Tu1250 Clinical Response to Medical Treatment and Prognosis of Cronkhite-Canada Syndrome -A Japanese Nationwide Survey

Abstract

Background: Cronkhite-Canada Syndrome (CCS) is an uncommon gastrointestinal polyposis syndrome that exists mostly in Japan characterized by dermatologic manifestations associated with chronic diarrhea, malnutrition, and protein wasting that can be fatal in as high as 50% if untreated or if treatment is delayed or inadequate. Due to its rarity, its subjects cannot be studied in clinical trials. Here, we report patient characteristics derived from a national database in an effort to identify prognostic factors and to improve treatment outcomes. Method: Retrospective analysis of 150 patients with CCS from a national database including 80 institutions specializing in gastroenterology. Clinical features including endoscopic findings, treatment, prognosis, and response to medical therapy were included. This study was supported by Intractable Disease, Health and Labor Sciences research groups for the Japanese Ministry of Health, Labor and Welfare. Results: Patient's age was 68.1±9.7 and treatment duration was 6.0±4.6years. CCS-related polyposis endoscopically confirmed to be throughout the gastrointestinal tract. Of the 140 patients who received steroids, 5 failed to respond, 2 underwent colectomy due to massive bleeding, 2 received cyclosporine, and 1 received biologics. Improvement of diarrhea followed by recovery of hypoalbuminemia was observed usually within 3 months after the start of medical therapy, with weight gain and improvement of dermatologic manifestations occurring at 5-6.5 months, and improvement of endoscopic appearance by 7.7 months. In 17%, no improvement of polyposis occurred despite clinical response. CCS-related gastric and colonic polyps progressed to advanced gastric and colon cancer in 7 of 107 and 15 of 120, respectively, suggesting the importance of endoscopic follow-up. Among those who discontinued steroid therapy, 7.4% developed advanced cancer, compared with 2.7% in those who maintained clinical remission with steroids. No patient who received nutritional support alone experienced clinical remission. An induction dose of steroid of >0.5mg/kg, followed, in some cases, with steroidmaintenance appeared beneficial for preventing the risk of recurrence of CCS-related polyps, reducing cancer risk, underscoring the importance of maintaining endoscopic remission. As for prognosis, 108 patients were alive and 22 had expired. The causes of death were colon cancer (1), gastric cancer (2), other malignancies (5), and other diseases, but none died of malnutrition. Conclusion: Contrary to earlier reports, the prognosis of CCS has greatly improved through improved medical treatment, although the course of CCS is relentlessly progressive with high cancer risk. A sufficiently high induction steroid dose, long-term steroidmaintenance, and aggressive nutritional support appear to improve the natural history of CCS.