Effect of Antithrombotic Therapy and Long Endoscopic Submucosal Dissection Procedure Time on Early and Delayed Postoperative Bleeding.

Background: Recent updated guidelines of the Japanese Society of Gastroenterology recommend the use of a single dose of antiplatelet agents in patients undergoing endoscopic submucosal dissection (ESD). However, the postoperative bleeding risk after gastric ESD associated with the continuation or interruption of antithrombotic therapy remains controversial. We aimed to evaluate whether certain factors including interrupted antithrombotic therapy could affect early and delayed post-ESD bleeding risk.

Leu72Met408 Polymorphism of the Ghrelin Gene Is Associated With Early Phase of Gastric Emptying in the Patients With Functional Dyspepsia in Japan.

Background/aims: There are no available data about the relationship between ghrelin gene genotypes and early phase of gastric emptying in functional dyspepsia (FD) as defined by Rome III classification.

Methods: We enrolled 74 patients presenting with typical symptoms of FD and 64 healthy volunteers. Gastric motility was evaluated using the 13C-acetate breath test.

Water-soluble vitamin deficiencies in complicated peptic ulcer patients soon after ulcer onset in Japan.

We investigated over time whether contemporary Japanese patients with complicated peptic ulcers have any water-soluble vitamin deficiencies soon after the onset of the complicated peptic ulcers. In this prospective cohort study, fasting serum levels of water-soluble vitamins (vitamins B1, B2, B6, B12, C, and folic acid) and homocysteine were measured at 3 time points (at admission, hospital discharge, and 3 mo after hospital discharge). Among the 20 patients who were enrolled in the study, 10 consecutive patients who completed measurements at all 3 time points were analyzed.

Impact of sleep disorders, quality of life and gastric emptying in distinct subtypes of functional dyspepsia in Japan.

Background/aims: The association between clinical symptoms, gastric emptying, quality of life and sleep disorders in distinct functional dyspepsia (FD) patients has not been studied yet in detail.

Methods: We enrolled 79 FD patients (postprandial distress syndrome [PDS], n = 65; epigastric pain syndrome [EPS], n = 47; EPS-PDS overlap, n = 33) and 44 healthy volunteers. Gastric motility was evaluated.

Impact of coexisting irritable bowel syndrome and non-erosive reflux disease on postprandial abdominal fullness and sleep disorders in functional dyspepsia.

Background/aims: The association between clinical symptoms and sleep disorders in functional dyspepsia (FD)-overlap syndrome has not been studied in detail.

Methods: The subjects were 139 patients with FD, 14 with irritable bowel syndrome (IBS), 12 with nonerosive reflux disease (NERD), and 41 healthy volunteers. Gastric motility was evaluated with the (13)C-acetate breath test.

The preproghrelin 3056 TT genotype is associated with the feeling of hunger and low acylated ghrelin levels in Japanese patients with Helicobacter pylori-negative functional dyspepsia.

Objective: An impairment of gastric motility is strongly associated with the pathophysiology of functional dyspepsia (FD). Plasma ghrelin is one of the key molecules linked to gastric motility. Therefore, this study aimed to evaluate whether ghrelin (GHRL) gene polymorphisms are associated with clinical symptoms, the plasma ghrelin levels and gastric emptying in patients with FD as defined by the Rome III classification.

Sleep disorders in functional dyspepsia and future therapy.

Sleep disorder is a common medical problem. Sleep disorder has been associated with several diseases, including pulmonary disease, gastroesophageal reflux disease (GERD) and fibromyalgia. Interest in sleep phenomenology and gastrointestinal functioning has recently increased, because sleep disorder causes significant morbidity, as evidenced by the increased need for general medical and mental health treatment for emotional problems.

Impact of sleep disorders in Japanese patients with functional dyspepsia (FD): nizatidine improves clinical symptoms, gastric emptying and sleep disorders in FD patients.

Background And Aims: The association between functional dyspepsia (FD) and sleep disorders has yet to be studied in detail. The aim of this study is to evaluate the risk factors associated with sleep disorders and the clinical response to nizatidine therapy for sleep disorders in Rome III-based FD patients.

Methods: We enrolled 94 FD patients and 52 healthy volunteers.

Classification of patients who experience a higher distress level to transoral esophagogastroduodenoscopy than to transnasal esophagogastroduodenoscopy.

Background: In Japanese routine clinical practice, endoscopy is generally carried out without sedation. The present study aimed to identify the factors essential for appropriate selection of transnasal esophagogastroduodenoscopy (TN-EGD) as an alternative to unsedated transoral esophagogastroduodenoscopy (TO-EGD).

