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BACKGROUND AND STUDY AIM: Malignant change can occur in gastric ulcer but guideline recommendations for follow-endoscopy (FU-OGD) are conflicting. This study aims to determine rate of malignancy and need for follow-up for gastric ulcers. PATIENTS AND METHODS: Patients with a first diagnosis of gastric ulcer between January 2012 and September 2013 were studied by analyzing endoscopic assessments, dysplasia, and malignancy yield and the influence of risk factors on the likelihood of benign disease. RESULTS: In a cohort of 432 patients with gastric ulcer (53 % male, mean age 65 years) dysplasia or neoplasia were found in 27 (19 adenocarcinomas, 2 cases of dysplasia, 5 lymphomas, 1 melanoma; malignancy yield 6 %). Twenty-five (93 %) cases were diagnosed on first biopsy. The cancer yield of FU-OGD after initially benign biopsy was 0.9 %. Binary logistic regression analysis revealed that endoscopically benign appearance (odds ratio 0.004 95 % CI 0 - 0.576; P = 0.029), benign histology on first biopsy (odds ratio 0 95 % CI 0 - 0.39; P = 0.011) and lower number of ulcers (odds ratio 0.22 (95 % CI 0.05 - 0.99); P = 0.049) were independent predictors of benign disease. All dysplastic and neoplastic cases would have been identified by a combination of initial biopsies plus repeat endoscopy with further biopsies for endoscopically suspicious appearances. CONCLUSIONS: In this large cohort 6 % of gastric ulcers were found to be malignant, highlighting the need for all gastric ulcers to be biopsied. The cancer yield of FU-OGD after benign biopsies was low. We have demonstrated that the combination of benign index histology and no endoscopic suspicion of malignancy can predict benign disease. We recommend that all gastric ulcers to be biopsied. Risk stratification could potentially reduce need for FU-OGD.

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BACKGROUND & AIMS: Patients with celiac disease (CD) often report symptoms compatible with irritable bowel syndrome (IBS). However, the prevalence of these symptoms in patients with CD and their relation to adherence to a gluten-free diet (GFD) have not been assessed systematically. METHODS: We searched MEDLINE, EMBASE, and EMBASE Classic (through July 2012) to identify cross-sectional surveys or case-control studies reporting prevalence of IBS-type symptoms in adult patients (≥ 16 years old) with established CD. The number of individuals with symptoms meeting criteria for IBS was extracted for each study, according to case or control status and adherence to a GFD. Pooled prevalence and odds ratios (ORs), with 95% confidence intervals (CIs), were calculated. We analyzed data from 7 studies with 3383 participants. RESULTS: The pooled prevalence of IBS-type symptoms in all patients with CD was 38.0% (95% CI, 27.0%-50.0%). The pooled OR for IBS-type symptoms was higher in patients with CD than in controls (5.60; 95% CI, 3.23-9.70). In patients who were nonadherent with a GFD, the pooled OR for IBS-type symptoms, compared with those who were strictly adherent, was 2.69 (95% CI, 0.75-9.56). There was also a trend toward a higher OR for IBS-type symptoms among patients who did not adhere to the GFD, compared with controls (12.42; 95% CI, 6.84-11.75), compared with that observed for adherent CD patients vs controls (4.28; 95% CI, 1.56-11.75). CONCLUSIONS: IBS-type symptoms occur frequently in patients with CD and are more common than among controls. Adherence to a GFD might be associated with a reduction in symptoms.

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Irritable bowel syndrome (IBS) is a chronic functional disorder of the gastrointestinal tract of unknown etiology. The diagnosis of IBS is made clinically, using symptom-based criteria such as the Manning or Rome criteria. Medical therapy for this condition has traditionally been directed towards symptom relief, using fiber or antispasmodic agents. In recent years, emerging data have confirmed the efficacy of antidepressants, psychological therapies, 5-HT(3) antagonists, 5-HT(4) agonists, and probiotics in the short-term treatment of IBS, although whether these therapies influence the long-term course of the disease is unknown. Increasing knowledge regarding the pathophysiological mechanisms underlying IBS has resulted in a number of novel molecular treatments, which show promise. These include therapies targeting gastrointestinal mucosal chloride channels and guanylate cyclase-C receptors, as well as highly selective agents influencing serotonergic transmission that, at the time of writing, do not appear to have any severe deleterious effects. In this article we provide a summary of current and emerging therapies in this field.

