Results

1
A pilot feasibility study of screening for
Barretts oesophagus with a novel non-endoscopic
capsule sponge device in a primary care setting
  S. R. Kadri1 , I. Debiram1, M Das1, P.
Lao-Sirieix1, M. O'Donovan1, J. M. Blazeby2, H.
Morris3, F. Walter4, J. Emery5, R. C.
Fitzgerald11Cancer Cell Unit, Hutchison-MRC
Research Centre, Cambridge, 2Dept of Surgery and
Dpt. of Social Medicine, University of Bristol,
Bristol, 3Cancer Cell Unit, General Practice and
Primary Care Research Unit, 4Cancer Cell Unit,
General Practice and Primary Care Research Unit,
Cambridge, United Kingdom, 5Cancer Cell Unit,
University of Western Australia, Perth, Australia

• Results
• Recruitment
• 507 out of 4417 patients were eligible to
  take part in the study
• 131 of them (25.5) participated in the study
• Demographics
• Male-female ratio was 1.11
• Mean age was 61.7 years
• The mean BMI was 30.5 (range 20-48) for males
  and 29.6 (range 20- 48) for females
• The mean waist to hip ratio was 0.95 (moderate
  risk) for males and 0.83 for females (moderate
  risk)

Biomarker Identification The samples retrieved
were processed to a paraffin block and slides
were stained for a panel of biomarkers validated
in known BE (n26) and healthy volunteers (n25
table1) Table 1

• Introduction
• Barretts oesophagus occurs in 2-4 of the
  population and is undiagnosed in majority of the
  cases
• In order to reduce population mortality from
  oesophageal cancer systematic diagnosis of
  Barretts oesophagus through screening merits
  consideration
• Population screening using endoscopy is not
  recommended due to logical and cost
  considerations
• We have developed a non-endoscopic screening test
  using a capsule sponge device.
• Sample collected from this then tested with
  immunocytological markers specific for Barretts
  oesophagus (Lao-Sirieix et al. Gut, 2007)

  Sensitivity Specificity PPV NPV Correct Proportion
Alcian blue (AB) 68 96 94 76 82
TFF3 28 88 70 56 59
Mcm combination1 (M 1) 60 65 63 63 63
Mcm combination1 (M2) 60 62 60 62 61
Mcm 2 alone 56 50 54 52 53
TFF3 and AB 72 88 86 77 80
M1 intensity gt 2 44 96 92 64 71
M1 and AB and TFF3 84 62 68 80 73
M2 and AB and TFF3 88 62 69 84 75
AB and TFF3 and M1 intensity gt2 80 85 83 81 82
AB and M1intensity gt 2 76 92 90 80 84
Reflux symptoms

• Aim
• The overall purpose of the Barretts Oesophagus
  Screening Trial (BEST) is to determine the
  ability of the capsule sponge test to diagnose
  Barretts oesophagus in a primary care setting in
  comparison with the gold standard endoscopy. 500
  individuals with a history of reflux will be
  recruited
• Primary endpoints
• Recruitment rates including demographics of
  participants and feasibility of identifying an
  at-risk population in general practice
• Acceptability of the screening test in a
  primary care population
• Potential psychological harms associated with
  the screening test
• Secondary endpoint
• Increase sensitivity and specificity of test by
  employing novel biomarkers
• The data presented here are the pilot
  data from GP surgeries in East Anglia

• 94/129 (73) had ongoing reflux and 12 (9)
  had symptoms more than once a day.
• 19(15) had poorly controlled symptom despite
  being on medication

• The best combination of biomarkers were Alcian
  blue and M1 intensity gt2
• It yielded a sensitivity of 76 and a
  specificity of 92

Anxiety associated with Screening
Prevalence of Barretts Oesophagus in our ongoing
study
Feelings about Barretts Oesophagus

• Prevalence of Barretts oesophagus with
  intestinal metaplasia was 4 (3) out of 129 on
  endoscopy. Male to Female ratio was 11 and the
  mean age at diagnosis was 60 yrs
• Diagnosis of BE was made in 3 out of 4 using
  the sample obtained from the capsule sponge
  device using the best combination of biomarkers.
  All 3 patients diagnosed on sponge test had
  length of BE 2cm circumference and one patient
  who could not be diagnosed had lt 2cm
  circumference of BE on endoscopy

Mean score
Capsule sponge device
Day 0
Day 7
Day 90
Day 0
Day 7
P 0.517
P 0.6087
Day 90
P lt0.001
P lt0.001
Between Day 0 day 90 P 0.6273
Between Day 0 day 90 P lt0.001

• 25 of contacted patients participate in this
  screening study. This response is similar to the
  response noted in the previous primary care
  reflux related questionnaire study 5
• Screening did not induce unnecessary general
  anxiety. Patients had only short lived anxiety
  related to a diagnosis of Barretts oesophagus
• The capsule sponge is safe and was well
  tolerated
• These pilot data are encouraging for the
  ongoing study

Conclusion

• Patients general anxiety levels were not
  increased by undergoing screening but their
  anxiety related to a diagnosis of BE increased
  significantly at day 7 (plt0.0001) and reverted
  back to baseline at day 90

This device is MHRA approved in April 2008
(Patent number W007/045896)

• Methodology
• Study inclusion criteriaarched to identify
• Patients 50-70 years old
• Received acid suppressant therapy for gt3 months
  in the last 5 years
• Exclusion criteria
• Patients who had undergo endoscopy in the past
  one year
• Patients known to have Barretts oesophagus
• Patients with significant co-morbid diseases
• Reflux symptoms were assessed using a validated
  reflux questionnaire
• Patients completed the Spielberger state-trait
  anxiety inventory (STAI) , Cancer worry scale
  questionnaires at day 0, 7 and 90 to assess the
  impact of screening on anxiety.
• Acceptability of the capsule sponge was
  measured using a 10 point visual analogue scale
  (0 is unpleasant and 10 is enjoyable) at day 0 ,7
  and day 90

Demographics
Acceptability of capsule sponge device

• The acceptability rating was 6 (range 2-10)
  on the day of the test, 5.5 (range 2-8) on the
  7th day and 4.5 (range 2- 7) out of 10 on day 90
• 2 failed to swallow the sponge
• There were no adverse affects

Sample staining
Acknowledgments We wish to thank the patients who
generously helped with this study and staff of
the Clinical Investigation Ward. This
purpose-built facility has enabled the research
team to conduct the study in a safe clinical
environment and with participant numbers not
otherwise possible in a hospital setting  
Visual analogue scale
Contact sk543_at_hutchison-mrc.cam.ac.uk