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- The first case from Pakistan: a case report.

Chronkhite-Canada Syndrome is characterised by diffuse gastrointestinal polyposis, dystrophic changes of the fingernails, cutaneous hyperpigmentation, alopecia, diarrhoea, weight loss, and abdominal pain. This disease is also associated with peripheral neuropathies and autoimmune disorders. Its association with other diseases may cause the polyps to turn into malignant tumours and worsen the condition. The first-line treatment is a combination of prednisone and mesalamine. NSAIDs and antibiotic administration is based on the symptoms and needs of patients. Here, we describe a 51-year-old male who presented to us with abdominal pain and significant weight loss. His physical examination showed dystrophic nails, alopecia and hyperpigmentation. Endoscopy and colonoscopy showed multiple polyps. His manifestations were consistent with Cronkhite-Canada syndrome. We prescribed oral corticosteroids, which improved his condition.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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 30-80 mg 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%). CONCLUSION: 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.

A case of Cronkhite-Canada syndrome with repeated linked color imaging observation of the subepithelial capillary network in the colon.

Cronkhite-Canada syndrome (CCS) is a non-hereditary disorder characterized by non-neoplastic gastrointestinal polyposis and ectodermal changes. While corticosteroids are considered effective, some cases are refractory. A 48-year-old woman presented with diarrhea, anorexia, and epigastralgia lasting for 3 months. She suffered from alopecia and nail dystrophy. Gastrointestinal endoscopy with histological examination confirmed non-neoplastic polyposis from the stomach to the rectum, confirming the diagnosis of CCS. Linked color imaging (LCI) with magnified endoscopy revealed a ribbon-like proliferation of capillaries surrounding the pits in the colonic mucosa. Histologically, the polyps had dilated glands, edematous stroma with inflammatory cell infiltrates and increased capillaries just beneath the epithelium. Immunohistochemical examination confirmed the expression of vascular endothelial growth factor (VEGF), mainly in the superficial epithelial and crypt cells. Steroid therapy was ineffective, and concomitant infliximab therapy provided symptomatic relief. Although symptoms rapidly improved with combination therapy, capillary hyperplasia and slight inflammation persisted in the colon mucosa after polyp resolution. Withdrawal of steroid treatment resulted in flare-ups of symptoms and polyps. Repeated magnified observations at LCI during post-relapse retreatment clearly captured the resolution process of both neovascularization and inflammation. Once the capillary hyperplasia and inflammation subsided, the steroid could be tapered off without relapse. To our knowledge, this is the first report describing the involvement of VEGF-induced angiogenesis and LCI findings in CCS; LCI observations are useful not only in the active phase of CCS, but also in determining subtle capillary hyperplasia and residual inflammation in remission, which may be an indicator of continued treatment.

Cronkhite-Canada Syndrome: A rare Case Report from Nepal.

Cronkhite-Canada syndrome first described in 1955, is a rare clinical syndrome of unknown etiology. Since then, more than 500 cases have been reported worldwide in the literature. The disease is characterized by diffuse gastrointestinal polyposis, dystrophic changes of the fingernails, cutaneous hyperpigmentation, alopecia, diarrhea, weight loss, and abdominal pain. A 84-year-old woman was admitted in our hospital with severe dehydration following diarrhea and epigastric discomforts. She also had dystrophic change of fingernails, and pigmentation of the palm and alopecia, all of which began several months ago. Endoscopy showed numerous, dense, tiny red polyps throughout the stomach, and duodenum. Her clinical manifestations and endoscopy were consistent with Cronkhite-Canada syndrome. We prescribed oral corticosteroids, which dramatically improved her condition. We here report rare case of Cronkhite-Canada syndrome who presented to our hospital. Keywords: Cronkhite-canada syndrome; gastrointestinal polyposis; onychodystrophy nail.

Sustained clinical response to infliximab in refractory Cronkhite-Canada syndrome.

A 59-year-old man with refractory Cronkhite-Canada syndrome (CCS) had poor clinical response to high-dose intravenous steroids, azathioprine, total parenteral nutrition and best supportive care. He remained highly symptomatic with abdominal pain, diarrhoea, recurrent sepsis and profound weight loss. Infliximab induction was given as rescue therapy, with marked clinical improvement observed within 3 weeks. This allowed steroid taper. Within 12 months of infliximab therapy, he achieved complete clinical remission and returned to his baseline weight and a full oral diet. Sequential endoscopies observed significant regression of previous marked gastrointestinal polyposis, including histological remission on colonic biopsies at 3.5 and 5 years of treatment. He currently remains in remission following 6 years of combination therapy with 5 mg/kg 8 weekly infliximab and azathioprine, and there is ongoing discussion with regard to the benefits and risks of therapy de-escalation. This case demonstrates the effectiveness of infliximab in inducing and maintaining remission in refractory CCS.

