy to detect Barrett’s neoplasia.
- Prasad GA, Bansal A, Sharma P, Wang KK. Predictors of progression in Barrett’s esophagus: Current knowledge and future directions. Am J Gastroenterol. 2010;105:1490-1502. doi: 10.1038/ajg.2010.2
- Arnold M, Abnet CC, Neale RE, et al. Global burden of 5 major types of gastrointestinal cancer. Gastroenterology. 2020;159:335-349.e15. doi: 10.1053/j.gastro.2020.02.068
- Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73:17-48. doi: 10.3322/caac.21763
- He H, Chen N, Hou Y, et al. Trends in the incidence and survival of patients with esophageal cancer: A SEER database analysis. Thorac Cancer. 2020;11:1121-1128. doi: 10.1111/1759-7714.13311
- Shaheen NJ, Falk GW, Iyer PG, Souza RF, Wani S. Guideline to practice: Diagnosis and management of Barrett’s esophagus: An updated ACG guideline. Am J Gastroenterol. 2022;117:1177-1180. doi: 10.14309/ajg.0000000000001788
- 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. doi: 10.1016/j.cgh.2008.11.024
- 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. doi: 10.1016/j.gie.2012.05.007
- Sturm MB, Wang TD. Endoscopic imaging techniques: Beyond narrow band. Am J Gastroenterol. 2018;113(8):1103-1107. doi: 10.1038/s41395-018-0054-3
- Struyvenberg MR, de Groof AJ, van der Putten J, et al. A computer-assisted algorithm for narrow-band imaging-based tissue characterization in Barrett’s esophagus. Gastrointest Endosc. 2021;93(1):89-98. doi: 10.1016/j.gie.2020.05.050
- ASGE Technology Committee, Thosani N, Abu Dayyeh BK, et al. ASGE technology committee systematic review and meta-analysis assessing the ASGE preservation and incorporation of valuable endoscopic innovations thresholds for adopting real-time imaging-assisted endoscopic targeted biopsy during endoscopic surveillance of Barrett’s esophagus. Gastrointest Endosc. 2016;83(4):684- 698.e7. doi: 10.1016/j.gie.2016.01.007
- Dulak AM, Stojanov P, Peng S, et al. Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity. Nat Genet. 2013;45:478-486. doi: 10.1038/ng.2591
- Chen J, Jiang Y, Chang TS, et al. Multiplexed endoscopic imaging of Barrett’s neoplasia using targeted fluorescent heptapeptides in a phase 1 proof-of-concept study. Gut. 2021;70:1010-1013. doi: 10.1136/gutjnl-2020-322945
- Chen J, Jiang Y, Chang TS, et al. Detection of Barrett’s neoplasia with a near-infrared fluorescent heterodimeric peptide. Endoscopy. 2022;54:1198-1204. doi: 10.1055/a-1801-2406
- Chen J, Zhou J, Gao Z, et al. Multiplexed targeting of Barrett’s neoplasia with a heterobivalent ligand: Imaging study on mouse xenograft in vivo and human specimens ex vivo. J Med Chem. 2018;61:5323-5331. doi: 10.1021/acs.jmedchem.8b00405
- Chen J, Gao Z, Li G, Wang TD. Dual-modal in vivo fluorescence and photoacoustic imaging using a heterodimeric peptide. Chem Commun (Camb). 2018;54:13196-13199. doi: 10.1039/c8cc06774k
- Jiang Y, Gong Y, Rubenstein JH, Wang TD, Seibel EJ. Toward real-time quantification of fluorescence molecular probes using target/background ratio for guiding biopsy and endoscopic therapy of esophageal neoplasia. J Med Imaging (Bellingham). 2017;4(2):024502. doi: 10.1117/1.JMI.4.2.024502
- Jiang Y, Chen J, Gong C, Wang TD, Seibel EJ. Deep-learning-based real-time and automatic target-to-background ratio calculation in fluorescence endoscopy for cancer detection and localization. Diagnostics (Basel). 2022;12:2031. doi: 10.3390/diagnostics12092031