Rupert WL LeongDirector of EndoscopySenior Staff Specialist GastroenterologistConcord & Bankstown HospitalsConjoint Associate Professor UNSW

AIBDA SymposiumAIBDA Symposium

Colorectal Cancer SurveillanceColorectal Cancer SurveillanceWhat should we be doing? What should we be doing?

New endoscopy New endoscopy techniques and targeted techniques and targeted

biopsies are now the biopsies are now the standard of care standard of care

• standard white light & random biopsies FAIL to identify treatable flat dysplasia

• newer imaging techniques improves yield 3-10X

• newer techniques recommended by guidelines

• newer techniques are already utilized locally & overseas

Definitions• “new”

– chromoendoscopy (1977+, colitis 2003+) – high definition, zoom endoscopy (2003+)– NBI (2006+)– + targeted biopsies

• “old”– 4 quadrant biopsies every 10cm

PLUS biopsies of any lesions

– 2000cm2 colon SA vs 1.32cm2 random SA33 random biopsies sample <0.1% of the bowel

Why newer endoscopic techniques are required?

• Surveillance colonoscopy in IBD– >33 random colonic biopsies

– interval colorectal cancers (white light)

– 2% of gastroenterologists take >20 biopsies

– >33 biopsies samples only a v small part of the colon

Eaden et al. GI Endosc 2000

Connell et al. Gastroenterol 1994

Rubin et al. Gastroenterol 19921992

Kandiel et al. Visible Human J Endosc. 2008

What is being done? Australia

• online survey– 57%57% use NBI or chromoendoscopy

• others HD, zoom scopes

– 37% perform recommended biopsies

• expert opinion promotes CEFok I, et al. J Gastroenterol Hepatol 2010 (Abst)

Majority of GE already use

newer endoscopic techniques

Efthymiou, Taylor, Kamm, et al. Inflamm Bowel Dis. 2011

What is Being Done? Overseas

• Academic Medical Centre, Amsterdam: – Profs Paul Fockens, Evelien Dekker

•7

Centres of excellence use

newer techniques

Why newer endoscopic techniques are required?

Sporadic Cancer

Normal Colon

Aberrant crypt foci Adenoma Carcinoma

Normal Colon Inflammation

FlatDysplasia

Carcinoma

IBD Cancer

How newer techniques identify flat dysplasia?

• improved resolution, magnification– increases sensitivity, delineates extent

• differential light or dye interaction– improve the yield of dysplasia

Tada et al. Endosc. 1977;8:70–74.

Chromoendoscopy

Is chromoendoscopy difficult? No

• reusable catheter • 2 vials

1. methylene blue 0.1% absorptive (vital)2. indigo carmine 0.1-0.5% topography

1ml dye + 9ml N Saline

Is it difficult? No

– don’t need to learn Kudo classification– don’t need to describe pit pattern

• most evidence at present remains chromoendoscopy

• NBI: vascular network, lesion-mucosa interface

• CE is not required IFIF there is already visible cancer; which is TOO LATE!

• how did it get there?

poor surveillance technique!

• HGD – no invasion– no LN metastasis

Does it work? Yes

Which technique has a higher yield of dysplasia?

• New

• CE in predicting neoplasia: sensitivity 97%; specificity 93%• duration CE = 44 minutes, conventional 35 minutes (ns)

CE in UC Surveillance

• Methylene-blue magnifying CE in UC ≥ 8yr

Kiesslich et al. Gastroenterol 2003

Conventional (n = 81)

Chromoendoscopy(n = 84)

P

Intra-epithelial neoplasias - low grade- high grade

82

248 <0.005

Cancer 1 3 (2 A’s, 1 B) ns

Flat mucosa IN 4 (on random Bx) 24 <0.001

CE in UC Surveillance

• back-to-back conventional colonoscopy vs indigo carmine 0.1% CE

• n=100; 46 neoplastic lesions in 19 patients

Rutter et al. Gut 2004

Conventional (n = 100)

CE(n = 100)

P

Dysplasia:- non-targeted- pre-dye target- dye targeted

- 0/ 2,904 biopsies- 2/ 43 (15-20mm)

- *+7/ 114 (2-6mm)

0.020.06

*

Duration (median) 11min 10min ns

CE in UC Surveillance

• High magnification CE (indigo carmine 0.5%) vs conventional colonoscopy

• n=738; UC ≥ 8 years

Hurlstone et al. Endoscopy 2005

Conventional (n = 350)

High Mag-CE(n = 350)

P

Intra-epith neoplasia- non-targeted- targeted

24- 38/12,482 (0.14%)

- 3/369 (1.6%)

69- 20/12,850 (0.16%)

- 49/644 (8%)

