Ulceration of the Small and Large Bowel Mucosain Resection Specimens of Cystic Fibrosis Patients with Fibrosing Colonopathy

Abstract

Fibrosing colonopathy (FC), observed in cystic fibrosis patients taking high-strength pancreatic enzyme preparations, is characterized by progressive obstruction of the ascending colon, with long-segment fusiform stenosis due to the deposition of submucosal fibrous tissue. The pathogenesis is uncertain, although direct toxic damage to the colonic mucosa by a constituent of such preparations has been proposed as an explanation. Mucosal defects and rectal bleeding have been observed by colonoscopy in cystic fibrosis patients at risk for and with evident FC. In a quantitative, observational study, mucosal defects were studied in six ileo-cecal resection specimens with FC confirmed by three independent pathologists' review. Representative areas (2.5-cm-long segments) were taken of terminal ileum, cecal colon, and ascending colon both at the site of most severe stenosis and at the most distal ascending colon site available; after processing with paraffin, the areas were serially sectioned at 500-μm intervals for the preparation of 5-μm sections for microscopical assessment. Marking in each section the area affected by (repairing) ulceration, and using three-dimensional reconstructions of the bowel lining, individual mucosal lesions were reconstructed. Using the reconstructed bowels, point scoring analysis of the area fraction affected by ulceration as well as the area of individual lesions was carried out. Lesions of variable age were found in the terminal