IBD high risk groups

IBD high risk groups

Ulcerative colitis

Value (95% CI) CRC prevalence (%) 3.7 (3.2-4.2) Overall annual CRC incidence (%) 0.3 (0.2-0.4) Annual CRC incidence in first decade of UC (%) 0.2 (0.1-0.2) Annual CRC incidence in second decade of UC (%) 0.7 (0.4-1.2) Annual CRC incidence in third decade of UC (%) 1.2 (0.7-1.9) Eaden, JA et al. Gut 2001; 48: 526-35

Population-based studies Study Location Dates Person-year Inc. Relative risk (%) (95% CI) Palli et al 1 Italy 1978-1992 689 0.12 1.79 (0.9-3.3) Winther et al 2 Denmark 1962-1987 1160 0.06 1.05 (0.6-1.8) Bernstein et al 3 Canada 1984-1997 2672 0.16 2.75 (1.9-4.0) Lakatos et al 4 Hungary 1974-2004 723 0.15 - Jess et al 5 Minnesota 1940-2001 378 0.1 1.1 (0.4-2.4) 1-Palli, D et al. Gastroenterol 2000; 119: 647-53; 2-Winther, KV et al. Gastroenterol 2003; 125: 1576-82 3-Bernstein, CN et al. Cancer 2001; 91: 854-62; 4-Lakatos, L et al. Inflam. Bowel. Dis. 2006; 12: 205-11 5-Jess, T et al. Gastroenterol 2006;130:1039-46

Ulcerative colitis Disease duration Extent of inflammatory bowel disease Age at onset Family history Primary Sclerosing cholangitis (PSC) Severity of inflammation Dysplasia

Ulcerative colitis Disease duration Extent of inflammatory bowel disease Age at onset Family history Severity of inflammation Primary Sclerosing cholangitis (PSC) Dysplasia

Copenhagen N=783 Diagnosis: 1960-1978 Observation: 6.7 years (1-18) Cumulative colectomy rate (18 years): 31% Annual risk CRC: 0.07% Cumulative risk after 18 years: 1.4% (0.7-2.8) Hendriksen, C et al. Gut 1985; 26: 158-63

Copenhagen N=1161 Diagnosis: till 1987 Observation: 11.7 years (0-26) Cumulative colectomy rate (25 years): 32.4% Cumulative risk after 25 years: 3.1% (0.0-6.8) Langholz, E et al. Gastroenterol 1992; 103: 1444-51

Ulcerative colitis Disease duration Extent of inflammatory bowel disease Age at onset Family history Primary Sclerosing cholangitis (PSC) Severity of inflammation Dysplasia

Gyde et et al. Gut 1998; 29: 206-17

Ulcerative colitis Disease duration Extent of inflammatory bowel disease Age at onset Family history Severity of inflammation Primary Sclerosing cholangitis (PSC) Dysplasia

Age at onset UC Age groups (years) Male IRR Female IRR All IRR Birth 39 years 17.3 (5.20-65.6) 7.64 (1.52-35.5) 12.4 (5.04-31.7) 40 59 years 3.37 (1.54-6.90) 1.62 (0.56-3.85) 2.44 (1.35-4.17) 60 + years 2.12 (1.16-3.67) 2.05 (1.07-3.66) 2.09 (1.36-3.11) Total 3.17 (2.18-4.62) 2.16 (1.39-3.36) 2.71(2.04-3.59) Bernstein CN et al. Cancer 2001;91;854-62

Age at onset UC Age groups Duration Disease Observed Expected SIR 95% CI 0 29 years < 14 yr 12 4.9 2.5 1.3-4.3 > 15 yr 18 5.2 3.4 2.0-5.4 30 49 years < 14 yr 22 15.8 1.4 0.9-2.1 > 15 yr 21 13.8 1.5 0.9-2.3 > 50 years < 14 yr 36 38.9 0.9 0.7-1.3 > 15 yr 70 59.2 1.2 0.9-1.5 Karlén P et al. Am J Gastroenterol 1994;94;1047-1052

Gyde et et al. Gut 1998; 29: 206-17

Ulcerative colitis Disease duration Extent of inflammatory bowel disease Age at onset Family history Severity of inflammation Primary Sclerosing cholangitis (PSC) Dysplasia

