Endoscopic and clinical evaluation of treatment and prognosis of Cronkhite-Canada syndrome: a Japanese nationwide survey

Abstract

Background: First reported in 1955, Cronkhite-Canada syndrome (CCS), a rare syndrome characterized by ectodermal abnormalities and inflammatory changes of the gastrointestinal tract mucosa, has been associated with a poor prognosis and life-threatening malignant complications. In a large population survey, we endeavored to characterize the course and treatment outcome of CCS through clinical and endoscopic assessment, and to explore its optimal treatment and surveillance strategy.

Methods: A retrospective analysis of 210 patients with CCS was conducted via a questionnaire-based nationwide survey of 983 teaching hospitals located throughout Japan. We assessed clinical features, endoscopic findings, treatments used, and short- and long-term outcomes.

Results: The average age at diagnosis was 63.5 years. In all cases, upper or lower gastrointestinal tract polyposis was confirmed, accompanied by characteristic ectodermal abnormalities. Of the treatments used, oral corticosteroids (30-49 mg/day) were the most effective treatment for active disease, with adjunctive nutritional support considered beneficial. With corticosteroid treatment, abdominal symptoms were relieved within a few months, whereas polyp regression often required more than 6 months. Maintenance of endoscopic remission with or without steroids for 3 years significantly lowered the development of CCS-related cancer, compared with relapsers or nonresponders, underscoring the importance of sustained endoscopic remission for cancer prevention.

Conclusions: The prognosis of CCS has greatly improved through the use of improved medical treatment. Although CCS continues to be relentlessly progressive, carrying a high cancer risk, a sufficient dose and duration of corticosteroid therapy accompanied by nutritional support and periodic endoscopic surveillance appears to improve its natural history.

Keywords: Acquired gastrointestinal polyposis syndrome; Colon cancer; Gastric cancer; Malnutrition.

Fig. 1

Endoscopic findings of gastrointestinal polyps in patients with Cronkhite–Canada syndrome. A distribution and size of polyps. The outer circle shows the distribution pattern, and the inner circle shows the predominant size of the polyps. Data are expressed as the percentage of the total number of patients. The dominant types in the small intestine were sparsely distributed smaller polyps. The polyps in the stomach were more confluent than those in the colon (81.9 % vs 54.5 %, p < 0.01), and smaller (in the stomach 18.1 % were larger than 15 mm, 51.4 % were 5–10 mm, and 30.5 % were smaller than 5 mm, and in the colon 30.4 % were larger than 15 mm, 44.6 % were 5–10 mm, and 25 % were smaller than 5 mm; p < 0.05). B endoscopic appearance of polyps. Appearance was classified into four categories (edematous, engorged, with erosion, or with hemorrhage) according to the most dominant appearance. C the endoscopic appearance in the mucosa between the polyps was classified as normal or abnormal. Abnormal usually indicates edematous or reddish coarser mucosa than normal (74 % in the stomach and 57.6 % in the colon, p < 0.01)

Fig. 2

Flow diagram of treatment choice and clinical course of patients with Cronkhite–Canada syndrome (CCS) *1 of 23 patients without steroid treatment, eight patients were treated with nutritional therapy and 15 patients underwent surgical/endoscopic treatment alone. *2 among 30 patients who failed to respond to corticosteroid treatment, seven patients showing progressive disease required intensive therapy with calcineurin inhibitors (n = 4), octreotide (n = 1), anti-TNF-α agents (n = 1), and colectomy (n = 1). With the exception of one patient treated with a calcineurin inhibitor who failed to respond, the others attained endoscopic response

Fig. 3

The cumulative clinical remission rate over time and mean time to remission. Asterisk the mean time to remission is significantly longer compared with the mean time for diarrhea (p < 0.05 vs diarrhea), dagger p < 0.05 versus onychodystrophy, S.E. standard error

Fig. 4

Three-year outcome of steroid treatment in 108 patients who attained a good response. Of the 108 patients, 66 achieved a long-term response (36 “complete remission” and 30 “partial remission”), and 42 had no long-term response (16 “episodic active” and 26 “chronic active”). Among those patients, the occurrence of cancer (4 gastric cancer and 14 colon cancer) and Cronkhite–Canada syndrome (CCS)-related death (one death due to sepsis caused by colitis, two deaths due to gastric cancer, and four deaths due to colon cancer) are shown