Gastrointestinal graft-versus-host-disease (GI-GVHD) is a major cause of nonrelapse mortality after hematopoietic stem cell transplantation (HSCT) necessitating endoscopic examinations and biopsies for diagnosis. Fecal calprotectin (CPT) has been widely used in gastrointestinal inflammation, but comprehensive data in GI-GVHD are lacking.

Alterations in the neuro-immune axis contribute toward viscerosensory nerve sensitivity and symptoms in Irritable Bowel Syndrome (IBS). Inhibitory factors secreted from immune cells inhibit colo-rectal afferents in health, and loss of this inhibition may lead to hypersensitivity and symptoms. We aimed to determine the immune cell type(s) responsible for opioid secretion in humans and whether this is altered in patients with IBS. The β-endorphin content of specific immune cell lineages in peripheral blood and colonic mucosal biopsies were compared between healthy subjects (HS) and IBS patients. Peripheral blood mononuclear cell (PBMC) supernatants from HS and IBS patients were applied to colo-rectal sensory afferent endings in mice with post-inflammatory chronic visceral hypersensitivity (CVH). β-Endorphin was identified predominantly in monocyte/macrophages relative to T or B cells in human PBMC and colonic lamina propria. Monocyte derived β-endorphin levels and colonic macrophage numbers were lower in IBS patients than healthy subjects. PBMC supernatants from healthy subjects had greater inhibitory effects on colo-rectal afferent mechanosensitivity than those from IBS patients. The inhibitory effects of PBMC supernatants were more prominent in CVH mice compared to healthy mice due to an increase in μ-opioid receptor expression in dorsal root ganglia neurons in CVH mice. Monocyte/macrophages are the predominant immune cell type responsible for β-endorphin secretion in humans. IBS patients have lower monocyte derived β-endorphin levels than healthy subjects, causing less inhibition of colonic afferent endings. Consequently, altered immune function contributes toward visceral hypersensitivity in IBS.

Gastric marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma accounts for 40–50% of primary gastric lymphomas. Helicobacter pylori infection plays an important role in the pathogenesis. The phenotype of MALT lymphoma is variable, and lesions may appear as ulcers, nodules, thickening of folds, or erosions. This article is part of an expert video encyclopedia.

Irritable bowel syndrome (IBS) is associated with visceral hyperalgesia and frequently occurs after a transient gastrointestinal infection. Only a proportion of patients with acute gastroenteritis develop post-infectious IBS suggesting differences in host response to inflammatory stimuli. We aimed to investigate this concept by characterizing visceral sensitivity in two rat strains, following a chemically induced colitis.

Symptomatic upper gastrointestinal involvement of Crohn's disease is rare, with only approximately 4% developing upper gastrointestinal symptoms. This manifestation is often associated with a worse prognosis and a more severe course of the disease.

Tumors of the gastroesophageal junction are among the most frequent cancers in the upper gastrointestinal tract. Here the authors demonstrate morphologic findings, classification according to the Siewert classification, and endosonographic staging. This article is part of an expert video encyclopedia.

Fundic gland polyps are the most common gastric polyps, accounting for half of all gastric polyps, most commonly occurring in middle-aged women; they vary from 2 to 5 mm in size and are either single or multiple. Sporadic fundic gland polyps (FGPs) are benign gastric polyps without any malignant transformation and therefore do not require follow-up or treatment. In patients with polyposis syndromes, especially familial adenomatous polyposis, the incidence and burden of FGPs is markedly increased. For these patients endoscopic follow-up is recommended because of the increased risk for development of gastric neoplasia. This article is part of an expert video encyclopedia.

39 of 41 subjects who completed the sleep questionnaire.There was a sleep initiation problem in all subjects with fibromyalgia or both conditions compared to 83% IBS subjects.Scores indicative of clinically significant depression (T score ≥70) occurred in 3 subjects with IBS, 4 subjects with fibromyalgia, and 3 subjects with both.Scores indicative of clinical significant anxiety (T score ≥70) occurred in 3 subjects with IBS, 2 subjects with fibromyalgia, and 4 subjects with both.Parents scored depression and anxiety higher than subjects.Parents were more likely to score their children as having clinically significant depression and anxiety.Child psychological distress increased with functional disability scores [P=0.0003].There was no such relationship seen with parents' report of child's psychological distress and disability.Conclusion: Functional pain syndromes are associated with disability in children and adolescents.IBS is not as disabling as fibromyalgia.Regardless of the diagnosis, parents view their children as more disabled than reported by the children.Many children and adolescents have more than one functional pain syndrome and/or psychological comorbid conditions contributing to their disability.

