Screening for dysplasia and TP53 mutations in closed rectal stumps of patients with ulcerative colitis or Crohn disease.

BACKGROUND: Patients who undergo colectomy due to intractable chronic inflammatory bowel disease (IBD) may keep a closed rectal stump for several years, which may be at increased risk of malignant transformation owing to residual inflammatory activity. We examined a hospital series of patients with ulcerative colitis or Crohn colitis to describe the clinical, endoscopical and histological features of the closed rectal stump and to screen for dysplasia and mutations in the TP53 tumour suppressor gene. METHODS: During rigid proctoscopy, rectal mucosal biopsy specimens and rectal lavage fluid were collected from 42 patients. Biopsy specimens were examined histologically, and genomic DNA extracted from frozen biopsies and lavage fluid was analysed for mutations in TP53 exons 4-9. RESULTS: The median disease duration was 8.5 years (range 1.3-34 years). No endoscopic or histological signs of dysplasia or carcinoma were seen and no mutations in the TP53 gene were detected in any biopsy or lavage fluid specimens. Histological moderate to severe mucosal inflammation was present in 78% (33/42) of the patients, however, and rectal stump involution was noted in 43% (18/42). CONCLUSION: No signs of malignancy or premalignant degeneration were detected in this prospective series of IBD patients with a closed rectal stump. Although this is reassuring for patients, the presence of moderate to severe inflammation in the majority of rectal stumps indicates a role for adjuvant molecular markers to improve colorectal cancer surveillance on this subgroup of IBD patients.

Intestinal and extra-intestinal cancer in Crohn's disease: follow-up of a population-based cohort in Copenhagen County, Denmark.

AIM: To determine the long-term risk of intestinal and extra-intestinal malignancies in Crohn's disease patients in Copenhagen County, Denmark. METHODS: In Copenhagen County, a strictly population-based cohort of 374 patients with Crohn's disease diagnosed between 1962 and 1987 was followed until 1997 in order to determine the long-term risk of intestinal and extra-intestinal malignancies. Information on cancer occurrence was provided by the Danish National Cancer Registry and confirmed by the examination of hospital files. The observed number of cases was compared with the expected number, calculated from individually computed person-years at risk and 1995 cancer incidence rates for the background population. RESULTS: The risk of small bowel adenocarcinoma was significantly increased, independent of age and gender (standardized morbidity ratio, 66.7; 95% confidence interval, 18.1-170.7). The risk of colorectal cancer was not increased, either in the total group of patients or in patients with colonic Crohn's disease exclusively (standardized morbidity ratio, 1.64; 95% confidence interval, 0.20-5.92). Extra-intestinal cancer did not occur more frequently than expected. CONCLUSIONS: This population-based study of patients with Crohn's disease revealed no increase in colorectal cancer risk, possibly due to maintenance treatment with 5-aminosalicylic acid preparations and surgery in treatment failure. In contrast, the risk of small bowel cancer was increased more than 60-fold, but the numbers were small. The risk of extra-intestinal cancer was not increased and no lymphomas were observed.

Inflammatory bowel disease (ulcerative colitis and Crohn's disease): diagnostic criteria and differential diagnosis.

Chronic inflammatory bowel diseases (i.e., ulcerative colitis and Crohn's disease) are syndromes in which standardized criteria are necessary in the diagnostic process. The present review is based on the diagnostic criteria used at our institution. We base the diagnosis of ulcerative colitis and Crohn's disease on combined information from the patient history, and radiological, endoscopic and histological findings after exclusion of neoplastic and infectious disease. The patient history must include precise information on the nature and duration of symptoms as well as the presence of relevant influential factors such as travel activity, drug intake and sexual habits. In immunocompromised patients extensive microbiological investigations are required to exclude infection. Typical radiological and colonoscopic findings in ulcerative colitis are mucosal inflammatory changes extending circumferentially and continuously from the rectum and proximally in the colon. In contrast, Crohn's disease is most frequently located in the small bowel and in case of colonic involvement, the rectum is often spared. The best predictors of Crohn's disease are discontinuous lesions, cobblestones and apthous ulceration. Histological changes such as abnormal mucosal architecture and lamina propria cellularity, neutrophil polymorph infiltration and epithelial cell abnormality are useful and reproducible features in the evaluation of colorectal biopsy specimens. The inflammatory bowel diseases, ulcerative colitis and Crohn's disease, continue to be etiological and diagnostic challenges. Increased use of standardized criteria and diagnostic algorithms are essential instruments to improve the overall quality of the management of patients with these diseases.