1. Colitis associated cancer: risk and surveillance
Risk and risk factors of CRC in IBD
Molecular pathways of CRC in IBD
Surveillance colonoscopy
Chemoprevention

2. Prevalence and aetiology of colorectal cancer in the general population
Choi PM et al. Gut 1994;35:950-4
Gyde S et al. Gastroenterology 1982;83:36-43

3. Major risk factors Young age at onset Long-disease duration
Extensive disease
Primary sclerosing cholangitis
Genetic susceptibility
Ekbon A et al. Lancet 1990;336:357-9
Langholz E et al. Gastroenterology 1992;103:
Ekbom A et al. NEJM 1990;323:
Munkholm P et al. Gastroenterology 1993;38:
Broome U et al. Gut 1996;38:610-5
Marchesa P et al Am J Gastroenterol 1997;92:1285-8
Nuako KW wr al Gastroenterology 1998;115:
Askling J et al. Lancet 2001;357:262-6

4. Age of onset and CRC risk in Ulcerative Colitis
Age at diagnosis (yr) SIR* (95% CI)
( )
( )
( )
( )
( )
 ( )
Ekbom A et al. NEJM 1990; 323:
* Standardized Incidence Ratio

5. Age of onset and CRC risk in Chron’s Colitis
Age at diagnosis (yr) SIR* (95% CI)
 ( )
 ( )
Ekbom A et al. Lancet 1990; 336:
* Standardized Incidence Ratio

6. Incidence rate of CRC for any patient with UC: overall and by decade
Eaden JA et al. Gut 2001; 48:

7. Cumulative risk of developing colorectal cancer in ulcerative colitis
Eaden JA et al. Gut 2001; 48:

8. Extent of disease and CRC risk in Ulcerative Colitis
Extent of disease SIR* (95% CI)
Proctitis ( )
Left-sided colitis ( )
Pancolitis ( )
Ekbom A et al. NEJM 1990; 323:
* Standardized Incidence Ratio

9. Extent of disease and CRC risk in Chron’s Colitis
Extent of disease SIR* (95% CI)
Terminal ileum ( )
Terminl ileum+part of colon ( )
Colon only ( )
Any colon involvement ( )
Ekbom A et al. Lancet 1990; 336:
* Standardized Incidence Ratio

10. CRC risk in patients with Primary Sclerosing Cholangitis and Ulcerative Colitis
Soetikno RM et al. Gastrointest Endosc 2002; 56: 48-54

11. Colorectal cancer in ulcerative colitis by geographical location
Eaden JA et al. Gut 2001; 48:

12. Colorectal cancer in Crohn’s disease by geographical location
Persson PG et al. Gastroenterology 1994;107:1675-9
Fireman Z et al. Scand J Gastroenterol 1989; 24:
Jess T et al. Gastroenterology 2000; 118: 1472
Munkholm P et al. Gastroenterology 1993;105:
Gillen CD et al. Gut 1994;35:651-5

13. Family history as a risk factor for CRC in IBD
Patients Family history of CRC RR (95% CI)
UC No
Yes (1.0 – 4.1)
CD No
Yes (1.4 – 9.4)
Askling J et al. Gastroenterology 2001; 120:

14. Molecular pathway of CRC in IBD
Itzkowitz S. J Clin Gastroenterol 2003; 36 (S1): S70-S74

15. Pittfalls of Surveillance Colonoscopy
Not proven to reduce mortality from CRC
Sampling error
Experience of local histologist
Low interobserver agreement for low-grade dysplasia
Not universally accepted guidelines

16. Colonoscopic surveillance in UC
Choi PM et al. Gastroenterology 1993;105:

17. Colorectal cancer prevention in ulcerative colitis
Karlen P et al. Gut 1998;42:711-14
Eaden J et al. APT 2000;14:

18. Stage of CRC diagnosed during surveillance program
Author Dukes A Dukes B Dukes C Metastatic
Rosenstock
Jones
Lennard-Jones
Brostrom
Nugent
Lashner
Rozen
Connell

19. Surveillance colonoscopy programme in UC
Case Dukes
Surveillance group
I A
II A
III A
IV A
V B
Non surveillance group
I B
II C
III C
IV C
Hata K et al. Br J Cancer 2003;89:

