Early onset of ulcerative colitis : long-term follow-up with special reference to colorectal cancer and primary sclerosing cholangitis.

Ulcerative colitis is a chronic inflammatory disease that mainly affects the colon and rectum. Onset of disease is most common between the ages of 15-35 years. There is an observed increased risk of colorectal cancer associated with the disease. The risk is often described to be 2% after 10 years, 8% after 20 years and 18% after 30 years disease. Since 1977, all known patients with ulcerative colitis in the catchment area of Ornskoldsvik Hospital have been invited to attend a colonoscopic surveillance programme. At endpoint of the studies included in this thesis there were 214 patients that had attended the surveillance programme. The aims of these studies have been to evaluate the efficiency of the surveillance programme, analyse the impact of findings of DNA aneuploidy, and determine the outcome for patients that underwent limited resections instead of complete proctocolectomy. Further, we have studied the long-term outcome for patients who had an early onset of disease and analysed the expression of cytokeratin 7 and 20 in respect to findings of dysplasia, DNA aneuploidy and colorectal cancer. At the end of the studies the prevalence for ulcerative colitis was 261/100 000 and the incidence rate was 7.6/100 000/year. During the period 1977-2005, four patients died of ulcerative colitis. Nine colorectal cancers were diagnosed in eight patients, one of whom died of the cancer. Fifty-two patients had findings of dysplasia and five of these patients developed colorectal cancer. In the subgroup of patients studied (N= 147) for DNA aneuploidy, 20 were found to have specimens with DNA aneuploidy on at least one occasion. The sensitivity of aneuploidy for development of dysplasia (LGD or higher) was found to be 0.50 and the specificity 0.94. The investigation of the outcome for the patients that underwent limited resections of the colon or rectum showed that none of the patients under surveillance died of colorectal cancer or metachronous cancer in their remaining colon or rectum. A separate study concerning early onset of ulcerative colitis revealed no particular increased risk of colorectal cancer in this cohort but a fairly high incidence of primary sclerosing cholangitis was seen. In the analyses of cytokeratins it was found that 7 out of 10 patients with low-grade dysplasia and 3 of 6 with high-grade dysplasia were positive for CK7. Our results indicate a possible relationship between the expression of CK7 and CK20 and neoplastic development of colorectal mucosa in patients with ulcerative colitis. The studies on which this thesis is based, were performed on a relatively small number of patients, however the time of observation was long and, most importantly, the patients were from a well defined catchment area. We conclude that the surveillance programme has been efficient in minimising the risk of lethal colorectal cancer. Analysing DNA ploidy helps to target the patients that need more attention but the method cannot stand alone. Our study on cytokeratins points to a relationship between dysplasia and CK7 but the results are preliminary and further studies needs to be done. We have shown that it is safe to do a limited colorectal resection in respect to lethal colorectal cancer. Early onset of ulcerative colitis as a risk factor for colorectal cancer was not found in the group we have studied, which could be due to effective surveillance and/or medication. A fairly high operation rate in this group may also have contributed. The most important variable in the beneficial outcome regarding lethal colorectal cancer in these studies is, in our opinion, the outstanding compliance of the patients to the colonoscopic surveillance programme.