Family history Family history CRC O E SIR (95% CI) RR (95%CI) All patients Total 143 9.7 15 (12-17) NO 130 9.3 14 (11-17) 1 Yes 13 0.4 31(16-52) 2.5 (1.4-4.4) UC Total 103 5.2 20 (16-24) NO 95 5.0 19 (15-23) 1 Yes 8 0.2 34 (15-68) 2.0 (1.0-4.1) Askling J et al. Gastroenterol 2001;120.1356-1362

Ulcerative colitis Disease duration Extent of inflammatory bowel disease Age at onset Family history Primary Sclerosing cholangitis (PSC) Severity of inflammation Dysplasia

PSC PSC- UC (n=58) 10 20 25 Years CRC risk 9 31 50 (%) UC (n=40) 10 20 25 CRC risk 2 5 10 Years (%) Broome, U et al. Hepatology 1995; 22: 1404-8

Ulcerative colitis Disease duration Extent of inflammatory bowel disease Age at onset Family history Primary Sclerosing cholangitis (PSC) Severity of inflammation Dysplasia

Normal Mucosa Inflammation Carcinoma

Severity of inflammation 3 P<0.001 Score of inflammation 2.5 2 1.5 1 0.5 p=0.001 Colonoscopic inflammation Histological inflammation 0 Controls UC-Carcinoma Rutter et al. Gastroenterol 2004;126:451-459

Severity of inflammation Variable Group odds ratio (95% CI) p value Normal colonic no 1 yes 0.38 (0.19-0.73) 0.003 Inflammatory polyps no 1 yes 2.29 (1.28-4.11) 0.005 Colonic stricture no 1 yes 4.62 (1.03-20.8) 0.05 Rutter MD et al. Gut 2004;53.1813-1816

Ulcerative colitis Disease duration Extent of inflammatory bowel disease Age at onset Family history Primary Sclerosing cholangitis (PSC) Severity of inflammation Dysplasia

Normal Mucosa Inflammation Dysplasia

Dysplasia Probability of finding cancer If colectomy done Immediately After follow-up Low-grade 1 3/16 (19%) 17/204 (8%) Low-grade 2 2/11 (19%) Low-grade 3 2/10 (20%) 7/36 (19%) 1-Bernstein et al. Lancet 1994; 343: 71-4 ; 2-Ullman et al. Gastroenterol 2003;125: 1311-9 3-Rutter, DR et al. Gastroenterol 2006; 130: 1030-1038

Dysplasia Progression of LGD to HGD or cancer Year Hospital LGD (n) Rate Connel et al 1 1994 St. Marks 9 54% - 5 years Ullman et al 3 2003 M. Sinai 46 53% - 5 years Rutter et al 3 2006 St. Marks 47 23% - 5 years Lindberg et al 4 1996 Huddinge 37 35% - 20 years Lim et al 5 2003 Leeds,UK 29 10% - 10 years 1-Connel et al. Gastroenterol 1994 ; 2-Ullman et al. Gastroenterol 2003;125: 1311-9 3-Rutter, DR et al. Gastroenterol 2006; 4- Lindber et al. Scand J Gastroenterol 1996;31:1195-2041030-1038;5-Lim et al.

Dysplasia Probability of finding cancer If colectomy done Immediately After follow-up DALM 1 17/40 (43%) - High-grade 1 10/24 (42%) 15/47 (32%) High-grade 2 8/12 (67%) - High-grade 3 5/11 (46%) 2/ 8 (25%) 1-Bernstein et al. Lancet 1994; 343: 71-4 ; 2-Connel et al. Gastroenterol 1994; 107: 934-44 3-Rutter, DR et al. Gastroenterol 2006; 130: 1030-1038

Crohn s disease

Canavan et al. Alimentary Pharmacol Thera 2006;23;1097-1104

Crohn s disease Colonic disease Study N Colonic Disease CRC (n=) SIR or RR SIR or RR (colonic disease) Weedon et al 1973 449 356 8 26.6(8.6-34.4) NR Gyde et al 513 381 9 4.3 (p<.001) 23.8(p<.001) 1980 Greenstein et al 579 327 7 NR 6.9 (p<.001) 1981 Gillen et al 281 214 8 3.4(1.47-6.71) 18.2 1994 Ekbom et al 1655 830 12 2.5(1.3-4.3) 5.6(2.1-12.2) 1990 Jess et al 314 223 6 1.9(0.7-4.1) 0.8(0.02-4.7) 2006 Friedman S. Gastroenterol Clin N Am 2006;35;621-639

