DOP058 Does biologic therapy increase the risk for fistula-associated mucinous adenocarcinoma in long standing perianal Crohn's disease?

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Abstract

Background: Perianal adenocarcinoma in Crohn's disease is rare and poorly known. Single cases or small series have been reported identifying long-standing perianal disease as a risk factor. The effectiveness of biologic therapy combined with surgical drainage has been widely proved while a possible relationship between biologics and perianal carcinoma development has been suggested. The objective of the study was to evaluate features and outcomes of fistula-associated anal mucinous adenocarcinoma in perianal Crohn's Disease together with the influence of biologic therapy on its incidence

Methods: Among 535 patients operated in our Unit for perianal Crohn's Disease since 2005, in 12 patients (2.24%) a fistula-associated anal mucinous adenocarcinoma was diagnosed. We retrospectively reviewed their medical records to characterize presentation, treatment, and clinical outcome. Additional 40 pts with long-standing PCD and without cancer were selected and included in the study in order to evaluate the influence of biologics on adenocarcinoma development

Results: Average age at diagnosis was 53.4 years. All patients had long-standing fistulas (mean duration of disease of 21.3 (15–29) years). Ten had been treated with biologics in different settings (before/after surgery). All patients had extensive local disease; abdominoperineal resection (10 pts) or pelvic exenteratio (2 pts) was performed. Seven patients died due to metastatic disease and 5 are alive with evidence of recurrency.

Overall risk of cancer was not influenced by the use of biologics (2.7% vs 1.8% respectively, p=n.s.). However, considering surgical history, risk of cancer was significantly increased if biologic therapy had been previously given in patients with undrained chronic tracts (62.4% vs 7.9%, p=0.02). On the other hand, prolonged biologic therapy administered in patients after surgical drainage of fistulas did not increase the risk (20.5% vs 12.9%, p=n.s.). This was confirmed by a multivariate analysis evaluating duration of disease, biologics type and treatment strategy

Conclusions: Perianal mucinous adenocarcinoma in CD is being increasingly reported. The Outcome, even after aggressive surgical treatment, is poor. Our data show that the risk of occurrence of mucinous adenocarcinoma is significantly increased in patients with long-standing disease when biologic therapy is not preceded by complete surgical excision of all the fistulous tracts, thus suggesting that immunomodulation could play a key role in the progression from chronic inflammation left in situ to carcinoma. In patients with long-standing disease surgical drainage with biopsies of the fistulous tracts is mandatory prior to initiating biological therapy

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