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BACKGROUND: Rectal epithelial cell mitosis and crypt size, as well as expression of proinflammatory genes including macrophage migration inhibitory factor (MIF), are increased 6 months after Roux-en-Y gastric bypass (RYGB) in morbidly obese patients. Tests were carried out to determine whether these putative colorectal cancer risk biomarkers remained elevated long term after RYGB, and the mechanistic basis, as well as the functional consequences, of Mif upregulation in intestinal epithelial cells was investigated. METHODS: Rectal mucosa and blood were obtained a median of 3 years after RYGB from the original cohort of patients with RYGB (n = 19) for crypt microdissection, real-time PCR, immunohistochemistry for MIF and immunoassay of proinflammatory markers. Immunohistochemistry for Mif and bromodeoxyuridine labelling were performed on AhCre⁺ mouse and Apc(Min/⁺) mouse (with and without functional Mif alleles) intestine, respectively. RESULTS: Rectal epithelial cell mitosis and crypt size remained elevated 3 years after RYGB compared with preoperative values (1.7- and 1.5-fold, respectively; p < 0.05). There was a 40-fold (95% CI 13 to 125) increase in mucosal MIF transcript levels at 3 years associated with increased epithelial cell MIF protein levels. Conditional Apc loss in AhCre⁺ mice led to increased epithelial cell Mif content. Mif deficiency in Apc(Min/⁺) mice was associated with a combined defect in intestinal epithelial cell proliferation and migration, which was reflected by the longitudinal clinical data. CONCLUSIONS: Mucosal abnormalities persist 3 years after RYGB and include elevation of the protumorigenic cytokine MIF, which is upregulated following Apc loss and which contributes to intestinal epithelial cell homeostasis. These observations should prompt clinical studies of colorectal neoplastic risk after RYGB.

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BACKGROUND AND AIMS: The relationship between obesity, weight reduction, and future risk of colorectal cancer is not well understood. Therefore, we compared mucosal biomarkers in normal weight individuals [body mass index (BMI), 18.5-24.9 kg/m(2)] with those in morbidly obese patients (BMI >40 kg/m(2)) before and 6 months after Roux-en-Y gastric bypass (RYGB). METHODS: Rectal epithelial cell mitosis, crypt area, and crypt branching were measured following whole crypt microdissection. Apoptosis was measured by immunohistochemistry for neo-cytokeratin 18 on fixed tissue sections. Serum levels of C-reactive protein and cytokines were assayed in combination with quantification of mucosal proinflammatory gene expression by real-time RT-PCR. RESULTS: Twenty-six morbidly obese patients (mean BMI, 54.4 kg/m(2)) had significantly increased mitosis, crypt area, and crypt branching (all P < 0.01) compared with 21 age- and sex-matched normal weight individuals (mean BMI, 22.5 kg/m(2)). Morbidly obese patients underwent a mean excess weight loss of 41.7% at a mean of 26 weeks after RYGB. Surprisingly, this was associated with a further increase in mitosis and decreased apoptosis of epithelial cells. At the same time, lower levels of serum C-reactive protein and interleukin-6 following RYGB were accompanied by a reduction in mucosal IL-6 protein content but elevated mucosal expression of other proinflammatory genes such as cyclooxygenase-1 and cyclooxygenase-2. CONCLUSIONS: Mucosal biomarkers, accepted as indicators of future colorectal cancer risk, are increased in morbidly obese patients compared with normal weight controls. The hyperproliferative state that exists 6 months after RYGB may have important implications for long-term colorectal cancer risk in bariatric surgery patients.

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OBJECTIVE: the Barthel Index (BI) has been recommended for the functional assessment of older people but the reliability of the measure for this patient group is uncertain. To investigate this issue we undertook a systematic review to identify relevant studies from which an overview is presented. METHOD: studies investigating the reliability of the BI were obtained by searching Medline, Cinahl and Embase to January 2003. Screening for potentially relevant papers and data extraction of the studies meeting the inclusion criteria were carried out independently by two researchers. RESULTS: the scope of the 12 studies identified included all the common clinical settings relevant to older people. No study investigated test-retest reliability. Inter-rater reliability was reported as 'fair' to 'moderate' agreement for individual BI items, and a high percentage agreement for the total BI score. However, these findings were difficult to interpret as few studies reported the prevalence of the disability categories for the study populations. There may be considerable inter-observer disagreement (95% CI of +/-4 points). There was evidence that the BI might be less reliable in patients with cognitive impairment and when scores obtained by patient interview are compared with patient testing. The role of assessor training and/or guidelines on the reliability of the BI has not been investigated. CONCLUSIONS: although the BI is highly recommended, there remain important uncertainties concerning its reliability when used with older people. Further studies are justified to investigate this issue.

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