Cases Report the Cronkhite-Canada Syndrome: Improving the Prognosis.

Cronkhite-Canada syndrome (CCS) is a rare nongenetic polyposis syndrome first reported by Cronkhite and Canada in 1955. Up to the present time, the literature consists of ∼400 cases of CCS with the majority being reported from Japan although 49 cases have been described in China.CCS is characterized by diffuse polyposis of the digestive tract in association with ectodermal changes, such as onychomadesis, alopecia, and cutaneous hyperpigmentation. The principal symptoms of CCS are diarrhea, weight loss, abdominal pain, and other gastrointestinal complications, such as protein-losing enteropathy and malnutrition.It has been traditional to consider that CCS is associated with a poor prognosis. This paper describes a relatively mild case and reviews the literature, which more recently, suggests that it may be a more benign condition that might actually be reversible with treatment.There is some evidence that infection or disturbed immunity may be involved in the pathophysiology and that targeting such abnormalities could have therapeutic potential.A strong case could be made for establishing an international case registry for this disease so that the pathophysiology, treatment, and prognosis could become much better understood.

Chemoprevention of intestinal adenomatous polyposis by acetyl-11-keto-beta-boswellic acid in APC(Min/+) mice.

Acetyl-11-keto-beta-boswellic acid (AKBA) is a derivative of boswellic acid, which is an active component of the gum resin of Boswellia serrata. AKBA has been used as an adjuvant medication for treatment of inflammatory diseases. In this study, we aimed to evaluate the efficacy of AKBA as a chemopreventive agent against intestinal adenomatous polyposis in the adenomatous polyposis coli multiple intestinal neoplasia (APC(Min/+) ) mouse model. APC(Min/+) mice were administered AKBA by p.o. gavage for 8 consecutive weeks. The mice were sacrificed and the number, size and histopathology of intestinal polyps were examined by light microscopy. AKBA decreased polyp numbers by 48.9% in the small intestine and 60.4% in the colon. An even greater AKBA effect was observed in preventing the malignant progression of these polyps. The number of large (>3 cm) colonic polyposis was reduced by 77.8%. Histopathologic analysis demonstrated a significant reduction in the number of dysplastic cells and in the degree of dysplasia in each polyp after AKBA treatment. There was no evidence of high grade dysplasia or intramucosal carcinoma in any of the polyps examined within the treated group. More interestingly, interdigitated normal appearing intestinal villi were observed in the polyps of the treated group. During the course of the study, AKBA was well tolerated by the mice with no obvious signs of toxicity. Results from immunohistochemical staining, Western blotting and enzyme-linked immunosorbent assay indicated that the chemopreventive effect of AKBA was attributed to a collection of activities including antiproliferation, apoptosis induction, antiangiogenesis and anti-inflammation. AKBA was found to exert its chemopreventive action through the inhibition of the Wnt/ß-catenin and NF-κB/cyclooxygenase-2 signaling pathways. Our findings suggest that AKBA could be a promising regimen in chemoprevention against intestinal tumorigenesis.

A case of Cronkhite-Canada syndrome presenting with adenomatous and inflammatory colon polyps.

BACKGROUND: A 72-year-old man was referred for evaluation of dysgeusia, diarrhea and anorexia. 3 months prior he began to experience taste changes, a decline in appetite and 3-7 loose, non-bloody stools per day. Nausea and lower abdominal cramping subsequently developed and he lost 22.68 kg in weight. His past medical history included atrial fibrillation treated with anticoagulation and digoxin. In the past, he had experienced markedly increased levels of triglycerides and was being treated for this condition with a lipid-lowering agent. There was no family history of colorectal neoplasia or IBD. He was a non-smoker and did not drink alcoholic beverages. INVESTIGATIONS: Medical history, physical examination, laboratory evaluation (including 72 h stool collection), upper endoscopy, colonoscopy and histologic analysis of biopsy samples. DIAGNOSIS: Cronkhite-Canada syndrome. MANAGEMENT: Prednisone (40 mg orally once daily, eventually tapered to 10 mg orally once daily), a histamine-2-receptor blocker and oral micronutrient supplementation (iron, vitamins A, E and D and a multivitamin). Removal of all visible polyps from the anal verge to 25 cm endoscopically by snare polypectomy or with hot biopsy forceps, followed by subtotal colectomy with end-to-side ileorectostomy.

