Cronkhite-Canada Research Articles

Cronkhite-Canada syndrome tends to be accompanied by colorectal cancer: Report of seven cases.

Cronkhite-Canada syndrome (CCS) can be difficult to diagnose. To diagnose CCS, it is important to perform endoscopic examination for patients with chronic diarrhea, check for the presence or absence of polyposis, and evaluate inflammation in the mucosa between the polyps. This study reported seven cases of CCS. The age of the patients, which included four men and three women, ranged 48-72 years, and all patients were Asian. The most common symptom among these patients was chronic diarrhea. Three of the patients had rectal cancer. In two patients, the lesions were detected at an early stage and resected via endoscopic treatment. CCS is associated with a high risk of malignant gastrointestinal lesions, especially rectal cancers, and periodic surveillance endoscopy and careful observation are required.

S5098 Cronkhite-Canada Syndrome: A Rare Presentation for Weight Loss, Diarrhea and Protein-Losing Enteropathy

S5098 Cronkhite-Canada Syndrome: A Rare Presentation for Weight Loss, Diarrhea and Protein-Losing Enteropathy

S3073 Cronkhite-Canada Syndrome Presenting as Severe Protein-Losing Enteropathy: A Case Report

S3073 Cronkhite-Canada Syndrome Presenting as Severe Protein-Losing Enteropathy: A Case Report

A case of membranous nephropathy complicated by Cronkhite-Canada syndrome successfully treated with mizoribine.

Cronkhite-Canada syndrome (CCS) is a non-hereditary disorder characterized by non-neoplastic hamartomatous gastrointestinal polyposis, hair loss, nail atrophy, hyperpigmentation, and diarrhea. While the relationship between CCS and nephritis remains unclear, seven cases of nephritis complicated by CCS have been reported to date, all of which were membranous nephropathy (MN). A 57-year-old man presented with taste disturbance, hair loss, nail plate atrophy, skin pigmentation, and frequent diarrhea. Endoscopic findings showed multiple polyposis of the stomach and large intestine. Given the above, he was diagnosed with CCS. The symptoms gradually improved with prednisolone treatment, although urinary protein and hypoproteinemia appeared during the tapering of prednisolone. He was diagnosed with MN using a renal biopsy, and immunofluorescence microscopy with IgG subclass staining showed predominantly diffuse granular capillary wall staining of IgG4. The cause of secondary MN was not found, including malignant tumors. Nephrotic-range proteinuria persisted despite treatment with prednisolone and cyclosporine. Additional treatment with mizoribine resulted in incomplete remission type 1 of nephrotic syndrome, suggesting that mizoribine may be a treatment option for patients with CCS with steroid-resistant MN. Considering a high prevalence of hypoproteinemia due to chronic diarrhea and protein-losing enteropathy in patients with CCS, proteinuria might be overlooked; thus, follow-up urinalysis would be recommended in patients with CCS.

Cronkhite‒Canada syndrome as inflammatory hamartomatous polyposis: new evidence from whole transcriptome sequencing of colonic polyps

BackgroundCronkhite-Canada syndrome (CCS) is a rare, nonhereditary disease characterized by diffuse gastrointestinal polyposis and ectodermal abnormalities. Although it has been proposed to be a chronic inflammatory condition, direct evidence of its pathogenesis is lacking. This study aims to investigate the pathophysiology of CCS by analyzing transcriptomic changes in the colonic microenvironment.MethodsNext-generation sequencing-based genome-wide transcriptional profiling was performed on colonic hamartomatous polyps from four CCS patients and normal colonic mucosa from four healthy volunteers. Analyses of differential expression and multiple enrichment analyses were conducted from the molecular level to the cellular level. Quantitative real-time PCR (qRT-PCR) was carried out to validate the sequencing accuracy in samples from six CCS patients and six healthy volunteers.ResultsA total of 543 differentially expressed genes were identified, including an abundance of CC- and CXC-chemokines. Innate immune response-related pathways and processes, such as leukocyte chemotaxis, cytokine production, IL-17, TNF, IL-1 and NF-kB signaling pathways, were prominently enhanced in CCS colonic polyps. Upregulation of wound healing, epithelial-mesenchymal transition, Wnt, and PI3K-Akt signaling pathways were also observed. Enrichment analyses at different levels identified extracellular structure disorganization, dysfunction of the gut mucosal barrier, and increased angiogenesis. Validation by qRT-PCR confirmed increased expression of the LCN2, IL1B, CXCL1, and CXCL3 genes in CCS colonic polyps.ConclusionsThis case-control whole transcriptome analysis of active CCS colonic hamartomatous polyps revealed intricate molecular pathways, emphasizing the role of the innate immune response, extracellular matrix disorganization, inflammatory cell infiltration, increased angiogenesis, and potential epithelial to mesenchymal transition. These findings supports CCS as a chronic inflammatory condition and sheds light on potential therapeutic targets, paving the way for more effective and personalized management of CCS in the future.

