Studies in longstanding ulcerative colitis with special reference to malignant transformation of the colorectal mucosa.

The risk of colorectal carcinoma was estimated retrospectively in a cohort of patients with ulcerative colitis from three defined geographical areas (West Midlands and Oxford regions, England and Stockholm County, Sweden). The cohort consisted of 824 primary referral patients with a diagnosis of ulcerative colitis established within five years from onset of symptoms between 1945-1965. All patients were 15 years of age or more at onset and they were followed for a minimum of 17 years and a maximum of 38 years. There was an eight-fold risk of developing colorectal cancer in the series as a whole, relative to that of the general population. In extensive colitis the risk was nineteen-fold. The cumulative risk of developing cancer in extensive colitis was 12% after 25 years of disease duration. No significant effects of the cancer risk for age at onset, sex or referral centre were detected. Abnormal, aneuploid DNA-content of cell nuclei in colorectal mucosal biopsies was found in five out of 53 patients with longstanding, total ulcerative colitis in a prospective study using flow cytometric DNA-analyses. Findings of DNA-aneuploidy were found at repeated examinations in four of these patients and there was a correlation with precancerous, mucosal changes (dysplasia) found at histological examination. In one patient DNA-aneuploidy preceded the finding of a carcinoma (Dukes' A) in the colon. Microspectrophotometry of imprint preparations from mucosal biopsies was compared to flow cytometry for detection of nuclear DNA-aneuploidy in seven patients with ulcerative colitis in a prospective study. DNA-aneuploidy was detected in five patients in eight separate locations of the colon and rectum. There was a good conformity between the two methods in the detection of DNA-aneuploidy, which was detected in non-dysplastic mucosa as well as in association with dysplasia. In a fifteen year follow-up surveillance program, comprising 72 patients with total ulcerative colitis, colonoscopy was performed at fixed intervals and biopsies sampled from ten predetermined locations in the colon and rectum. Definite dysplasia developed in 12 patients, two of which had carcinoma (Dukes' A). Nine patients were selected for prophylactic colectomy due to findings of dysplasia. A sequential development of dysplasia was found in seven patients. The cumulative risk of developing at least low grade dysplasia was 14% after 25 years of disease duration. Using flow cytometry, DNA-aneuploidy was detected in 12 out of 59 patients, significantly correlating with low and high grade dysplasia.(ABSTRACT TRUNCATED AT 400 WORDS)