Magnetic resonance colonography without bowel cleansing: a prospective cross sectional study in a screening population.

BACKGROUND AND AIMS: To evaluate the diagnostic accuracy of magnetic resonance colonography (MRC) without bowel cleansing in a screening population and compare the results to colonoscopy as a standard of reference. METHODS: 315 screening patients, older than 50 years with a normal risk profile for colorectal cancer, were included in this study. For MRC, a tagging agent (5.0% Gastrografin, 1.0% barium sulphate, 0.2% locust bean gum) was ingested with each main meal within 2 days prior to MRC. No bowel cleansing was applied. For the magnetic resonance examination, a rectal water enema was administered. Data collection was based on contrast enhanced T1 weighted images and TrueFISP images. Magnetic resonance data were analysed for image quality and the presence of colorectal lesions. Conventional colonoscopy and histopathological samples served as reference. RESULTS: In 4% of all colonic segments, magnetic resonance image quality was insufficient because of untagged faecal material. Adenomatous polyps >5 mm were detected by means of MRC, with a sensitivity of 83.0%. Overall specificity was 90.2% (false positive findings in 19 patients). However, only 16 of 153 lesions <5 mm and 9 of 127 hyperplastic polyps could be visualised on magnetic resonance images. CONCLUSIONS: Faecal tagging MRC is applicable for screening purposes. It provides good accuracy for the detection of relevant (ie, adenomatous) colorectal lesions >5 mm in a screening population. However, refinements to optimise image quality of faecal tagging are needed.

Molecular classification of patients with unexplained hamartomatous and hyperplastic polyposis.

CONTEXT: Significant proportions of patients with hamartomatous polyposis or with hyperplastic/mixed polyposis remain without specific clinical and molecular diagnosis or present atypically. Assigning a syndromic diagnosis is important because it guides management, especially surveillance and prophylactic surgery. OBJECTIVE: To systematically classify patients with unexplained hamartomatous or hyperplastic/mixed polyposis by extensive molecular analysis in the context of central rereview of histopathology results. DESIGN, SETTING, AND PATIENTS: Prospective, referral-based study of 49 unrelated patients from outside institutions (n = 28) and at a comprehensive cancer center (n = 21), conducted from May 2, 2002, until December 15, 2004. Germline analysis of PTEN, BMPR1A, STK11 (sequence, deletion), SMAD4, and ENG (sequence), specific exon screening of BRAF, MYH, and BHD, and rereview of polyp histology results were performed. MAIN OUTCOME MEASURES: Molecular, clinical, and histopathological findings in patients with unexplained polyposis. RESULTS: Of the 49 patients, 11 (22%) had germline mutations. Of 14 patients with juvenile polyposis, 2 with early-onset disease had mutations in ENG, encoding endoglin, previously only associated with hereditary hemorrhagic telangiectasia; 1 had hemizygous deletion encompassing PTEN and BMPR1A; and 1 had an SMAD4 mutation. One individual previously classified with Peutz-Jeghers syndrome had a PTEN deletion. Among 9 individuals with an unknown hamartomatous polyposis, 4 had mutations in STK11 (1), BMPR1A (2), and SMAD4 (1). Of the 23 patients with hyperplastic/mixed polyposis, 2 had PTEN mutations. Substantial discrepancies in histopathology results were seen. CONCLUSIONS: Systematic molecular classification of 49 patients with unexplained hamartomatous or hyperplastic polyposis uncovered a potential novel susceptibility gene, ENG, for juvenile polyposis. Importantly, given the substantial proportion of patients found to have germline mutations, more extensive analysis of the known susceptibility genes is indicated. Rereview of histology results by a dedicated gastrointestinal pathologist should be considered routinely, as organ-specific surveillance rests on defining syndromic diagnosis.

Multiple lymphomatous polyposis of the gastrointestinal tract.