Differential Diagnoses and Management Approaches for Gastric Polyposis

Multiple gastric polyps are observed in various polyposis syndromes and conditions associated with polypoid lesion development in the stomach. Polyposis syndromes often occur concurrently with specific malignant tumors and can manifest at any point in an individual’s lifespan, thus explaining the diversity in surveillance methods. Furthermore, genetic counseling and surveillance are essential not only for the patients themselves but also for their blood relatives. Therefore, the accurate diagnosis and appropriate surveillance of multiple gastric polyps are crucial for improving patient outcomes. This review aims to provide essential information on such lesions along with representative endoscopic images of familial adenomatous polyposis, Peutz-Jeghers syndrome, Cowden syndrome, Cronkhite-Canada syndrome, juvenile polyposis syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, neuroendocrine tumors in autoimmune gastritis, proton pump inhibitor-related gastric mucosal changes, and multiple submucosal heterotopic glands. We wish for this review to serve as a valuable resource for endoscopists seeking to deepen their comprehension of gastric polyposis.

A case report of Cronkhite–Canada syndrome first encounterd at a hospital in northern Vietnam

Introduction and importance: Cronkhite–Canada syndrome (CCS) is an extremely rare non-inherited syndrome first described in 1955 with only about 500 more cases reported so far. Since the aetiology of the disease remains unknown, there were no specific treatments in consensus. In many countries, CCS is a completely new condition that may confuse physicians at first encounter. Lessons should be learned from these cases by gastrointestinal specialists to be aware of this condition in any circumstances. Case presentation: The authors reported a case study of a 45-year-old Vietnamese male with CCS diagnosis, which encountered at our centre for the first time. Clinical discussion: The definitive diagnosis was provided by combining clinical characteristics, and endoscopic and histopathologic features, after excluding other causes of gastrointestinal polyposis. The patient responds to corticosteroids, proton pump inhibitors, and nutritional support right after treatment. After 1 year of treatment, his symptoms ameliorated completely although colon polyps insignificantly reduced. Conclusion: Gastroenterologists should always be aware of patients with CCS with the following symptoms: gastrointestinal hamartomatous polyps, diarrhoea, and the dermatologic triad of alopecia, hyperpigmentation, and onychodystrophy.

Human intestinal organoids from Cronkhite-Canada syndrome patients reveal link between serotonin and proliferation.

Cronkhite-Canada Syndrome (CCS) is a rare, noninherited polyposis syndrome affecting 1 in every million individuals. Despite over 50 years of CCS cases, the etiopathogenesis and optimal treatment for CCS remains unknown due to the rarity of the disease and lack of model systems. To better understand the etiology of CCS, we generated human intestinal organoids (HIOs) from intestinal stem cells isolated from 2 patients. We discovered that CCS HIOs are highly proliferative and have increased numbers of enteroendocrine cells producing serotonin (also known as 5-hydroxytryptamine or 5HT). These features were also confirmed in patient tissue biopsies. Recombinant 5HT increased proliferation of non-CCS donor HIOs and inhibition of 5HT production in the CCS HIOs resulted in decreased proliferation, suggesting a link between local epithelial 5HT production and control of epithelial stem cell proliferation. This link was confirmed in genetically engineered HIOs with an increased number of enteroendocrine cells. This work provides a new mechanism to explain the pathogenesis of CCS and illustrates the important contribution of HIO cultures to understanding disease etiology and in the identification of novel therapies. Our work demonstrates the principle of using organoids for personalized medicine and sheds light on how intestinal hormones can play a role in intestinal epithelial proliferation.

