Pelvic pouch in ulcerative colitis : surgical refinement and long-term mucosal outcome

University dissertation from Stockholm : Karolinska Institutet, Department of Medicine at Huddinge University Hospital

Abstract: The surgical technique in performing restorative proctocolectomy has been extensively developed since its introduction in 1978. Recurrent attacks of inflammation in the neorectal ileal pouch mucosa, pouchitis, well known also from the Kock pouches, occur in a substantial number of the patients, and constitute the major clinical long-term problem observed. Persistent severe mucosal atrophy may develop in a subgroup of patients experiencing severe attacks of pouchitis and those patients may be prone to develop neoplastic changes. The aims of the presented studies were: 1. to evaluate the surgical and functional outcome of use of stapling technique in pouch construction and in performing the ileoanal anastomosis with omission of mucosectomy and a defunctioning loop ileostomy, 2. to elucidate the incidence of pouchitis and evaluate possible predictive factors, 3. to investigate the occurrence of, and possible risk factors associated with neoplastic transformation of the pelvic pouch mucosa, and 4. to investigate whether gene mutations are present in the ileal mucosa in patients with neoplastic mucosal changes. Twenty patients operated on with stapling technique in pouch and anastomosis without mucosectomy and without a defunctioning loop ileostomy were compared with a matched control group of patients with handsewn pouch and handsewn anastomosis after mucosectomy, and with a loop ileostomy. Anastomotic complications occurred in two patients in the study group, and further seven patients had prolonged postoperative temperature. Six patients in the control group developed stenosis in the anastomosis or in the levator plane. In the study group, duration of surgery and total hospital stay was shorter, there was less bleeding, and nocturnal continence was improved. Evacuation rate was higher during the first year of pouch in function, but not onwards. A consecutive and prospectively followed series, where stapling technique was used in construction of the pouch and the ileoanal anastomosis, was evaluated. In nine patients, a primary covering loop ileostomy was constructed. Eight patients (10.4%) developed pelvic sepsis and got a secondary defunctioning loop ileostomy, four out of these eight patients had been preoperatively treated with corticosteroids and/or immunosuppressants. After loop closure, the functional outcome in these eight patients was not impaired. Three patients developed symptoms from remaining rectal mucosa requiring secondary transanal mucosectomy with reconstruction of the ileoanal anastomosis. At 12 months followup, the median evacuation frequency per 24 hours was 6.0, and the median nocturnal evacuation frequency was 1.0. Minor incontinence daytime occurred in 9.4% of the patients and nighttime in 10.6%. Incidence of pouchitis was studied in 149 patients during in median 54 months of follow-up. 'Me diagnosis was based on clinical symptoms and endoscopic findings. A scoring system for grading in mild and severe pouchitis was designed. The incidence of a first attack was highest during the first six-month period of pouch in function and levelled off after two years. The absolute cumulative risk for development of pouchitis was 51% after four years. Less than 10% of the patients had severe chronic symptoms, and two patients of these undewent pouch excision. Seven patients with persistent severe ileal pouch mucosal atrophy were compared with 14 controls with no or slight atrophy, matched for pouch duration. Multiple biopsies from five prospectively defined locations were taken at flexible endoscopy, assessed histopathologically, and by DNA flow cytometry. The median age at UC onset was significantly lower in the study group, and the incidence of pouchitis was significantly higher. In the study group, five patients were found to have definite dysplasia, and two of these also had multiple findings of DNA-aneuploidy. None of the patients in the control group displayed dysplasia, nor DNA-aneuploidy (P<0.001). In those patients having displayed definite dysplasia, special assessment with respect to genetic alterations in K-ras, chromosome 5q, 17p and 18q was made in a further study. No signs of alterations were found in K-ras, 17p or l8q. Loss of heterozygosity at 5q15-22 was found in one patient, but without findings of concomitant dysplasia or DNA-aneuploidy. Histological and DNA/gene alterations may all reflect early events in neoplastic transformation of the ileal pelvic pouch mucosa, and surveillance seems prudent in this subgroup of pouch patients.

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