title: 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.
abstract: BACKGROUND
  Barrett's esophagus (BE) is a commonly undiagnosed condition that predisposes to esophageal adenocarcinoma. Routine endoscopic screening for BE is not recommended because of the burden this would impose on the health care system. The objective of this study was to determine whether a novel approach using a minimally invasive cell sampling device, the Cytosponge, coupled with immunohistochemical staining for the biomarker Trefoil Factor 3 (TFF3), could be used to identify patients who warrant endoscopy to diagnose BE.
  
  
  RESULTS
  A case-control study was performed across 11 UK hospitals between July 2011 and December 2013. In total, 1,110 individuals comprising 463 controls with dyspepsia and reflux symptoms and 647 BE cases swallowed a Cytosponge prior to endoscopy. The primary outcome measures were to evaluate the safety, acceptability, and accuracy of the Cytosponge-TFF3 test compared with endoscopy and biopsy. In all, 1,042 (93.9%) patients successfully swallowed the Cytosponge, and no serious adverse events were attributed to the device. The Cytosponge was rated favorably, using a visual analogue scale, compared with endoscopy (p < 0.001), and patients who were not sedated for endoscopy were more likely to rate the Cytosponge higher than endoscopy (Mann-Whitney test, p < 0.001). The overall sensitivity of the test was 79.9% (95% CI 76.4%-83.0%), increasing to 87.2% (95% CI 83.0%-90.6%) for patients with ≥3 cm of circumferential BE, known to confer a higher cancer risk. The sensitivity increased to 89.7% (95% CI 82.3%-94.8%) in 107 patients who swallowed the device twice during the study course. There was no loss of sensitivity in patients with dysplasia. The specificity for diagnosing BE was 92.4% (95% CI 89.5%-94.7%). The case-control design of the study means that the results are not generalizable to a primary care population. Another limitation is that the acceptability data were limited to a single measure.
  
  
  CONCLUSIONS
  The Cytosponge-TFF3 test is safe and acceptable, and has accuracy comparable to other screening tests. This test may be a simple and inexpensive approach to identify patients with reflux symptoms who warrant endoscopy to diagnose BE.
authors: MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, United Kingdom.
authors: Caryn S
authors: CS
authors: Ross-Innes
authors: MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, United Kingdom.
authors: Irene
authors: I
authors: Debiram-Beecham
authors: Department of Histopathology, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors: Maria
authors: M
authors: O'Donovan
authors: MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, United Kingdom.
authors: Elaine
authors: E
authors: Walker
authors: MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, United Kingdom.
authors: Sibu
authors: S
authors: Varghese
authors: MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, United Kingdom.
authors: Pierre
authors: P
authors: Lao-Sirieix
authors: University College London Hospital, London, United Kingdom.
authors: Laurence
authors: L
authors: Lovat
authors: Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom.
authors: Michael
authors: M
authors: Griffin
authors: Nottingham Queen's Medical Centre, Nottingham, United Kingdom.
authors: Krish
authors: K
authors: Ragunath
authors: University College London Hospital, London, United Kingdom.
authors: Rehan
authors: R
authors: Haidry
authors: Nottingham Queen's Medical Centre, Nottingham, United Kingdom.
authors: Sarmed S
authors: SS
authors: Sami
authors: Nottingham Queen's Medical Centre, Nottingham, United Kingdom.
authors: Philip
authors: P
authors: Kaye
authors: University College London Hospital, London, United Kingdom.
authors: Marco
authors: M
authors: Novelli
authors: Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom.
authors: Babett
authors: B
authors: Disep
authors: Cancer Prevention Trials Unit, London, United Kingdom.
authors: Richard
authors: R
authors: Ostler
authors: Cancer Prevention Trials Unit, London, United Kingdom.
authors: Benoit
authors: B
authors: Aigret
authors: Cancer Prevention Trials Unit, London, United Kingdom.
authors: Bernard V
authors: BV
authors: North
authors: Queen Alexandra Hospital, Portsmouth, United Kingdom.
authors: Pradeep
authors: P
authors: Bhandari
authors: St Mark's Hospital, London, United Kingdom.
authors: Adam
authors: A
authors: Haycock
authors: East and North Hertfordshire NHS Trust-QEII and Lister Hospitals, Welwyn Garden City and Stevenage, United Kingdom.
authors: Danielle
authors: D
authors: Morris
authors: Northern Region Endoscopy Group, United Kingdom; North Tyneside General Hospital, North Shields, United Kingdom.