S2916 From Rarity to Recognition: A Case Report of Cronkhite-Canada Syndrome

S2916 From Rarity to Recognition: A Case Report of Cronkhite-Canada Syndrome

Endoscopic features help to identify the histopathological patterns of colorectal polyps in Cronkhite-Canada syndrome.

Cronkhite-Canada syndrome (CCS) is a rare nonhereditary gastrointestinal hamartomatous polyposis syndrome with a high risk of colorectal cancerogenesis. It is challenging to discriminate adenomas from nonneoplastic colorectal polyps macroscopically. This study aimed to explore the endoscopic features of different histopathological patterns of colorectal polyps in CCS. Sixty-seven lesions from 23 CCS patients were prospectively biopsied or resected during the colonoscopic examinationfor histopathological analysis. The Fisher's exact test and multivariate logistical analysis were conducted to reveal the predictive endoscopic features of CCS polyps with low-grade dysplasia (LGD) and adenomas. There were seven (10.4%) adenomas, 20 (29.9%) CCS-LGD, and 40 (59.7%) nonneoplastic CCS polyps. Polyps were large (>20 mm) in none of the adenomas, 30.0% of CCS-LGD polyps, and 2.5% of nonneoplastic CCS polyps (P < 0.001). The color of the polyps was whitish for 71.4% of adenomas, 10.0% of CCS-LGD polyps, and 15.0% of nonneoplastic CCS polyps (P = 0.004). Pedunculated polyps were detected in 42.9% of adenomas, 45.0% of CCS-LGD polyps, and 5.0% of nonneoplastic CCS polyps (P < 0.001). The proportions of types IV and VI in the Kudo classification were 42.9%, 95.0%, and 35.0% in adenomatous, CCS-LGD, and nonneoplastic CCS polyps, respectively (P = 0.002). The endoscopic activity was in remission for 71.4% of adenomas, 5.0% of CCS-LGD polyps, and 10.0% of nonneoplastic CCS polyps (P < 0.001). Endoscopic features, including the size, color, sessility, Kudo's pit pattern classification of polyps, and endoscopic activity, help identify the histopathological patterns of colorectal polyps in CCS.

Deep vein thrombosis in a patient with Cronkhite-Canada syndrome: a complex case report

BackgroundCronkhite-Canada syndrome (CCS) is a rare disease characterized by generalized gastrointestinal polyps, ectodermal abnormalities and variable gastrointestinal symptoms. Few cases to date have described complications with deep vein thrombosis (DVT). Here we reported a rare case of CCS concomitant with DVT. The patient’s clinical details, endoscopic findings, safety, and efficacy are reported.Case presentationA 58-year-old patient was admitted to our hospital with recurrent diarrhea, overall abnormal appearance, including hyperpigmentation, hair loss and onychodystrophy, and multiple polyps distributed along the gastrointestinal tract except the esophagus. After considerable assessment, the patient was diagnosed with CCS. She was also diagnosed with concurrent DVT, nephrotic syndrome, and infectious enteritis during the course of disease. After treatment with a combination of methylprednisolone, mesalazine, antibiotics, rivaroxaban, and nutritional support during the 24 months of following the patient in this case, the clinical manifestations and endoscopic findings reached complete remission two years after the diagnosis.ConclusionTo our knowledge, this study is the first case of CCS complicated with DVT reported in China. Although rare, it is important to consider that DVT may occur after CCS and that it is vital to conduct careful follow-up.

Cronkhite-Canada syndrome: treatment responses and improved overall survival.