Patients And Methods: Subjects in this prospective cohort study comprised consecutive outpatients who underwent EGD at a single center.

Implication of antithrombotic agents on potential bleeding from endoscopically determined peptic ulcers, incidentally detected as surrogate markers for nsaids-associated ulcers complication.

Background And Aim: Little is known about the clinical significance of treatment for endoscopically determined peptic ulcers (EPU), incidentally detected as surrogate endpoints for non-steroidal anti-inflammatory drugs (NSAIDs)-associated ulcers complication, such as overt bleeding and perforation. Even uncomplicated-EPU without overt bleeding signs when antithrombotic agents (AT) were cotherapied may be of potential bleeding sites. The aim of the present study was to evaluate whether microcytic anemia, implying potential bleeding, is associated with NSAIDs-associated EPU or cotherapies with AT.

Pathophysiology of functional dyspepsia.

Functional dyspepsia is a highly prevalent and heterogeneous disorder. Functional dyspepsia involves many pathogenic factors, such as gastric motility disorders, visceral hypersensitivity, psychological factors, Helicobacter pylori infection, and excessive gastric acid secretion. The present article provides an overview of pathogenetic factors and pathophysiologic mechanisms.

The incidence of deep vein thrombosis in Japanese patients undergoing endoscopic submucosal dissection.

Background: Endoscopic submucosal dissection (ESD) is more invasive than other common endoscopic procedures and may increase the risk for deep vein thrombosis (DVT)/pulmonary embolism. The incidence of DVT/pulmonary embolism after ESD has not been adequately studied.

Objective: To evaluate DVT incidence and disease-specific features of D-dimer levels in ESD patients.

Migration of eosinophils and CCR2-/CD68-double positive cells into the duodenal mucosa of patients with postinfectious functional dyspepsia.

Objectives: Recent studies have shown that postinfectious functional dyspepsia (FD) symptoms may persist after elimination of gastrointestinal (GI) infection as well as postinfectious irritable bowel syndrome accompanying colonic inflammation. However, it is unclear whether intestinal chronic inflammation can contribute to clinical symptoms of certain FD patients such as postinfectious FD. To determine the relationship between local inflammation of the duodenum and clinical symptoms, we evaluated the infiltration of several phenotypes of duodenal inflammatory cells as well as gastric motility using (13)C urea breath test in postinfectious FD patients.

Celecoxib inhibits CD133-positive cell migration via reduction of CCR2 in Helicobacter pylori-infected Mongolian gerbils.

Background/aims: To see whether celecoxib prevents gastric cancer occurrence by disrupting the progression of chronic gastritis into gastric carcinoma through its inhibition of the migration of CD133-positive cells, one of the surface markers of bone marrow-derived cells, in Helicobacter pylori-infected gerbils.

Methods: 70 gerbils were divided into six groups. Group 1 gerbils served as control (n = 6).

The prokinetic effect of mosapride citrate combined with omeprazole therapy improves clinical symptoms and gastric emptying in PPI-resistant NERD patients with delayed gastric emptying.

Background: Previous studies have shown that non-erosive reflux disease (NERD) patients are less sensitive to proton pump inhibitor (PPI) treatment than patients with erosive reflux disease. The aim of this study was to investigate whether treatment with prokinetics in addition to omeprazole therapy would improve clinical symptoms, gastric emptying and esophageal peristalsis in PPI-resistant NERD patients with or without delayed gastric emptying.

Methods: Subjects were 64 consecutive patients presenting with typical symptoms of PPl-resistant NERD (n = 44) and 20 healthy volunteers.

Impact of quadruple regimen of clarithromycin added to metronidazole-containing triple therapy against Helicobacter pylori infection following clarithromycin-containing triple-therapy failure.

Background: The establishment of an optimal second-line regimen for Helicobacter pylori infection is required. Although quadruple therapy should overcome resistance to either clarithromycin or metronidazole, the effects of a quadruple regimen in second-line therapy are unknown. This study aims to evaluate the efficacy of triple therapy composed of proton pump inhibitor/amoxicillin plus metronidazole with the combined additive effects of clarithromycin as a second-line quadruple therapy against H.

Comparison of gastric emptying and plasma ghrelin levels in patients with functional dyspepsia and non-erosive reflux disease.

Background And Aims: The symptoms of postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS), the two subtypes of functional dyspepsia (FD) under the new Rome III classification, tend to overlap with those of non-erosive reflux disease (NERD). Plasma ghrelin levels have been associated with gastric motility; however, clinical studies have yet to examine this relationship among patients with PDS, EPS or NERD. Thus, this study aims to evaluate the correlation between gastric emptying and ghrelin levels as possible candidate factors for gastric motility in these diseases.