CONTEXT: Gastrointestinal multiple lymphomatous polyposis is a rare type of malignant lymphoma that has aggressive biological behavior, early systemic dissemination and poor prognosis. It is considered to be a manifestation of non-Hodgkin lymphoma and represents the gastrointestinal counterpart of mantle cell nodal lymphoma. OBJECTIVE: A case of gastrointestinal multiple lymphomatous polyposis is presented and the anatomopathological, clinical, diagnostic and treatment aspects of this unusual neoplasia are discussed. CASE REPORT: The patient was a 59-year-old white male with a complaint of asthenia, night sweating, alteration in intestinal habit and weight loss over the preceding two months. The physical examination showed pallid mucosa and a palpable mass in the epigastrium and mesogastrium. Endoscopy of the upper digestive tract showed the presence of gastric and duodenal polyps. An opaque enema showed multiple polypoid lesions, especially in the cecum. A rectal biopsy revealed infiltration of the mucosa and submucosa by diffuse lymphoma consisting of small cleaved cells. Immunohistochemical study showed lymphocytes that expressed the antibody CD20 (L-26) and light-chain kappa (k) immunoglobulin, but not light-chain lambda (l) immunoglobulin. The patient presented a condition of acute intestinal obstruction with the presence of a mesenteric mass formed by agglutinated lymph nodes that surrounded the proximal ileum, thereby obstructing its lumen. He was submitted to a segmental enterectomy and gastrotomy with excisional biopsies of the gastric polypoid lesions. After two cycles of chemotherapy there was a worsening of the general state, with an increase in the dimensions of the abdominal masses and sepsis, accompanied by progressive respiratory insufficiency, leading to death.

[One case of Cronkhite-Canada syndrome, in which the course from onset to spontaneous curing could be followed].

The case is a 62 years old male. No polyposis was found by upper gastrointestinal endoscopy or barium enema examination performed at the time of cholecystectomy in March 1994. Symptoms such as dysgeusia, diarrhea, loss of hair and atrophy of nails began to appear from May. Examination of the digestive tract performed in October revealed clustered polyposis in the stomach, duodenum, small intestine and large intestine. Pathologically, all the polyps were found to be of the juvenile type, so a diagnosis of Cronkhite-Canada syndrome (CCS) was made. Histologic patterns of rectal polyp after polypectomy showed well differentiated adenocarcinoma continuous with the juvenile type polyp. The above-mentioned symptoms improved with the clinical course. At present, 6 years after the development of the disease, no recurrence of polyposis in the stomach and large intestine has been found. Our results suggest that ectodermal changes and lesions of the digestive tract in CCS appear and disappear in a short time.

Multiple lymphomatous polyposis of the gastrointestinal tract

CONTEXTO: A polipose linfomatosa múltipla gastrintestinal é tipo raro de linfoma maligno de comportamento biológico agressivo, com disseminação sistêmica precoce e prognóstico sombrio. A polipose linfomatosa múltipla gastrintestinal é considerada manifestação do linfoma não-Hodgkin e representa a contraparte gastrintestinal do linfoma nodal das células do manto. OBJETIVO: O presente estudo descreve caso de polipose linfomatosa múltipla gastrintestinal e discute os aspectos anatomopatológicos, clínicos, diagnósticos e terapêuticos desta inusitada neoplasia. RELATO DE CASO: Homem de 59 anos, branco, apresentou-se ao nosso serviço com queixa de astenia, suores noturnos, alteração do hábito intestinal e emagrecimento há dois meses. O exame físico mostrou mucosa descorada e massa palpável no epigástrio e mesogástrio. A endoscopia digestiva alta revelou pólipos gástricos e duodenais. O enema opaco mostrou lesões polipóides múltiplas, principalmente no ceco. A biópsia retal revelou infiltração da mucosa e submucosa por linfoma difuso de células pequenas clivadas. O estudo imuno-histoquímico mostrou linfócitos que expressavam o anticorpo CD20 (L26) e imunoglobulina de cadeia leve kappa (k), porém não expressava imunoglobulina de cadeia leve lambda (l). O doente apresentou abdome agudo obstrutivo devido a massa mesentérica formada por linfonodos aglutinados ao redor do íleo proximal e obstruindo seu lúmen. O enfermo foi submetido a enterectomia segmentar e gastrotomia com biópsias excisionais das lesões polipóides gástricas. Após dois ciclos de quimioterapia, houve piora do estado geral, com aumento das dimensões das massas abdominais e sepse, acompanhada por insuficiência respiratória progressiva e óbito.