What are clinical and endoscopic predictors of CRC in IBD?
Reported estimates of overall CRC risk in UC vary substantially, with studies from tertiary referral centres generally reporting higher rates than population-based surveys. A meta-analysis of 116 international studies found an overall prevalence of CRC to be 3.7% in any patient with UC, increasing to 5.4% for those with pancolitis. The risk of CRC in CD has been less well studied, but overall seems similar to that in UC. Emerging evidence indicates that various disease-related factors significantly influence an individual’s risk for CRC in IBD.
Disease duration is recognised to be a risk factor for CRC in IBD. The development of cancer within 8-10 years of disease onset is unusual. A meta-analysis of 116 studies concluded that the risk of CRC in UC was 2% after 10 years, 8% after 20 years, and 18% after 30 years. An association between disease duration and CRC risk in CD is less clear. The development of CRC within eight years has been reported in up to 40% of some pathology series, though epidemiological studies have generally shown CD related CRC to be more common in patients with long disease duration.
In both ulcerative colitis and Crohn’s disease, patients with more extensive disease are at increased risk of CRC. Disease extent is defined on the basis of macroscopic and histological changes at any time during a patient’s illness. In a combined British and Swedish study the relative risk for patients with total ulcerative colitis was 19.2, and for those with left-sided disease, a relative risk of 2.8 was reported. In a separate Swedish cohort study, the relative risk for patients with pancolitis, left-sided colitis, and proctitis was 14.8 (95% CI, 11.4-18.9), 2.8 (95% CI, 1.6-4.4) and 1.7 (95% CI, 0.8-3.2), respectively. In contrast, the CRC risk is not increased in UC patients with proctitis or procto-sigmoiditis or individuals with ileal or ileocaecal CD.
Primary Sclerosing Cholangitis (PSC)
UC patients with co-existing PSC are especially at risk of developing colonic neoplasia. Dysplasia occurred in 45% of patients with both PSC and UC compared with 16% with UC only (p<0.002). The absolute cumulative risk of developing CRC with UC and PSC was 9%, 31% and 50% at 10 years, 20 years, and 25 years respectively. The comparative rates for CRC in patients with UC only were 2%, 5% and 10% (p<0.001). Data concerning CRC incidence in patients with CD and PSC are unknown.
Family History of Sporadic CRC
According to a registry-based follow-up series, a personal family history of CRC was associated with a 2.5-fold increased risk of CRC in patients with IBD (RR 2.5; 95% C.I. 1.4-4.4). Moreover, patients with IBD who had a first-degree relative diagnosed with CRC before the age of 50 years had an even higher risk of developing CRC themselves (RR 9.2;95% CI, 3.7-23).
The most important predictive factor for the development of CRC in IBD is the presence of mucosal dysplasia. Dysplasia is classified on the basis of its severity, and a progression from low grade to high grade has been demonstrated in some (but not all cases) before malignancy ensues. The diagnosis and classification of dysplasia is qualitative and subject to inter-observer variability. Preferably, its diagnosis and grading should be confirmed by a second independent experienced gastrointestinal pathologist. The Vienna classification is an internationally agreed standard which grades dysplasia in IBD based on the severity of histological changes. Depending on its severity and gross appearance, dysplasia is associated with a high risk of imminent or established colorectal cancer.
Severity of Endoscopic and Histologic Inflammation
Recent studies indicate that neoplastic transformation in IBD is related to the degree of mucosal inflammation. A case-control study of 68 patients with UC showed that the degree of colonoscopic (OR 2.5; p<0.001) or histologic (OR 5.1; p<0.001) inflammation was associated with the development of CRC. Importantly, this study also showed that colitic patients without evidence of inflammation did not have an increased risk of developing CRC (OR 0.28; 95% C.I. 0.19-73). Gupta reported that overall inflammation score was positively associated with the development of high grade dysplasia and CRC but not with low grade dysplasia. Other endoscopic indicators of past inflammation have been shown to be associated with an increased CRC risk in UC, including colonic strictures, a shortened tubular colon and the presence of post-inflammatory polyps.
In CD, clinical studies have consistently shown that CRC may develop in intestinal segments that have been bypassed or complicated by strictures or fistulae. Patients with complicated anorectal disease are particularly at risk of anorectal malignancy.
- Eaden JA, Abrams KR, Mayberry JF. The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut 2001 Apr;48(4):526-35 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11247898].