Stromal or mesenchymal neoplasms affecting the gastrointestinal (GI) tract typically present as subepithelial neoplasms. The most common group consists of neoplasms that are collectively referred to as GI stromal tumors (GISTs). They are most often located in the stomach and proximal small intestine.1 Because all GISTs are now regarded as potentially malignant (especially those larger than 1 cm), consensus classifications focus on stratifying lesions (clinicopathobiologic risk categorization) according to the relative risk of recurrence and metastasis.2 This article is part of an expert video encyclopedia.

Objective The gut is a major site of contact between immune and sensory systems and evidence suggests that patients with irritable bowel syndrome (IBS) have immune dysfunction. Here we show how this dysfunction differs between major IBS subgroups and how immunocytes communicate with sensory nerves. Design Peripheral blood mononuclear cell supernatants from 20 diarrhoea predominant IBS (D-IBS) patients, 15 constipation predominant IBS (C-IBS) patients and 36 healthy subjects were applied to mouse colonic sensory nerves and effects on mechanosensitivity assessed. Cytokine/chemokine concentration in the supernatants was assessed by proteomic analysis and correlated with abdominal symptoms, and expression of cytokine receptors evaluated in colonic dorsal root ganglia neurons. We then determined the effects of specific cytokines on colonic afferents. Results D-IBS supernatants caused mechanical hypersensitivity of mouse colonic afferent endings, which was reduced by infliximab. C-IBS supernatants did not, but occasionally elevated basal discharge. Supernatants of healthy subjects inhibited afferent mechanosensitivity via an opioidergic mechanism. Several cytokines were elevated in IBS supernatants, and levels correlated with pain frequency and intensity in patients. Visceral afferents expressed receptors for four cytokines: IL-1β, IL-6, IL-10 and TNF-α. TNF-α most effectively caused mechanical hypersensitivity which was blocked by a transient receptor potential channel TRPA1 antagonist. IL-1β elevated basal firing, and this was lost after tetrodotoxin blockade of sodium channels. Conclusions Distinct patterns of immune dysfunction and interaction with sensory pathways occur in different patient groups and through different intracellular pathways. Our results indicate IBS patient subgroups would benefit from selective targeting of the immune system.

group.Only 37% of the PPI group had documented indication for PPI use.Conclusions: SBP is common problem with cirrhotic patients.There are many risk factors associated with developing SBP, and one of these may be the use of PPIs.Our study found that the use of PPIs and lower ascitic albumin level may predispose patients to more severe infections and increase mortality.This is an important consideration when prescribing PPIs in cirrhotic patients.

OBJECTIVES: Immune activation may have an important pathogenic role in the irritable bowel syndrome (IBS). While little is known about immunologic function in functional dyspepsia (FD), we have observed an association between cytokine secretion by peripheral blood mononuclear cells (PBMCs) and symptoms in IBS. Upper gastrointestinal inflammatory diseases are characterized by enhanced small bowel homing alpha 4-, beta 7-integrin, chemokine receptor 9 (CCR9) positive T lymphocytes. We hypothesized that increased cytokine release and elevated circulating small bowel homing T cells are linked to the severity of symptoms in patients with FD. Thus, we aimed to (i) compare cytokine release in FD and healthy controls (HCs), (ii) quantify "gut homing" T cells in FD compared with HC and patients with IBS, and (iii) correlate the findings to symptom severity and gastric emptying.METHODS: PBMC from 45 (Helicobacter pylori negative) patients with FD (Rome II) and 35 matched HC were isolated by density gradient centrifugation and cultured for 24 h. Cytokine production (tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6, IL-10) was measured by enzyme-linked immunosorbent assay. CD4+alpha 4 beta 7+CCR9+ T cells were quantified by flow cytometry in FD, HC and 23 patients with IBS. Gastric emptying was measured by scintigraphy. Symptom severity was assessed utilizing the standardized Gastrointestinal Symptom Score.RESULTS: FD patients had significantly higher TNF-alpha (107.2 +/- 42.8 vs. 58.7 +/- 7.4 pg/ml), IL-1 beta (204.8 +/- 71.5 vs. 80.2 +/- 17.4 pg/ml), and IL-10 (218 +/- 63.3 vs. 110.9 +/- 18.5 pg/ml) levels compared with HC, and enhanced gut homing lymphocytes compared with HC or IBS. Cytokine release and CD4+alpha 4 beta 7+CCR9+ lymphocytes were correlated with the symptom intensity of pain, cramps, nausea, and vomiting. Delayed gastric emptying was significantly associated (r = 0.78, P = 0.021) with CD4+alpha 4 beta 7+CCR9+ lymphocytes and IL-1 alpha, TNF-a, and IL-10 secretion.CONCLUSIONS: Cellular immune activation with increased small bowel homing T cells may be key factors in the clinical manifestations of H. pylori negative FD.