<0.0001

Cancer 1 3 ns

Duration (median) 13min 24min <0.02

CE in Colitis Surveillance

• CE (methylene blue 0.01%) vs WLE • n=102; UC or Crohns colitis

Marion et al. Am J Gastroienterol 2008

Conventional (n = 102)

CE(n = 102)

P

Dysplasia- non-targeted- targeted

3/3264 Bx LGD12/50 LGD1/50 HGD

16/82 LGD1/82 HGD

0.001

Duration (median) 15min 22min ns

0.09%

20.7%

Dysplasia Yield

ConventionalConventional ChromoendoscopyChromoendoscopy PP

Kiesslich

Gastro. 2003 (n = 163)

3X <0.005

35min 44min ns

Rutter

Gut 2004

(n = 100)

3.5X 0.02

11min 10min ns

Hurlstone Endos. 2005

(n = 350)

10X <0.0001

13min 24min

Marion

AJG 2008

(n = 102)

230X <0.0002

15min 22min

NBI vs CE UC Surveillance

• high-res NBI vs high-res CE • n=60; randomised cross-over; colitis >8yr

• BOTH: newer techniques – equivalent

Pellise M, et al. Gastrointest Endosc 2011

NBI(n = 33/27)

CE(n = 27/33)

P

Per-Pt true pos 11/16 12/16 0.727

Withdrawal time 15.7 26.9 <0.01

• 466 surveillance colonoscopies (167 pt) • 11,772 biopsies

van den Broek Am J Gastroenterol 2011

• 1 LGD = positive on random biopsies (all others were targeted biopsies)

Is it recommended? • CCFA: endorses the incorporation of

chromoendoscopy into surveillance colonoscopy… Itzkowitz, Present. Inflamm Bowel Dis 2005

BSG 2011

chromoendoscopy should be the default technique

Does it matter?

• long term outcomes chronic colitis in Australia

• life-time colon cancer risk: 35%

Selinger et al. J Gastroenterol Hepatol. 2011(abst)

New Endoscopic Techniques

• cheap & easy • effective in finding more EARLY dysplasia • acceptable to doctors/ nurses/

pathologists• already performed & recommended

vs random biopsies• slow • difficult for doctors/ nurses/ pathologists • ineffective in finding dysplasia

• IBD Colorectal Cancer Surveillance: What should we be doing?

• purpose of surveillance: find treatable lesions not to miss them

• we should use newer endoscopy techniques

Rupert WL LeongDirector of EndoscopySenior Staff Specialist GastroenterologistConcord & Bankstown HospitalsConjoint Associate Professor UNSW

AIBDA SymposiumAIBDA Symposium

Colorectal Cancer SurveillanceColorectal Cancer SurveillanceWhat should we be doing? What should we be doing?

New endoscopy New endoscopy techniques and targeted techniques and targeted

biopsies are now the biopsies are now the standard of care standard of care

• IBD Colorectal Cancer Surveillance: What should we be doing?

• 10cm 4 quadrant biopsies –negligible yield, samples only 0.01% of colon, expensive pathology, unpopular in Australia

• purpose of surveillance: find early lesions not to miss them

Is it messy?

• A little bit

• But far fewer histology bottles!

Costs

• chromoendoscopy = cheap

• all new video endoscopes = higher resolutions

• large-screen monitors

Is it difficult? No

Strict patient selection: colitis; remission/ steroids

Unmask: bowel prep, wash, insufflation Reduce peristalsis: buscopan, glucagon

Full segmental stainAdd dyeCrypt/ surface irregularities Endoscopic targeted biopsies

Kiesslich et al. Gastroenterol 2003

Procedure/ Withdrawal Times

ConventionalConventional ChromoendoscopyChromoendoscopy PP

Kiesslich

Gastro. 2003 (n = 163)

3X <0.005

35min 44min ns

Rutter

Gut 2004

(n = 100)

3.5X 0.02

11min 10min ns

Hurlstone Endos. 2005

(n = 350)

10X <0.0001

13min 24min

Marion

AJG 2008

(n = 102)

230X <0.0002

15min 22min

Time Saving

• reduced numbers of normal and futile random biopsies

• pathology cost savings

• proper surveillance – may increase repeat colonoscopy interval time (to be validated)

What about training & safety?

• no accreditation recommendations• dyes are safe

– methylene blue: good experience – indigo carmine: inert

• can still perform random biopsies– document disease activity

New Endoscopic Techniques

• cheap & easy • effective in finding more EARLY dysplasia • acceptable to doctors/ nurses/

pathologists• already performed & recommended

vs random biopsies• slow • difficult for doctors/ nurses/ pathologists • ineffective in finding dysplasia