Praveen Rajasekhar

WEO CRC SC Meeting DDW 2013

DDW 2013

Possible conflicts of interest*

Sponsor

WEO Colorectal Cancer Screening Meeting, Orlando, May 17, 2013

No conflicts of interest to declare

DISCARD II When can we leave polyps

behind?
Presenter: Dr Praveen Rajasekhar (Clinical Research Fellow)
Institution: Northern Region Endoscopy Group
* Past 24 months

Dr Praveen Rajasekhar, Northern Region Endoscopy Group

Background

Methods of providing an optical

diagnosis

High quality colonoscopy can influence incidence

through the detection and resection of premalignant
colorectal adenomas.
The majority of polyps detected are small or diminutive
with little chance of harbouring cancer or advanced
histology1.
The ability to accurately provide an optical diagnosis
would allow us to leave distal hyperplastic polyp in situ
and resect and discard small adenomas.

White light (WL)

Traditional chromoendoscopy

1. Gupta et al. Gastrointest Endosc. 2012 May; 75(5): 1022-30

1. Kudo et al. Gastrointest Endosc. 1996;44:8-14

2. Togashi K et al. Dis Colon Rectum 1999;42:1602-8

Dr Praveen Rajasekhar, Northern Region Endoscopy Group

Electronic Chromoendoscopy
FICE
Sensitivity of 92.7% can be achieved1.

i-Scan
Sensitivity of 95%, specificity of 82% and accuracy of 92%2.

NBI
Meta-analysis demonstrated sensitivity of 91.0% (CI 87. 93.5)
and specificity of 82.6% (79.0-85.7)3.
Surveillance: agreed with histology in 92.5% (CI 87.9-96.3)
1. Pohl et al. Gut. 2009:58;73-8
2. Pigo et al. Int Journ Colorectal Dis. 2013;28:399-406
3. McGill et al. Gut. 2013: Apr; Epub

Dr Praveen Rajasekhar, Northern Region Endoscopy Group

Accurate in expert hands1.

Not in widespread use in the UK.
Shallow learning curve2.

Electronic chromoendoscopy
i-Scan Pentax.
Fujinon Intelligent Colour Enhancement FICE.
Narrow band imaging (NBI) - Olympus.

Dr Praveen Rajasekhar, Northern Region Endoscopy Group

Detect Inspect Characterise Resect

and Discard - DISCARD
Aimed to evaluate whether optical diagnosis for small
polyps using NBI is feasible and safe.
Single expert centre.
Four colonoscopists of varying experience
2 experts (>10,000 colonoscopies, >1000 cases with NBI).
1 trainee (<500 colonoscopies, <50 cases with NBI).
1 nurse endoscopists (>3000 colonoscopies, <10 cases with
NBI).

Primary outcome: accuracy of optical diagnosis in

differentiating adenomas from non-neoplastic lesions.

Dr Praveen Rajasekhar, Northern Region Endoscopy Group

Praveen Rajasekhar
WEO CRC SC Meeting DDW 2013

Detect Inspect Characterise Resect

and Discard - DISCARD

Detect Inspect Characterise Resect

and Discard - DISCARD

Summary of per polyp results1

Significant difference in accuracy between expert and

non-experts (95% vs. 87%).
The accuracy of surveillance interval provided by
optical diagnosis was 98%.
Cost savings were up to 77%.
Histopathology
Clinic follow-up

1. Ignjatovic et al. Lancet Oncol;10:1171-8

Dr Praveen Rajasekhar, Northern Region Endoscopy Group

Dr Praveen Rajasekhar, Northern Region Endoscopy Group

What about non-expert centres?

DISCARD II Funded by the NIHR

Recent study in Holland has suggested that accuracy

is lower among non-experts1.
Three non-academic endoscopists
An optical diagnosis per polyp and surveillance interval
(when possible) was provided.
Sensitivity and specificity per polyp was 77.0% (95%
CI 68.4 83.8) and 78.8% (95% CI 70.6 85.2).
Surveillance interval incorrect in 19%.

Prospective, blinded calibration study.

Performed within the Northern Region Endoscopy
Group (NREG)
Multi-centre study
6 district general (community) hospitals.

A total of 37 colonoscopists

NHS Bowel Cancer Screening Programme colonoscopists

Physicians
Surgeons
Nurse endoscopists

1. Kuiper T et al. Clin Gastroenterol Hepatol. 2012; 10:1016-20

Dr Praveen Rajasekhar, Northern Region Endoscopy Group

DISCARD II

Dr Praveen Rajasekhar, Northern Region Endoscopy Group

NICE classification1

All colonoscopists had to pass a validated training

module1.
Thirty still, non-magnified photographs of polyps in NBI
before and after a training module.
Takes approximately 20 minutes to complete.
Utilises the NICE classification to help distinguish
between hyperplastic and adenomatous polyps.