authors: Stephen
authors: S
authors: Attwood
authors: Northern Region Endoscopy Group, United Kingdom; County Durham and Darlington NHS Foundation Trust, Durham, United Kingdom.
authors: Anjan
authors: A
authors: Dhar
authors: Northern Region Endoscopy Group, United Kingdom; South Tyneside NHS Foundation Trust, South Shields, United Kingdom.
authors: Colin
authors: C
authors: Rees
authors: Northern Region Endoscopy Group, United Kingdom; North Tees and Hartlepool NHS Foundation Trust, Stockton-on-Tees, United Kingdom.
authors: Matthew D D
authors: MD
authors: Rutter
authors: Cancer Prevention Trials Unit, London, United Kingdom.
authors: Peter D
authors: PD
authors: Sasieni
authors: MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, United Kingdom.
authors: Rebecca C
authors: RC
authors: Fitzgerald
mesh_terms: D000368:Aged; D001471:Barrett Esophagus / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D016022:Case-Control Studies; D016145:Endoscopy, Digestive System / Q000295:instrumentation*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000032:analysis / Q000378:metabolism*; D012680:Sensitivity and Specificity; D000071165:Trefoil Factor-3
chemical_list: D015415:Biomarkers; D010455:Peptides; C082495:TFF3 protein, human; D000071165:Trefoil Factor-3
references: Gut. 2012 Jul;61(7):970-6
references: 21997553
references: Gut. 2009 Apr;58(4):530-5
references: 19036949
references: Gastroenterology. 2014 Jan;146(1):316-317
references: 25284828
references: Nat Rev Clin Oncol. 2012 Mar 20;9(5):278-87
references: 22430857
references: Clin Gastroenterol Hepatol. 2011 Mar;9(3):220-7; quiz e26
references: 21115133
references: Nat Genet. 2014 Aug;46(8):837-843
references: 24952744
references: Gut. 2015 Jan;64(1):20-5
references: 24700439
references: Gastroenterology. 2012 Nov;143(5):1179-1187.e3
references: 22885331
references: Gastroenterology. 2011 Mar;140(3):e18-52; quiz e13
references: 21376939
references: JAMA. 2014 Mar 26;311(12):1209-17
references: 24668102
references: Gastroenterology. 2013 Aug;145(2):312-9.e1
references: 23673354
references: J Thorac Cardiovasc Surg. 2011 Jan;141(1):39-47
references: 21055772
references: Gastroenterology. 2003 Dec;125(6):1670-7
references: 14724819
references: Gastroenterology. 2013 Jul;145(1):87-95
references: 23542069
references: Gastroenterology. 1993 Jul;105(1):40-50
references: 8514061
references: Gut. 2009 Nov;58(11):1451-9
references: 19651633
references: Am J Gastroenterol. 2004 Sep;99(9):1657-66
references: 15330898
references: Gastroenterology. 2013 Jan;144(1):62-73.e6
references: 23041329
references: Gastroenterology. 2004 Jul;127(1):310-30
references: 15236196
references: Gastroenterology. 2011 Mar;140(3):1084-91
references: 21376940
references: Ann Intern Med. 2011 Nov 15;155(10):687-97, W214-5
references: 22006930
references: Gut. 2008 Oct;57(10):1354-9
references: 18424568
references: Gastroenterology. 2002 Aug;123(2):461-7
references: 12145799
references: Gut. 2014 Jan;63(1):7-42
references: 24165758
references: Gut. 2002 Mar;50(3):378-81
references: 11839718
references: N Engl J Med. 2014 Apr 3;370(14):1287-97
references: 24645800
references: Gut. 2005 May;54(5):710-7
references: 15831922
references: Gastroenterology. 2005 Dec;129(6):1825-31
references: 16344051
references: Am J Gastroenterol. 2006 Jan;101(1):12-7
references: 16405528
references: N Engl J Med. 2011 Oct 13;365(15):1375-83
references: 21995385
references: JAMA. 2013 Aug 14;310(6):627-36
references: 23942681
references: Cancer Prev Res (Phila). 2012 Sep;5(9):1115-23
references: 22787114
references: BMJ. 2010 Sep 10;341:c4372
references: 20833740
references: N Engl J Med. 2009 May 28;360(22):2277-88
references: 19474425
references: J Med Screen. 2000;7(2):105-10
references: 11002452
references: PLoS One. 2014 Apr 15;9(4):e94163
references: 24736597