Acceptability and Adequacy of a Non-endoscopic Cell Collection Device for Diagnosis of Barrett’s Esophagus: Lessons Learned



Endoscopic screening for Barrett’s esophagus (BE) is common, costly, and underperformed in at-risk people. A non-endoscopic cell collection device can be used to collect esophageal cells, enabling BE screening.


This study assessed the acceptability and adequacy of a commercial non-endoscopic cell collection device in a US population.


Six sites enrolled patients with confirmed BE or heartburn/regurgitation for ≥ 6 months. Patients underwent administration of the device, consisting of a sponge encapsulated in a capsule. The capsule dwelled in the stomach for 7.5 min and was retracted via an attached suture. An adequate sample was ≥ 1 columnar cell by H&E staining. Sample quality was rated using a 0–5 scale, with 0 = no columnar cells and 5 = plentiful groups. Trefoil Factor 3 (TFF3) staining was performed. Accuracy was assessed using esophagogastroduodenoscopy (EGD)/biopsy as the gold standard.


Of 191 patients, 99.5% successfully swallowed the device. Overall sample adequacy was 91% (171/188), with 84% (158/188) high quality. The detachment rate was 2/190 (1%). Overall sensitivity, specificity, and accuracy of the assay with TFF3 staining were 76%, 77%, and 76%. Sensitivity, specificity, and accuracy for ≥ 3 cm BE were 86%, 77%, and 82%. Asked if willing to repeat the procedure, 93% would, and 65% indicated a preference for the device over EGD.


This study demonstrated a high rate of sample adequacy and promising acceptability of this non-endoscopic sampling device in a US population. Diagnostic characteristics suggest that non-endoscopic assessment of BE deserves further development as an alternative to endoscopy.

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  1. 1.

    Pohl H, Sirovich B, Welch HG. Esophageal adenocarcinoma incidence: are we reaching the peak? Cancer Epidemiol Biomarkers Prev. 2010;19:1468–1470

    Article  Google Scholar 

  2. 2.

    Thrift AP. Barrett’s esophagus and esophageal adenocarcinoma: how common are they really? Dig Dis Sci. 2018;63:1988–1996.

    Article  PubMed  Google Scholar 

  3. 3.

    Eloubeidi MA, Mason AC, Desmond RA, El-Serag HB. Temporal trends (1973–1997) in survival of patients with esophageal adenocarcinoma in the United States: a glimmer of hope? Am J Gastroenterol. 2003;98:1627–1633.

    Article  PubMed  Google Scholar 

  4. 4.

    Shaheen NJ, Falk GW, Iyer PG, Gerson LB. American College of G ACG clinical guideline: diagnosis and management of Barrett’s Esophagus. Am J Gastroenterol. 2016;111:30–50.

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Spechler SJ, Sharma P, Souza RF, Inadomi JM, Shaheen NJ. American Gastroenterological Association medical position statement on the management of Barrett’s esophagus. Gastroenterology. 2011;140:1084–1091

    Article  Google Scholar 

  6. 6.

    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.

    Article  PubMed  Google Scholar 

  7. 7.

    Phoa KN, van Vilsteren FGI, Weusten BLAM et al. Radiofrequency ablation vs endoscopic surveillance for patients with barrett esophagus and low-grade dysplasia a randomized clinical trial. Jama-J Am Med Assoc. 2014;311:1209–1217.

    CAS  Article  Google Scholar 

  8. 8.

    Shaheen NJ, Sharma P, Overholt BF et al. Radiofrequency ablation in Barrett’s esophagus with dysplasia. N Engl J Med. 2009;360:2277–2288.

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Shaheen NJ, Provenzale D, Sandler RS. Upper endoscopy as a screening and surveillance tool in esophageal adenocarcinoma: a review of the evidence. Am J Gastroenterol. 2002;97:1319–1327.

    Article  PubMed  Google Scholar 

  10. 10.

    Vaughan TL, Fitzgerald RC. Precision prevention of oesophageal adenocarcinoma. Nat Rev Gastroenterol Hepatol. 2015;12:243–248.

    Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Wani S, Williams JL, Komanduri S, Muthusamy VR, Shaheen NJ. Endoscopists systematically undersample patients with long-segment Barrett’s esophagus: an analysis of biopsy sampling practices from a quality improvement registry. Gastrointest Endosc. 2019.

    Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    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

    Article  Google Scholar 

  13. 13.