Bisphosphonate increases risk of gastroduodenal ulcer in rheumatoid arthritis patients on long-term nonsteroidal antiinflammatory drug therapy.

Background: Rheumatoid arthritis (RA) patients are at increased risk of peptic ulcers (PU) induced by nonsteroidal antiinflammatory drugs (NSAIDs). However, the impact of potential drug interactions on the development of PU has yet to be determined in a daily clinical setting. The aim was to estimate the clinical important interactions for PU presented by comedication in Japanese RA outpatients on long-term NSAID treatment.

Extracellular HSP70 blocks CD40L-induced apoptosis and tubular formation in endothelial cells.

Background: Recent studies have shown that CD40, a key player in angiogenesis and tubular formation, is an extracellular receptor of the heat shock protein 70 (HSP70)-peptide complex in endothelial cells. The aim of the present study was to determine the effect of extracellular HSP70 treatment on CD40L-suppressed apoptosis and CD40L-induced tubular formation in human umbilical vein endothelial cells (HUVEC).

Methods: The apoptotic index of CD40L-stimulated HUVEC with or without recombinant human HSP70 was evaluated using terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling assay analysis.

Celecoxib inhibits apurinic/apyrimidinic endonuclease-1 expression and prevents gastric cancer in Helicobacter pylori-infected mongolian gerbils.

Background And Aims: The aim of this study was to see whether administration of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, could prevent the development of gastric cancer via inhibition of apurinic/apyrimidinic endonuclease-1 (APE-1) expression induced by Helicobacter pylori infection.

Methods: 70 Mongolian gerbils were divided into 6 groups. Group 1 gerbils served as controls (n = 6).

Expression of apurinic/apyrimidinic endonuclease-1 (APE-1) in H. pylori-associated gastritis, gastric adenoma, and gastric cancer.

Background And Aim: Apurinic/apyrimidinic endonuclease-1 (APE-1) is a key enzyme in DNA base excision repair (BER), linked to cancer chemosensitivity. However, little is known about the localization of APE-1 in Helicobacter pylori-infected gastric mucosa or its role in the development of gastric cancer. To investigate the role of APE-1 in the development of gastric cancer, we examined APE-1 expression and localization in cultured cells and gastric biopsies from patients with H.

Monocyte chemoattractant protein 1 and CD40 ligation have a synergistic effect on vascular endothelial growth factor production through cyclooxygenase 2 upregulation in gastric cancer.

Background: Recent studies have reported that expression of monocyte chemoattractant protein 1 (MCP-1) and its receptor (CCR2) and CD40 ligation on mesenchymal cells play important roles in tumor development. Cyclooxygenase 2 (COX-2) has also been shown to contribute to tumor angiogenesis. We examined the interaction between MCP-1 and CD40 ligation in mesenchymal cells in gastric cancer to determine the effect of these factors on vascular endothelial growth factor (VEGF) production via upregulation of COX-2 expression.

COX-2 and CCR2 induced by CD40 ligand and MCP-1 are linked to VEGF production in endothelial cells.

Recent studies have reported that expression of MCP-1 and its receptor, CCR2; and CD40-CD40 ligand (CD40L) interaction on mesenchymal cells play important roles in tumor development. Studies have also connected MCP-1, CCR2, and CD40L to COX-2 expression. The aim of this study was to examine the effect of MCP-1/CCR2 and CD40-CD40L interaction on COX-2 and VEGF expression in endothelial cells.

Celecoxib inhibits Cdx2 expression and prevents gastric cancer in Helicobacter pylori-infected Mongolian gerbils.

Background/aim: The aim of this study was to see whether administration of celecoxib, a selective COX-2 inhibitor, prior to the appearance of intestinal metaplasia could prevent the development of gastric cancer in Helicobacter pylori-infected Mongolian gerbils.

Methods: Fifty-two Mongolian gerbils were divided into 3 groups and given 5 biweekly doses of N-methyl-N-nitrosourea (MNU; 30 ppm). At week 12, group 2 (n = 20) and group 3 (n = 22) gerbils were then given an injection of H.

Rebamipide reduces indomethacin-induced gastric injury in mice via down-regulation of ICAM-1 expression.

Non-steroidal anti-inflammatory drugs (NSAIDs) induced gastric mucosal injury occurs through subsequent events following free radical production derived from activated neutrophils. In this study, we hypothesized that rebamipide, a novel anti-ulcer agent, exerts a protective effect on NSAID-induced gastric injury through its antioxidant properties. The protective effect of rebamipide in a mouse model of indomethacin-induced gastric injury and mechanisms for this effect were investigated.