Endoscopic methods for detecting malignancy in patients with ulcerative colitis and primary sclerosing cholangitis

Abstract

Ulcerative colitis (UC) is a chronic ulcerative inflammatory bowel disease affecting the mucosa of the large intestine. UC patients have an increased risk for the development of colorectal cancer mainly associated with long duration and extensive involvement of the colitis. The preferred method for detecting malignancy or premalignant changes has for almost three decades been endoscopic colonoscopic surveillance and there is still no consensus of its clinical value. An important extra-intestinal complication affecting 5-7 % of all UC patients is primary sclerosing cholangitis (PSC). Patients with both UC and PSC run an increased risk for developing malignancies in both the bile ducts and the colonic mucosa. There are considerable difficulties in detecting bile duct malignancy in patients with PSC.

Aims: To assess the clinical value and the role of dysplasia in a 20 years colonoscopic surveillance program in patients with UC. To find if patients with both UC and PSC run a higher risk for developing colorectal malignancy/dysplasia than patients with UC only. Analyze if malignancy develops at different locations in UC patients with and without PSC and if long time treatment with Sulfasalazine/5 ASA influences the incidence of colorectal malignancy. To evaluate the diagnostic possibilities in conjunction with endoscopic retrograde cholangiopancreatography (ERCP) for detecting malignancy in biliary strictures, especially in patients with PSC, by evaluating the cholangiogram, the brush cytology, the cellular DNA content by flow cytometry, and the tumor markers CEA and CA 19-9 in bile and serum.

Materials and Methods: Two series of patients were studied. The first series consisted of 143 patients with extensive UC, observed in a 20 years prospective colonoscopic surveillance program. Colonoscopy with multiple biopsies was performed every second year in search for precancerous changes (dysplasia). The second series consisted of 57 patients with bile duct strictures, identified during ERCP. Two radiologists blindly evaluated all cholangiograms. Brush samples from the strictures were taken for cytology and evaluation of DNA content by flow cytometry. To increase the number of cell nuclei for flow cytometry the standard preparation method were compared to a new developed enzyme technique. The tumor markers CA 19-9 and CEA were determined both in serum and in bile fluid.

Results and Conclusions: The colonoscopic surveillance revealed dysplasia/cancer in 55 patients; 7 of these patients had carcinomas, and 2 were in a potentially curable stage (Dukes group A). Low-grade dysplasia had a high predictive value for the development of malignancy. Regular colonoscopy constitutes a possible way for surveillance of patients with chronic extensive UC and may also identify patients with dysplasia and prevent malignant transformation. The observed mortality in the UC group undergoing colonoscopic surveillance was the same as the expected in a non-diseased background population. UC patients with PSC constitute an important and independent risk group for malignancy, not only for cholangiocarcinoma but also for colorectal dysplasia/cancer. A tendency towards a proximal location in the colon of colorectal dysplasia/cancer may suggest an influence of toxic bile in the carcinogenic process, in patients with PSC. Long time treatment with Sulfasalazine/5 ASA did not influence the incidence of colorectal malignancy. Flow cytometry of cells from biliary strictures obtained at ERCP is a feasible method and with the new enzyme method a significant increase in cell content was achieved. An ERCP procedure with brush cytology, DNA analysis, and determination of S-CA 19-9 and S-CEA may increase the possibility of distinguishing between malignant and benign biliary strictures, especially in PSC patients.