Cronkhite-Canada syndrome (CCS) is considered a relentlessly progressive disease with high mortality rates. Although disease understanding and treatment options have greatly improved, the prognosis from these advancements has not been well documented. This study aimed to evaluate treatment outcomes and overall survival of CCS. Seventeen patients who were diagnosed and treated over a 20-year period at Mayo Clinic (Rochester, Minnesota) were included. Data were abstracted, which included clinical and endoscopic manifestations, treatment course, and survival outcomes. The median (interquartile range) duration of follow-up was 8.3 (3.7-15.8) years. All patients received an initial prednisone dose equivalence of 30-80mg daily, and five patients required steroids at the time of the last follow-up. Twelve patients trialed thiopurine therapy, and ten patients continued with a thiopurine until the last follow-up. Fifteen patients achieved clinical complete remission, and eleven patients achieved endoscopic complete remission after pharmacotherapy initiation. Seven patients required gastrointestinal surgeries during their disease course. The 5-year overall survival was 93.3% (95% confidence interval (CI): 81.5-100%), and the 3-year relapse-free survival was 82.4% (95% CI: 66.1-100%). The prognosis and overall survival of patients with CCS have markedly improved with advancement in disease understanding and therapies. Pharmacotherapy, including corticosteroids and immunomodulators, is effective in inducing and maintaining remission, and gastrointestinal surgery is commonly needed as an adjunct for managing CCS disease complications.

Cronkhite-Canada Syndrome Presenting with life-threatening protein-losing enteropathy: a case report

Background: Cronkhite Canada Syndrome (CCS) is a rare gastrointestinal polyposis syndrome. The diagnosis of CCS is made by clinical, endoscopic and histopathological findings. Chronic diarrhea, malnutrition, alopecia, skin hyperpigmentation, onychodystrophy, hypogeusia, protein loss due to chronic inflammatory changes in the intestinal mucosa are common findings.Nutritional support, high protein diet, antibiotics, correction of electrolyte imbalance, and corticosteroids are frequently used in CCS treatment. Aim of the study: Here we present a newly diagnosed Cronkhite Canada Syndrome patient who has suffered life-threatening protein loss. Material and methods: Medical documentation was used. Case report: A 62-year-old male patient presented with bloodless diarrhea, happening 8-10 times a day for 4 months, and general condition disorder. On admission, arterial blood pressure was 80/50 mm/hg, pulse was 110 per minute and body temperature was 38.8°C. In laboratory tests, total protein: 38 mg/dl and albumin: 20 g/L.Upper and lower gastrointestinal system (GIS) endoscopy revealed 2-20 mm polyps in the stomach, duodenum, colon, and a small amount in the distal esophagus. Pathological examination of polypectomy materials revealed edematous and inflamed lamina propria consisting of plasma cells, neutrophils and eosinophils.The patient benefited from total parenteral nutrition, high protein dietary supplementation, antibiotic therapy and was followed with upper and lower GIS endoscopy. Conclusions: CCS is a rare disease that can cause life-threatening hypoalbuminemia and requires close follow-up.

Protein-Losing Enteropathy, Anasarca and Dermatological Manifestations on People of Advanced Age: Don't Overlook the Diagnostic Hypothesis of a Cronkhite Canada Syndrome

Cronkhite-Canada syndrome is a rare and non-genetic syndrome of unknown etiology, characterized by diffuse gastrointestinal polyposis, the dermatological triad (nail distrophy, hyperpigmentation, alopecia), diarrhea, weight loss and abdominal pain. Herein, we describe a late-onset case that experienced relief after prednisone treatment. It is very important keep in mind the clinical hypothesis of this syndrome, because an early diagnosis can help reduce morbidity and mortality associated with this pathology, which is often life threatening

Clinical and Endoscopic Response to Anti-Tumor Necrosis Factor-Alpha Antibody Therapy in a Patient With Cronkhite-Canada Syndrome.

Cronkhite-Canada syndrome (CCS) is an acquired polyposis syndrome with gastrointestinal and extraintestinal manifestations. Given its rarity and lack of standard treatment, diagnosis and treatment are challenging. Steroid therapy and nutritional support are conventional treatments. There is no consensus on management of steroid-refractory cases. Here, we report the diagnosis and treatment course of a 54-year-old Asian male with CCS, whose initial treatment with prednisone 60 mg a day led to partial response and disease flare up during prednisone tapering. The use of infliximab and azathioprine led to promising remission of his symptoms.

Cronkhite-Canada Syndrome Mimicking COVID-19-related Symptoms.

