AccScience Publishing / GTM / Online First / DOI: 10.36922/gtm.2223
CASE REPORT

Targeted detection of Barrett’s neoplasia: A case report

Tse-Shao Chang1 Jing Chen2 Richard S. Kwon2 Yang Jiang3 Eric J. Seibel3 D. Kim Turgeon2 Thomas D. Wang1,2,4*
Show Less
1 Department of Mechanical Engineering, College of Engineering, University of Michigan, Ann Arbor, Michigan, United States of America
2 Department of Internal Medicine, Division of Gastroenterology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, United States of America
3 Department of Mechanical Engineering, Human Photonics Laboratory, College of Engineering, University of Washington, Seattle, Washington, United States of America
4 Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, Michigan, United States of America
Global Translational Medicine 2024, 3(2), 2223 https://doi.org/10.36922/gtm.2223
Submitted: 10 November 2023 | Accepted: 22 February 2024 | Published: 3 May 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

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.

Keywords
Barrett’s esophagus
High-grade dysplasia
Esophageal adenocarcinoma
Peptide
Heterodimer
Epidermal growth factor receptor
Human epidermal growth factor receptor
Imaging
Funding
This work is supported by the National Institutes of Health (CA163059).
References
  1. 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

 

  1. 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

 

  1. Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73:17-48. doi: 10.3322/caac.21763

 

  1. 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

 

  1. 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

 

  1. 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

 

  1. 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

 

  1. 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

 

  1. 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

 

  1. 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

 

  1. 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

 

  1. 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

 

  1. 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

 

  1. 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

 

  1. 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

 

  1. 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

 

  1. 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
Conflict of interest
Jing Chen and Thomas D. Wang are inventors on patents filed by the University of Michigan on the peptide heterodimer used in the study. Eric J. Seibel is an inventor on patents filed by the University of Washington on the mmSFE. The remaining authors declare that they have no conflicts of interest.
Share
Back to top
Global Translational Medicine, Electronic ISSN: 2811-0021 Published by AccScience Publishing