- Hamilton SR. Colorectal carcinoma in patients with Crohn's disease. Gastroenterology 1985 Aug;89(2):398-407 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/2989075].
- Stahl TJ, Schoetz DJ Jr, Roberts PL, Coller JA, Murray JJ, Silverman ML, et al. Crohn's disease and carcinoma: increasing justification for surveillance? Dis Colon Rectum 1992 Sep;35(9):850-6 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/1511645].
- Gillen CD, Walmsley RS, Prior P, Andrews HA, Allan RN. Ulcerative colitis and Crohn's disease: a comparison of the colorectal cancer risk in extensive colitis. Gut 1994 Nov;35(11):1590-2 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/7828978].
- Ekbom A, Helmick C, Zack M, Adami HO. Increased risk of large-bowel cancer in Crohn's disease with colonic involvement. Lancet 1990 Aug 11;336(8711):357-9 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/1975343].
- Gyde SN, Prior P, Allan RN, Stevens A, Jewell DP, Truelove SC, et al. Colorectal cancer in ulcerative colitis: a cohort study of primary referrals from three centres. Gut 1988 Feb;29(2):206-17 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/3345932].
- Ekbom A, Helmick C, Zack M, Adami HO. Ulcerative colitis and colorectal cancer. A population-based study. N Engl J Med 1990 Nov 1;323(18):1228-33 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/2215606].
- Farraye FA, Odze RD, Eaden J, Itzkowitz SH. AGA technical review on the diagnosis and management of colorectal neoplasia in inflammatory bowel disease. Gastroenterology 2010 Feb;138(2):746-74, 774.e1-4; quiz e12-3 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20141809].
- Practice Parameters Committee of the American College of Gastroenterology, Kornbluth A, Sachar DB. Ulcerative colitis practice guidelines in adults: American College Of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol 2010 Mar;105(3):501-23; quiz 524 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20068560].
- Brentnall TA, Haggitt RC, Rabinovitch PS, Kimmey MB, Bronner MP, Levine DS, et al. Risk and natural history of colonic neoplasia in patients with primary sclerosing cholangitis and ulcerative colitis. Gastroenterology 1996 Feb;110(2):331-8 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/8566577].
- Broomé U, Löfberg R, Veress B, Eriksson LS. Primary sclerosing cholangitis and ulcerative colitis: evidence for increased neoplastic potential. Hepatology 1995 Nov;22(5):1404-8 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/7590655].
- Askling J, Dickman PW, Karlén P, Broström O, Lapidus A, Löfberg R, et al. Family history as a risk factor for colorectal cancer in inflammatory bowel disease. Gastroenterology 2001 May;120(6):1356-62 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11313305].
- Itzkowitz SH. Molecular biology of dysplasia and cancer in inflammatory bowel disease. Gastroenterol Clin North Am 2006 Sep;35(3):553-71 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16952740].
- Bernstein CN. Surveillance programmes for colorectal cancer in inflammatory bowel disease: have we got it right? Gut 2008 Sep;57(9):1194-6 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18719132].
- Schlemper RJ, Riddell RH, Kato Y, Borchard F, Cooper HS, Dawsey SM, et al. The Vienna classification of gastrointestinal epithelial neoplasia. Gut 2000 Aug;47(2):251-5 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/10896917].
- Rutter M, Saunders B, Wilkinson K, Rumbles S, Schofield G, Kamm M, et al. Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis. Gastroenterology 2004 Feb;126(2):451-9 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/14762782].
- Gupta RB, Harpaz N, Itzkowitz S, Hossain S, Matula S, Kornbluth A, et al. Histologic inflammation is a risk factor for progression to colorectal neoplasia in ulcerative colitis: a cohort study. Gastroenterology 2007 Oct;133(4):1099-105; quiz 1340-1 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17919486].
- Rutter MD, Saunders BP, Wilkinson KH, Rumbles S, Schofield G, Kamm MA, et al. Cancer surveillance in longstanding ulcerative colitis: endoscopic appearances help predict cancer risk. Gut 2004 Dec;53(12):1813-6 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15542520].
- Connell WR, Sheffield JP, Kamm MA, Ritchie JK, Hawley PR, Lennard-Jones JE. Lower gastrointestinal malignancy in Crohn's disease. Gut 1994 Mar;35(3):347-52 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/8150345].