Cronkhite-Canada Syndrome Associated with Gastric Outlet Obstruction and Membranous Nephropathy: A Case Report and Review of the Literature.

A 47-year-old man presented with dysgeusia, anorexia, and diarrhea. An endoscopic evaluation showed widespread gastrointestinal nodular inflammation and polyps. The pathological findings were consistent with Cronkhite-Canada Syndrome (CCS). Prednisolone therapy resulted in clinical improvement. However, CCS relapse complicated with gastric obstruction was observed during drug tapering. Although his symptoms disappeared after the reintroduction of steroids, he developed membranous nephritis. Additional cyclosporine A (CyA) treatment dramatically improved his proteinuria and residual gastrointestinal polyposis. The clinical symptoms resolved with steroid treatment, while CyA was effective for both CCS lesions and membranous nephropathy. CyA might therefore be a potential treatment option for CCS associated with membranous nephropathy.

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

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: report of a rare case and review of the literature.

Cronkhite-Canada syndrome is rarely encountered in clinical practice. Notably, most patients with Cronkhite-Canada syndrome exhibit hypoalbuminemia. Because the cause of Cronkhite-Canada syndrome is unknown, no specific treatment method has been established. Here, we describe a 59-year-old woman with Cronkhite-Canada syndrome in whom clinical manifestations were considerably relieved after treatment with prednisone.

Successful Treatment of Juvenile Polyposis of Infancy With Sirolimus.

Juvenile polyposis syndrome is a rare autosomal dominant condition characterized by multiple hamartomatous polyps throughout the gastrointestinal tract. Juvenile polyposis of infancy is a generalized severe form of juvenile polyposis syndrome associated with a poor prognosis. A 47-month-old female infant presented initially with gastrointestinal bleeding and protein-losing enteropathy at 4 months of age. At the age of 12 months, the condition worsened, requiring albumin infusions every 24 to 48 hours and red blood cell transfusions every 15 days. Upper gastrointestinal endoscopy, colonoscopy, and small-bowel enteroscopy revealed diffuse polyposis that was treated with multiple endoscopic polypectomies. Despite subtotal colectomy with ileorectal anastomosis, protein-losing enteropathy and bleeding persisted, requiring continued blood transfusions and albumin infusions. A chromosomal microarray revealed a single allele deletion in chromosome 10q23, involving both the PTEN and BMPR1A genes. Loss of PTEN function is associated with an increased activation of the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway involved in cell proliferation. Treatment with sirolimus, an mTOR inhibitor, was initiated with the aim of inhibiting polyp growth. Soon after initiation of treatment with sirolimus, blood and albumin infusions were no longer needed and resulted in improved patient growth and quality of life. This case represents the first detailed report of successful drug therapy for life-threatening juvenile polyposis of infancy.

Active-Site Tryptophan, the Target of Antineoplastic C-Terminal Binding Protein Inhibitors, Mediates Inhibitor Disruption of CtBP Oligomerization and Transcription Coregulatory Activities.

C-terminal binding proteins (CtBP1/2) are oncogenic transcriptional coregulators and dehydrogenases often overexpressed in multiple solid tumors, including breast, colon, and ovarian cancer, and associated with poor survival. CtBPs act by repressing expression of genes responsible for apoptosis (e.g., PUMA, BIK) and metastasis-associated epithelial-mesenchymal transition (e.g., CDH1), and by activating expression of genes that promote migratory and invasive properties of cancer cells (e.g., TIAM1) and genes responsible for enhanced drug resistance (e.g., MDR1). CtBP's transcriptional functions are also critically dependent on oligomerization and nucleation of transcriptional complexes. Recently, we have developed a family of CtBP dehydrogenase inhibitors, based on the parent 2-hydroxyimino-3-phenylpropanoic acid (HIPP), that specifically disrupt cancer cell viability, abrogate CtBP's transcriptional function, and block polyp formation in a mouse model of intestinal polyposis that depends on CtBP's oncogenic functions. Crystallographic analysis revealed that HIPP interacts with CtBP1/2 at a conserved active site tryptophan (W318/324; CtBP1/2) that is unique among eukaryotic D2-dehydrogenases. To better understand the mechanism of action of HIPP-class inhibitors, we investigated the contribution of W324 to CtBP2's biochemical and physiologic activities utilizing mutational analysis. Indeed, W324 was necessary for CtBP2 self-association, as shown by analytical ultracentrifugation and in vivo cross-linking. Additionally, W324 supported CtBP's association with the transcriptional corepressor CoREST, and was critical for CtBP2 induction of cell motility. Notably, the HIPP derivative 4-chloro-HIPP biochemically and biologically phenocopied mutational inactivation of CtBP2 W324. Our data support further optimization of W318/W324-interacting CtBP dehydrogenase inhibitors that are emerging as a novel class of cancer cell-specific therapeutic.