CD Young age at onset Study N Colonic Disease CRC (n=) SIR or RR SIR or RR (colonic disease) Weedon et al 449 356 8 1973 Gyde et al 513 381 9 1980 26.6(8.6-34.4) NR 4.3 (p<.001) 23.8(p<.001) Greenstein et al 579 327 7 NR 6.9 (p<.001) 1981 Gillen et al 281 Only patients 214 < 21 years 8 at onset of CD 3.4(1.47-6.71) 18.2 1994 Ekbom et al 1655 830 12 2.5(1.3-4.3) 5.6(2.1-12.2) 1990 Jess et al 314 223 6 1.9(0.7-4.1) 0.8(0.02-4.7) 2006 Weedon Dd et al. N E J Med 1973;289;1099-102

CD Young age at onset Study N Colonic Disease CRC SIR or RR SIR or RR Age of onset (n=) CRC Risk (colonic disease) < Weedon 30 yr et al 449 35620.9 (6.8-48.7) 8 26.6(8.6-34.4) NR 1973 > 30 yr 2.2 (0.6-5.7) Gyde et al 513 381 9 4.3 (p<.001) 23.8(p<.001) 1980 Greenstein et al 579 327 7 NR 6.9 (p<.001) Ekbom et al. Lancet 1990;336:357-9 1981 Gillen et al 281 214 8 3.4(1.47-6.71) 18.2 1994 Ekbom et al 1655 830 12 2.5(1.3-4.3) 5.6(2.1-12.2) 1990 Jess et al 314 223 6 1.9(0.7-4.1) 0.8(0.02-4.7) 2006

CD Young age at onset Study N Colonic Disease CRC SIR or RR SIR or RR Age at onset (n=) CRC Risk (colonic disease) Weedon < 30 etyr al 449 356 22 (2.7-80.3) 8 26.6(8.6-34.4) NR 1973 Gyde et al 513 381 9 4.3 (p<.001) 23.8(p<.001) 1980 Greenstein et al 579 327 7 NR 6.9 (p<.001) 1981 Jess T et al. Gastroenterol 2006;130:1039-46 Gillen et al 281 214 8 3.4(1.47-6.71) 18.2 1994 Ekbom et al 1655 830 12 2.5(1.3-4.3) 5.6(2.1-12.2) 1990 Jess et al 314 223 6 1.9(0.7-4.1) 0.8(0.02-4.7) 2006 Friedman S. Gastroenterol Clin N Am 2006;35;621-639

CD Extent of disease Extensive CD (n=125) CRC risk 22 years 8% Extensive UC (n=486) CRC risk 20 years 7% Gillen CD et al. Gut 1994; 35: 1590-2

CD Duration of the disease CD (n=314) 1 5 15 25 CRC risk 0.3 1.6 2.4 Years (%) CD 2 10 20 30 CRC risk 2.9 5.6 8.3 Years (%) 1-Jess T et al. Gastroenterol 2006; 130:1039-46 2-Canavan et al. Alimentary Pharmacol Therap. 2006; 23:1097-1104

Dysplasia Distant dysplasia in CRC Patients with CRC Patients with distant dysplasia Craft et al 2 2(100%) Simpson et al 3 1(33%) Petras et al 6 4(67%) Cooper et al 2 1(50%) Hamilton et al 10 6(60%) Richards et al 5 5(100%) Stahl et al 22 6(27%) Sigel et al 19 9(41%) Adapted from Ullman. J Clin Gastroenterl 2003;36:s76

Strictures % OF MALIGNANT STRCTURES 12 10 8 6 4 2 0 N= 132 0-9 10-12 >20 Years of Crohn s disease Yamazaki Y et al. Am J Gastroenterol 1991;86:882-885

CD Ulcerative colitis Disease duration Colonic disease Age at onset Dysplasia Stenosis Diversion segment Disease duration Extent of inflammatory bowel disease Age at onset Family history Primary Sclerosing cholangitis (PSC) Severity of inflammation Dysplasia

IBD high risk groups Minor risk Mild disease activity High risk group Chronic active Severe activity PSC Chronic active Severe activity Young age onset Long duration Total colectomy