Introduction: Increasing evidence suggests that chronic stress alters behavior and modifies epigenetic regulation of genes in the central nervous system. DNA methylation, catalyzed by DNA methyltransferases (DNMTs), is an important epigenetic mechanism of transcriptional control of gene expression. We reported previously that chronic psychological stress induced visceral hyperalgesia and differential alterations in the expression of several genes in DRG neurons innervating the colon in the rat. A potential role for epigenetic regulation in peripheral sensory pathways has not been investigated. Objectives: We examined the hypothesis that DNMTs play an important role in the regulation of chronic stress-induced visceral hyperalgesia. Methods: Male rats were exposed to 1-hour water avoidance (WA) stress daily for 10 consecutive days as a chronic stress paradigm. SiRNA for DNMT1 was administrated in situ to L6-S2 DRGs every other day during the stress procedure. The visceromotor response (VMR) to colorectal distension was measured. Retrograde labeling with cholera toxin B (CTB)-FITCwas employed to identify colonDRG neurons. Immunofluorescence andWestern blot analysis were used to assess protein expression. In Vitro studies were performed in isolated control DRGs in the presence or absence of corticosterone (CORT; 10 μM) and RU-486 (corticoid receptor antagonist, 500 nM). Results: WA stress rats demonstrated significant increases in the level of DNMT1 and DNMT3b but not DNMT3a in L6-S2 DRGs compared with the controls. Enzyme activity assessment showed a 42% increase in DNMT1 activity in L6-S2 DRGs in stressed rats. Immunofluorescence studies revealed a significant increase in DNMT1 in small-sized, C-fiber neurons in WA stressed rats (52.3±2.2%) compared with the control (31.7±1.6%). Retrograde labeling demonstrated that 72.0±2.1% of the CTB-FITC labeled colonic DRG neurons were positive for DNMT1 in stressed rats compared to 40.0±6.5% in controls (P<0.05; n=4). The VMR in WA stressed rats was increased 68% and 92% above control responses at pressures of 40 and 60 mm Hg, respectively. Treatment of stressed rats with siRNA for DNMT1 prevented the VMR enhancement and changes in DNMT1 proteins levels in L6-S2 DRGs. In addition, treatment of control L6-S2 DRGs In Vitro with CORT (10 μM) increased DNMT1 expression level that was prevented by RU-486 (500 nM) (P<0.05). Conclusions: These data support the novel and provocative interpretation that: 1. Chronic stress induces epigenetic regulation of genes in primary nociceptive neurons; 2. DNA methyltransferase 1 (DNMT1) plays an important role in modulation of chronic stress-induced visceral hyperalgesia; and 3. DNA methyltransferases represent a potential target for treatment of functional GI disorders associated with visceral hyperalgesia.

Diese Übersichtsarbeit stellt neue medikamentöse Ansätze in der Behandlung der chronischen idiopathischen Obstipation und des Reizdarmsyndroms mit vorwiegender Obstipation vor. Dabei werden neue verfügbare Medikamente, Prucaloprid und Lubiproston, kurz mit ihrem Angriffspunkt und Nebenwirkungsprofil erläutert. Zusätzlich wird auf neue Präparate wie Renzaprid und Linaclotid eingegangen, die bereits erste positive Ergebnisse bei der Obstipation zu verzeichnen haben. Insgesamt stehen damit nach der Marktrücknahme von Tegaserod aufgrund kardialer Neben wirkungen wieder potente Medikamente zur Behandlung einer Obstipation zur Verfügung.