Case report of patient with a Cronkhite-Canada syndrome: sustained remission after treatment with corticosteroids and mesalazine.

BACKGROUND: Cronkhite-Canada syndrome is a rare disease of unknown etiology and the optimal treatment for this syndrome is unknown. CASE PRESENTATION: We present the case of a man who at the age of 66.0 years was diagnosed with Cronkhite-Canada syndrome (CCS). In addition to watery diarrhea, alopecia, and a complete loss of toenails and fingernails, the patient had been suffering from dysgeusia and rapid weight loss of more than 10.0 kg within a few months. The patient had recently incurred a distal radius fracture. During the initial endoscopy an extensive polyposis of the stomach and jejunum was found. The diagnosis of CCS was made and after initiation of a steroid therapy his diarrhea improved immediately. A discontinuation of the steroid therapy was not possible and mesalazine (1000 mg t.i.d.) was added to prednisolone (10.0 mg/d). This therapy led to a remission within 6.0 months with weight gain and normalization of serum albumin levels. The prednisolone dose was reduced to 7.5 mg/d. During the following year, the steroids could be further reduced and nails had regrown again. Within three years, all polyps had disappeared and the steroid therapy was finished while the dosage of mesalazine was reduced in a stepwise fashion. Four years later, the mesalazine was stopped and more than 14.0 years after the initial diagnosis the patient is still in complete remission without any treatment. CONCLUSION: The optimal treatment for CCS is unknown. In our case, the initial combination therapy of corticosteroids plus mesalazine followed by a mesalazine monotherapy has led to a remarkable long-lasting remission with complete resolution of all intestinal polyps.

Recombinant Thrombomodulin Used to Successfully Treat Cronkhite-Canada Syndrome with Disseminated Intravascular Coagulation due to Sepsis in a Compromised Patient.

Cronkhite-Canada syndrome (CCS) is a rare non-inherited disease characterized by gastrointestinal polyposis, chronic diarrhea, ectodermal dysplasia, skin hyperpigmentation, hair loss and nail atrophy. Although the efficacy of corticosteroid and immunomodulatory agents has been demonstrated, no standard therapy regimen has been established, and the prognosis of CCS is still poor due to various complications. We here in report a CCS patient complicated with severe sepsis and disseminated intravascular coagulation who was successfully treated by combined modality therapies, including recombinant human soluble thrombomodulin.

Kaposi sarcoma-associated herpesvirus/human herpesvirus 8-associated extracavitary primary effusion lymphoma presenting as multiple lymphomatous polyposis.

Primary effusion lymphoma (PEL) is a distinct clinicopathological entity usually characterized by presentation as a lymphomatous body cavity effusion in the absence of solid tumor mass or dissemination during its clinical course. PEL can also rarely occur as a solid lymphoma involving nodal and extranodal sites and is referred to as extracavitary PEL. Here we report a unique case of extracavitary PEL in a 49-year-old HIV-seropositive patient who presented with vague abdominal pain and 20-lb weight loss. Esophagogastroduodenoscopy and colonoscopy revealed more than 100 broad-based intestinal polyps ranging from 2 mm to 3 cm in size, spreading from the duodenum to the rectum as a typical impression of "intestinal polyposis syndrome." Multiple biopsies demonstrated sheets of large lymphoid cells with characteristic features of extracavitary PEL with strong Kaposi sarcoma-associated herpesvirus/human herpesvirus 8 virus positivity by immunohistochemistry. Extracavitary PEL presenting as distinctive multiple lymphomatous polyposis as manifested in the case has not been described previously.

Nail Matrix Pathology in Cronkhite-Canada Syndrome: The First Case Report.

Cronkhite-Canada Syndrome (CCS) presents with gastrointestinal polyposis and the triad of cutaneous abnormalities including nail dystrophy, alopecia, and hyperpigmentation of the skin. The etiology is not well understood. The histology of skin lesion in CCS has not been routinely described. Especially, the nail matrix pathology has not been reported. In this study, the authors report the nail matrix pathology in a patient with CCS. Interestingly, the histologic evaluation revealed matrix hypergranulosis. Because matrix hypergranulosis is commonly found in several inflammatory nail diseases, this discovery points out that an inflammatory process is probably one of the important pathogeneses in CCS.