20. should be performed, respectively,
Sampling error
To exclude dysplasia
with 95% or 90% confidence
should be performed, respectively,
56 or 33 biopsies
Rubin CE et al. Gastroenterology 1992; 103:
Connell WR et al. Gastroenterology 1994; 107:

21. Inter-observer agreement for diagnosis of dysplasia
Ranging from 42% to 65% of the slides
examined by experienced pathologist
Melville DM et al. Hum Pathol 1989;20(10):

22. How gastroenterologists screen for colonic cancer in ulcerative colitis: time of onset of surveillance programm
Eaden JA et al. Gastrointest Endosc 2000;51:123-8

23. How gastroenterologists screen for colonic cancer in ulcerative colitis: number of biopsies taken at colonoscopy
Eaden JA et al. Gastrointest Endosc 2000;51:123-8

24. Guidelines for Colorectal Cancer Screening and Surveillance
“Individuals with longstanding IBD
(pancolitis for 8 or more years or,
left-sided colitis for 15 or more years)
may undergo colonoscopic surveillance
with systematic biopsies every 1-3 years…
ALTHOUGH
there is no direct evidence supporting this practice.”
Gastrointest Endosc 2000; 51(6):

25. Clinical guidelines and rationale for CRC surveillance in patients with long-standing IBD
Surveillance every 1-2 yrs after 8 yrs of disease in patients
with pancolitis or after 15 yrs in those with left-sided colitis
Biopsy specimens should be taken every 10 cm in all 4
quadrants and that additional biopsies should be taken of
strictures and mass lesions other than pseudopolyps.
Polyps that appear potentially dysplastic can be removed by
polypectomy with biopsy of adjacent flat mucosa to determine
if dysplasia is present
No direct supporting evidence and no RCT of surveillance
colonoscopy in patients with IBD
Winawer S et al. Gastroenterology 2003;124:

26. High-grade and Low-grade Dysplasia
Patients with high-grade dysplasia or multifocal low-grade
dysplasia in flat mucosa – if confirmed by experienced
pathologist – should be advised to undergo colectomy
Dysplasia-associated lesion or mass (DALMs) is a
dysplastic mass lesion and is an indication for colectomy
Management of patients with unifocal low-grade dysplasia is
still controversial and colectomy does not share the same
consesus as high-grade or multifocal low-grade dysplasia
Winawer S et al. Gastroenterology 2003;124:

27. Progression of Flat Low-Grade Dysplasia to advanced neoplasia in patients with ulcerative colitis
----- multifocal
….. unifocal
any
Ullman TA et al. Gastroenterology 2003;125:
Ullman TA et al. Am J Gastroenterol 2002;97:

28. Surveillance Strategy
High-grade
Dysplasia
Low-grade
Dysplasia
Indefinite
Dysplasia No
Dysplasia
Polyp
Flat
Polyp
Flat or
COLECTOMY
Completely removed
and no dysplasia
elsewhere ?
Repeat colonoscopy
in 3-6 months:
LGD confirmed ?
Repeat
colonoscopy
in 6-12 months
Repeat
colonoscopy
In 1 – 2 years
yes no
yes no

29. Chromoendoscopy for the detection of intraepithelial neoplasia and colon cancer in UC
Kiesslich R et al. Gastroenterology 2003;124:

30. Correlation between aminosalicylate use and the incidence of cancer
Eaden JA et al. APT 2000; 14:

31. Mesalazine and apoptosis in CRC
Bus PJ et al. APT 1999;13:

32. Folic Acid supplementation and CRC risk in ulcerative colitis
Lashner BA et al. Gastroenterology 1997;112:29-32
Lashner BA et al. Gastroenterology 1989;97:255-9

33. Ursodeoxycholic Acid as a chemopreventive agent in patients with UC and PSC
Pardi DS et al. Gastroenterology 2003;124:

34. Conclusions CRC is an important complication of long standing
UC/CD colitis
Surveillance colonoscopy probably beneficial,
even though not fully evidence-based
Aminosalicylates, ursodiol, folate supplemantation
may contribute to a reduction of CRC
incidence or mortality