    Montgomery E, Bronner MP, Goldblum JR et al. Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation. Hum Pathol. 2001;32:368–378

    CAS  Article  Google Scholar 

  14. 14.

    Ormsby AH, Petras RE, Henricks WH et al. Observer variation in the diagnosis of superficial oesophageal adenocarcinoma. Gut. 2002;51:671–676

    CAS  Article  Google Scholar 

  15. 15.

    Mastracci L, Piol N, Molinaro L et al. Interobserver reproducibility in pathologist interpretation of columnar-lined esophagus. Virchows Arch. 2016;468:159–167.

    Article  PubMed  Google Scholar 

  16. 16.

    Ross-Innes CS, Debiram-Beecham I, O’Donovan M et al. Evaluation of a minimally invasive cell sampling device coupled with assessment of trefoil factor 3 expression for diagnosing Barrett’s esophagus: a multi-center case-control study. PLoS Med. 2015;12:e1001780.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Kadri SR, Lao-Sirieix P, O’Donovan M et al. Acceptability and accuracy of a non-endoscopic screening test for Barrett’s oesophagus in primary care: cohort study. BMJ. 2010;341:c4372.

    Article  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Lao-Sirieix P, Boussioutas A, Kadri SR et al. Non-endoscopic screening biomarkers for Barrett’s oesophagus: from microarray analysis to the clinic. Gut. 2009;58:1451–1459.

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Januszewicz W, Tan WK, Lehovsky K et al. Safety and Acceptability of Esophageal Cytosponge Cell Collection Device in a Pooled Analysis of Data From Individual Patients. Clin Gastroenterol Hepatol 2019;17:647–656.

    Article  PubMed  Google Scholar 

  20. 20.

    Fitzgerald RC, di Pietro M, O’Donovan M et al. Cytosponge-trefoil factor 3 versus usual care to identify Barrett’s oesophagus in a primary care setting: a multicentre, pragmatic, randomised controlled trial. Lancet. 2020;396:333–344.

    Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Iqbal U, Siddique O, Ovalle A, Anwar H, Moss SF. Safety and efficacy of a minimally invasive cell sampling device ('Cytosponge’) in the diagnosis of esophageal pathology: a systematic review. Eur J Gastroenterol Hepatol. 2018;30:1261–1269.

    Article  PubMed  Google Scholar 

  22. 22.

    Peery AF, Dellon ES, Lund J et al. Burden of gastrointestinal disease in the United States: 2012 update. Gastroenterology 2012;143:1179–1187

    Article  Google Scholar 

  23. 23.

    Ross-Innes CS, Chettouh H, Achilleos A et al. Risk stratification of Barrett’s oesophagus using a non-endoscopic sampling method coupled with a biomarker panel: a cohort study. Lancet Gastroenterol Hepatol. 2017;2:23–31.

    Article  PubMed  Google Scholar 

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The authors thank the staff and participants of the study for their valuable contributions. Alex Shih, PhD (Medtronic), provided statistical support and Katherine E. Liu, PhD (Medtronic), provided medical writing support for this study.


This study was funded by Medtronic.

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All authors were involved in the design, data collection, data analysis or data interpretation of this study. NS drafted the manuscript and all authors participated in revision of the manuscript for important intellectual content.

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Correspondence to Nicholas J. Shaheen.

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Conflict of interest

Nicholas J. Shaheen has served as a consultant for Cernostics, Lucid, and Cook Medical, and has received research funding from Medical, C2 Therapeutics, Medtronic, Interpace Diagnostics, CDx Medical, EndoStim and Ironwood Pharmaceuticals. Maria O’Donovan has served as a consultant for Medtronic plc. She is named on patents relating to the original Cytosponge design and TFF3 assay licensed to Medtronic. She is a cofounder of Cyted Ltd. V. Raman Muthusamy has served as a consultant for Boston Scientific, Interpace Diagnostics, Medtronic, and Torax Medical (Ethicon), and has received research funding from Boston Scientific and Medtronic. Sachin Wani has served as a consultant for Boston Scientific, Medtronic, Interpace Diagnostics and Cernostics.

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Shaheen, N.J., Komanduri, S., Muthusamy, V.R. et al. Acceptability and Adequacy of a Non-endoscopic Cell Collection Device for Diagnosis of Barrett’s Esophagus: Lessons Learned. Dig Dis Sci (2021).

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  • Barrett’s esophagus
  • Screening
  • Non-endoscopic
  • Esophageal adenocarcinoma