Chronic inflammatory bowel disease and cancer

Colorectal cancer represents the major cause for excess morbidity and morta lity by malignant disease in ulcerative colitis as well as in Crohn's disea se. The risk for ulcerative colitis associated colorectal cancer is increas ed at least 2-fold compared to the normal population and colorectal cancer is observed in 5.5-13.5% of all patients with ulcerative colitis and 0.4-0. 8% of patients with Crohn's disease. Established risk factors include long duration of the disease, large extent of the disease, low activity of the d isease, young age at onset, presence of complicating primary sclerosing cho langitis or stenotic disease and possibly lack of adequate surveillance, in adequate pharmacological therapy, folate deficiency and non-smoking. Crohn' s disease is associated with an increased risk of colorectal carcinoma in p atients with long-standing disease, strictures and fistulae under the condi tion that the colon is involved, tumors of the small intestine may occur oc casionally. Extracolonic malignancies are rare, with the exception of bilia ry tract cancer. Ulcerative colitis associated colorectal cancer typically can occur in the entire colon, is often multifocal and of undifferentiated histology. Stage distribution and prognosis of ulcerative colitis associate d colorectal cancer appears to be similar to that of sporadic colorectal ca ncer with an overall survival of about 40% (15-65%) after 5 years with tumo r stage at diagnosis being the most important predictive parameter for surv ival. Tumor markers helpful for the diagnosis of sporadic colorectal cancer fail to differentiate between inflammatory response and malignant transfor mation. In contrast the histologic evidence of dysplasia was shown to be a strong indicator of underlying carcinoma or developing malignant transforma tion. The presence of a surface projection termed dysplasia associated lesi on or mass is highly indicative of underlying or associated cancer. While t he routinely performed search for dysplasia is hampered by high interobserv er variation the demonstration of DNA-aneuploidy or genetic changes which m ay confirm the ongoing malignant transformation has not yet become clinical routine. The genetic alterations found in ulcerative colitis associated co lorectal cancer involve many of the same targets found in sporadic colorect al tumors and include multiple sites of allelic deletion, microsatellite in stabilities, and mutations of APC, p53, Ki-ras as well as MSH2 and other ge nes. The progression of dysplasia to carcinoma is generally accompanied by an accumulation of these mutations and the similarities in the biology of c olorectal cancer associated with ulcerative colitis and sporadic colorectal cancer appear to outweigh their difference. In regard to the management of dysplasia and cancer, the role of surveillance programs for the early dete ction of ulcerative colitis associated colorectal cancer at a curable stage is still under debate. Although these programs failed at tumor prevention and lethal carcinomas are still found inadvertently in patients under surve illance, the majority of surveillance programs could reduce mortality by de tecting more cancers at a still curable stage. Current recommendations for surveillance include, therefore, biennial colonoscopy with extensive biopsi es after 8-10 years of total colitis or after 15-20 years of left-sided col itis. In the presence of cancer or unequivocal high-grade dysplasia and/or dysplasia associated lesion or mass proctocolectomy is considered adequate. The evidence of low-grade dysplasia should be confirmed before proctocolec tomy is considered.