Survival Times of Patients With Menetrier's Disease and Risk of Gastric Cancer.

BACKGROUND & AIMS: Menetrier's disease is a rare acquired disorder associated with giant gastric folds along with protein-losing enteropathy, low stomach acid, or achlorhydria, and histologic features of massive foveolar hyperplasia. Little is known about the etiology, clinical features, or epidemiology of this disorder, including risk of gastric cancer. We investigated the outcomes and characteristics of patients with Menetrier's disease, including development of gastric cancer and survival times. METHODS: We performed a case-control study of all Menetrier's disease cases (n = 76; mean age, 56 ± 45 y; 59% male; mean body mass index, 24) diagnosed at Mayo Clinic, Rochester, MN, from January 1975 through 2005. Diagnosis of Menetrier's disease was based on a combination of clinical, endoscopic, radiologic, and histologic features. Patients with dyspepsia who underwent gastric biopsy analysis were included as controls. We obtained demographic, clinical history, laboratory, imaging, histopathology, and follow-up data from medical records. Clinical characteristics of Menetrier's disease were analyzed using descriptive statistics. The Kaplan-Meier method was used to estimate overall survival in cases. RESULTS: Clinical features found in a significantly higher proportion of patients with Menetrier's disease than controls included vomiting, abdominal pain, postprandial fullness, and weight loss of 10 lb or more. Smoking was associated with Menetrier's disease (P = .002 vs controls), but not alcohol use. Infection with Helicobacter pylori was not associated with Menetrier's disease (2.6% of patients vs 4.0% of controls; P = 1.00). There was no significant difference between patients with Menetrier's disease vs controls in proportions with inflammatory bowel disease. Gastric cancer developed in 8.9% of patients with Menetrier's disease by 10 years after the Menetrier's disease diagnosis vs 3.7% of controls over the same time period (P = .09). Of patients with Menetrier's disease, 72.7% and 65.0% survived for 5 and 10 years, respectively, compared with 100% of controls (P < .0001 for both time periods). CONCLUSIONS: In a case-control study of 76 patients with Menetrier's disease, we found this rare disorder to be associated with increased mortality. Patients with Menetrier's disease therefore should be followed up with surveillance endoscopy.

The role of cellular senescence in the gastrointestinal mucosa.

Cellular senescence is a biologically irreversible state of cell-growth arrest that occurs following either a replicative or an oncogenic stimulus. This phenomenon occurs as a response to the presence of premalignant cells and appears to be an important anticancer mechanism that keeps these transformed cells at bay. Many exogenous and endogenous triggers for senescence have been recognized to act via genomic or epigenomic pathways. The most common stimulus for senescence is progressive loss of telomeric DNA, which results in the loss of chromosomal stability and eventual unregulated growth and malignancy. Senescence is activated through an interaction between the p16 and p53 tumor-suppressor genes. Senescent cells can be identified in vitro because they express senescence-associated ß-galactosidase, a marker of increased lysosomal activity. Cellular senescence plays an integral role in the prevention and development of both benign and malignant gastrointestinal diseases. The senescence cascade and the cell-cycle checkpoints that dictate the progression and maintenance of senescence are important in all types of gastrointestinal cancers, including pancreatic, liver, gastric, colon, and esophageal cancers. Understanding the pathogenic mechanisms involved in cellular senescence is important for the development of agents targeted toward the treatment of gastrointestinal tumors.

Diagnostic performance of two confocal endomicroscopy systems in detecting Barrett's dysplasia: a pilot study using a novel bioprobe in ex vivo tissue.

BACKGROUND: There are currently 2 existing confocal laser endomicroscopy (CLE) platforms: probe-based CLE (pCLE) and endoscope-based CLE (eCLE) systems, each with its own criteria for identifying dysplasia in Barrett's esophagus (BE). The diagnostic performance of these 2 systems has not been directly compared. DESIGN: Preclinical, feasibility study. OBJECTIVES: We compared the interrater agreement and diagnostic performance of the pCLE and eCLE systems. In addition, we evaluated a new BE endomicroscopy criteria based on fluorescent glucose intensity uptake. PATIENTS: Thirteen patients with Barrett's esophagus and high-grade dysplasia or early cancer undergoing 16 EMR. INTERVENTION: CLE imaging was performed using two different probes with 2-[N-(7-nitrobenz-2-oxa-1,3-diaxol-4-yl)amino]-2-deoxyglucose, a fluorescent glucose analog with preferential uptake in dysplastic mucosa to supply contrast. Four quadrants were imaged per specimen with a total of 64 imaged mucosal sites presented to three gastroenterologists. MAIN OUTCOME MEASUREMENTS: Interobserver agreement and accuracy for dysplasia was assessed of images classified according to Miami criteria, stacked eCLE images classified using the Mainz criteria and a novel fluorescence intensity criteria. RESULTS: The interrater agreements were 0.17, 0.68, and 0.87 for the Miami, Mainz, and the fluorescence intensity criteria, respectively. Overall accuracy in detecting dysplasia was 37% (95% CI, 30.3-43.9), 44.3% (95% CI, 37.3-50.9), and 78.6% (95% CI, 72.2-83.3) for the Miami, Mainz, and the fluorescence intensity criteria, respectively. LIMITATIONS: This imaging technique and proposed fluorescence intensity criteria using 2-[N-(7-nitrobenz-2-oxa-1,3-diaxol-4-yl)amino]-2-deoxyglucose in EMR tissue will require in vivo validation and cannot be directly used with the current eCLE and pCLE clinical applications. CONCLUSIONS: In this preclinical feasibility study, the use of an eCLE system with a topical fluorescent contrast in ex vivo EMR tissue demonstrated higher interrater agreement and accuracy.

The role of allergy evaluation in adults with eosinophilic esophagitis.

BACKGROUND: Allergy evaluation and skin prick testing for foods are recommended in all patients with eosinophilic esophagitis. However, the yield of allergy evaluation in adult eosinophilic esophagitis is not known. GOALS: To determine the yield of allergy evaluation in adults with eosinophilic esophagitis. STUDY: All adult patients in the Cleveland Clinic eosinophilic esophagitis registry between January 2006 and April 2008 were identified. Diagnosis was based on clinical presentation and endoscopy with biopsies showing > or = 15 eosinophils/hpf. From this group, all patients referred for allergy evaluation were identified. Allergy evaluation consisted of skin testing to foods in all patients. Selected patients underwent skin testing to inhalants based on the presence of concomitant allergic rhinitis and/or asthma. Immediate hypersensitivity skin testing was performed and scored by standard methodology. Patients were referred on an ad hoc basis by the gastroenterologist and not based on a priori identification of an allergic diathesis. RESULTS: Twenty-six out of 68 patients (38%) completed allergy evaluation. Thirteen out of 26 patients (50%) demonstrated a positive skin test to > or = 1 food allergen. Of the 15 patients who underwent skin testing for inhalants, 14 (93%) had a positive skin test to 1 or more inhalants. In total 21/26 patients (81%) had > or = 1 allergen identified, 16/26 (62%) had > or = 5 allergens identified, and 4/26 (15%) had > or = 10 allergens identified (range: 0 to 20 allergens identified). Peanut, egg white, soybean, cow's milk, and tree nuts were the most common food allergens identified. CONCLUSIONS: Allergy evaluation has a high yield in adult eosinophilic esophagitis as 81% of referred patients had one or more allergens identified and 50% had one or more skin tests positive to foods. Allergy evaluation should be considered in adult patients with eosinophilic esophagitis.