ibd and colorectal cancer surveillance - weo€¦ · cause of death in 10-15% of ibd crohns colitis...

IBD and colorectal cancer surveillance

Combined Colorectal Symposium Sunday 24 Sep 2017 Combined Colorectal Symposium S-12 13:30-15:00 Room S426+S427 (4/F)

IBDSydney

Prof Rupert Leong

why screen? when, on whom, how often? how to screen? how to manage dysplasia?

Prof Rupert Leong

Protection

mesalazine, azathioprine, ursodeoxycholic

acid

Inflammation

Dysplasia

Cancer

Immutable Risks Modifiable Risks

young age diagnosis active disease

extensive colitis backwash ileitis

foreshortened colon

pseudopolyps

family history CRC

primary sclerosing

cholangitis

Rutter Gastroenterol 2004 Rubin Gastroenterol 2006 (abst)

Gupta Gastroenterol 2007 Jess Am J Gastro 2007

Prof Rupert Leong

Beaugerie N Engl J Med 2015

Aberrant Crypt → Dysplasia → Sporadic Cancer

Inflammation → Flat Dysplasia → Colitis-Associated Cancer

polyp

flat dysplasia

APC aneuploidy

methylation

MSI k-ras

COX-2 c-SRC DCC/ DPC4 p53

P53, LOH DCC c-SRC k-ras APC

Prof Rupert Leong

Aberrant Crypt → Dysplasia → Sporadic Cancer

Inflammation → Flat Dysplasia → Colitis-Associated Cancer

easy to identify and treat

hard to identify and treat

Sporadic

Colitis

Prof Rupert Leong

*

Prof Rupert Leong

cause of death in 10-15% of IBD Crohns colitis similar to ulcerative colitis

ECCO statement 8C (UC 2017) Surveillance colonoscopy may permit earlier detection of colorectal cancer with a corresponding improved prognosis [EL 3]

ulcerative colitis Crohns disease

RR (95% CI) 2.7 (1.9-4.0) 2.6 (1.7-4.1)

Absolute cumulative CRC frequency 8% 20 years 7% 20 years

Bernstein Cancer 2001

decreased interval cancer, probably acceptable cost benefit

Collins Cochrane 2006

Prof Rupert Leong

risk increases with duration of IBD

0

5

10

15

20

25

0 10 20 30

Selinger, Leong Clin Gastroenterol Hepatol 2014

Eaden Gut 2001

2001 1 in 5

2014 1 in 14

0

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15

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25

0 10 20 30

High Low

Cu

mu

lati

ve R

isk

of C

RC

(%

)

Asia Pacific Cohort Prevalence Duration UC

Vellore, India Venkataraman J Gastro Hep 2005

532 UC 0.9% CRC 4.4% <20yr 5.8% >20yr

extent

Mumbai, India

Desai World J Gastro 2015 430 UC 2.8% CRC extent duration

active colitis

New Dehli, India

Bopanna UEGJ 2017 1,012 2.0% CRC 1.5% 10yr 7.2% 20yr

23.6% 30yr

KASID, Korea

Kim B J Gastro Hep 2009 7,061 UC 0.37% CRC 0.7% 10yr 7.9% 20yr

33.2% 30yr

Guangzhou, China

Gong Dig Dis Sci 2012 3,922 UC 0.87% CRC 1.2% 10yr 3.6% 20yr

14.4% 30yr

Taipei, Taiwan

Wei J Chin Med Assoc 2013 406 UC 1.5% CRC

Sydney, Australia

Selinger Clin Gastro Hep 2014 504 UC 4.8% CRC 1% 10yr 3% 20yr 7% 30 yr

Prof Rupert Leong

0

5

10

15

20

25

0 10 20 30

Selinger, Leong Clin Gastroenterol Hepatol 2014

Eaden Gut 2001

2001 1 in 5

2014 1 in 14

0

5

10

15

20

25

0 10 20 30

High Low

Cu

mu

lati

ve R

isk

of C

RC

(%

)

Commence

Surveillance Program

Prof Rupert Leong

at least distal colitis 8 years following symptom onset

primary sclerosing cholangitis: annual

This Photo by Unknown Author is licensed under CC BY-SA

ECCO e-guide 2017

http://ramblingsofapr.com/2013/04/15/timehop-back-to-re-lived-content/

https://creativecommons.org/licenses/by-sa/3.0/



Prof Rupert Leong

Interval Risk Factors

Yearly primary sclerosing cholangitis

family history of colorectal cancer <50yo

stricture, pseudopolyps, shortened colon

previous dysplasia

3-yearly inactive disease

family history CRC >50yo

moderate-to-severe colitis

5-yearly 2 previous colonoscopies macroscopically &

colitis <50% of colon surface area

normal-to-mild inflammation

ECCO e-guide NHMRC Surveillance Guidelines

Prof Rupert Leong

detect & enhance flat lesions

Class Dye

contrast: topography • indigocarmine 0.1 – 0.5%

absorptive: vital • methylene blue 0.1% (intestinal)

• crystal violet 0.1% (intestinal, gastric)

• Lugol’s 3% (glycogen)

reactive: chemical • acetic acid 3% (keratin)

• Congo red (pH)

