The Long-Term Clinical and Endoscopic Outcomes of Cronkhite–Canada Syndrome

Abstract

INTRODUCTION: The prognosis of Cronkhite–Canada syndrome (CCS) is considered poor. Despite the recent therapeutic improvements, the survival outcomes and prognostic factors have been less studied. This study aimed to investigate the long-term clinical and endoscopic outcomes of CCS. METHODS: Thirty-one patients diagnosed since 1999 and followed up for over 6 months were included. Data regarding survival outcomes, clinical symptoms, endoscopic findings, and treatment were collected and analyzed. R (version 3.6.1) was used to perform the survival analyses. RESULTS: The median (interquartile range) follow-up time was 42.5 (19.5–85.8) months. The 5-year overall survival (OS) was 87.4%. The maximum gastric polyp size over 2 cm was associated with worse OS (Hazard ratio [HR]: 18, 95% confidence interval [CI]: 1.6–210, P = 0.021). The 3-year relapse-free survival (RFS) after corticosteroid treatment was 66.8%. Age older than 60 years (HR: 7.0, 95% CI: 1.5–33.0, P = 0.015) and maximum gastric polyp size over 2 cm (HR: 6.0, 95% CI: 1.6–23.0, P = 0.009) were associated with worse RFS. Twenty-three patients received follow-up endoscopic examinations, with a median (interquartile range) follow-up time of 29.0 (14.0–53.5) months. Eight (34.8%) and 12 (52.2%) patients achieved complete remission under gastroscopy and colonoscopy, respectively. Colonic lesions showed a tendency of earlier responses compared with gastric lesions (25.0 [11.3–39.8] months vs 31.0 [21.0–39.8] months). DISCUSSION: Patients with CCS usually responded well to glucocorticoids with a fairly good 5-year survival rate. Large gastric polyp was associated with worse OS and RFS, whereas age older than 60 years was another predictor for worse RFS. Diffuse gastrointestinal lesions partly or completely resolved after treatment, and colonic lesions showed a better response than gastric lesions.

Cronkhite–Canada syndrome: An investigation in clinical features and pathogenesis

“…strategies. 5 The underlying mechanism of CCS remains rarely investigated. One whole exome sequencing (WES) study identified a rare protein kinase DNA-activated catalytic subunit DNA variant that might be related to CCS pathogenesis.…”

Cronkhite-Canada syndrome with steroid dependency: A case report

“…More than 35% of patients failed to achieve long-term clinical remission after corticosteroid administration, and relapse occurred during or after the cessation of glucocorticoid use. A proportion of patients were prescribed low-dose (5-10 mg/d) corticosteroids or immuno-suppressants to counteract the tendency to relapse[ 5 ].…”

“…Cronkhite-Canada syndrome (CCS) is a rare gastrointestinal polyposis syndrome characterized by dermatologic manifestations associated with chronic diarrhoea, malnutrition, and enteric protein wasting resulting from chronic inflammatory changes in the intestinal mucosa[ 1 - 3 ]. Since the disease was first described in 1955, only approximately 500 patients with CCS have been reported worldwide, among which over 70% were from Japan[ 2 , 4 , 5 ]. Although disease presentation has been well described, there is no consensus on the management of CCS.…”

Hamartomatous polyposis syndrome associated malignancies: Risk, pathogenesis and endoscopic surveillance

“…A total of 31%–71% of patients develop colorectal adenoma during the disease course, 36,37 and a small proportion of patients develop gastric and duodenal adenomas 36 . Our previous study has shown that three (12.5%) of 24 patients with CCS developed malignancy within a median follow‐up of 42.5 months 38 . Patients with CCS complicated by parenteral malignancies, such as giant cell bone tumor, 39 cholangiocarcinoma 40 and multiple myeloma, 41 have also been reported.…”

“…Although endoscopic surveillance may improve the prognosis of HPS, it is still difficult to discriminate between hamartoma polyps and hamartoma polyps with dysplasia and sporadic adenoma. The classic Kudo classification of colon polyps has shown their disadvantage for discrimination in patients with CCS 38 . Table 1 shows the features and recommendations for endoscopic surveillance of HPS.…”