1. Ignjatovic et al. Gastrointestin Endosc. 2011;73:128-33

1. Hewett D, Rex D. NBI Training module.

Dr Praveen Rajasekhar, Northern Region Endoscopy Group

Dr Praveen Rajasekhar, Northern Region Endoscopy Group

Praveen Rajasekhar
WEO CRC SC Meeting DDW 2013

Pop Quiz

Dr Praveen Rajasekhar, Northern Region Endoscopy Group

Pop Quiz

Dr Praveen Rajasekhar, Northern Region Endoscopy Group

Pop Quiz

Dr Praveen Rajasekhar, Northern Region Endoscopy Group

Pop Quiz

Dr Praveen Rajasekhar, Northern Region Endoscopy Group

Outcome measures

Statistical Analyses

Primary outcome: to assess the accuracy with which

surveillance interval could be determined by optical
diagnosis.

Designed to estimate a test sensitivity of 95% (with a

95% CI +/-2.5%).

Secondary outcomes:

Per polyp sensitivity, specificity and accuracy.

False negative rate
Learning curve and maintenance of quality of optical diagnosis
Cost saving

Dr Praveen Rajasekhar, Northern Region Endoscopy Group

Estimate we will require 2500 in total to get 290

patients with at least one adenoma in whom a
surveillance interval (including no surveillance).
A proportion of histopathological samples (20%) will be
double reported.

Dr Praveen Rajasekhar, Northern Region Endoscopy Group

Praveen Rajasekhar
WEO CRC SC Meeting DDW 2013

Patient eligibility

Phases of DISCARD II

Inclusion criteria:

Phase 1

Attending for non-emergency colonoscopy.

Over 18 years of age
Able to provide valid written, informed consent.

Exclusion criteria:
Known IBD
Known polyposis syndromes.
Pregnant (self reported)

Phase 2
As for phase 1.
Polyps < 10mm detected.

Dr Praveen Rajasekhar, Northern Region Endoscopy Group

Study flow chart

Dr Praveen Rajasekhar, Northern Region Endoscopy Group

Polyp assessment

Eligible + consents

Baseline data
collection

Colonoscopy

No polyps < 10mm = phase 1

Eligible.
Consent provided.
Baseline data collected (demographics, social history, past
medical history, drug history).
No polyps or only polyp >10mm found.

Polyps < 10mm = phase 2

When a polyp is detected:

Assess with white light (WL).

Size (mm).
Site.
Shape (Paris classification).
Photograph (WL and NBI).
Assessed with NBI (as per NICE classification).
Optical diagnosis (adenoma, hyperplastic, other, cancer).
Confidence level given.
Resected or biopsied (optical diagnosis not provided to lab).
Surveillance interval if all polyps <10mm.

Research nurse/fellow present for data collection

Dr Praveen Rajasekhar, Northern Region Endoscopy Group

Dr Praveen Rajasekhar, Northern Region Endoscopy Group

Other data at colonoscopy

Surveillance interval

Indication for procedure.

Total colonoscopy time.

All histological surveillance intervals (according to BSG

guidelines) assigned by Principal Investigator at each
site.

Quality of bowel preparation.

Blinded to optical diagnosis.

Colonoscope and processor used.

Hypothetical surveillance interval provided with

colonoscopy and histology results in isolation.

Immediate complications.

Dr Praveen Rajasekhar, Northern Region Endoscopy Group

Clinical surveillance interval provided taking into

account other factors.
Dr Praveen Rajasekhar, Northern Region Endoscopy Group

Praveen Rajasekhar
WEO CRC SC Meeting DDW 2013

Progress

Further work

Training module successful at improving test scores

(including those with no previous endoscopy
experience).
Recruitment commenced in July 2012: one unit opened
initially as pilot site.
All sites now recruiting.
Over 600 patients recruited of whom 44% entered
phase 2.
Currently scheduled to complete recruitment ahead of
target.

Generalisability of optical diagnosis using NBI.

Dr Praveen Rajasekhar, Northern Region Endoscopy Group

Acceptability of a resect and discard policy

Clinicians
Patients
National societies

Durability of training.
Ongoing quality assurance.
Intermittent histological validation
Predicted ADR?
Dr Praveen Rajasekhar, Northern Region Endoscopy Group

Pop Quiz Results

Study Team

Polyp 1 = HP

Polyp 2 = Adenoma
Polyp 3 = Adenoma
Polyp 4 = Adenoma

Dr Praveen Rajasekhar, Northern Region Endoscopy Group

Professor Colin Rees

Professor Brian Saunders
Dr Ana Ignjatovic
Dr James East
Dr Matt Rutter
Professor James Mason
Dr Helen Close
Mrs Rebecca Maier
Dr Helen Hancock

Dr Praveen Rajasekhar, Northern Region Endoscopy Group

Thank you for listening

Any Questions?

Dr Praveen Rajasekhar, Northern Region Endoscopy Group