クロンカイト・カナダ症候群

This article reports a case of a patient with Cronkhite-Canada syndrome combined with sigmoid colon cancer and early esophageal cancer. In this case, CCS was diagnosed simultaneously with the discovery of sigmoid colon cancer and early esophageal cancer. After radical resection of sigmoid colon cancer, the patient received hormone therapy for 12 months. The symptoms such as diarrhea, hair loss, and malnutrition were relieved, and the gastric-duodenal and colonic polyp-like lesions were reduced. The early esophageal cancer was followed up for 3 years, but no active treatment was given for the early esophageal cancer. It is rare for both colon cancer and early esophageal cancer to occur simultaneously on the basis of CCS. To improve the understanding of the diagnosis and treatment of this disease and postoperative management, the case is reported as follows.

BACKGROUND Cronkhite-Canada syndrome (CCS) is a rare gastrointestinal polyposis disorder with more than 500 cases worldwide. It is associated with high mortality rates and complex pathogenesis. Owing to its rarity and fragmented evidence base, the overall publication patterns and evolving research focus of CCS have not been systematically mapped. This study performed a Web of Science Core Collection (WoSCC)-based bibliometric analysis and knowledge mapping to summarize research output, collaboration patterns, and topic evolution in CCS. MATERIAL AND METHODS Based on 256 English publications on CCS retrieved from the WoSCC, bibliometric analysis and visualization were conducted using CiteSpace and VOSviewer to examine publication trends, collaboration networks, and keyword evolution. RESULTS Research on CCS showed a fluctuating growth trend, with a slowed growth observed after 2023. The United States, China, and Japan contributed the highest number of publications. Collaboration network analysis suggested relatively limited international cooperation, and high-yield institutions showed low centrality (centrality <0.1). Keyword co-occurrence and burst analyses indicated an evolving research focus from disease characterization to mechanistic exploration and clinical management in recent years. CONCLUSIONS This WoSCC-based bibliometric analysis summarizes publication patterns, major contributors, and evolving research topics in CCS. These findings reflect trends in the indexed literature and bibliometric indicators rather than direct advances in clinical outcomes or mechanisms. Future studies can benefit from strengthening international collaboration and integrating multicenter evidence to support more robust mechanistic and clinical investigations in CCS.

BACKGROUND/AIM: Immunosuppressive and nutritional treatments have improved the prognosis of Cronkhite-Canada syndrome (CCS). CCS-associated polyps are benign and categorized into hamartomatous, inflammatory, hyperplastic, and adenomatous polyps; however, the development of gastrointestinal cancer is considered the most significant prognostic factor for CCS. Although the adenoma-carcinoma sequence and inflammation-associated carcinogenesis are two major pathways for the development of colorectal cancers (CRCs), it remains largely unknown which pathway plays critical roles in the development of CRCs in CCS. Inflammation-associated carcinogenesis might be involved in the development of CRCs associated with CCS because CCS-associated polyps are characterized by submucosal infiltration of immune cells. Given the fact that proinflammatory cytokines including interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α underlie the pathogenesis of inflammation-associated carcinogenesis, we examined the involvement of proinflammatory cytokines in the transformation of CCS-associated polyps into CRCs. PATIENTS AND METHODS: Three cases of CCS were enrolled: two cases with concurrent CRCs and a single case without CRC. mRNA was isolated from non-cancerous CCS-associated polyps and subjected to reverse transcription quantitative polymerase chain reaction to determine expression of proinflammatory cytokines. Colonic biopsy samples were isolated from non-tumor portions of patients with colonic adenoma to determine mRNA expression of proinflammatory cytokines in healthy colonic mucosa. RESULTS: Higher mRNA expression of IL-6, but not IL-1β or TNF-α, in non-cancerous CCS-associated polyps was observed in two patients with CCS and concurrent CRCs as compared with four healthy colonic mucosal samples and a patient with CCS without CRC. CONCLUSION: IL-6-mediated inflammation-associated carcinogenesis might be involved in the transformation of CCS-associated polyps into CRC.

OBJECTIVE: To explore the involvement of neutrophil dysregulation in Cronkhite-Canada syndrome (CCS) and to identify serum biomarkers for its diagnosis and disease activity assessment. METHODS: We performed comprehensive serum proteomic analysis using data-independent acquisition (DIA) on samples from patients with active CCS (aCCS) and healthy controls (HCs). Candidate proteins were further evaluated by parallel reaction monitoring (PRM). An independent validation cohort including cases with aCCS, remitting CCS (rCCS), and HCs was then assessed using enzyme-linked immunosorbent assay (ELISA). In addition, previously generated transcriptomic data and immunofluorescence staining of colonic polyps were used to assess local neutrophil extracellular trap (NET)-related immune changes in intestinal tissues. RESULTS: Proteomic screening identified 362 differentially expressed proteins, and bioinformatic analysis consistently highlighted pathways related to neutrophil activation, acute inflammation, and NET formation. Key neutrophil-associated proteins, including myeloperoxidase (MPO), lipocalin-2 (LCN2), and matrix metalloproteinase-9 (MMP-9), were significantly upregulated. PRM validated seven upregulated candidate proteins. In the independent validation cohort, compared with HCs, serum MPO-DNA complexes, LCN2, and MMP-9 were significantly elevated in aCCS patients, whereas MPO-DNA complexes and MMP-9 were significantly reduced in rCCS cases. Tissue-level transcriptomic and immunofluorescence analyses further supported NET-related immune activation in CCS colonic polyps. Receiver operating characteristic curve analysis demonstrated favorable diagnostic performance for these biomarkers. CONCLUSIONS: Our findings support the involvement of neutrophil dysregulation and NET-associated pathways in CCS pathobiology. Serum MPO-DNA complexes, LCN2, and MMP-9 may serve as promising non-invasive biomarkers for diagnosis and disease activity monitoring. Further studies incorporating disease control cohorts and mechanistic validation are warranted.

BACKGROUND Cronkhite-Canada syndrome (CCS) is a rare, nonhereditary gastrointestinal polyposis syndrome characterized by diffuse polyps, diarrhea, malnutrition, and ectodermal changes. It can mimic inflammatory bowel disease (IBD), leading to misdiagnosis and delayed treatment. Here, we present a case of CCS that was initially thought to be Crohn's disease, managed with vedolizumab, and ultimately required total parenteral nutrition (TPN) due to severe malnutrition. CASE REPORT A 65-year-old man presented with a history of 2 months of watery diarrhea, weight loss, postprandial abdominal pain, dysgeusia, and nail dystrophy. He was initially diagnosed with Crohn's disease based on colonoscopy and biopsies. His symptoms were initially managed with prednisone and vedolizumab. However, 8 months later, he developed worsening dysgeusia, anorexia, and further weight loss. A follow-up esophagogastroduodenoscopy (EGD) showed large nodular polyps in the stomach and duodenum, with chronic inflammation, epithelial hyperplasia, and mucosal edema on biopsy. In a multidisciplinary review, the clinical picture was deemed more consistent with CCS rather than Crohn's disease. Vedolizumab was continued due to partial symptomatic relief. Endoscopic or surgical gastrostomy was deferred due to severe malnutrition and extensive gastric involvement, and TPN was initiated. CONCLUSIONS This case highlights the diagnostic complexity and clinical severity of CCS, which can closely mimic IBD. Although the patient had a partial response to vedolizumab, the progression of disease led to severe malnutrition requiring TPN. Early recognition and aggressive nutritional and medical management are essential for managing this debilitating condition.