Prof Rupert Leong

Conventional Chromoendoscopy P

Kiesslich

Gastro. 2003

(n = 163)

10 / 81 32 / 82 <0.005

35min 44min

Rutter

Gut 2004

(n = 100)

0 / 2,904 random 7 / 114 targeted 0.02

11min 10min

Hurlstone Endos. 2005

(n = 350)

3 / 369 49 / 644 <0.0001

13min 24min

Marion

AJG 2008

(n = 102)

0.58% 43% <0.0002

22min 15min

chromoendoscopy improves identification of dysplasia [level 1 evidence]

Prof Rupert Leong

40 years surveillance (St Marks, UK)

Increased use of chromoendoscopy

Decrease in interval cancer

Chromoendoscopy: little training, cheap, effective

Leong RW GI Endosc Clin N Am. 2014

Prof Rupert Leong

chromoendoscopy is suggested rather than white-light colonoscopy – Dye based contrast improve epithelial surface detail – targeted biopsies less costly, more effective than

WLC with random biopsies – increase duration of colonoscopy by 11 minutes

Laine Gastroenterol 2015

Prof Rupert Leong

incremental yield of dysplasia higher for chromoendoscopy

Laine Gastroenterol 2015

Prof Rupert Leong

Additional cameras

330˚ field of view Leong RW Gastroenterol 2017

0

10

20

30

40

50

60

70

80

90

100

Dysplasia Miss Rate

con

ven

tio

na

l co

lon

osc

op

y

FU

SE

P=0.0001

Dysplasia miss rate

n=1,000 yield: 0.2% per-biopsy 12/94 subjects with dysplasia identified by random

biopsies

random biopsies recommended previous neoplasia PSC tubular colon

Moussata Gut 2017

Prof Rupert Leong

No of Subjects (n)

Dysplasia Yield % n (95% CI)

%

Targeted biopsies white light without chromoendoscopy

+9

18.0% 16/89 (10.0-26.0)

16.0% Targeted biopsies with chromoendoscopy

10 +7 unique

13.5% 10/74 (5.7-21.3)

Random biopsies 2 +0 unique

0.3% 2/687 (0.0-0.7)

0.3%

P<0.0001

Leong RW Gastroenterol 2017

little advantage with random biopsies

Prof Rupert Leong

Raised

Resectable Not

Resectable

colectomy colectomy

Confirm with 2nd GI pathologist

Prof Rupert Leong

Resectable Irresectable

avoid “DALM”

Prof Rupert Leong

Colectomy Multifocal Unifocal

EMR where visible, close surveillance or Colectomy

LGD HGD

individualise multi-disciplinary

Gastroenterologists n=218

Colorectal Surgeons n =46

P

Knowledge of guidelines (median, IQR)

14 (11-17) 12 (8-16) <0.001

PSC 92% 66% <0.001

Proctitis 17% 51% <0.001

Ileal CD 7% 23% <0.001

predictors of adherence to guidelines:

gastroenterologist (P=0.03)

high knowledge score (P=0.04)

Leong Gastrointest Endosc 2015

Prof Rupert Leong

survey: dye-less vs dye-based chromoendoscopy methylene blue: 27% indigo carmine: 22% narrow band imaging: 54%

Leong Gastrointest Endosc 2015

1995 1997 1999 2001 2003 2005 2007 2009 2011 2013 2015

USA UK NZ Holland Aust

Bernstein Eaden Gearry van Rijn Leong

AJG GIE Dis Col Rect World J Gas GIE

nationwide surveys: 1995 – 2015

improved surveillance performance over time

Prof Rupert Leong

NBI has similar sensitivity than chromoendoscopy

NBI: 8 minutes faster (P<0.001)

per lesion neoplasia detection P=0.79 OR 1.09 (0.6-2.0)

Chromo-endoscopy

n=66

NBI n=65

total neoplastic lesions

31 21

% lesions neoplastic

17.4% 16.3%

Bisschops Gut 2017

Old Paradigm New Paradigm

Western Western & Asia Pacific

OLD PARADIGM NEW PARADIGM



Ulcerative colitis UC & Crohns disease





High rate of dysplasia Lower rate of dysplasia






Invisible dysplasia (SD) Visible dysplasia (HD)

Pre-chromoendoscopy Chromoendoscopy (NBI?)








“DALM” dysplasia-associated lesion or mass

Lesions endoscopically “resectable” or “irresectable”








“DALM” dysplasia-associated lesion or mass

Lesions endoscopically “resectable” or “irresectable”

metachronous dysplasia, colectomy

Endoscopically resected lesion followed by close surveillance


Kisiel Aliment Pharm Ther 2013

Prof Rupert Leong

control inflammation: mucosal healing high risk: PSC, foreshortened colon, prior

dysplasia quality surveillance, chromoendoscopy if high

risk increasing in Asia Pacific

IBDSydney

Prof Rupert Leong

Prof Rupert Leong

biomarkers: risk prediction systems eg faecal DNA testing

can image-enhanced surveillance increase surveillance intervals?

cost effectiveness change natural history in era of biological

agents?

ibd and colorectal cancer surveillance - weo€¦ · cause of death in 10-15% of ibd crohns colitis...

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