Long‐term cancer risk of the anorectal cuff following restorative proctocolectomy assessed by p53 expression and cuff dysplasia

Abstract

Restorative proctocolectomy (RP) for ulcerative colitis (UC) retains a 'cuff' of columnar rectal epithelium that has unknown risk of malignant change. Markers of malignant potential in UC include aberrant p53 expression and dysplasia. We undertook a prospective study comprising serial surveillance biopsy and assessed the occurrence of aberrant p53 expression, epithelial dysplasia and carcinoma in the retained anorectal cuff following stapled RP. A total of 110 patients who underwent stapled RP for UC between 1988 and 1998 were followed up by cuff surveillance biopsies under general anaesthesia. Histological samples were analysed by a specialist colorectal pathologist for the presence of rectal mucosa, dysplasia and carcinoma. Immunohistochemistry for p53 expression was performed for each most recent cuff biopsy. Median follow-up was 56 months (12-145) and median time since diagnosis of UC was 8.8 years (2-32). Rectal mucosa was obtained from the cuff in 65% of biopsies. No overt carcinomas developed during the follow-up period and there was no dysplasia or carcinoma in any cuff biopsy. The p53 overexpression was identified in 38 specimens (50.6%), but was also identified in controls (3/3 colitis, 3/3 ileal pouch and 6/6 stapled haemorrhoidectomy donuts). The lack of carcinoma and dysplasia in the columnar cuff epithelium specimens is reassuring. The lack of stabilized p53 and absence of a relationship between p53 stabilization and dysplasia up to 12 years after pouch formation suggests neoplastic transformation is a rare event. Furthermore, p53 expression was not useful in surveillance of cuff biopsies from patients who have undergone RP for UC and the search should continue for alternative predysplastic markers. These data suggest that in patients who do not have high-grade dysplasia or colorectal cancer at the time of RP, cuff surveillance in the first decade after pouch formation is unnecessary. However, we consider regular cuff surveillance biopsies should continue for patients with high-grade dysplasia, whether or not there was a carcinoma in the original colectomy specimen.