Abstract is missing (Short communication)

The genomic landscape of Cronkhite-Canada syndrome: Possible clues for pathogenesis.

Cronkhite-Canada syndrome (CCS) is a rare hamartomatous polyposis syndrome with a proposed association with chronic autoimmune inflammation. To date, genetic background of patients with CCS remains less investigated. In this study we aimed to explore the genomic landscape of CCS. Whole exome sequencing was performed on peripheral blood samples extracted from 18 patients with CCS. Potential function-impacting germline variants were filtered by R software. Through systematic data analysis, a number of genetic variants were identified. Enrichment analysis was performed using the R package ClusterProfiler. Overall, 3960 low-frequency (<0.05 or not reported in the Exome Aggregation Consortium East Asian, 1000 Genomes, or ESP6500 database) potentially function-impacting germline variants were identified, with 18 genes (FDFT1, LOC400863, MUC3A, MUC4, ZNF806, GXYLT1, MUC6, PABPC3, PSPH, ZFPM1, CIC, LOC283710, ARSD, GOLGA6L2, LOC388282, SLC25A5, TMEM247, WDR89) involved over half the patients. Functional enrichment of these genes revealed several biological processes in relation to innate immune responses and glycosylation. Only one likely pathogenic germline variant of an hamartomatous polyposis syndrome-associated gene, PTCH1, was detected in one patient. CCS has genomic alteration patterns completely distinct from those of traditional hamartomatous polyposis syndrome. The germline mutation landscape indicates potential roles of innate immune responses and glycosylation in the pathogenesis of CCS.

Cronkhite-Canada syndrome: a retrospective analysis of four cases at a single medical center

Objective Cronkhite-Canada syndrome (CCS) is a rare disease that is characterized by multiple gastrointestinal polyps and ectodermal abnormalities. This study aimed to improve the understanding of CCS by presenting our patient data. Methods Clinical features, treatment, and outcomes of four CCS patients at a single medical center were retrospectively analyzed. Results The age of the patients ranged from 32 to 61 years (mean: 49.5 years), including three men and one woman. All the patients presented with gastrointestinal symptoms, ectodermal abnormalities, and multiple gastrointestinal polyps. Two patients showed abnormal immune indices. Three patients underwent magnetic resonance enterography, and the typical manifestations of small intestine involvement were diffuse wall thickening, high signal intensity on diffusion-weighted imaging, obvious enhancement, and multiple small nodular enhancements of the small intestine. The main histological manifestations were chronic inflammation and hyperplastic, adenomatoid, and hamartomatoid polyps. Eosinophilic infiltration was observed in two patients. One patient had rectal adenocarcinoma at the time of diagnosis. All the four patients received prednisone at a dose of 0.75–1 mg/kg/day, and had their gastrointestinal symptoms gradually resolved (including two with ectodermal abnormality and endoscopic remission). Two patients are currently receiving low-dose prednisone (2.5–5 mg/day) with no recurrence after a 1.5- and 6-year follow-up periods, respectively. Conclusion Magnetic resonance enterography has the potential to evaluate small-intestinal lesions in CCSs. Long-term therapy with low doses of prednisone may be beneficial in maintaining remission.

Clinical and Radiological Features of Cronkhite–Canada Syndrome: A Case Report

AbstractCronkhite–Canada syndrome is a rare non-hereditary disease characterized by gastrointestinal hamartomatous polyposis and protein-losing enteropathy. The presenting symptoms are onychodystrophy, skin pigmentation, alopecia, weight loss, and diarrhea. Diagnosis is suggested by a combination of clinical, imaging, and endoscopy findings, and histology is necessary for confirmation. Here we describe a case of a 54-year-old man presenting with watery diarrhea, colicky abdominal pain, nasal obstruction, and weight loss for 6 months. Endoscopy showed multiple polyps in the stomach, duodenum, and colon. These were seen on computed tomography (CT) enterography along with polyps in the small bowel. A final diagnosis was made after the biopsy.

A Case of Medically Refractory Cronkhite-Canada Syndrome That Was Improved by Surgical Resection of the Main Lesion

A Case of Medically Refractory Cronkhite-Canada Syndrome That Was Improved by Surgical Resection of the Main Lesion